Prospective Cytokine Profiling in Aqueous Humor Reveals a Proinflammatory Microenvironment in Highly Dense Nuclear Cataracts.

Purpose: To investigate if the cytokine profile in the aqueous humor (AH) of cataract patients varies according to cataract type and severity. Methods: This prospective study included 397 eyes of 397 patients (median age, 76 years; range, 30-94 years) who underwent standard small-incision phacoemulsification surgery. Cataracts were graded using the LOCS III system: mild (≤3), moderate (3.5-5), and severe (≥5). Biometric measurements from the IOL master 700 (Zeiss, Oberkochen, Germany) were used to differentiate between thick (>4.5 mm) and thin lenses. Information about age, gender, and self-reported diseases was obtained from patient records. Eleven different proteins were measured in AH using a multiplex cytokine assay (AYOXXA Biosystems, Cologne, Germany), including IL- 6, IL-8, angiopoietin 2, C-reactive protein (CRP), vascular endothelial growth factor A (VEGF-A), platelet-derived growth factor BB, placental growth factor, CXCL12, CXCL13, and CXCL10. Statistical analysis was performed using R and included nonparametrical testing, linear regression, and k-means clustering. Results: Higher nuclear LOCS grades correlated with increased levels of CCL2 (360 vs. 387 vs. 517 pg/mL, P < 0.001), VEGF-A (270 vs. 292 vs. 390 pg/mL, P = 0.012), IL-8 (3.1 vs. 4.2 vs. 5.7 pg/mL, P = 0.018), and CXCL10 (52 vs. 61 vs. 90 pg/mL, P = 0.003). No associations were observed for cortical and subcapsular cataracts. Thicker lenses were associated with significantly increased levels of CRP, CXCL10, CXCL12, IL-6, IL-8, and VEGF-A. Conclusions: The cytokine profile of AH varies based on cataract grading and lens thickness. In highly dense nuclear cataracts, CCL2, VEGF-A, IL-8, and CXCL10 were elevated.