Birdshot chorioretinopathy: current knowledge and new concepts in pathophysiology, diagnosis, monitoring and treatment

Abstract

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: ORPHA179OMIM: 605808.

Functionally distinct ERAP1 and ERAP2 are a hallmark of HLA-A29-(Birdshot) Uveitis

“…Although 90% of all cases carried either a risk allele for rs2287987 or rs10044354, 50% of all cases were positive for the combined haplotype. A proportion of Birdshot patients may have self-limiting disease, while others will develop irreversible retinal dysfunction and blindness [13]. It will be interesting to evaluate the potential relation between ERAP haplotypes and clinical outcome (e.g., electroretinography) in follow-up studies.…”

“…It will be interesting to evaluate the potential relation between ERAP haplotypes and clinical outcome (e.g., electroretinography) in follow-up studies. This was not possible because of the relatively limited sample size, owing to low prevalence of this rare disease [13,14]. This limitation also hampered the investigation for association with other SNPs with evidence for more moderate effect size (e.g.…”

“…Balancing selection maintains ERAP2 deficiency in one-quarter of the population [9] and drives the polymorphic ERAP1 gene to encode various protein haplotypes (allotypes) [10], few of which paradoxically confer or reduce risk for developing MHC-I-opathies [8]. To date, ERAP allotype studies have been limited to the relatively more common MHC-I-opathies [11][12][13]. In contrast, Birdshot uveitis or Birdshot chorioretinopathy (from here on 'Birdshot') is a severe, extremely rare eye condition (~1-5 cases/500,000) [13,14] that is characterized by enhanced IL-23-IL-17 pathway activation [14][15][16], and occurs exclusively in HLA-A29positive individuals [18].…”

“…To date, ERAP allotype studies have been limited to the relatively more common MHC-I-opathies [11][12][13]. In contrast, Birdshot uveitis or Birdshot chorioretinopathy (from here on 'Birdshot') is a severe, extremely rare eye condition (~1-5 cases/500,000) [13,14] that is characterized by enhanced IL-23-IL-17 pathway activation [14][15][16], and occurs exclusively in HLA-A29positive individuals [18]. A previous genome-wide association study in Birdshot highlighted strong involvement of the ERAP region on chromosome 5q15 [20].…”

Birdshot Chorioretinopathy

“…BirdShot ChorioRetinopathy (BSCR) [1][2][3][4] is a non-infectious, bilateral, panuveitis associated with distinctive, widely distributed, yellow-white choroiditis spots. Women are affected slightly more often than men and virtually all patients are Caucasian adults.…”