Although teleophthalmology has gained traction in recent years, it is at the center of the coronavirus disease pandemic. However, most hospitals are not ready owing to a severe lack of real-world experience. Furthermore, a limited number of studies have evaluated telemedicine applications on remote islands. This study aimed to evaluate real-world clinical and referral accuracy, image quality, physician-perceived diagnostic certainty, and patient satisfaction with telemedicine eye screening using a novel handheld fundus camera in a rural and medically underserved population. This prospective study included 176 eyes from a remote island. All participants underwent a comprehensive ophthalmic examination. Nonmydriatic retinal images obtained using a handheld fundus camera were reviewed by two retinal specialists to determine image quality, diagnosis, and need for referrals. The agreement of diagnosis between image-based assessments was compared with that of binocular indirect ophthalmoscopic assessments. Image quality of fundus photographs was considered acceptable or ideal in 97.7% and 95.5% of eyes assessed by two reviewers, respectively. There was considerable agreement in diagnosis between the indirect ophthalmoscopic assessment and image-based assessment by two reviewers (Cohen's kappa = 0.80 and 0.78, respectively). Likewise, substantial agreement was achieved in the referrals. The sensitivity for referable retinopathy from the two reviewers was 78% (95% confidence interval [CI], 57%-91%) and 78% (95% CI, 57%-91%), whereas specificity was 99% (95% CI, 95%-99%] and 98% (95% CI, 93%-99%), respectively. For physicians' perceived certainty of diagnosis, 93.8% and 90.3% were considered either certain or reliable. Overall, 97.4% of participants were satisfied with their experiences and greatly valued the telemedicine services. Novel fundus camera-based telemedicine screening demonstrated high accuracy in detecting clinically significant retinopathy in real-world settings. It achieved high patient satisfaction and physician-perceived certainty in diagnosis with reliable image quality, which may be scaled internationally to overcome geographical barriers under the global pandemic.