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Introduction: This study aimed to discover and document the potential of visual and ocular sequelae of computer vision syndrome (CVS) among medical students. Methods: This cross-sectional case-control study was conducted on medical students (n=4030) of five universities in Egypt. All students completed a specially designed and validated CVS questionnaire survey (CVS-F3). Students with ≥5 CVS symptoms constituted a risk group (n=352), while students with 1-4 CVS symptoms constituted a low-symptoms group (n=3067). Students from the control and risk groups were examined using objective methods, such as visual acuity, subjective refraction, dry eye disease tests, and anterior segment and fundus examinations. Students who complained of visual blur underwent multifocal electroretinography mfERG examinations (mfERG group). Results: The CVS-F3 indicated that 84.8% of students had complaints that might be related to CVS, however, our ophthalmic examination group revealed only a 56% CVS prevalence rate. The most common single screen type used by 70.4% of students was the smartphone, and the most common complaint was headache (50.2%). Multivariate logistic regression analysis revealed that CVS was significantly associated with increased screen-hours, including >2 screen-hours daily (odds ratio [OR], 2.48; P2 screen-hours at night (OR, 1.79; P=0.003), and ≥3 screen-years (OR, 1.69; P=0.006). In the mfERG group, 37% demonstrated reduced amplitudes of mfERG rings and quadrants, indicating reduced foveal responses. Conclusion: CVS-questionnaires overestimate the true CVS prevalence and sequelae, which could be accurately detected by objective ophthalmic examination. Smartphones primarily caused CVS among students, with CVS severity increasing in correlation with shorter eye-to-screen distance and frequent use. Contact lens wearing doubled the risk of CVS development and augmented its severity. CVS might affect macular integrity with screen-induced foveal dysfunction. Clinical Trials Registration: PACTR201811618954630.