Eylea FDA Approved as First Medication for Retinopathy of Prematurity

■ Regeneron Pharmaceuticals announced that the US Food and Drug Administration (FDA) has approved Eylea (aflibercept) injection to treat preterm infants with retinopathy of prematurity (ROP). Following this first pediatric approval, Eylea is now indicated to treat 5 retinal conditions caused by ocular angiogenesis.

“Retinopathy of prematurity is a leading cause of childhood blindness worldwide. Until now, the only FDA-approved treatment in common use was laser photocoagulation, a complex and lengthy procedure that permanently ablates retina tissue and is stressful not only for infant patients but also the family navigating a delicate time after a preterm birth,” said George D. Yancopoulos, MD, PhD, president and chief scientific officer of Regeneron, and a principal inventor of Eylea.

The FDA approval is supported by data from 2 randomized global phase 3 trials — FIREFLEYE (n=113) and BUTTERFLEYE (n=120) — investigating Eylea 0.4 mg vs laser photocoagulation in infants with ROP. Eylea is being jointly developed by Regeneron and Bayer. The lead sponsors of the trials were Regeneron for BUTTERFLEYE and Bayer for FIREFLEYE. In both trials, approximately 80% of Eylea-treated infants achieved an absence of both active ROP and unfavorable structural outcomes at 52 weeks of age, which is better than would have been expected without treatment.

No new Eylea safety signals were observed in either trial. Adverse events in both trials were consistent with infant prematurity or to the injection procedure, and with the AEs in similar ROP trials.

The 23rd Annual Retina Fellows Forum

CARL AWH, MD, FASRS

Seventy-five second-year vitreoretinal fellows from throughout North America recently attended the 23rd annual Retina Fellows Forum in Chicago for a weekend of interactive education and socializing. David S. Boyer, MD, FASRS, delivered the distinguished guest lecture, “Lessons Learned to Succeed in Private Practice.”

The fellows enjoyed a weekend of energetic panel discussions covering a broad spectrum of medical and surgical retina issues. New this year were panel discussions on “How to Succeed in Professional Societies and Ad Boards” and on “Retina Practice Models: Strengths and Limitations.” The academic portion of the meeting concluded with the “Real World” panel discussion, during which the faculty and fellows discussed job selection, contract negotiation, practice building strategies, staff management issues, and work-life balance.

The faculty of 9 leading retina specialists was headed by course director Carl Awh, MD, FASRS, and course codirectors Tarek Hassan, MD, FASRS, and David Chow, MD, FASRS. The meeting concluded with the hotly contested Retina Fellows Forum bowling tournament, this year won by Dr. Christina Weng’s team.

FDA Approves ML6710i Photodynamic Laser for Use With Visydyne

■ Bausch + Lomb and Modulight, a biomedical laser company, announced that the FDA has approved the ML6710i photodynamic laser for use with Visudyne (verteporfin), an injectable photosensitizer drug, for the treatment of patients with predominantly classic subfoveal choroidal neovascularization, or the creation of abnormal choroidal blood vessels due to AMD. ML6710i is a transportable ophthalmic laser that is controlled via a tablet mobile application. The laser’s beam shaping unit, which can be fit into all common slit lamps, is formed into a circular, uniform spot to enable efficient treatment delivery of Visudyne. The cloud-connected laser platform is expected to be available for use by eye care professionals during the first half of 2023.

“Eye care professionals now have a new state-of-the-art photodynamic laser that addresses a significant unmet need in photodynamic therapy and is specifically designed to deliver Visudyne to patients who suffer from wet AMD with persistent fluid,” Christina Ackermann, president of ophthalmic pharmaceuticals for Bausch + Lomb, said in a news release.

