Background: Prolonged usage of topical antiglaucoma medications may result in ocular surface disease (OSD) that impairs both life quality and medication adaptation. Objective: The aim of the current study is to assess corneal epithelial thickness (CET) changes using anterior segment optical coherence tomography (AS-OCT) in patients using topical combination of beta-blockers and carbonic anhydrase inhibitors (CAIs). Patients and Methods: A total of 100 eyes of 80 participants were assessed in a randomized controlled clinical trial. Group A included 50 eyes of 40 glaucoma patients treated with combined topical Beta-blockers and CAIs with at least 3-month duration, while Group B included 50 eyes of 40 healthy participants with completely normal ophthalmological examination. All candidates received AS-OCT imaging with subsequent automated CET and total corneal thickness (CT) mapping. Results: Group < /em> A had a mean age of 49.84 (SD 4.83) years, while Group B had a mean age of 49.44 (SD 4.81) years (P=0.679). CET was considerably lower in all regions in Group A 45.94 (SD 3.96) µm compared to Group B 54.54 (SD 3.16) µm; (P-value<0.001). Regarding CT, 8 out of 25 regions were significantly lower in eyes of Group A compared to Group B. There were significant positive correlations between break up time test (BUT) and CET in Group A. Conclusion: Topical antiglaucomatous medications seem to affect CET in glaucoma patients as CET was thinner in glaucoma patients, in all regions, than controls, while these medications seem to focally affect CT in some regions. Further studies are required to assess the clinical implications of these findings.