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. 2021 Jan 5;10(1):3.
doi: 10.1167/tvst.10.1.3. eCollection 2021 Jan.

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

Ruben Jauregui  1   2 , Yan Nuzbrokh  1   2 , Pei-Yin Su  1 , Jana Zernant  1 , Rando Allikmets  1   3 , Stephen H Tsang  1 , Janet R Sparrow  1
Affiliations

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

Ruben Jauregui et al. Transl Vis Sci Technol. .

Abstract

Purpose: To compare the detection of retinal pigment epithelium (RPE) atrophy in short-wavelength (SW-AF) and near-infrared autofluorescence (NIR-AF) images in Stargardt disease (STGD1) patients.

Methods: SW-AF and NIR-AF images (115 eyes from 115 patients) were analyzed by two independent graders. Hypoautofluorescent (hypoAF) areas, indicative of RPE atrophy, were measured, and the two modalities were compared.

Results: Patients were segregated into four groups: nascent (6 [5%]), widespread (21 [18%]), discrete (55 [48%]), and chorioretinal atrophy (33 [29%]). The areas of hypoAF were larger in NIR-AF compared to SW-AF images in discrete (3.9 vs. 2.2 mm2, P < 0.001) and chorioretinal atrophy (12.7 vs. 11.4 mm2, P = 0.015). Similar findings were observed qualitatively in nascent and widespread atrophy patients. Using the area linear model (ALM), lesion area increased at similar rates in SW-AF and NIR-AF images of discrete atrophy (0.20 vs. 0.32 mm2/y, P = 0.275) and chorioretinal atrophy (1.30 vs. 1.74 mm2/y, P = 0.671). Using the radius linear model (RLM), the lesion effective radius also increased similarly in SW-AF and NIR-AF images in discrete (0.03 vs. 0.05 mm2/y, P = 0.221) and chorioretinal atrophy (0.08 vs. 0.10 mm2/y, P = 0.754) patients.

Conclusions: NIR-AF reveals a larger area of RPE atrophy in STGD1 patients compared to SW-AF images, but rates of lesion enlargement in the two modalities are similar.

Translational relevance: Measurements of RPE atrophy by AF imaging are crucial for monitoring STGD1 disease progression and given our findings we advocate greater use of NIR-AF for patients.

Keywords: Stargardt disease; near-infrared autofluorescence; short-wavelength autofluorescence.

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Conflict of interest statement

Disclosure: R. Jauregui, None; Y. Nuzbrokh, None; P.-Y. Su, None; J. Zernant, None; R. Allikmets, None; S.H. Tsang, None; J.R. Sparrow, None

Figures

Figure 1.
Figure 1.
Phenotypes of recessive Stargardt disease in SW-AF and NIR-AF. (A) Patients characterized as presenting with nascent RPE atrophy exhibited early atrophic changes observed as small areas of hypoAF confined to the macula. (B) Patients that presented with widespread RPE atrophy phenotype exhibited disease that extended beyond the macula and throughout the posterior pole. Macular hypoAF was observed on both SW-AF and NIR-AF images, with the majority of flecks appearing as hyperAF on SW-AF images and hypoAF in NIR-AF images. (C) Patients that presented with the discrete RPE atrophy phenotype exhibited well-delineated areas of macular hypoAF in both SW-AF and NIR-AF images. On SD-OCT scans, fragmented remnants of the EZ band and collapse of the overlying retinal layers were visible in the lesion area. Transmission of the SD-OCT signal into the choroid was also observed, further suggestive of RPE atrophy. (D) Patients that presented with the chorioretinal RPE atrophy exhibited well-demarcated areas of hypoAF on SW-AF and NIR-AF images, with the intensity of the hypoAF comparable to that of the optic disk. On SD-OCT scans, complete disappearance of the outer retinal layers and thinned retina were observed, with a high level of signal transmission beyond the retina.
Figure 2.
Figure 2.
Bland-Altman plots showing the difference in size of the atrophic lesions in SW-AF and NIR-AF. For both patients with discrete (A) and chorioretinal atrophy (B), the size of the atrophic lesions appeared larger in NIR-AF images compared to SW-AF images. The numbers in parentheses represent the 95% confidence intervals for both the mean and the limits of agreement (±1.96 SD).
Figure 3.
Figure 3.
Progression of recessive Stargardt disease in SW-AF and NIR-AF. Patient 10 (A, B) presented with a phenotype showing discrete RPE atrophy at presentation (visit 1, A). On a follow-up visit five years later (visit 2, B), the areas of atrophy had increased in size in both SW-AF and NIR-AF images. Patient 46 (C, D) exhibited a phenotype of chorioretinal atrophy at visit 1 (C) and visit 2 (D) five years later, with the atrophic lesions also increasing in size between the two visits. The measured areas of atrophy are delineated in green.
Figure 4.
Figure 4.
Rates of lesion enlargement calculated from linear regressions. The graphs demonstrate linear regressions for calculating the rate of lesion enlargement observed on SW-AF and NIR-AF images with the area linear model for discrete atrophy (A) and chorioretinal atrophy (B) patients. Similar graphs for rates calculated with the radius linear model are presented for patients with discrete (C) and chorioretinal atrophy (D).
Figure 5.
Figure 5.
Role of genotype, age, and other potential factors in the presenting phenotype of recessive Stargardt disease. Patient 78 (28 years old, A), Patient 43 (30 years old, B), and Patient 98 (62 years old, C) all presented with recessive Stargardt disease caused by the variants c.3050+5G>A and p.G1961E. Patient 98 presented with a chorioretinal phenotype of RPE atrophy, suggestive of more advanced disease, whereas both Patients 78 and 43 presented with a less-severe discrete phenotype of RPE atrophy. Similarly, Patient 68 (72 years old, D) and Patient 70 (76 years old, E) are both of similar age and both carry the pathogenic variants p.D1532N and p.G1961E, yet Patient 70 presented with a more advanced phenotype. These images suggest that the presenting phenotype of recessive Stargardt disease is influenced by genotype, age, and other potential factors such as environmental.
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