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Key Points Question What are the enablers and barriers of patient engagement for app-based home vision monitoring at scale? Findings In this cohort and survey study including 417 adults, 258 patients were active users (61.9%) of whom 166 patients (64.3%) were compliant users. Engagement was positively associated with higher comfort with technology, White British ethnicity, visual acuity, neovascular age-related macular degeneration diagnosis, and the number of intravitreal injections and was negatively associated with increased age. Meaning These findings suggest effective smartphone app-based home vision monitoring should address the risk factors for low engagement and digital exclusion during clinical practice setting deployment., This cohort study examines the associations between patient characteristics and clinical measures with vision monitoring app uptake and engagement., Importance Telemedicine is accelerating the remote detection and monitoring of medical conditions, such as vision-threatening diseases. Meaningful deployment of smartphone apps for home vision monitoring should consider the barriers to patient uptake and engagement and address issues around digital exclusion in vulnerable patient populations. Objective To quantify the associations between patient characteristics and clinical measures with vision monitoring app uptake and engagement. Design, Setting, and Participants In this cohort and survey study, consecutive adult patients attending Moorfields Eye Hospital receiving intravitreal injections for retinal disease between May 2020 and February 2021 were included. Exposures Patients were offered the Home Vision Monitor (HVM) smartphone app to self-test their vision. A patient survey was conducted to capture their experience. App data, demographic characteristics, survey results, and clinical data from the electronic health record were analyzed via regression and machine learning. Main Outcomes and Measures Associations of patient uptake, compliance, and use rate measured in odds ratios (ORs). Results Of 417 included patients, 236 (56.6%) were female, and the mean (SD) age was 72.8 (12.8) years. A total of 258 patients (61.9%) were active users. Uptake was negatively associated with age (OR, 0.98; 95% CI, 0.97-0.998; P = .02) and positively associated with both visual acuity in the better-seeing eye (OR, 1.02; 95% CI, 1.00-1.03; P = .01) and baseline number of intravitreal injections (OR, 1.01; 95% CI, 1.00-1.02; P = .02). Of 258 active patients, 166 (64.3%) fulfilled the definition of compliance. Compliance was associated with patients diagnosed with neovascular age-related macular degeneration (OR, 1.94; 95% CI, 1.07-3.53; P = .002), White British ethnicity (OR, 1.69; 95% CI, 0.96-3.01; P = .02), and visual acuity in the better-seeing eye at baseline (OR, 1.02; 95% CI, 1.01-1.04; P = .04). Use rate was higher with increasing levels of comfort with use of modern technologies (β = 0.031; 95% CI, 0.007-0.055; P = .02). A total of 119 patients (98.4%) found the app either easy or very easy to use, while 96 (82.1%) experienced increased reassurance from using the app. Conclusions and Relevance This evaluation of home vision monitoring for patients with common vision-threatening disease within a clinical practice setting revealed demographic, clinical, and patient-related factors associated with patient uptake and engagement. These insights inform targeted interventions to address risks of digital exclusion with smartphone-based medical devices.