Lens Opacity in ABCA4-Associated Stargardt Disease Patients in the ProgStar Study

Purpose: The purpose of this study was to estimate lens opacity (LO) and associated risk factors in patients with ABCA4 associated Stargardt disease (STGD1). Methods: This is a secondary analysis of the multicenter ProgStar study. Patients with molecularly confirmed STGD1 aged ≥6 years from the United States and Europe were enrolled and followed for 2 years. LO was graded using the Age-Related Eye Disease Study (AREDS) protocol during slit lamp examinations. Baseline prevalence and 2-year incidence of LO were estimated. Logistic regression with generalized estimating equation was used to identify risk factors associated with LO. Results: Of the 259 participants, 54% were women, 86% were Caucasian, and the median age of STGD1 symptom onset was 19 years. At baseline, median age = 31 (interquartile range [IQR] = 21-44, range = 6-68) years; LO prevalence = 14.3% (69/483) of study eyes. Older age and later disease symptom onset were significantly associated with LO prevalence: for every decade older, adjusted odds ratio (adjOR) = 4.6 (95% confidence interval [CI] = 2.6-7.9); adjOR for every decade later in symptom onset = 0.7 (95% CI = 0.4-1.0). Among the 354 eyes without LO at baseline, 2-year incidence was 5.6%. Older age was associated with incidence: adjOR for every decade older = 4.1 (95% CI = 1.8-9.1). Posterior-subcapsular cataract was rare and nuclear cataract was the most prevalent or incident type. Conclusions: LO prevalence in ProgStar is higher than in age-matched general population. Age and age of symptom onset were risk factors of LO, suggesting both biological and accelerated aging due to retinal degeneration in STGD1. Trials of STGD1 should closely monitor safety in the anterior segment and consider excluding patients expecting cataract surgery soon.