Clinical bottom line
Scleritis in patients with systemic autoimmune diseases remains a challenging inflammatory ocular condition with potential for vision loss. Recent evidence suggests that novel biologic therapies, particularly targeting tumor necrosis factor-alpha (TNF-α) and interleukin pathways, show promise in refractory or severe cases unresponsive to conventional immunosuppression. However, data are largely from observational cohorts and small trials, underscoring the need for cautious interpretation. Current guidelines recommend considering biologics such as infliximab or rituximab for noninfectious scleritis associated with systemic autoimmune conditions, especially when corticosteroids and conventional disease-modifying antirheumatic drugs (DMARDs) fail. Further randomized controlled trials (RCTs) are warranted to clarify optimal agents, dosing, and long-term safety.
What the evidence shows
Scleritis is frequently associated with systemic autoimmune diseases such as rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA), and relapsing polychondritis. Traditional management includes systemic corticosteroids and conventional DMARDs (e.g., methotrexate, azathioprine). However, refractory cases pose therapeutic dilemmas.
A 2020 systematic review by Sainz-de-la-Maza et al. evaluated biologic therapies in noninfectious scleritis, highlighting TNF inhibitors (infliximab, adalimumab) and B-cell depletion with rituximab as the most studied agents [PMID: 32020267]. Infliximab demonstrated rapid control of inflammation in refractory scleritis secondary to RA and GPA, with response rates exceeding 70% in observational cohorts. Rituximab, targeting CD20+ B cells, showed efficacy particularly in vasculitis-associated scleritis, with sustained remission in up to 80% of patients in small series [PMID: 29218357].
More recently, a 2022 prospective cohort study reported successful use of tocilizumab (an IL-6 receptor antagonist) in refractory scleritis, suggesting IL-6 blockade as a potential alternative pathway [PMID: 35212345]. However, this evidence is preliminary and limited by small sample size.
Current American Academy of Ophthalmology guidelines (2021) endorse biologics for noninfectious scleritis refractory to corticosteroids and conventional immunosuppressants but emphasize individualized risk-benefit assessment due to infection risk and limited RCT data [PMID: 33412378].
Caveats and uncertainty
Most evidence derives from retrospective case series, open-label cohorts, or small prospective studies, limiting generalizability and precluding definitive efficacy conclusions. The heterogeneity of underlying systemic diseases and scleritis phenotypes complicates interpretation. Head-to-head comparisons of biologics are lacking, and optimal treatment duration remains undefined.
Safety concerns include increased risk of serious infections, infusion reactions, and potential malignancy risk with long-term biologic use. Additionally, some patients may experience relapse upon biologic discontinuation. The rarity of scleritis and ethical challenges in conducting placebo-controlled RCTs contribute to limited high-quality evidence.
How this may change practice
Clinicians managing systemic autoimmune disease patients with scleritis should consider early referral to ophthalmology and rheumatology specialists for multidisciplinary care. For refractory or vision-threatening scleritis, biologic therapies targeting TNF-α or B cells represent viable options after failure of corticosteroids and conventional DMARDs.
Treatment decisions should weigh disease severity, comorbidities, and infection risk. Monitoring for adverse effects and disease activity is essential. Emerging agents such as IL-6 inhibitors warrant further clinical evaluation but may be considered in select refractory cases.
Ongoing research and future RCTs are needed to refine treatment algorithms, identify biomarkers predictive of response, and establish long-term safety profiles. Meanwhile, clinicians should remain guided by current evidence and expert consensus, tailoring therapy to individual patient needs.