New Data on Drusen Could Lead to Early Diagnosis and Treatment of AMD

■ Two separate eye diseases may contribute to AMD, according to a study from New York Eye and Ear Infirmary of Mount Sinai. The research is the first to demonstrate that 2 different types of deposits — subretinal drusenoid deposits (SDD) and drusen in the retina — may contribute to early AMD. The researchers measured the autofluorescence and evaluated OCT scans in 18 patients (32 eyes) with advanced AMD and GA. The team then measured the brightness of the fluorescent light coming from these regions and found it was twice as bright in patients with SDD when compared to those with drusen. Drusen formation can be slowed by vitamin supplements to prevent vision loss, but there is no known treatment for SDDs and they pose a greater threat of advanced AMD.

Mount Sinai researchers previously found that patients with SDDs are likely to have heart damage from heart failure and heart attacks, or advanced heart valve disease, or strokes associated with carotid artery disease. “We think the SDDs result from deficient blood flow to the eye caused by these vascular diseases. This work should prompt retinal specialists to look for both drusen and SDDs with OCT, to best counsel patients,” R. Theodore Smith, MD, PhD, professor of ophthalmology at the Icahn School of Medicine at Mount Sinai, said in a news release.

Study Shows Inequities and Research Gaps in Ophthalmology

■ Substantial research gaps exist within the ophthalmic literature according to a study titled, “Inequities and Research Gaps in Ophthalmology,” published online in JAMA Ophthalmology. The comprehensive review of 75 publications from 2016 to 2021, led by Christian Hemmerich, BS, from Oklahoma State University, revealed research gaps with respect to the lesbian, gay, bisexual, transgender, and queer (LGBTQ) community, race and ethnicity, and rural and under-resourced areas.

The researchers suggest future studies should examine barriers to clinical study and medical trainee recruitment, as well as patient values and preferences, and should investigate the implementation of telemedicine in under-resourced areas. The authors noted, “Deficient ophthalmologic care is costly to patients, making the identification of groups not receiving adequate care of vital importance. The current landscape of equity in ophthalmic care has yet to be thoroughly investigated and is important to ensure inclusivity and patient-centered care.”

FDA Accepts NDA for MydCombi Ophthalmic Spray for Mydriasis

■ Eyenovia announced that its NDA for MydCombi ophthalmic spray has been accepted by the FDA. MydCombi is a drug-device duo that comprises the company’s first-in-class combination of tropicamide and phenylephrine for in-office mydriasis administered via its investigational Optejet technology.

The MydCombi NDA is supported by 2 completed phase 3 clinical trials, MIST-1 and MIST-2. MIST-1 compared MydCombi to phenylephrine alone and tropicamide alone, while MIST-2 compared MydCombi to placebo. All treatments were administered using Optejet technology. The volume of drug administered with Optejet is less than 20% of that delivered using conventional eyedroppers, thus reducing overexposure to drug and preservatives.

ZETA-1 Trial Shows Potential of Oral APX3330 to Slow Worsening of DR

■ Ocuphire Pharma announced top-line efficacy and safety results from its ZETA-1 phase 2 trial evaluating oral APX3330 for the treatment of diabetic retinopathy (DR). Oral APX3330 did not achieve its primary endpoint, but it achieved statistical significance on a key prespecified secondary endpoint — binocular 3-step or more worsening of diabetic retinopathy severity score — and demonstrated favorable safety and tolerability, signifying a potential noninvasive option for protection of vision in both eyes in DR patients.

The randomized, double-masked, placebo-controlled phase 2 trial was conducted at 25 US sites and enrolled 103 patients, with at least 1 eye meeting criteria for moderately severe to severe nonproliferative DR or mild PDR.

“Although we did not meet the primary endpoint — a precedented endpoint for local administration of anti-VEGF intravitreal injections — we are pleased that the ZETA-1 results on key prespecified endpoints demonstrated positive outcomes with a favorable systemic and ocular safety profile that support our plans to move forward to an end-of-phase 2 meeting with the FDA,” Mina Sooch, MBA, founder and CEO of Ocuphire Pharma, said in a news release.

