Objective:To observe and evaluate the predictive value of serum cystatin C (Cys-C) on the risk of sight-threatening diabetic retinopathy (STDR).Methods:A non-randomized controlled cross-sectional clinical study. Ninety-two patients with type 2 diabetes mellitus (T2DM) who were admitted to Department of Ophthalmology of Beijing Tsinghua Changgung Hospital from January 2022 to October 2022 were included in the study. Among them, 50 were male, 42 cases were female, with the mean age of (58.24±12.49) years. The mean duration of T2DM was (13.18±8.35) years, of which 38 cases had a duration of ≥10 years. Twenty-nine cases complicated with hypertension, of which 16 cases had a duration of ≥10 years. Seventeen cases complicated with chronic kidney disease stage 2 and 23 cases were treated with lipid-lowering drugs. Hemoglobin Alc, serum Cys-C, serum lipids and renal function were tested, and urinary microalbumin/creatinine ratio (ACR) was calculated. According to the 2003 American Academy of Ophthalmology "Clinical Guidelines for Diabetic Retinopathy (DR)" and international clinical DR severity grading standards, the patients were divided into STDR and non-STDR groups, with 44 and 48 cases in each group, respectively. STDR was defined as severe non-proliferative DR, proliferative DR, and macular edema. Logistic regression was used to analyze the independent risk factors of STDR in T2DM patients. Receiver operating characteristic curve (ROC curve) was used to calculate and analyze the area under ROC curve (AUC) and the predictive value of serum Cys-C and ACR in predicting STDR in T2DM patients.Results:Serum Cys-C levels in STDR and non-STDR groups were 1.10 (0.94, 1.28) and 0.91 (0.83, 1.02) mg/L, respectively, with ACR of 4.29 (1.05, 21.89) and 1.39 (0.77, 3.80) mg/mmol, respectively. Compared with non-STDR group, serum Cys-C and ACR in STDR group were higher, and the difference was statistically significant ( Z=-3.984, -3.280; P<0.05). Multivariate logistic regression analysis showed that serum Cys-C was an independent risk factor for STDR (odds ratio=1.337, 95% confidence interval 1.145-2.090, P=0.033), and the risk of STDR increased by 33.7% for every 0.1 mg/L increase in serum Cys-C. ROC analysis results showed that serum Cys-C> 1.065 mg/L combined with ACR> 5.84 mg/mmol predicted the AUC of STDR in T2DM patients was 0.661, with the specificity of 95.8%. Conclusions:The high serum Cys-C level is an independent risk factor for STDR in T2DM patients. Serum Cys-C has high predictive value for the occurrence of STDR.