Stem Cell and Gene Therapies Show Promise for Retinal and Optic Nerve Disease

A stem cell-derived therapy for advanced geographic atrophy (GA) improved vision and showed signs of retinal preservation in a phase Ib trial, while the world's first gene therapy for optic neuropathies has been administered to a living patient. These developments highlight how regenerative and gene-based approaches are moving toward clinical use in eye diseases that currently lack restorative treatments.

ASP7317, an RPE cell therapy derived from human embryonic stem cells, was evaluated in nine patients with GA and severe vision impairment (17-37 letters) in three dose-defined cohorts. Best corrected visual acuity improved from baseline to 52 weeks with all three dose levels, with the largest improvement in the mid-level dose (9.08 letters). GA area size remained stable, and optical coherence tomography detected signs of retinal preservation, including increased retinal pigment epithelium-Bruch's membrane thickness. The treatment was generally well tolerated, with no graft failure and no tumors; the most common ocular adverse event was conjunctival hemorrhage (five patients), and diarrhea was the most common systemic adverse event (three patients).

In June, Life Biosciences conducted the world's first gene therapy designed to treat optic neuropathies on a living patient. The phase 1 trial of ER-100 targets open-angle glaucoma and aims to reprogram adult cells into more stem-like states using three genes: OCT4, SOX2, and KLF4 (OSK). Previous animal studies showed partial success but also the risk of tumor formation, and experts noted the treatment would likely need refinement. The company's chief scientific officer stated that controlled OSK expression has restored visual function in animal models.

In retinal vascular disease, next-generation anti-VEGF agents such as aflibercept 8 mg and faricimab are extending treatment intervals and improving durability. In case reports, a patient with central retinal vein occlusion extended to at least 8 weeks on aflibercept 8 mg, a wet age-related macular degeneration patient reached 13 weeks on faricimab, and a diabetic macular edema patient extended to 16 weeks after adding an adjunctive subtenon triamcinolone acetonide injection. Clinicians noted that second-generation agents appear superior to bevacizumab in reducing central subfield thickness and durability.

For glaucoma, research increasingly focuses on neuroprotection independent of intraocular pressure reduction. Mechanisms such as oxidative stress, excitotoxicity, mitochondrial dysfunction, and neuroinflammation contribute to retinal ganglion cell death. Nicotinamide (vitamin B3), a precursor to NAD, has emerged as a promising neuroprotective therapy, while memantine failed to show significant benefit in phase III trials.