AAO CEO Dr. Parke to Step Down

The Academy applauds successes achieved during his tenure.

■ After an eventful and productive 12-year tenure as CEO of the American Academy of Ophthalmology (AAO), David W. Parke II, MD, announced he will step down as the leader of the organization. The search for a new CEO will begin in the near future.

“Helping to lead the American Academy of Ophthalmology and serve my colleagues and their patients has been, and always will be, the highlight of my professional career,” noted Dr. Parke. “It is an honor to work with the dedicated professionals who staff the Academy and who volunteer in its initiatives. I couldn’t be prouder of the work they do and its impact. I pledge to remain active in whatever way best serves the organization and my beloved profession.”

“Under his leadership, the Academy has enjoyed tremendous success and weathered daunting challenges, growing stronger every year of his tenure,” said Tamara R. Fountain, MD, president of the Academy. “From the founding of the IRIS Registry and the creation of the new public museum to leading the Academy and its members through COVID-19, he has embodied and vastly expanded the strengths of the organization.”

Prior to becoming Academy CEO, Dr. Parke served for 17 years as president and CEO of the Dean McGee Eye Institute and Edward L. Gaylord Professor and Chair of the Department of Ophthalmology in the University of Oklahoma College of Medicine.

Kodiak Launches Phase 3 Trial for Monthly Wet AMD Dosing

Company to pursue a broad product label.

■ Kodiak Sciences has attracted much positive attention for its KSI-301 antibody biopolymer conjugate (ABC) platform across a range of retinal diseases in clinical trials because of its durability beyond existing treatments. However, the company recently announced a new pivotal trial that calls for monthly dosing of KSI-301, which would match the same dosing schedule as currently approved treatments.

“Developing and launching a novel anti-VEGF medicine with extended durability is the central principle of our KSI-301 development program,” said Jason Ehrlich, MD, PhD, chief medical officer of Kodiak, in a news release. “In the last quarter we have continued to make substantial progress in the recruitment of our pivotal studies evaluating long-interval dosing of KSI-301. Toward our goal of having KSI-301 be the anti-VEGF medicine of choice for all eligible patients, and through our continued engagement with the retina community, we have also learned that physicians and retina practices would like to see our labeling for KSI-301 include the option for more frequent dosing. This reduces barriers to reimbursement that have impeded the commercial uptake of other anti-VEGF medications in the past.

“A study of more intensive dosing also allows us to explore the potential for improved treatment outcomes in certain patients,” Dr. Ehrlich continued. “Thus, we are launching the DAYLIGHT study, which will evaluate monthly dosing of KSI-301 in patients with wet AMD. We believe that pursuing a very broad product label will provide physicians with the flexibility, agency, and reimbursement confidence required to individualize treatment for their patients. Based on our discussions with regulators, we also believe the DAYLIGHT study will provide the safety database needed to support monthly labeling not only in wet AMD but in the DME and RVO indications in the [United States] as well. We expect recruitment in DAYLIGHT will begin in the summer of 2021, and we plan to include data from this fifth pivotal study of KSI-301 in our initial BLA submission.”

DAYLIGHT will be an intensive treatment study of KSI-301 in treatment-naïve wet AMD patients. Patients will be randomized to receive either KSI-301 on a monthly dosing regimen or to receive standard-of-care aflibercept (Eylea; Regeneron). The primary endpoint is evaluated at 10 months.

Pneumatic Retinopexy Favored in RD Study

A minimally invasive procedure has superior functional outcomes to vitrectomy.

■ INTERNATIONAL NEWS – A minimally invasive retinal reattachment procedure that can be done in an ophthalmologist’s office leads to better long-term integrity and structure of the retina’s photoreceptors. The study, published in JAMA Ophthalmology and led by researchers at St. Michael’s Hospital of Unity Health Toronto, contributes to a growing body of evidence pointing toward pneumatic retinopexy (PnR) as the better first-line retinal reattachment technique to achieve the best visual outcomes.

“Our study shows there is a difference in the long-term integrity of the photoreceptors between different surgical techniques, and these anatomic differences were associated with visual outcomes,” said co-principal investigator Rajeev H. Muni, MD, a vitreoretinal surgeon at St. Michael’s.

