Abstract
Purpose :
To describe the patterns of fundus autofluorescence (FAF) and its association with visual function, molecular subtype and electrophysiological data in young patients with mutations in the BBS1 gene.
Methods :
An observational, cross sectional, retrospective analysis of 15 patients <18yrs of age with molecularly confirmed BBS1 from 13 pedigrees was carried out. Data were collected on clinical eye findings, FAF, electroretinogram, and flash and pattern visual evoked potentials. FAF images were obtained with either ultrawide-field imaging (Optos, Dunfermline) or the Heidelberg Spectralis OCT (Heidelberg Engineering, Heidelberg).
Results :
Of the 15 patients, 9 were homozygous for the M390R (H-M390R) mutation (median age 12.4y, range 6y-17.7y), 5 were compound heterozygous (CHet) with at least one M390R allele (median age 11y, range 7.3y-12.7y) and 1 was homozygous for A145G (age 16.8y). In the H-M390R group, the 6 youngest patients (6y-13.7y) showed similar patterns of focal foveal hyperFAF, while the 3 older ones (13.8-17.7y) had individually different patterns (in ascending age: perifoveal hyperFAF, scattered specks of macular hypoFAF, and concentric rings of abnormal FAF). For the other mutations, FAF patterns were of a complex bullseye pattern with multiple rings of varying FAF size and intensity. Two sibships had strikingly similar FAF patterns among themselves. Visual acuity (VA) was better in the H-M390R group vs the CHet group (mean logMAR VA:0.28±0.22 vs 0.53±0.16). Colour vision (Ishihara tests available for 12/15) was present only in the 4 youngest H-M390R patients. The mixed rod cone ERG b-wave amplitude was better preserved relative to the 5th centile in the H-M390R group at 1.1 (range 0.24-2.4) vs 0.14 (range 0.0-0.47) in the CHet group. This was despite the older mean age at the time of electrodiagnostic testing in the H-M390R group (12y vs 8y).
Conclusions :
Young BBS1 patients with homozygous M390R mutations show a distinctive foveal hyperFAF when VA, colour vision and ERG findings are normal or minimally affected. Patients with this common mutation develop evidence of functional loss as they enter their teenage years. This recognisable pattern of FAF imaging provides further insight into the relationship of age, molecular genotype, and retinal phenotype at early stages of the retinal dystrophy in BBS1.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.