Association between glycated hemoglobin levels and changes in aqueous humor inflammatory cytokines during sequential cataract surgeries in patients with type 2 diabetes mellitus: A retrospective study

Cataract is a common ocular complication of diabetes mellitus (DM), characterized by chronic inflammation and oxidative stress. Sequential bilateral cataract surgery provides a unique model to explore intraocular immune modulation under different systemic metabolic conditions. This study aimed to evaluate the relationship between preoperative glycated hemoglobin (HbA1c) levels and inter-eye variations in aqueous humor inflammatory cytokines among patients with type 2 diabetes mellitus. A retrospective analysis was performed on 88 patients with type 2 diabetes mellitus who underwent bilateral phacoemulsification cataract surgery with intraocular lens implantation between January 2023 and January 2025. Aqueous humor samples were collected at the beginning of each surgery, and the concentrations of inflammatory cytokines (interleukin-6 [IL-6], interleukin-8 [IL-8], tumor necrosis factor-alpha, monocyte chemoattractant protein-1, and interleukin-10) were measured using a multiplex immunoassay. Patients were stratified into 3 groups according to HbA1c levels (<7.0%, 7.0–8.9%, and ≥9.0%). The interocular differences in cytokine concentrations (Δcytokines) were compared among groups, and multivariate regression analysis was performed to evaluate the associations between HbA1c, surgical interval, and Δcytokines. IL-6 and IL-8 levels were significantly higher in second-eye surgeries compared with first-eye surgeries ( P < .001). HbA1c was positively correlated with ΔIL-6 ( r = 0.48, P < .001) and ΔIL-8 ( r = 0.42, P = .002), independent of age, sex, and diabetic retinopathy severity. Patients with HbA1c ≥ 9.0% had nearly twofold higher ΔIL-6 than those with HbA1c < 7.0%. Longer surgical intervals (≥28 days) further amplified these inflammatory differences (interaction P = .031). Poor glycemic control and extended surgical intervals synergistically enhance intraocular inflammation during sequential cataract surgery in diabetic patients. Optimizing HbA1c and minimizing inter-surgery intervals may mitigate postoperative inflammatory risk and improve surgical outcomes.