Real-World Data Show Iluvien Reduces DME Treatment Burden

■ Alimera Sciences, Inc. reported that the number of patients receiving 1 or fewer anti-VEGF injections per year for diabetic macular edema (DME) after an Iluvien (fluocinolone acetonide 0.19) injection increased three-fold compared to prior to an Iluvien injection. The real-world data, which were from Alimera’s 24-month phase 4 PALADIN study, also showed that after Iluvien, half as many patients needed more than 4 DME treatments.

Iluvien uses microdosing technology to release submicrogram levels of fluocinolone acetonide for 36 months to reduce the recurrence of disease and number of treatments. The outcomes, which were presented at the 2021 American Society of Retina Specialists meeting, analyzed a subset of 83 eyes that was divided based on the number of supplemental treatment events — including laser, intravitreal anti-VEGF, and steroid — per year before and after receiving Iluvien. In a press release, David Dyer, MD, Alimera Sciences’ chief retina specialist, said the real-world data support the premise of Iluvien’s NEW DAY study. “In the NEW DAY study, we believe that Iluvien, due to its long-term durability and anti-inflammatory properties, can significantly reduce the need for frequent and recurring injections compared to the leading anti-VEGF.”

Atsena Therapeutics Unveils XLRS Novel Gene Therapy

■ Atsena Therapeutics unveiled its preclinical gene therapy program for X-linked retinoschisis (XLRS), a monogenic disease caused by mutations in the RS1 gene and characterized by schisis. Atsena’s XLRS gene therapy program leverages AAV.SPR, a novel capsid that spreads laterally beyond the subretinal injection site, enabling safe and efficient transduction of the central retina. A preclinical study demonstrated that AAV.SPR promotes transgene expression beyond subretinal injection bleb margins.

At clinically relevant doses, AAV.SPR efficiently transduces foveal cones without the need for surgical detachment and does not cause inflammation. “The ability to safely and efficiently target foveal cones and to transduce wider expanses of retinal tissue represents a major leap forward in our field,” Shannon Boye, PhD, founder and director of Atsena, said in a news release.

Suprachoroidal AU-011 Promising in Patients With Choroidal Melanoma

■ Aura Biosciences presented interim phase 2 data evaluating the safety of suprachoroidal (SC) administration of AU-011, its lead product candidate for the first-line treatment of primary choroidal melanoma, at the 2021 meeting of the American Society of Retina Specialists. The primary objective of the study is to assess safety and efficacy of AU-011 via SC administration for purposes of treating primary indeterminate lesions and choroidal melanoma.

There have been no related serious adverse events, dose-limiting toxicities, or grade 3 adverse events observed during the study. The phase 2 trial is comprised of an open-label, dose-escalation phase and a randomized, masked dose-expansion phase that is assessing the safety and efficacy of ascending single and repeat doses of AU-011 via SC administration, followed by 1 or 2 laser applications per treatment. “These interim data demonstrate that suprachoroidal administration may improve the therapeutic index and optimize treatment parameters,” said Prithvi Mruthyunjaya, MD, MHS, director, ocular oncology service, Byers Eye Institute at Stanford University, who presented the data.

The randomized phase of the trial is planned to begin in the second half of 2022 in patients who have documented tumor growth to establish the safety and efficacy of AU-011. The maximum treatment regimen anticipated for the randomized phase is 3 cycles of 3 weekly treatments of AU-011 at a dose of 80 µg with 2 laser administrations.

Complementary Visual Health Device Companies Join Forces

■ France-based Luneau Technology Group announced its merger with Optovue Inc, a privately held medical device company, headquartered in Fremont, CA. The combined company will offer a more comprehensive portfolio of advanced visual health solutions. Optovue develops high-speed OCT and OCTA technology, and Luneau Technology manufactured wavefront-based diagnostic solutions.

Marc Abitbol, MD, CEO of Luneau Technology, will preside over the newly merged company, and Optovue CEO Peter Wyles will join the global leadership team. “Optovue’s OCT expertise, stellar reputation, and primary position in the medical eye care market, and complementary portfolio of products, make us an ideal partner,” said Dr. Abitbol, in a news release, “so our combined company can offer complete end-to-end solutions in retail, refraction, and medical markets for primary eye care.”

Shortly before the two companies merged, Luneau Technology USA announced that its new, multimodal anterior-segment and posterior-segment analysis device, Visionix VX650, is now FDA-approved and available for sale in the United States. Later this year, Optovue will be launching a new OCTA screening device.

