Baseline Fundus Autofluorescence Patterns In Leber Congenital Amaurosis (LCA) Patients With RPE65 Or LRAT Mutations

Abstract

Purpose: : Fundus autofluorescence (FAF) is a measure of lipofuscin accumulation in the retina, which reflects the activity of both the retinoid cycle and the ability of the retinal pigment epithelial (RPE) to phagocytose the photoreceptor (PR) outer segments. It is potentially an excellent measure of viability of the PR-RPE interface and an equally excellent parameter of efficacy of gene replacement or drug therapy in currently ongoing LCA treatment trials. Our purpose was to determine the baseline characteristics of fundus autofluorescence (FAF) in blind patients due to LRAT or RPE65 mutations. Previously FAF was found to be absent in patients with RPE65 mutations.

Methods: : LCA patients with two LRAT or two RPE65 mutations were tested for FAF and OCT by the Heidelberg Spectralis, using the 488 nm blue light stimulus. Patients were age-matched and best corrected Snellen or ETDRS visual acuities were measured. Correlations were made between FAF patterns, VA, age, genotypes and OCT results.

Results: : Three patients with LRAT mutations and 9 patients with RPE65 entered the study. Unlike previous studies, we found that all LCA patients with either RPE65 or LRAT mutations maintain some FAF, albeit abnormal. We found three very significant patterns of autofluorescence, including 1. A wide perifoveal band of FAF surrounding an absent center of FAF; 2. A marbleleized pattern of FAF and 3. An inferior stippling pattern of FAF. We are currently correlating these patterns with age, OCT parameters, genotype, mutation severity and acuities.

Conclusions: : Unlike previous reports of absent FAF in all patients with LCA due to RPE65 mutations, we here report three patterns of FAF. These are the first reports of FAF patterns in LCA patients with LRAT mutations. Despite the fact that LRAT and RPE65 mutations cause blocks in the retinoid cycle, and prevent the formation of 11 cis retinal, we document lipofuscin accumulation, suggesting a low level of retinoid cycle activity. These FAF patterns are helpful at baseline to determine efficacy and safety of treatments for LCA.

Keywords: photoreceptors • retinal degenerations: hereditary • ipofuscin