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Page 251 Saleh et al. J Transl Genet Genom 2021;5:250-64 https://dx.doi.org/10.20517/jtgg.2021.23

continuous areas (3/37) of photoreceptor and retinal pigment epithelial dystrophy. In one patient, W-OCT
identified peripheral lesions that were not detectable in wide-field FAF and NIA. In 48/52 patients, two causative
mutations in the ABCA4 gene were identified, while the remaining four patients carried one pathogenic ABCA4
variant.

Conclusion: W-OCT as well as wide-field FAF and NIA document lesions in the retinal mid- and far periphery in the
majority of ABCA4-IRD patients and provide means for detailed analysis of progression and future treatment
planning and monitoring.

Keywords: ABCA4, inherited retinal dystrophies, optical coherence tomography, fundus autofluorescence, near-
infrared autofluorescence, wide-field imaging

INTRODUCTION
ABCA4-associated inherited retinal dystrophies (ABCA4-IRD) present predominantly as autosomal
recessive macular dystrophy (Stargardt disease) or autosomal recessive cone-rod dystrophy, but they can
also present as autosomal recessive retinitis pigmentosa, autosomal recessive cone dystrophy, and age-
[1]
related macular degeneration type 2 . Thus far, 1530 genetic variants have been described in the ABCA4
gene and classified as variants of disparate severity on the clinical phenotype expression . Although
[2-4]
clinical manifestations of ABCA4-IRD can be variable, lesions are usually similar in both eyes of one
patient. Generally, fleck-like lesions and atrophic alterations initially manifest at the posterior pole, and
during progression areas outside of the macula present alterations visible on ophthalmoscopy.

Detailed retinal imaging, identifying more lesions than are clinically visible, has demonstrated characteristic
alterations of ABCA4-IRD on fundus autofluorescence (FAF), near-infrared autofluorescence (NIA), and
optical coherence tomography (OCT) . Typical findings are fleck-like lesions with increased or reduced
[5-8]
FAF or NIA intensity, partially corresponding to subretinal material (SRM) on OCT as well as focal or
widespread areas with markedly reduced FAF and NIA intensity corresponding to photoreceptor and
retinal pigment epithelial (RPE) loss on OCT. Whereas wide-field imaging for FAF and NIA has been used
for more than 16 years, wide-field OCT (W-OCT) extending peripherally of the macular area has only
become available recently. Until now, the relevance of W-OCT imaging has predominantly been evaluated
[9]
with respect to repeatability of measurements ; normal retinal structures, especially the nerve fiber layer
and choroidal layers [10-17] ; and glaucoma-associated pathologies [18-22] . Studies regarding retinal disorders
focused on diabetic retinopathy [23-27] , central serous chorioretinopathy , or alterations associated with
[28]
myopia [29,30] , whereas retinal dystrophies have rarely been examined by W-OCT [31-34] and, if so, only in small
patient series. When comparing these W-OCT studies, it has to be kept in mind that the terms “wide-field”
and “ultra-wide-field” have been used for similar ranges of measured areas, and sometimes the measured
area has not been reported and can only be surmised from the presented images.

In the present study, we evaluated the information provided by W-OCT [55 × 25 degree field (16.1 mm ×
7.3 mm)] compared to conventional macular OCT [M-OCT; 20 × 20 degree field (6.2 mm × 6.2 mm)] in a
large series of genetically confirmed ABCA4-IRD patients.

METHODS
Included in this study was a consecutive series of unrelated patients with ABCA4-IRD who underwent W-
OCT imaging during their initial or follow-up visit in a specialized IRD center between September 2015 and
January 2021. ABCA4-IRD was defined as the presence of two likely pathogenic or pathogenic ABCA4 gene
mutations or a single likely pathogenic or pathogenic ABCA4 gene mutation with clinical findings