Loss of Peripheral Vision in Human ABCA4-Associated Retinal Degenerations

Abstract

Purpose: : Mutations in ABCA4 (ABCR) cause autosomal recessive forms of human retinal degeneration (RD) with early macular involvement. The spectrum of peripheral retinal involvement in ABCA4-RD is less completely understood. We evaluated peripheral function in a cohort of patients with ABCA4-RD.

Methods: : The study population of 57 unrelated patients were examined clinically and with dark- and light-adapted static perimetry performed across the visual field. Rod- and cone-mediated sensitivity losses were calculated at each locus compared to mean normal data. Results from peripheral loci were averaged to obtain rod- and cone-mediated sensitivity loss in each patient; "periphery" was defined as eccentricities >=30 deg (9 mm) from the anatomical fovea. Standardized full-field ERGs were also recorded in a subset of 42 patients and compared to psychophysical results.

Results: : Using peripheral rod and cone sensitivity loss data, patients were divided into two groups: Group 1 (24/57) had normal sensitivity; Group 2 (33/57) had abnormalities in rod and/or cone sensitivity. Group 2 patients tended to be older at the time of examination (38+/-18 yrs) compared to Group 1 (31+/-12 yrs), but the difference was not significant. Best corrected visual acuities ranged from 20/20 to 20/400 (mean 20/40) in Group 1 as compared to 20/20 to counting fingers (mean 20/80) in Group 2; the difference was significant (P<0.01). Peripheral rod and cone sensitivity loss was well correlated with ERG results. All included patients were compound heterozygous for ABCA4 mutations. The distribution of allele types showed no obvious differences between groups: missense mutations were 38/48 (80%) vs. 51/66 (77%), presumed intronic and splice site mutations were 5/48 (10%) vs. 8/66 (12%), and premature terminations or small insertion/deletions were 5/48 (10%) vs. 7/66 (11%), in Groups 1 and 2, respectively. Some alleles showed a skewed distribution between the groups but many common alleles occurred with similar frequency in both groups.

Conclusions: : Involvement of the peripheral retina in addition to macular disease can have severe consequences for quality of life. In our cohort of patients with ABCA4-RD, at least 58% showed dysfunction of the peripheral retina. Further understanding of the relationship between ABCA4 genotype and phenotype will be critical for selecting suitable candidates and targeting appropriate retinal locations for therapy in future clinical trials.

Keywords: retinal degenerations: hereditary