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Topic: Numerous smartphone applications have been devised for diagnosis, treatment, and symptom management in ophthalmology. Despite the importance of systematic evaluation of the purpose, target disease, effectiveness, and utility of smartphone applications to their effective utilization, few studies have formally evaluated their validity, reliability, and clinical utility. Clinical Relevance: This report identifies smartphone applications with potential for clinical implementation in ophthalmology and summarizes the evidence on their practical utility. Methods: We searched PubMed and EMBASE on July 28, 2022, for articles reporting original data on the effectiveness of treatment, disease detection, diagnostic accuracy, disease monitoring, and usability of smartphone applications in ophthalmology published between January 1, 1987, and July 25, 2022. Their quality was assessed using the Joanna Briggs Institute Critical Appraisal Checklist. Results: The initial search yielded 510 articles. After removing 115 duplicates and 285 articles based on inclusion and exclusion criteria, the full texts of the remaining 110 articles were reviewed. Furthermore, 71 articles were included in the final qualitative synthesis. All studies were determined to be of high (87.3%) or moderate (12.7%) quality. In terms of respective application of interest, 24 (33.8%) studies assessed diagnostic accuracy, 17 (23.9%) assessed disease detection, and 3 (4.2%) assessed intervention efficacy. A total of 48 smartphone applications were identified, of which 27 (56.3%) were publicly available. Seventeen (35.4%) applications included functions for ophthalmic examinations, 13 (27.1%) included functions aimed at disease detection, 10 (20.8%) included functions to support medical personnel, five (10.4%) included functions related to disease education, and three (6.3%) included functions to promote treatment adherence for patients. The largest number of applications targeted amblyopia (18.8%), followed by retinal disease (10.4%). Two (4.2%) smartphone applications reported significant efficacy in treating diseases. Conclusion: In this systematic review, a comprehensive appraisal is presented on studies related to diagnostic accuracy, disease detectability, and efficacy of smartphone applications in ophthalmology. Forty-eight applications with potential clinical utility are identified. Appropriate smartphone applications are expected to enable early detection of undiagnosed diseases via telemedicine and prevent visual dysfunction via remote monitoring of chronic diseases. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.