Progression of Stargardt disease as measured by spectral-domain optical coherence tomography (SD-OCT) in the ProgStar Study

Abstract

Purpose : To evaluate progression of loss in various retinal layers in patients with Stargardt disease type 1 (STGD1) based on 6 months follow-up of SD-OCT findings in the prospective Natural History of the Progression of Atrophy Secondary to Stargardt Disease (ProgStar) Study.

Methods : Patients with molecularly (ABCA4 gene mutations) confirmed STGD1 were enrolled. SD-OCT scans were obtained at baseline from a 20^oX20^o scan area centered on the fovea and was repeated at month 6 using the built-in follow-up mode. Retinal layers were semi-automatically segmented to identify: retinal pigment epithelium (RPE), inner segments (IS), outer segments (OS), and outer nuclear layer (ONL). The thicknesses of individual layers and the proportions of damage/tissue loss relative to the scanned area were calculated by a custom software within the total scanned area (TSA), central subfield (CS; 0.5mm radius), inner ring (IR; 0.5-1.5mm) and outer ring (OR; 1.5-3mm).

Results : Study demographics and statistics are shown in Tables 1&2. At baseline, OS and IS had the greatest loss in area within the TSA (31%; SD 30; and 29%; SD 29.6, respectively), followed by RPE (8.2%; SD 10.4) and ONL (1.9%; SD 4.1). CS showed the biggest losses with 96.3% (SD 13.7) loss in OS, 95.6% (SD 15.3) in IS, 66% (SD 4.1) in RPE, and 32% (SD 3.7) in ONL. At month 6, the greatest progression was observed in IS with 2.6% of additional loss within the TSA, followed by RPE (2.2%), ONL (1.5%), and lastly OS (1.4%). Changes in ONL and RPE lost areas were largest within the CS with 17.4% and 9.7% of additional loss, respectively, then within IR (5.4% and 7.3%), and lastly within OR (0.4%, and 1.2%). Changes in IS and OS layers were largest within IR (5% and 2.8%, respectively), then within OR (2.3% and 1.2%), and were minimal within CS (1.3% and 0.9%, respectively). All these changes were significant (p<0.001). ONL showed the biggest loss in mean thickness at month 6 (2µm; p<0.001), which was most pronounced within CS subfield (7.3µm; p<0.001).

Conclusions : Statistically significant loss in outer retinal layers can be detected by SD-OCT over 6 months in patients with STGD1. While several outcome variables including the loss in IS, OS, and ONL areas within the central 6mm look promising as surrogate biomarkers, additional data is needed to validate their use as endpoints to demonstrate halting or slowing of disease progression.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.