Mount Sinai Study Could Lead to Early Diagnosis and Treatment of AMD

■ Two separate eye diseases — drusen and subretinal drusenoid deposits (SDDs) — may contribute to age-related macular degeneration (AMD), according to a new study from New York Eye and Ear Infirmary of Mount Sinai. “For the first time, we were able to measure autofluorescence, with ultrasensitive detectors to study advanced AMD, and we found it was consistently twice as bright in the patients with SDDs as those with drusen when they reached advanced AMD, and came from a unique diseased layer. Combined with our prior research, this provides conclusive evidence that 2 different disease processes in AMD are taking place, one with darker fluorescence and drusen, and one with brighter fluorescence and SDDs, and they need to be treated differently,” lead author R. Theodore Smith, MD, PhD, professor of ophthalmology at the Icahn School of Medicine at Mount Sinai, said in a press release.

Early Anti-VEGF Treatment Yields No Visual Acuity Benefit

■ Although early anti-VEGF treatment of diabetes-related eye disease slowed progression to severe disease, it did not improve visual acuity (VA) compared with treating more severe disease once it developed, according to final 4-year results from a DRCR Retina Network clinical study. Researchers evaluated whether treating people with nonproliferative diabetic retinopathy with aflibercept (Eylea; Regeneron) could prevent vision loss. The study enrolled 328 participants. Two-year results suggested that while preventive treatment reduced the risk of developing diabetic macular edema or proliferative diabetic retinopathy, there was no evident benefit to vision. The final 4-year results reinforce the earlier finding, with no statistical difference in either VA or rates of vision loss between the 2 groups.

Clearside Releases Positive Data From Extension Study of CLS-AX in Wet AMD

■ Clearside Biomedical announced positive results from the extension study of its OASIS phase 1/2a clinical trial of CLS-AX (axitinib injectable suspension) administered by suprachoroidal injection via Clearside’s SCS Microinjector in wet AMD participants. These results include the final 6-month data from all participants in the extension study and augment the previously reported 3-month results and interim extension data.

In all participants in the trial, CLS-AX was well tolerated and demonstrated an excellent safety profile across all time points and doses. The full extension study data showed promising durability, with 67% of participants going at least 6 months without additional treatment, and 50% of participants going beyond 6 months. “We are preparing for and expect to initiate a randomized, controlled, double-masked, phase 2b clinical trial in the first quarter of this year,” Thomas A. Ciulla, MD, MBA, former Clearside Biomedical chief medical officer and chief development officer, said in a news release.

FDA Fast Tracks Investigation of EA-2353 for Retinitis Pigmentosa

■ Endogena Therapeutics announced that the FDA has designated the investigation of EA-2353 for the treatment of retinitis pigmentosa (RP) as a Fast Track development program. EA-2353 selectively activates endogenous retinal stem and progenitor cells, which differentiate into photoreceptors and can potentially preserve or restore visual function. The Fast Track designation will enable the company to have more frequent communications with the FDA on the development of EA-2353 and allow more rapid regulatory review of the future new drug application. Endogena Therapeutics is currently conducting a phase 1/2a dose-escalation to examine the safety, tolerability, and preliminary efficacy of EA-2353 administered by intravitreal injection in patients with RP.

Frontera Therapeutics Doses First Patient in Wet AMD Gene Therapy Trial

■ Frontera Therapeutics announced that it has dosed the first patient in a clinical trial of its gene therapy product, FT-003, at the Ophthalmology Hospital of Tianjin Medical University in Tianjin, China. FT-003 is being studied for the treatment of wet AMD and is Frontera’s second gene therapy product candidate to enter the clinic. FT-003 is designed as a one-time treatment.

Two of Frontera’s gene therapy product candidates, FT-001 for Leber congenital amaurosis-2 (LCA-2) and FT-003 for wet AMD, have entered clinical development. “We expect to have initial clinical results for both FT-001 and FT-003 later this year,” Yong Dai, PhD, founder and CEO of Frontera, said in a news release.

FDA to Give Aflibercept Priority Biologics License Application Review

■ Regeneron Pharmaceuticals announced that the FDA has accepted for priority review the Biologics License Application (BLA) for aflibercept 8 mg for treatment of patients with wet AMD, diabetic macular edema (DME), and diabetic retinopathy. The FDA target action date is June 27, 2023, following the use of a priority review voucher. The BLA is supported by positive data from 2 pivotal trials — PULSAR in wet AMD and PHOTON in DME. In both trials, patients treated with aflibercept 8 mg (PULSAR n=673; PHOTON n=491) met the primary endpoint of noninferiority in vision gains for both the 12-week and 16-week dosing regimens after initial monthly doses at 48 weeks compared to patients treated with an aflibercept (Eylea; Regeneron) injection (PULSAR n=336; PHOTON n=167) 8-week dosing regimen. The lead sponsors of the trials were Regeneron for PHOTON and Bayer for PULSAR.

