AdaptRx: Surrogate Marker for Vision Loss in AMD

DESCRIPTION (provided by applicant): Apeliotus Technologies proposes to develop a new clinical trial endpoint for age-related macular degeneration (AMD) based on dark adaptation. A major challenge in attacking AMD is the lack of adequate clinical trial endpoints. Visual acuity is currently the only accepted functional endpoint; however it is minimally impacted until the late stages of the disease when substantial vision loss has already occurred. Consequently, early-stage AMD trials are economical infeasible, requiring five to seven years and/or thousands of patients to detect a meaningful visual acuity affect. Dark adaptation is a clinical hallmark of early AMD, and is therefore an ideal candidate to address this challenge. Our AdaptRx dark adaptometer uses a proprietary method for measuring dark adaptation speed (the rate of transition from being light adapted to being dark adapted) that has been shown to be a sensitive biomarker for AMD starting at its earliest stages. The goal of this project is to validate dark adaptation as a surrogate marker for future vision loss using the AdaptRx. The specific aims for this SBIR Phase I feasibility proposal are: (1) development of a sensitive, quantitative dark adaptation protocol suitable for clinical trial use, and (2) clinical confirmation that this protocol quantifies dark adaptation speed for early and intermediate AMD patients (the target treatment population). Pilot studies have identified several promising protocols. They will be evaluated with a cohort of benchmark AMD patients to select the best option, and the ability of the selected protocol to reproducibly discriminate early and intermediate AMD patients will then be tested in a small clinical study (N=32). If we are successful, a follow-on SBIR Phase II proposal will be submitted for a multi-year prospective study of AMD patients to validate that dark adaptation impairment predicts imminent visual acuity loss. Pennsylvania State College of Medicine, Harvard Medical School and the National Eye Institute are collaborating with Apeliotus Technologies on this project. PUBLIC HEALTH RELEVANCE: Age-related macular degeneration (AMD) is the leading cause of adult blindness in developed countries. It affects over 30 million people worldwide, including one in six over age 65 and one in three over age 75. A clinical trial endpoint sensitive to early AMD would accelerate the development of early- stage interventions aimed at arresting or curing this disease before the devastation of late-stage vision loss and blindness.