CLINICAL TRIAL UPDATE

DRY AMD

NEW: Study: A Staged Study of the Safety and Effectiveness of ASP7317 in Senior Adults Who Are Losing Their Clear, Sharp Central Vision Due to Dry Age-related Macular Degeneration

ClinicalTrials.gov Identifier: NCT03178149

Sponsor: Astellas Institute for Regenerative Medicine

Purpose: This study is looking at a new treatment for slowing or reversing dry AMD, called ASP7317. ASP7317 is a specially created type of cells derived from stem cells. ASP7317 cells are injected into the macula of the eye. Immunosuppressive medicines (called IMT) are also taken around the time of injection of the cells to prevent the body from rejecting them.

Design: Randomized, parallel assignment, no masking

Number of Patients: 150

Inclusion Criteria: Subject has atrophy secondary to AMD in the study eye. Subject has the border of the area of definite decreased autofluorescence (DDAF) in the study eye, within the vascular arcades (criterion not applicable for subjects in dose escalation stage). Subject has a best corrected visual acuity (BCVA) score ≤37 early treatment diabetic retinopathy study (ETDRS) letters, in the study eye, at the second assessment during the screening visit between 4 and 23 ETDRS letters. In the dose escalation stage for the first dose cohort only, the study eye must be between light perception and ≤ 23 ETDRS letters at the second assessment during the screening visit. Subject has stable BCVA, in the study eye, to ensure stability of the visual acuity measures for study analyses (criterion not applicable for subjects in dose escalation stage). Subject has spectral domain-optical coherence tomography (SD-OCT) scans obtained of the study eye at the screening visit of suitable quality for grading retinal microstructures. Subject, at the screening visit, must have in the study eye an area with reduced retinal function and evidence of structural retinal preservation between the border of the area of atrophy and the vascular arcades, as determined by the subject selection committee (SSC) (criterion not applicable for subjects in dose escalation stage). Subject is recommended by the SSC for trial participation.

Exclusion Criteria: The following conditions are exclusionary if present in the study eye, unless otherwise specified. Foveal sparing as determined by either of the following methods (criterion not applicable for subjects in dose escalation stage): Any of the 9 loci in central square of the macula test grid with ≥ 0 dB sensitivity based on microperimetry testing at the prescreening or screening visit assessments. Presence of potentially viable photoreceptors, as evidenced by presence of ellipsoid zone (EZ), ≤ 250. Subject has evidence of prior or active choroidal neovascularization (CNV). Evidence of CNV will be assessed by the image reading center through review of the screening fundus photographs, fluorescein angiography (FA) and SD-OCT images. Evidence of CNV seen on 1 or more imaging modality is exclusionary. Subject has macular atrophy due to causes other than AMD. Subject has pathologic myopia defined as a spherical equivalent of > 8.00 diopters or axial length > 28 mm at the prescreening or screening visit, or myopic macular degeneration. Subject has a contraindication to pupil dilation. Subject has any other current sight-threatening ocular disease. Subject has presence of a posterior staphyloma. Subject has a current or prior history of optic neuropathy. Subject has presence of a macular hole. Subject has presence of macular schisis. Subject has a current or prior history of retinal dystrophy, retinitis pigmentosa, chorioretinitis, central serous choroidopathy, diabetic retinopathy, diabetic macular edema, vasoocclusive disease or other retinal vascular disease (e.g., compromised blood-retinal barrier) or retinal degenerative disease other than AMD. Subject has a prior history of retinal detachment within the vascular arcades. Subject has nevus of Ota (oculodermal melanocytosis), a choroidal pigmented lesion showing characteristics associated with high risk of malignancy (e.g., orange pigmented or elevated lesions) or a choroidal nevus within the macula. Subject has presence of submacular scarring. Subject has presence of an ocular toxoplasmosis scar or suspected active infection (or presence of elevated immunoglobulin M [IgM] toxoplasmosis titer). Subject has an abnormality of vitreoretinal interface (i.e., vitreomacular traction, epiretinal membranes, etc.) which can interfere with measurement of macular thickness or with the potential for macular structural damage. Subject has an intraocular pressure (IOP) of < 6 mmHg at the screening or first baseline (day -21) visits. Subject has presence of glaucomatous optic atrophy or uncontrolled intraocular pressure (IOP), or is using more than 2 agents to control IOP. Subject has active or history of uveitis. Subject has obscured ocular media opacity (e.g., corneal scars, lens opacities, vitreous abnormalities, etc.) at the screening or first baseline (day -21) visits such that reliable evaluations of the posterior segment cannot be performed. Subject has any other current ocular condition that can interfere with the assessment of disease progression including but not limited to accumulation of intraretinal fluid, subretinal fluid, sub-retinal pigment epithelial/epithelium (RPE) fluid or cyctoid macular edema. Subject has monocular vision. Subject has a history of ocular cancer in either eye.

Information: astellas.registration@astellas.com

Study: First in Human Study to Evaluate the Safety and Tolerability of GEM103 in Geographic Atrophy Secondary to Dry Age Related Macular Degeneration

ClinicalTrials.gov Identifier: NCT04246866

Sponsor: Gemini Therapeutics, Inc.

Purpose: The study is designed to identify the maximum tolerated dose (MTD) for intravitreal (IVT) administration of GEM103 in subjects with geographic atrophy (GA) secondary to dry AMD. Safety and tolerability of a single dose of GEM103 will be assessed based on the occurrence of dose-limiting toxicities (DLTs). Each subject will be followed for safety, pharmacokinetic (PK), clinical, and biomarker evaluations. Three escalating dose cohorts are planned.

Design: Nonrandomized, sequential assignment, no masking

Number of Patients: 12

Inclusion Criteria: At least 50 years old at the time of signed informed consent. Genetic variant eligibility. Able to cooperate sufficiently for adequate ophthalmic visual function testing and anatomic assessment and provide informed consent prior to initiation of any study procedure. Best corrected visual acuity (BCVA) in study eye between 5-35 letters. Confirmed diagnosis of central GA in the study eye and eligible total GA lesion size.

Exclusion Criteria: Carriers of specified high-genetic risk AMD variants. Presence of the following ocular conditions - in the study eye: Exudative AMD or choroidal neovascularization (CNV); Any ocular disease or condition that could impact the subject's ability to participate in the study or be a contraindication to IVT injection; Intraocular surgery (including intraocular lens replacement surgery) within 3 months prior to consent. Presence of any of the following ocular conditions - in either eye: History of herpetic infection; Ongoing treatment with antiangiogenic therapies in the fellow eye or completed treatment in the study eye. Any prior or ongoing medical condition (e.g. ocular other than dry AMD, systemic, psychiatric) or clinically significant screening laboratory value that may present a safety risk, interfere with study compliance, interfere with consistent study follow-up, or confound data interpretation throughout the longitudinal follow-up period. Female subjects must not be pregnant or lactating. Current use of medications known to be toxic to the lens, retina, or optic nerve.

Information: clinicaltrials@geminitherapeutics.com

Study: Carbidopa-Levodopa in Dry AMD With Geographic Atrophy

ClinicalTrials.gov Identifier: NCT03451500

Sponsor: Robert W. Snyder, MD, PhD, PC

Purpose: The Investigators will evaluate the safety and tolerability of carbidopa-levodopa in patients with Neovascular AMD and measure the effects on visual acuity and retinal abnormalities due to "wet" (neovascular) AMD. The Investigators will evaluate the safety and tolerability of carbidopa-levodopa in patients with Dry AMD and Geographic Atrophy, and measure the effects on visual acuity, area of geographic atrophy and other retinal abnormalities due to "dry" AMD.

Design: Parallel assignment, randomized, prospective, placebo-controlled

Number of Patients: 7

Inclusion Criteria: A diagnosis of dry AMD with geographic atrophy in 1 or both eyes. In patients with geographic atrophy in both eyes, the eye with the larger area of geographic atrophy will be designated eye A and the eye with the smaller area of geographic atrophy will be designated eye B. Normal or dry AMD of any grade in the second eye; Age 50-85 years; Willingness to maintain AREDS vitamin supplements throughout the study, or remain off these supplements for the duration of the study, if not taking them prior to the study; signed informed consent.

Exclusion Criteria: Any previous or current use of L-DOPA containing medication or dopamine agonist medication, or any planned use of any of these agents, except for study medication, during the study; Concurrent use of monoamine oxidase (MAO) inhibitors; Any eye condition, disease, or history of trauma in either eye, which can impair vision, except cataract or cataract surgery; BCVA worse than 20/100 in the eye with better BCVA; Current, or history of, neovascular AMD in either eye; Neurologic conditions which can impair vision; Parkinson's Disease; Significant orthostatic hypotension, defined as a drop in systolic blood pressure, immediately upon changing from the supine to standing position, of >19 mmHg, or a symptomatic drop in systolic blood pressure, immediately upon changing from the supine to standing position; Significant ECG abnormalities, as judged by the Investigator; Estimated glomerular filtration rate (eGFR) <20 ml/min; Liver enzymes >3x the upper limit of normal; HbA1C >9.0; Any other significant lab abnormalities, as judged by the Investigator. Women of childbearing potential; Known retinal hemorrhage; Subjects who are not fluent in English.

Study: Study of Photobiomodulation to Treat Dry Age-Related Macular Degeneration (LIGHTSITE III)

ClinicalTrials.gov Identifier: NCT04065490

Sponsor: LumiThera, Inc.

Purpose: This LIGHTSITE III study is a double-masked, sham-controlled, parallel design, prospective multi-site study for the use of PBM as a treatment for visual impairment in subjects with dry AMD.

Design: Randomized, parallel assignment, quadruple masking

Number of Patients: 96

Inclusion Criteria: Male or female at least 50 years of age at Screening visit. ETDRS BCVA letter score of between 50* and 75* (Snellen equivalent of 20/100 to 20/32). *If the subject meets this criterion at the Screening Visit, but the Baseline BCVA letter score is between 48 and 77, the subject may be entered in the study. Diagnosis of dry AMD as defined by the presence of the following: Drusen that are intermediate in size or larger (63 μm or larger in diameter) with at least a few (3) being regular drusen and not pseudodrusen and/or geographic atrophy (GA) visible on 2 of the following: color fundus images, OCT and/or FAF, to be confirmed by the reading center. Able to communicate well with the Investigator and able to understand and comply with the requirements of the study. Informed of the nature of this study and has provided written, informed consent in accordance with institutional, local and national regulatory guidelines.

Exclusion Criteria: Current or history of neovascular maculopathy that includes any of the following (to be confirmed by the reading center): Choroidal neovascularization (CNV) defined as pathologic angiogenesis originating from the choroidal vasculature that extends through a defect in Bruch's membrane; Serous and/or hemorrhagic detachment of the neurosensory retina or retinal pigment epithelial (RPE); Retinal hard exudates (a secondary phenomenon resulting from chronic intravascular leakage); Subretinal and sub-RPE fibrovascular proliferation; Disciform scar (subretinal fibrosis). Presence of center involving GA within the central ETDRS 1 mm diameter at Screening, to be confirmed by the reading center. Media opacities, including cataracts, which might interfere with visual acuity or imaging in the study eye(s). Subjects should not be entered if there is likelihood that they will require cataract surgery in the study eye in the next 24 months. Posterior capsule opacification, which might interfere with visual acuity or imaging in the study eye(s). Subjects should not be entered if there is likelihood that they will require surgery in the study eye in the next 24 months. Invasive eye surgery (eg cataract, capsulotomy) on a qualifying eye within 3 months prior to screening. Ocular disorder or disease that partially or completely obstructs the pupil (eg posterior synechia in uveitis). Visually significant disease in any ocular structure apart from dry AMD (eg diabetic macular edema, glaucoma (using >2 eye drop medications, uncontrolled IOP and/or central/paracentral visual field loss), glaucoma surgery, active uveitis, active vitreous disease, intraocular tumor, retinal vascular diseases). Ocular disorder or disease other than dry AMD that could cause drusen (glomerulonephritis Type 2, Autosomal dominant drusen), GA (North Carolina dystrophy) or mitochondrial diseases (parafoveal petaloid GA, Stargardt disease). Presence or history of disease or condition affecting functional vision without obvious structural abnormalities (eg amblyopia, stroke, nystagmus). Serious medical illness that will prevent the subject from performing study activities (including cardiac, hepatic, renal, respiratory, endocrinologic, neurologic, or hematologic disease) or, in the judgement of the Investigator, is likely to require surgical intervention or hospitalization at any point during the study. Presence of or history of malignancy within the past 5 years other than non-melanoma skin or squamous cell cancer or cervical carcinoma in-situ. Is non-ambulatory. Presence or history of known light sensitivity to yellow light, red light, or near infrared radiation (NIR), or if they have a history of light activated CNS disorders (eg epilepsy, migraine). Use of any photosensitizing agent (eg topicals, injectables, oral) within 30 days of treatment without consulting subject's physician. History of drug, alcohol or substance abuse within 3 months prior to Screening. Has received an investigational drug or treatment with an investigational device within 3 months prior to Screening. If on any antioxidant or vitamin Age-Related Eye Disease Study (AREDS) supplement for dry AMD, has not been stabilized for a minimum of 1 month prior to Screening. Subjects are considered to be stable if they are taking the AREDS supplements consistently as prescribed by their treating doctor. Has received Low Vision Rehab/Therapy within 30 days prior to Screening or intends to receive during the study. Has an open sore(s) that may come in contact with the Valeda System, has periorbital skin erythema or is prone to such conditions with exposure to light. In the opinion of the Investigator, is unlikely to comply with the study protocol.

Information: ctedford@lumithera.com, ccroissant@lumithera.com

Study: Comparing the Efficacy and Safety of Biosimilar Candidate Xlucane Versus Lucentis in Patients With nAMD (XPLORE)

ClinicalTrials.gov Identifier: NCT03805100

Sponsor: Xbrane Biopharma AB; Stada Arzneimittel AG

Purpose: The objectives of the study are to demonstrate the equivalence of Xlucane to Lucentis in treatment of subjects with wet (ie, neovascular) age-related macular degeneration (wAMD).

Design: Randomized, parallel assignment, double masked

Number of Patients: 580

Inclusion Criteria: Written and signed informed consent form obtained at screening, before any study-related procedures. Willingness and ability to undertake all scheduled visits and assessments as judged by the investigator. Newly diagnosed, active subfoveal Choroidal Neovascularization (CNV) lesion secondary to age-related macular degeneration (AMD) in the study eye. Note: Active CNV indicates the presence of leakage as evidenced by Fluorescein Angiography (FA) and intra- or subretinal fluid as evidenced by Optical Coherence Tomography (OCT) which must be confirmed by the central reading center during Screening: The area of CNV must be ≥50% of the total lesion area in the study eye, and total lesion area ≤9.0 Disc Areas (DA) in size (including blood, scars, and neovascularization) as assessed by FA in the study eye. Best Corrected Visual Acuity (BCVA) of ≤73 and ≥49 ETDRS letter score in the study eye, using ETDRS chart (20/40 to 20/100 Snellen equivalent) at Screening. Fellow eye should not be expected to need any anti-VEGF treatment for the duration of study participation. Age ≥50 years at screening. Male and female subjects of childbearing potential must be willing to completely abstain or agree to use an appropriate method of contraception, from the time of signing informed consent and for the duration of study participation through 3 months, following the last dose of study drug.

Exclusion Criteria: Any previous intervention including pharmacological treatment, laser and/or surgery for wAMD in either eye; (exception: vitamin supplementation for AMD prevention). Any previous vitreoretinal surgery in the study eye for any cause. Any previous IVT treatment including any anti-VEGF medications, steroids and/or any other investigational medication in either eye. The use of long-acting steroids, either systemic or intraocular in any eye, in the 18 months before planned initiation of study treatment. (Note: Iluvien [fluocinolone acetonide intravitreal], current or planned implantation during the study, is prohibited.) Subfoveal fibrosis, atrophy or scarring extending >50% of total lesion area, in the study eye as assessed by the investigator at screening and confirmed by the central reading center prior to randomization. Choroidal neovascularization in either eye due to non-AMD causes (eg, DME, RVO, ocular histoplasmosis or trauma, etc.) as assessed by FA and confirmed by central reading center. Active or recent (within 28 days prior to randomization) intraocular, extraocular, and periocular inflammation or infection in either eye. History of idiopathic or autoimmune-associated uveitis in either eye. Infectious conjunctivitis, keratitis, scleritis or endophthalmitis in either eye. Unmedicated intraocular pressure (IOP) ≥30 mmHg at Screening in either eye. Topical ocular corticosteroids administered for ≥30 consecutive days in the study eye within 90 days prior to Screening. Spherical equivalent of the refractive error in the study eye demonstrating more than 8 diopters of myopia. Corneal transplant or corneal dystrophy in the study eye. History of rhegmatogenous retinal detachment in the study eye. History of macular hole in the study eye. Retinal pigment epithelial tear or rip, involving the macula in the study eye as assessed by FA and confirmed by the central reading center. Current vitreous hemorrhage in the study eye. Subretinal hemorrhage that is ≥50% of the total lesion area in the study eye, or if the subretinal hemorrhage involves the fovea is 1 or more DA (≥2.54 mm²) in size in the study eye, as assessed by FA and confirmed by the central reading center. Other intraocular surgery (including cataract surgery) in the study eye within the 3 months prior to baseline. The yttrium aluminum garnet [YAG] posterior capsulotomy is allowed not later than 4 weeks prior to screening. Any concurrent intraocular condition in the study eye (eg, cataract or diabetic retinopathy) that, in the opinion of the investigator, could require treatment during the study period to prevent or treat loss of visual acuity. Significant media opacities (including cataract) in the study eye interfering with BCVA assessment or fundus imaging (FA/FP/OCT). Aphakia or absence of the posterior capsule in the study eye, unless it occurred as a result of a YAG posterior capsulotomy in association with prior posterior chamber intraocular lens implantation. Presence of advanced glaucoma or optic neuropathy that involve(s) or threaten(s) the central visual field in the study eye (as judged by the investigator). History of glaucoma filtering surgery or argon laser trabeculoplasty in the study eye (Exception: Laser iridotomy and selective laser trabeculoplasty are allowed). Uncontrolled ocular glaucoma or hypertension in the study eye, defined as IOP ≥25 mmHg despite treatment with anti-glaucoma medication. Any previous systemic anti-VEGF treatment (eg, bevacizumab). Contraindication for Lucentis (hypersensitivity to ranibizumab or to any of the study treatment excipients). Current treatment for active systemic infection. Females who are pregnant, nursing, planning a pregnancy during the study, or of childbearing potential and not using a reliable method of contraception and/or not willing to use a reliable method of contraception during their participation in the study. Participation in another clinical trial within the previous 3 months or any other clinical trial of anti-angiogenic drugs. Reasonable suspicion of other disease or condition that might render the subject at a high risk of treatment complications or otherwise confound interpretation of the study results (as judged by the investigator). PK subgroup only: Contraindication for additional blood sampling (as judged by the investigator).

Information: xbregistry@xbrane.com

Study: A Clinical Trial Designed to Evaluate the Safety and Exploratory Efficacy of 1.0 Mg Luminate (Alg-1001) As A Treatment for Non-Exudative Macular Degeneration

ClinicalTrials.gov Identifier: NCT03626636

Sponsor: Allegro Ophthalmics, LLC

Purpose: To evaluate the safety and exploratory efficacy of 1.0 mg of Luminate in patients with intermediate nonexudative macular degeneration.

Design: Randomized, double masked

Number of Patients: 40

Inclusion Criteria: Male or female patients, 50 to 85 years of age at screening visit; subject has signed the informed consent form; subjects with non-exudative AMD having ETDRS BCVA between 33 and 72 letters read (equivalent to 20/40 - 20/200 on Snellen chart) with the level of vision caused by the non-exudative AMD and no other factor/s; subjects with symptomatic decrease in visual acuity in the last 12 months; Subjects with combination of areas of RPE disturbances (hyper or hypopigmentation) and/or >1 large druse(n) (>125 microns) and/or multiple intermediate drusen (62-124 microns) in the macula as confirmed by the central reading center; subjects with evidence of reasonably well-preserved areas of RPE by clinical examination and well-defined RPE and outer segment ellipsoid line by OCT examination in the central 1 mm of the macula as confirmed by the central reading center. More specifically, reasonable reasonably well- preserved central 1 mm of the macula means: the RPE and outer retinal layers throughout the central 1 mm are intact; no signs of NVAMD such as intraretinal or sub retinal fluid, or sub retinal hyper-reflective material; no serous pigment epithelium detachments >100 microns in height.

Exclusion Criteria: Females who are pregnant, nursing, planning a pregnancy during the study or who are of childbearing potential not using a reliable method of contraception and/or not willing to maintain a reliable method of contraception during their participation in the study. Women of childbearing potential with a positive urine pregnancy test administered at baseline are not eligible to receive study drug. Participation in an investigational drug or device study within 90 days of screening; subjects with active exudative AMD in the fellow eye; subjects who had anti-VEGF IVT in either eye in the past 90 days; subjects with pigment epithelium detachments; subjects with active exudative AMD; subjects with any prior retina surgery; subjects with pathology that could prevent observation and follow-up of macular structures and measurement of BCVA (ie, advanced primary open angle glaucoma, any stage of normal tension glaucoma and corneal opacification); subjects that are likely to require cataract surgery in the opinion of the investigator within the study protocol period.

Information: info@allegroeye.com

Study: Safety and Efficacy Study of OpRegen for Treatment of Advanced Dry-Form Age-Related Macular Degeneration

ClinicalTrials.gov Identifier: NCT02286089

Sponsor: Cell Cure Neurosciences Ltd.

Purpose: The main objective of the study is evaluation of the safety and tolerability of OpRegen - human embryonic stem cell-derived retinal pigment epithelial (RPE) cells. The study will also include initial exploration of the ability of transplanted OpRegen cells to engraft, survive, and moderate disease progression.

Design: No masking, single group

Number of Patients: 24

Inclusion Criteria: Age 50 and older; Diagnosis of dry (non-neovascular) age related macular degeneration in both eyes; Funduscopic findings of dry AMD with progressive geographic atrophy in the macula; Best corrected central visual acuity equal or less than 20/200 in cohorts 1-3 and 20/64-20/250 in cohort 4 in the study eye by ETDRS vision testing; Vision in the non-operated eye must be better than or equal to that in the operated eye; Subjects with sufficiently good health to allow participation in all study-related procedures and complete the study follow-up period (medical records); Ability to undergo a vitreoretinal surgical procedure under monitored anesthesia care; Blood counts, blood chemistry, coagulation and urinalysis without abnormal significance; Negative for TB (cohort 4), HIV, HBC, and HCV, negative for CMV IgM and EBV IgM; Patients with no history of malignancy (other than a non-melanoma skin cancer). For cancers in remission for more than 5 years enrollment is allowed with concurred documented approval of principal investigator and oncologist prior to enrollment; Willing to defer all future blood and tissue donation; Able to understand and willing to sign informed consent.

Exclusion Criteria: Evidence of neovascular AMD by history, as well as by clinical exam, fluorescein angiography (FA), or ocular coherence tomography (OCT) at baseline in either eye; History or presence of diabetic retinopathy, vascular occlusions, uveitis, Coat's disease, glaucoma, cataract or media opacity preventing posterior pole visualization or any significant ocular disease other than AMD that has compromised or could compromise vision in the study eye and confound analysis of the primary outcome; History of retinal detachment repair in the study eye; Axial myopia greater than -6 diopters; At least 2 months following cataract removal in the study eye and Yttrium Aluminum Garnet (YAG) laser capsulotomy in the study eye in the past 4 weeks and any other ocular surgery in the study eye in the past 3 months prior to implantation; History of cognitive impairments or dementia; Contraindication for systemic immunosuppression; History of any condition other than AMD associated with choroidal neovascularization in the study eye (eg, pathologic myopia or presumed ocular histoplasmosis); Any type of systemic disease or its treatment, in the opinion of the Investigator, including any medical condition (controlled or uncontrolled) that could be expected to progress, recur, or change to such an extent that it may bias the assessment of the clinical status of the patient to a significant degree or put the patient at special risk. Female; pregnancy or breastfeeding; Current participation in another clinical study. Past participation (within 6 months) in any clinical study of a drug administered systemically or to the eye. Currently receiving aspirin, aspirin containing products and/or any other coagulation modifying drugs which cannot be discontinued 7 days prior to surgery; History of cancer (other than a non-melanoma skin cancer). For cancers cured more than 5 years ago, enrollment is allowed with concurred documented approval of principal investigator and oncologist prior to enrollment.

Information: maria@cellcure.co.il; grazag@biotimeinc.com

Study: Alpha MSH in Ocular Disease

ClinicalTrials.gov Identifier: NCT03451578

Sponsor: Duke University

Purpose: The purpose of this study is gaining a better understanding of a molecule called alpha melanocyte stimulating hormone (alpha MSH) and its potential role in your retinal disease. Alpha MSH has been shown to have an important role in the regulation of ocular immunity in animal models of inflammatory retinal diseases and retinal dystrophies, and there may be a protective effect of alpha MSH. By studying the levels of alpha MSH in your eye, we may better understand its role in advanced dry macular degeneration. By studying the levels of this molecule, we hope to better understand if it may be a good target for future treatment.

Design: Single group, no masking, diagnostic

Number of Patients: 60

Inclusion Criteria: 60 years or older; diagnosis of advanced dry macular degeneration with foveal geographic atrophy; limited vision or blindness (20/100 or worse) in that eye; pseudophakia (prior cataract surgery in that eye).

Information: latoya.greene@duke.edu

Study: Zimura in Subjects with Geographic Atrophy Secondary to Dry Age-Related Macular Degeneration

ClinicalTrials.gov Identifier: NCT02686658

Sponsor: Ophthotech Corporation

Purpose: The objectives of this study are to evaluate the safety and efficacy of intravitreous administration of Zimura when administered in subjects with geographic atrophy (GA) secondary to dry age-related macular degeneration (AMD).

Design: Randomized, parallel assignment, quadruple masking

Number of Patients: 200

Inclusion Criteria: Subjects of either gender aged ≥50 years; diagnosis of Non-foveal GA secondary to dry AMD.

Exclusion Criteria: Evidence of choroidal neovascularization (CNV); GA secondary to any condition other than AMD; any prior treatment for AMD or any prior intravitreal treatment for any indication in either eye, except oral supplements of vitamins and minerals; any intraocular surgery or thermal laser within 3 months of trial entry; any prior thermal laser in the macular region, regardless of indication; any ocular or periocular infection in the 12 weeks; previous therapeutic radiation in the region of the study eye; any sign of diabetic retinopathy in either eye.

