LAUSR

ABSTRACT Purpose: To investigate the prevalence and characteristics of peripheral pigmented retinal lesions and the associated clinical and genetic findings in patients with pathogenic variants in the ABCA4 gene. Methods: Records at a single tertiary hospital were retrospectively reviewed to identify the presence of peripheral pigmented retinal lesions on wide-field retinal imaging in patients with ABCA4-associated disease, compared with an RDS/PRPH2 cohort, and an age-matched control group. Data on patient demographics, genetic variants, severity of disease, and phenotype were collected and assessed. Results: Of 91 patients with at least one pathogenic variant in the ABCA4 gene and fundal changes consistent with ABCA4 retinal dystrophy, 15 (16.5%) had peripheral pigmented retinal lesions in 20 eyes, and were bilateral in 6 patients. These flat, subretinal lesions were located in the mid- or far periphery, not involving the macula, and had well-defined borders. Most affected eyes had a solitary lesion (n = 18) with lesions more commonly present in the temporal half of the retina. Twenty-one unique genetic variants in ABCA4 were associated with these lesions. In 26 subjects (52 eyes) with RDS/PRPH-2-associated IRD, and in 30 age-matched controls (60 eyes), only one control eye had a pigmented lesion consistent with congenital hypertrophy of the retinal pigment epithelium and there were no peripheral pigmented lesions. Conclusions: Almost one-fifth of patients with ABCA4-associated retinopathy have peripheral pigmented retinal lesions. The presence of these lesions is associated with more severe disease with an earlier onset than in patients without the lesions, and is an aid to diagnosis.