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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.

IMPORTANCE The best treatment option for primary vitreoretinal lymphoma (PVRL) without signs of central nervous system lymphoma (CNSL) involvement determined on magnetic resonance imaging or in cerebrospinal fluid is unknown. OBJECTIVE To evaluate the outcomes of treatment regimens used for PVRL in the prevention of subsequent CNSL. DESIGN, SETTING, AND PARTICIPANTS A retrospective cohort study was conducted at 17 referral ophthalmologic centers in Europe. We reviewed clinical, laboratory, and imaging data on 78 patients with PVRL who did not have CNSL on presentation between January 1, 1991, and December 31, 2012, with a focus on the incidence of CNS manifestations during the follow-up period. INTERVENTIONS The term extensive treatment was used for various combinations of systemic and intrathecal chemotherapy, whole-brain radiotherapy, and peripheral blood stem cell transplantation. Therapy to prevent CNSL included ocular radiotherapy and/or ocular chemotherapy (group A, 31 patients), extensive systemic treatment (group B, 21 patients), and a combination of ocular and extensive treatment (group C, 23 patients); 3 patients did not receive treatment. A total of 40 patients received systemic chemotherapy. MAIN OUTCOMES AND MEASURES Development of CNSL following the diagnosis of PVRL relative to the use or nonuse of systemic chemotherapy and other treatment regimens. RESULTS Overall, CNSL developed in 28 of 78 patients (36%) at a median follow-up of 49 months. Specifically, CNSL developed in 10 of 31 (32%) in group A, 9 of 21 (43%) in group B, and 9 of 23 (39%) in group C. The 5-year cumulative survival rate was lower in patients with CNSL (35% [95% CI, 50% to 86%]) than in patients without CNSL (68% [95% CI, 19% to 51%]; P = .003) and was similar among all treatment groups (P = .10). Adverse systemic effects occurred in 9 of 40 (23%) patients receiving systemic chemotherapy; the most common of these effects was acute renal failure. CONCLUSIONS AND RELEVANCE In the present series of patients with isolated PVRL, the use of systemic chemotherapy was not proven to prevent CNSL and was associated with more severe adverse effects compared with local treatment.

Background To study the results of the translocation of a free autologous retinal pigment epithelium (RPE)-choroid graft after removal of a subfoveal choroidal neovascular membrane in patients with exudative age-related macular degeneration (AMD), and to determine whether preoperative variables may predict visual outcome at 1 year after surgery. Methods Prospective interventional case series of 84 eyes of 83 consecutive eligible patients with exudative AMD with a minimal follow-up of 1 year after surgery. Of this group, 45, 24 and 11 patients reached a follow-up of respectively 2, 3 and 4 years. Pre-and postoperative evaluation included ETDRS visual acuity (VA), fixation testing and color fundus photography. Preoperative fluorescein angiograms were assessed by masked readers for lesion size, size of hemorrhage and lesion composition according to the MPS criteria. The relationship between lesion composition adjusted for preoperative delay and VA, lesion size, percentage of blood, and visual outcome at 1 year after surgery was analyzed. Results The mean VA (logMAR) improved slightly at 1 and 2 years (0.89, Δ=−0.06), 3 years (0.79, Δ=−0.16) and 4 years (0.74, Δ=−0.21) after surgery. Five patients had a preoperative VA better than 20/80, compared to 19 out of 84, six out of 45, four out of 24 and two out of 11 after 1, 2, 3 and 4 years respectively. Fixation was located on the graft in 62 patients (74%) up to the last examination. Predominantly classic and occult lesions had a significant better prognosis than minimally classic or hemorrhagic (≥50% blood) lesions. Retinal detachment occurred in seven patients; two caused by rhegmatogenous detachment and five caused by proliferative vitreoretinopathy. In 11 eyes, a recurrent or persisting neovascular membrane was observed. Conclusion An autologous free RPE-choroid graft may stabilize or improve vision in patients with exudative AMD up to 4 years after surgery.

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