The National Eye Institute Prospective ABCA4 Retinopathy Natural History Study: Two Year Imaging Analysis

Abstract

Purpose : The purpose of this study is to investigate the progression of maculopathy in ABCA4 disease using autofluorescence imaging techniques.

Methods : Fifty-five patients were enrolled in the prospective Natural History of ABCA4-related Retinopathies study at the National Institutes of Health (NCT01736293), requiring at least one ABCA4 mutation and a clinical diagnosis of Stargardt disease or cone-rod dystrophy. Participants underwent comprehensive ophthalmic evaluations including short-wavelength autofluorescence (SW-AF) (Heidelberg 488/500nm), and near infrared autofluorescence (NIR-AF) (795/810nm) at two baseline visits and subsequent yearly visits. Areas of hypo-autofluorescence were demarcated using the Heidelberg Spectralis RegionFinder software in all but 14 visit points. For those images that could not be processed using RegionFinder, the images were exported and analyzed in ImageJ.

Results : Of the 55 patients that were enrolled in this study to date, 37 have completed their follow up through year two. Age at baseline examination ranged from 12 to 67 years with visual acuity from 20/16 to 20/500. Forty six patients had measurable hypo-autoflourecense (SW-AF) at baseline either by RegionFinder or ImageJ analysis ranging from an area of 0.055mm² to 68.440mm² (8.121 ± 13.098 mm²); -1.260 to 1.835 log mm² (0.494 ± 0.674 log mm²). The median rate of change in atrophy was found to be 0.111 log mm² (0.983 mm²) over two years’ time in one eye with a median slope change of SW-AF log mm² of 0.049 (95% CI: 0.060-0.136), equivalent to 11.9%. This suggests the area of hypo-autofluorescence will double every eight years. The zone of hypo-autofluorescense on NIR-AF was on average 2.294 ±2.522 times larger than that measured on SW-AF in all but two patients, with a range of 0.054 to 12.565.

Conclusions : Given the emergence of therapeutic options for patients with ABCA4-related retinopathies, it is essential to describe the natural history of the disease and identify biomarkers which may accurately be used as outcome measures in future trials. The slope of the progression of atrophy as measured by fundus hypo-autofluorescence in patients with ABCA4-related retinopathies can be one such measure where treatment efficacy may be monitored by its effect on this slope. Further analysis and comparison with functional measures and genotype are necessary for a more complete understanding of the disease process.

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