Regenxbio Presents Interim Data of RGX-314 Using Navxpress Platform

■ Regenxbio announced results from a phase 2 bridging study evaluating the pharmacodynamics, safety, and efficacy of RGX-314, a potential one-time therapy delivered subretinally using cGMP material produced by the company’s Navxpress bioreactor platform process.

The phase 2 study evaluated RGX-314 using subretinal delivery across 2 dose levels (6.4x10¹⁰ GC/eye and 1.3x10¹¹ GC/eye) in 60 patients with wet AMD. The recently announced data are from the 2 high-dose cohorts. Patients in the 2 high-dose cohorts demonstrated stable-to-improved best corrected visual acuity and central retinal thickness, and meaningful reductions in anti-VEGF burden, with a majority of subjects being injection free.

“Our focus on early product quality and process control allows us to efficiently transition from clinical trials to commercial readiness,” said Curran Simpson, chief operating officer of Regenxbio, in a news release.

FDA Accepts Oxular Limited’s IND for Suprachoroidal OXU-001 for DME

■ Oxular Limited announced that the FDA has accepted its Investigational New Drug (IND) application for suprachoroidal OXU-001 for the treatment of DME. The IND enables advancement of the OXEYE phase 2 trial, which will evaluate the safety and efficacy of OXU-001 for retinal disorders, beginning with DME. In 12-month preclinical studies, OXU-001 was well tolerated, and related pharmacokinetic data confirmed that therapeutic drug levels were consistently maintained in target retinal tissues. These data suggest that a single treatment of OXU-001 may provide up to 12-month treatment effects with an improved clinical safety profile.

Ocular Therapeutix Reports Interim Data From Phase 1 OTX-TKI Trial

■ Ocular Therapeutix announced interim 10-month data from its phase 1 clinical trial evaluating OTX-TKI, an axitinib intravitreal hydrogel implant in development for the treatment of wet AMD, diabetic retinopathy, and other retinal diseases. The trial is evaluating a 600-µg dose of OTX-TKI in a single implant, with a 2-mg aflibercept (Eylea; Regeneron) injection 4 weeks after the implant, compared to 2 mg aflibercept injections administered every 8 weeks. The subjects who were rescue-free up to month 7 (73%) continued to demonstrate OTX-TKI’s extended duration of action and remained rescue free up to month 10. Overall, a 92% reduction in treatment burden was observed in OTX-TKI treated subjects for up to 10 months.

Genentech Announces Positive New Phase 3 Vabysmo Data

■ Genentech announced positive new data from 2 global phase 3 studies, BALATON and COMINO, evaluating Vabysmo (faricimab-svoa) in macular edema due to branch retinal vein occlusion and central retinal vein occlusion at 24 weeks. The studies showed that treatment with Vabysmo resulted in early and sustained improvement in vision, meeting the primary endpoint of noninferior visual acuity gains compared to treatment with aflibercept (Eylea; Regeneron). Vabysmo also showed rapid and robust drying of retinal fluid from baseline, as measured by reduction in central subfield thickness. “These encouraging results reinforce the potential of Vabysmo as a new treatment option for people experiencing vision loss associated with retinal vein occlusion,” Levi Garraway, MD, PhD, Genentech chief medical officer and head of global product development, said in a news release.

Ocuphire Releases New Oral APX3330 Diabetic Retinopathy Trial Data

■ Ocuphire announced top-line efficacy and safety results from its ZETA-1 phase 2 trial evaluating oral APX3330 for the treatment of diabetic retinopathy. APX3330 did not meet the primary endpoint of percentage of patients with a ≥2-step improvement in DRSS at week 24 in the study eye. However, the drug did achieve statistical significance on a key prespecified secondary endpoint — binocular 3-step or more worsening of DRSS. In a news release, Mina Sooch, MBA, founder and CEO of Ocuphire Pharma, said, “Although we did not meet the primary endpoint, 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.”

Nanotechnology May Improve Gene Therapy for Blindness

■ An approach that uses lipid nanoparticles (LNPs) to deliver strands of messenger ribonucleic acid (mRNA) inside the eye to treat blindness has been developed by researchers from Oregon Health & Science University and Oregon State University. A study detailing their findings was published in Science Advances. After injecting this nanoparticle-based gene therapy into the eyes of mice and nonhuman primates (NHPs), the research team used a variety of imaging techniques to examine the treated eyes. The animals’ retinal tissue glowed green, illustrating that the lipid nanoparticle shell reached photoreceptors and that the mRNA it delivered successfully entered the retina and created green fluorescent protein. This research marks the first time that lipid nanoparticles are known to have targeted photoreceptors in a nonhuman primate. The researchers concluded, “The translation of our results into the NHP eye highlights the advancement of LNP-mRNA delivery toward clinical application for inherited retinal diseases.”

