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

Area of Science:

• Ophthalmology
• Immunology
• Endocrinology

Background:

• Diabetic retinopathy (DR) is a leading cause of vision loss.
• Interleukin-6 (IL-6) is implicated in inflammatory processes contributing to DR pathogenesis.
• Current treatments for DR have limitations, necessitating novel therapeutic strategies.

Purpose of the Study:

• To investigate the association between systemic IL-6 inhibitor use and the risk of incident DR.
• To evaluate the impact of IL-6 inhibitors on DR progression and vision-threatening complications.
• To assess the effect of IL-6 inhibitors on the need for retinal interventions.

Main Methods:

• Retrospective propensity score-matched cohort study using the US TriNetX electronic health record network.
• Inclusion of adults with type 1 or type 2 diabetes, with primary analysis of 2,605 patients receiving IL-6 inhibitors and 2,605 matched controls.
• Assessment of incident DR, DR progression (NPDR to PDR), vision-threatening complications (DME, VH, NVG), and retinal interventions (anti-VEGF, PRP, PPV) over 5 years.

Main Results:

• IL-6 inhibitor use was associated with significantly lower 5-year risks of incident nonproliferative DR (NPDR), proliferative DR (PDR), diabetic macular edema (DME), and vitreous hemorrhage (VH).
• Reduced risks were observed for DR progression and vision-threatening complications among patients with baseline NPDR.
• Retinal intervention rates (anti-VEGF, PRP, PPV) were significantly lower in the IL-6 inhibitor group.

Conclusions:

• Systemic IL-6 inhibitor use is linked to a reduced risk of incident DR, DR progression, and associated vision-threatening complications.
• The findings suggest that modulating the IL-6 pathway may offer a protective effect against diabetic eye disease.
• Further prospective studies are warranted to confirm these findings and explore the therapeutic potential of IL-6 inhibitors in DR management.