Functional Analysis of Retinal Flecks in Stargardt Disease

Abstract

PURPOSE: To evaluate visual function of flecked areas in a series of patients with Stargardt disease (STGD) and compare them with adjacent non flecked areas. METHODS: Twenty-seven patients with STGD, ABCA4 mutations and yellowish retinal flecks at fundus examination were recruited. Microperimetry with the Nidek MP-1 and fundus autofluorescence imaging (FAF) were performed in all the patients (27 eyes) while spectral-domain optical coherence tomography (SD-OCT) was performed in a subgroup of patients (20 eyes). Visual sensitivity (in dB) for each hyperfluorescent flecked area on FAF was compared with the value of the nearest adjacent non-flecked area in the MP-1 grid and at approximately the same distance from the fovea. Retinal structure in some of the flecked areas tested by microperimetry was analysed with SD-OCT. All patients were screened for mutations in the ABCA4 gene by APEX array and direct sequencing. RESULTS: A total of 1836 locations (68 locations for each eye with the 10-2 program) were tested with the MP-1 and 97 corresponded to hyperautofluorescent flecks. A repeated measure, linear regression analysis was used to evaluate differences between visual sensitivity associated with the 97 flecked areas with those in the 97 neighbouring non-flecked areas. The difference was statistically significant (p<0.001) (flecked areas 12.89 +/- 3.86 dB vs. non-flecked areas 14.40 +/- 3.53 dB, respectively). SD-OCT in the flecked areas revealed the presence of hyperreflective dome-shaped lesions in the outer retina located at the level of the retinal pigment epithelium (RPE), with dislocation or disruption of the photoreceptor layer. CONCLUSIONS: In STGD hyperfluorescent flecks on FAF are associated with decreased visual sensitivity compared to adjacent non-flecked areas and with an alteration of the photoreceptor layer on OCT. Flecks do not represent only a typical ophthalmoscopic feature but correspond, in some cases, to retinal damage that contributes to patients' visual loss.