Comparison of Clinical Features and Visual Outcome between Sympathetic Ophthalmia and Vogt-Koyanagi-Harada Disease in Chinese Patients.

PURPOSE: To characterize the clinical features of sympathetic ophthalmia (SO) and compare SO and Vogt-Koyanagi-Harada (VKH) disease in Chinese patients. DESIGN: Retrospective case series. PARTICIPANTS: A total of 131 consecutive SO and 500 VKH disease patients randomly selected from among those referred to our uveitis center from April 2008 through June 2018. METHODS: History, extraocular and ocular findings, best-corrected visual acuity (BCVA), auxiliary examination findings, complications, and therapeutic effects were analyzed retrospectively in SO and VKH disease patients. MAIN OUTCOME MEASURES: Visual outcome, extraocular and ocular findings, and therapeutic effects. RESULTS: Sympathetic ophthalmia manifested as posterior uveitis (68.8%) within 2 weeks and equal involvement of anterior and posterior segment (44.4%), respectively, was observed between 2 weeks and 2 months after disease onset. Two months after disease onset, SO patients showed sunset glow fundus (51.2%) and granulomatous anterior uveitis (27.3%). Vogt-Koyanagi-Harada disease patients mainly showed posterior uveitis (100%), anterior segment involvement (92.4%) associated with posterior uveitis (84.9%), and granulomatous anterior uveitis (97.4%) accompanying sunset glow fundus (91.5%) in the 3 periods mentioned above. The frequencies of extraocular manifestations were lower in SO patients (24.4%) as compared with VKH disease patients (84.8%; P < 0.001). Best-corrected visual acuity of SO patients improved from 0.68±0.86 logarithm of the minimum angle of resolution (logMAR) to 0.47±0.78 logMAR (P = 0.01), and BCVA of VKH disease patients improved from 0.67±0.79 logMAR to 0.24±0.53 logMAR (P < 0.001) at 12 months of follow-up. A worse BCVA was noted in SO patients compared with VKH disease patients after treatment (P = 0.003). Kaplan-Meier survival analysis showed that the risk of loss of useful vision in SO patients was significantly higher than that of VKH disease patients (P < 0.001). CONCLUSIONS: Chinese SO and VKH disease patients have a different evolutionary process. The frequency of extraocular manifestations in SO patients is much lower as compared with VKH disease patients. Visual outcome is worse in SO as compared with VKH disease.

Immunogenetics and clinical phenotype of sympathetic ophthalmia in British and Irish patients.

BACKGROUND/AIMS: Sympathetic ophthalmia (SO) is a classic example of autoimmune disease where human leucocyte antigen (HLA) genomic associations could provide further understanding of mechanisms of disease. This study sought to assess HLA genetic polymorphism in British and Irish patients with SO, and to assess whether HLA gene variants are associated with clinical phenotype or disease severity. METHODS: High resolution DNA based HLA typing using polymerase chain reaction sequence specific primers was performed in 27 patients with SO and 51 matched healthy controls. Clinical phenotype and markers of disease severity were determined prospectively in 17 newly diagnosed patients and from medical record review and repeat clinical examination in 10 previously diagnosed patients. RESULTS: HLA-Cw*03 (p=0.008), DRB1*04 (p=0.017), and DQA1*03 (p=0.014) were significantly associated with SO. For class II alleles at higher resolution, only HLA-DRB1*0404 (relative risk (RR) = 5.6, p = 0.045) was significantly associated with SO. The highest relative risk for any of the associated haplotypes was with HLA-DRB1*0404-DQA1*0301 (RR=10.9, p=0.019). Patients with the DRB1*04-DQA1*03 associated haplotype were significantly more likely to develop SO earlier, with fewer inciting ocular trauma events, and to require more systemic steroid therapy to control inflammatory activity. CONCLUSIONS: Sympathetic ophthalmia is associated with HLA-DRB1*04 and DQA1*03 genotypes in white patients, similar to Japanese patients. Differences in DRB1*04 gene variant associations (-0404 in Britain and Ireland and -0405 in Japan) may have implications for HLA peptide binding in disease initiation. The DRB1*04-DQA1*03 haplotype is a marker of increased SO susceptibility and severity, as in Vogt-Koyanagi-Harada disease, which also has similar clinicopathological and HLA associations.

HLA associations and ancestry in Vogt-Koyanagi-Harada disease and sympathetic ophthalmia.

A strong association with HLA antigens DR4, DRw53, and Bw54 has previously been reported among Japanese patients with Vogt-Koyanagi-Harada disease (VKH) and sympathetic ophthalmia (SO). In the United States, no firm association between HLA-A or -B loci and VKH has been found previously; testing for HLA-DR loci has not been performed to date. The authors performed HLA typing of 23 American patients with VKH and 8 patients with SO. When VKH patients were compared with racially matched controls without disease and patients with other types of uveitis, strong associations with HLA-DR4 and HLA-DRw53 were found. The strongest associations observed in this sample were with HLA-DQw3, an antigen which is in positive linkage disequilibrium with DR4, and with the HLA-DR4/DQw3 haplotype. The small number of patients with SO precluded statistical analysis; however, similar HLA associations were noted. The patients also were questioned regarding their ancestry. The anecdotal association of VKH with American Indian ancestry was confirmed. It appears that the ethnoracial association may be explained by HLA type. One possible explanation for identical HLA associations in two diseases with different precipitating events yet similar ocular manifestations is development of an altered immune response to exogenous microbial antigen with subsequent autoimmunity. Further definition of the genetic susceptibility to VKH and SO may help define the pathophysiology of both diseases and allow the prediction of which patients are at increased risk for SO.