Evaluating ocular health in retinal gene therapies

Abstract

Inherited retinal disease (IRD) refers to a heterogeneous group of genetic eye disease that causes progressive vision loss and was once regarded untreatable. However, regulatory approval for Luxturna (voretigene neparvovec-rzyl) for patients with biallelic mutation in the RPE65 gene has heralded new optimism for patients with the disease. One critical question in designing clinical trial in patients with IRD is choosing appropriate outcome measures to assess the retina, taking into consideration the slow disease progression and the inherent low vision associated with the disease. In this review, the functional and structural endpoints that have been utilised in human retinal gene therapy clinical trials in patient selection as well as measures of safety and efficacy are described. For clinicians, an appreciation of these specialised measures of eye health in a patient with IRD will enhance understanding of retinal health assessments, disease prognosis as well as facilitating discussions with patients potentially eligible for retinal gene therapy clinical trial.

Keywords: Endpoint; low vision; outcome measure; retinal gene therapy.