Abstract
Purpose :
Outcome measures sensitive to disease progression are needed for advanced ABCA4 retinopathy when atrophy extends beyond the macula. We aimed to quantify expansion rate (ER) of retinal pigment epithelium (RPE) atrophy in ABCA4 retinopathy using ultra-widefield fundus autofluorescence (UWFAF). Further, we sought to determine whether atrophy continues to expand over an extended time scale in patients with advanced atrophy and to investigate associations with atrophy size and age.
Methods :
We analyzed one eye from 15 patients with molecularly confirmed ABCA4 retinopathy enrolled in a prospective natural history study with ≥6.8 years of longitudinal follow-up. Atrophy was defined by the boundaries of definitely decreased autofluorescence, outlined manually from multiple UWFAF images covering nominally 200o of the retina at each time point.
Results :
At baseline, patients’ median age [interquartile range, IQR] was 46.3 years [41.6, 56.9] with a median VA of 20/160 [20/160,20/250]. Median follow-up was 9.8 years [7.6, 11.0] and a median of 24 UWFAF images [18, 28] were analyzed per eye across a median of 9.0 visits [8, 10]. Plots of atrophy (mm2) and square root (sqrt) atrophy (mm) against time were well described by linear functions in 14 patients; exponential growth was observed for one patient. Median rates of atrophy expansion (AE) were 0.95 mm2/year [0.689, 2.578] for linear growth and 0.20 mm/year [0.10, 0.38] for sqrt growth. Notably, atrophy expanded linearly (AE = 5.28 mm2/y; sqrt AE = 0.26 mm/y) for the patient with the largest atrophy at baseline (DDAF = 80 mm2; sqrt DDAF = 8.9 mm) and patient with the highest atrophy growth rate (AE = 10.2 mm2/y; sqrt AE = 0.77 mm/y) from baseline atrophy of 11 mm2 (sqrt atrophy = 3.32 mm). Median area of atrophy at baseline was 6.7 mm2 [1.2, 10.2] corresponding to median sqrt atrophy of 2.59 mm [1.10, 3.2]. ER was not correlated with age or size of atrophy at baseline.
Conclusions :
UWFAF imaging may be used to measure areas of RPE atrophy extending beyond the central retina. The data from this small cohort suggest that atrophy continues to expand linearly (or exponentially in one case) in patients with large areas of atrophy at baseline and/or for patients with high atrophy ERs. Measurement of RPE atrophy from UWFAF imaging may serve as a suitable outcome measure in clinical trials of advanced ABCA4 retinopathy.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.