Ocular complications and disease control in chronic uveitis treated with systemic immunomodulatory therapy

A new study found that systemic immunomodulatory therapy (IMT) may be better for treating chronic uveitis compared with local steroid therapy. Systemic IMT results in fewer ocular complications and better control of inflammation, reported first author Sofia Miguez, MD. She is a resident at the Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, and reported her study results at the 2026 EnVision Summit in Puerto Rico from February 13-16.

“Chronic uveitis is a formidable challenge that accounts for about 10% of cases of preventable blindness in the US. The clinical struggle involves a balancing act in that prolonged inflammation must be suppressed to prevent ocular damage, but long-term administration of steroids has systemic side effects,” Miguez explained.

She and her colleagues conducted a retrospective cohort study in which they compared two primary maintenance strategies to treat chronic uveitis, local steroid therapy and systemic IMT.

The advantages of local therapy are higher intraocular levels with minimal systemic absorption; however, the downsides are increased intraocular pressure (IOP) and cataracts. Systemic IMT provides broad immunosuppression and continues control of inflammation but develops systemic side effects, Miguez explained.

Patients were included in the study who had chronic noninfectious uveitis treated with monotherapy. The patients were treated for 3 years.

What were the results of the comparison of local therapy with systemic IMT?

“The findings were striking,” she commented. “Local ocular steroid therapy was associated with significantly higher risk across all primary ocular outcomes compared with systemic IMT,” she reported.

In the local steroid therapy group, the investigators saw a 2.6 times higher risk of new glaucoma diagnosis, a 1.9 times higher risk of the need for new IOP-lowering medications, and 2.2 times higher risks of both cataract surgery and glaucoma surgery.

When the investigators looked at inflammatory control, they found that local ocular steroid therapy was associated with higher rates of development of cystoid macular edema (CME) and epiretinal membranes (ERM) compared with systemic IMT, ie, 3.4 times higher risk of new CME and 2.0 times higher risk of new ERM.

The key takeaways

“The results indicated that local ocular steroid therapy is associated with 2 times higher rates of development of glaucoma and cataract, a 3.4 times higher rate of new CME, and a 2.0 times higher rate of new ERM, which suggests worse inflammatory control with local steroid therapy,” Miguez commented.

She pointed out that the study results agreed with the follow-up of the 7-year Multicenter Uveitis Steroid Treatment Trial^1, which also showed better outcomes associated with long-term systemic therapy for controlling uveitis.

“The volume of this real-world data is compelling,” she stated.

“Chronic noninfectious uveitis treated with systemic IMT is associated with fewer ocular complications and better control of inflammation. The results suggest that systemic IMT may be a more reliable long-term strategy and reduce the cumulative risk of ocular damage,” Miguez concluded.

The investigators hypothesized that local therapy may underperform because intermittent administration may facilitate low-grade smoldering inflammation, leading to a reactive rather than preventative approach. In contrast, systemic IMT provides consistent immunosuppression, prevents inflammatory flares, and provides prophylactic disease control and superior outcomes, she explained.

Miguez was joined in this study by Charles Zhang, MD; Hannah L. Walsh, MD; and Thomas A. Albini, MD.

Reference

1. Kempen JH, Altaweel MM, Holbrook JT, Sugar EA, Thorne JE, Jabs DA. Writing Committee for the Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study Research Group. Association between long-lasting intravitreous fluocinolone acetonide implant vs systemic anti-inflammatory therapy and visual acuity at 7 years among patients with intermediate, posterior, or panuveitis. JAMA. 2017;317:1993-2005.doi: 10.1001/jama.2017.5103