Research: quest for cataract reversal continues

NEI researchers announced that they have identified an enzyme that helps reverse cataracts in an animal model. According to the NIH press release, the research began with the investigators learning that hibernating ground squirrels develop lens clouding at 4 degrees Celsius that then reverses as the temperature warms; in contrast, the rat model used in this study as a non-hibernating animal also develops cataracts at low temperatures, but these cataracts do not reverse upon rewarming. The researchers investigated the reversible cataracts in hibernating animals using stem cells from the ground squirrels, identifying the ubiquitin-proteasome system, which, according to the study published in the Journal of Clinical Investigation, “played a vital role in minimizing the aggregation of the lens protein αA-crystallin (CRYAA) during rewarming.” Within this system, they identified RNF114 as a key enzyme responsible for aiding in this reversal and maintaining lens protein homeostasis. The researchers then delivered RNF114 to rats with cold-induced cataracts and zebrafish with cataracts due to oxidative stress, reducing lens opacities in these models. The investigators concluded that the “newly identified E3 ubiquitin ligase RNF114, related to [αA-crystalline lens protein], offers a promising avenue for treating cataracts with protein aggregates.”

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First allogenic cell therapy for treating corneal endothelial disease

Aurion Biotech announced that it began the commercial launch of Vyznova (neltependocel) in Japan for treatment of bullous keratopathy. This, the company thinks, is the first approved cell therapy for treatment of corneal disease. According to the press release, more than 25 years has gone into the development of neltependocel. In the U.S. and Canada, Aurion Biotech has completed enrollment and dosing of 97 participants in its Phase 1/2 trial. The FDA has granted Aurion Biotech a Breakthrough Therapy designation and Regenerative Medicines Advanced Therapy designation for neltependocel.

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Enrollment complete in Phase 2b geographic atrophy treatment study

Aviceda Therapeutics announced that it has completed enrollment for its Phase 2b study assessing safety and efficacy of AVD-104 for geographic atrophy (GA) secondary to AMD. The study will evaluate two doses of AVD-104 (a low dose and a high dose) and avacincaptad pegol (Izervay), enrolling about 100 patients in each arm. Patients will be dosed for 12 months and have the opportunity to remain in the study for an additional 12 months. The primary endpoint is difference in growth rate of the GA area at 12 months in the AVD-104 treated groups compared to the avacincaptad pegol group at 12 months, measured by fundus autofluorescence. Twelve-month data from this study is expected in the second half of 2025. The Phase 2a study had found no ocular or systemic serious adverse events to the drug at 3 months after one intravitreal injection, and the treatment “led to greater reduction in GA lesion progression, improved hyperautofluorescence imaging outcomes in the junctional zone at the border of growing GA lesions, and stabilization or gain of best-corrected visual acuity,” according to the company.

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European agency maintains negative opinion for intravitreal pegcetacoplan for geographic atrophy

The European Medicines Agency’s Committee for Medicinal Products for Human Use confirmed its prior negative opinion, issued in June 2024, for the marketing authorization application of intravitreal pegcetacoplan (Apellis Pharmaceuticals) for treatment of geographic atrophy secondary to AMD. Pegcetacoplan was approved as SYFOVRE for this indication in the U.S. in February 2023, making it the first FDA approved treatment for geographic atrophy.

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Companies partner to further development of new glaucoma drug

Nicox and Glaukos entered into an exclusive research and license option agreement to further development of Nicox’s NCX 1728, a nitric oxide-donating phosphodiesterase-5 inhibitor. According to the company’s press release, Glaukos will fund evaluation of NCX 1728 in preclinical research as it explores indications for treatment of glaucoma and retinal diseases. Glaukos will have the options to license NCX 1728 for development.

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ASCRS news and events

• 2025 ASCRS Annual Meeting: Registration is now open for the ASCRS Annual Meeting, taking place April 25–28, in Los Angeles, California.
• ASCRS Live!: This educational dinner series is heading to several cities across the U.S. in 2024. Registration is open for the events in Atlanta, Georgia, on October 3, San Diego, California, on November 7, and Charlotte, North Carolina, on November 14.
• ASCRS Foundation: Nominations are open for the Resident Excellence Award, which awards 10 exemplary residents a travel grant, 4 nights’ accommodation, complimentary registration, and invitations to leadership and social events at the 2025 ASCRS Annual Meeting. The Foundation is also accepting nominations for the Chang-Crandall Humanitarian Award.
• ASCRS 50th Anniversary: ASCRS members from the 50 states are sending in their perspectives on the Society, its impact on their career, and its influence on the specialty as a whole. Stay tuned each week through April 2025 for a new video.

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Research highlights

• A prospective cohort study published in the Journal of Cataract & Refractive Surgery evaluated the potential for contamination in reusing surgical materials in cataract surgery. Samples were taken from surgical instruments and products that were reused in consecutive cataract surgeries, cultured and evaluated for bacterial and fungal growth, and compared to positive controls monitored for 7 days. Group 1 for sampling/culturing included cannulas, syringes, phaco and I/A tips and sleeves that were sterilized between cases with immediate use steam sterilization; Group 2 included instruments that were used repeatedly without sterilization (phaco tubing and handpieces); and Group 3 included residual fluid from balanced salt solution bags that continued to be used for several patients. The study included 3,333 samples collected from the 3 groups. According to the paper, in all samples, no bacterial or fungal growth occurred on cultures, and of 3,241 cases that followed these protocols, no eyes developed endophthalmitis within 6 weeks postop.
• A case series prospective observational study evaluated whether guttae from Fuchs endothelial corneal dystrophy could be removed with polishing without Descemet stripping and if reduced guttae could be maintained postop with cultured corneal endothelial cell (CEC) transplant therapy. The case series included eyes that had endothelial failure due to Fuchs that received CEC transplant therapy (n=15). The main outcome was the proportion of guttae in the observed area in the early postop period (within 1 year) compared to the late postop period (after 3 years). The investigators found that all eyes exhibited confluent guttae preoperatively. In the early postop period, the guttae were typical in 5 eyes, atypical in 7 eyes, and there was no guttae in 3 eyes. The authors reported the median percentage of typical, atypical, and no guttae groups were 31.8%, 44.4%, and 16.2%, respectively, in the early phase, and 42.2%, 38.2%, and 18.8%, respectively, in the late phase. With these findings, the authors concluded that guttae can be removed through scraping/polishing of the abnormal extracellular matrix and degenerated CECs, without removal of Descemet’s membrane, and the cultured CEC transplant did not increase guttae out to 3 years postop. This research is published in JAMA Ophthalmology.

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Product news

• Lumibird Medical announced the launch of OMNICAD, a diagnostic imaging system for ocular surface disease that performs assessments of blink, tear film stability, lipid analysis, tear meniscus, and meibography, in less than 5 minutes.
• Eyenovia announced the launch and commercial availability of clobetasol propionate ophthalmic suspension, 0.05%, for postop inflammation and pain after ocular surgery.

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