Purchase this article with an account.
Liangbo Linus Shen, Mengyuan Sun, Holly Grossetta Nardini, Lucian V Del Priore; Natural History of Recessive Stargardt Disease in Untreated Eyes: An Analysis of Study- and Individual-level Data. Invest. Ophthalmol. Vis. Sci. 2019;60(9):5014.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Controversy exists regarding the natural history of atrophic lesion secondary to recessive Stargardt disease (STGD) 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.
We searched in 5 databases for studies that monitored atrophic lesion progression in untreated eyes with STGD over ≥ 6 months. We extracted both study- and individual-level data from the included studies, and analyzed both levels of data using 3 models: (1) the area linear model (ALM), in which the lesion area enlarges linearly with time, (2) the radius linear model (RLM), in which the lesion radius expands linearly with time, and (3) the area exponential model (AEM), in which the lesion area changes exponentially with time. A horizontal translation factor was added to shift each dataset to correct for differences in subjects’ entry time into the studies. The model that best fit data was determined by the predicted age of lesion onset and dependence of growth rate on baseline lesion size.
Of 1630 articles screened, we identified 9 studies that met our inclusion criteria. Among them, we extracted study-level data from all 9 studies (990 eyes) and individual-level data from 5 studies (228 eyes). Cumulative study- and individual-level datasets fit along a straight line in the RLM after horizontal translation (r2 = 0.98 and 0.93, respectively; Fig. 1 and 2). The age of onset of atrophy predicted by the RLM (21.0 ± 4.0 years) is similar to the reported age of onset (20.7 ± 3.4 years); in contrast, the predictions by the ALM and AEM deviate by more than 5 years (Fig. 1C). Based on the individual-level data, the growth rate of effective lesion radius was found independent of the baseline lesion size (r = 0.06); in comparison, the growth rate of area and natural log of area is significantly dependent on the baseline lesion size (r = 0.47 and -0.33, respectively).
The progression of atrophic lesion secondary to STGD best fits the RLM for both study- and individual-level data (growth rate = 0.091 mm/yr). This may assist the design of clinical trials on STGD.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
Fig. 1. Study-level data. (A, B) Before and after horizontal translations. (C), Age of atrophy onset.
Fig. 2. Individual-level data. (A, B) Before and after horizontal translations.
This PDF is available to Subscribers Only