KCNV2-associated Retinopathy: Detailed Retinal Phenotype and Structural Endpoints - KCNV2 Study Group Report 2.

PURPOSE To describe the detailed retinal phenotype of KCNV2-associated retinopathy. STUDY DESIGN Multicenter international retrospective case series. METHODS Review of retinal imaging including fundus autofluorescence (FAF) and optical coherence tomography (OCT), including qualitative and quantitative analyses. RESULTS Three distinct macular FAF features were identified: i) centrally increased signal (n=35, 41.7%), ii) DAF (n=27, 31.1%), and iii) ring of increased signal (n=37, 44.0%). Five distinct FAF groups were identified based on combinations of those characteristics, with 23.5% of patients changing FAF group over a mean (range) follow-up of 5.9 years (1.9-13.1 years). Qualitative assessment was performed by grading OCT into five grades: (i) continuous EZ (20.5%), (ii) EZ disruption (26.1%), (iii) EZ absence, without optical gap and with preserved retinal pigment epithelium (RPE) complex (21.6%); iv) loss of EZ and an hyporeflective zone at the foveola (6.8%); and (v) outer retina and RPE complex loss (25.0%). Eighty-six patients had scans available from both eyes, with 83 (96.5%) having the same grade in both eyes, and 36.1% changed OCT grade over a mean follow-up of 5.5 years. The annual rate of ONL thickness change was similar for right and left eyes. CONCLUSION KCNV2-associated retinopathy is a slowly progressive disease with early retinal changes, which are predominantly symmetric between eyes. The identification of a single OCT or FAF measurement as an endpoint to determine progression that applies to all patients may be challenging; although ONL thickness is a potential biomarker. Findings suggest a potential window for intervention until 40 years of age.