Using data from a randomized trial conducted at St. Michael’s Hospital, researchers compared the retinal scans of 72 patients who had retinal reattachment using PPV and 73 patients who had retinal reattachment using the minimally invasive PnR at 12 months postoperatively. In PnR, a small gas bubble is used to close the retinal tear and allow the fluid to reabsorb naturally and slowly. The imaging showed that discontinuity, an absence of a part of the photoreceptor layer, was more common at 12 months postoperatively among patients who had pars-plana vitrectomy surgical reattachment than in patients who had the PnR procedure. Discontinuity indicates damage to cells that are critical for vision, and this damage was found to be associated with worse visual outcomes.

Novartis Halts 3 Beovu Trials

Trials were terminated due to incidence of intraocular inflammation.

■ A high rate of intraocular inflammation (IOI), including cases of retinal vasculitis (RV) and retinal vascular occlusion (RO), has again been noted with Novartis’s anti-VEGF brolucizumab (Beovu), which was approved in 2019 for wet AMD. Novartis reported the adverse events when it released the first interpretable 1-year results of the phase 3 MERLIN study, a 2-year study assessing the efficacy and safety of brolucizumab 6 mg vs aflibercept 2 mg (Eylea; Regeneron) given every 4 weeks following the loading phase in patients with wet AMD who have persistent retinal fluid despite anti-VEGF therapy.

The drug met MERLIN’s primary endpoint of noninferiority in change in BCVA from baseline and superiority on select anatomic secondary endpoints at year 1 vs aflibercept when given every 4 weeks following the loading phase. However, given every 4 weeks in MERLIN, IOI including RV and RO were reported with a higher frequency in the Beovu 6 mg arm than in the arm receiving aflibercept 2 mg (IOI: 9.3% vs 4.5%, of which RV: 0.8% vs 0.0% and RO: 2.0% vs 0.0%). The overall rate of vision loss (15 letters or more) due to all causes was 4.8% in the brolucizumab arm and 1.7% in the aflibercept arm.

Novartis evaluated all ongoing brolucizumab clinical programs assessing studies with 4-week dosing intervals after the loading phase. In the interest of patient safety, Novartis has decided to terminate the MERLIN study as well as the RAPTOR and RAVEN studies, which were assessing the efficacy and safety of brolucizumab with 6 initial monthly injections in retinal vein occlusion. All other relevant ongoing trial protocols will be amended to discontinue 4-week dosing intervals after the loading phase.

AGTC Reports Positive Early XLRP Data

Applied Genetic Technologies Corporation reported new positive data from the ongoing X-linked retinitis pigmentosa (XLRP) phase 1/2 clinical gene therapy trial, including 12-month data from groups 5 (n=6) and 6 (n=2) reflecting a 50% response rate among patients who met the inclusion criteria for the Skyline and Vista trials and 24-month data from 2 of 3 group 4 patients providing preliminary evidence of response durability. Taken together, these data add to the body of evidence suggesting that durable improvements in visual sensitivity and visual acuity may be achieved in patients receiving AGTC’s XLRP product candidate while continuing to demonstrate a favorable safety profile.

“The rate and durability of response for improvements in retinal sensitivity are very promising, as are continued trends of increased visual acuity at Month 12 in some patients,” said Robert Sisk, MD, associate professor of ophthalmology at the University of Cincinnati and Cincinnati Eye Institute, and an investigator on AGTC’s XLRP phase 1/2 clinical trial.

International Group Classifies 25 Types of Uveitis

An international coalition of eye researchers used machine learning to develop classification criteria for 25 of the most common types of uveitis, a collection of over 30 diseases characterized by inflammation inside the eye. The Standardization of Uveitis Nomenclature (SUN) Working Group, funded by the NEI, published its classification criteria in the American Journal of Ophthalmology.

“In the past, clinical research in the field of uveitis has been hampered by the lack of widely accepted and validated diagnostic criteria,” said Douglas A. Jabs, MD, MBA, the SUN project leader and professor of epidemiology and ophthalmology, Johns Hopkins Bloomberg School of Public Health. “These classification criteria are a major step forward for epidemiologic studies, translational studies, pathogenesis research, outcomes research, and clinical trials. They hopefully will yield better disease-specific approaches to diagnosis and treatment.”