Aldeyra Submits NDA for ADX-2191 to Treat Primary Vitreoretinal Lymphoma

■ Aldeyra Therapeutics announced the submission of a New Drug Application (NDA) to the FDA for ADX-2191 (methotrexate injection, USP), an investigational drug candidate, for the treatment of primary vitreoretinal lymphoma (PVL). The NDA is supported by a combination of published literature on the safety and efficacy of methotrexate for the treatment of PVL and safety data from the recently completed phase 3 GUARD trial of ADX-2191 for the prevention of proliferative vitreoretinopathy. During the phase 3 GUARD trial, no safety signals were observed, ADX-2191 was well tolerated, and there were no observed treatment-emergent serious adverse events.

“Compounding methotrexate for intravitreal injection — the current standard of care for PVL — poses several challenges for physicians and patients, including risk of infection and increased injection volume potentially leading to ocular hypertension and corneal inflammation. ADX-2191 is a novel formulation of methotrexate that is designed to be vitreous compatible and has the potential to be the first marketed drug for patients suffering from primary vitreoretinal lymphoma,” Todd C. Brady, MD, PhD, Aldeyra president and CEO, said in a news release.

FDA Clears Exegenesis NDA for Neovascular AMD Gene Therapy

■ Exegenesis Bio announced that the FDA has cleared its Investigational New Drug (IND) application for EXG102-031, a recombinant adeno-associated virus (rAAV)–based gene therapy that is being studied for the treatment of neovascular AMD. EXG102-03, which is administered as an intraocular injection, expresses a therapeutic fusion protein that can bind/neutralize all known subtypes of VEGF and angiopoietin-2. A phase 1 clinical trial to evaluate safety and tolerability, as well as visual acuity and central retinal thickness, in patients with nAMD is set to begin in the first quarter of 2023.

“We are pleased to have reached this critical milestone and look forward to accelerating development of our gene therapy pipeline and bringing these innovative treatments to patients worldwide,” Zhenhua Wu, CEO of Exegenesis Bio, said in a news release.

NIH Uses 3D Bioprinting to Create Retina Tissue for AMD Research

■ National Eye Institute researchers used patient stem cells and 3D bioprinting to produce a combination of cells that form the outer blood-retina barrier. The technique provides a theoretically unlimited supply of patient-derived tissue to study degenerative retinal diseases.

The researchers reported that tissue analyses and genetic and functional testing shows that the printed tissue looks and behaves similarly to native outer blood-retina barrier tissue. Their study observations included: Under induced stress, printed tissue exhibited patterns of early AMD such as drusen deposits undern the retinal pigment epithelium and progression to late dry AMD; low oxygen induced a wet AMD-like appearance; and anti-VEGF drugs suppressed vessel overgrowth and migration and restored tissue morphology.

“By printing cells, we’re facilitating the exchange of cellular cues that are necessary for normal outer blood-retina barrier anatomy. For example, presence of RPE cells induces gene expression changes in fibroblasts that contribute to the formation of Bruch’s membrane — something that was suggested many years ago but wasn’t proven until our model,” Kapil Bharti, PhD, who heads the NEI section on ocular and stem cell translational research, said in a news release.

Verana Health Study Uncovers Dry AMD Risk of Progression by Stage

■ Verana Health announced publication of its study, “Dry Age-related Macular Degeneration: Distribution of Visual Acuity and Progression Risk in a Large Registry,” which explored how patients progress through the stages of dry AMD. Researchers analyzed real-world data from the AAO IRIS Registry, which contains ophthalmic records for more than 75 million patients over approximately 10 years. A cohort of approximately 645,000 patients with confirmed dry AMD was identified and disease progression was tracked over 4 years. The researchers arrived upon several conclusions: Patients with intermediate dry AMD were 4 times more likely to progress to GA than patients with mild dry AMD; there was a larger variation in visual acuity among patients with geographic atrophy compared to those with mild or intermediate dry AMD; VA progression generally is faster with each progressive dry AMD stage; and disease progression to geographic atrophy and wet AMD occurred much faster once a patient reached the intermediate dry AMD stage.

