Macular Morphological and Functional Evaluation in Italian Patients with Stargardt Disease

Abstract

Purpose: : Autosomal recessive Stargardt disease (STGD) has been associated with substantial genetic and phenotypic heterogeneity. By systematic clinical analyses of STGD patients with complete genetic data (i.e., identified mutations on both alleles of the ABCA4 gene), we set out to determine the range of disease expression in the macula and to correlate these with specific ABCA4 alleles.

Methods: : 86 patients from 64 families with STGD/fundus flavimaculatus were investigated. All patients were submitted to complete ophthalmologic examination, optical coherence tomography, microperimetry, electroretinogram, multifocal ERG and ABCA4 gene analysis.

Results: : Two main disease expressions were observed among the examined patients. Severe macular disease group had mean visual acuity of 0.1 ± 0.05, mean foveal thickness 137.8 ± 10.4 µm, mean retinal sensitivities of 0,7 ± 0.4 dB, abnormal ERG response, mfERG within noise level in all six macular rings and no is/os layer visible at OCT examination. Mild macular disease group had mean visual acuity of 0.3 ± 0.06, mean foveal thickness 143.5 ± 6.86 µm, and mean retinal sensitivities 12.63 ± 1.1 dB, normal ERG response and multifocal ERG response for ring 1 and 2 within noise level while the response density in the most peripheral eccentricity was only slightly smaller than that measured in the control groups. The OCT revealed a preserved IS/OS in extra foveal region in 19 out of 21 patients. A significant difference between the two groups was observed in relation to visual acuity (P<0.05), retinal sensitivities (P< 0.001), preserved IS/OS (P< 0.001). mfERG was recordable in the mild group and extinguished in all patients of the severe macular group. Genetic analysis of the ABCA4 gene revealed, in the severe group, more frequent deletions, stop codons and insertions as compared to the mild phenotype group (p <0.05).

Conclusions: : This study documented morphological and functional variability of the clinical expression of STGD and allowed to distinguish different classes of disease severity, partially correlated to the genotype, allowing a better defined prognosis. These findings suggest criteria for identifying appropriate candidates with specific ABCA4 variants for upcoming human gene therapy trials in ABCA4 disease.

Keywords: macula/fovea • pathology: human • genetics