The National Eye Institute Prospective ABCA4 Retinopathy Natural History Study: Two Year Analysis of OCT and MP1

Abstract

Purpose : To investigate the growth of central atrophy in ABCA4 retinopathy over 2 years using en face OCT and MP1.

Methods : Fifty-five patients with at least one ABCA4 mutation and a clinical diagnosis of Stargardt disease or cone-rod dystrophy were enrolled in the prospective Natural History of ABCA4-related Retinopathies study at NIH (NCT01736293). Central retinal structure was analyzed with spectral domain OCT and retinal sensitivity measured with MP1 at baseline, 6, 12, and 24 months. The area of en face OCT central atrophy was calculated as the Riemann sum of the distance between intact EZ band edges x distance between B-scans. The area of non-responsive retina on MP1 was estimated from the number of dense scotoma points. The growth of en face OCT central atrophy (mm/yr) was derived from linear regression fit to the plot of square root of area of atrophy as a function of time.

Results : Of the 36 patients with 2 years of follow-up, the rate of growth of central atrophy could be determined in 26 patients, and the rate of growth of non-responsive retina on MP1 could be measured in 20 patients. Mean (±SD) area of OCT atrophy at baseline was 2.77± 0.97 mm (range 0.96 – 4.73 mm) which correlated with age (P=0.002; R²=0.32). The rate of growth of en face OCT atrophy (median = 0.089 mm/yr) spanned a wide range, from minimal change (0.036 mm/yr) to high rates of growth (0.141 mm/yr). The rate of growth of en face OCT atrophy was not correlated with age or size of atrophy at baseline.
Bland Altman plots indicated a higher rate of growth of non-responsive area on MP1 compared with central atrophy growth. As the size of central atrophy increased, the rate of growth of non-responsive area was higher than for growth of central atrophy. The rate of growth of en face OCT atrophy correlated with rate of change in mean sensitivity of responding points on MP1 (P=<0.036; R²=0.22) and number of MP1 points that decreased by 8dB (P=<0.005; R² = 0.37). Growth of en face OCT atrophy was not correlated with the rate of change of mean perilesional sensitivity.

Conclusions : These results indicate that en face OCT may be used to quantify the rate of growth of central atrophy in ABCA4 retinopathy. These results also indicate that structural changes in the EZ band correlate with functional changes in retinal sensitivity and that with more advanced disease, function may be altered faster than changes in structure.

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