To evaluate dry eye parameters, corneal topographic features, corneal densitometric changes, and anterior segment parameters in patients receiving systemic isotretinoin treatment. This prospective cross-sectional study included 66 eyes of 33 patients who were started on oral isotretinoin therapy for severe acne vulgaris. All patients were evaluated in terms of ocular surface tests such as tear break-up time (TBUT) and Schirmer-1 and were asked to fill in the ocular surface disease index (OSDI) questionnaire. Corneal densitometric and topographic measurements were obtained using the Scheimpflug imaging system. The mean age of the patients was 19.9 ± 1.6 years, and 21 (63.6%) of the participants were female. The mean OSDI score was significantly higher in the third month than before treatment (20.05 ± 19.38, vs. 26.96 ± 22.94, p = 0.00, respectively). The mean values of the TBUT test were significantly lower in the third month than before treatment (9.06 ± 4.40 sec, vs. 10.71 ± 4.61 sec, p = 0.02, respectively). Mean scores of the Schirmer 1 test showed no statistically significant difference between before treatment and the third month (16.08 ± 8.40 mm, vs. 16.08 ± 8.50 mm, p = 1, respectively). There was no statistically significant difference between before treatment and the third month in the majority of the densitometry measurements in concentric zones. However, the difference tended to be significant between the groups concerning posterior zone 0–2 mm (11.01 ± 0.85 GSU vs. 10.62 ± 0.89 GSU, p = 0.006). The RMS LOAs (front), RMS Total (Total), RMS LOAs Total (Total), RMS HOAs Total (Total), Kmax, CCT, and CoV values were significantly higher in the third month than before treatment (p < 0.05 for all). The dermatology specialists should be aware of the ocular complications of systemic isotretinoin therapy. Therefore, a complete ophthalmologic examination for the prompt apprehension and management of ocular involvement is essential in patients under isotretinoin therapy to increase ocular comfort and adherence to the therapy. [ABSTRACT FROM AUTHOR]