The aim of this study is to analyze the correlation between baseline cytokine levels in the aqueous humor and the response to anti-vascular endothelial growth factor (VEGF) treatment in DME patients.

The patients with diabetic macular edema (DME) who received intravitreal injection of Aflibercept for 3 times in Shenyang Aier Excellence Eye Hospital from October 2021 to July 2023 were collected. Among them, there were 36 males (36 eyes) and 29 females (29 eyes)with an average age of (54.5±11.4) years (ranged from 29 to 79) years old. According to the decrease of central macular thickness (CMT) after three months of treatment, all patients were divided into response group and non-response group. Best corrected visual acuity (BCVA), intraocular pressure (IOP), CMT, and the aqueous cytokine levels of patients before and after treatment for 3 months were detected. BCVA, age, course of diabetes, IOP and other measurement data, after the normal test, if conformed to the normal distribution, were expressed as ±s, and compared by by independent sample t test for the inter group , and paired t test for the intra group. Quantitative data that did not follow a normal distribution were represented as median and interquartile (non interquartile range) and compared using Mann-Whitney U test. Gender was represented by cases and percentages, and compared using χ². Using multiple logistic regression analysis was to explore potential risk factors for non response to anti VEGF drugs. The correlation between different cytokines and the decrease in CMT was used Spearman correlation analysis.

The BCVA of the affected eye before and after treatment were (1.10±0.27) logarithm of the minimum angle of resolution (logMAR) and (0.61±0.30) logMAR, respectively. The CMT of the affected eye before and after treatment were (583.54±108.05)μm, and (419.95±80.01) μm, respectively . The differences were statistically significant (t=12.166, 11.447; P<0.05). The IOP of the affected eye before and after treatment were (15.98±2.68) mmHg (1 mmHg=0.133 kPa) and (15.88±2.48) mmHg, respectively, with no statistically significant difference (t=0.736, P>0.465). The baseline aqueous humor VEGF, intercellular adhesion molecule (ICAM), and interleukin (IL)-8 levels in the non-response group were 114.00(88.75, 156.85)pg/ml, 1891.30(1124.60, 2673.00)pg/ml and 57.70(49.40, 76.15)pg/ml, respectively, while those in the responsive group were 190.40(147.50, 333.70)pg/ml, 6821.80(4387.15, 9079.75)pg/ml and 26.50(19.70, 40.90)pg/ml, with statistical significance between them (Z=3.612, 6.291, 5.700; P<0.05). The levels of basic fibroblast growth factor (bFGF), IL-6, and vascular cell adhesion molecule (VCAM) in aqueous humor of the non-response group were 8.90 (4.80, 22.05)pg/ml, 61.90 (19.35, 134.60)pg/ml, and 2528.60 (919.65, 3353.30)pg/ml, respectively, while those of the responsive group were 13.80 (4.20, 31.95)pg/ml, 76.00 (31.70, 235.9)pg/ml, and 2480.60 (1086.55, 3656.00)pg/ml, with no statistically significant differences (Z=0.585, 1.596, 0.525; P>0.05). The age, course of disease, glycated hemoglobin, baseline visual acuity, baseline IOP, baseline CMT, as well as aqueous humor VEGF, bFGF, IL-6, VCAM, IL-8, and ICAM were used for multivariate logistic regression analysis to explore impact factors for anti VEGF treatment response, but no independent risk factors were found (β=-0.466, -2.012, 6.723, -8.634, 3.664, -0.009, 0.049, -0.109, -0.032, 0.007, -1.068, 0.015; P>0.05). According to Spearman correlation analysis, the levels of VEGF and ICAM were positively correlated with the decrease in CMT, and there was statistical significance (r=0.262, 0.750, P<0.05). The level of IL-8 was negatively correlated with the decrease in CMT with a statistical significance (r=-0.628, P<0.05). The levels of bFGF, IL-6, and VCAM were not correlated with CMT decrease without a statistically significance (r=0.127, 0.098, -0.241; P>0.05).

The levels of VEGF, ICAM-1, and IL-8 in aqueous humor are correlated with treatment response, which can be used to predict the therapeutic effect of anti VEGF in DME patients.