Abstract:AIM: To explore the predictive efficacy of NVU, Nrf2 and HO-1 on retinal injury in AMD susceptible population, and to provide laboratory reference indicators for screening and stratified management of individuals at high risk of injury in this population. MethodsThis study is a prospective study. The study included a period of time from April 2023 to March 2025. A total of 185 AMD-susceptible people were screened and included. All subjects were treated with traditional Chinese medicine and followed up for 12 months. The deadline for follow-up was unified in March 2026. According to whether retinal injury occurred during the follow-up period, the patients were divided into injury group and non-injury group. The probability of overall retinal injury was 35 %. Collect the baseline data of the subjects ; the retinal injury indexes were evaluated by OCT and fluorescence angiography. Peripheral blood was collected, and NVU function index and Nrf2 and HO-1 expression were detected by ELISA, and the differences between the two groups were compared. The data were analyzed by SPSS 26.0. The measurement data were analyzed by mean ± standard deviation ( t test ), the count data rate ( χ2 test ), Spearman analysis correlation, multivariate Logistic regression screening independent influencing factors, ROC curve evaluation predictive value, P < 0.05 for the difference was statistically significant..Results After 12 months of follow-up, 65 of 185 AMD susceptible people had retinal injury, with an incidence of 35.00 %. The macular foveal retinal thickness, retinal nerve fiber layer thickness and choroidal thickness in the injury group were significantly lower than those in the non-injury group, and the retinal injury score was significantly higher than that in the non-injury group ( all P < 0.001 ). The levels of vascular endothelial growth factor ( VEGF ) and endothelin-1 ( ET-1 ) in the injury group were significantly higher than those in the non-injury group, and the levels of tight junction protein 1 ( ZO-1 ) and occludin were significantly lower than those in the non-injury group ( all P < 0.001 ). The expression levels of Nrf2 and HO-1 protein in the injury group were significantly lower than those in the non-injury group ( all P < 0.001 ). Spearman correlation analysis showed that the expression of Nrf2 and HO-1 protein was positively correlated with retinal structure index and NVU tight junction protein ( r = 0.692-0.776, all P < 0.01 ), and negatively correlated with VEGF, ET-1 and retinal injury score ( r = -0.802--0.741, all P < 0.01 ). Multivariate Logistic regression analysis showed that advanced age, low Nrf2 expression, low HO-1 expression, high VEGF and low ZO-1 were independent risk factors for retinal injury in AMD susceptible population ( all P < 0.05 ). ROC curve analysis showed that the area under the curve ( AUC ) of combined detection of Nrf2, HO-1, VEGF and ZO-1 in predicting retinal injury was 0.921, the sensitivity was 98.38 %, and the specificity was 83.33 %. The predictive value was significantly higher than that of single index ( all P < 0.001 ).Conclusions NVU combined with Nrf2 and HO-1 related indicators can be used to predict the early risk of retinal injury in AMD susceptible population and guide the refined follow-up management of high-risk subjects.