Atrophy Expansion Rates in Stargardt Disease Using Ultra-Widefield Fundus Autofluorescence

• Main Authors: Rachael C. Heath Jeffery, MChD, MPH, Jennifer A. Thompson, PhD, Johnny Lo, PhD, Tina M. Lamey, PhD, Terri L. McLaren, BSc, Ian L. McAllister, MD, David A. Mackey, MD, Ian J. Constable, MD, John N. De Roach, PhD, Fred K. Chen, MBBS, PhD
• Format: Article
• Language: English
• Published: Elsevier 2021-03-01
• Series: Ophthalmology Science
• Subjects: ABCA4-associated retinopathy; Clinical trial end point; Inherited retinal disease; Macular dystrophy; Retinal dystrophy; Retinal imaging
• Online Access: http://www.sciencedirect.com/science/article/pii/S2666914521000038

Purpose: To investigate atrophy expansion rate (ER) using ultra-widefield (UWF) fundus autofluorescence (FAF) in Stargardt disease (STGD1). Design: Retrospective, longitudinal study. Participants: Patients with biallelic ABCA4 mutations who were evaluated with UWF FAF and Heidelberg 30° × 30° and 55° × 55° FAF imaging. Methods: Patients with atrophy secondary to STGD1 were classified into genotype groups: group A, biallelic severe or null-like variants with early-onset disease; group B, 1 intermediate variant in trans with severe or null-like variant; and group C, 1 mild variant in trans with severe or null-like variant or late-onset disease. The boundaries of definitely decreased autofluorescence (DDAF) were outlined manually and areas (in square millimeters) were recorded at baseline and follow-up. Bland-Altman analysis was conducted to examine agreement between observers and devices. Linear mixed modeling was used to evaluate predictors of ER in DDAF area and square root area (SRA). Main Outcome Measures: Patient and ocular predictors of DDAF area ER and DDAF SRA ER included age at onset, duration of symptoms, genotype group, baseline visual acuity, and baseline atrophy size. Results: A total of 138 eyes from 69 patients (33 men [47%]; mean age ± standard deviation, 41 ± 20 years; range, 10–83 years) carrying 61 unique ABCA4 variants were recruited. Ultra-widefield FAF measurements were equivalent to Heidelberg 30° × 30° imaging. Baseline DDAF area was the only significant predictor of DDAF area ER (P < 0.001). Age at baseline and genotype group were predictors for DDAF SRA ER. Definitely decreased autofluorescence area ER ranged from 4.65 mm2/year (group A) to 0.62 mm2/year (group C). Conclusions: Ultra-widefield FAF is a feasible and reliable method for assessing atrophy ER in STGD1. The value of ABCA4 mutation severity in predicting atrophy ER warrants further investigation.