The Visual Acuity Course in Stargardt Disease

• Published in: American journal of ophthalmology Vol. 279; pp. 234 - 241
• Main Authors: Pas, Jeroen A.A.H., Valkenburg, Dyon, Li, Catherina H.Z., Groenewoud, Johannes M.M., Collin, Rob W.J., IntHout, Joanna, Dhooge, Patty P.A., Hoyng, Carel B.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2025
• Subjects: inherited retinal diseases; Stargardt disease type 1; visual acuity; visual acuity; inherited retinal diseases; Stargardt disease type 1
• ISSN: 0002-9394; 1879-1891; 1879-1891
• DOI: 10.1016/j.ajo.2025.07.024

•Visual acuity decline in Stargardt disease type 1 follows a nonlinear pattern and is depending on the age of symptom onset.•Visual acuity may be an impractical end point for clinical trials in Stargardt disease type 1, due to the substantial number of patients that would be required to reach sufficient statistical power.•The natural history course of visual acuity decline presented in this study may help clinicians in counseling 3 patients. To model the natural history of visual acuity decline in Stargardt disease type 1 using a nonlinear approach, evaluate its variability across different onset groups, and assess the feasibility of using visual acuity as a primary end point in clinical trials. Retrospective natural history study. We included 327 patients with a genetically confirmed diagnosis of Stargardt disease type 1 and ≥2 visual acuity measurements over time. Visual acuity was assessed using Snellen or Early Treatment of Diabetic Retinopathy Study charts and converted to LogMAR for analysis. The mean visual acuity decline was calculated, and a sigmoid curve was used to model the nonlinear progression of visual acuity decline, resulting in varying rates of decline for early-onset (age ≤10 years), intermediate-onset (11-44 years), and late-onset (≥45 years) groups. Sample size calculations were performed based on the outcomes, using visual acuity as a primary end point. Visual acuity decline rate. Visual acuity decline rates differed per disease stage, with a highest decline when visual acuity is 0.3 LogMAR (0.227 LogMAR/y). When comparing the nonlinear models, both early-onset and late-onset groups showed a significantly steeper decline rate compared with intermediate onset for both the OD and the OS (P < .001). Sample size calculations showed that 139 patients are needed for a 3-year clinical trial, only including patients with a visual acuity of 0.3 LogMAR and assuming 80% treatment effect. Visual acuity decline in Stargardt disease type 1 follows a nonlinear course, varying by age of onset. We found that a large sample size is required for visual acuity–based trials, which makes visual acuity an impractical primary end point. However, the generated models in this study will help clinicians in counseling their patients.