At-Home OCT Feasibility Study Results Released

■ Notal Vision reported feasibility results from its US study of Notal Home OCT, an investigational teleconnected home-use optical coherence tomography platform, at the 2021 meeting of the Retina Society and the American Society of Retina Specialists. The study evaluated the ability of subjects who have wet AMD to perform sequential daily self-imaging of their eyes for 3 months.

A cohort of 15 subjects with an average age of 70.4 years and a visual acuity ranging from 20/20 to 20/200 self-imaged at home for 90 days. Of the overall imaging attempts, 96% were successfully completed in a median time of 40 seconds, with 97% of images meeting the predefined criteria of good quality. Optical coherence tomography images were processed for identification and quantification of retinal fluid by Notal OCT Analyzer (NOA), a deep-learning algorithm. Scan quality criteria was met in 93% of scans for the algorithm to perform fluid quantification. In 83% of the images, investigators and the NOA agreed on the absence or presence of fluid. “Home OCT patient monitoring has great potential to help reduce treatment burden on patients and caregivers, supporting long-term adherence to therapy and improved outcomes,” Nancy Holekamp, MD, a principal investigator of the study and director of the retina service at Pepose Vision Institute, said in a news release.

In related news, Notal Vision recently announced the artificial intelligence-based analysis of the 10 millionth test performed by over 20,000 patients with the company’s ForeseeHome device, which is part of a comprehensive remote monitoring service for patients who have intermediate AMD and are at risk of developing wet AMD.

Eyepoint Reports Positive Interim Data From DAVIO Trial

■ Eyepoint Pharmaceuticals, Inc. announced 6-month interim data from the Durasert and Vorolanib in Ophthalmology (DAVIO) phase 1 clinical trial of EYP-1901, a bioerodible sustained-delivery intravitreal anti-VEGF treatment targeting wet AMD. The interim results of the trial, which enrolled 17 patients who had been treated for wet AMD, showed 76% of patients did not require rescue at up to 4 months, and 53% of patients did not require rescue at up to 6 months following a single dose of EYP-1901. Patients had stable and sustained BCVA (-2.5 letters) and central subfield thickness (-2.7 μm); they had a 79% reduction in treatment burden at 6 months; and there was a median time to rescue of 6 months across all patients. There were no reports of ocular serious adverse events (SAE) or drug-related systemic SAEs, nor were there any reports of vitreous floaters, endophthalmitis, retinal detachment, implant migration in the anterior chamber, retinal vasculitis, or posterior-segment inflammation.

“These results are not only promising as we plan to move EYP-1901 into phase 2 in wet AMD, but also for the potential to change the treatment paradigm for many wet AMD patients,” Jay S. Duker, MD, chief operating officer of Eyepoint Pharmaceuticals, said in a news release.

Anatomic and Functional Improvement Reported in 4 Opregen Patients

■ Lineage Cell Therapeutics, Inc., released updated interim results from a Phase 1/2a clinical study of Opregen, an investigational allogenic retinal pigment epithelium (RPE) cell transplant therapy for the treatment of dry age-related macular degeneration (AMD). The study enrolled 24 patients in 4 cohorts. Michael S. Ip, MD, from the University of California, Los Angeles, presented the data in November at the American Academy of Ophthalmology annual meeting. He reported that outcomes continue to demonstrate that a single administration of Opregen can provide anatomical and functional improvements in patients who have dry AMD with geographic atrophy (GA); that 3 cases of retinal restoration have shown evidence of markedly smaller areas of atrophy at 12 months post treatment; that the data reflect stability or trends toward improvement in key retinal structures in treated eyes; and that statistically significant differences in visual acuity continue to be observed in cohort 4 patients between Opregen-treated and fellow untreated eyes.

“When Opregen is implanted in the transitional zones of the GA in patients with less advanced disease, reversing damage, or even simply arresting further progression for several years, has been shown to be possible. In addition to being well tolerated to date, the durability of changes to areas of atrophy and improvements in visual acuity observed point to the urgency to further evaluate Opregen in a larger, controlled trial,” Brian M. Culley, Lineage CEO said in a news release.

In December, Lineage also reported that restoration of retinal tissue was observed in a fourth patient enrolled in the study. Retinal tissue restoration and improved visual acuity has now been observed in all 4 better vision patients treated in cohort 4, where surgeons successfully covered the majority of the area of atrophy with a suspension of Opregen cells. Outer retinal layer restoration, which was observed using clinical high-resolution OCT, was evidenced by the presence of new areas of RPE monolayer with overlying ellipsoid zone, external limiting membrane, and outer nuclear layer, which were not present at the time of baseline assessment. These new and additive findings continue to support the company’s view that atrophic AMD is not an irreversible, degenerative condition and that some portion of diseased retinal tissue may be recoverable.