Information: lillian.vazquez@ophthotech.com

Study: Study of Subretinal Implantation of Human Embryonic Stem Cell-Derived RPE Cells in Advanced Dry AMD

ClinicalTrials.gov Identifier: NCT02590692

Sponsor: Regenerative Patch Technologies, LLC

Purpose: The phase 1/2a clinical trial is designed to assess the feasibility of delivery and safety of human embryonic stem cell-derived RPE cells on a parylene membrane (CPCB-RPE1) in patients with advanced, dry age-related macular degeneration.

Design: Single Group Assignment, Open

Number of Patients: 20

Inclusion Criteria: Patients able to understand and willing to sign the informed consent. Adult male or female patients with the age of 55 to 85 (inclusive) years who are not employees of the trial sites; in sufficiently good health to reasonably expect survival for at least 5 years after treatment; clinical findings consistent with advanced dry AMD with evidence of 1 or more areas of ≥1.25 square millimeter of geographic atrophy involving the central fovea; geographic atrophy defined as attenuation or loss of RPE as observed by biomicroscopy, OCT, or FAF; the best-corrected visual acuity (BCVA) of the eye to receive the implant will be equal or worse than 20/200 in the first half of the study patients and between 20/80 and 20/400 (inclusive) in the second half of the patients. The BCVA of the eye that is NOT to receive the implant will be better or equal to the eye that will receive the implant; medically suitable to undergo pars plana vitrectomy and the surgical implant procedure, including being able to position postoperatively and use postoperative medications as required; medically suitable for general anesthesia or monitored intravenous sedation, if needed; patients who are pseudophakic or aphakic in the study eye; if designated as an organ donor, willing to forego live organ donation; willing to consent to the postmortem removal of the implant from the treated eye for the sponsor's analysis. The patient may also elect to donate the implanted and fellow, untreated eye, for histological analysis; able to understand the requirements of the study and willing and able to participate in long-term follow-up.

Exclusion Criteria: Presence of active or inactive choroidal neovascularization (CNV); presence or history of retinal dystrophy, retinitis pigmentosa, chorioretinitis, central serous choroidopathy or any other inflammatory ocular disease except dry eye syndrome; presence or history of severe, end-stage corneal dystrophy; history of steroid induced ocular hypertension or glaucoma; presence of moderate to severe glaucomatous optic neuropathy in the study eye, uncontrolled IOP, use of 2 or more topical agents to control intraocular pressure; history of glaucoma-filtering surgery; presence of moderate to severe nonproliferative diabetic retinopathy in the study eye; presence of any proliferative diabetic retinopathy in the study eye; presence of uncontrolled diabetes mellitus (HbA1c >8) at the time of screening; history of retinal detachment or retinal detachment repair in the study eye other than peripheral retinal tears or holes treated exclusively with laser or cryotherapy; presence of any other sight-threatening ocular disease; history of cognitive impairments or dementia which may impact the patient's ability to participate in the informed consent process and to appropriately complete evaluations; history of any immunodeficiency; evidence of herpetic or other viral eye disease; any current use of immunosuppressive therapy other than intermittent or low dose corticosteroids; participation within previous 3 months in any clinical trial of a drug by ocular or systemic administration (within previous 18 months for sustained release products); axial myopia of greater than -8 diopters in the eye that is to be implanted; axial length greater than 28 mm in the eye that is to be implanted; history of malignancy within the past 5 years (with the exception of successfully treated [excised] basal cell carcinoma [skin cancer] or successfully treated squamous cell carcinoma of the skin); history of myocardial infarction in previous 12 months; alanine transaminase/aspartate aminotransferase (ALT/AST) >3.0 times the upper limit of normal or any known liver disease; renal insufficiency, as defined by estimated creatinine clearance of <45 mL/min; a positive (or "reactive") test for HIV, or Hepatitis B, or Hepatitis C. A hemoglobin concentration of less than 10 gm/dL, a platelet count of less than 100K/µL or an absolute neutrophil count of less than 1000/µL at study entry; ocular lens removal within the previous 6 weeks in either eye; any other ocular surgery in the study eye in the previous 3 months; if female, pregnancy, the wish to become pregnant, or lactation; any other medical condition, which, in the Investigator's judgment, will interfere with the patient's ability to comply with the protocol, compromises patient safety, or interferes with the interpretation of the study results.

Information: GAquino@laretina.com

Study: An Open-Label, Phase 1 Clinical Study to Evaluate the Safety and Tolerability of Subcutaneous Elamipretide in Subjects with Intermediate Age-Related Macular Degeneration

ClinicalTrials.gov Identifier: NCT02848313

Sponsor: Stealth BioTherapeutics

Purpose: To test 40 mg of elamipretide administered as a once daily 1.0 mL subcutaneous injection for 12 weeks.

Design: Safety, Single Group, No Masking, Treatment

Number of Patients: 40

Inclusion Criteria: No evidence of choroidal neovascularization (active or prior history) in the study eye; geographic atrophy may be multifocal, but the cumulative GA lesion size must be: ≥1.27 mm² (approximately ≥0.5 DA) and ≤10.16 mm² (approximately ≤4 DA); must reside completely within the FAF imaging field (field 2 to 30-degree image centered on the fovea); presence of measurable hyper autofluorescence adjacent to the discrete foci of GA. OR Intermediate AMD - high-risk drusen without GA disease group.

Exclusion Criteria: Age-related macular degeneration with any evidence of central GA (ie, involving the fovea); atrophic retinal disease because of causes other than AMD; presence or diagnosis of exudative AMD or choroidal neovascularization in the study eye; history of diabetic retinopathy (a history of diabetes mellitus without retinopathy is not a criterion for exclusion); presence of vitreous hemorrhage; history of retinal detachment or macular hole (stage 3 or 4) in the study eye; presence of macular pucker.

Information: kit.oldham-creamer@stealthbt.com

Study: TOGA: Clinical Study to Evaluate Treatment with ORACEA for Geographic Atrophy

ClinicalTrials.gov Identifier: NCT01782989

Sponsor: Paul Yates, MD, PhD/MEDARVA

Purpose: To evaluate the efficacy and safety of ORACEA in the treatment of geographic atrophy due to dry age-related macular degeneration.

Design: Randomized, Parallel Assignment, Double-Blind, Treatment

Number of Patients: 286

Inclusion Criteria: Best-corrected visual acuity of 20/20 to 20/400 in the study eye; best-corrected visual acuity of hand motion or better in the nonstudy eye; clinical diagnosis of geographic atrophy secondary to nonexudative age-related macular degeneration in at least 1 eye (study eye); geographic atrophy lesions of ≥0.5 and ≤7.0 MPS disc areas.

Exclusion Criteria: History of or active presence of choroidal neovascularization secondary to exudative age-related macular degeneration in the study eye; history of or active presence of choroidal neovascularization secondary to exudative AMD in the nonstudy eye requiring any treatment within 12 months prior to day 0.

Information: pay2x@virginia.edu, aml7q@virginia.edu

Study: Evaluation of Oral Minocycline in the Treatment of Geographic Atrophy Associated With AMD

ClinicalTrials.gov Identifier: NCT02564978

Sponsor: National Eye Institute

Purpose: To see if minocycline is safe for people with GA and if it helps preserve their vision.

Design: Single Group Assignment, No Masking, Treatment

Number of Patients: 60

Inclusion Criteria: Participant must be 55 years or older; must have evidence of early or intermediate AMD as defined by characteristic presence of drusen and/or pigmentary changes; participant must be able to swallow capsules.

Exclusion Criteria: Participant is on ocular or systemic medications known to be toxic to the lens, retina or optic nerve (eg, ethambutol, chloroquine, or hydroxychloroquine); participant has a condition that would preclude participation in the study.

Information: Angela.kibiy@nih.gov

Study: METforMIN: Metformin for the Minimization of Geographic Atrophy Progression in Patients With AMD

ClinicalTrials.gov Identifier: NCT02684578

Sponsor: University of California, San Francisco

Purpose: To determine whether metformin, an FDA-approved drug for the treatment of type II diabetes, is a safe and effective treatment to decrease the progression of geographic atrophy in nondiabetic patients with age-related macular degeneration.

Design: Randomized, Safety/Efficacy, Parallel Assignment, Single-Blind, Treatment

Number of Patients: 186

Inclusion Criteria: Subject must have evidence of advanced dry AMD, defined by the characteristic presence of drusen and/or pigmentary changes, as well as geographic atrophy; subject must have clear ocular media and adequate pupillary dilation; study eye must have best corrected visual acuity (BCVA) of 20/20-20/400.

Exclusion Criteria: Subjects with insufficient baseline size of geographic atrophy, less than 1.25 mm² (0.5 Macular Photocoagulation Study Disc Areas). GA is defined as 1 or more well-defined and often circular patches of partial or complete depigmentation of the RPE, typically with exposure of underlying choroidal blood vessels. Even if much of the RPE appears to be preserved and large choroidal vessels are not visible, a round patch of RPE partial depigmentation may be classified as early GA. The GA in the study eye must be able to be photographed in its entirety, and it must not be contiguous with any areas of peripapillary atrophy, which can complicate area measurements.

Information: eyestudy@ucsf.edu

WET AMD

NEW: Study: A Phase II Study of RBM-007 Alone and RBM-007 With Eylea^® in Subjects With Wet Age-related Macular Degeneration (TOFU)

ClinicalTrials.gov Identifier: NCT04200248

Sponsor: Ribomic USA Inc

Purpose: This is a multicenter, active-controlled, double masked study assessing the safety, efficacy and durability of four monthly intravitreal (IVT) injections of RBM-007 monotherapy, and four monthly RBM-007 injections in combination with Eylea dosed at every other month, compared to Eylea monotherapy dosed at every other month in approximately eighty-one subjects with exudative age-related macular degeneration (AMD).

Design: Randomized, parallel assignment, double masking

Number of Patients: 81

Inclusion Criteria: Provide signed written informed consent. Male or female 55 years of age or older on the date of signing the consent and able and willing to comply with all treatment and study procedures. Diagnosis of exudative age-related macular degeneration in the study eye, for which previous standard treatment with intravitreal anti-vascular endothelial growth factor agents (at least 4 injections over the past 8 months) has demonstrated incomplete resolution of exudation, as assessed by spectral domain optical coherence tomography. Presence of macular edema or subretinal fluid. Absence of central atrophy or retinal epithelial tear in the fovea or any condition preventing visual acuity improvement in the study eye. Visual acuity of 78 to 24 letters (20/32 to 20/320) in the study eye. Visual acuity of 24 letters (20/320) or better in the fellow eye. Reasonably clear media and some fixation in the study eye to allow for good quality tomography and fundus photography.

Exclusion Criteria: Use of any of the following treatments or anticipated use of any of the following treatments to the study eye: Any intravitreal treatment within 4 weeks prior to Baseline (visit 1). Intravitreal or periocular corticosteroid, within 90 days prior to visit 1 (day 1) and throughout the study. Fluocinolone acetonide intravitreal implant, within 12 months prior to visit 1 (day 1) and throughout the study. Visudyne photodynamic therapy, within 90 days prior to visit 1 (day 1) and throughout the study. Uncontrolled or advanced glaucoma, evidenced by an intraocular pressure of >21 mmHg or cup/disc ratio > 0.8 while on medical therapy, or chronic hypotony (<6 mmHg) in the study eye. Evidence of any other ocular disease other than wet age-related macular degeneration in the study eye that may confound the outcome of the study History of vitrectomy in the study eye. Need for ocular surgery in the study eye during the course of the study. YAG laser capsulotomy within 30 days prior to visit 1 (day 1) in the study eye. Intraocular surgery, including lens removal or laser, within 90 days prior to visit 1 (day 1) in the study eye.

Information: yusuf.ali@ribomic.com; daniel.pereira@ribomic.com

Study: A Study to Evaluate the Efficacy and Safety of KSI-301, an Anti-VEGF Antibody Biopolymer Conjugate, Versus Aflibercept in Patients with Neovascular (Wet) Age-Related Macular Degeneration (DAZZLE)

ClinicalTrials.gov Identifier: NCT04049266

Sponsor: Kodiak Sciences Inc

Purpose: This study will evaluate the efficacy, safety, durability, and pharmacokinetics of KSI-301 administered at 12, 16 and 20 weeks intervals as specified in the protocol, compared with aflibercept once every 8 weeks (Q8W), in participants with treatment-naïve neovascular (wet) age-related macular degeneration (nAMD).

Design: Randomized, parallel assignment

Number of Patients: 368

Inclusion Criteria: Signed informed consent prior to participation in the study. Active, treatment-naïve choroidal neovascularization (CNV) secondary to AMD. BCVA ETDRS score between 80 and 25 letters (Snellen equivalent of 20/25 to 20/320), inclusive. Other protocol-specified inclusion criteria may apply.

Exclusion Criteria: CNV secondary to other causes in the Study Eye. Any history of macular pathology unrelated to AMD but affecting vision or contributing to subretinal or intraretinal fluid. Any history or evidence of a concurrent intraocular condition in the Study Eye that, in the judgment of the Investigator, could require either medical or surgical intervention during the study to prevent or treat visual loss. Active ocular or periocular infection or inflammation. Prior administration of any approved or investigational treatment for neovascular AMD in the Study Eye. Uncontrolled glaucoma in the Study Eye. Women who are pregnant or lactating or intending to become pregnant during the study. Stroke or myocardial infarction in the 6-month period prior to Day 1. Uncontrolled blood pressure defined as a systolic value >180 mmHg or diastolic value ≥100 mmHg while at rest. History of a medical condition that, in the judgment of the Investigator, would preclude scheduled study visits, completion of the study, or a safe administration of investigational product. Other protocol-specified exclusion criteria may apply.

Information: KSI-CL-102@kodiak.com

Study: A Study Assessing AR-13503 Implant Alone and in Combination with Aflibercept in Subjects With nAMD or DME

ClinicalTrials.gov Identifier: NCT03835884

Sponsor: Aerie Pharmaceuticals

Purpose: First-in-human study of the safety of AR-13503 sustained release intravitreal implant in subjects with neovascular age-related macular degeneration (nAMD) and subjects with diabetic macular edema (DME).

Design: Randomized, sequential assignment, single

Number of Patients: 102

Inclusion Criteria: Inclusion Criteria for Subjects with Neovascular Age-Related Macular Degeneration (nAMD) or Diabetic Macular Edema (DME): 50 years of age or older. Presence of active subfoveal or juxtafoveal Choroidal Neovascularization (CNV) (any subtype) with leakage affecting the fovea secondary to Age-Related Macular Degeneration (AMD). Best Corrected Visual Acuity (BCVA) in the study eye at Baseline (Day 0): Stage 1: between 65 and 10 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (20/50 and 20/640 Snellen equivalent) Stage 2: between 65 and 20 ETDRS letters (20/50 and 20/400 Snellen equivalent). Able and willing to give signed informed consent and follow study instructions. Inclusion Criteria for Subjects with DME: Subjects with Diabetic Macular Edema (DME) must meet all the following criteria to enter into the study: 18 years of age or older. Type 1 or 2 diabetes mellitus with center-involved DME. BCVA in the study eye at Baseline (Day 0): Stage 1: between 65 and 10 ETDRS letters (20/50 and 20/640 Snellen equivalent) Stage 2: between 65 and 20 ETDRS letters (20/50 and 20/400 Snellen equivalent). Able and willing to give signed informed consent and follow study instructions.

Exclusion Criteria: Exclusion Criteria for Subjects with Neovascular Age-Related Macular Degeneration (nAMD): Ophthalmic: Use of intravitreal aflibercept within 8 weeks, ranibizumab or bevacizumab within 6 weeks. History of vitreoretinal surgery in the study eye. Any ocular disease in the study eye that in the Investigator and Reading Center's opinion may confound assessment of the macula, affect central vision, confound results, or preclude improvement in visual acuity. Any current or history of periocular or intraocular inflammation or evidence of infection in either eye. Media clarity insufficient to obtain quality fundus and OCT images in the study eye. Systemic: History or current systemic condition that in the Investigator opinion preclude the safe administration of the study treatment or confound results. History of allergy or sensitivity to fluorescein or povidone iodine. Women of childbearing potential who are pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of birth control. Participation in an investigational study within 30 days of Screening. Exclusion Criteria for Subjects with DME: Ophthalmic: Use of intraocular or periocular corticosteroids within 6 months, aflibercept within 8 weeks, ranibizumab or bevacizumab within 6 weeks. History of vitreoretinal surgery in the study eye. High risk proliferative diabetic retinopathy in the study eye and related complications. Structural damage to the center or the macula that is likely to preclude improvement in visual acuity in the study eye after resolution of the DME. Media clarity insufficient to obtain quality fundus and OCT images in the study eye. Systemic: History or current medical condition that in the Investigator's opinion preclude the safe administration of the study treatment or confound results. History of allergy or sensitivity to fluorescein or povidone iodine. Women of childbearing potential who are pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of birth control. Participation in an investigational study within 30 days of Screening.

Information: nramirez@aeriepharma.com, pbraswell@aeriepharma.com

Study: A Depot Formulation of Sunitinib Malate (GB-102) Compared to Aflibercept in Subjects with Wet AMD (ALTISSIMO)

ClinicalTrials.gov Identifier: NCT03953079

Sponsor: Graybug Vision

Purpose: Phase 2b, multicenter, visual examiner-masked, randomized active-controlled, parallel-arm design study to evaluate the safety and duration of repeated IVT injections of 3 dose levels of GB‑102 compared with aflibercept.

Design: Randomized, parallel assignment, single masking

Number of Patients: 220

Inclusion Criteria: Males or females ≥50 years of age. Presence of a CNV lesion secondary to AMD treated with at least 3 prior IVT injections of an anti-VEGF agent (aflibercept, bevacizumab, or ranibizumab). Demonstrated response to prior anti-VEGF treatment since diagnosis. BCVA of 35 letters or better.

Exclusion Criteria: History, within 6 months prior to screening, of any of the following: myocardial infarction, any cardiac event requiring hospitalization, treatment for acute congestive heart failure, transient ischemic attack, or stroke. Uncontrolled hypertension, diabetes mellitus or IOP. Chronic renal disease. Abnormal liver function. Women who are pregnant or lactating.

Information: vsmith@graybug.com

Study: Study to Assess the Efficacy and Safety of Brolucizumab 6mg Compared to Aflibercept 2 mg in a Treat-to-control Regimen (TALON)

ClinicalTrials.gov Identifier: NCT04005352

Sponsor: Novartis Pharmaceuticals

Purpose: The study is a 64-week randomized, double-masked, multi-center, active-controlled, two-arm study in patients with nAMD (neovascular age related macular degeneration) who have not previously received anti-VEGF (vascular endothelial growth factor) treatment. Patients who consent will undergo screening assessments to evaluate their eligibility based on the inclusion and exclusion criteria.

Design: Randomized, parallel assignment, triple masking

Number of Patients: 692

Inclusion Criteria: Signed informed consent must be obtained prior to participation in the study. Male or female patients ≥50 years of age at screening who are treatment naïve. Active choroidal neovascularization (CNV) secondary to AMD that affects the central subfield, including retinal angiomatous proliferation (RAP) with a CNV component, confirmed by presence of active leakage from CNV seen by fluorescein angiography and sequelae of CNV, eg pigment epithelial detachment (PED), subretinal or sub-retinal pigment epithelium (sub-RPE) hemorrhage, blocked fluorescence, macular edema (study eye). Presence of intraretinal fluid (IRF) or subretinal fluid (SRF) that affects the central subfield, as seen by Spectral Domain Optical Coherence Tomography (SD-OCT) (study eye). Best-corrected visual acuity (BCVA) score between 83 and 38 letters, inclusive, using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts at both screening and baseline visit (study eye).

Exclusion Criteria: Ocular conditions/disorders at screening or baseline which could, in the opinion of the investigator, prevent response to study treatment or may confound interpretation of study results, compromise visual acuity or require planned medical or surgical intervention during the first 12-month study period, structural damage of the fovea, atrophy or fibrosis at the center of the fovea (study eye). Any active intraocular or periocular infection or active intraocular inflammation, at screening or baseline (study eye). Uncontrolled glaucoma defined as intraocular pressure (IOP) >25 mmHg on medication, or according to investigator's judgment, at screening or baseline (study eye). Ocular treatments: previous treatment with any anti-vascular endothelial growth factor (VEGF) drugs or investigational drugs, intraocular or periocular steroids, macular laser photocoagulation, photodynamic therapy, vitreoretinal surgery, intraocular surgery (study eye). Stroke or myocardial infarction during the 6-month period prior to baseline. Systemic anti-VEGF therapy at any time.

Information: novartis.email@novartis.com

Study: A Clinical Effectiveness Study Examining the Efficacy and Safety of ONS-5010 in Subjects with Neovascular Age-related Macular Degeneration (AMD)

ClinicalTrials.gov Identifier: NCT03834753

Sponsor: Outlook Therapeutics, Inc.

Purpose: This research study will examine the safety and effectiveness of ONS-5010 in participants with AMD. The goal is to prevent vision loss by evaluating the effectiveness of ONS-5010 as compared with ranibizumab.

Design: Randomized, parallel assignment, double masking

Number of Patients: 220

Inclusion Criteria: Active primary or recurrent Subfoveal Choroidal Neovascularization lesions secondary to Age-related macular degeneration (AMD) in the study eye; Best corrected visual acuity of 25-60 letters read (20/60 to 20/320 Snellen equivalent). Study eye must: have active leakage on fluorescein angiogram involving the fovea, have edema involving the fovea, be free of foveal scarring, be free of foveal atrophy.

Exclusion Criteria: Previous use of anti-VEGF or bevacizumab within 6 weeks; Previous subfoveal focal laser photocoagulation in the study eye; Laser photocoagulation (juxtafoveal or extrafoveal) in the study eye within 1-month preceding randomization; Any concurrent intraocular condition in the study eye that may require medical or surgical intervention or contribute to vision loss within 1 year; Active intraocular inflammation (grade trace or above) in the study eye; Current vitreous hemorrhage in the study eye; Polypoidal choroidal vasculopathy (PCV) confirmed by indocyanine green angiography (ICGA); History of idiopathic or autoimmune-associated uveitis in either eye; Infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye; Uncontrolled glaucoma in the study eye (defined as intraocular pressure ≥30 mmHg despite treatment with anti-glaucoma medication); Premenopausal women not using adequate contraception; Current treatment for active systemic infection; Known allergy to any component of the study drug or history of allergy to fluorescein or indocyanine green, not amenable to treatment.

Information: ClinicalStudies@outlooktherapeutics.com

Study: Post Intravitreal Injection Topical NSAID vs Patching

ClinicalTrials.gov Identifier: NCT03918590

Sponsor: The New York Eye & Ear Infirmary

Purpose: A prospective randomized trial, to evaluate postinjection comfort measures comparing topical NSAID (nepafenac 0.3% suspension) and patching.

Design: Randomized, parallel assignment

Number of Patients: 60

Inclusion Criteria: 18 years of age or older; already scheduled for anti-VEGF injection based on standard of care for disease process. Ability to provide written informed consent; Capable of complying with study protocol. Volunteer written informed consent with the understanding that consent may be withdrawn by the subject at any time without prejudice to future care.

Exclusion Criteria: History of past intraocular injection of steroid medication. Experiencing baseline eye pain; monocular; nonstudy eye with VA<20/100. Unwilling or unable to follow or comply with all study related procedures.

Study: Efficacy and Safety Trial of Conbercept Intravitreal Injection for Neovascular Age-related Macular Degeneration (PANDA-1)

ClinicalTrials.gov Identifier: NCT03577899

Sponsor: Chengdu Kanghong Biotech Co., Ltd.

Purpose: The purpose of this clinical study is to evaluate the efficacy and safety of 2 different levels of conbercept intravitreal (IVT) injection as compared to the approved vascular endothelial growth factor (VEGF) antagonist active control, aflibercept intravitreal injection (2.0 mg/eye, Eylea), in subjects with neovascular AMD.

Design: Randomized, parallel assignment, quadruple masking

Number of Patients: 1,140

Inclusion Criteria: Men and women ≥50 years of age at the screening visit; Females must be at least 1 year postmenopausal, or surgically sterilized, or, if of childbearing potential, must have a negative pregnancy test at the screening visit; Women of childbearing potential must agree to use a highly effective method of contraception throughout the study. Have received no previous treatment for neovascular AMD, including laser photocoagulation and/or photodynamic therapy (PDT) and/or IVT VEGF antagonists (treatment naïve) and; Have active subfoveal choroidal neovascularization (CNV) lesions secondary to AMD (including polypoidal choroidal vasculopathy (PCV)) evidenced by subfoveal fluorescein angiography (FA) leakage, or definite subfoveal fluid by SD-OCT in the study eye at screening; Have a ETDRS BCVA letter score of 78 to 25 in the study eye at screening; Are willing and able to sign the study written informed consent form (ICF).

Exclusion Criteria: Have had any prior ocular or systemic treatment (investigational or approved) or surgery for the treatment of neovascular AMD in the study eye except dietary supplements or vitamins; Have participated as a subject in any interventional clinical trial within 1 month (30 days) prior to baseline visit; Have a subretinal hemorrhage that is either 50% or more of the total lesion area, or blood is under the fovea and is 1 or more disc areas in size (greater than 2.5 mm2) in the study eye at screening; Have any retinal pigment epithelial tears or rips in the study eye at screening or upon examination at baseline; Have any vitreous hemorrhage in the study eye upon examination at baseline or history of vitreous hemorrhage within 8 weeks prior to screening; Have any other cause of CNV; Have had prior pars plana vitrectomy in the study eye; Have presence of a full thickness macular hole at screening or upon examination at baseline or a history of a full thickness macular hole in the study eye; Have prior trabeculectomy or other filtration surgery in the study eye; Have uncontrolled glaucoma; Have active intraocular inflammation in either eye at screening or upon examination at baseline or a history of uveitis in either eye; Have aphakia or pseudophakia with absence of posterior capsule (unless it occurred as a result of yttrium aluminum garnet (YAG) posterior capsulotomy) in the study eye; Significant media opacities, including cataract, in the study eye that, in the opinion of the Investigator, could require either medical or surgical intervention during the study period; Have any use of long acting intraocular steroids, including implants, within 6 months prior to day 1, baseline; Have any known allergy to povidone iodine or known serious allergy to the fluorescein sodium for injection in angiography; Any history of known contraindications indicated in the Food and Drug Administration (FDA)-approved label for the active control; If female, be pregnant (positive urine pregnancy test at screening) or breastfeeding.

Information: panda@cnkh.com

Study: Efficacy and Safety Trial of Conbercept Intravitreal Injection for Neovascular Age-related Macular Degeneration (PANDA-2)

ClinicalTrials.gov Identifier: NCT03630952

Sponsor: Chengdu Kanghong Biotech Co., Ltd.