In uveitis, inflammation can be seen in the anterior chamber (anterior uveitis), vitreous (intermediate uveitis), choroid, or retina (posterior uveitis), or all of these (panuveitis). Disease course, complications of uveitis, and the effect on vision vary dependent on the specific disease. Some uveitis appears abruptly and resolves. However, many cases are recurrent or chronic, requiring long-term therapy. Symptoms may include floaters, vision loss, pain, and light sensitivity.

Until recently, classification of uveitis was based on the primary location of inflammation. However, types of uveitis affecting the same anatomic location can have different causes, courses, prognoses, and treatment needs.

“The agreement among uveitis experts on the diagnosis of individual diseases was modest at best. So, we set off to try to provide clarity, using informatics, formal consensus techniques, and technology to assist in classifying each uveitic disease,” said Jabs.

Eyepoint Wet AMD Trial Fully Enrolled

Eyepoint Pharmaceuticals has completed patient enrollment of its phase 1 DAVIO clinical trial of EYP-1901 as a potential twice-yearly sustained delivery anti-VEGF treatment targeting wet AMD. EYP-1901 combines a bioerodible formulation of Eyepoint’s proprietary Durasert drug-release technology and vorolanib, a tyrosine kinase inhibitor.

“We are pleased to report the completion of enrollment of all 3 dose cohorts in our ongoing phase 1 trial of EYP-1901,” said Nancy Lurker, CEO of Eyepoint Pharmaceuticals. We remain on track to provide interim data from the trial in the fourth quarter of 2021.”

The ongoing DAVIO trial is an open-label 12-month dose-escalation trial examining wet AMD patients who were responsive to previous anti-VEGF therapies. The primary endpoint of the trial is safety and key secondary endpoints are changes in BCVA and central subfield thickness. EYP-1901 is delivered via a single intravitreal injection in the physician's office. The company anticipates that 6-month interim data will include initial safety and efficacy evaluations.

Half-dose PDT Effective in Chronic CSC

In the Spectra study of 107 patients with chronic CSC that was presented at the 2021 ARVO virtual annual meeting, half-dose photodynamic therapy (PDT) was found more effective in controlling subretinal fluid (SRF) than oral eplerenone. Patients were randomized in a 1:1 fashion for inclusion in the trial from 3 participating centers in Europe. The patients underwent either ICGA-guided half-dose PDT (50 J/cm², 83 seconds, 689 nm) with treatment starting 15 minutes after verteporfin infusion or oral eplerenone treatment for a total of 12 weeks. Eplerenone was started at 25mg/day for the first week and then increased to 50mg/day for the following weeks. At the 3-month evaluation, crossover treatment was considered if there was persistent SRF on OCT. The primary endpoint was absence of SRF on OCT.

Of the 96 patients evaluated at the 3-month visit, 38 of 46 (83%) patients in the eplerenone group and 11 of 50 (22%) patients in the half-dose PDT group had persistent SRF on OCT. Of 90 patients evaluated at the final 12-month visit, 38 of 39 (97%) in the group with primary resolution after half-dose PDT, 7 of 7 (100%) in the group with primary resolution after eplerenone, 30 of 35 (85.7%) in the group who received crossover from eplerenone to half-dose PDT, and 5 of 9 (55.5%) in the group who received crossover from half-dose PDT to eplerenone group, had a complete resolution of SRF on OCT. Most of the patients treated with half-dose PDT in either the primary group or crossover treatment group had complete resolution of SRF at 12 months. Out of patients that crossed over from PDT to eplerenone, 5 of 9 (56%) had complete resolution of SRF at 12 months. At 12 months, the half-dose PDT group had a significantly greater improvement in BCVA. The study concluded that half-dose PDT is the treatment of choice for achieving complete resolution of SRF in chronic CSCR even after initial treatment with eplerenone.

DORC Launches Trocar Cannula System

DORC is launching the new Eva Aveta trocar cannula system. This is the first system to feature the patent-pending “Push-Fit” infusion connection, plus a unique laser-etched retention feature. Benefits to surgeons and patients also include improved flow rates, a smaller working size, and more stable intraoperative IOP.

