Abstract
Purpose :
Stargardt disease is the most common cause of inherited macular dystrophy, and clinical trials of gene therapy for the condition are currently underway. Most published studies of progression in Stargardt disease have used en face imaging, including fundus autofluorescence, which primarily assesses atrophy of the retinal pigment epithelium (RPE). Little is known regarding the rate of thinning within other retinal sublayers and its regional variation in the macula. This study elucidates the pattern of retinal sublayer thinning in Stargardt disease and assesses the rate of thinning over time.
Methods :
Optical coherence tomography (OCT) volume scans from 111 patients with molecularly-confirmed ABCA4-associated Stargardt disease were segmented using the Iowa Reference Algorithms (ver. 3.8.0) and compared to 35 normal control eyes. Segmentation surfaces were manually corrected as needed, and retinal sublayer thicknesses within ETDRS subfields (center subfield, inner and outer rings) were computed per visit per patient. For those with longitudinal imaging (ABCA4, n=60; controls, n=35), the rate of change in retinal sublayer thicknesses was measured using the initial and last follow-up scan (mean follow-up 2.3 years for both ABCA4 and controls).
Results :
Baseline retinal thicknesses (Fig. 1) were thinner in Stargardt patients than controls for all sublayers, with the exception of the nerve fiber layer, which was similar, and RPE, which was slightly thicker. These differences were most pronounced in the center subfield. In the outer ring, sublayer thicknesses were similar between Stargardt patients and controls, with the greatest difference in the outer nuclear layer (ONL). Stargardt patients had a rate of photoreceptor (ONL to outer segments) thinning that was similar in all subfields, whereas the RPE thinned fastest in the center subfield (Fig. 2).
Conclusions :
Stargardt disease possesses a distinct pattern of retinal thinning depending on sublayer and subfield. Longitudinal, OCT-based assessment of retinal thinning may provide objective measures of progression or treatment response for clinical trials. Significant variation in foveal preservation is seen, and analysis of retinal sublayer changes may help stratify individual susceptibility and provide insight into pathophysiologic mechanisms based on the sequence of retinal thinning over time.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.