Ophthalmological screening for cytomegalovirus retinitis (CMVR) for HIV/AIDS patients is important to prevent lifelong blindness. Previous studies have shown good properties of automated CMVR screening using digital fundus images. However, the application of a deep learning (DL) system to CMVR with ultra-wide-field (UWF) fundus images has not been studied, and the feasibility and efficiency of this method are uncertain.In this study, we developed, internally validated, externally validated, and prospectively validated a DL system to detect AIDS-related from UWF fundus images from different clinical datasets. We independently used the InceptionResnetV2 network to develop and internally validate a DL system for identifying active CMVR, inactive CMVR, and non-CMVR in 6960 UWF fundus images from 862 AIDS patients and validated the system in a prospective and an external validation data set using the area under the curve (AUC), accuracy, sensitivity, and specificity. A heat map identified the most important area (lesions) used by the DL system for differentiating CMVR.The DL system showed AUCs of 0.945 (95 % confidence interval [CI]: 0.929, 0.962), 0.964 (95 % CI: 0.870, 0.999) and 0.968 (95 % CI: 0.860, 1.000) for detecting active CMVR from non-CMVR and 0.923 (95 % CI: 0.908, 0.938), 0.902 (0.857, 0.948) and 0.884 (0.851, 0.917) for detecting active CMVR from non-CMVR in the internal cross-validation, external validation, and prospective validation, respectively. Deep learning performed promisingly in screening CMVR. It also showed the ability to differentiate active CMVR from non-CMVR and inactive CMVR as well as to identify active CMVR and inactive CMVR from non-CMVR (all AUCs in the three independent data sets >0.900). The heat maps successfully highlighted lesion locations.Our UWF fundus image-based DL system showed reliable performance for screening AIDS-related CMVR showing its potential for screening CMVR in HIV/AIDS patients, especially in the absence of ophthalmic resources.© 2024 The Authors.