“The clinical recommendation we can draw from this study is that if you have a patient with intermediate AMD, you need to watch them more closely than someone with mild dry AMD, and these findings highlight the need for new medication options to reverse or delay the worsening of dry AMD and improve the quality of life for patients,” Theodore Leng, MD, director of research at the Byers Eye Institute at Stanford University School of Medicine and a Verana Health medical advisor, said in a news release.

Ocuphire Receives PDUFA Date for Nyxol Eye Drops for Mydriasis Reversal

■ Ocuphire announced that the US Food and Drug Administration (FDA) has accepted its New Drug Application (NDA) for Nyxol (phentolamine ophthalmic solution 0.75%) for the treatment of pharmacologically induced mydriasis produced by adrenergic agonist and/or parasympatholytic agents. The FDA assigned a Prescription Drug User Fee Act (PDUFA) date of September 28, 2023. Nyxol modulates the pupil size by blocking the α1 receptors found only on the iris dilator muscle, without affecting the ciliary muscle.

The NDA was supported by positive results from the MIRA clinical program involving more than 600 subjects, including the MIRA-1 phase 2b trial, MIRA-2 and MIRA-3 phase 3 pivotal trials, and MIRA-4 phase 3 pediatric trial. The MIRA-2 and MIRA-3 trials successfully met their primary and key secondary endpoints, demonstrating statistically significant superiority of Nyxol compared to placebo to rapidly return dilated eyes to their baseline pupil diameter as early as 60 and 90 minutes.

Flavoprotein Fluorescence Could Help Detect Inherited Retinal Dystrophies

■ OcuSciences announced the publication of a study of rare inherited mitochondrial diseases in Ophthalmology Genetics. The observational study, led by Elias Traboulsi, MD, MEd, director of the Center for Genetic Eye Diseases at Cleveland Clinic Cole Eye Institute, revealed that a novel flavoprotein fluorescence (FPF) measure can differentiate between patients diagnosed with inherited retinal dystrophies and their age-matched controls. Furthermore, the FPF results correlated with fundus autofluorescence findings, suggesting clinical utility of the rapid, automated measure.

The final analysis cohort included 242 images from 157 patients with genetically confirmed rod-cone dystrophy, Stargardt disease, Bardet-Biedl syndrome, and mitochondrial ATP synthase mutation. Patients were imaged with OcuSciences’ OcuMet Beacon, an automated, rapid retinal imager that assesses mitochondrial function by interrogating flavoproteins, to capture and quantify their FPF signal. Mean FPF intensity and heterogeneity was significantly higher in patients with inherited retinal dystrophies than age-matched controls.

“These findings suggest that FPF could be used as an additional tool in the assessment and diagnosis of patients with inherited retinal dystrophies. More studies are needed to help elucidate how this imaging modality could be implemented clinically,” Dr. Traboulsi said in a news release.

American Macular Degeneration Foundation Announces New Research Grants

■ The American Macular Degeneration Foundation (AMDF) is investing $1.1 million in studies aimed at AMD prevention, risk reduction, new treatment protocols, and cures. The nonprofit announced its expanded slate of grants in the wake of recently released figures that put the number of Americans with some form of sight-stealing eye disease at 20 million.

Among the grants are the Stargardt Breakthrough Award to develop a treatment and delivery system to rescue retinal defects in a rare form of Stargardt macular degeneration (STGD3) and possibly late AMD; the Breakthrough Award for a study to determine how the time that elapses from the onset of wet AMD symptoms to the first anti-VEGF injection correlates to short-term and long-term visual outcomes; the Breakthrough Award extension to continue testing gene-based interventions that could attenuate the progression of AMD and possibly prevent its development; and the Breakthrough Award extension to continue to elucidate new biological pathways involved in AMD and identify new therapeutic targets.

