May 31, 2019 Conference


Natural History of Stargardt Disease in Untreated Eyes: An Analysis of Study- and Individual-level Data

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Mr. Liangbo (Linus) Shen, Yale School of Medicine, Yale University (Presenter)
Ms. Mengyuan Sun, Department of Molecular Biophysics and Biochemistry, Yale University
Holly Grossetta Nardini, Harvey Cushing/John Hay Whitney Medical Library, Yale University
Dr. Lucian Del Priore

Purpose: Controversy exists regarding the natural history of atrophic lesion secondary to recessive Stargardt disease (STGD1) with the reported growth rates of lesion area varying widely across clinical trials. We performed a study- and individual-level analysis to investigate how the lesions grow over time in untreated eyes.

Methods: We searched in MEDLINE, Embase, Web of Science,, Pubmed, and Google Scholar up to November 20, 2018 for studies that monitored atrophic lesions progression by fundus autofluorescence (FAF) in untreated eyes with STGD1 for ?6 months. We analyzed both study- and individual-level data from the included studies using three models: the area linear model (ALM), radius linear model (RLM), and area exponential model (AEM), in which the area, radius, and natural log-transformed area changes linearly with time, respectively. A horizontal translation factor was added to shift each dataset to correct for differences in subjects’ entry time into the studies [1-3]. The best model was determined by the predicted age of lesion onset and dependence of growth rates on baseline lesion sizes. The risk of bias was assessed using the Newcastle-Ottawa Scale.

Results: Of 1503 articles screened, 7 studies (564 eyes) met our inclusion criteria. Cumulative study- and individual-level datasets fit along a straight line in the RLM after introducing horizontal translation factors to correct for different entry times (r2 = 0.99 and 0.93, respectively). The growth rate of effective lesion radius was 0.104 mm/year (95% Confidence Interval = 0.086-0.123 mm/year). The age of atrophy onset predicted by the RLM (22.7±5.0 years) is remarkably similar to the reported age of onset of symptoms (22.1±3.1 years); in contrast, the predictions by the ALM and AEM deviate from this number by >5 years. Based on the individual-level data, the effective radius growth rate was independent of the baseline lesion size (r = 0.06); in comparison, the growth rates of area and natural log-transformed area were significantly dependent on the baseline lesion size (r = 0.47 and -0.33, respectively).

Conclusions: The progression of STGD1 lesions followed the RLM in both study- and individual-level data. The effective radius growth rate of atrophic lesions could serve as a reliable outcome measure to monitor STGD1 progression.