Retina Surgery Research Shows Inferior Results for Minority Patients

■ New research from Boston Medical Center found that Black and Hispanic patients treated with surgery for retinal detachment had worse vision results than White patients. Charts of 124 Black and Hispanic patients and 71 White patients who were treated surgically for retinal detachment were examined, and demographics, preoperative characteristics, and surgical outcomes were compared. The analysis suggests that higher rates of proliferative vitreoretinopathy (PVR) in minority patients may contribute to these findings. Researchers believe that larger-scale studies are needed to support the findings regarding higher risk for PVR in minority patients, but if these findings are verified, physicians may need to change their surgical approach to retinal detachment with procedures that may more fully address this risk factor.

FDA Clears HuidaGene’s IND Application to Treat Inherited Blindness

■ HuidaGene Therapeutics announced that the FDA has cleared its IND application for the planned multinational clinical trial of HG004 for the treatment of RPE65 mutation-associated inherited retinal dystrophies. Based on the head-to-head preclinical comparison study of HG004 and adeno-associated virus serotype 2 (AAV2) at the same dose, the recovery of retinal functions increased by 67.6% (HG004) and 35.8% (AAV2 products) when compared to the wild-type mice in the RPE65 knockout murine model at week 17, after a single injection. HG004 demonstrates better transduction efficiency of the retinal pigment epithelium compared with AAV2 and has the potential to lower the total vector doses, which may reduce the risk of AAV vector-associated immunogenicity or ocular adverse events in humans.

Survey Shows Lack of Knowledge About AMD Among Older Americans

■ An online survey of 1,008 US adults age 40 and older revealed a lack of knowledge about AMD. Nearly 20% of those surveyed actively avoid having their eyes dilated during eye exams; 78% did not know straight lines appearing wavy or distorted was a symptom of AMD; only 51% were aware that a gradual or sudden loss of central vision or a dark, blurry area in the center of vision is an AMD symptom; 83% did not know that obesity increases the risk of developing AMD; 74% did not identify excessive sun exposure as a risk factor; and nearly 67% of those surveyed did not know blindness and vision loss could potentially be prevented with injections. The survey was commissioned by American Society of Retina Specialists (ASRS) and conducted by Atomik Research Insights & Analytics.

Radiosurgery for Ocular Melanomas Is a Viable Option

■ A study of robot-assisted radiosurgery in choroidal and ciliary body melanomas conducted at the department of ophthalmology of Ludwig-Maximilians-University and the European CyberKnife Center in Munich, Germany, found that for centers without access to brachytherapy, robotic CyberKnife radiosurgery may be a viable alternative. The researchers demonstrated that a minimum dose of 21 Gy over a single session can provide a 7-year tumor control rate of 91.3% and a globe salvage rate of 75.0%. The eye was retained in 506 patients (85.2%), with enucleation required primarily owing to tumor recurrence or secondary glaucoma. The overall 5-year survival rate was 89.8%. Of the patients who died, 48.8% died owing to melanoma progression.

Study Examines Reasons Patients Abandon Low-vision Devices

■ A study to investigate abandonment rates of near-vision low-vision devices (LVDs) and factors that influence abandonment among patients attending a tertiary low-vision rehabilitation center in South India revealed that 22% of the patients had abandoned the use of the prescribed device at the 1-year follow-up. The reasons for no longer using the device included device-related issues such as the device being too complex or cumbersome to use and psychological issues such as frustration with the use of the device or self-consciousness. Patients reporting no change in their quality of life had a higher likelihood of abandoning the device compared with those who reported some change. The abandonment rate for near-vision LVDs in South India was comparable to rates reported in high-income countries.

Rates and Risk of Recurrent Uveitis Following COVID-19 Vaccination

■ A retrospective study demonstrated an increased risk of uveitis flare following a first dose of COVID vaccination. Subjects were identified from the Inflammatory Eye Disease Registry at the Auckland District Health Board; 4,184 eyes of 3,008 patients were included in the study with a total of 8,474 vaccinations given during the study period. Reactivation of pre-existing uveitis — both infectious and non-infectious — after vaccination with BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech) was found to be more prevalent in patients with a history of chronic disease or a shorter period of quiescence, with a higher risk of flare after the first dose and the highest hazard of flare at 2 months. The authors suggest that patients at risk of uveitis flare after COVID-19 vaccination may benefit from pretreatment prior to vaccination and careful monitoring after the vaccine is administered.

