Systemic Interleukin-6 Inhibition and Risk of Diabetic Retinopathy Development and Progression
In brief
Systemic IL-6 inhibitors cut five-year diabetic retinopathy risk by about half
In a propensity-matched US cohort of 2,605 diabetic patients on IL-6 inhibitors versus 2,605 controls, the drug class lowered five-year incidence of non-proliferative retinopathy, proliferative retinopathy, macular edema and vitreous hemorrhage by roughly 50% and reduced need for anti-VEGF, laser and surgery. Results were consistent across comparisons, but prospective trials are required to confirm a therapeutic role.
- Journal
- Ophthalmology (Q1)
- Published
- 3 August 2026
- Study design
- Prospective / inception cohort
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- Ahmed Abdi, Ahmed Alshaikhsalama, Zuhair Zaidi, Amer F Alsoudi, Melissa Yuan, Lisa J Faia, et al.
- PMID
- 42546975
- DOI
- 10.1016/j.ophtha.2026.07.029
Why clinicians should know about it
- Picked for Ophthalmology (top studies of the week, 9 August 2026): Prospective cohort, IL‑6 inhibitors lower DR incidence/progression
Abstract
PURPOSE: To evaluate whether systemic interleukin-6 (IL-6) inhibitor use is associated with reduced risk of incident diabetic retinopathy (DR), DR progression, vision-threatening complications, and retinal interventions in adults with diabetes. DESIGN: Retrospective propensity score-matched cohort study. PARTICIPANTS: Adults with type 1 or type 2 diabetes were identified using the US TriNetX electronic health record network from January 1, 2004, through May 30, 2026. After 1:1 propensity score matching, the primary analysis included 2,605 diabetic patients receiving IL-6 inhibitors and 2,605 matched diabetic controls. The secondary analysis included 1,057 matched patients per group with known nonproliferative diabetic retinopathy (NPDR). METHODS: Cohorts were matched on baseline characteristics, medication exposure, inflammatory disease burden, and ophthalmic history. The primary analysis assessed incident DR among patients without baseline retinopathy. Secondary analyses evaluated progression from NPDR to proliferative diabetic retinopathy (PDR) and compared IL-6 inhibitors with alternative immunosuppressants. Sensitivity analyses compared IL-6 inhibitors with intravitreal steroid injections among patients with severe NPDR or PDR and evaluated outcomes by IL-6 inhibitor occurrence frequency. MAIN OUTCOME MEASURES: Risk ratios for incident NPDR, PDR, vitreous hemorrhage (VH), diabetic macular edema (DME), neovascular glaucoma (NVG), and receipt of anti-vascular endothelial growth factor (anti-VEGF) injections, panretinal photocoagulation (PRP), and pars plana vitrectomy (PPV) at 1, 3, and 5 years. RESULTS: In the primary analysis, IL-6 inhibitor use was associated with significantly lower 5-year risks of NPDR (RR: 0.50; 95% CI: 0.42-0.60), PDR (RR: 0.47; 95% CI: 0.35-0.61), DME (RR: 0.37; 95% CI: 0.27-0.51), and VH (RR: 0.41; 95% CI: 0.28-0.61), with no significant difference in NVG. Anti-VEGF therapy, PRP, and PPV use were also significantly lower at 5 years. Among patients with baseline NPDR, IL-6 inhibitor use was associated with lower 5-year risks of progression to PDR, DME, VH, NVG, and retinal interventions. Findings were consistent in active comparator analyses. CONCLUSIONS: Systemic IL-6 inhibitor use was associated with lower risk of incident DR, DR progression, vision-threatening complications, and retinal interventions over 5 years, with findings persisting in active comparator and sensitivity analyses. Prospective studies are needed to evaluate whether IL-6 pathway modulation may have a therapeutic role in diabetic eye disease.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.