Design: Randomized, parallel assignment, quadruple masking

Number of Patients: 1,140

Inclusion Criteria: Men and women ≥50 years of age at the screening visit; females must be at least 1 year postmenopausal, or surgically sterilized, or, if of childbearing potential, must have a negative pregnancy test at the screening visit; o women of childbearing potential must agree to use a highly effective method of contraception throughout the study. Have received no previous treatment for neovascular AMD, including laser photocoagulation and/or photodynamic therapy (PDT) and/or IVT VEGF antagonists (treatment naïve) and; Have active subfoveal choroidal neovascularization (CNV) lesions secondary to AMD (including polypoidal choroidal vasculopathy (PCV)) evidenced by subfoveal fluorescein angiography (FA) leakage, or definite subfoveal fluid by SD-OCT in the study eye at screening; Have a ETDRS BCVA letter score of 78 to 25 in the study eye at screening; Are willing and able to sign the study written informed consent form (ICF).

Exclusion Criteria: Have had any prior ocular or systemic treatment (investigational or approved) or surgery for the treatment of neovascular AMD in the study eye except dietary supplements or vitamins; Have participated as a subject in any interventional clinical trial within 1 month (30 days) prior to baseline visit; Have a subretinal hemorrhage that is either 50% or more of the total lesion area, or blood is under the fovea and is 1 or more disc areas in size (greater than 2.5 mm2) in the study eye at screening; Have any retinal pigment epithelial tears or rips in the study eye at screening or upon examination at baseline; Have any vitreous hemorrhage in the study eye upon examination at baseline or history of vitreous hemorrhage within 8 weeks prior to screening; Have any other cause of CNV; Have had prior pars plana vitrectomy in the study eye; Have presence of a full thickness macular hole at screening or upon examination at baseline or a history of a full thickness macular hole in the study eye; Have prior trabeculectomy or other filtration surgery in the study eye; Have uncontrolled glaucoma; Have active intraocular inflammation in either eye at screening or upon examination at baseline or a history of uveitis in either eye; Have aphakia or pseudophakia with absence of posterior capsule (unless it occurred as a result of yttrium aluminum garnet (YAG) posterior capsulotomy) in the study eye. Significant media opacities, including cataract, in the study eye that, in the opinion of the Investigator, could require either medical or surgical intervention during the study period; Have any use of long acting intraocular steroids, including implants, within 6 months prior to day 1, baseline; Have any known allergy to povidone iodine or known serious allergy to the fluorescein sodium for injection in angiography; any history of known contraindications indicated in the Food and Drug Administration (FDA)-approved label for the active control; if female, be pregnant (positive urine pregnancy test at screening) or breastfeeding.

Information: panda@cnkh.com

Study: A Study to Assess the Safety, Tolerability and Effectiveness of MT-0814 for the Treatment of Age-related Macular Degeneration

ClinicalTrials.gov Identifier: NCT03869684

Sponsor: Senju Pharmaceutical Co., Ltd.

Purpose: Age-related macular degeneration (AMD) is the leading cause of blindness among adults in North America. The current standard of care for patients with wet AMD is anti-VEGF therapy which must be administered by an injection into the eye every 4-8 weeks. MT-0814 is being developed for the treatment of patients with exudative AMD, and could offer an alternative, safer and less burdensome therapy.

Design: Randomized, parallel assignment, quadruple masking

Number of Patients: 35

Inclusion Criteria: Must agree to sign informed consent form, and to comply with protocol requirements, including study visits. Must have clear optic media in the study eye that is capable of producing high-quality fundus images.

Exclusion Criteria: Has active CNV due to causes other than AMD in the study eye. Has retinal vascular disease or retinal degeneration other than AMD in the study eye. Has had intraocular surgery, cataract surgery or LASIK surgery on the study eye within 90 days prior to the study. Has had yttrium aluminum garnet (YAG) laser capsulotomy on the study eye within 30 days prior to the study. Has active inflammation, infection, or other severe ocular disease in either eye. Has aphakia in the study eye. Has uncontrolled glaucoma or a history of previous glaucoma filter surgery in either eye. Is a contact lens wearer and is unable to discontinue their use in both eyes for the duration of the study. Has a serious allergy to or experienced a prior significant adverse reaction to fluorescein angiography (FA) or indocyanine green angiography (ICGA). Has participated in any other clinical trial and/or has taken any investigational drug or product within 90 days prior to the study.

Information: sara.gonzales@ppdi.com

Study: AAVCAGsCD59 for the Treatment of Wet AMD

ClinicalTrials.gov Identifier: NCT03585556

Sponsor: Hemera Biosciences

Purpose: Patients with treatment naive wet AMD will receive an intravitreal anti-VEGF injection at day 0 followed by an intravitreal injection of AAVCAGsCD59 at day 7. Patients will be followed monthly through Month 12 and receive an intravitreal anti-VEGF injection as needed based on an increase in central subfoveal thickness (CST) of >50 micrometers on OCT from day 0, new subretinal hemorrhage on clinical exam, and/or loss of 10 or more ETDRS letters from the previous month exam.

Design: Single group, no masking

Number of Patients: 25

Inclusion Criteria: Men or women 50 years of age or older. Treatment naive Wet AMD with no evidence of subretinal fibrosis under the fovea. Presence of intraretinal and/or subretinal fluid on OCT. Best corrected visual acuity (BCVA) Snellen equivalent 20/25 to 20/400 in the study eye using ETDRS charts at a starting distance of 4m. Adequate pupillary dilation to permit ocular examination and testing. Ability and willingness to return for all scheduled visits and assessments. Understand and comply with the clinical protocol and provide written informed consent prior to any study-related procedure. All fertile men must be willing to use barrier contraception during the study. Women of childbearing potential must have a negative pregnancy test and agree to use effective contraception for the duration of the trial. A woman of childbearing potential is defined as any female who has had menses within the last 2 years or has not undergone a hysterectomy or surgical sterilization.

Exclusion Criteria: Wet AMD secondary to non-AMD etiologies. Subretinal hemorrhage that interferes with the ability to adequately measure visual acuity or follow retinal or subretinal fluid collection on OCT. Serous pigment epithelial detachment (PED) that is >50% of the CNV lesion, >400µm in any diameter, or presence of an RPE tear. Presence of polypoidal choroidal vasculopathy (PCV), retinal angiomatous proliferation (RAP), central serous retinopathy, or symptomatic vitreomacular adhesion. Previous macular laser photocoagulation for CNV, photodynamic therapy (PDT), ocular radiation, or subretinal surgery for CNV in the study eye. History of conditions in the study eye which might alter visual acuity or interfere with study testing including clinically significant macular edema, central retinal vein occlusion, macular branch retinal vein occlusion, and optic neuropathy. Active uncontrolled glaucoma with IOP>30 mmHg despite treatment with glaucoma medications, cup-to-disc ratio of >0.9, visual field defects secondary to glaucoma that involve the macula, and optic atrophy from glaucoma. Likely candidate for intraocular surgery (including cataract surgery) in the study eye during the clinical trial. Acute or chronic infection in the study eye. History of uveitis unrelated to eye surgery in the study eye or opposite eye requiring treatment with topical corticosteroids or systemic immunosuppression within 24 months of enrollment. Any contraindication to intravitreal injection. Use intravitreal (study eye) corticosteroids within 3 months prior to screening. Any of the following underlying systemic diseases: Unstable or severe cardiovascular disease, eg, congestive heart failure (New York Heart Association Functional class III or IV), myocardial infarction within 6 months, ventricular tachyarrhythmias requiring ongoing treatment, unstable angina, or critical limb ischemia; Cerebrovascular disease within 12 months prior to screening that impairs the patient's ability to participate in the clinical trial; Dementia or neurodegenerative disease (eg, Alzheimer's disease, Parkinson's disease) of a level that prevents adequate evaluation of the subject during the study; Has an active malignancy or is currently undergoing treatment for an active malignancy at screening, or has a history of malignancy that precludes completion of this 12-month study; Immunocompromised conditions and/or need for immunosuppressive therapy. Any significant poorly controlled illness that would preclude study compliance and follow-up. Current or prior use of any medication known to be toxic to the retina or optic nerve including, but not limited, to chloroquine/hydrochloroquine, deferoxamine, phenothiazines and ethambutol. Previous treatment with any ocular or systemic gene transfer product. Received any investigational product within 120 days prior to screening. Any psychological, familial, sociological, geographical, or other condition that would preclude study compliance and follow-up.

Information: info@hemerabiosciences.com

Study: A Study to Evaluate the Efficacy and Safety of Faricimab in Participants with Neovascular Age-Related Macular Degeneration (TENAYA)

ClinicalTrials.gov Identifier: NCT03823287

Sponsor: Hoffman-La Roche

Purpose: This study will evaluate the efficacy, safety, durability, and pharmacokinetics of faricimab administered at intervals as specified in the protocol, compared with aflibercept once every 8 weeks (Q8W), in participants with neovascular age-related macular degeneration (nAMD).

Design: Randomized, parallel assignment, triple masking

Number of Patients: 640

Inclusion Criteria: Treatment-naïve choroidal neovascularization (CNV) secondary to age-related macular degeneration (nAMD) in the study eye; ability to comply with the study protocol, in the investigator's judgment; for women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use acceptable contraceptive measures that result in failure rate <1% per year during the treatment period and for at least 3 months after the final dose of study treatment.

Exclusion Criteria: Uncontrolled blood pressure, defined as systolic blood pressure >180 millimeters of mercury (mmHg) and/or diastolic blood pressure >100 mmHg while a patient is at rest on day 1; pregnancy or breastfeeding, or intention to become pregnant during the study; CNV due to causes other than AMD in the study eye; any history of macular pathology unrelated to AMD affecting vision or contributing to the presence of intraretinal or subretinal fluid in the study eye; any concurrent intraocular condition in the study eye that, in the opinion of the investigator, could either reduce the potential for visual improvement or require medical or surgical intervention during the study; uncontrolled glaucoma in the study eye; any prior or concomitant treatment for CNV or vitreomacular-interface abnormalities in the study eye; prior IVT administration of faricimab in either eye; history of idiopathic or autoimmune-associated uveitis in either eye; active ocular inflammation or suspected or active ocular or periocular infection in either eye.

Information: global-roche-genentech-trials@gene.com

Study: A Study to Evaluate the Efficacy and Safety of Faricimab in Participants with Neovascular Age-Related Macular Degeneration (LUCERNE)

ClinicalTrials.gov Identifier: NCT03823300

Sponsor: Hoffman-La Roche

Design: Randomized, parallel assignment, triple masking

Number of Patients: 640

Information: global-roche-genentech-trials@gene.com

Study: Intense Treatment Regimen With Intravitreal Aflibercept Injection (I-TRAP)

ClinicalTrials.gov Identifier: NCT03594461

Sponsor: Vitreous-Retina-Macula Consultants of New York

Purpose: This study will evaluate the safety and efficacy of intense dosing for a limited period in patients who demonstrate refractory disease on monthly IAI. Patients will be followed for 52 weeks.

Design: Randomized, parallel assignment, no masking

Number of Patients: 30

Inclusion Criteria: Age ≥50 years; choroidal neovascularization related to age-related macular degeneration; prior treatment with any anti-VEGF agent for ≥12 months; prior treatment with at least 5 consecutive IAI at baseline with an average treatment interval of maximum 35 days; presence of foveal fluid at most recent clinical visit occurring 30 (+/-5) days following the most recent IAI; willing and able to comply with clinic visits and study-related procedures; provide signed informed consent.

Exclusion Criteria: Monocular patients; patients with a previous history of macular thermal laser or PDT; confounding ocular conditions in the study eye that may affect interpretation of OCT, BCVA or assessment of macular appearance (eg, cataract, epiretinal membrane, retinal vascular occlusive disease); intraocular surgery (including cataract surgery) in the study eye within 2 months preceding baseline; history of vitrectomy surgery, submacular surgery, or other surgical intervention for AMD in the study eye; active intraocular inflammation (grade trace or above) in the study eye; history of rhegmatogenous retinal detachment or macular hole (Stage 3 or 4) in the study eye; uncontrolled glaucoma in the study eye (defined as IOP ≥30 mmHg despite treatment with anti-glaucoma medication); history of cerebral vascular accident, myocardial infarction, transient ischemic attacks within 3 months of study enrollment; patients on systemic anti-VEGF treatment; pregnant or breastfeeding women; sexually active men* or women of childbearing potential** who are unwilling to practice adequate contraception prior to the initial dose/start of the first treatment, during the study, and for at least 3 months after the last dose. Adequate contraceptive measures include stable use of oral contraceptives or other prescription pharmaceutical contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device; bilateral tubal ligation; vasectomy; condom plus contraceptive sponge, foam, or jelly, or diaphragm plus contraceptive sponge, foam, or jelly. *Contraception is not required for men with documented vasectomy. **Postmenopausal women must be amenorrheic for at least 12 months in order not to be considered of childbearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.

Information: sariahpersaud@vrmny.com, rsalgado@vrmny.com

Study: Exploratory Study to Investigate the Bioactivity, Ocular and Systemic Safety, Tolerability, and Pharmacokinetics Following Single and Multiple Intravitreal Administrations of KSI-301 in Subjects With wAMD, DME and RVO

ClinicalTrials.gov Identifier: NCT03790852

Sponsor: Kodiak Sciences, Inc.

Purpose: This is a Phase 1b open-label study to assess the bioactivity, ocular and systemic safety, tolerability, and pharmacokinetics of repeated injections of KSI-301 at 2 dose levels: 2.5 mg and 5 mg.

Design: Randomized, parallel assignment, no masking

Number of Patients: 50

Inclusion Criteria: Wet AMD Cohort: Treatment naïve wet age-related macular degeneration involving the fovea. A lesion area <30 mm2 (12 disc areas) of any lesion type. BCVA ETDRS letter score ≤78 and ≥23 (⁓20/25 to ⁓20/320 Snellen equivalent) in the study eye. Decrease in vision in the study eye determined by the investigator to be primarily the result of wet AMD.

Exclusion Criteria: Wet AMD Cohort: Choroidal neovascularization due to causes other than age-related macular degeneration in the study eye. Geographic atrophy and/or subretinal fibrosis involving the fovea of the study eye. Prior intravitreal anti-VEGF therapy in the study eye.

Information: jehrlich@kodiak.com, pablovm@kodiak.com

Study: Study of Safety and Efficacy of Brolucizumab 6 mg Dosed Every 4 Weeks Compared to Aflibercept 2 mg Dosed Every 4 Weeks in Patients with Retinal Fluid Despite Frequent Anti-VEGF Injections (MERLIN)

ClinicalTrials.gov Identifier: NCT03710564

Sponsor: Novartis Pharmaceuticals

Purpose: The purpose of this study is to compare safety and efficacy of brolucizumab 6 mg dosed every 4 weeks to aflibercept 2 mg dosed every 4 weeks in those nAMD patients with retinal fluid despite frequent anti-Vascular Endothelial Growth Factor (VEGF) injections.

Design: Multicenter, randomized, double-masked

Number of Patients: 500

Inclusion Criteria: Sign informed consent; diagnosis of wet age-related macular degeneration (AMD); currently receiving anti-VEGF injections.

Exclusion Criteria: Active infection or inflammation in either eye; significant fibrosis in the study eye; recent ocular surgery; uncontrolled glaucoma; previous treatment with brolucizumab in the study eye; use of medications as specified in the protocol; pregnant, nursing; of child-bearing potential unless using highly effective method of contraception; other protocol-defined inclusion/exclusion criteria may apply.

Information: novartis.email@novartis.com

Study: ADVM-022 Gene Therapy for Wet AMD (OPTIC)

ClinicalTrials.gov Identifier: NCT03748784

Sponsor: Adverum Biotechnologies, Inc.

Purpose: ADVM-022 (AAV.7m8-aflibercept) is a gene therapy product developed for the treatment of neovascular (wet) age-related macular degeneration (wet AMD). Wet AMD is a serious condition and the leading cause of blindness in the elderly. The available therapies for treating wet AMD require lifelong intravitreal (IVT) injections every 4-12 weeks to maintain efficacy. A one-time administration of ADVM-022 has the potential to treat wet AMD by providing durable expression of therapeutic levels of intraocular anti-VEGF protein (aflibercept) and preserving the vision of patients. ADVM-022 is designed to reduce the current treatment burden and the adverse events (AEs) associated with chronic IVT injections.

Design: Nonrandomized, sequential assignment, open label

Number of Patients: 18

Inclusion Criteria: Age ≥50; diagnosis of neovascular (wet) AMD; BCVA ETDRS Snellen equivalent between ≤20/80 and ≥20/320 for the first (sentinel) patient in each cohort followed by BCVA ETDRS Snellen equivalent between ≤20/40 and ≥20/320 for the rest of the cohort; subjects must be under active anti-VEGF treatment for wAMD and received a minimum of 2 injections within 4 months prior to screening; up to a maximum of 6 injections within 8 months prior to screening; demonstrated a meaningful response to anti-VEGF therapy; willing and able to provide consent.

Exclusion Criteria: History of retinal disease in the study eye other than wet AMD; fibrosis or atrophy, retinal epithelial tear in the center of the fovea in the study eye, or any condition preventing visual acuity improvement; history of retinal detachment (with or without repair) in the study eye; history of vitrectomy, trabeculectomy, or other filtration surgery in the study eye; uncontrolled glaucoma in the study eye; any prior treatment with photodynamic therapy or retinal laser for the treatment of wet AMD and any previous therapeutic radiation in the region of the study eye; any previous intraocular or periocular surgery on the study eye within 6 months; acute coronary syndrome, myocardial infarction or coronary artery revascularization, CVA, TIA in the last 6 months; uncontrolled hypertension defined as average SBP ≥160 mmHg or an average DBP ≥100 mmHg.

Information: stong@adverum.com

Study: A Phase III Study to Evaluate the Port Delivery System Implant with Ranibizumab Compared with Monthly Ranibizumab Injections in Participants with Wet Age-Related Macular Degeneration (Archway)

ClinicalTrials.gov Identifier: NCT03677934

Sponsor: Hoffman-La Roche

Purpose: Study GR40548 is a Phase III, randomized, multicenter, open-label (visual assessor [VA]-masked), active-comparator study designed to assess the efficacy, safety, and pharmacokinetics (PK) of 100mg/ml delivered via the Port Delivery System (PDS) compared with ranibizumab intravitreal injections at 0.5 mg (10 mg/mL) in participants with neovascular age-related macular degeneration (nAMD).

Design: Randomized, parallel assignment, single masking

Number of Patients: 360

Inclusion Criteria: Age ≥50 years, at time of signing Informed Consent Form. Initial diagnosis of exudative neovascular age-related macular degeneration (nAMD) within 9 months prior to the screening visit. Previous treatment with at least 3 anti-vascular endothelial growth factor (anti-VEGF) intravitreal injections for nAMD per standard of care within 6 months prior to the screening visit. Demonstrated response to prior anti-VEGF intravitreal treatment since diagnosis. Best-corrected visual acuity (BCVA) of 34 letters or better.

Exclusion Criteria: Subfoveal fibrosis or subfoveal atrophy in study eye. Subretinal hemorrhage that involves the center of the fovea in study eye. History of vitrectomy surgery, submacular surgery, or other surgical intervention for AMD in study eye. Prior treatment with Visudyne, external-beam radiation therapy, or transpupillary thermotherapy in study eye. Previous intraocular device implantation in study eye. Previous laser (any type) used for AMD treatment in study eye. Treatment with anti-VEGF agents other than ranibizumab within 1 month prior to the randomization visit in either eye. Prior participation in a clinical trial involving anti-VEGF drugs within 6 months prior to the randomization visit, other than ranibizumab in either eye. CNV due to other causes, such as ocular histoplasmosis, trauma, or pathologic myopia in either eye. Uncontrolled blood pressure. History of stroke within the last 3 months prior to informed consent. Uncontrolled atrial fibrillation within 3 months of informed consent. History of myocardial infarction within the last 3 months prior to informed consent. History of other disease, metabolic dysfunction, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of ranibizumab or placement of the Implant and that might affect interpretation of the results of the study or renders the participant at high risk of treatment complications in the opinion of the investigator. Current systemic treatment for a confirmed active systemic infection. Chronic use of oral corticosteroids. Active cancer within 12 months of randomization. Previous participation in any non-ocular (systemic) disease studies of investigational drugs within 1 month preceding the informed consent (excluding vitamins and minerals).

Information: global-roche-genentech-trials@gene.com

Study: Efficacy of Biweekly Ranibizumab (0.5 mg) for Exudative Macular Degeneration Retinal Edema Refractory to Anti-VEGF

ClinicalTrials.gov Identifier: NCT03071055

Sponsor: Southeast Clinical Research Associates, LLC

Purpose: This is a 24 week open label study to assess the efficacy of biweekly ranibizumab for patients with retinal fluid due to exudative macular degeneration refractory to monthly therapy.

Design: Nonrandomized, single group assignment, open label

Number of Patients: 20

Inclusion Criteria: Age >50 years, exudative age related macular degeneration in study eye involving the fovea, Best Corrected Visual Acuity (by ETDRS) letter score in study eye of <85 and >24 (approximate Snellen equivalent 20/20 to 20/320), persistent intraretinal or subretinal fluid on SD OCT despite a minimum of 5 intravitreal anti-VEGF injections administered every 4-6 weeks in the in the 6 months preceding enrollment in the study eye, at least 30 days from last intravitreal anti-VEGF injection in the study eye.

Exclusion Criteria: Patient who are receiving systemic anti-VEGF or proangiogenic therapy, patients on chronic high doses corticosteroid therapy (>than 10 mg of oral prednisone or equivalent greater than 10 days), patients on chronic immunosuppressant therapy, patients on drugs known to have toxic side effects on the retina, eg, hydroxychloroquine, history of intravitreal corticosteroids in study eye within 4 months of baseline, uncontrolled hypertension (defined as systolic >180 mm Hg and/or diastolic >100 mm Hg while patient is sitting), history of stroke or APTC event in the previous year, any intraocular surgery in study eye within 90 days of baseline, presence of vitreomacular traction in study eye, presence of significant epiretinal proliferation in study eye, evidence of active infection in either eye, uncontrolled glaucoma in the study eye defined as a pressure >25 mmHg on maximal medical therapy.

Information: aprice@ceenta.com, ana@ceenta.com

Study: DECO: Open-Label Study of Intravitreal ICON-1 in Patients with Choroidal Neovascularization Secondary to Age-related Macular Degeneration (AMD)

ClinicalTrials.gov Identifier: NCT03452527

Sponsor: Iconic Therapeutics, Inc.

Purpose: The purpose of this study is to evaluate the safety and effects of repeated intravitreal injections of ICON-1 0.6 mg administered as maintenance therapy or in combination with aflibercept in patients with wet macular degeneration.

Design: Randomized, parallel assignment, open label

Number of Patients: 20

Inclusion Criteria: Males or females of any race, ≥50 years of age, active primary CNV secondary to AMD in the study eye.

Exclusion Criteria: Any prior treatment of CNV or advanced AMD in the study eye, except for dietary supplements or vitamins, any intraocular or ocular surface surgery (including cataract surgery and laser procedures) in the study eye within 3 months, vitrectomy in the study eye.

Information: clinicaltrials@iconictherapeutics.com

Study: ZEBRA: Ziv-aflibercept Efficacy in Better Regulating AMD

ClinicalTrials.gov Identifier: NCT03423823

Sponsor: Kapil Kapoor

Purpose: This is a randomized, open-label, interventional, controlled study to determine the effects of Zaltrap on Neovascularized Wet Macular Degeneration as compared to the control anti-vascular endothelial growth factor ("anti-VEGF") injections (bevacizumab, ranibizumab, or aflibercept).

Design: Randomized, parallel assignment, no masking

Number of Patients: 100

Inclusion Criteria: Are age 50-99; have neovascular AMD with an eye undergoing maintenance treatment with 1 or more of the following anti-VEGF drugs: bevacizumab, ranibizumab, or aflibercept; have an eye undergoing treatment that is of low visual potential (20/200 Snellen equivalent or worse) and the contralateral eye must have better visual potential; are willing and able to provide signed informed consent and willing to undertake all scheduled study-related assessments, visits, and treatments; have received an intravitreal injection of 1 of the drugs listed above within 120 days of day 1 of the trial. Both males and females will be enrolled.

Exclusion Criteria: Active intraocular inflammation or infection; history of vitreous hemorrhage within 3 months prior to day 1 of the study; Uncontrolled ocular hypertension or glaucoma in the study eye (defined as IOP >25 mmHg or a Cup to Disc ratio >0.8 despite treatment with anti-glaucoma medication) or any such condition which the investigator feels may warrant a glaucoma filtering surgery during the study; history of stroke within the last 3 months prior to day 1 of the study; History of myocardial infarction within the last 3 months prior to day 1 of the study; Undergone intraocular surgery or laser treatments within the last 3 months; significant epiretinal membrane (ERM) or vitreomacular traction (VMT) causing distortion of macular anatomy; No use of ocular corticosteroids within the last 6 months and no use of systemic corticosteroids at a dose of >10 mg/day; Not have active malignancies within the last 12 months except appropriately treated carcinoma in situ of the cervix, melanoma, and prostate cancers treated with a curative intent; Inability to comply with study or follow-up procedures; Women who may become pregnant or lactating or intend to become pregnant during the study; Women who are of childbearing potential, including women who have had tubal ligation, must have a blood test within 21 days prior to day 1 of the study. A woman is considered to not be of childbearing potential if she is postmenopausal or has undergone hysterectomy and/or bilateral oophorectomy. Postmenopausal is defined as 12 consecutive months with no menses without an alternative medical cause.

Information: research@wagnerretina.com

Study: Short-term Clinical Effects of Intravitreal Aflibercept Injection 2.0 mg as a Predictor of Long-Term Results

ClinicalTrials.gov Identifier: NCT01657669

Sponsor: Retina Research Institute, LLC

Purpose: This is an open label study to evaluate 2.0 mg intravitreal aflibercept injection administered in subject who have active choroidal neovascularization due to Age Related Macular Degeneration (AMD).

Design: Single Group Assignment, No Masking, Treatment

Number of Patients: 22

Inclusion Criteria: Ability to provide written informed consent and comply with study assessments for the full duration of the study. Age 50 years and above. Choroidal neovascularization secondary to AMD with central retinal thickness greater than or equal to 300 um. Best corrected visual acuity in the study eye between 20/40 and 20/400 using an ETDRS chart.

