Systemic Interleukin-6 Inhibition and Risk of Diabetic Retinopathy Development and Progression

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.

Retrospective propensity score-matched cohort study.

Adults with type 1 or type 2 diabetes were identified using the US TriNetX network from January 1, 2004, through May 30, 2026. After 1:1 propensity score matching, the primary analysis included 2605 IL-6 inhibitor users and 2605 matched controls. The secondary analysis included 1057 matched patients per group with known nonproliferative DR (NPDR).

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 DR (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 at IL-6 inhibitor occurrence frequency.

Risk ratios for incident NPDR, PDR, vitreous hemorrhage (VH), diabetic macular edema (DME), neovascular glaucoma (NVG), and receipt of anti-VEGF injections, panretinal photocoagulation (PRP), and pars plana vitrectomy (PPV) at 1, 3, and 5 years.

In the primary analysis, IL-6 inhibitor use was associated with significantly lower 5-year risks of NPDR [risk ratio (RR): 0.50; 95% confidence interval (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. Use of anti-VEGF therapy, PRP, and PPV was 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.

Systemic IL-6 inhibitor use was associated with a lower risk of incident DR, DR progression, vision-threatening complications, and retinal interventions over 5 years. Prospective studies are needed to evaluate whether IL-6 pathway modulation may have a therapeutic role in diabetic eye disease.

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.