Chorioretinitis

Four inflammatory diseases are strongly associated with Major Histocompatibility Complex class I (MHC-I) molecules: birdshot chorioretinopathy (HLA-A*29:02), ankylosing spondylitis (HLA-B*27), Behçet's disease (HLA-B*51), and psoriasis (HLA-C*06:02). The endoplasmic reticulum aminopeptidases (ERAP) 1 and 2 are also risk factors for these diseases. Since both enzymes are involved in the final processing steps of MHC-I ligands it is reasonable to assume that MHC-I-bound peptides play a significant pathogenetic role. This review will mainly focus on recent studies concerning the effects of ERAP1 and ERAP2 polymorphism and expression on shaping the peptidome of disease-associated MHC-I molecules in live cells. These studies will be discussed in the context of the distinct mechanisms and substrate preferences of both enzymes, their different patterns of genetic association with various diseases, the role of polymorphisms determining changes in enzymatic activity or expression levels, and the distinct peptidomes of disease-associated MHC-I allotypes. ERAP1 and ERAP2 polymorphism and expression induce significant changes in multiple MHC-I-bound peptidomes. These changes are MHC allotype-specific and, without excluding a degree of functional inter-dependence between both enzymes, reflect largely separate roles in their processing of MHC-I ligands. The studies reviewed here provide a molecular basis for the distinct patterns of genetic association of ERAP1 and ERAP2 with disease and for the pathogenetic role of peptides. The allotype-dependent alterations induced on distinct peptidomes may explain that the joint association of both enzymes and unrelated MHC-I alleles influence different pathological outcomes.

Birdshot chorioretinopathy (BCR) is a rare form of chronic, bilateral, posterior uveitis with a distinctive clinical phenotype, and a strong association with HLA-A29. It predominantly affects people in middle age. Given its rarity, patients often encounter delays in diagnosis leading to delays in adequate treatment, and thus risking significant visual loss. Recent advances have helped increase our understanding of the underlying autoimmune mechanisms involved in disease pathogenesis, and new diagnostic approaches such as multimodality imaging have improved our ability to both diagnose and monitor disease activity. Whilst traditional immunosuppressants may be effective in BCR, increased understanding of immune pathways is enabling development of newer treatment modalities, offering the potential for targeted modulation of immune mediators. In this review, we will discuss current understanding of BCR and explore recent developments in diagnosis, monitoring and treatment of this disease. Synonyms for BCR: Birdshot chorioretinopathy, Birdshot retinochoroiditis, Birdshot retino-choroidopathy, Vitiliginous choroiditis. Orphanet number: ORPHA179 OMIM: 605808.

Toxoplasmic retinochoroiditis is deemed a local event, which may fail to evoke a detectable systemic immune response. A correct diagnosis of the disease is a necessary basis for estimating its clinical burden. This is not so difficult in a typical clinical picture. In atypical cases, further diagnostic efforts are to be installed. Although the aqueous humor may be analyzed for specific antibodies or the presence of parasitic DNA, the DNA burden therein is low, and in rare instances a confirmation would necessitate vitreous sampling. A laboratory confirmation of the diagnosis is frustrated by individual differences in the time elapsing between clinical symptoms and activation of specific antibody production, which may result in false negatives. In congenital ocular toxoplasmosis, a delay in the onset of specific local antibody production could reflect immune tolerance. Herein, the authors attempt to provide a simple and practicable algorithm for a clinically tailored diagnostic approach in atypical instances.

ObjectivesTo describe a rare phenotype of birdshot chorioretinitis (BSCR) characterised by diffuse retinal depigmentation and to evaluate its relationship with disease chronicity and visual outcomes.MethodsThis observational study included patients from the CO-BIRD cohort with ultra-widefield fundus imaging. Retinal depigmentation was graded using the albinism scale by Kruijt et al. (grades 0-3). Eyes with a grade ≥ 2 in at least one image were included. Disease activity and severity were assessed using best-corrected visual acuity (BCVA), vision-related quality of life (VFQ-25), visual field testing and multimodal imaging.ResultsAmong 1016 eyes (508 patients), 52 eyes (26 patients, 5.1%) had depigmentation grade ≥ 2; 22 eyes (2.2%) reached grade 3. Fifteen years after symptom onset, BCVA worse than 0.7 logMAR occurred in 42.1% of grade 3 versus 5.0% of grade 2 eyes (p = 0.014). VFQ-25 scores were similarly reduced in both groups. Grade 3 was associated with a lower risk of optic disc oedema (HR = 0.38; p = 0.028) and a non-significant reduction in macular oedema risk. Choroidal neovascularisation occurred only in grade 3 (40.9%). Grade 3 was linked to worse BCVA (p = 0.012), higher pattern standard deviation (p = 0.011), and a history of active disease. Compared with previously published CO-BIRD data, grade 3 showed faster BCVA decline (p = 0.044) and greater cumulative loss (p = 0.001).ConclusionDiffuse retinal depigmentation resembling albinism is an uncommon but severe expression of BSCR, indicative of chronic disease and associated with poorer visual outcomes.