Retinal and Visual Function Phenotype Associated With CEP290 Mutations

Abstract

Purpose: : To define the retinal phenotype associated with mutations in the CEP290 gene.

Methods: : Sixteen patients (ages 1-48 years) with mutations in CEP290 representing 14 unrelated families were evaluated by ocular examination, kinetic and achromatic static perimetry, full field sensitivity, optical coherence tomography (OCT), near infrared fundus autofluorescence imaging, transient pupillary light reflex (TPLR) and electroretinography (ERG).

Results: : Patients presented in early infancy with severe visual loss, hyperopia and nystagmus. Visual acuity (VA) ranged from 20/800 to no light perception, with rare exceptions (two patients had VA of 20/50 in at least one eye). Kinetic visual fields were measurable in only four patients; there were very limited central fields and/or small temporal islands of vision. Full-field sensitivity testing (FST) showed >4 log units of sensitivity loss or were not measurable. TPLR thresholds to brief stimuli (0.1s) in patients with measurable vision were elevated by >5 log units, when measurable. ERGs were not detectable. Despite severe visual loss, the photoreceptor layer (outer nuclear layer; ONL) in the central retina was measurable in all patients and extended to different eccentricities from the foveal center. ONL thickness at the fovea could be within normal limits or reduced. A layer of inner/outer segment remnants was evident between the photoreceptors and the RPE. A normal organization of these layers was not observed even at the youngest ages (first decade of life) examined. The inner retina in regions of photoreceptor loss was thickened suggesting a retinal remodeling process. OCT images indicated optic disc drusen in many patients. Near infrared reflectance imaging suggested preserved RPE in retinal regions with retained photoreceptors.

Conclusions: : CEP290

Keywords: retinal degenerations: hereditary • imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound)