Longitudinal Changes of Fundus Autofluorescence and Correlation With Visual Acuity in ABCA4 -Associated Stargardt Disease

Purpose: To assess cross-sectional and longitudinal relationships between fundus autofluorescence (FAF) and visual acuity (VA) in ABCA4-associated Stargardt disease (STGD1). Methods: Secondary analysis used data from 301 STGD1 participants (566 study eyes) enrolled in the international ProgStar studies. The study reading center graded the FAF images qualitatively and quantitatively, including areas of atrophy reflected as definitely decreased autofluorescence (DDAF) and questionably decreased autofluorescence (QDAF). Linear models estimated cross-sectional and longitudinal associations between the growth of DDAF area and total DAF area (i.e., sum of DDAF and QDAF areas) and change in VA. Results: At the first visit, the median age was 30 years (range, 7-69); 55% were women. Mean ± SD VA was 0.73 ± 0.36 logMAR; mean total DAF area was 3.4 ± 3.8 mm2; and 42% of eyes had no DDAF. Cross-sectionally, increasing age and duration of symptoms, younger age of symptom onset, and larger QDAF area were significantly associated with worse VA (P < 0.05). Mean follow-up was 3.3 years (range, 0.5-10.3). There was no statistically significant relationship between growth of total DAF or DDAF areas and change in VA (P > 0.05). Conclusions: Characteristics other than DAF area (e.g., flecks presence) may influence VA. Some patients remained DDAF free longitudinally and thus would be excluded in STGD1 trials that use DDAF as the primary endpoint. The cross-sectional relationship between DAF and VA confirmed the association of VA with retinal pigment epithelium (RPE) structure. The lack of a significant association between growth in DAF areas with change in VA over follow-up points to challenges resulting from slow progression and large VA variability. Exploring outcome measures from other modalities is warranted for designing STGD1 trials.