Lucentis Biosimilar Passes Equivalency Test

A 477-patient, 48-week phase 3 study conducted by the international Columbus AMD Study Group found that the Lucentis biosimilar FYB201 (Formycon) met the safety and efficacy criteria to be judged as equivalent to the reference drug despite a lightly lower increase in BCVA (+5.1 vs +5.6) at the 8-week primary endpoint. Findings were reported in the journal Ophthalmology.

JCyte Says New Biomarker Will Help Guide Pivotal RP Study

JCyte has identified a positive biomarker in its phase 2b (JCell cell transplantation) retinitis pigmentosa (RP) study that the company will use as an important guide in its upcoming pivotal trial. Patients treated with a single 6-million JCell dose demonstrated an early, sustained, and significant mean improvement in the primary endpoint of BCVA from baseline to 12 months. All key secondary visual function endpoints in the target population were aligned with the BCVA data, with meaningful improvements in peripheral visual field area, contrast sensitivity, and the ability of these patients to ambulate better in lower light settings as measured by the Low Luminance Mobility Test (LLMT).

A detailed analysis by the Cleveland Clinic Cole Eye Institute identified central foveal thickness, measured by spectral-domain optical coherence tomography (SD-OCT), as a positive anatomical marker for response to jCell, which jCyte believes will be an important factor in the inclusion criteria for the phase 3 pivotal study. A strong, statistically significant correlation was seen between central foveal thickness (CFT) and all 5 visual function clinical trial endpoints in the target patient population treated with a single 6-million (high dose) cell dose, with higher CFT values corresponding to greater improvements in each endpoint. A moderate to strong correlation was also seen in the high-dose target group between all trial endpoints and mid-subfield mean ellipsoid zone (EZ) thickness.

“The identification of these important structural predictors of response aligns nicely with the RP patient population expected to respond to jCell treatment based upon its paracrine mechanism of action,” said Sunil Srivastava, MD, from the Cleveland Clinic Cole Eye Institute, lead investigator for the OCT analysis.

AAO Calls for Adoption of DICOM Imaging Format

The American Academy of Ophthalmology is urging ophthalmic imaging device manufacturers to standardize image formats to comply with the Digital Imaging and Communications in Medicine (DICOM) standard. DICOM is recognized in the United States and throughout the world as the medical imaging standard.

The AAO says that widespread adoption of a uniform standard can revolutionize ophthalmology practices by promoting more efficient patient care, enabling the creation of comprehensive datasets for research and big data analyses, and developing algorithms for machine learning and artificial intelligence. This recommendation has already been endorsed by the American Society of Retina Specialists.

Lead author Aaron Y. Lee, MD, MSCI, makes clear that the current lack of standardization in ophthalmology is holding back progress in the profession.

“The new horizon of tools for digital health care rely on being able to interact algorithmically and extract data at scale,” said Dr. Lee in a news release. “There has been great progress with electronic health record data becoming standardized and available directly to patients, but the same has not yet happened for imaging and functional testing data that we routinely collect in our clinics.” Dr. Lee stressed that the benefit to patients would be significant. As physicians gain better access to images and reports, they can provide faster and more coordinated care, he said.

Early Plasma Kallikrein Response in DME

Rezolute announced positive top-line results from its first-in-human phase 1a clinical study of RZ402, the company’s investigational oral plasma kallikrein inhibitor (PKI), for the treatment of DME. Single-dose oral administration of RZ402 to 30 healthy volunteers resulted in plasma concentrations that substantially exceeded target pharmacologically active drug levels, demonstrating the potential for once-daily dosing, and supporting the advancement of developmental activities toward phase 2, including a phase 1b multiple-ascending-dose study. RZ402 was generally safe and well tolerated at all doses tested, without dose-limiting toxicities.

“We’re in need of new treatments in the clinical care of patients with diabetic eye diseases,” said Robert B. Bhisitkul, MD, PhD, professor of ophthalmology and retinal specialist at the University of California San Francisco School of Medicine. “Pioneering research has strongly implicated the kallikrein-kinin system in the development of diabetic retinopathy and macular edema. A novel plasma kallikrein inhibitor has potential to give patients with diabetic macular edema an alternative therapeutic option. Oral delivery would provide the possibility of earlier treatment intervention and enable a patient-controlled regimen with advantages in comfort, convenience, and continuous drug levels in the retinal microvasculature.”