Molecular Heterogeneity Within the Clinical Diagnosis of Pericentral Retinal Degeneration

Abstract

METHODS. Patients were screened for an annular ring scotoma ranging from 38 to 408 (n ¼ 28, ages 24-71) with kinetic perimetry. All patients had pigmentary retinopathy in the region of the dysfunction. Further studies included cross-sectional and en face imaging, static chromatic perimetry, and electroretinography. Molecular screening was performed.RESULTS. Genotypes of 14 of 28 PRD patients were identified: There were mutations in eight different genes previously associated with autosomal dominant or autosomal recessive RDs. Kinetic fields monitored in some patients over years to more than a decade could be stable or show increased extent of the scotoma. Electroretinograms were recordable but with different severities of dysfunction. Patterns of photoreceptor outer nuclear layer (ONL) loss corresponded to the distribution of visual dysfunction. Outer nuclear layer thickness topography and en face imaging indicated that the greatest disease expression was in the area of known highest rod photoreceptor density.CONCLUSIONS. Molecular heterogeneity was a feature of the PRD phenotype. Many of the molecular causes were also associated with other phenotypes, such as maculopathies, typical retinitis pigmentosa (RP) and cone-rod dystrophy. The pericentral pattern of retinal degeneration is thus confirmed to be an uncommon phenotype of many different genotypes rather than a distinct disease entity.

Clinical and Genetic Analysis of a European Cohort with Pericentral Retinitis Pigmentosa

“…Similarly, Berson et al [29] reported that 54% of RP patients aged ≥40 years had a visual acuity of 20/40 or better (85% in our cases aged ≥40 years). Furthermore, the GVF area estimated in pericentral RP was wider compared to typical RP, in agreement with the above-cited studies [3][4][5]. In particular, the GVF area measured with V4e target appeared markedly more preserved in pericentral RP patients compared to a large cohort (n = 601) of typical RP patients recruited in a clinical trial investigating the effects of vitamin A treatment in RP [30].…”

“…Pericentral RP was found to be associated with a better visual acuity compared to typical RP. Indeed, almost all patients (85.2%) showed a preserved BCVA of 20/40 or better in at least one eye, in line with the previous studies on pericentral RP that reported a percentage of 71% and 94% [3][4][5]. In particular, in a large US cohort of typical RP (about 900 cases), only 55% of subjects had a visual acuity of 20/40 or better [27].…”

“…Genetic defects underlying pericentral RP are overall overlapping those causing mild forms of typical RP, as previously suggested [4]. While previous studies [3][4][5] found pericentral RP cases almost exclusively in the context of non-syndromic forms, we observed a high prevalence of pericentral RP within the syndromic RP group, mainly in Usher syndrome. In agreement, variants in USH2A were detected in over 40% of the solved cases in our cohort.…”

“…In agreement, variants in USH2A were detected in over 40% of the solved cases in our cohort. A high frequency of USH2A mutations among cases with pericentral RP has not been previously reported [4,5,22,23]. Different studies identified RHO [4,24] or ABCA4 [5] defects as the most common cause.…”

Cone Vision Changes in the Enhanced S-Cone Syndrome Caused byNR2E3Gene Mutations

“…At later disease stages, there is normal sensitivity across the visual field and an annular ring of S-cone dysfunction that can coincide with pigmentary changes in a region extending from approximately 108 to 408, a region that has been described as pericentral or near peripheral. 30 These data confirm the impression from the sample of six patients ( Figs. 2A-F).…”