Ophthalmology Month in Review: September 2024

If this ophthalmology month in review for September 2024 is any indication, recent advancements in gene therapies and treatments for vision-related conditions could significantly improve patient outcomes and quality of life.

In September, ATSN-101 gene therapy demonstrated notable safety and efficacy in patients with Leber congenital amaurosis 1, while Nanoscope Therapeutic's MCO-010 gene therapy received US Food and Drug Administration (FDA) support for its Phase 3 trial targeting Stargardt disease. Additionally, oral gildeuretinol acetate showed significant reductions in geographic atrophy (GA) growth associated with age-related macular degeneration (AMD), and phentolamine ophthalmic solution provided rapid reversal of mydriasis, leading to FDA approval. Meanwhile, studies underlined the psychological impacts of vision loss, highlighting a higher risk of depression in retinitis pigmentosa patients and suggesting that correcting vision impairment could prevent nearly 20% of dementia cases in older adults.

ATSN-101 Gene Therapy Reports Positive Data in Phase 1/2 Trial

ATSN-101 subretinal gene therapy showed a strong safety profile and significant improvements in visual function in patients with Leber congenital amaurosis 1 (LCA1) due to GUCY2D mutations, according to Phase 1/2 trial data. High-dose ATSN-101 treatment resulted in an average 20 dB improvement in dark-adapted full-field stimulus test (FST), with two patients experiencing over 40 dB improvements. These results indicate the potential efficacy of gene therapy for patients with LCA1, even after years of blindness.

Nanoscope Reports Positive End-of-Phase 2 Meeting for MCO-010 Gene Therapy

On September 12, 2024, Nanoscope Therapeutics announced a successful End-of-Phase 2 meeting with the FDA for its MCO-010 gene therapy targeting severe vision loss caused by Stargardt disease. The FDA's support enables the initiation of a Phase 3 trial, which will assess the safety and efficacy of a single dose of MCO-010 compared to a sham injection. This advancement represents a potential breakthrough in providing a restorative treatment for patients with Stargardt disease, moving beyond traditional vision rehabilitation approaches.

SAGA: Oral Gildeuretinol Achieves Meaningful Reduction in GA Growth Rate

On September 17, 2024, Alkeus Pharmaceuticals announced that oral gildeuretinol acetate (ALK-001) significantly reduced lesion growth in patients with GA secondary to AMD after 24 months. The Phase 3 SAGA trial also demonstrated a statistically significant slowing of low-luminance visual acuity (LLVA) decline, a key secondary endpoint, with a favorable safety profile. These findings will be presented as a late-breaking abstract at the 128th Meeting of the American Academy of Ophthalmology (AAO) in Chicago.

Phentolamine Ophthalmic Solution 0.75% Achieves Rapid Reversal of Mydriasis

Results from the Phase 3 MIRA-2 and MIRA-3 trials showed phentolamine ophthalmic solution 0.75% (RYZUMVI™) effectively and safely reversed pharmacologically-induced mydriasis within 60 to 90 minutes. The trials demonstrated a statistically significant reduction of 3 to 4 hours in time to return to baseline pupil diameter compared with placebo. These results formed the basis for FDA approval, highlighting the clinical benefit of phentolamine ophthalmic solution for patients requiring faster recovery from pupil dilation.

Retinitis Pigmentosa Diagnosis Intensifies Risk of Depressive Disorder

A nationwide cohort study in Korea found that patients with retinitis pigmentosa (RP) had a higher incidence of newly diagnosed depressive disorder compared with the general population. The 10-year cumulative incidence of depressive disorder in these patients was around 18%, with a higher rate among women and those aged 40 and older. These findings emphasized the importance of integrating mental health care into the overall management plan for patients with RP, particularly given the progressive nature of the condition and its notable impact on quality of life.

Correcting Vision Impairment May Prevent Dementia in Older Adults

A recent study in JAMA Ophthalmology found nearly 20% of dementia cases in US adults aged 71 and older could potentially be prevented by addressing correctable vision impairments. The analysis showed that contrast sensitivity impairment had the highest impact on dementia risk, with a population attributable fraction of 15%, compared to distance and near visual acuity. The investigative team emphasized the importance of incorporating vision health into dementia prevention strategies to address modifiable risk factors.