Photoreceptor layer topography in children with leber congenital amaurosis caused by RPE65 mutations

Abstract

Purpose: To study the topography of photoreceptor loss early in the course of Leber congenital amaurosis (LCA) caused by RPE65 mutations.

Methods: Young patients with RPE65-LCA (n = 9; ages, 6-17 years) were studied with optical coherence tomography (OCT) in a wide region of central retina. Outer nuclear layer (ONL) thickness was mapped topographically and compared with that in normal subjects and in older patients with RPE65-LCA.

Results: Photoreceptor layer topography was abnormal in all young patients with RPE65-LCA. Foveal and extrafoveal ONL was reduced in most patients. There were interindividual differences, with ONL thicknesses at most retinal locations ranging from near the detectability limit to a significant fraction of normal. These differences were not clearly related to age. In most patients, there was a thinner ONL inferior to the fovea compared with that in the superior retina. Summary maps obtained by aligning and averaging photoreceptor topography across all young patients showed a relative preservation of ONL in the superior-temporal and temporal pericentral retina. These retinal regions also showed the greatest magnitude of interindividual variation.

Conclusions: Photoreceptor loss in the foveal and extrafoveal retina was prominent, even in the youngest patients studied. Differences in the topography of residual photoreceptors in children with RPE65-LCA suggest that it may be advisable to use individualized ONL mapping to guide the location of subretinal injections for gene therapy and thereby maximize the potential for efficacy.

FIGURE 1

Photoreceptor layer thickness topography of two young patients with RPE65-LCA compared with patterns in two older patients. (A, B) Cross-sectional scans along the vertical meridian in a 15-year-old normal subject and a 10-year-old patient with RPE65-LCA. (C) Normal topography of ONL thickness as an average map based on a group of six normal subjects. (D, E) Patients at 6 and 10 years of age compared with (F, G) two patients in their early 20s. Traces of major blood vessels and location of the optic nerve head are overlaid on each map (depicted as right eyes). T, temporal; N, nasal; S, superior; I, inferior. Bottom left: color scale for ONL thickness.

FIGURE 2

Photoreceptor layer thickness topography of seven other young patients with RPE65-LCA. (A–G) Individual ONL topography maps of patients with RPE65-LCA ranging in age from 7 to 17 years. (H) Average topography based on the results of all nine patients. Inset: SD of thickness, in gray scale. Bottom left: ONL thickness color scale.

FIGURE 3

Summary maps of photoreceptor ONL loss topography in young patients with RPE65-LCA. (A) Average photoreceptor losses mapped to a color scale across an expanse of central retina in the nine young patients (ages, 6–17 years). All data are depicted as a right eye. (B) Profiles of individual data sets along four radii extending from the fovea (F) along the superior-temporal (S-T), temporal (T), superior (S), and inferior (I) meridians. Gray traces: individual data: bold black traces: average profile.