Impact of HLA-B51 on uveitis and retinal vasculitis: data from the AIDA International Network Registries on ocular inflammatory disorders

Background: Non-infectious uveitis (NIU) represents a difficult-to-manage condition characterized by intraocular inflammation that can potentially cause irreversible ocular damage, ultimately leading to a poor visual outcome. Genetic predisposition, including the human leukocyte antigen (HLA), is strongly associated with the development of several diseases. The pathogenetic and clinical relevance of HLA subtypes such as HLA-B51 on Behçet’s disease (BD)-related uveitis and NIU unrelated to BD is largely unknown. Methods: Data were prospectively collected from the International AIDA Network Registry for BD and the International AIDA Network Registry for uveitis. We assessed differences between groups (NIU unrelated to BD and positive for HLA-B51, BD-related uveitis positive for HLA-B51 and BD-related uveitis negative for HLA-B51) in terms of long-term ocular complications, visual acuity measured by best corrected visual acuity (BCVA), and anatomical patterns. The occurrence of retinal vasculitis and macular edema over time was also examined. Results: Medical charts of 213 patients meeting inclusion criteria (for a total of 341 eyes) were enrolled in the study. No differences in terms of complications were observed between groups (p=0.465). With regard to visual acuity, an overall significant difference was detected in median BCVA (p= 0.046) which did not maintain statistical significance after Bonferroni correction during post-hoc analysis of pair comparisons (p=0.060). Concerning anatomical pattern, anterior uveitis was significantly overrepresented among patients with NIU testing positive for HLA-B51 (p<0.001). Retinal vasculitis demonstrated a significantly higher prevalence in NIU-affected patients who tested positive for HLA-B51, irrespective of the associated systemic diagnosis of BD (p=0.025). On the contrary, no differences emerged between groups in the occurrence rate of cystoid macular edema (p=0.99). Conclusions: Patients with NIU testing positive for HLA-B51 exhibit an overall unfavorable visual prognosis and an increased likelihood of experiencing episodes of retinal vasculitis throughout the course of the disease, irrespective of a systemic diagnosis of BD. The rate of long-term structural complications as well as visual acuity are comparable between NIU cases unrelated to BD but testing positive for HLA-B51 and uveitis associated with BD. Therefore, it is recommended to screen patients with NIU for HLA-B51, even in the absence of typical Behçet's disease features, emphasizing the necessity for a closer follow-up schedule.