First Patient Dosed in Part B of KALAHARI DME Study

■ Brussels-based biopharmaceutical company Oxurion NV announced that the first patient has been dosed in part B of KALAHARI, its 2-part, randomized, prospective, multicenter study assessing multiple injections of THR-149 in DME patients. THR-149 is being developed as a treatment for the 40% to 50% of DME patients who respond suboptimally to anti-VEGF therapy. The primary objective of part B is to assess the difference in treatment effect between the selected dose from part A of THR-149 (0.13 mg) and aflibercept, from baseline to month 3, in terms of increase in best-corrected visual acuity (BCVA), which is the primary endpoint.

This part of the study will enroll just over 100 patients who have previously shown suboptimal response to anti-VEGF. In part B, which is double-masked and controlled, the high dose of THR-149 selected from part A will be evaluated against aflibercept as the active comparator.

Results from part A demonstrated that all dose levels of THR-149 had a positive safety profile. In terms of efficacy, a rapid onset of action was observed with the highest dose of THR-149 (0.13 mg) delivering the greatest improvement in mean BCVA of 6.1 letters at month 3. Within this group, 63% of patients showed at least a 5-letter gain, 38% achieved at least a 10-letter gain, and 13% achieved at least a 15-letter gain at month 3.

“Positive results from this phase 2 trial would confirm THR-149’s potential to provide a much-needed treatment option for DME patients who fail to respond or respond suboptimally to existing anti-VEGF treatment,” said Tom Graney, CFA, chief executive officer of Oxurion, in a news release.

First Patients Dosed in Oculis Phase 3 DIAMOND Trial

■ Oculis, a biopharmaceutical company, announced that the first patients have been dosed in its phase 3 DIAMOND trial evaluating the efficacy and safety of OCS-01 in diabetic macular edema (DME). OCS-01 is a novel, high-concentration, preservative-free, topical formulation of dexamethasone (DSNP) that opens up the possibility of using an eye drop to treat DME patients at all stages of disease. OCS-01 has been shown to improve visual acuity and reduce central macular thickness in DME patients compared to vehicle and demonstrated a promising safety profile in 144 patients in the phase 2b DX-211 trial.

The phase 3 DIAMOND trial is a pivotal, double-masked, randomized, vehicle-controlled, multicenter, multicountry study whose primary endpoint is the mean change in best-corrected visual acuity on the Early Treatment Diabetic Retinopathy Study chart, with a numerical increase indicating improvement. The secondary endpoint will assess the mean change in macular thickness.

“The availability of an effective topical eye drop treatment for DME would be transformational for patients and would provide an earlier treatment option for ophthalmologists,” said Ramin Tadayoni, MD, Oculis scientific advisory board member and professor of ophthalmology at University of Paris, in a news release.

Heru Expands Capabilities of Wearable Diagnostics Platform

■ Medical software company Heru, Inc., is expanding the capabilities of re:Vive, its wearable diagnostic solution, to include color vision, contrast sensitivity, and dark adaptation — 3 new testing modalities that will enable 6 vision exams to be performed with a single, wearable platform. The cloud-based diagnostic tool enables physicians to diagnose and manage more patients and provides additional avenues for reimbursement because the new testing strategies are co-billable with visual field, optical coherence tomography, and office visits, according to the company. “These new modalities represent significant advancement in the way physicians screen and diagnose for visual disorders and highlight our dedication to delivering best-in-class technology to the market,” Heru’s CEO and founder, Mohamed Abou Shousha, MD, PhD, said in a press release.

The color vision (CPT 92283) exam features a screening color vision test (Ishihara) and the Farnsworth D-15 extended color vision test. If a patient fails the Ishihara test, the platform automatically conducts a D-15 exam. The contrast sensitivity exam allows clinicians to show patients the effects of diminishing vision and provides an efficient way to monitor and document macular health. The dark adaptation (CPT 92284) modality enables clinicians to evaluate retinal function by measuring a patient’s dark adaptation, which is associated with early diagnosis of AMD.

ALTISSIMO Extension Study Reports 12-Month Injection Duration

■ Graybug Vision, Inc. presented data from an 18-month extension of its phase 2b ALTISSIMO trial of GB-102 at the American Academy of Ophthalmology meeting. GB-102 is a twice-yearly injectable formulation of sunitinib malate, for the treatment of wet AMD. The extension data demonstrated up to 6 months longer duration, which resulted in 55% of GB-102 (1 mg) patients experiencing a treatment duration of 12 months or longer, while maintaining visual acuity and central retinal thickness.