Exclusion Criteria: Pregnancy (positive urine pregnancy test) or lactation. Premenopausal women not using adequate contraception. The following are considered effective means of contraception: surgical sterilization or use of oral contraceptives, barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel, an IUD, or contraceptive hormone implant or patch. Participation in a study or an investigational drug or device within the past 30 days prior to enrolling in the study. Presence of significant subfoveal fibrosis or atrophy. Previously treated subjects: Prior treatment with anti-VEGF therapy in the study eye within 28 days of baseline More than 6 prior treatments with anti-VEGF therapy in the study eye within 1 year. Prior treatment with PDT within the past 3 months or more than 2 prior PDT treatments. Prior treatment with intravitreal aflibercept injection Prior treatment with triamcinolone in the study eye within 6 months of baseline. Prior treatment with dexamethasone in the study eye within 30 days prior to baseline. Intraocular surgery (including cataract surgery) in the study eye within 2 months preceding baseline. History of vitrectomy surgery, submacular surgery, or other surgical intervention for AMD in the study eye. Active intraocular inflammation (grade trace or above) in the study eye. Current vitreous hemorrhage in the study eye. History of rhegmatogenous retinal detachment or macular hole (Stage 3 or 4) in the study eye. Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye. Uncontrolled glaucoma in the study eye (defined as IOP greater than or equal to 30 mmHg despite treatment with anti-glaucoma medication). History of cerebral vascular accident, myocardial infarction, transient ischemic attacks within 3 months of study enrollment. History of allergy to fluorescein, ICG or iodine, not amenable to treatment. History of retinal pigment epithelial tear or rip.

Study: NEAMES: Episcleral Brachytherapy for the Treatment of Wet AMD

ClinicalTrials.gov Identifier: NCT02988895

Sponsor: Salutaris Medical Devices, Inc.

Purpose: This is a prospective, single-arm, open-label, safety, usability and tolerability trial of Strontium 90 (Sr90) beta radiation episcleral brachytherapy in subjects receiving aflibercept therapy pro re nata (PRN) for the treatment of early neovascular age-related macular degeneration (nAMD) lesions. Secondary aims are to observe clinical outcomes of area of leakage, subretinal fluid, lesion size, visual acuity, and anti-vascular endothelial growth factor (anti-VEGF) treatment burden.

Design: Single Group, No Masking, Treatment

Number of Patients: 20

Inclusion Criteria: Diagnosis of CNV due to nAMD; Male or female aged 50 years or older; Documented continued care for nAMD since diagnosis; Patients must have demonstrated clinical or OCT/angiographic evidence that, in the investigator's opinion, requires treatment with anti-VEGF therapy; BCVA 20/40 - 20/200 Snellen equivalent in study eye; Actively leaking CNV as determined by FA.

Exclusion Criteria: Females of child-bearing potential (defined as <2 years postmenopausal) CNV other than due to nAMD; Subfoveal lesion hemorrhage obscuring >50% of lesion; CNV lesion with greatest linear dimension >2mm as determined by Intravenous Fluorescein angiography; Presence of subretinal fibrosis in the study eye; Existing Retinal Pigment Epithelial tear; Previous treatment (excluding vitamins) for nAMD in the study eye other than aflibercept anti-VEGF therapy in the last 6 months; A change in anti-VEGF agent in the previous 2 administrations; Anticipate a change to the anti-VEGF agent during the conduct of the study; Previous intraocular surgery in study eye other than for uncomplicated phacoemulsification cataract extraction; Other clinically significant ocular co-morbidity including, but not limited to, optic glaucoma, optic neuropathy of any cause, maculopathy/retinopathy of any cause other than nAMD, and scleritis; Refractive error of -6D or greater (spherical equivalent) or demonstrated myopic degeneration; Media opacity sufficient to preclude adequate fundoscopy, OCT or angiography; Uncontrolled systemic diseases (eg, controlled hypertension is acceptable); Type I or type II diabetes mellitus; Clinically significant previous radiation to the eye; Unable to discontinue anticoagulation or dual anti-platelet therapy for 7 days before and after the study intervention.; Patient unsuitable for IV or local anesthesia; Any contraindication to anti-VEGF, fluorescein, topical and local anesthetics, topical antiseptics, or topical antibiotics to be used during the study; Active ocular or periocular infection or intraocular inflammation; Only eligible eye is the best seeing eye; Any condition which, in the investigators' opinion, would conflict or otherwise prevent the subject from complying with the required procedures, schedule or other study conduct.

Information: mdrew@salutarismd.com

Study: Carbidopa-levodopa in Neovascular AMD

ClinicalTrials.gov Identifier: NCT03022318

Sponsor: Robert W. Snyder, MD, PhD, PC

Design: Nonrandomized, Parallel Assignment, No Masking, Treatment

Number of Patients: 52

Inclusion Criteria: A diagnosis of AMD with choroidal neovascularization (CNV) in 1 eye; not previously treated with anti-VEGF injections; normal or dry AMD of any grade in the second eye; age 50 to 85; willingness to maintain AREDS vitamin supplements throughout the study, or remain off these supplements for the duration of the study, if not taking them prior to the study; signed informed consent.

Exclusion Criteria: Any current use of L-DOPA containing medication or dopamine agonist medication, or any planned use of any of these agents, except for study medication, during the study; concurrent use of monoamine oxidase (MAO) inhibitors; any eye condition, disease, or history of trauma in either eye, which can impair vision, except cataract or cataract surgery; BCVA worse than 20/160 in the better eye; wet AMD in the second eye; neurologic conditions which can impair vision; Parkinson disease; significant orthostatic hypotension, defined as a drop in systolic blood pressure, immediately upon changing from the supine to standing position, of >19 mmHg, or a symptomatic drop in systolic blood pressure, immediately upon changing from the supine to standing position; significant ECG abnormalities, as judged by the investigator; estimated glomerular filtration rate (eGFR) <20 mL/min; Liver enzymes >3x the upper limit of normal; HbA1c >9.0; any other significant lab abnormalities, as judged by the investigator; women of childbearing potential; known retinal hemorrhage; subjects who are not fluent in English.

Information: tcfaganmd@gmail.com; rsnyder781@gmail.com

Study: Dose Ranging Study of Carbidopa-levodopa

ClinicalTrials.gov Identifier: NCT03023059

Sponsor: Robert W. Snyder, MD, PhD, PC

Purpose: The Investigators will evaluate the safety and tolerability of carbidopa-levodopa in patients with Neovascular AMD who are already on treatment with anti-VEGF intraocular injections, and measure the effects on visual acuity, retinal abnormalities due to "wet" AMD, and document the number of anti-VEGF injections required during the study.

Design: Single Group, No Masking, Treatment

Number of patients: 52

Inclusion Criteria: A diagnosis of AMD with choroidal neovascularization (CNV) in 1 eye; not previously treated with anti-VEGF injections, OR on anti-VEGF injections for at least 3 months, and meets criteria for a repeat injection, OR patients, who have completed Study 001, may enter this trial at the point of initiation of the month of treatment with the dose of carbidopa-levodopa, that they received in Study 001; normal or dry AMD of any grade in the second eye; willingness to maintain AREDS vitamin supplements throughout the study, or remain off these supplements for the duration of the study, if not taking them prior to the study; informed consent at baseline.

Exclusion Criteria: Any current use of L-DOPA containing medication or dopamine agonist medication, or any planned use of any of these agents, except for study medication, during the study; concurrent use of monoamine oxidase (MAO) inhibitors; any eye conditions, disease, or history of trauma in either eye, which can impair vision, except cataract or cataract surgery; BCVA worse than 20/60 in the better eye; wet AMD in the second eye; neurologic conditions which can impair vision; Parkinson’s Disease; significant orthostatic hypotension, defined as a drop in systolic blood pressure, immediately upon changing from the supine to standing position, of >19 mmHg, or a symptomatic drop in systolic blood pressure, immediately upon changing from the supine to standing position; significant ECG abnormalities, as judged by the investigator; estimated glomerular filtration rate (eGFR) ,20 ml/min; liver enzymes >3x the upper limit of normal; HbA1C>9.0; any other significant lab abnormalities, as judged by the investigator; women of childbearing potential; known retinal hemorrhage; subjects who are not fluent in English.

Information: tcfaganmd@gmail.com, rsnyder781@gmail.com

Study: IAI-OCTA: A study of OCT-Angiography Analysis Efficacy

ClinicalTrials.gov Identifier: NCT03022292

Sponsor: University of California, Los Angeles

Purpose: This study is utilizing a new, FDA approved, nonstandard of care technology (OCT-Angiography by Optovue) to image and evaluate the treatment outcomes of using standard of care Intravitreal Aflibercept Injections for their approved use in patients diagnosed with neovascular AMD who are naive to previous Anti-VEGF therapies.

Design: Single Group Assignment, No Masking

Number of Patients: 30

Inclusion Criteria: Older than 50; willing to participate in the study and able to follow study criteria and protocol; the study eye is treatment naïve regarding treatment of neovascular AMD; subject is willing and able to comply with clinic visits and study-related procedures; subject is able to provide signed informed consent; subject is able to understand and complete study-related questionnaires; subject is not currently involved with any other clinical study; BCVA with ETDRS Snellen equivalent of 20/400 or better and 20/32 or worse; sufficiently clear media (cornea, anterior chamber, lens, vitreous) for OCT, FA and fundus photography; IOP of 25 mmHg or less in the study eye, with or without use of ocular hypotensive agents; prior focal corticosteroid treatment is allowed, as long as the study eye is not involved. However prior (within 90 days of day 0) or current systemic corticosteroid therapy (oral or intravenous corticosteroid treatment) is not permitted.

Exclusion Criteria: Any prior treatment of neovascular AMD in the eye proposed for enrollment including previous anti-vascular endothelial factor (anti-VEGF) therapy, photodynamic therapy (PDT), radiation therapy, corticosteroid treatment, surgical treatment for CNV, thermal laser treatment, and any other prior intravitreal treatment for neovascular AMD (except minerals and vitamins); known serious allergies to aflibercept, fluorescein dye, Indocyanine Green (ICG), shellfish, drugs for pupillary dilation, topical anesthetic, or sterilizing solution (eg, Betadine Solution); prior or current systemic anti-VEGF therapy; pregnant or breast-feeding women; sexually active men or women of childbearing potential who are unwilling to practice adequate contraception during the study (adequate contraceptive measures include stable use of oral contraceptives or other prescription pharmaceutical contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device [IUD]; bilateral tubal ligation; vasectomy; condom plus contraceptive sponge, foam, or jelly, or diaphragm plus contraceptive sponge, foam, or jelly); contraindication to pupillary dilation in study eye; any condition (including inability to read visual acuity charts, or language barrier) that may preclude subjects ability to comply with the study protocol and requirements; presence of any advanced systemic condition or end-stage disease, such as advanced Alzheimer Syndrome, end-stage cancer, etc., which will likely prevent subject from completing study; previous therapeutic radiation in the region of the study eye; prior retinal pigment epithelial (RPE) tear in study eye; prior ocular surgery (except YAG laser capsulotomy) for study within the past 90 days; anticipated ocular surgery 9except YAG laser capsulotomy) for the next 12 months; prior vitrectomy in the study eye; presence of any causes of CNV and PED other than due to AMD or presence of ocular disease other than AMD affecting study eye, ie presumed ocular histoplasmosis syndrome, android streaks, pathologic myopia.

Information: harmon@jsei.ucla.edu, downey@jsei.ucla.edu

Study: RGX-314 Gene Therapy for Neovascular AMD Trial

ClinicalTrials.gov Identifier: NCT03066258

Sponsor: Regenxbio Inc.

Purpose: To test RGX-314’s ability to treat neovascular AMD.

Design: Nonrandomized, sequential assignment, no masking, treatment

Number of Patients: 18

Inclusion Criteria: Patients ≥50 years with a diagnosis of subfoveal CNV secondary to AMD in the study eye receiving prior intravitreal anti-VEGF therapy; BCVA between ≤20/100 and ≥20/400 (≤53 and ≥19 Early Treatment Diabetic Retinopathy Study [ETDRS] letters) for the first patient in each cohort followed by BCVA between ≤20/63 and ≥20/400 (≤75 and ≥35 ETDRS letters) for the rest of the cohort; history of need for and response to anti-VEGF therapy; response to anti-VEGF at trial entry (assessed by SD-OCT at week 1); must be pseudophakic (status post cataract surgery) in the study eye; AST/ALT <2.5×ULN; TB <1.5×ULN; PT <1.5×ULN; Hb >10 g/dL (males) and >9 g/dL (females); Platelets >100×10^3/µL; eGFR >30 mL/min/1.73 m^2; must be willing and able to provide written, signed informed consent.

Exclusion Criteria: CNV or macular edema in the study eye secondary to any causes other than AMD; any condition preventing visual acuity improvement in the study eye, eg, fibrosis, atrophy, or retinal epithelial tear in the center of the fovea; active or history of retinal detachment in the study eye; advanced glaucoma in the study eye; history of intravitreal therapy in the study eye, such as intravitreal steroid injection or investigational product, other than anti-VEGF therapy, in the 6 months prior to screening; presence of an implant in the study eye at screening (excluding intraocular lens); myocardial infarction, cerebrovascular accident, or transient ischemic attacks within the past 6 months; uncontrolled hypertension (systolic blood pressure [BP] >180 mmHg, diastolic BP >100 mmHg) despite maximal medical treatment.

Information: patientadvocacy@regenxbio.com

Study: Evaluating RXI-109 to Reduce the Progression of Subretinal Fibrosis in Subjects With NVAMD

ClinicalTrials.gov Identifier: NCT02599064

Sponsor: RXi Pharmaceuticals

Purpose: To evaluate the safety, tolerability and clinical activity of RXI-109 administered by intravitreal injection to reduce the progression of subretinal fibrosis in subjects with advanced neovascular age-related macular degeneration.

Design: Safety/efficacy, open label, single group, treatment

Number of Patients: 9

Inclusion Criteria: Subjects presenting with advanced NVAMD in the study eye with BCVA ≤20/200 potentially due to subretinal fibrosis involving the fovea; BCVA ≥20/800 in the contralateral eye and better than the study eye; ≥50 years of age; subfoveal CNV of any type.

Exclusion Criteria: Presence of other causes of CNV including pathologic myopia, ocular histoplasmosis syndrome, angioid streaks, choroidal rupture, and multifocal choroiditis.

Information: clinicaloperations@rxipharma.com

Study: PREVENT: Prophylactic Ranibizumab for Exudative Age-Related Macular Degeneration

ClinicalTrials.gov Identifier: NCT02140151

Sponsor: Southern California Desert Retinal Consultants

Purpose: To determine whether quarterly injections of ranibizumab may prevent eyes with dry age-related macular degeneration from progressing to wet age-related macular degeneration.

Design: Randomized, Efficacy, Parallel Assignment, Single-Blind, Prevention

Number of Patients: 100

Inclusion Criteria: Nonexudative age-related macular degeneration (AMD) in 1 eye (study eye); history of exudative AMD in 1 eye only (fellow eye) diagnosed within 5 years of study enrollment.

Exclusion Criteria: Presence of ocular conditions with increased risk of choroidal neovascularization (CNVM) or pigment epithelial detachment (PED), including presumed ocular histoplasmosis syndrome (POHS), traumatic choroidal rupture, angioid streaks, pathologic myopia (spherical equivalent of ≥-8 diopters or axial length of ≥25 mm), multifocal choroiditis, macular choroidal nevus, polypoidal choroidal vasculopathy (PCV), etc.

Information: mlalezary@desertretina.com

DIABETIC MACULAR EDEMA

Study: Efficacy and Safety of Brolucizumab vs Aflibercept in Patients with Visual Impairment Due to Diabetic Macular Edema (DME)

ClinicalTrials.gov Identifier: NCT03917472

Sponsor: Novartis Pharmaceuticals

Purpose: The purpose of this study is to evaluate the efficacy and safety of brolucizumab vs. aflibercept in the treatment of patients with visual impairment due to DME.

Design: Randomized, parallel assignment, triple masking

Number of Patients: 500

Inclusion Criteria: Signed informed consent must be obtained prior to participation in the study. Patients with type 1 or type 2 diabetes mellitus (DM) and Hemoglobin A1c (HbA1c) ≤ 12% at screening. Study eye: Visual impairment due to DME with: Best-corrected visual acuity (BCVA) score between 73 and 23 letters, inclusive, using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts at an initial testing distance of 4 meters. DME involving the center of the macula, with Central Subfield Thickness (CSFT) ≥ 320 µm on Spectral Domain Optical Coherence Tomography (SD-OCT).

Exclusion Criteria: High-risk proliferative diabetic retinopathy (PDR) in the study eye. Concomitant conditions or ocular disorders in the study eye which confound interpretation of study results, compromise visual acuity or require medical or surgical intervention. Any active intraocular or periocular infection or active intraocular inflammation in the either eye. Uncontrolled glaucoma in the study eye. Presence of amblyopia, amaurosis or ocular disorders in the fellow eye with BCVA <20/200. Use of anti-VEGF therapies, intraocular surgery or laser photocoagulation (macular or panretinal) in the study eye during the 3-month period prior to baseline. Use of intraocular or periocular corticosteroids in the study eye during the 6-month period prior to baseline and use of fluocinolone acetonide intravitreal (IVT) implant (Iluvien) at any time prior to baseline. Prior investigational drugs in either eye, vitreoretinal surgery in the study eye at any time prior to baseline.

Information: novartis.email@novartis.com

Study: The Study to YD312 Tablet in Patients with Diabetic Macular Edema

ClinicalTrials.gov Identifier: NCT03635814

Sponsor: YD Global Life Science Co., Ltd.

Purpose: This study objectives is to evaluate the efficacy of YD312 to improve visual acuity in patients with diabetic macular edema (DME) compared to placebo and determine optimal dose of phase 2b study.

Design: Randomized, parallel assignment

Number of Patients: 100

Inclusion Criteria: Subject who is male or female ≥19 years of age. Subject who has a diagnosis of Type 1 or 2 diabetes. Subject who has study eye with definite retinal thickening due to diabetic macular edema involving the center of the macula. Subject who has voluntarily signed an informed consent form. Randomization Inclusion Criteria: Study eye must be eligible for the following criteria at randomization: Subject who has study eye with central subfield thickness (CST) of ≥300 μm on optical coherence tomography (OCT). Subject who has study eye with an early treatment diabetic retinopathy study (ETDRS) best-corrected visual acuity (BCVA) letter score ranging from 39 to 78, inclusive (approximate Snellen equivalent of 20/32 - 20/160).

Exclusion Criteria: Subject who has study eye with any of the following criteria: Subject whose primary cause of macular edema is non-diabetic disease/condition (eg, cataract extraction, vitreomacular interface abnormalities). Subject who is expected to have no improvement of decreased visual acuity in the opinion of investigator, even if macular edema is resolved (eg, foveal atrophy, abnormal pigmentation, dense subfoveal hard exudate). Subject who has proliferative diabetic retinopathy. Subject who took the following within 3 months before randomization: Focal/grid laser photocoagulation, Intravitreal/circumbulbar corticosteroid, anti-VEGF and pro-VEGF (but, no wash-out period is required for the corticosteroid eyedrops). Subject who took panretinal photocoagulation (PRP) or intravitreal dexamethasone implant within 6 months before randomization. Subject who has a history of vitrectomy. Subject who took major ophthalmic surgeries (all intraocular surgeries including cataract extraction and scleral buckle) within 6 months before randomization. Subject who had systemic treatment of corticosteroid or anti-VEGF within 3 months before randomization. Subject who administered vaccinium myrtillus extract or dobesilate calcium within 2 weeks before randomization. Subject who is suspected to require administration/treatment of drug/procedure that may affect the efficacy evaluation before the participation of clinical trial or during clinical trial (refer to '10.4 Combination Therapy and Contraindication'). Subject who has the following illness or abnormal laboratory test values: Subject who has a hypersensitivity to any excipients of the investigational product or similar class of drug and ingredient. Subject who has uncontrolled hypertension (SBP >160 mmHg or DBP >100 mmHg). Subject who has uncontrolled diabetes (HbA1c >10.0%). Subject who has uncontrolled glaucoma in either eye (intraocular pressure (IOP) >24 mmHg on medication or according to the investigator's judgment). ANC <1.5 × 109/L. Platelet <125 × 109/L. Total bilirubin >1.5 × ULN. AST or ALT >2 × ULN. Clcr* <40 mL/min. * Clcr (Cockcroft-Gault formula). = [(140 - age) x weight(kg) (x 0.85 for females)] / [72 x serum creatinine (Scr) (mg/dL)]. Severe heart failure (NYHA class III/IV). Malignant tumor within 5 years before randomization. Subject who is known to be HIV positive, is active hepatitis B patient or carrier, or is hepatitis C patient. Ocular inflammatory diseases such as uveitis, conjunctivitis, and blepharitis in either eye. However, the participation of subject in this study is considered at the discretion of investigator. Unstable angina, myocardial infarction, transient ischemic attack, cerebral infarction, coronary artery bypass surgery, or transluminal coronary angioplasty within 6 months before screening. Pregnant woman, lactating woman, or female or male subject of childbearing potential. *hormonal contraceptives, intrauterine contraceptive device, sterilization of spouse (eg, vasectomy, tubal ligation), double-barrier method (eg, combinational use of spermicides and condoms, diaphragm, contraceptive sponge, of FemCap). Subject who took administration/procedure of other investigational products or medical devices within longer period between 30 days before screening or over 5time half-life. Subject, at the discretion of the investigator, who is unsuitable to participate in the study.

Study: This Study Will Evaluate the Efficacy, Safety, and Pharmacokinetics of the Port Delivery System with Ranibizumab (PDS) in Participants with Diabetic Macular Edema (DME) Compared with Intravitreal Ranibizumab (Pagoda)

ClinicalTrials.gov Identifier: NCT04108156

Sponsor: Hoffmann-La Roche

Purpose: This study will evaluate the efficacy, safety, and pharmacokinetics of the PDS in participants with diabetic macular edema (DME) when treated every 24 weeks (Q24W) compared with intravitreal ranibizumab 0.5 mg every 4 weeks (Q4W).

Design: Randomized, parallel assignment, single masking

Number of Patients: 545

Inclusion Criteria: Age ≥18 years at time of signing Informed Consent Form. Documented diagnosis of diabetes mellitus (Type 1 or Type 2). HbA1c level of ≤10% within 2 months prior to screening or at screening. Study eye: Macular thickening secondary to DME involving the center of the fovea with CST ≥325 um on SD-OCT at screening. BCVA of ≥25 letters.

Exclusion Criteria: High-risk proliferative diabetic retinopathy. Active intraocular inflammation (grade trace or above). Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis of either eye. Uncontrolled ocular hypertension or glaucoma and any such condition the investigator determines may require a glaucoma-filtering surgery during a patient's participation in the study. Cerebrovascular accident or myocardial infarction within 6 months prior to randomization. Atrial fibrillation diagnosis or worsening within 6 months prior to randomization. Uncontrolled blood pressure.

Information: global-roche-genentech-trials@gene.com

Study: A Depot Formulation of Sunitinib Malate (GB-102) in Subjects with Diabetic Macular Edema and Retinal Vein Occlusion

ClinicalTrials.gov Identifier: NCT04085341

Sponsor: Graybug Vision

Purpose: Phase 2a multicenter, open-label, parallel-arm design study to evaluate the safety, tolerability and pharmacodynamics of a single intravitreal injection comparing 2 dose levels of GB-102 on subjects with diabetic macular edema and retinal vein occlusion.

Design: Nonrandomized, parallel assignment, no masking

Number of Patients: 20

Inclusion Criteria: Males or females ≥21 years of age. Known diagnosis of macular edema secondary to diabetic macular edema or retinal vein occlusion treated with at least 3 prior IVT injections of an anti-VEGF agent (aflibercept, bevacizumab, or ranibizumab). Demonstrated response to prior anti-VEGF treatment since diagnosis. BCVA of 31 letters or better.

Information: vsmith@graybug.com

Study: A Study Assessing AR-13503 Implant Alone and in Combination with Aflibercept in Subjects With nAMD or DME

ClinicalTrials.gov Identifier: NCT03835884

Sponsor: Aerie Pharmaceuticals

Design: Randomized, sequential assignment, single

Number of Patients: 102

Inclusion Criteria: Inclusion Criteria for Subjects with Neovascular Age-Related Macular Degeneration (nAMD) or Diabetic Macular Edema (DME): 50 years of age or older. Presence of active subfoveal or juxtafoveal Choroidal Neovascularization (CNV) (any subtype) with leakage affecting the fovea secondary to AMD. Best corrected visual acuity (BCVA) in the study eye at Baseline (Day 0): Stage 1: between 65 and 10 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (20/50 and 20/640 Snellen equivalent) Stage 2: between 65 and 20 ETDRS letters (20/50 and 20/400 Snellen equivalent). Able and willing to give signed informed consent and follow study instructions. Inclusion Criteria for Subjects with DME: Subjects with diabetic macular edema (DME) must meet all the following criteria to enter into the study: 18 years of age or older. Type 1 or 2 diabetes mellitus with center-involved DME. BCVA in the study eye at Baseline (Day 0): Stage 1: between 65 and 10 ETDRS letters (20/50 and 20/640 Snellen equivalent) Stage 2: between 65 and 20 ETDRS letters (20/50 and 20/400 Snellen equivalent). Able and willing to give signed informed consent and follow study instructions.

Exclusion Criteria: Exclusion criteria for subjects with neovascular age-related macular degeneration (nAMD): Ophthalmic: Use of intravitreal aflibercept within 8 weeks, ranibizumab or bevacizumab within 6 weeks. History of vitreoretinal surgery in the study eye. Any ocular disease in the study eye that in the Investigator and reading center's opinion may confound assessment of the macula, affect central vision, confound results, or preclude improvement in visual acuity. Any current or history of periocular or intraocular inflammation or evidence of infection in either eye. Media clarity insufficient to obtain quality fundus and OCT images in the study eye. Systemic: History or current systemic condition that in the Investigator opinion preclude the safe administration of the study treatment or confound results. History of allergy or sensitivity to fluorescein or povidone iodine. Women of childbearing potential who are pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of birth control. Participation in an investigational study within 30 days of Screening. Exclusion Criteria for Subjects with DME: Ophthalmic: Use of intraocular or periocular corticosteroids within 6 months, aflibercept within 8 weeks, ranibizumab or bevacizumab within 6 weeks. History of vitreoretinal surgery in the study eye. High risk proliferative diabetic retinopathy in the study eye and related complications. Structural damage to the center or the macula that is likely to preclude improvement in visual acuity in the study eye after resolution of the DME. Media clarity insufficient to obtain quality fundus and OCT images in the study eye. Systemic: History or current medical condition that in the Investigator's opinion preclude the safe administration of the study treatment or confound results. History of allergy or sensitivity to fluorescein or povidone iodine. Women of childbearing potential who are pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of birth control. Participation in an investigational study within 30 days of Screening.

