Eyeworld

EW INTERNATIONAL 74 December 2016 by Stefanie Petrou Binder, MD, EyeWorld Contributing Writer yet know its exact role. There are now more than 130 subtypes of this gene being described, so the more we know, the more complicated it becomes. Furthermore, microbes and the microbiome are repeatedly implicated in this disease," he said. In addition to HLA-B27, studies have identified ERAP-1 and IL-23R among many other genes found in association with AAU. A recent large multicenter study indicates that patients with ankylosing spondyli- tis (AS) and AAU share the genetic marker ERAP-1, which shows strong evidence of gene-gene interactions 2 and points to new mechanisms of disease pathogenesis, Dr. Wakefield said. HLA-B27/ERAP-1 gene-gene interactions have been noted in patients with AAU, AS, psoriasis, and Behçet's disease, usually showing antigen-related affects, which may be indicative of a common process, he said. "There is a genotype/pheno- type correlation in individuals with AAU and diseases such as idiopathic AU, ankylosing spondylitis, inflam- matory bowel disease, and others, although with variations to the ob- served pattern. There may be some association here, but it will unfortu- nately involve long-term prospective studies," Dr. Wakefield said. Pathogenesis In spite of their important contri- butions, gene studies fail to explain the actual pathogenesis of AAU. One hypothesis proposes that HLA-B27 molecules present as "self-peptides" or antigen, and are autoreactive. Dr. Wakefield cited an investigation that used mass spectroscopy and multiple reaction monitoring, demonstrating B27 binding variants with as many as 2,000 different peptides. 3 The study showed that the majority of peptides were endogenous, probably reflecting the normal physiological function of HLA-B27. It was not possible to distinguish peptides that bound to disease-related allotypes like HLA-B2705 when compared with non-disease-related allotypes, like HLA-B2709, suggesting a more quantitative than qualitative disease predisposition. Dr. Wakefield said that in addition, 418 peptides ho- mologous to microbial peptides were between eyes or recurs in the same eye, occasionally involving both eyes simultaneously. The sudden onset limited duration (6 to 8 weeks) episode of intraocular inflammation is centered on the iris and ciliary body with non-specific clinical signals including anterior chamber flare, keratic precipitates, synechiae, hypotony, and anterior vitreous cellular infiltrate. AAU can be polygenic and is fre- quently associated with spondyloar- thropathies (SpA). Genetic associa- tions between AAU and SpA cluster around immunologic pathways, such as IL-17 and IL-23 pathways, antigen processing and presentation, and lymphocyte development and activation. "HLA-B27 seems to be the most important gene, although we do not the prevention of the disease and its complications," Dr. Wakefield said in his presentation, "Acute anterior uveitis – immunopathogenesis of a common uveitis entity." Genetic associations Recent evidence reveals that around half of all patients with AAU are HLA-B27 positive. 1 HLA-B27 has a large number of subtypes, one of which, HLA-B2705, carries twice the risk for AAU in homozygotes. With- in the HLA-B27 subgroup of patients with AAU, there is heterogeneity of clinical features, natural history, associated systemic diseases, and response to treatment. HLA-B27 associated AAU is typically associated with either a single episode or recurrent episodes of AAU that classically alternates Studies identify new approaches to fight acute anterior uveitis U nderstanding the immuno- pathophysiology of acute anterior uveitis (AAU) and its vision-threatening complications is key to unlocking new therapeutic options. New developments in AAU research are offering alternate angles for approaching therapy and a more de- tailed understanding of this disease, according to a leading expert in the field, Denis Wakefield, MD, Prince of Wales Hospital, University of New South Wales, Sydney, Australia. Speaking at the 2016 German Ophthalmological Society (DOG) meeting, Dr. Wakefield offered a de- tailed account of what we now know about the complexity of AAU patho- genesis, shedding a hopeful light on the future of AAU intervention. AAU is the most common type of uveitis. Large surveys published over the last 10 years have consis- tently shown its high prevalence, representing between 40% and 60% of uveitis cases including interme- diate uveitis, posterior uveitis, and panuveitis. "The high prevalence of AAU brings a burden of responsibility to the ophthalmologist. There have been exciting new developments in the study of HLA-B27-related disease that have major implications for our understanding of the pathogenesis of AAU, the most common type of uveitis. Genetic and immunological studies will undoubtedly lead to new therapeutic approaches for the treatment of AAU and hopefully to Understanding AAU pathophysiology Presentation spotlight Genotype phenotype correlation in patients with anterior uveitis Source: Denis Wakefield, MD " There have been exciting new developments in the study of HLA-B27-related disease that have major implications for our understanding of the pathogenesis of AAU, the most common type of uveitis. " –Denis Wakefield, MD

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