A genome-wide association study identifies a functional ERAP2 haplotype associated with birdshot chorioretinopathy.

Birdshot chorioretinopathy (BSCR) is a rare form of autoimmune uveitis that can lead to severe visual impairment. Intriguingly, >95% of cases carry the HLA-A29 allele, which defines the strongest documented HLA association for a human disease. We have conducted a genome-wide association study in 96 Dutch and 27 Spanish cases, and 398 unrelated Dutch and 380 Spanish controls. Fine-mapping the primary MHC association through high-resolution imputation at classical HLA loci, identified HLA-A*29:02 as the principal MHC association (odds ratio (OR) = 157.5, 95% CI 91.6-272.6, P = 6.6 × 10(-74)). We also identified two novel susceptibility loci at 5q15 near ERAP2 (rs7705093; OR = 2.3, 95% CI 1.7-3.1, for the T allele, P = 8.6 × 10(-8)) and at 14q32.31 in the TECPR2 gene (rs150571175; OR = 6.1, 95% CI 3.2-11.7, for the A allele, P = 3.2 × 10(-8)). The association near ERAP2 was confirmed in an independent British case-control samples (combined meta-analysis P = 1.7 × 10(-9)). Functional analyses revealed that the risk allele of the polymorphism near ERAP2 is strongly associated with high mRNA and protein expression of ERAP2 in B cells. This study further defined an extremely strong MHC risk component in BSCR, and detected evidence for a novel disease mechanism that affects peptide processing in the endoplasmic reticulum.

An investigation of the disc hyperfluorescence in Fuchs uveitis syndrome using optical coherence tomography imaging.

PURPOSE: To identify the frequency of disc hyperfluorescence, and to use optical coherence tomography to look for vitreopapillary traction as a possible underlying cause. METHODS: Eight patients with presumed Fuchs uveitis syndrome were included. A complete ocular examination, fundus fluorescein angiography, and spectral-domain optical coherence tomography for optic nerve head were performed. RESULTS: There were 4 males and 4 female patients, and the mean age at diagnosis was 41.7 years. The most common ocular symptom was floaters (5/9). The range of initial visual acuity was 6/5-6/12. The most frequent clinical sign was inflammatory cells in the anterior chamber (9/9). Fundus fluorescein angiography showed disc hyperfluorescence in all but 1 patient. Optical coherence tomography did not show evidence of vitreopapillary traction in all eyes but one eye. CONCLUSION: We think that the high frequency of disc hyperfluorescence on fundus fluorescein angiography is an indication of an inflammatory process rather than a mechanical one.

Pointwise linear regression analysis of serial Humphrey visual fields and a correlation with electroretinography in birdshot chorioretinopathy.

AIMS: To investigate deterioration in serial Humphrey visual fields (HVFs) using pointwise linear regression (PLR) analysis in patients with birdshot chorioretinopathy (BCR) monitored with full field electroretinography (ERG). METHODS: Retrospective review of the case notes, HVFs and ERG of patients under treatment for BCR at Moorfields Eye Hospital between 1998 and 2014. Eyes with ERG recorded using protocols to incorporate International Society for Clinical Electrophysiology of Vision standards and at least five reliable Swedish Interactive Testing Algorithm standard 24-2 HVFs were included. HVFs were analysed by PLR analysis of luminance sensitivity using the Progressor software and linear regression analysis of mean deviation (MD). RESULTS: 202 HVFs from 31 eyes of 16 patients were analysed. Mean follow-up was 60.25 months. MD remained stable in all eyes. PLR analysis detected progressive field loss in 10 eyes (seven patients). The mean (SD) slope of change at progressing points was -1.83 (0.90) db/year (p<0.05). ERG worsened in 3 of the 10 eyes with field loss. Although there was no clear relationship between patterns of field loss and electrophysiological dysfunction, more extensive field loss was associated with more marked ERG abnormalities and rod system involvement. CONCLUSIONS: This study demonstrates that PLR analysis can identify field loss despite a stable MD and stable and even normal electrophysiology in BCR, thus establishing a role for regular standardised monitoring of visual fields as an adjunct to electrophysiology in order to facilitate more accurate characterisation of retinal dysfunction and hence enabling better-informed treatment decisions and monitoring of treatment efficacy.