“As a foundation, we share the hopes of our supporters, that through carefully identified research and education we can allow patients and caregivers to live their fullest lives with this disease, and prevent future generations from losing their sight,” Chip Goehring, president and founder of AMDF, said in a news release. RP

Study Evaluates Effect of Dietary Nitrates on AMD Progression

Dietary nitrate intake is associated with a lower risk for progression of age-related macular degeneration (AMD), according to research led by Geoffrey K. Broadhead, MD, PhD, from the National Eye Institute. Dr. Broadhead and colleagues examined the association between dietary nitrate intake and AMD progression using data from the prospective Age-Related Eye Disease Study (AREDS) and AREDS2 randomized clinical trial cohorts and extended follow-up studies.

The researchers found that in the combined AREDS/AREDS2 cohort, dietary nitrate intake was associated with a reduced risk for progression to late AMD, and the risks for geographic atrophy (GA) and neovascular AMD (nAMD) were also reduced. Increased nitrate intake was associated with a reduced risk for late AMD and GA, but not with nAMD in AREDS. No association between nitrate intake and late AMD or nAMD was seen in AREDS2. An association was noted between Mediterranean dietary patterns and dietary nitrate intake.

The authors concluded, “The findings of this cohort study suggest that dietary nitrate intake was associated with lower AMD risk. However, this association disappeared after adjusting for Mediterranean dietary patterns. Further research is needed before dietary nitrate intake can be recommended as a therapy for AMD.”

Parexel Move Aims to Increase Diversity in Ophthalmic Clinical Trials

Parexel, one of the largest clinical research organizations (CROs), has entered an agreement with MyEyeDr. to refer its patients into existing and future ophthalmology clinical trials. MyEyeDr. will be part of Parexel’s Community Alliance Network, a program geared toward integrating clinical research into the community health care setting to better serve patients and create opportunities for increased diversity in clinical trials.

By leveraging MyEyeDr.’s more than 850 offices across 28 states, the CRO will be able to disseminate information directly to the types of patients needed for ophthalmology studies. The team is currently collaborating on recruitment for a diabetic retinopathy clinical trial, with plans to expand into additional therapeutic areas.

“Meeting patients where they already are — such as centers providing annual routine eye exams and other vision care — is vital to the development of new therapies. By fostering relationships with the broader health-care community, we’re able to raise awareness and ensure more patients are exposed to clinical research as a care option, in turn increasing our reach for clinical trial recruitment and, ultimately, speeding the availability of life-changing treatments,” Clare Grace, PhD, chief patient officer for Parexel, said in a news release.

Rezolute Announces Phase 2 Study of Oral Drug for DME

Rezolute announced that it has initiated a phase 2 proof-of-concept study for RZ402, a plasma kallikrein inhibitor (PKI) being developed as an oral therapy for the treatment of diabetic macular edema (DME). The phase 2 study is a multicenter, randomized, double-masked, placebo-controlled, parallel-arm study to evaluate the safety, efficacy, and pharmacokinetics of RZ402 administered as monotherapy over 12 weeks in participants with DME who are naïve to or have received limited anti-VEGF injections. The study population will include patients with mild-to-moderate nonproliferative diabetic retinopathy, central subfield thickness of ≥320 µm (or corresponding values), and BCVA of ≤78. Patients who have previously received more than 3 anti-VEGF injections prior to the study will be excluded.

“By targeting an alternative pathway and route of administration to the current standard of care, we believe that orally administered RZ402 has the potential to be a less burdensome and more beneficial treatment option for all patients with DME, including the approximately 50% of patients who don’t adequately respond to anti-VEGFs,” Raj Agrawal, MD, vice president and head of ophthalmologic clinical development at Rezolute, said in a news release.

Pixium Publishes Data From Second-generation Prima Implant Study

Pixium Vision announced publication of a study exploring the potential of its second-generation Prima implant for atrophic AMD. The research demonstrates that the implant could pave the way to prosthetic vision with acuity exceeding 20/100, which is 5 times higher than the current best prosthetic acuity, and that with electronic magnification it may reach 20/20.

The authors reported that their novel design enables customized field shaping based on individual retinal thickness and distance from the implant. The new implants, which were developed in collaboration with Pixium Vision’s academic partner, Stanford University, leverage existing Prima design with significant increase in spatial resolution.