Information: nramirez@aeriepharma.com, pbraswell@aeriepharma.com

Study: A Phase I Study of Episcleral Dexamethasone for Treatment of Macular Edema

ClinicalTrials.gov Identifier: NCT04005430

Sponsor: Targeted Therapy Technologies, LLC

Purpose: This phase I trial will assess primarily the safety and secondarily anti-inflammatory effect of Episcleral Dexamethasone in patients suffering from refractory diabetic macular edema.

Design: Single group assignment, no masking

Number of Patients: 3

Inclusion Criteria: Type I or II diabetes; age ≥18 years; visual acuity letter score in study eye <70 and ≥25 letters (approximate Snellen equivalent 20/32 to 20/320); ophthalmoscopic evidence of center-involved DME, within the central subfield (CSF); OCT CSF thickness value (microns): Zeiss Cirrus: ≥290 in women; ≥305 in men; Heidelberg Spectralis: ≥305 in women; ≥320 in men; Previous treatment with laser, anti-VEGF therapy and/or intravitreal steroids; No previous history of glaucoma or steroid-induced intraocular pressure response in either eye.

Exclusion Criteria: History of chronic renal failure requiring dialysis or kidney transplant; Retinal or optic nerve neovascularization on clinical exam, fundus photographs, or fluorescein angiograms; Evidence of external ocular infection; History of open-angle glaucoma or intraocular pressure ≥25 mmHg; History of steroid-induced IOP elevation that required IOP-lowering treatment; History of prior herpetic ocular infection; History of intravitreal or periocular corticosteroids within 3 months prior to enrollment; History of macular laser photocoagulation within 4 months prior to enrollment; History of antiangiogenic therapy within 4 weeks prior to enrollment; History of panretinal photocoagulation (PRP) within 4 months prior to enrollment or anticipated need for PRP in the next 6 months following enrollment; Presence of vitreomacular traction, epiretinal membrane, tractional retinal detachment, vitreous hemorrhage and or any ocular condition that the investigator judges could interfere in the safety and efficacy assessments; No other major non-diabetic pathology, or anticipation of such in the next 6 months following enrollment that in the opinion of the investigator would substantially and adversely affect assessment of safety and toxicity during the study; Participation in another clinical trial of non-approved medical treatment within 3 months prior to enrollment; Degenerative myopia; Malignant intraocular disease; Inability to understand informed consent, cooperate with testing or return to follow-up visits; Pregnant or lactating women; Co-existent ocular disorder of the cornea, lens or media that will interfere with assessment of safety or efficacy.

Information: Novartis.email@novartis.com

Study: Multiple Dose Safety and Efficacy of LKA651 in Patients with Diabetic Macular Edema

ClinicalTrials.gov Identifier: NCT03927690

Sponsor: Novartis Pharmaceuticals

Purpose: To evaluate the safety and efficacy of LKA651 in patients with macular edema from diabetic macular edema (DME).

Design: Randomized, parallel assignment, quadruple masking

Number of Patients: 90

Inclusion Criteria: Written informed consent must be obtained before any assessment is performed. Male and female patients age 18 to 85 years of age inclusive at screening. Presence of type I or type II diabetes mellitus. The ETDRS letter score in the study eye must be between 24 and 70 letters (approximate Snellen equivalent of 20/40-20/320). The non-study eye (fellow eye) should be ≥34 letters or better (approximate Snellen equivalent of 20/200) at screening. Presence of DME in the study eye, with decrease in vision due to foveal thickening of central macular thickness ≥320 µm in the central subfield, as assessed on SD-OCT and confirmed by the central reading center at screening.

Information: Novartis.email@novartis.com

Study: The Use of a Combination of Ozurdex and Eylea Versus Eylea Monotherapy for Diabetic Macular Edema: A Prospective, Comparative Trial (COED Trial)

ClinicalTrials.gov Identifier: NCT03984110

Sponsor: Texas Retina Associates

Purpose: The Use of a Combination of Ozurdex and Eylea Versus Eylea Monotherapy for Diabetic Macular Edema.

Design: Randomized, single group assignment, no masking

Number of Patients: 50

Inclusion Criteria: Type 1 or 2 diabetic patients; At least 18 years of age, understands the language of the informed consent, and is willing and able to provide written informed consent before any study procedures; Pseudophakic or phakic lens status with intact posterior lens capsule and/or Nd:YAG laser capsulotomy that in the investigator's opinion is not likely to permit dislocation of Ozurdex implant into the anterior chamber; Center-involving DME >300 µm; Baseline BCVA between 20/40 - 20/320; Eyes with intraocular pressure (IOP) ≤21 and / or treatment with <2 topical IOP-lowering medications (eyes with history of previous angle -closure or similar conditions that have been successfully treated with either laser or surgical intervention are allowed as long as the visual fields and optic nerves have been stable for >1 year prior to study entry and the patient has been and can be safely dilated).

Exclusion Criteria: Patients with active or suspected ocular or periocular infections including most viral diseases of the cornea and conjunctiva, including active epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, mycobacterial infections, and fungal diseases. Patients with known hypersensitivity to any components of Eylea or Ozurdex; Patient has suffered from a stroke or transient ischemic attack (TIA) in the last 6 months; Patients using topical anti-inflammatory medication for the duration of the study; Patients with ACIOL (anterior chamber intraocular lens) and rupture of the posterior lens capsule; Prior panretinal photocoagulation or macular laser treatments within 90 days of screening; Previous vitrectomy; Any ocular condition that in the opinion of the investigator would not permit improvement of visual acuity with resolution of DME (eg, foveal atrophy, pigment abnormalities, dense subfoveal hard exudates and/or poor foveal architecture suggestive of photoreceptor loss); Patients with retinal diseases other than diabetes that can affect macular edema; Eyes with a history of advanced glaucoma (optic nerve head change consistent with glaucoma damage and/or glaucomatous visual field loss), uncontrolled ocular hypertension (baseline IOP >21 mmHg despite use of ≥2 topical IOP-lowering medication); Eyes with a history of steroid response (ie, increase of ≥5 mmHg IOP following topical steroid treatment); Female patients who are pregnant or breastfeeding; Patients who are unable to attend scheduled follow-up visits throughout the 24-week study; Any intravitreal anti-VEGF treatment to study eye within 3 months prior to Day 1; Use of systemic steroid, anti-VEGF or pro-VEGF treatment within 4 months prior to enrollment or anticipated use during the study (these drugs are prohibited from use during the study); History of any previous treatment in the study eye with an ocular corticosteroid implant (eg, Iluvien, Ozurdex, Retisert); Has scarring from laser photocoagulation in the study eye that would compromise VA; or scarring or abnormality from other macular condition, in the investigator's medical judgement, would limit VA (such as an epiretinal membrane or macular hole); Has significant media opacity precluding evaluation of retina and vitreous in the study eye. This includes cataract that is felt to be a major contributor to reduced visual acuity and/or likely to undergo surgical repair within 3 months of randomization. Has any uncontrolled systemic disease that, in the opinion of the Investigator, would preclude participation in the study (eg, infection, uncontrolled elevated blood pressure, cardiovascular disease, poor glycemic control) or put the subject at risk due to study treatment or procedures; Has had a myocardial infarction, other acute cardiac event requiring hospitalization, stroke, transient ischemic attack, or treatment for acute congestive heart failure within 1 month before enrollment.

Information: kduignan@texasretina.com, sarceneaux@texasretina.com

Study: Long Term Safety of Cooling Anesthesia for Intravitreal Injection (COOL-2)

ClinicalTrials.gov Identifier: NCT03956797

Sponsor: Recens Medical, Inc.

Purpose: The purpose of this clinical study is to evaluate the long term safety and efficacy of cooling anesthesia application to the eye as anesthesia for intravitreal injection using a novel cooling anesthesia device.

Design: Randomized, sequential assignment, no masking

Number of Patients: 60

Inclusion Criteria: Men and women >18 years old at screening visit. Men and women who are undergoing intravitreal injections in either 1 eye or both eyes with either Lucentis or Eylea as part of their normal standard of care with a 30-gauge needle. Subject has received a minimum of 3 intravitreal injections in the study eye prior to the study visit. Subject is willing and able to sign the study written informed consent form (ICF).

Exclusion Criteria: History of presence of scleromalacia; Preexisting conjunctival, episcleral or scleral defects; Less than 18 years of age; Unable to provide informed consent; Has received less than 3 injections in the study eye; Active severe eye disease not controlled with artificial tears and requiring Restasis or other prescription drugs for dry eye. History of Endophthalmitis with intravitreal injection; History of uveitis; History of retinal detachment in either eye; History of vitrectomy; Subjects who received administration of cooling anesthesia as part of the COOL-1 study will not be excluded and are eligible to participate in this study.

Information: arshad.khanani@gmail.com

Study: Cataract DME - Peri vs Intraop

ClinicalTrials.gov Identifier: NCT03920878

Sponsor: Emory University

Purpose: Goals of the study are to evaluate how peri-operative versus intra-operative anti-VEGF intravitreous injections affect visual acuity (BCVA) in patients with persistent diabetic macular edema who are undergoing cataract surgery; and to evaluate how peri-operative versus intra-operative anti-VEGF intravitreous injections affect OCT CSF thickness and total number of postoperative injections in patients with diabetic macular edema who are undergoing cataract surgery.

Design: Randomized, parallel assignment

Number of Patients: 60

Inclusion Criteria: Adults over age 18 with diabetes mellitus, diabetic macular edema and visually significant cataracts planning to undergo cataract surgery.

Exclusion Criteria: Patients who have undergone panretinal photocoagulation (PRP) in prior 4 months or an ocular condition (other than cataract and DME) that might affect visual acuity during course of study. Patients with history of vitrectomy. Patients with neovascular glaucoma.

Information: ahendrick@emory.edu

Study: A Pilot Study Evaluating Photobiomodulation Therapy for Diabetic Macular Edema (AE)

ClinicalTrials.gov Identifier: NCT03866473

Sponsor: Jaeb Center for Health Research

Purpose: Randomized clinical trial evaluating the effect of photobiomodulation compared with sham on central subfield thickness (CST) in eyes with central-involved DME and good vision.

Design: Randomized, single group assignment

Number of Patients: 134

Inclusion Criteria: Age ≥18 years; Diagnosis of diabetes mellitus (type 1 or type 2). Any one of the following will be considered to be sufficient evidence that diabetes is present: Current regular use of insulin for the treatment of diabetes; Current regular use of oral anti-hyperglycemia agents for the treatment of diabetes; Documented diabetes by American Diabetes Association and/or the World Health Organization criteria; Able and willing to provide informed consent. At least 1 eye meeting the following criteria: Best corrected E-ETDRS visual acuity letter score ≥79 (ie, 20/25 or better); Ophthalmoscopic evidence of central-involved DME, confirmed by CST on spectral domain OCT: Zeiss Cirrus: ≥290µm in women, and ≥305µm in men, Heidelberg Spectralis: ≥305µm in women, and ≥320µm in men; Media clarity, pupillary dilation, and study participant.

Exclusion Criteria: History of chronic renal failure requiring dialysis or kidney transplant. A condition that, in the opinion of the investigator, would preclude participation in the study (eg, unstable medical status that might preclude completion of follow-up). Initiation of intensive insulin treatment (a pump or multiple daily injections) within 4 months prior to randomization or plans to do so in the next 4 months. Participation in an investigational trial that involved treatment within 30 days of randomization with any drug/device that has not received regulatory approval for the indication being studied. Note: study participants cannot participant in another investigational trial that involves treatment with an investigational drug or device while participating in the study. Systolic blood pressure above 180 or diastolic blood pressure above 110. If blood pressure is brought below 180 systolic and 110 diastolic by anti-hypertensive treatment, individual can become eligible. Systemic anti-vascular endothelial growth factor (anti-VEGF) or pro-VEGF treatment within 4 months prior to randomization. These drugs should not be used during the study. For women of child-bearing potential: pregnant or intending to become pregnant within the next 8 months. Women who are potential study participants should be questioned about the potential for pregnancy. Investigator judgment is used to determine when a pregnancy test is needed. Individual is expecting to move out of the area during the 8 months of the study. A participant will be excluded if the study eye meets any of the following criteria: Macular edema is considered to be due to a cause other than DME. An eye should not be considered eligible if: (1) the macular edema is considered to be related to ocular surgery such as cataract extraction or (2) clinical exam and/or investigator assessment of OCT suggests that vitreoretinal interface abnormalities (eg, a taut posterior hyaloid or epiretinal membrane) are contributing to the macular edema. An ocular condition is present such that, in the opinion of the investigator, any visual acuity loss would not improve from resolution of macular edema (eg, foveal atrophy, pigment abnormalities, dense subfoveal hard exudates, nonretinal condition). An ocular condition is present (other than DME) that, in the opinion of the investigator, might affect visual acuity during the course of the study or require intraocular treatment (eg, vein occlusion, uveitis or other ocular inflammatory disease, neovascular glaucoma, etc.) Cataract is present that, in the opinion of the investigator, may alter visual acuity during the course of the study. History of major ocular surgery (including cataract, scleral buckle, any intraocular surgery, etc.) within prior 4 months or major ocular surgery anticipated during the study period. Any history of prior laser or other surgical, intravitreal, or peribulbar treatment for DME or DR (such as panretinal photocoagulation, focal/grid macular photocoagulation, intravitreal or peribulbar corticosteroids, or anti-VEGF) within the prior 12 months. If treatment was given more than 12 months prior, no more than 4 prior intraocular injections. Enrollment will be limited to a maximum of 15 percent of the planned sample size with any history of anti-VEGF treatment and a maximum of 15% with any history of PRP. Anticipated need to treat DME or DR during the study period. History of topical steroid or non-steroidal anti-inflammatory drug treatment within 30 days prior to randomization. History of YAG capsulotomy performed within 2 months prior to randomization. Any history of vitrectomy. Aphakia. Uncontrolled glaucoma.

Information: drcrnet@jaeb.org

Study: Micropulse for Suppression of Diabetic Macular Edema (PULSE)

ClinicalTrials.gov Identifier: NCT03519581

Sponsor: University of California, Davis; IRIDEX Corporation

Purpose: The purpose of this study is to determine if early intervention with micropulse laser treatment in eyes with good visual acuity (20/32 or better) will improve or stabilize vision loss due to the complications of diabetic macular edema.

Design: Randomized, parallel assignment, double masking

Number of Patients: 30

Inclusion Criteria: Age ≥18 years; Type 1 or type 2 diabetes mellitus; Clinical evidence of center-involved DME confirmed on OCT, and defined by OCT; Central Subfield (CSF) thickness at the time of randomization by the following: Zeiss Cirrus: 275μ in women, and 290μ in men; Heidelberg Spectralis: 290μ in women, and 305μ in men; Best corrected visual acuity of 20/32 or better on ETDRS testing.

Exclusion Criteria: Macular edema from causes other than DME; An ocular condition is present such that in the opinion of the investigator, visual acuity would not improve from resolution of macular edema (ie, foveal atrophy, pigment abnormalities, dense hard exudates); An ocular condition is present other than DME which may contribute to macular edema (ie, vein occlusion, ERM, uveitis, RP). Cataract that in the opinion of the investigator may alter visual acuity throughout the course of the study; History of prior laser or other surgical, intravitreal, or peribulbar treatment for DME in the study eye within the prior 6 months. More than 4 prior intraocular injections for treatment of DME at any time; More than 1 prior focal/grid macular photocoagulation session for treatment of DME at any time; History of topical steroid or NSAID treatment within 30 days prior to randomization; History of PRP within 4 months prior to randomization or anticipated need for PRP in the 6 months following randomization. Any history of vitrectomy. History of major ocular surgery (cataract extraction, scleral buckle, any intraocular surgery, etc.) within prior 4 months or anticipated within the next 6 months following randomization. History of YAG capsulotomy performed within 2 months prior to randomization. Aphakia. Exam evidence of external ocular infection, including conjunctivitis, chalazion, or significant blepharitis.

Information: clwallace@ucdavis.edu

Study: Post Intravitreal Injection Topical NSAID vs Patching

ClinicalTrials.gov Identifier: NCT03918590

Sponsor: The New York Eye & Ear Infirmary

Purpose: A prospective randomized trial, to evaluate postinjection comfort measures comparing topical NSAID (nepafenac 0.3% suspension) and patching.

Design: Randomized, parallel assignment

Number of Patients: 60

Inclusion Criteria: 18 years of age or older; Already scheduled for anti-VEGF injection based on standard of care for disease process. Ability to provide written informed consent; Capable of complying with study protocol. Volunteer written informed consent with the understanding that consent may be withdrawn by the subject at any time without prejudice to future care.

Exclusion Criteria: History of past intraocular injection of steroid medication. Experiencing baseline eye pain; Monocular; non-study eye with VA<20/100. Unwilling or unable to follow or comply with all study related procedures.

Study: Laser vs Bevacizumab Injection Alone in Treatment of Diabetic Macular Edema

ClinicalTrials.gov Identifier: NCT02229175

Sponsor: University of California, San Francisco

Purpose: The purpose of this randomized clinical trial is to determine whether subvisible laser in combination with intravitreal bevacizumab is non-inferior compared to current standard of care (intravitreal bevacizumab alone) in achieving favorable outcomes for visual acuity, mean macular thickness, and patient quality of life, and has fewer needed intravitreal bevacizumab injections throughout the course of the 12 month study period.

Design: Randomized, parallel assignment, double masking

Number of Patients: 60

Inclusion Criteria: Inclusion criteria include adults ≥18 years with type 1 or 2 diabetes mellitus with DME secondary to diabetes mellitus involving the center of the macula in the study eye and with a decrease in vision is determined to be primarily the result of DME in the study eye. The study eye must have a BCVA ETDRS letter score of 50 to 24 (20/30 to 20/320) in the study eye. The patient should be on a stable medical diabetic regimen that is not expected to change.

Exclusion Criteria: Patients are excluded if they have had laser photocoagulation (panretinal or macular) in the study eye within 90 days of Day 1, more than 2 previous macular laser treatments in the study eye, previous use of intraocular or periocular corticosteroids in the study eye within 90 days of Day 1, previous treatment with antiangiogenic drugs in either eye (pegaptanib sodium, bevacizumab, ranibizumab, or aflibercept) within 45 days of Day 1, active proliferative diabetic retinopathy (PDR) in the study eye, with the exception of inactive, regressed PDR, uncontrolled diabetes mellitus, as defined by HbA1c >12%, or a patient who is functionally monocular, as defined by the clinician or vision worse than 20/400 in the fellow eye even if that eye is otherwise eligible for the study.

Information: stewartj@vision.ucsf.edu; Catherine.Psaras@ucsf.edu

Study: Steroid vs Anti-vascular Endothelial Growth Factor for Diabetic Macular Edema Prior to Phacoemulsification (STAMP)

ClinicalTrials.gov Identifier: NCT03832179

Sponsor: Bay Area Retina Associates

Purpose: The primary objective of this study is to compare the efficacy of antecedent intravitreal anti-vascular endothelial growth factor therapy vs Ozurdex in reducing postcataract surgery related macular edema in patients with pre-existing diabetic macular edema.

Design: Randomized, parallel assignment, no masking

Number of Patients: 32

Inclusion Criteria: Age >18 years of age; diagnosis of diabetes (Type 1 or 2) with a concomitant diagnosis of diabetic macular edema as demonstrated on spectral domain optical coherence tomography (Heidelberg Spectralis); >250 microns central foveal thickness; able and willing to provide informed consent.

Exclusion Criteria: Significant renal disease; a condition that in the opinion of the investigator would preclude participation; participation in another investigational trial within 30 days of randomization; application of focal macular laser within 120 days of enrollment; administration of Iluvien implant within 3 years of enrollment; administration of intravitreal triamcinolone within 3 months of enrollment; administration of any anti-vascular endothelial growth factor agent within 30 days of enrollment; known hypersensitivity to any of the investigational products; blood pressure >180/110; women who are pregnant, lactating, or intend to become pregnant within 1 year of randomization; vulnerable populations- including but not limited to wards of the state, cognitively impaired individuals, prisoners, institutionalized individuals; individual is planning on moving within 6 months of study enrollment; macular edema secondary to cause other than diabetic macular edema; ocular condition that, in the opinion of the investigators, may affect course of macular edema during course of study (vein occlusion, uveitis, etc.); evidence of ocular infections; evidence of uncontrolled glaucoma; known hypersensitivity to any components of bevacizumab, ranibizumab, aflibercept, or Ozurdex.

Information: cluo@bayarearetina.com, fahmed@bayarearetina.com

ClinicalTrials.gov Identifier: NCT03790852

Sponsor: Kodiak Sciences, Inc.

Purpose: This is a phase 1b open-label study to assess the bioactivity, ocular and systemic safety, tolerability, and pharmacokinetics of repeated injections of KSI-301 at 2 dose levels: 2.5 mg and 5 mg.

Design: Randomized, parallel assignment, no masking

Number of Patients: 50

Inclusion Criteria: DME Cohort: Treatment naïve diabetic macular edema. BCVA ETDRS letter score ≤78 and ≥23 (⁓20/25 to ⁓20/320 Snellen equivalent) in the study eye. Central subfield thickness (CST) of ≥300 microns on SD-OCT (Heidelberg Spectralis or equivalent). Decrease in vision in the study eye determined by the investigator to be primarily the result of DME.

Exclusion Criteria: DME Cohort: Initial diagnosis of DME of more than 6 months from screening in the study eye. Hard exudates in the fovea. Prior intravitreal anti-VEGF therapy or steroid injection, or steroid implant (dexamethasone or triamcinolone) in the study eye. Moderate or dense vitreous hemorrhage preventing clear. visualization of the macula or optic disc in the study eye. Fibrovascular proliferation or tractional retinal detachment in the posterior pole in the study eye. If traction is present outside the posterior pole, it should be considered not at risk of increasing and threatening the macula with the use of anti-VEGF injections, in the investigator's judgement.

Information: jehrlich@kodiak.com, pablovm@kodiak.com

Study: Cooling Anesthesia for Intravitreal Injection (COOL-1)

ClinicalTrials.gov Identifier: NCT03732287

Sponsor: Recens Medical, Inc.

Purpose: The purpose of this clinical study is to evaluate the safety and efficacy of cooling anesthesia application to the eye as anesthesia for intravitreal injection using a novel cooling anesthesia device and determine the effects of temperature and duration of application on subjective pain after intravitreal injection.

Design: Nonrandomized, sequential assignment

Number of Patients: 40

Inclusion Criteria: Men and women >18 years old at screening visit. Men and women who are undergoing intravitreal injections in either one or both eyes with either Lucentis or Eylea as part of their normal standard of care with a 30 gauge needle. Subject has received a minimum of 3 intravitreal injections in the study eye prior to the study visit. Subject is willing and able to sign the study written informed consent form (ICF).

Exclusion Criteria: History of presence of scleromalacia; preexisting conjunctival, episcleral or scleral defects; less than 18 years of age; unable to provide informed consent; has received less than 3 injections in the study eye; active severe eye disease not controlled with artificial tears and requiring Restasis or Xiidra drops. History of endophthalmitis with intravitreal injection; history of uveitis; history of retinal detachment in either eye; history of vitrectomy.

Information: arshad.khanani@gmail.com

Study: A Study to Evaluate the Efficacy and Safety of RO6867461 in Participants with Diabetic Macular Edema (RHINE)

ClinicalTrials.gov Identifier: NCT03622593

Sponsor: Hoffman-La Roche

Purpose: This study will evaluate the efficacy, safety, and pharmacokinetics of RO6867461 administered at 8-week intervals or as specified in the protocol following treatment initiation, compared with aflibercept once every 8 weeks (Q8W), in participants with diabetic macular edema (DME).

Number of Patients: 900

Design: Randomized, parallel assignment, triple masking

Inclusion Criteria: Type 1 or type 2 diabetes mellitus and hemoglobin A1c (HbA1c) of less than or equal to (≤) 10%. Macular thickening secondary to diabetic macular edema (DME) involving the center of the fovea. Decreased visual acuity attributable primarily to DME. Ability and willingness to undertake all scheduled visits and assessments. For women of childbearing potential: agreement to remain abstinent or use acceptable contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 3 months after the final dose of study treatment.

Exclusion Criteria: Currently untreated diabetes mellitus or previously untreated patients who initiated oral anti-diabetic medication or insulin within 3 months prior to day 1. Uncontrolled blood pressure, defined as a systolic value greater than (>)180 millimeters of mercury (mmHg) and/or a diastolic value >100 mmHg while a patient is at rest. Currently pregnant or breastfeeding, or intend to become pregnant during the study. Treatment with panretinal photocoagulation or macular laser within 3 months prior to day 1 to the study eye. Any intraocular or periocular corticosteroid treatment within the past 6 months prior to day 1 to the study eye. Prior administration of IVT RO6867461 in either eye. Active intraocular or periocular infection or active intraocular inflammation in the study eye. Any current or history of ocular disease other than DME that may confound assessment of the macula or affect central vision in the study eye. Any current ocular condition which, in the opinion of the investigator, is currently causing or could be expected to contribute to irreversible vision loss due to a cause other than DME in the study eye. Other protocol-specified inclusion/exclusion criteria may apply.

Information: global-roche-genentech-trials@gene.com

Study: A Study to Evaluate the Efficacy and Safety of RO6867461 in Participants with Diabetic Macular Edema (YOSEMITE)

ClinicalTrials.gov Identifier: NCT03622580

Sponsor: Hoffman-La Roche

Number of Patients: 900

Design: Randomized, parallel assignment, triple masking

Information: global-roche-genentech-trials@gene.com

Study: Comparative Study to Evaluate the Efficacy and Safety of MYL-1701P and Eylea in Subjects with Diabetic Macular Edema

ClinicalTrials.gov Identifier: NCT03610646

Sponsor: Mylan Inc.

Purpose: Three hundred and twenty-four (324) eligible adult subjects with diabetes mellitus with central DME involvement will be randomized 1:1 to intravitreal treatment with MYL-1701P or Eylea.

