Abstract
Purpose :
There is increasing scientific evidence that inflammation plays a pathogenic role in diabetic retinopathy (DR). Such observations provide strong rationale to determine whether intraocular cytokines are markers of disease severity and predict risk of progression.
Methods :
The INSPIRE study is a prospective, placebo-controlled, 3-year interventional study that randomized 118 adult type II diabetic patients with moderate nonproliferative diabetic retinopathy (NPDR) to either topical ketorolac 0.45% or placebo in double-masked fashion. 23 adult type II diabetic patients with no DR and 23 adult type II diabetic patients with proliferative diabetic retinopathy (PDR) were also enrolled. All 164 enrolled diabetic patients underwent complete ophthalmic examination of both eyes along with multimodal imaging: OCT, OCTA, and fundus photography. All patients underwent blood draws and bilateral aqueous biopsies for cytokine analysis. All enrolled patients will have repeat testing as above every 4 months for 3 years for a total of 10 study visits. 100 age-matched patients without diabetes had blood and aqueous fluid collected from one eye only and tested for 29 different inflammatory cytokines for cross-comparison analysis.
Results :
Aqueous samples from 328 eyes of 164 diabetic patients were tested at baseline for 29 different inflammatory cytokines. IL-6 measured on average 5.46 pg/ml (±7.28 SD), 17.63 pg/ml (±49.61 SD), 22.87 pg/ml (±33.68 SD) in diabetic patients with no DR, moderate DR, and PDR respectively. The difference in IL-6 was significant between patients with no DR and PDR (P < 0.001) and approached significance between no DR and moderate DR (P < 0.10). IL-8 measured on average 4.8 pg/ml (±3.92 SD), 9.06 pg/ml (±10.63 SD), 11.51 pg/ml (±6.25 SD) in diabetic patients with no DR, moderate DR, and PDR respectively. Significant differences existed between diabetic patients with no DR and PDR (P < 0.001) and no DR and moderate DR (P < 0.01). VEGF measured on average 12.06 pg/ml (±9.69 SD) in patients without diabetes and 61 pg/ml (±31.88 SD), 110.15 pg/ml (±82.37 SD), 190.18 pg/ml (±124.68 SD) in diabetic patients with no DR, moderate DR, and PDR respectively. Differences between all groups were significant (P < 0.001). Analysis of the remaining 26 cytokines is ongoing.
Conclusions :
IL-6, IL-8, and VEGF levels measured from the aqueous of patients with DR correlated with disease severity.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.