Analysis of Fundal Autofluorescence Images in a Cohort of Individuals With Mutations in Ush2a

Abstract

Purpose:: Analysis of fundal autofluorescence images in a cohort of individuals with mutations in USH2A

Methods:: Usher syndrome (USH) is a genetically heterogeneous group of disorders resulting in hearing loss and retinitis pigmentosa. USH2A is the most frequent molecular subtype of USH in the UK. Prospective clinical and molecular analysis was undertaken in a cohort of 56 affected individuals with USH resident in the UK (age range 14-68yrs, mean age 38 yrs). Direct sequencing of the coding regions and flanking intronic sequences of USH2A was performed. Retinal function was assessed in terms of visual acuity, goldman visual fields and international-standard pattern and full-field electroretinography (ERG). Fundus phenotypes were assessed clinically and by fundus autofluorescence (AF) and OCT-3 imaging.

Results:: All patients had full-field ERGs consistent with rod-cone dystrophy or severe photoreceptor dystrophy and all had at least one definite null allele (either a frameshift or a termination codon) in the USH2A gene. AF imaging revealed a perifoveal ring of high density in 53/56 (95%) individuals. The area within the ring correlated positively with both the pattern ERG P50 amplitude (r=0.8, p<0.01) and the visual field size V4e isopter (r=0.5, p<0.01), indicating different degrees of macular sparing. High density AF at the fovea was present in 27/56 (48%) individuals (mean age 45 years, mean LogMAR 0.5, p<0.01). Ten of these 27 individuals also had evidence of intraretinal cystic spaces on OCT-3 imaging. None of the remaining 29 cases with normal foveal AF had intraretinal cystic spaces on OCT-3 imaging (mean age 33yrs, mean LogMAR=0.1, p<0.01). Areas of low density AF in the peri-foveal region were present in 21/56 (38%) of individuals; this subgroup had worse mean visual acuity (LogMAR=0.53) and was older (mean=50yrs, p<0.01). .

Conclusions:: Fundus autofluorescence images in patients with USH2 had recognisable features which correlate with altered visual function. High density parafoveal AF rings are commonly present and may encircle areas of preserved photopic function. Central high density AF manifested in older patients and may be associated with worse visual acuity and intraretinal cystic spaces. With increasing age, parafoveal atrophy may occur.

Keywords: retinal degenerations: hereditary • imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound) • gene screening