The present study revealed a correlation between HLA04 allele and visual outcomes before and after initiating systemic corticosteroid therapy in treatment-naïve patients with VKH disease. Also, although the statistical study did not yield significant results, we speculate that CRT and CCT might show significant differences with greater numbers of cases of homozygotes, heterozygotes, and normal subjects. These thicknesses may be associated with the final prognosis of the disease [13]. The duration from first visit to steroid administration was very short. This was taken as a likely reason for the low recurrence rate for VKH compared with other reports without the use of immunosuppression therapy [7].
Previous studies have reported that HLAs represent a set of cell surface molecules mediating leukocyte interactions. HLA therefore plays an important role in immune system function as well as in the pathogenesis of autoimmune diseases, including VKH. Almost 40 years ago, an association between HLA-BW22J and VKH was reported [14]. Since then, more articles have been published regarding the associations of different HLA types to VKH. Among these, most investigations have focused on the HLA-DR4 serotype and its corresponding allele, HLA-DRB1*04 [15]. Shi et al. reported a meta-analysis confirming the association between VKH and HLA-DR4/DRB1*04, finding that the strength of association differed between ethnic groups, and identifying HLA-DRB1*0404, 0405, and 0410 as risk sub-alleles, and 0401 as a protective sub-allele [16,17].
In this study, linear regression showed significant differences in logMAR BCVA at baseline between the three groups of homozygotes, heterozygotes, and normal subjects.
For groups not having HLA-DR4/DRB1*04, the diagnosis may be not typical for VKH. However, both homozygous and heterozygous groups showed findings above the regression equation line, and were considered to have certain statistical meaning.
In the study of type 1 diabetes in Japanese, disease susceptibility has been found to differ between homozygotes and heterozygotes [18]. Similarly, disease susceptibility to VKH may differ between homozygotes and heterozygotes. Both before and after steroid treatment, homozygotes displayed the best post-treatment visual acuity. Normal subjects (no HLA-DRB1*04 allele) showed the poorest visual acuity after treatment. This indicates that therapeutic response and sensitivity to steroid treatment may depend on allele HLA-DRB1*04. An understanding of the pathogenic conditions that must exist to explain these results is difficult to reach. However, previous reports using methods such as haplotype linkage disequilibrium have suggested associations with genes closely related to immunity and inflammation, such as the IKBL gene and TNFA gene present in HLA class III [19,20,21].
The HLA-DRB1*04 allele is known to represent a disease-associated gene that is frequently found in VKH, but our study suggested the possibility of disease resistance in association with this allele. On the other hand, another report found that presence of the HLA-DRB1*04 allele was related to the prolongation of VKH in Japanese patients [22].
We know that the HLA-DRB1*04 allele is the key to VKH, but the details remain elusive. According to the previous report, CCT correlates with vision prognosis in VKH [23]. However, in this case series with possible problems in the limited number of cases, the correlation between allele HLA-DRB1*04 and CCT could not be determined. In addition, in the case of regression analysis, an explanatory variable that roughly divided the number of cases by 15 was considered appropriate [24].
In the future, the complete genetic predisposition of VKH is expected to be elucidated, leading to the development of next-generation treatments and preventive measures.
We acknowledge these potential issues, as well as the need for future worldwide studies into the correlation between the HLA-DRB1*04 allele and visual outcomes in VKH.