ALTISSIMO comprised 2 phases. The first was a 12-month core study, in which GB-102 patients were dosed at day 1 and month 6, whereas a control arm received aflibercept every other month. The second phase was a 6-month extension study, in which patients were monitored without additional treatment to determine the duration of effect measured from their last treatment during the core study.

The phase 2b 18-month extension trial comprised 56 patients who had been diagnosed with wet AMD within 18 months and had at least 3 prior anti-VEGF injections, including 1 within the prior 21 days. The study included GB-102 1 mg and 2 mg dosing groups that received treatment at day 1 and month 6, as well as a third group that received aflibercept 2 mg every 2 months. Before the study, patients in the GB-102 1 mg group had an average of 10.1 injections per year. After initiating treatment with GB-102, the average was 3.8 injections per year.

In a news release, Parisa Zamiri, MD, PhD, chief medical officer of Graybug, said the newest data suggest that GB-102 1 mg has the potential to significantly improve compliance compared to the current standard of care.

Studies Examine Impact of COVID-19 on Visual Health and Eye Care

■ Research and analysis are shedding light on how the COVID-19 virus is impacting vision and the provision of eye care. In a recent study published in the American Journal of Ophthalmology, Teo et al performed a literature review of 31 studies reporting on 1,373 subjects and found that there was a significantly higher likelihood of retinal microvasculopathy in subjects with COVID-19 compared to controls, and optical coherence tomography angiography (OCTA) revealed reduced vessel density and enlarged foveal avascular zones in subjects with COVID-19 compared to controls. The authors concluded, “Our results suggested that COVID-19 related retinal microvasculopathy is a significant ocular manifestation of COVID-19 and may herald future retinal complications. These microvascular impairments might [have] occurred antecedent to clinically visible changes and could be detected early by OCTA. These findings are significant due to the large numbers [of people who have] COVID-19 and need to be recognized by ophthalmologists as a potential long-term sequalae of the disease.”

Another literature review, published in the Journal of Neuro-Ophthalmology, demonstrated that impaired vision may be the initial manifestation of COVID-19, that all sections of the visual tract may be affected and causative for visual impairment in COVID-19 patients, and that SARS-CoV-2 manifests along the visual tract with ischemia, focal infection, and immunological reactions. The authors report that visual impairment in SARS-CoV-2-infected patients may be due to infection of lacrimal glands (dacryoadenitis), conjunctivitis, tonic pupils, vitritis, central retinal artery/venous occlusion, retinitis, retinal bleeding, panuveitis, anterior ischemic optic neuropathy, optic nerve stroke, optic neuritis, optic perineuritis, or occipital ischemic stroke, and advise clinicians to be aware that visual disturbances can be the presenting symptom of COVID-19.

Verana Health, a digital health company, analyzed data from the American Academy of Ophthalmology’s (AAO) Intelligent Research in Sight (IRIS) Registry and reported on the impact of the COVID-19 on the ophthalmic community at AAO’s annual meeting. Among its findings: In March 2020, the Academy advised ophthalmologists to cease all but urgent and emergent care to protect physicians, staff, and patients from the spread of the novel SARS-CoV-2 virus. In the month following this recommendation, daily patient visits dropped to 45,000 per day, about 33% of the prepandemic average of 143,000 per day. Continued analysis revealed that daily patient visits rebounded from May to July 2020, and have since stabilized, albeit at a still-reduced volume compared to 2019.

Additional analysis of IRIS Registry data shows unequivocally that, while sight-threatening conditions continued to be treated during the pandemic, elective cataract surgery was dramatically affected by public health guidance. Monthly cataract surgery volume has been lower, compared to 2019, for every month since the start of the pandemic.

Study Reveals Dosing Variability Risk With Prefilled Aflibercept Syringes

■ Roger A. Goldberg, MD, MBA, reported that there is a potential for overdosing of aflibercept (Eylea, Regeneron), as a result of small misalignment of the plunger when administering the drug in prefilled syringes. He presented his findings at the American Academy of Ophthalmology 2021 annual meeting. According to Dr. Goldberg, this misalignment can lead to a doubling of the volume delivered, and this is likely due to the internal diameter of the syringes and the thickness of the dose mark. Dr. Goldberg said proper adherence to the instructions for use can minimize this dosing error. RP