FDA Grants IND Application Clearance for ONL1204 Ophthalmic Solution

■ ONL Therapeutics announced that the FDA has authorized the company to proceed with the IND application for ONL1204 ophthalmic solution, a first-in-class small-molecule Fas inhibitor. The company intends to initiate a phase 2 clinical study of ONL1204 ophthalmic solution in patients suffering from macula-off rhegmatogenous retinal detachment (RRD) at sites in the United States in the second quarter of 2023. ONL1204 is designed to protect key retinal cells, including photoreceptors, from cell death that occurs across a range of retinal diseases and conditions.

Canadian Study Shows Obesity Is Linked to Macular Degeneration

■ Life stressors such as obesity reprogram immune system cells and make them destructive to the eye as it ages, according to research performed at Hôpital Maisonneuve-Rosement, in Montreal, Canada. Researchers found that transient obesity or a history of obesity leads to persistent changes in the DNA architecture within immune cells, making them more susceptible to producing inflammatory molecules.

“Our findings provide important information about the biology of the immune cells that cause AMD and will allow for the development of more tailored treatments in the future,” study author Masayuki Hata, MD, PhD, said in a news release.

Vitrectomy for TRD Associated With High Reattachment Rates But Limited Postoperative Vision

■ Pars plana vitrectomy (PPV) for diabetic tractional retinal detachment (TRD) is associated with high anatomic reattachment but limited final vision postoperatively, according to a systematic review and meta-analysis. This information may be useful for counseling patients with diabetic TRD, given that higher preoperative visual acuity is associated with higher postoperative vision. The study was designed to determine anatomic and functional outcomes of PPV for the treatment of TRD in people with diabetes.

Out of the 406 evaluated studies (MEDLINE and Embase), 3,839 eyes were eligible and included for analysis. The overall failure rate of retinal reattachment after 1 surgery was 5.9%, and the mean final VA was 0.94. People with higher preoperative VA achieved higher postoperative vision. Study authors concluded early intervention should be considered and discussed with patients.

EyeArt Artificial Intelligence System Gets Expanded EU MDR Certification

■ Eyenuk’s EyeArt autonomous artificial intelligence system (version 3.0) has been granted a new European Commission (EC) certification as a Class IIb medical device under the EU’s Medical Devices Regulation 2017/745 (MDR) to detect signs of diabetic retinopathy including diabetic macular edema, AMD, and glaucomatous optic nerve damage using computerized analysis of images of the retina. This EC certification makes the EyeArt AI system the first and only autonomous AI solution with Class IIb MDR CE marking for the automated detection of all 3 eye diseases, and will allow detection of the diseases in a single exam using the same set of retinal images.

Short-term SING Implantable Miniature Telescope Data Published

■ Outcomes from a study of the Smaller-Incision New-Generation Implantable Miniature Telescope (SING IMT) study were recently published in the Journal of Clinical Medicine. This noncomparative retrospective study, which included 24 patients, is the first and largest single-surgeon case series to evaluate the short-term (3-month) safety and efficacy of the device, in patients with disciform scars or geographic atrophy at baseline.

Among the key findings from this study are that by months 1 and 3, the study eye had significantly higher best-corrected distance and near visual acuity than the fellow eye, and the average change in study eye best-corrected distance and near visual acuity from baseline was +7.3±5.1 letters (P<.0001) at 1 month, increasing to +14.9±7.1 letters (P<.0001) at 3 months.

Aura Announces Bel-sar Positive Safety and Efficacy Data

■ Aura Biosciences presented positive interim phase 2 safety and efficacy data of belzupacap sarotalocan (bel-sar; AU-011), for the first-line treatment of patients with early-stage choroidal melanoma with suprachoroidal administration, at the Macula Society 46^th annual meeting in Miami, Florida.

“With an average of 9 months of follow-up for patients treated with 3 cycles of therapy, the data show an excellent response to the therapy with 89% to 100% tumor control. In addition, the safety profile to date has been favorable ,with only 1 patient losing visual acuity and no treatment-related SAEs,” Ivana Kim, MD, director of the Ocular Melanoma Center at Massachusetts Eye and Ear, said in a news release.

Harrow Acquires US Rights to Five Branded Ophthalmic Products

■ Harrow announced its acquisition of the exclusive US commercial rights to 5 branded ophthalmic products: Ilevro, Nevenac, Vigamox, Maxidex, and Triesence. Harrow and the seller have entered into an estimated 6-month transition period, during which the seller will continue to sell the products in the United States and transfer all net profits from the products to Harrow. RP