Number of Patients: 324

Design: Randomized, parallel assignment, triple masking

Inclusion Criteria: Male or female subjects age ≥18 years. Subjects have type 1 or type 2 diabetes mellitus who present with central DME involvement in the study eye. The cause of decreased vision in the study eye has been attributed primarily to DME by the Investigator. Subject is able to understand and voluntarily provide written informed consent to participate in the study. If female of childbearing potential, the subject must have a negative serum pregnancy test at the screening visit and a negative urine pregnancy test at baseline visit, and should not be nursing or planning a pregnancy. If female, subject must be: Surgically sterilized via hysterectomy, bilateral oophorectomy, or bilateral tubal ligation; or of childbearing potential and practicing an acceptable form of birth control (defined as the use of an intrauterine device; a barrier method, like condom, with spermicide; any form of hormonal contraceptives; or abstinence from sexual intercourse) starting 60 days prior to dosing and continuing at least 90 days following the last treatment. Of non-childbearing potential (ie, postmenopausal for at least 1 year). If male, subject must be surgically or biologically sterile. If not sterile, the subject must agree to use an acceptable form of birth control with sexual partner (as described in inclusion criteria #6b of protocol) or abstain from sexual relations during the study period and up to 90 days following the last treatment dose. Subject is willing to comply with the study duration, study visits and study related procedures.

Exclusion Criteria: Subjects with known hypersensitivity to aflibercept or any of the excipients. Subjects with current or planned use of systemic medications known to be toxic to the lens, retina or optic nerve, including deferoxamine, chloroquine/hydroxychloroquine, tamoxifen, phenothiazines and ethambutol. Subjects with uncontrolled hypertension defined as systolic blood pressure >160 mmHg or diastolic blood pressure >95 mmHg. Subjects with a history of cerebrovascular accident or myocardial infarction within 6 months of randomization. Subjects who have only 1 functional eye, even if the eye met all other study requirements, or who have an ocular condition on the fellow eye with a poorer prognosis than the study eye.

Information: PrasannaC.Ganapathi@mylan.in

Study: Study of Efficacy and Safety of Brolucizumab vs Aflibercept in Patients with Visual Impairment Due to Diabetic Macular Edema (KESTREL)

ClinicalTrials.gov Identifier: NCT03481634

Sponsor: Novartis Pharmaceuticals

Purpose: The purpose of this study is to evaluate the efficacy and safety of brolucizumab in treatment of patients with visual impairment due to diabetic macular edema (DME).

Design: Parallel assignment, double masking

Number of Patients: 534

Inclusion Criteria: Written informed consent before any assessment; Patients with type 1 or type 2 diabetes mellitus and HbA1c of ≤10% at screening; Medication for the management of diabetes stable within 3 months prior to randomization and is expected to remain stable during the course of the study

Exclusion Criteria: Active proliferative diabetic retinopathy in the study eye; Active intraocular or periocular infection or active intraocular inflammation in study eye; Uncontrolled glaucoma in the study eye defined as intraocular pressure (IOP) >25 millimeters mercury (mmHg); Previous treatment with anti-VEGF drugs or investigational drugs in the study eye; Stroke or myocardial infarction during the 6-month period prior to baseline; Uncontrolled blood pressure defined as a systolic value ≥160 mmHg or diastolic value ≥100 mmHg; Other protocol-specified inclusion/exclusion criteria may apply.

Information: novartis.email@novartis.com

Study: Phase 4 IOP Signals Associated with ILUVIEN (PALADIN)

ClinicalTrials.gov Identifier: NCT02424019

Sponsor: Alimera Sciences

Purpose: The specific objectives include the study of intraocular pressure (IOP) related data in patients who received ILUVIEN and how it relates to the patient's experiences following prior treatment with a course of corticosteroid which did not result in a clinically significant IOP elevation.

Design: Single group, no masking

Number of Patients: 153

Inclusion Criteria: Patients who are eligible for treatment with ILUVIEN based on the prescribing information.

Exclusion Criteria: Patients who are unable to understand and sign the informed consent form.

Study: ROBIN: A Study That Tests BI 1467335 in Patients with Diabetic Eye Disease (Diabetic Retinopathy). It Looks at the Way BI 1467335 is Taken up, the Effects it Has, and How Well it is Tolerated.

ClinicalTrials.gov Identifier: NCT03238963

Sponsor: Boehringer Ingelheim

Purpose: The main objective is to evaluate ocular and systemic safety and tolerability of BI 1467335 as well as whether BI 1467335 monotherapy has a potential to improve retinal lesions in patients with moderately severe Non-proliferative diabetic retinopathy (NPDR) (DRSS level 47) or severe Non-proliferative diabetic retinopathy (NPDR) (DRSS level 53), without Center-involved diabetic macular edema (CI-DME).

Design: Randomized, parallel assignment, double blind

Number of Patients: 100

Inclusion Criteria: Of legal age (according to local legislation, usually ≥18 years) at screening, male or female patients (women of childbearing potential (WOCBP) must be ready and able to use 2 methods of contraception with at least one of them being a highly effective method of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly), diagnosis of diabetes mellitus (type 1 or type 2), glycosylated hemoglobin (HbA1c) ≤12% at screening, non-proliferative diabetic retinopathy (NPDR) without center-involved diabetic macular edema (CI-DME) in the study eye at screening with NPDR level 47 or level 53, as determined by the Central reading center (CRC) by using the DR severity scale (DRSS), best corrected visual acuity ETDRS letter score ≥70 letters in the study eye at screening, media clarity, pupillary dilation and individual cooperation sufficient for adequate retinal examination including fundus photographs and Optical Coherence Tomography (OCT), signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial.

Exclusion Criteria: Cataract surgery performed within 6 months prior to screening or planned during the trial, or any additional eye disease in the study eye that, in the opinion of the investigator, could compromise or alter visual acuity during the course of the study (eg, vein occlusion, uncontrolled intraocular pressure (IOP) >24 mmHg on optimal medical treatment, glaucoma with visual field loss, uveitis or other ocular inflammatory disease, vitreomacular traction, monocular vision, history of ischemic optic neuropathy, or genetic disorders such as retinitis pigmentosa), active center-involved DME (CI-DME) on clinical examination and Optical Coherence Tomography (OCT) central subfield thickness above 300 μm in the study eye, as measured by Optovue Optical Coherence Tomography (OCT) Heidelberg OCT, anterior segment and vitreous abnormalities in the study eye that would compromise the adequate assessment of the best corrected visual acuity or an adequate examination of the posterior pole, evidence of neovascularization on clinical examination including active neovascularization of the iris (small iris tufts are not an exclusion) or angle neovascularization in the study eye, ruled out by gonioscopy (documented in the last 4 weeks before screening or performed at screening), prior panretinal photocoagulation (defined as ≥100 burns placed previously outside of the posterior pole) in the study eye, history of DME or DR treatment with macular laser within 3 months prior to screening, or intraocular injections of medication within 6 months prior to screening, and no more than 4 prior intraocular injections in the study eye at any time in the past, patients treated with Monoamine Oxidase (MAO) inhibitors or drugs that may have potential side effects due to MAO inhibition, current or planned, during the trial, use of medications known to be toxic to the retina, lens or optic nerve, or cause vision loss, patients who must or wish to continue the intake of other restricted medications or any drug considered likely to interfere with the safe conduct of the trial, estimated Glomerular filtration rate (eGFR) <60 mL/min/1.73m2 calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation at screening, or where the investigator expects filtration rate is likely to drop below 60 mL/min/1.73m2 during the trial, alanine transaminase (ALT) or aspartate transaminase (AST) greater than 2.0-fold the upper limit of normal, or total bilirubin >1.5x upper limit of normal, uncontrolled arterial hypertension defined as a single measurement of systolic blood pressure >180 mmHg, or 2 consecutive measurements of systolic blood pressure >160 mmHg and/or diastolic blood pressure >100 mmHg on optimal medical regimen at screening. If blood pressure is brought to ≤160/100 mmHg by antihypertensive treatment until randomization, individual can become eligible, Wolff-Parkinson-White Syndrome, baseline QTc >450 ms, family history of long QT, or on medication prolonging QT time at screening or planned initiation during the trial, diagnosis of a serious or unstable systemic or eye disease and other conditions that, in the clinical judgment of the investigator, are likely to interfere with the analyses of safety and efficacy in this study. Patients with an expected life expectancy of less than 2 years are also excluded, active known or suspected chronic or relevant acute infections, such as HIV (human immunodeficiency virus)\viral hepatitis, or tuberculosis. QuantiFERON TB test and HBs Ag test will be performed during screening. Patients with a positive test result may participate in the study if further work up (according to local practice/guidelines) establishes conclusively that the patient has no evidence of active infection, any documented active or suspected malignancy or history of malignancy within 5 years prior to screening, except appropriately treated basal cell carcinoma of the skin or in situ carcinoma of uterine cervix, chronic alcohol or drug abuse or any condition that, in the investigator's opinion, makes them an unreliable study participant or unlikely to complete the trial, known hypersensitivity to any component of the trial drug and/or allergy to fluorescein dye, major surgery (major according to the investigator's assessment) performed within 12 weeks prior to randomization or planned during the trial, eg, hip replacement, currently enrolled in another investigational drug trial, or less than 30 days or 5 times half-life of the investigational drug, whichever is longer, since ending another investigational drug trial from the screening visit in this trial or receiving other investigational treatment(s); patients participating in a purely observational trial will not be excluded, previous randomization in this trial, women who are pregnant, nursing, or who plan to become pregnant while in the trial, any other clinical condition that, in the opinion of the investigator, would jeopardize patient safety while participating in this clinical trial.

Study: A Dose Ranging Study of OPT-302 With Aflibercept for Persistent Diabetic Macular Edema

ClinicalTrials.gov Identifier: NCT03397264

Sponsor: Opthea Limited

Purpose: A 2 part, multi-center study consisting of a Phase 1b open label, sequential dose escalation followed by a Phase 2a randomized, double-masked, dose expansion evaluating OPT-302 in combination with aflibercept in participants with persistent central-involved Diabetic Macular Edema.

Design: Randomized, parallel assignment, quadruple masking

Number of Patients: 117

Inclusion Criteria: History of diabetic macular edema (DME) ≤1 year; persistent DME despite prior intravitreal anti-VEGF-A therapy with a suboptimal response; 3 or more prior anti-VEGF-A therapy intravitreal injections; EDTRS BCVA score ≤73 and ≥24 letters.

Exclusion Criteria: Ocular disorders or ocular treatments which may interfere with assessment of visual acuity, assessment of toxicity, or fundus photography in the Study Eye; HbA1c ≥12% and/or recent signs of uncontrolled diabetes; any clinically significant disorder or condition or disease (eg, cardiovascular, renal conditions) that would make the participant unsuitable for the study.

Information: info@opthea.com

Study: DRCR.Net Aflibercept vs Bevacizumab + Deferred Aflibercept for the Treatment of CI-DME (DRCR AC)

ClinicalTrials.gov Identifier: NCT03321513

Sponsor: Jaeb Center for Health Research

Purpose: To compare the efficacy of intravitreous aflibercept with intravitreous bevacizumab + deferred aflibercept if needed in eyes with CI DME and moderate vision loss.

Design: Randomized, parallel assignment, double masking

Number of Patients: 260

Inclusion Criteria: Best corrected Electronic-Early Treatment Diabetic Retinopathy Study visual acuity letter score <69 (ie, 20/50 or worse) and ≥24 (ie, 20/320 or better) within 8 days of randomization. On clinical exam, definite retinal thickening due to diabetic macular edema involving the center of the macula. Diabetic macular edema present on optical coherence tomography (OCT) within 8 days of randomization; Zeiss Cirrus central subfield: ≥290µm in women or ≥305µm in men; Heidelberg Spectralis central subfield: ≥305µm in women or ≥320µm in men; investigator must verify accuracy of OCT scan by ensuring it is centered and of adequate quality. Media clarity, pupillary dilation, and individual cooperation sufficient for adequate fundus photographs.

Exclusion Criteria: Macular edema is considered to be due to a cause other than diabetic macular edema. An eye should not be considered eligible if: (1) the macular edema is considered to be related to ocular surgery such as cataract extraction or (2) clinical exam and/or OCT suggest that vitreoretinal interface abnormalities (eg, a taut posterior hyaloid or epiretinal membrane) are the primary cause of the macular edema. An ocular condition is present such that, in the opinion of the investigator, visual acuity loss would not improve from resolution of macular edema (eg, foveal atrophy, pigment abnormalities, dense subfoveal hard exudates, nonretinal condition). An ocular condition is present (other than diabetes) that, in the opinion of the investigator, might affect macular edema or alter visual acuity during the course of the study (eg, vein occlusion, uveitis or other ocular inflammatory disease, neovascular glaucoma, etc.). Substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by 3 lines or more (ie, cataract would be reducing acuity to 20/40 or worse if eye was otherwise normal). History of an anti-vascular endothelial growth factor (anti-VEGF) treatment for diabetic macular edema (DME) in the past 12 months or history of any other treatment for DME at any time in the past 4 months (such as focal/grid macular photocoagulation, intravitreous or peribulbar corticosteroids). Enrollment will be limited to a maximum of 25% of the planned sample size with any history of anti-VEGF treatment for DME. Once this number of eyes has been enrolled, any history of anti-VEGF treatment for DME will be an exclusion criterion. History of pan-retinal photocoagulation within 4 months prior to randomization or anticipated need for pan-retinal photocoagulation in the 6 months following randomization. History of anti-VEGF treatment for a disease other than DME in the past 12 months. History of major ocular surgery (including vitrectomy, cataract extraction, scleral buckle, any intraocular surgery, etc.) within prior 4 months or anticipated within the next 6 months following randomization. History of YAG capsulotomy performed within 2 months prior to randomization. Aphakia. Exam evidence of external ocular infection, including conjunctivitis, chalazion, or significant blepharitis. Evidence of uncontrolled glaucoma.

Study: SwapTwo: Treatment of Diabetic Macular Edema with Aflibercept in Subjects Previously Treated with Ranibizumab or Bevacizumab

ClinicalTrials.gov Identifier: NCT02559180

Sponsor: Rishi Singh, MD, Cleveland Clinic Foundation/Regeneron

Purpose: To evaluate the safety and efficacy of treatment of diabetic macular edema with intravitreal aflibercept in subjects previously treated with intravitreal anti-VEGF agents (ranibizumab or bevacizumab).

Design: Single Group, Open Label, Treatment

Number of Patients: 20

Inclusion Criteria: Foveal-involving retinal edema secondary to DME based on investigator review of clinical exam and SD-OCT with central subfield thickness value of 325 microns by Zeiss Cirrus SD-OCT; E-ETDRS best-corrected visual acuity of: 20/25 to 20/400 in the study eye; history of previous treatment with anti-VEGF with at least 4 injections over the last 6 months.

Exclusion Criteria: Any prior or concomitant therapy with another investigational agent to treat DME in the study eye; prior panretinal photocoagulation in the study eye within the past 3 months; prior intravitreal anti-VEGF therapy in the study eye within 30 days of enrollment; prior systemic anti-VEGF therapy, investigational or FDA-approved, is only allowed up to 3 months prior to first dose, and will not be allowed during the study; previous treatment with intravitreal aflibercept injection; significant vitreous hemorrhage obscuring view to the macula or the retinal periphery as determined by the investigator on clinical exam.

Information: mcowend@ccf.org, singhr@ccf.org, borera@ccf.org

Study: Anti-VEGF Treatment for Prevention of PDR/DME

ClinicalTrials.gov Identifier: NCT02634333

Sponsor: Jaeb Center for Health Research

Purpose: To determine the efficacy and safety of intravitreous aflibercept injections vs sham injections (observation) for prevention of PDR or CI-DME in eyes at high risk for development of these complications.

Design: Randomized, Safety/Efficacy, Parallel Assignment, Double-Blind, Prevention

Number of Patients: 322

Inclusion Criteria: No evidence of neovascularization on clinical exam including active neovascularization of the iris (small iris tufts are not an exclusion) or angle neovascularization (if the angle is assessed); no evidence of neovascularization (NV) on fluorescein angiography within the 7-modified ETDRS fields, confirmed by the central Reading Center prior to randomization. The widest method of imaging available at the site must be used to document whether there is NV present in the periphery; however, presence of NV outside of the 7-modified ETDRS fields on ultrawide field imaging will not be an exclusion provided treatment is not planned; no center-involved diabetic macular edema (CI-DME) on clinical exam and optical coherence tomography (OCT) central subfield thickness must be below the following gender and OCT-machine specific thresholds.

Exclusion Criteria: Exam or photographic evidence of vitreous or preretinal hemorrhage presumed to be from PDR; history of prior vitreous hemorrhage or preretinal hemorrhage presumed to be from PDR; history of prior PRP (defined as ≥100 burns outside of the posterior pole); an ocular condition is present (other than diabetic retinopathy) that, in the opinion of the investigator, might alter visual acuity during the course of the study (eg, retinal vein or artery occlusion, uveitis or other ocular inflammatory disease, vitreomacular traction, etc.).

Information: www.jaeb.org

RETINAL VEIN OCCLUSION

NEW: Study: TLC399 (ProDex) in Subjects With Macular Edema Due to Retinal Vein Occlusion (RVO)

ClinicalTrials.gov Identifier: NCT03093701

Sponsor: Taiwan Liposome Company

Purpose: Randomized, double-masked trial designed to investigate the use of TLC399 (ProDex) in subjects with macular edema due to CRVO or BRVO.

Design: Randomized, parallel assignment, quadruple masking

Number of Patients: 61

Inclusion Criteria: Male or female, at least 18 years of age. Macular edema due to CRVO or BRVO. Best-corrected visual acuity (BCVA) score of 20/40 to 20/400. Mean central subfield thickness (CST) ≥350 um. Willing and able to comply with the study procedure and sign a written informed consent. Agree to use a medically acceptable form of birth control.

Exclusion Criteria: Poorly controlled diabetes. History of significant intraocular pressure (IOP) elevation to steroid treatment. History of ocular hypertension and glaucoma. Cataract surgery in the study eye within 3 months, or intraocular surgery within 6 months prior to screening. Use of hemodilution for the treatment of RVO. Use of IVT ranibizumab or bevacizumab in the study eye within 6 weeks prior to screening; or IVT aflibercept within 8 weeks prior to screening. IVT Ozurdex to the study eye within 6 months prior to screening. Prior use of Retisert or Iluvien. Use of systemic steroids or heparin within 1 month prior to screening.

Study: Assessing the Efficacy and Safety of Brolucizumab Versus Aflibercept in Patients With Visual Impairment Due to Macular Edema Secondary to Central Retinal Vein Occlusion (RAVEN)

ClinicalTrials.gov Identifier: NCT03810313

Sponsor: Novartis Pharmaceuticals

Purpose: The purpose of this study is to evaluate the efficacy and safety of brolucizumab in treatment of patients with macular edema (ME) secondary to central retinal vein occlusion (CRVO).

Design: Randomized, parallel assignment, triple masking

Number of Patients: 750

Inclusion Criteria: Signed informed consent must be obtained prior to participation in the study. Patients with visual impairment due to ME secondary to CRVO diagnosed < 6 months prior to screening. BCVA score between 78 and 23 letters, inclusive, using ETDRS visual acuity testing charts (approximate Snellen equivalent of 20/32 to 20/320) at both screening and baseline visits.

Exclusion Criteria: Concomitant conditions or ocular disorders in the study eye at screening or baseline which could, in the opinion of the investigator, prevent response to study treatment or may confound interpretation of study results, compromise visual acuity or require medical or surgical intervention during the first 12-month study period (e.g. structural damage of the fovea, vitreous hemorrhage, retinal vascular occlusion other than CRVO, retinal detachment, macular hole, or choroidal neovascularization of any cause, diabetic retinopathy (except mild non-proliferative) and diabetic macular edema). Any active intraocular or periocular infection or active intraocular inflammation (e.g. infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis, uveitis) in study eye at screening or baseline. Uncontrolled glaucoma in the study eye defined as intraocular pressure (IOP) > 25 mmHg on medication, or according to investigator's judgment, at screening or baseline. Presence of amblyopia, amaurosis or ocular disorders in the fellow eye with BCVA < 20/200 at screening (except when due to conditions whose surgery may improve VA, e.g. cataract). Previous treatment with any anti-VEGF therapy or investigational drugs in the study eye at any time prior to baseline. Previous use of intraocular or periocular steroids in study eye at any time prior to baseline. Macular laser photocoagulation (focal/grid) in the study eye at any time prior to baseline and peripheral laser photocoagulation in the study eye within 3 months prior to the baseline. Intraocular surgery in the study eye during the 3‑month period prior to baseline. Vitreoretinal surgery in the study eye at any time prior to baseline. Aphakia with the absence of posterior capsule in the study eye.

Information: novartis.email@novartis.com

Study: Assessing the Efficacy and Safety of Brolucizumab Versus Aflibercept in Patients With Visual Impairment Due to Macular Edema Secondary to Branch Retinal Vein Occlusion (RAPTOR)

ClinicalTrials.gov Identifier: NCT03802630

Sponsor: Novartis Pharmaceuticals

Purpose: The purpose of this study is to evaluate the efficacy and safety of brolucizumab in treatment of patients with macular edema (ME) secondary to branch retinal vein occlusion (BRVO).

Design: Randomized, parallel assignment, triple masking

Number of Patients: 500

Inclusion Criteria: Signed informed consent must be obtained prior to participation in the study. Patients with visual impairment due to ME secondary to BRVO diagnosed < 6 months prior to screening. BCVA score between 78 and 23 letters, inclusive, using ETDRS visual acuity testing charts (approximate Snellen equivalent of 20/32 to 20/320) at both screening and baseline visits.

Exclusion Criteria: Concomitant conditions or ocular disorders in the study eye at screening or baseline which could, in the opinion of the investigator, prevent response to study treatment or may confound interpretation of study results, compromise visual acuity or require medical or surgical intervention during the first 12-month study period (e.g. structural damage of the fovea, vitreous hemorrhage, retinal vascular occlusion other than BRVO, retinal detachment, macular hole, or choroidal neovascularization of any cause, diabetic retinopathy (except mild non-proliferative) and diabetic macular edema). Hemiretinal vein occlusion should be excluded. Any active intraocular or periocular infection or active intraocular inflammation (e.g. infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis, uveitis) in study eye at screening or baseline. Uncontrolled glaucoma in the study eye defined as intraocular pressure (IOP) > 25 mmHg on medication, or according to investigator's judgment, at screening or baseline. Presence of amblyopia, amaurosis or ocular disorders in the fellow eye with BCVA < 20/200 at screening (except when due to conditions whose surgery may improve VA, e.g. cataract). Previous treatment with any anti-VEGF therapy or investigational drugs in the study eye at any time prior to baseline. Previous use of intraocular or periocular steroids in study eye at any time prior to baseline. Macular laser photocoagulation (focal/grid) in the study eye at any time prior to baseline and peripheral laser photocoagulation in the study eye within 3 months prior to the baseline. Intraocular surgery in the study eye during the 3‑month period prior to baseline. Vitreoretinal surgery in the study eye at any time prior to baseline. Aphakia with the absence of posterior capsule in the study eye.

Information: novartis.email@novartis.com

Study: Phase I Study of Episcleral Celecoxib for Treatment of Macular Edema and Inflammatory Disorders of the Posterior Pole

ClinicalTrials.gov Identifier: NCT04120636

Sponsor: Targeted Therapy Technologies, LLC

Purpose: This phase I trial will assess primarily the safety and secondarily the anti-inflammatory and anti-neovascular effect of Episcleral Celecoxib in patients suffering from macular edema and other inflammatory disorders of the retina, choroid and vitreous.

Design: Single group, no masking

Number of Patients: 3

Inclusion Criteria: Age ≥18 years; Visual acuity letter score in study eye <70 and ≥25 letters (approximate Snellen equivalent 20/32 to 20/320); ophthalmoscopic evidence of center-involved macular edema, within the central subfield (CSF); inflammatory disorders of the sclera, choroid, retina or vitreous.

Exclusion Criteria: Inability to understand informed consent, cooperate with testing or return to follow-up visits; pregnant or lactating women; co-existent ocular disorder of the cornea, lens or media that will interfere with assessment of safety or efficacy.

Study: Episcleral Dexamethasone for Treatment of Macular Edema and Inflammatory Disorders of the Posterior Pole

ClinicalTrials.gov Identifier: NCT04120311

Sponsor: Targeted Therapy Technologies, LLC

Purpose: This phase I trial will assess primarily the safety and secondarily anti-inflammatory effect of Episcleral Dexamethasone in patients suffering from macular edema and other disorders of the retina, choroid and vitreous.

Design: Single group, no masking

Number of Patients: 3

Study: A Depot Formulation of Sunitinib Malate (GB-102) in Subjects with Diabetic Macular Edema and Retinal Vein Occlusion

ClinicalTrials.gov Identifier: NCT04085341

Sponsor: Graybug Vision

Design: Nonrandomized, parallel assignment, no masking

Number of Patients: 20

Information: vsmith@graybug.com

Study: Assessing the Efficacy and Safety of Brolucizumab Versus Aflibercept in Patients with Visual Impairment Due to Macular Edema Secondary to Central Retinal Vein Occlusion (RAVEN)

ClinicalTrials.gov Identifier: NCT03810313

Sponsor: Novartis Pharmaceuticals

Purpose: The purpose of this study is to evaluate the efficacy and safety of brolucizumab in treatment of patients with macular edema (ME) secondary to central retinal vein occlusion (CRVO).

Design: Randomized, parallel assignment, triple masking

Number of Patients: 750

Inclusion Criteria: Signed informed consent must be obtained prior to participation in the study. Patients with visual impairment due to ME secondary to BRVO diagnosed <6 months prior to screening. BCVA score between 78 and 23 letters, inclusive, using ETDRS visual acuity testing charts (approximate Snellen equivalent of 20/32 to 20/320) at both screening and baseline visits.

Exclusion Criteria: Concomitant conditions or ocular disorders in the study eye at screening or baseline which could, in the opinion of the investigator, prevent response to study treatment or may confound interpretation of study results, compromise visual acuity or require medical or surgical intervention during the first 12-month study period (eg structural damage of the fovea, vitreous hemorrhage, retinal vascular occlusion other than BRVO, retinal detachment, macular hole, or choroidal neovascularization of any cause, diabetic retinopathy (except mild non-proliferative) and diabetic macular edema). Hemiretinal vein occlusion should be excluded. Any active intraocular or periocular infection or active intraocular inflammation (eg infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis, uveitis) in study eye at screening or baseline. Uncontrolled glaucoma in the study eye defined as intraocular pressure (IOP) >25 mmHg on medication, or according to investigator's judgment, at screening or baseline. Presence of amblyopia, amaurosis or ocular disorders in the fellow eye with BCVA <20/200 at screening (except when due to conditions whose surgery may improve VA, eg cataract). Previous treatment with any anti-VEGF therapy or investigational drugs in the study eye at any time prior to baseline. Previous use of intraocular or periocular steroids in study eye at any time prior to baseline. Macular laser photocoagulation (focal/grid) in the study eye at any time prior to baseline and peripheral laser photocoagulation in the study eye within 3 months prior to the baseline. Intraocular surgery in the study eye during the 3‑month period prior to baseline. Vitreoretinal surgery in the study eye at any time prior to baseline. Aphakia with the absence of posterior capsule in the study eye.

