Patients with autoimmune disorders face higher risk of uveitis, research finds

A new large-scale study confirms a strong association between uveitis and a range of immune-mediated inflammatory diseases (IMIDs), underscoring the importance of early detection and coordinated care between ophthalmologists and rheumatologists. Uveitis, a group of ocular inflammatory conditions affecting any part of the eye, can lead to significant visual impairment if untreated. The study analyzed deidentified electronic health records from over 120 million patients in the TriNetX US Collaborative Network, assessing the relationship between uveitis and 12 IMIDs, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), ankylosing spondylitis, juvenile idiopathic arthritis (JIA), sarcoidosis, multiple sclerosis (MS), inflammatory bowel disease (IBD), psoriasis, scleroderma, giant cell arteritis (GCA), anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, and other systemic vasculitides.

The study was published in the American Journal of Ophthalmology and led by first author Nitesh Mohan, BS, of Cole Eye Institute, Cleveland Clinic, Case Western Reserve University, and Cleveland Clinic Lerner College of Medicine, in Cleveland, Ohio.

“The study results suggest that clinicians should maintain a high index of suspicion for uveitis in patients newly diagnosed with an IMID, particularly those with high risk, such as ankylosing spondylitis or JIA. Adult patients should receive urgent referral to an ophthalmologist with new onset of symptoms to identify active uveitis in order to allow early intervention and to prevent vision loss,” the study authors stated.

Researchers examined 3 primary associations: the risk of developing uveitis following an IMID diagnosis, the odds of having a prior IMID among uveitis patients, and the risk of developing an IMID after a uveitis diagnosis. For the first analysis, patients with any of the 12 IMIDs were compared with matched controls who had no IMID or prior uveitis diagnosis. Results showed that patients with IMIDs had a significantly higher risk of developing uveitis within five years. The greatest risk was observed in patients with ankylosing spondylitis (risk ratio [RR] = 7.71), JIA (RR = 5.13), and systemic vasculitis (RR = 4.61), while the lowest—but still significant—increases were seen in MS (RR = 1.64), IBD (RR = 1.84), and SLE (RR = 2.09).

The second analysis, a case-control study, examined the odds of prior IMID diagnoses among patients with uveitis compared with matched controls without uveitis. Patients with uveitis had higher odds of having a previous diagnosis of an IMID. The strongest associations were for JIA (odds ratio [OR] = 82.58), ankylosing spondylitis (OR = 38.91), and sarcoidosis (OR = 13.83). Even the lowest associations, including scleroderma (OR = 1.71), psoriasis (OR = 1.82), and MS (OR = 2.22), demonstrated a notable correlation between systemic autoimmune conditions and ocular inflammation.

The third analysis evaluated the risk of developing an IMID within five years after a uveitis diagnosis. Findings showed that patients with uveitis had an elevated risk of developing systemic inflammatory diseases, with the highest risks seen for JIA (RR = 23.32), ankylosing spondylitis (RR = 15.61), and sarcoidosis (RR = 9.99). Lower risks were observed for psoriasis (RR = 1.52), IBD (RR = 1.78), and scleroderma (RR = 2.12), but all were statistically significant.

The study emphasizes the bidirectional nature of the relationship between uveitis and IMIDs, suggesting that systemic inflammation may both predispose individuals to ocular disease and that uveitis may serve as an early marker of systemic autoimmunity. Researchers noted that systemic IMIDs often involve chronic immune activation, which can extend to ocular tissue, contributing to uveal inflammation. Upregulation of inflammatory pathways, including cytokines such as tumor necrosis factor–α, interleukin-17, and interleukin-6, likely plays a role in both systemic and ocular inflammation. Additionally, shared genetic predispositions, including HLA-B27 in ankylosing spondylitis and JIA, may underlie the particularly strong associations observed in these diseases.

The researchers recommend that clinicians maintain a high index of suspicion for uveitis in patients newly diagnosed with IMIDs, particularly those with ankylosing spondylitis or JIA. Adult patients with new ocular symptoms should receive urgent referral to an ophthalmologist to identify active uveitis early and prevent vision loss. Pediatric patients, especially those with JIA, may have asymptomatic uveitis and should follow American College of Rheumatology/Arthritis Foundation screening guidelines, which recommend ophthalmic evaluations every three months for higher-risk patients.

Conversely, the researchers stated that eye care providers evaluating patients with uveitis should screen for underlying systemic autoimmune conditions, even in the absence of a prior diagnosis, with a low threshold for referral to rheumatology. Patients should also be educated on potential signs of autoimmune disease, including rashes, joint pain, or fatigue, and encouraged to seek evaluation if symptoms arise.

The study acknowledges limitations inherent to retrospective analyses using electronic health records. Reliance on ICD coding may result in misclassification, and the analysis could not capture the exact subtype of uveitis or the true onset of IMIDs. Additionally, the study focused on a 5-year cumulative risk window, which may not reflect disease duration prior to formal diagnosis. Despite these limitations, the study provides comprehensive evidence of the temporal and bidirectional association between uveitis and systemic autoimmune disease, the researchers stated.

In conclusion, the findings reinforce the need for interdisciplinary collaboration among ophthalmologists, rheumatologists, and other specialists in managing patients with IMIDs and uveitis. Targeted screening and timely intervention may improve outcomes by mitigating both ocular and systemic complications associated with these conditions.

Reference:

1. Mohan N, Srivastava SK, Schulgit MJ, Hajj-Ali RA, Kaelber DC, Sharma S. Exploring the association between autoimmune and inflammatory diseases and uveitis. Am J Ophthalmol. 2026;284:101-109. doi:10.1016/j.ajo.2026.01.004