In the first part of the session on nonclinical ophthalmology studies, Dr. Sasseville focuses on key considerations for low molecular weight therapies. Age-related macular degeneration (AMD) has three discrete stages: early (often asymptomatic), intermediate, and late. About 10% of late-stage AMD cases develop into either wet (neovascularized) or dry AMD. Wet AMD is multi-factorial, and treatments vary depending on the underlying causes, while there are currently no approved therapies for dry AMD. Dry eye disease is also multi-factorial, with multiple available treatments. Another group of vision loss–causing conditions is inherited retinal diseases, with more than 250 implicated genes.

There are multiple routes of administration for ocular therapies. Intravitreal administration is the most common overall, while intracameral delivery is preferred for low molecular weight therapies. Other routes for these therapies include topical, subconjunctival, and suprachoroidal administration. Subretinal delivery is typically used for gene therapies.

Preclinical safety studies for ocular therapies generally involve four key elements: identifying a relevant animal model species, selecting routes of administration, determining study duration, and setting dosing frequency. Endpoints in ocular studies focus on structural and functional assessments, including examination of eye structures, measurement of retinal thickness and intraocular pressure, and imaging-based endpoints.

Ocular toxicity from systemic delivery is uncommon but can be a significant hurdle if it occurs, as side effects may include cataracts, edema, degeneration, and neuritis. Localized ocular toxicity is more common and requires careful analysis to identify and understand the causative factors.