To evaluate the effect of oral isotretinoin therapy on retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thickness by spectral domain optical coherence tomography (OCT). This prospective study included newly diagnosed nodulocystic acne patients about to receive isotretinoin treatment. Macular average GCL thickness and peripapillary average, temporal, nasal, inferior, and superior quadrant RNFL thickness were measured by OCT before and after isotretinoin treatment. Pre- and post-treatment measurements were compared with paired t test. Fifty-six eyes of 28 patients were included. The mean duration of the treatment was 6.5 +/- A 1.3 months. The mean average GCL thickness was 90.04 +/- A 5.87 (80-96) mu m at baseline and 90.75 +/- A 6.34 (81-96) mu m after treatment. The mean average RNFL thickness was 93.25 +/- A 6.06 mu m (84-107) before treatment and 93.05 +/- A 5.54 mu m (82-106) after treatment. There were no statistically significant differences between pre- and post-treatment values (all p > 0.05). A 6-month course of systemic isotretinoin therapy seems to have no unfavorable effect on retinal ganglion cells; however, larger studies with longer follow-up periods are needed to be conclusive.