Phenotypic characteristics and natural history of choroideremia.

Abstract

Purpose: To evaluate the clinical phenotype and natural history of choroideremia in a molecularly confirmed cohort of 26 patients

Methods: Retrospective observational case series. A comprehensive chart review of all the choroideremia cases seen at the hospital of SickKids was performed. Twenty-six subjects from 21 families with REP1 gene mutation were identified. Visual acuity, color vision, contrast sensitivity, fundus evaluation and Goldmann visual field were recorded. Spectral-domain optical coherence tomography data were analyzed when available. Patient’s data at their first visit was further analyzed based on age; two groups were created; Group-1 < 40 years of age, and group-2: 40 years or older. Follow-up data was collected when available (Range 0 -18 years).

Results: The mean age at presentation (n=26) was 40 years (range 11-68 years). Twenty one were categorized into group-1 and five as group-2. The mean visual acuity (at first visit) in the cohort was 0.08 LogMAR (range 0.0-0.48 LogMAR). 91% of group-1 subjects had visual acuity of 0.1 LogMAR or better; only 20% of group-2 subjects had visual acuity 0.1 LogMAR or better. At presentation, color vision was normal in 63% of group-1 and 20% of group-2 subjects. Contrast sensitivity was normal (1.5 LogMAR) in 69% of group-1, but all group-2 subjects had abnormal contrast sensitivity. Central visual field greater than 20^o x 20^o to Goldmann III4e target was maintained in 94% in group-1 and 25% in group-2.

Conclusions: Choroideremia is a progressive disorder, where central visual parameters appear to be severely compromised beyond 40 years of age. This study provides phenotypic characteristics of choroideremia at different ages that may guide the time of intervention in gene therapy trials.