Spatially Resolved Spectral Sensitivities as a Potential Read-out Parameter in Clinical Gene Therapeutic Trials.

ABSTRACT

PURPOSE: Spatially resolved functional assessment of rods and cones under photopic and scotopic conditions is desirable to evaluate the treatment outcome of gene therapeutic applications in inherited retinal disorders, such as early- onset severe retinal dystrophy (EOSRD) or achromatopsia. METHODS: A sample of 3 healthy subjects, 6 patients with RPE65 deficiency (aged 11-45 years), and 3 patients with cone dysfunction disorders underwent spectral sensitivity testing (SST) under conditions of dark and light adaptation using a Humphrey Field Analyzer modified perimeter. RESULTS: SST in healthy subjects revealed sensitivity curves corresponding well with the CIE (International Commission on Illumination) standard fundamentals. Absence of cone function was observed in patients with cone dysfunction disorders. In patients with RPE65 mutations, SST under conditions of both dark and light adaptation revealed similar curves at typical cone sensitivities. S cone-related thresholds were diminished in young patients (11-14 years) and absent in adults (19 years and over). CONCLUSION: In the present study, residual vision was cone mediated both under photopic and scotopic conditions in young patients with EOSRD associated with RPE65 mutations, but S cone function was severely reduced early on. In rod monochromats, vision was rod mediated both under conditions of dark and light adaptation. These observations are important for ongoing and future clinical trials employing gene therapeutic strategies in both rod-cone dystrophies and achromatopsia.