Opus Genetics Acquires Rights to Gene Therapies for Inherited Retinal Diseases

Opus Genetics announced that it has acquired the rights to 2 preclinical-stage adeno-associated virus (AAV)–based gene therapy product candidates for inherited retinal diseases (IRDs) from Iveric Bio. Opus will develop the novel gene therapy candidates to address bestrophin-1 (BEST1)-related inherited retinal diseases and rhodopsin-mediated autosomal dominant retinitis pigmentosa (RHO-adRP), respectively.

“IRDs are ideal targets for genetic therapies to stop the retinal degeneration and improve the lives of patients living with severe vision loss or blindness,” Bart P. Leroy, MD, PhD, head of the department of ophthalmology, and member of the Center for Medical Genetics at Ghent University and Ghent University Hospital in Belgium, said in a news release.

As part of the deal, Opus will assume responsibility for the global research, development, and commercialization of the BEST1 and RHO-adRP programs. Opus anticipates completing additional IND-enabling studies and filing an IND for BEST1 in the second half of 2023.

Higher Risk of Severe COVID-19 in AMD Patients May Have Genetic Basis

Age-related macular degeneration (AMD) is associated with a higher risk of severe SARS-CoV-2 complications — including respiratory failure and death (25%) — compared to type 2 diabetes (21%) and obesity (13%), according to researchers from Boston University Chobanian and Avedisian School of Medicine. The study that reported these findings was published in the online edition of the Journal of Clinical Medicine.

The researchers identified a novel association of AMD and SARS-CoV-2, with variants in the PDGFB gene. This gene encodes a platelet-derived growth factor (PDGF) that has a role in the changes that occur in AMD. They found that the connection between more severe COVID-19 outcomes and AMD was likely the result of genetic predisposition to dysfunction involving complement proteins and a higher level of PDGF in blood serum.

“Our analysis lends credence to previously reported clinical studies that found those with AMD have a higher risk for COVID-19 infection and severe disease, and that this increased risk may have a genetic basis,” study author Lindsay A. Farrer, PhD, Boston University chief of biomedical genetics, said in a news release.

Research to Prevent Blindness Reaches Major Funding Milestone

Research to Prevent Blindness (RPB) has announced a new roster of grant awardees. Grant recipients will perform research that provides critical insight into AMD, glaucoma, corneal transplantation, retinal degeneration disorders, ocular hypertension, keratoconus, night blindness, retinitis pigmentosa, and more. With this latest round of funding, RPB has provided more than $400 million in research funding to scientists at the nation’s leading medical institutions.

“I am proud that RPB has reached this funding milestone, but more importantly, I am extremely gratified by our impact on the trajectory of vision research in the United States,” Brian F. Hofland, PhD, president of Research to Prevent Blindness, said in a news release.

Newly announced departmental funding includes unrestricted grants to the University of California, San Diego School of Medicine; the Regents of the University of Michigan School of Medicine; and the University of Washington School of Medicine, as well as a challenge grant to the Ohio State University College of Medicine, among others.

Study Shows Lab-grown Cells Could Lead to Blindness Treatment

Lab-grown retinal cells can make successful synaptic connections and may open the door to clinical trials to treat blindness, according to David Gamm, MD, PhD, director of the McPherson Eye Research Institute at the University of Wisconsin-Madison. A decade ago, a team led by Dr. Gamm developed a way to grow organized clusters of cells, called organoids, that resemble retinal cells. Now, his team has found that the lab-grown cells from those organoids can be used as replacement parts for the cells that are lost in the course of retinal diseases.

Once they confirmed the presence of synaptic connections, the researchers analyzed the cells involved and found that the most common retinal cell types forming synapses were photoreceptors — rods and cones —which are lost in diseases like retinitis pigmentosa and AMD. “That was an important revelation for us. It really shows the potentially broad impact these retinal organoids could have,” Dr. Gamm said in a press release. Opsis Therapeutics is adapting the technology to treat eye disorders.