Factors Influencing Retinal Pigment Epithelium-Atrophy Progression Rate in Stargardt Disease

Abstract

To evaluate demographic, clinical, imaging, and genetic factors associated with retinal pigment epithelium enlargement in Stargardt disease (STGD1) and to measure the agreement between short-wavelength fundus autofluorescence (SW-FAF) and near-infrared fundus autofluorescence (NIR-FAF). Methods: Retrospective cohort study of patients with STGD1 with ≥2 gradable SW-FAF images. RPE-atrophy areas were measured on SW-FAF and NIR-FAF at each visit and regressed against time to obtain the rate of RPE-atrophy enlargement. Agreement between SW-FAF and NIR-FAF with regards to baseline atrophic areas and rates of enlargement was evaluated. Baseline factors predictive of faster SW-FAF RPE-atrophy enlargement were investigated with linear mixed models. Results: Fifty-four eyes of 28 patients (median age: 45 years; 13 males) were included. SW-FAF and NIR-FAF agreed well for slow rates of RPE-atrophy progression, but agreement decreased as the rate increased. Median (interquartile range [IQR]) rate of RPE-atrophy expansion was 0.18 (0.10-0.85) mm 2 /year on SW-FAF and 0.24 (0.08-0.33) mm 2 /year on NIR-FAF. Larger baseline RPE-atrophy area (estimate: 0.057 mm 2 /year, P < 0.001), worse visual acuity (0.305 mm 2 /year, P = 0.005), multifocal disease (0.401 mm 2 /year, P = 0.02), and SW-FAF pattern (0.534 mm 2 /year, P =0 .03) were associated with a faster rate of progression (predictive R 2 : 0.65). Conclusions: SW-FAF and NIR-FAF are not interchangeable in the evaluation of RPEatrophy enlargement, and both imaging modalities may be required for optimal detection of disease progression. A multivariable model based on baseline clinical and imaging information may identify patients at higher risk of fast disease progression. Translational Relevance: The knowledge of the agreement of different FAF modalities, the estimated rates of RPE-atrophy enlargement, and factors predictive of faster anatomic decay in STGD1 may allow tailored clinical management and better clinical trials design.

Retinal Pigment Epithelium Atrophy in Recessive Stargardt Disease as Measured by Short-Wavelength and Near-Infrared Autofluorescence

“…Nevertheless, the rates observed for both imaging modalities were faster in the chorioretinal group compared to the discrete. These results suggest that STGD1 progresses differently based on phenotype and/or disease stage, which has been suggested by previous studies by Fujinami et al 28 and Cicinelli et al, 26 albeit both with different phenotypic characterizations to ours. In the ProgStar studies, hypoAF areas defined as “definitely decreased autofluorescence (DDAF)” roughly correspond to the chorioretinal atrophy grouping in the current study, whereas “questionable decreased autofluorescence (QDAF)” correspond to the areas we refer to as discrete.…”

“…In a recent prospective study of 44 patients (88 eyes), Muller et al 16 studied AF abnormalities by measuring their eccentricity along a foveopapillary trajectory, rather than measuring the area, and found larger abnormalities in NIR-AF images. More recently, a study by Cicinelli et al 26 (54 eyes from 28 patients) reported that rates of RPE atrophy obtained from SW-AF and NIR-AF images are similar, but that the agreement decreased as the rate increased. As compared to these previous studies, the strength of ours is not only the much larger cohort size (115 eyes from 115 patients), but also the analysis based on phenotypic presentation and the calculations of lesion enlargement rates with two different models (ALM, RLM).…”

Stargardt disease and progress in therapeutic strategies

“…FAF imaging can also illustrate early macular RPE atrophy. Recent studies have demonstrated differences in atrophy between FAF images generated by near-infrared versus short-wavelength excitation light (23)(24)(25). Nearinfrared FAF has been recommended as an adjunct to short-wavelength FAF given the earlier detection of hypoautofluorescent lesions with excellent intra-and interobserver reliability of areas of decreased FAF.…”

Stargardt disease: Multimodal imaging: A review

“… 123 The growth rate of DDAF area has been reported to range from 0.39 to 2.45 mm 2 per year and this is highly dependent on the initial lesion size (Figure 8 ). 15 , 79 , 82 , 83 , 84 , 85 , 106 , 124 , 125 , 126 Subgroup analysis has shown significant variability in growth rate related to electrophysiology grouping, 84 , 121 , 125 , 127 FAF pattern grading 85 and baseline lesion size. 82 , 83 , 126 More recently, Georgiou et al 84 also reported a mean ER of 0.69, 0.78 and 0.40 mm 2 /year for children, adults with childhood‐onset and adults with late‐onset STGD1 suggesting the importance of genotype in determining ER.…”

“… 15 , 79 , 82 , 83 , 84 , 85 , 106 , 124 , 125 , 126 Subgroup analysis has shown significant variability in growth rate related to electrophysiology grouping, 84 , 121 , 125 , 127 FAF pattern grading 85 and baseline lesion size. 82 , 83 , 126 More recently, Georgiou et al 84 also reported a mean ER of 0.69, 0.78 and 0.40 mm 2 /year for children, adults with childhood‐onset and adults with late‐onset STGD1 suggesting the importance of genotype in determining ER. Fujinami et al 3 also assessed the effect of specific genotypes on DDAF progression and found an atrophy ER of 0.45 and 0.39 mm 2 /year in patients harbouring c.5461‐10T>C and c.6079C>T variants, respectively.…”