Information: novartis.email@novartis.com

Study: Treatment of Central Retinal Vein Occlusion Using Stem Cells Study (TRUST)

ClinicalTrials.gov Identifier: NCT03981549

Sponsor: The Emmes Company, LLC

Purpose: This study evaluates whether intravitreal autologous CD34+ stem cell therapy is safe, feasible and potentially beneficial in eyes with vision loss from central retinal vein occlusion (CRVO). Half of the participants will receive immediate cellular therapy followed by sham therapy 6 months later, while the other half will receive immediate sham therapy followed by cellular therapy 6 months later. Participants will be followed for a total of 2 years.

Design: Randomized, parallel assignment, triple masking

Number of Patients: 20

Inclusion Criteria: Clinical diagnosis of central retinal vein occlusion (CRVO) confirmed by review of medical records and screening assessment. Best Corrected Visual Acuity (BCVA) obtained during the screening period is in the range of 20/60+ to 20/400- (ETDRS letter score in the range of 18 to 63, inclusive). Duration of vision loss from CRVO ≥6 months to 3 years.

Exclusion Criteria: Previous eye treatment with intravitreal or periocular steroids, intravitreal injection, laser or intraocular surgery within 6 months prior to enrollment (ie, date ICF signed) or treatment expected during the study period. History of concurrent ocular herpes infection. Active non-herpetic eye infection diagnosed within 8 weeks from enrollment (ie, date Informed Consent Form (ICF) signed). Glaucoma requiring treatment with more than 1 medication, laser or intraocular surgery. Active uveitis or history of recurrent uveitis or uveitis involving the posterior segment. Presence of cataract that is impairing vision. Presence of lens or lens implant subluxation. History of ocular trauma that is currently impairing vision. History or concurrent optic nerve or retinal disease, including macular degeneration, myopic degeneration, retinitis pigmentosa, retinal tear or detachment. Active retinal or iris neovascularization. Macular edema requiring on-going therapy or where treatment is expected during the study period. Significant media opacity precluding view of the fundus for examination, photography or optical coherence tomography (OCT) including cataract and vitreous haze. High myopia (>9 diopters); Amblyopia; Other cause contributing to vision loss at screening. History of any of the following procedures: corneal transplant, glaucoma surgery, photodynamic therapy, retinal cryopexy, pneumatic retinopexy, intraocular oil or scleral buckle.

Information: dcmacias@ucdavis.edu, mesalvador@ucdavis.edu

Study: TLC399 (ProDex) in Subjects with Macular Edema Due to Retinal Vein Occlusion (RVO)

ClinicalTrials.gov Identifier: NCT03093701

Sponsor: Taiwan Liposome Company

Purpose: Randomized, double-masked trial designed to investigate the use of TLC399 (ProDex) in subjects with macular edema due to CRVO or BRVO.

Design: Randomized, parallel assignment

Number of Patients: 61

Inclusion Criteria: Male or female, at least 18 years of age; macular edema due to CRVO or BRVO; best-corrected visual acuity (BCVA) score of 20/40 to 20/400; mean central subfield thickness (CST) ≥350 um; willing and able to comply with the study procedure and sign a written informed consent; agree to use a medically acceptable form of birth control.

Exclusion Criteria: Poorly controlled diabetes; history of significant intraocular pressure (IOP) elevation to steroid treatment; history of ocular hypertension and glaucoma; cataract surgery in the study eye within 3 months, or intraocular surgery within 6 months prior to screening; use of hemodilution for the treatment of RVO; use of IVT ranibizumab or bevacizumab in the study eye within 6 weeks prior to screening; or IVT aflibercept within 8 weeks prior to screening; IVT Ozurdex to the study eye within 6 months prior to screening; prior use of Retisert or Iluvien; use of systemic steroids or heparin within 1 month prior to screening.

Study: Post Intravitreal Injection Topical NSAID vs Patching

ClinicalTrials.gov Identifier: NCT03918590

Sponsor: The New York Eye & Ear Infirmary

Purpose: A prospective randomized trial, to evaluate postinjection comfort measures comparing topical NSAID (nepafenac 0.3% suspension) and patching.

Design: Randomized, parallel assignment

Number of Patients: 60

Study: Study Assessing AR-1105 in Subjects with Macular Edema Due to Retinal Vein Occlusion (RVO)

ClinicalTrials.gov Identifier: NCT03739593

Sponsor: Aerie Pharmaceuticals

Purpose: This study will evaluate the safety, tolerability and efficacy of AR-1105 (dexamethasone implant) for the treatment of macular edema (ME) due to retinal vein occlusion (RVO). A more durable intravitreal implant containing a low dose of dexamethasone may result in less frequent retreatments, and potentially lower the incidence of steroid-related side effects without compromising efficacy.

Design: Randomized, parallel assignment, no masking

Number of Patients: 40

Inclusion Criteria: At least 18 years of age; Vision loss due to clinically detectable macular edema (ME) associated with either central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO). Subjects may be treatment-naïve, or if previously-treated with a steroid, must have demonstrated response to treatment; Duration of macular edema (ME) ≥9 months in subjects with CRVO and ≥12 months in subjects with BRVO. If both eyes are eligible, the study eye will be the eye with worse VA; Best-corrected visual acuity (BCVA) as measured by the early treatment of diabetic retinopathy study (ETDRS) methodology of between 25 and 70 letters, in the study eye and better than 35 letters, in the non-study eye; Retinal thickness in the central subfield of >290 µm (females) and >305 μm (males) if using a Cirrus (Zeiss) instrument, or if a Spectralis (Heidelberg) instrument is used, thickness should be >305 μm (females) or >320 μm (males) in the study eye; Be able to understand and willing to provide written informed consent. Be willing and able to adhere to the instructions set forth in the study protocol.

Exclusion Criteria: Ophthalmic: Presence of a clinically significant epiretinal membrane, active retinal or optic disc neovascularization, active or history of choroidal neovascularization, presence of rubeosis iridis; History or presence of herpetic infection, toxoplasmosis, chorioretinopathy. Subjects with moderate non-proliferative diabetic retinopathy or worse in either eye are excluded from participation; Any active infection; Aphakia, significant posterior capsule tear or iris trauma in the study eye; Anterior-chamber intraocular lens; Clinically significant media opacity; History of glaucoma or visual field loss; Ocular hypertension in the study eye at qualification, (with or without treatment); History of corticosteroid-induced IOP increase in either eye; Ocular condition in the study eye that, in the opinion of the investigator, would prevent a 15-letter improvement in visual acuity; Received an intraocular steroid injection or implant within 6 months or any anti-VEGF treatment within 2 months prior to screening. Prior treatment with RETISERT or ILUVIEN or panretinal photocoagulation (PRP) is exclusionary; Intraocular surgery (including laser refractive or eyelid surgery) within 3 months prior to visit 1 or anticipated need for ocular surgery or ophthalmic laser treatment during the study treatment period; Currently using topical corticosteroids in the vicinity of the eyes within the 1 month prior to visit 1; Periocular depot of steroids placed within 6 months prior to qualification; Ocular medications that are specifically disallowed in this protocol for any condition during the study or within the specified timeframe prior to visit 2’ Have progressive optic nerve disease or retinal disease other than retinopathy due to RVO that affects BCVA. Systemic: Currently using or anticipating the use of systemic corticosteroids during the study (with the exception of inhaled, intranasal or topical corticosteroids); Any clinically significant or uncontrolled serious or severe medical or psychiatric condition; Participation in any other clinical study within 30 days prior to visit 1; History of hypersensitivity or poor tolerance to any components of the preparations to be used in this study such as dexamethasone or biodegradable polymer (PLGA) excipients or fluorescein; Systemic condition that may confound the study outcome per the investigator's opinion; Women of childbearing potential who are pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of birth control.

Information: nramirez@aeriepharma.com; jlopez@aeriepharma.com

Study: Study of Comparative Treatments for Retinal Vein Occlusion 2 (SCORE2)

ClinicalTrials.gov Identifier: NCT01969708

Sponsor: The EMMES Corporation

Purpose: SCORE2 is a multicenter, prospective, randomized, phase III clinical trial in which all participants enrolled will be followed for up to 2.5 years. SCORE2 is designed as a non-inferiority trial, with study eyes randomized to intravitreal bevacizumab (1.25 mg) every 4 weeks vs intravitreal aflibercept (2.0 mg) every 4 weeks. SCORE2 aims to determine if bevacizumab is non-inferior to aflibercept for the treatment of macular edema associated with central retinal vein occlusion (CRVO), with the primary outcome of visual acuity measured at month 6.

Design: Randomized, parallel assignment, single masking

Number of Patients: 362

Inclusion Criteria: Participants must have center-involved macular edema secondary to CRVO. Eyes may be enrolled as early as the time of diagnosis of the macular edema. The definition of CRVO used in SCORE will also be used for the purposes of SCORE2: a CRVO is defined as an eye that has retinal hemorrhage or other biomicroscopic evidence of retinal vein occlusion (eg, telangiectatic capillary bed) and a dilated venous system (or previously dilated venous system) in all 4 quadrants. Due to the similarities of a hemiretinal vein occlusion (HRVO) to CRVO, HRVO will be classified as CRVO for the purposes of this clinical trial. Eyes classified as having a HRVO will be limited to no more than 25% of the planned sample size. A HRVO is defined as an eye that has retinal hemorrhage or other biomicroscopic evidence of retinal vein occlusion (eg telangiectatic capillary bed) and a dilated venous system (or previously dilated venous system) in 5 or more clock hours but less than all 4 quadrants. Typically, a HRVO is a retinal vein occlusion that involves 2 altitudinal quadrants. E-Early Treatment Diabetic Retinopathy Study (ETDRS)visual acuity score of greater than or equal to 19 letters (approximately 20/400) and less than or equal to 73 letters (approximately 20/40) by the ETDRS visual acuity protocol. The investigator must believe that a study eye with visual acuity between 19 and 33 letters is perfused. Retinal thickness on SD-OCT measurement, defined as central subfield thickness of 300 µm or greater. If the SD-OCT measurement is taken from a Heidelberg Spectralis Machine, the central subfield thickness should be 320 µm or greater. Media clarity, pupillary dilation and participant cooperation sufficient for adequate fundus photographs.

Exclusion Criteria: A condition that, in the opinion of the investigator, would preclude participation in the study (eg, chronic alcoholism or drug abuse, personality disorder or use of major tranquilizers indicating difficulty in long term follow-up, likelihood of survival of less than 12 months). Participation in an investigational trial within 30 days of study entry that involved treatment with any drug that has not received regulatory approval at time of study entry. History of allergy to any anti-VEGF agent, corticosteroid, or component of the delivery vehicle. The participant will be moving out of the area of the clinical site to an area not covered by another clinical site during the 12 months of the study. Positive urine pregnancy test: all women of childbearing potential (those who are premenopausal and not surgically sterilized) may participate only if they have a negative urine pregnancy test, and if they do not intend to become pregnant during the timeframe of the study. Women who are sexually active with a male partner must agree to use at least one of the following birth control methods: hormonal therapy such as oral, implantable or injectable chemical contraceptives; mechanical therapy such as spermicide in conjunction with a barrier such as a condom or diaphragm; intrauterine device (IUD); or surgical sterilization of partner. Women who are breast-feeding. Examination evidence of vitreoretinal interface disease (eg, vitreomacular traction, epiretinal membrane), either on clinical examination or OCT thought to be contributing to macular edema. An eye that, in the investigator's opinion, would not benefit from resolution of macular edema such as eyes with foveal atrophy, dense pigmentary changes or dense subfoveal hard exudates. Presence of an ocular condition that, in the opinion of the investigator, might affect macular edema or alter visual acuity during the course of the study (eg, age-related macular degeneration, uveitis or other ocular inflammatory disease, neovascular glaucoma, iris neovascularization, Irvine-Gass Syndrome, prior macula-off rhegmatogenous retinal detachment). Presence of a substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by 3 lines or more (ie, a 20/40 cataract). History of laser photocoagulation for macular edema within 3 months prior to randomization. History of intravitreal corticosteroid within 4 months of randomization. Intravitreal anti-VEGF injection within 2 months of randomization. Note: Enrollment will be limited to no more than 25% of the planned sample size with any history of anti-VEGF treatment. Once this number of eyes has been enrolled, any history of anti-VEGF treatment will be an exclusion criterion. For enrollment of study eyes with prior intravitreal anti-VEGF agents, in the opinion of the investigator, the treatment response to prior anti-VEGF treatment must be either incomplete or the study eye had developed recurrent CRVO-associated macular edema, such that the study eye would benefit from additional anti-VEGF treatment. History of peribulbar or retrobulbar corticosteroid use for any reason within 2 months prior to randomization. History of panretinal scatter photocoagulation (PRP) or sector laser photocoagulation within 3 months prior to randomization or anticipated within the next 3 months following randomization. History of major ocular surgery (including cataract extraction, scleral buckle, any intraocular surgery, etc.) within 4 months prior to randomization or anticipated within the next 6 months following randomization. History of yttrium aluminum garnet (YAG) capsulotomy performed within 2 months prior to randomization. Aphakia. Presence of an anterior chamber intraocular lens. Examination evidence of external ocular infection, including conjunctivitis, chalazion or significant blepharitis. History of macular detachment. Examination evidence of any diabetic retinopathy.

Information: https://secure.emmes.com/scoreweb

ClinicalTrials.gov Identifier: NCT03790852

Sponsor: Kodiak Sciences, Inc.

Design: Randomized, parallel assignment, no masking

Number of Patients: 50

Inclusion Criteria: RVO Cohort: Treatment naïve retinal vein occlusion with macular edema and secondary visual impairment. BCVA ETDRS letter score ≤78 and ≥23 (⁓20/25 to ⁓20/320 Snellen equivalent) in the study eye. Central subfield thickness (CST) of ≥300 microns on SD-OCT (Heidelberg Spectralis or equivalent). Branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO) are both eligible. Decrease in vision in the study eye determined by the investigator to be primarily the result of macular edema secondary to RVO.

Exclusion Criteria: RVO Cohort: Initial diagnosis of RVO of more than 4 months from screening in the study eye. Active retinal or iris neovascularization in the study eye. Prior intravitreal anti-VEGF therapy or steroid injection, or steroid implant (dexamethasone or triamcinolone) in the study eye.

Information: jehrlich@kodiak.com, pablovm@kodiak.com

UVEITIS

NEW: Study: A 48 Week Study to Evaluate the Efficacy and Safety of Two (2) EYS606 Treatment Regimens in Subjects With Active Chronic Non-infectious Uveitis (CNIU) (ELECTRO)

ClinicalTrials.gov Identifier: NCT04207983

Sponsor: Eyevensys

Purpose: The objective of the study is to evaluate the efficacy and safety of two different treatment regimens of EYS606.

Design: Randomized, parallel assignment

Number of Patients: 56

Inclusion Criteria: Subject must be 18 years of age or older. Subject must have a diagnosis of chronic non-infectious uveitis of any anatomic subtype (anterior, intermediate, posterior or panuveitis). Subject must have a history of chronic or recurrent non-infectious uveitis requiring or having required treatment with corticosteroids (systemic, periocular or intraocular) and/or systemic immunosuppressive medication(s) in the 12 months prior to the screening visit. Best corrected visual acuity of Study Part I: ≥ 5 and < 67 ETDRS letters in the study eye (equivalent to less than or equal to 20/50 but better than or equal to 20/800 Snellen). Study Part II: ≥ 5 and < 77 ETDRS letters in the study eye (equivalent to less than or equal to 20/32 but better than or equal to 20/800 Snellen). At the screening and baseline visits subject must have active chronic non-infectious uveitis as evidenced by at least one or more of the following in the study eye: Active retinal vasculitis (retinal vascular leakage) involving the posterior pole confirmed by the reading center. Vitreous haze grade ≥ 2+ (SUN classification). Anterior chamber cell grade ≥ 2+ (SUN classification); anterior chamber cells must be present for subjects with a diagnosis of chronic anterior non-infectious uveitis. Persistent macular edema (defined as central retinal thickness (CRT) > 300 microns or > 320 microns using Zeiss Cirrus and Topcon or Heidelberg Spectralis spectral domain ocular coherence tomography (SD-OCT) instruments, respectively) despite treatment with corticosteroids and/or immunosuppressive therapy for at least 4 weeks prior to screening. Subject receiving concomitant topical and/or systemic corticosteroids or allowed systemic immunosuppressive medications must have maintained the same treatment regimen (dosage/frequency) for at least 2 weeks prior to the baseline (V1) visit, (if applicable).

Information: ronald.buggage@eyevensys.com

Study: Efficacy and Safety of H.P. ACTHAR GEL in Adults with Retinal Vasculitis

ClinicalTrials.gov Identifier: NCT03066869

Sponsor: Ocular Immunology and Uveitis Foundation

Purpose: The purpose of this study is to evaluate the short- and long-term efficacy and safety of Acthar for the treatment of adults with non-infectious retinal vasculitis.

Design: Single group, no masking

Number of Patients: 40

Inclusion Criteria: Any adult patient with active retinal vasculitis (involving arteries or veins) as a manifestation of non-infectious ocular inflammatory disease; fundus must be viewable with wide-field FA in the study eye. If both eyes are involved, both are eligible for inclusion in the study. Patients already on nonsteroidal immunosuppressive therapy may continue on this during the study, but the dose must not be increased or decreased within 6 weeks of initiating the trial. Willing and able to sign the informed consent form.

Exclusion Criteria: Patients under age 18. Patients who are pregnant (must be ruled out in women of child-bearing age). Active infectious ocular or systemic disease. Patients with active infectious ocular or extraocular disease. Patients with history of malignancy, except for dermatologic entities of basal or squamous cell carcinoma which have been completely excised or removed previously. Patients with systemic illness involving abnormalities of the hypothalamic-pituitary-adrenal axis; patients with primary adrenocortical insufficiency or adrenocortical hyperfunction. Patients with known hypersensitivity to Acthar. Patients on other non-steroidal systemic immunomodulatory medications with dose adjusted sooner than 6 weeks prior to study drug administration. Patients currently on or recently treated with (within 6 weeks) systemic corticosteroid. Patients with periocular or intraocular injections of medications administered to help control inflammation sooner than 6 weeks prior to study drug administration. Patients with severe disease that warrants critical attention, deemed unsafe for the study by the investigator, or contraindicated, including but not limited to, patients with scleroderma, osteoporosis, systemic fungal infections, ocular herpes simplex, recent surgery, history of or the presence of a peptic ulcer, congestive heart failure, uncontrolled hypertension, or sensitivity to proteins of porcine origin. Administration of live or live attenuated vaccines is contraindicated in patients during the entire duration of the study and for 1 month prior.

Information: sfoster@mersi.com

Study: Assessment of the Anti-inflammatory Effects of Norflo Oro in Acute Relapses of HLA-B27 Associated Autoimmune Uveitis

ClinicalTrials.gov Identifier: NCT03584724

Sponsor: Eye Pharma; Bascom Palmer Eye Institute

Purpose: The purpose of this study is to explore the efficacy of Norflo Oro in the treatment of relapsing autoimmune uveitis (RAU), measured as a long term reduction of the frequency and the severity of relapses, in patients with HLA-B27 associated uveitis, under conditions of routine medical practice. The reduction of the mean number of relapses per patient between the year before study treatment and the study period will also be assessed.

Design: Randomized, parallel assignment, quadruple masking

Number of Patients: 5

Inclusion Criteria: Clinical diagnosis of HLA-B27 positive related uveitis in nonacute phase. At least 1 autoimmune uveitis relapse.

Exclusion Criteria: Use of supplements (nutraceuticals) or systemic therapy for uveitis with anti-inflammatory immunosuppressive or biological drugs within last 30 days. Anticipated need for systemic anti-inflammatory treatment during the study. Use of intravitreal peribulbar, sub-tenon, periocular injection in the previous 6 months. Long-term treatment with a systemic anti-inflammatory, immune suppressant drugs. Woman taking hormonal contraceptives, pregnant or breastfeeding.

Information: laceyfeigl@wustl.edu

Study: Tofacitinib for Inflammatory Eye Disease

ClinicalTrials.gov Identifier: NCT03580343

Sponsor: Washington University School of Medicine

Purpose: Non-infectious inflammatory eye disease, such as uveitis and scleritis, is a chronic, autoimmune process that leads to vision loss. While steroids are effective in the short term, the side-effect profile of chronic steroid use necessitates the identification of effective steroid-sparing therapies. Tofacitinib is a small molecule that inhibits the signaling pathways of multiple inflammatory cytokines. The investigators plan to evaluate whether tofacitinib may have efficacy for patients with uveitis and/or scleritis.

Design: Single group, no masking

Number of Patients: 5

Inclusion Criteria: Diagnosis of uveitis; a clinical response to steroids; active disease requiring at least 10mg of prednisone daily (or steroid equivalent).

Exclusion Criteria: Suspected or confirmed ocular infection; chronic or recurring infections, such as HIV; renal insufficiency that would preclude safe administration of tofacitinib.

Information: laceyfeigl@wustl.edu

Study: Adalimumab vs Conventional Immunosuppression for Uveitis Trial (ADVISE)

ClinicalTrials.gov Identifier: NCT03828019

Sponsor: JHSPH Center for Clinical Trials

Purpose: Based upon preliminary data, adalimumab, a fully-human, anti-TNF-α monoclonal antibody, now US FDA-approved for uveitis treatment, may be a superior corticosteroid-sparing agent than conventional immunosuppressive drugs. The ADVISE Trial is multicenter randomized, parallel-treatment, comparative effectiveness trial comparing adalimumab to conventional (small molecule) immunosuppression for corticosteroid spring in the treatment of non-infectious, intermediate, posterior, and panuveitides.

Design: Randomized, parallel assignment, no masking

Number of Patients: 222

Inclusion Criteria: Age 13 years or older; active or recently active (≤60 days) non-infectious, intermediate, posterior, or panuveitis; prednisone indication meets one of the following: a. Active uveitis requiring one of the following i. Initiation of prednisone at dose greater than 7.5 mg/day ii. Increasing prednisone dose to greater than 7.5 mg/day iii. Currently receiving dose greater than 7.5 mg/day; b. Inactive uveitis on current dose greater 7.5 mg/day. Initiation or addition of an immunosuppressive drug (ie, a conventional immunosuppressive drug or adalimumab) is indicated. If currently receiving a conventional immunosuppressive drug, the drug and dose have been stable for at least 30 days. Patient able and willing to self-administer subcutaneous injections or have a qualified person available to administer subcutaneous injections. If posterior segment disease is present, ability to assess activity in at least 1 eye with uveitis. Visual acuity of light perception or better in at least 1 eye with uveitis.

Exclusion Criteria: Active tuberculosis or untreated latent tuberculosis (eg, positive interferon-γ release assay [IGRA] test, such as Quantiferon-gold). Untreated active hepatitis B or C infection. Behçet disease. Multiple sclerosis. For patients with intermediate uveitis, abnormal magnetic resonance imaging (MRI) of the brain consistent with demyelinating disease. Use of anti-TNF monoclonal antibody therapy within past 60 days. History of adalimumab intolerance or ineffectiveness. Current treatment with an alkylating agent. Current treatment with more than 1 immunosuppressive drug, not including oral corticosteroids. Shorter-acting regional corticosteroids administered within the past 30 days in any eye(s) with uveitis. Long-acting ocular corticosteroid implants, ie, fluocinolone acetonide implant (eg, Retisert, Yutiq, Iluvien) placed within past 3 years unless uveitis is active in all eye(s) with an implant. Systemic disease that is sufficiently active such that it dictates therapy with systemic corticosteroids or immunosuppressive agents at the time of enrollment. Immunodeficiency disease for which immunosuppressive therapy would be contraindicated according to best medical judgment. Pregnancy, lactation, or for women of child-bearing potential unwillingness to use appropriate birth control for the duration of the trial. Medical problems or drug or alcohol dependence problems sufficient to prevent adherence to treatment and study procedures.

Information: jholbro1@jhu.edu, esugar2@jhu.edu

Study: OCT Technology Development to Assess Ocular Integrity and Characterize Ocular Integrity and Intraocular Scatterers

ClinicalTrials.gov Identifier: NCT03531853

Sponsor: Duke University

Purpose: The purpose of this study is to develop and demonstrate new technologies that will enable a non-contact, compact eye imaging system based on OCT to assist an early responder in acute care settings (like an emergency room) to help assess eye trauma and inflammation (swelling inside the eye).

Design: Single group, open label

Number of Patients: 75

Inclusion Criteria: Pre-clinical: employees or students (over the age of 18) of the Duke Eye Center or Biomedical Engineering willing to be imaged with OCT system; pilot (ER): patients (over the age of 18) presenting emergently to the Duke Emergency room with traumatic eye injuries and/or suspected open globe; pilot uveitis): patients presenting to the Duke Eye Center with active uveitis and microhyphema or hyphema; patients who have independently consented to undergo vitreous tap or biopsy for their uveitis care at the Duke Eye Center.

Exclusion Criteria: Preclinical: subject cannot be a direct report to any of the PIs or other key personnel of this study; pilot (ER): hemodynamically unstable, unable to consent; pilot (Uveitis): unable to consent; cornea or lens opacity/scar which would block the imaging modality.

Information: teresa.hawks@duke.edu

Study: Efficacy and Safety of H.P. Acthar Gel in Subjects with Severe Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis NIPPU

ClinicalTrials.gov Identifier: NCT03656692

Sponsor: Mallinckrodt

Purpose: The primary objective of this study is to explore the efficacy of Acthar in participants with severe Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis (NIPPU). in reducing aqueous and vitreous indicators of inflammation.

