Evaluation of patients with Stargardt disease by Microperimetry and Fundus Autofluorescence: identification of a new biomarker in defining the natural history of disease

Abstract

Purpose : We evaluated the progression of Stargardt disease due to ABCA4 mutations (STGD1) using Microperimetry (MP1) and Fundus Autofluorescence (FAF) imaging in order to investigate their capability to detect macular degeneration over a short-term follow-up (1 year).

Methods : We analyzed data from 57 patients with a clinical and molecular diagnosis of STGD1 (mean age: 33.5±1.8 years; mean disease duration: 13.4±1.3 years), undergoing a baseline and a follow-up visit, including best corrected visual acuity (BCVA), fundus examination, electroretinogram (ERG), FAF and MP1. Fundus and ERG were classified as shown in Fig. 1. To estimate disease progression, we evaluated definitely decreased autofluorescence (DDAF) from FAF images and absolute scotoma area from MP1. The study, approved by the Local Ethics Committee, adhered to the Declaration of Helsinki and each patient gave written informed consent.

Results : BCVA was 0.67±0.06 LogMAR. Fundus lesions were consistent with Fishman I phenotype in 22 patients (38.6%), with Fishman II phenotype in 17 patients (29.8%), and with Fishman III phenotype in 18 patients (31.6%). ERG responses were: Lois I in 29 patients (50.9%), Lois II in 24 patients (42.1%), and Lois III in 4 patients (7.0%). Absolute scotoma area was 5.54 ± 1.19 mm², whereas DDAF was 2.78 ± 0.44 mm². Actually, the absolute scotoma area was significantly greater than the DDAF (p = 0.009). Moreover, we observed a significant (p-value<0,001) correlation of the absolute scotoma area and of DDAF with age and duration of the disease, but not with the age of disease onset. Patients with Fishman III had significantly higher values of DDAF compared to the Fishman I phenotype and patients with Lois III presented areas of absolute scotoma significantly larger than the Lois group I. Finally, the longitudinal analysis showed that absolute scotoma area increased more quickly compared to DDAF (absolute scotoma: 1.41 mm² / year vs DDAF: 0.20 mm²/year).

Conclusions : The observation of a wider absolute scotoma area compared to DDAF at baseline and its faster progression suggest that a significant loss in photoreceptor function occurs before the death of retinal pigmented epithelium cells. This study shows that MP1 could be a sensible examination to evaluate retinal degeneration in STGD1 and consequently the effect of experimental treatments.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.