A Longitudinal Study of Stargardt Disease: Quantitative Assessment of Fundus Autofluorescence, Progression and Genotype Correlations

Abstract

 

Purpose

 

To investigate the progression of retinal atrophy in Stargardt disease (STGD) and correlate with clinical findings and genotype.

 

Methods

 

Full clinical examination and fundus autofluorescence (AF) imaging was undertaken in a cohort of 68 patients. The baseline data were compared with those at follow-up. Patients were classified into three AF subtypes: type 1 had a localised low signal at the fovea surrounded by a homogeneous background; type 2 had a localised low signal at the macula surrounded by a heterogeneous background with numerous foci of abnormal signal; type 3 had multiple low signal areas at the posterior pole with a heterogeneous background. At baseline, there were 19 patients with type 1, 41 with type 2, and 8 with type 3. The areas of reduced AF signal were measured with custom software and a yearly rate of atrophy enlargement (RAE) was calculated. Molecular screening of ABCA4 was undertaken.

 

Results

 

The median age at baseline was 30.5 years, with the follow-up interval being 9.1 years. 42% of type 1 showed enlargement of atrophy to progress to type 2. 12% of type 2 progressed to type 3. Median RAE (deg² /yr) based upon baseline AF subtypes was statistically significantly different: 0.70 in type 1, 7.46 in type 2, and 48.51 in type 3. ABCA4 variants were identified in 57 patients. There was a significant association between AF subtype and genotype.

 

Conclusions

 

The AF pattern at baseline influences the rate of atrophy progression and has genetic correlates. These data are likely to facilitate the study design and monitoring of therapeutic interventions.

 

 

AF images of a representative case at baseline and follow-up are shown.

 

Keywords: 696 retinal degenerations: hereditary • 550 imaging/image analysis: clinical