Design: Single group, open label

Number of Patients: 30

Inclusion Criteria: Participants must be adequately informed and understand the nature and risks of the study and must be able to provide a signature and date on the ICF. Participants must be ≥18 years of age at screening visit and can be male or female. Participants must have been diagnosed with current severe NIPPU and have active disease at the baseline visit as defined by the presence of at least 1 of the following parameters in at least 1 eye despite at least 2 weeks of maintenance therapy with oral prednisone 10 mg/day to ≤60 mg/day (or oral corticosteroid equivalent): Active, inflammatory, chorioretinal and/or inflammatory retinal vascular lesion. ≥2+ anterior chamber cells (Standardization of Uveitis Nomenclature [SUN] criteria). ≥2+ vitreous haze (Nussenblatt et al, 1985). Participants entering the study on 1 concomitant immunosuppressive therapy must not have had the dose increased in the 2 weeks prior to the baseline visit and must be within the following allowable doses at the baseline visit: Methotrexate ≤15 mg per week. Cyclosporin ≤4 mg/kg per day. Mycophenolate mofetil ≤2 g per day or an equivalent drug (eg, mycophenolic acid) at an equivalent dose that has been approved by the medical monitor (MM). Azathioprine ≤175 mg per day. Tacrolimus (oral formulation) ≤8 mg per day. Adalimumab 40 mg SC every other week. Participants must be willing to taper their current doses of corticosteroid and immunomodulatory therapy to the minimum effective dose during the study. Female Participants must be of nonchildbearing potential (history of hysterectomy, bilateral oophorectomy, or bilateral tubal ligation; or postmenopausal with no history of menstrual flow in the 12 months prior to the screening visit); or if of childbearing potential must be nonpregnant, nonlactating and agree to use effective contraception when with a male partner throughout study participation (through the Follow-up visit). Acceptable forms of contraception include hormonal measures (oral contraceptive pills, contraceptive patch, contraceptive ring, injections), intrauterine devices, double barrier method (condom plus diaphragm, condom or diaphragm plus spermicidal gel or foam), and abstinence.

Exclusion Criteria: Participant is from a vulnerable population, as defined by the US CFR Title 45, Part 46, Section 46.111(b) and other local and national regulations, including but not limited to, employees (temporary, part-time, full time, etc.) or a family member of the research staff conducting the study, or of the sponsor, or of the clinical research organization, or of the IRB/IEC. Participant has a history of sensitivity to ACTH preparations or sensitivity to porcine protein products. Participant has had recent (within the previous 6 months) diabetic retinopathy, age-related macular degeneration, intraocular surgery or ocular trauma, cataracts, or posterior capsule opacification. Participant is under treatment with any corticosteroids, immunosuppressants, immunomodulators, or biologic agents for a concomitant condition (eg, rheumatoid arthritis under treatment with a tumor necrosis factor- alpha [TNF-α] drug). Participants are specifically excluded for any of the following: Participant has received (glucocorticosteroid implant) within 3 years prior to the baseline visit or has had complications related to the device and/or Participant has had removal within 90 days prior to the baseline visit or has had complications related to the removal of the device. Participant has received intraocular or periocular corticosteroids within 30 days prior to baseline visit. Participant has proliferative or severe nonproliferative diabetic retinopathy or clinically significant macular edema due to diabetic retinopathy. Participant has neovascular/wet age-related macular degeneration. Participant has an abnormality of a vitreoretinal interface (ie, vitreomacular traction, epiretinal membranes, etc) with the potential for macular structural damage independent of the inflammatory process. Participant has a severe vitreous haze that precludes visualization of the fundus at the baseline visit. Participant has any known contraindication(s) to Acthar (Mallinckrodt Package Insert, 2018) including, but not limited to: Any known history of scleroderma, osteoporosis, or ocular herpes simplex. For the purposes of this study, osteoporosis is defined as evidence of current vertebral or long bone fracture, or lumbar T-score >2.0 SD below the mean of the reference population. Any primary adrenocortical insufficiency, or adrenal cortical hyperfunction. Any current congestive heart failure (defined as New York Heart Association. Participant has a history of chronic active hepatitis including active or chronic hepatitis B, or acute or chronic hepatitis C. Participant has a history of tuberculosis (TB) infection, any signs/symptoms of TB, or any close contact with an individual with an active TB infection. Participant has known immune compromised status (not related to disease/condition under study), including but not limited to, individuals who have undergone organ transplantation or who are known to be positive for the human immunodeficiency virus. Participant has any solid tumor malignancy currently diagnosed or undergoing therapy, or has received therapy for any solid tumor malignancy in the 5 years prior to the screening visit; with the exception of treated and cured basal cell carcinoma, treated and cured squamous cell carcinoma of the skin, and treated and cured carcinoma in situ of the cervix. Participant has any of the following laboratory abnormalities at the screening visit: Hemoglobin ≤8.0 g/dL. Platelets ≤50,000 cells/μL. Absolute neutrophil count (ANC) ≤1000 cells/μL. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin 2 times upper limit of normal (ULN). Glycosylated hemoglobin (HbA1c) 6.5. Positive Hepatitis B surface antigen (HBsAg) or Hepatitis B core antibody (HBcAb), or positive Hepatitis C virus antibody (HCV). (If HCV is positive at screening, HCV polymerase chain reaction [PCR] will be automatically analyzed. Participants with a positive HCV must have HCV PCR <25 IU/mL at the screening visit to be eligible). Participant has any other clinically significant disease, disorder or laboratory abnormality (including those listed on the Prescribing Information Section 5: Warnings and Precautions [Mallinckrodt Package Insert, 2018]) which, in the opinion of the investigator (by its nature or by being inadequately controlled), might put the patient at risk due to participation in the study, or may influence the results of the study or the Participant's ability to complete the study.

Information: sandra.greene@mnk.com; joseph.grieco@mnk.com

Study: A Phase III Study Assessing the Efficacy and Safety of Intravitreal Injections of 440 ug DE-109 for the Treatment of Active, Non-Infectious Uveitis of the Posterior Segment of the Eye (LUMINA)

ClinicalTrials.gov Identifier: NCT03711929

Sponsor: Santen Inc.

Purpose: This is a Phase III study to assess the efficacy and safety of DE-109 440 µg every 2 months in subjects with active, non-infectious uveitis of the posterior segment of the eye (NIU-PS).

Design: Randomized, parallel assignment, quadruple-blind, treatment

Number of Patients: 200

Inclusion Criteria: Noninfectious active uveitis of the posterior segment.

Exclusion Criteria: Females who are pregnant, nursing, or planning a pregnancy; confirmed or suspected infectious uveitis.

Information: clinicaltrials@santen.com

Study: ACTH as A Re-emerging theRapy for Uveitis (The ACTHAR Study) (ACTHAR)

ClinicalTrials.gov Identifier: NCT02931175

Sponsor: Quan Dong Nguyen

Purpose: The study aims to evaluate the potential role of ACTH gel in the management of non-infectious uveitis.

Design: Randomized, parallel assignment, no masking

Number of Patients: 36

Inclusion Criteria: In order to be eligible for the study, patients will be required to meet the criteria of 1 of the 3 following disease cohorts: Active disease and are receiving no treatment. Active disease is defined as having at least 1+ Vitreous Haze using the Standardized Uveitis Nomenclature (SUN) Working Group scale and/or at least 1+ Vitreous Cell Count using Foster & Vitale scale. Active disease and are receiving prednisone ≥10 mg/day (or equivalent dose of another corticosteroid) or at least 1 other systemic immunosuppressant (all systemic immunosuppressants other than corticosteroids will be discontinued 30 days prior to the first administration of the study drug on day 0). Patients receiving combination of prednisone ≥10 mg/day and at least 1 other systemic immunosuppressant are also eligible in this category. Have inactive disease, defined as having <= 0.5+ Vitreous Haze OR <= 0.5+ Vitreous Cell Count (SUN scale), and are receiving prednisone ≥10 mg/day (or equivalent dose of another corticosteroid) or at least 1 other systemic immunosuppressant (all systemic immunosuppressants other than corticosteroids will be discontinued 30 days prior to the first administration of the study drug on day 0). Patients receiving combination of prednisone ≥10 mg/day and at least 1 other systemic immunosuppressant are also eligible in this category.

Exclusion Criteria: Subjects who have any of the following at the screening visit are not eligible for enrolment in this study: Any significant ocular disease that could compromise vision in the study eye. These include, but are not limited to: Diabetic retinopathy: proliferative diabetic retinopathy (PDR) or non-proliferative diabetic retinopathy (NPDR) that compromise the vision. Age-related macular degeneration; Myopic degeneration with active subfoveal choroidal neovascularization. Advanced glaucoma status post trabeculectomy or tube/valve placement. Any of the following treatments within 90 days prior to day 0 or anticipated use of any of the following treatments to the study eye: Intravitreal injections (including but not limited to steroids or anti-vascular endothelial growth factors); Posterior subtenon's steroids. Intraocular surgery within 90 days prior to day 0 in the study eye; Capsulotomy within 30 days prior to day 0 in the study eye; Any known ocular surgery (including cataract extraction or capsulotomy) of the study eye anticipated within the first 180 days following day 0; Intraocular pressure(IOP) ≥25 mmHg in the study eye (glaucoma patients maintained on no more than 2 topical medications with IOP <25 mmHg are allowed to participate); Pupillary dilation inadequate for quality stereoscopic fundus photography in the study eye; Media opacity that would limit clinical visualization; Presence of any form of ocular malignancy in the study eye, including choroidal melanoma; History of herpetic infection in the study eye or adnexa; Presence of known active or inactive toxoplasmosis in either eye; Presence of ocular or periocular infection in either eye; Participation in other investigational drug or device clinical trials within 30 days prior to day 0, or planning to participate in other investigational drug or device clinical trials within 180 days following day 0. This includes both ocular and non-ocular clinical trials. Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization. Prior treatment with any cell-depleting therapies, including investigational agents or approved therapies, some examples are anti-cluster of differentiation (CD) 4, anti- cluster of differentiation (CD)5, anti-cluster of differentiation (CD) 3, anti-cluster of differentiation (CD)19 and anti-cluster of differentiation (CD)20. Treatment with intravenous gamma globulin, plasmapheresis or Prosorba column within 6 months of baseline. Immunization with a live/attenuated vaccine within 4 weeks prior to baseline. Previous treatment with ACTHAR within 3 months of day 0 of study visit. Any previous treatment with alkylating agents such as chlorambucil, or with total lymphoid irradiation.

Information: imaging@oirrc.net

Study: Safety and Efficacy of an Injectable Fluocinolone Acetonide Intravitreal Insert

ClinicalTrials.gov Identifier: NCT01694186

Sponsor: pSivida Corp.

Purpose: This is a phase 3, multi-national, multi-center, randomized, masked, controlled study to evaluate the safety and efficacy of an injectable fluocinolone acetonide intravitreal (FAI) insert for the management of subjects with non-infectious uveitis affecting the posterior segment of the eye. Patients will be randomized to receive either a sham injection or the FAI insert and will be observed for 3 years following treatment.

Design: Randomized, parallel assignment, double masking

Number of Patients: 129

Inclusion Criteria: Male or non-pregnant female at least 18 years of age at time of consent. One or both eyes having a history of recurrent non-infectious uveitis affecting the posterior segment of the eye with or without anterior uveitis >1 year duration. At the time of enrollment (day 1), study eye has <10 anterior chamber cells/HPF and a vitreous haze ≤grade 2. Visual acuity of study eye is at least 15 letters on the ETDRS chart. Subject is not planning to undergo elective ocular surgery during the study. Subject has ability to understand and sign the Informed Consent Form. Subject is willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures. During the 12 months prior to enrollment (day 1), the study eye has either received treatment: systemic corticosteroid or other systemic therapies given for at least 3 months, and/or at least 2 intra- or peri-ocular administrations of corticosteroid for management of uveitis OR the study eye has experienced recurrence: at least 2 separate recurrences of uveitis requiring systemic, intra- or peri-ocular injection of corticosteroid.

Exclusion Criteria: Allergy to fluocinolone acetonide or any component of the FAI insert. History of posterior uveitis only that is not accompanied by vitritis or macular edema. History of iritis only and no vitreous cells, anterior chamber cells or vitreous haze. Uveitis with infectious etiology. Vitreous hemorrhage. Intraocular inflammation associated with a condition other than noninfectious uveitis (eg, intraocular lymphoma). Ocular malignancy in either eye, including choroidal melanoma. Toxoplasmosis scar in study eye or scar related to previous viral retinitis. Previous viral retinitis. Current viral diseases of the cornea and conjunctiva including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella, mycobacterial infections of the eye or fungal diseases of ocular structures. Media opacity precluding evaluation of retina and vitreous. Peripheral retinal detachment in area of insertion. Diagnosis of any form of glaucoma or ocular hypertension in study eye at screening, unless study eye has been previously treated with an incisional surgery procedure that has resulted in stable IOP in the normal range (10-21 mmHg). Intraocular pressure (IOP) >21 mmHg or concurrent therapy at screening with any IOP-lowering pharmacologic agent in the study eye. Chronic hypotony (<6 mmHg). Ocular surgery on the study eye within 3 months prior to study day 1. Capsulotomy in study eye within 30 days prior to study day 1. Prior intravitreal treatment of study eye with Retisert within 36 months prior to study day 1. Prior intravitreal treatment of study eye with Ozurdex within 6 months prior to study day 1. Prior intravitreal treatment of study eye with Triesence or Trivaris within 3 months prior to study day 1. Prior peri-ocular or subtenon steroid treatment of study eye within 3 months prior to study day 1. Subjects requiring chronic systemic or inhaled corticosteroid therapy (>15mg prednisone daily) or chronic systemic immunosuppressive therapy. Excluding certain skin cancers (specifically, basal cell carcinoma and squamous cell carcinoma), any malignancy receiving treatment, or in remission less than 5 years prior to study day 1. Subjects who have tested positive for human immune deficiency virus (HIV), tuberculosis or syphilis. Systemic infection within 30 days prior to study day 1. Any severe acute or chronic medical or psychiatric condition that could increase the risk associated with study participation or could interfere with the interpretation of study results and, in the judgment of the investigator, could make the subject inappropriate for entry into this study. Any other systemic or ocular condition which, in the judgment of the investigator, could make the subject inappropriate for entry into this study. Treatment with an investigational drug or device within 30 days prior to study day 1. Pregnant or nursing females; females of childbearing potential who are unwilling or unable to use an acceptable method of contraception as outlined in this protocol from at least 14 days prior to study day 1 until the month 12 visit. Subjects unlikely to comply with the study protocol or who are likely to be lost to follow-up within 3 years.

Study: Humboldt: Efficacy and Safety of Filgotinib in Adults with Active Noninfectious Uveitis

ClinicalTrials.gov Identifier: NCT03207815

Sponsor: Gilead Sciences

Purpose: The primary objective of this study is to evaluate the efficacy of filgotinib vs placebo for the treatment of the signs and symptoms of noninfectious uveitis in participants failing treatment for active noninfectious uveitis.

Design: Randomized, parallel assignment, double masking, treatment

Number of Patients: 110

Inclusion Criteria: Is diagnosed with noninfectious intermediate-, posterior-, or panuveitis; Must have active uveitic disease at the day 1/baseline visit as defined by the presence of at least 1 of the following parameters in at least 1 eye despite 2 weeks or more of maintenance therapy with oral prednisone (≥10 mg/day to ≤60 mg/day) or oral corticosteroid equivalent: Active, inflammatory, chorioretinal and/or inflammatory retinal vascular lesion; ≥2+ anterior chamber cells per the Standardization of Uveitis Nomenclature (SUN) criteria; ≥2+ vitreous haze per the National Eye Institute/Standardization of Uveitis Nomenclature (NEI/SUN) criteria. No evidence of active tuberculosis (TB), history of prior TB or latent TB meeting the screening criteria.

Exclusion Criteria: Adults with severe glaucoma at screening are not eligible to participate; severe glaucoma is defined as: Intraocular pressure of ≥25 mmHg and on ≥2 glaucoma medications and/or; Any evidence of glaucomatous optic nerve injury. Confirmed or suspected infectious uveitis, including but not limited to infectious uveitis due to TB, cytomegalovirus (CMV), Human T-Lymphotropic Virus Type 1 (HTLV-1), Whipple's disease, Herpes Zoster virus (HZV), Lyme disease, toxoplasmosis and herpes simplex virus (HSV). Adults with a prior failure of anti-tumor necrosis factor (TNF) therapy or previous exposure to any biologic therapy (except intravitreal anti-vascular endothelial growth factor [VEGF] therapy) with a potential therapeutic impact on noninfectious uveitis within 90 days of day 1/ baseline are not eligible to participate.

Information: GileadClinicalTrials@gilead.com

Study: MERIT: Macular Edema Ranibizumab v. Intravitreal Anti-inflammatory Therapy Trial

ClinicalTrials.gov Identifier: NCT02623426

Sponsor: JHSPH Center for Clinical Trials

Purpose: This trial will compare the relative efficacy and safety of intravitreal methotrexate, intravitreal ranibizumab, and the intravitreal dexamethasone implant for the treatment of uveitic macular edema persisting or reoccurring after an intravitreal corticosteroid injection. MERIT is a parallel design (1:1:1), randomized comparative trial with an anniversary close-out at the 6-month clinic visit. The primary outcome is percent change in central subfield thickness from the baseline OCT measurement to the 12 week visit.

Design: Randomized, parallel assignment, single masking, treatment

Number of Patients: 240

Inclusion Criteria: 18 years of age or older; at least 1 eye must meet all of the following conditions; Inactive or minimally active noninfectious anterior, intermediate, posterior or panuveitis, as defined by SUN132 criteria as ≤0.5+ anterior chamber cells, ≤0.5+ vitreous haze grade and no active retinal/choroidal lesions for a minimum of 4 weeks; Macular edema (ME) defined as the presence of macular thickness greater than the normal range for the OCT machine being used (see cut points below), regardless of the presence of cysts, following an intravitreal corticosteroid injection (≥4 weeks following intravitreal triamcinolone injection or ≥12 weeks following intravitreal dexamethasone implant injection); Greater than 300 μm for Zeiss Cirrus Greater than 320 μm for Heidelberg Spectralis Greater than 300 μm for Topcon 3DOCT; baseline fluorescein angiogram that, as assessed by the study ophthalmologist, is gradable for degree of leakage in the central subfield; Best corrected visual acuity (BCVA) 5/200 or better; baseline intraocular pressure >5 mm Hg and ≤21 mm Hg (current use of ≤3 intraocular pressure-lowering medications and/or prior glaucoma surgery are acceptable (Note: combination medications, eg, Combigan, are counted as 2 IOP-lowering medications); Media clarity and pupillary dilation sufficient to allow OCT testing and assessment of the fundus.

Exclusion Criteria: History of infectious uveitis in either eye; History of infectious scleritis of any type in either eye (Note: History of noninfectious scleritis that has been active in past 12 months is an eye-level exclusion -see #13 below); History of keratitis (with the exception of keratitis due to dry eye) in either eye; History of central serous retinopathy in either eye; Active infectious conjunctivitis in either eye; Oral prednisone dose >10 mg per day (or of an alternative corticosteroid at a dose higher than that equipotent to prednisone 10 mg per day) OR oral prednisone dose ≤10 mg per day at baseline that has not been stable for at least 4 weeks (note: if patient is off of oral prednisone at baseline (M01 study visit) dose stability requirement for past 4 weeks does not apply); Systemic immunosuppressive drug therapy that has not been stable for at least 4 weeks (note: use of systemic methotrexate is acceptable as long as regimen has been stable for at least 4 weeks); Use of oral acetazolamide or other systemic carbonic anhydrase inhibitor at baseline; Known allergy or hypersensitivity to any component of the study drugs; For women of childbearing potential: pregnancy, breastfeeding, or a positive pregnancy test; unwilling to practice an adequate birth control method (abstinence, combination barrier and spermicide, or hormonal) for duration of trial; Eye level exclusion criteria - at least 1 eye that meets all inclusion criteria cannot have any of the following conditions: History of infectious endophthalmitis; History of severe glaucoma as defined by optic nerve damage (cup/disc ratio of ≥0.9 or any notching of optic nerve to the rim); History of active noninfectious scleritis in past 12 months (Note: History of noninfectious scleritis is acceptable if the last episode of active scleritis resolved at least 12 months prior to enrollment); Presence of an epiretinal membrane noted clinically or by OCT that per the judgment of study ophthalmologist may be significant enough to limit improvement of ME (ie, causing substantial wrinkling of the retinal surface); Torn or ruptured posterior lens capsule; Presence of silicone oil; Ozurdex administered in past 12 weeks; Anti-VEGF agent, intravitreal methotrexate, or intravitreal/periocular corticosteroid administered in past 4 weeks; Fluocinolone acetonide implant (Retisert) placed in past 3 years.

Information: jholbro1@jhu.edu, esugar2@jhu.edu

Study: STAR Study: Ustekinumab (STELARA) for the Treatment of Active Sight-Threatening Uveitis

ClinicalTrials.gov Identifier: NCT02911116

Sponsor: National Eye Institute (NEI)

Purpose: The study objective is to investigate the safety, tolerability and potential efficacy of subcutaneous injections of ustekinumab as a possible treatment for active intermediate uveitis, posterior uveitis or panuveitis.

Design: Prospective, nonrandomized, uncontrolled

Number of Patients: 7

Inclusion Criteria: Participant has the ability to understand and sign the informed consent document; Participant is 18 years of age or older; Participant has negative purified protein derivative (PPD) or quantiferon testing done within 3 months prior to enrollment or had latent tuberculosis (TB) but has completed prophylactic anti-TB treatment; Participant has active intermediate uveitis, posterior uveitis or panuveitis in at least 1 eye requiring systemic therapy. Participant has visual acuity in at least 1 eye of 20/400 or better. Participant is willing and able to comply with the study procedures. Female participants of childbearing potential must not be pregnant or breast-feeding, have a negative pregnancy test at screening and must be willing to undergo pregnancy testing throughout the study. Both female participants of childbearing potential and male participants able to father a child must have (or have a partner who has) had a hysterectomy or vasectomy, be completely abstinent from intercourse or must agree to practice 2 effective methods of contraception throughout the course of the study and for 6 weeks after the last investigational product injection.

Exclusion Criteria: Participant has a significant active infection (an infection requiring treatment as determined by the medical team), including active tuberculosis or human immunodeficiency virus (HIV). Participant received a live vaccination within the past 6 weeks. Participant is expected to receive a live vaccination at any time during the study. Participant received the BCG vaccine within the past year. Participant is expected to receive the BCG vaccine at any time during the study or up to 1 year after discontinuing ustekinumab. Participant has a history of cancer (other than a nonmelanoma skin cancer) diagnosed within the past 5 years. Participant has received intraocular (or periocular) steroid or anti-vascular endothelial growth factor (VEGF) injections within the last 6 weeks. Participant received rituximab within the last 6 months or another biologic agent (eg, infliximab, daclizumab, adalimumab) within the last 2 months. Participant has received alkylating agents (eg, cyclophosphamide, chlorambucil) within the last 9 months. Participant has a known hypersensitivity to ustekinumab or any of its components.

Information: dobiyor@mail.cc.nih.gov

Study: SAVE-2: Intravitreal Sirolimus as Therapeutic Approach to Uveitis

ClinicalTrials.gov Identifier: NCT01280669

Sponsor: Stanford University, Santen Inc.

Purpose: The purpose of this study is to find out about the safety and effectiveness of 2 different doses the study drug, sirolimus, administered intravitreally in patients with uveitis.

Design: Randomized, parallel assignment, no masking

Number of Patients: 30

Inclusion Criteria: >12 years of age, able to give consent, have diagnosis of uveitis, have active uveitis, defined as having at least 1+ Vitreous Haze and/or at least 1+ Vitreous Cell Count (SUN scale), and: are receiving no treatment; or are receiving: prednisone ≥10 mg/day (or equivalent dose of another corticosteroid), or at least 1 systemic immunosuppressant other than corticosteroids, or combination of prednisone ≥10 mg/day (or equivalent dose of another corticosteroid) and other systemic immunosuppressant. Have inactive disease, defined as having 0.5+ vitreous haze or less and 0.5+ or less vitreous cell count (SUN scale), and are receiving: prednisone <10 mg/day (or equivalent dose of another corticosteroid), or at least 1 systemic immunosuppressant other than corticosteroids, or combination of prednisone <10 mg/day (or equivalent dose of another corticosteroid) and other systemic immunosuppressant. Have posterior, intermediate, or panuveitis; for panuveitis, if an anterior component is present, it must be less than the posterior component. Sufficient inflammation to require systemic treatment and, based on the Investigator's decision, warrants intravitreal treatment. Best-corrected ETDRS visual acuity of 20/400 or better (approximately 20 letters) in the study eye. Best-corrected ETDRS visual acuity of 20/400 or better in the fellow eye (approximately 20 letters).

Exclusion Criteria: Patients with bilateral uveitis who are receiving systemic immunosuppressive therapy (eg, methotrexate, cyclosporine, cyclophosphamide, chlorambucil, mycophenolate mofetil, tacrolimus, or azathioprine) other than prednisone or other corticosteroids for the treatment of uveitis and the uveitis in the fellow eye, in the opinion of the Investigator, cannot be controlled with standard local therapies alone; Any significant ocular disease that could compromise the visual outcome in the study eye. Intravitreal injections (including but not limited to anti-vascular endothelial growth factors 60 days prior to the baseline; Posterior subtenon's or intravitreal injection of steroids 90 days prior to baseline; Intraocular surgery within 90 days prior to day 0 in the study eye; Capsulotomy within 30 days prior to day 0 in the study eye; History of vitreoretinal surgery or scleral buckling within 90 days prior to day 0 in the study eye; Any ocular surgery (including cataract extraction or capsulotomy) of the study eye anticipated within the first 180 days following day 0; Intraocular pressure ≥25 mmHg in the study eye (glaucoma patients maintained on no more than 2 topical medications with IOP <25 mmHg are allowed to participate); Pupillary dilation inadequate for quality fundus photography in the study eye; Media opacity that would limit clinical visualization, intravenous fluorescein angiography (IVFA), or OCT evaluation in the study eye; Presence of any form of ocular malignancy in the study eye, including choroidal melanoma; History of herpetic infection in the study eye or adnexa; Presence of known active or inactive toxoplasmosis in either eye; Ocular or periocular infection in either eye; Participation in other investigational drug or device clinical trials within 30 days prior to day 0, or planning to participate in other investigational drug or device clinical trials within 180 days following day 0. This includes both ocular and nonocular clinical trials.

Information: ndquan@stanford.edu, lgreer7@stanford.edu

PentaVision

Retinal Physician

CLINICAL TRIAL UPDATE

DRY AMD

WET AMD

DIABETIC MACULAR EDEMA

RETINAL VEIN OCCLUSION

Recommendations

What to Read Next

PentaVision

Retinal Physician

CLINICAL TRIAL UPDATE

DRY AMD

WET AMD

DIABETIC MACULAR EDEMA

RETINAL VEIN OCCLUSION

Recommendations

What to Read Next

A Summary of the 48th Annual Aspen Retinal Detachment Society Meeting

An Eye on Patient Education

Antiviral Drug Should Not Cause Retinal Toxicity

Coronavirus Delays Pivotal Retinal Trials