Purpose The aim of this study was to evaluate the ability of optical coherence tomography (OCT) to detect the changes in retinal nerve fiber layer (RNFL) after reaching target intraocular pressure (IOP) in glaucomatous patients. Patients and methods Thirty-two (58 eyes) patients with a clinical diagnosis of primary open-angle glaucoma were assessed as regards peripapillary RNFL thickness and optic nerve head parameters by 3D-OCT for a follow-up period of 6 months. The drugs used to reach target IOP were Twinzol (dorzolamide 2%/timolol 0.5%) eye drops 5 ml and Ioprost (Latanoprost) 0.005% (50 mcg/ml) eye drops 3 ml. Eleven patients were treated with Twinzol only and reached target IOP after adding Ioprost. Eight patients were treated with Ioprost only and reached target IOP after adding Twinzol, and 13 patients had no added treatment, where four reached target IOP by Ioprost only, six reached target IOP by Twinzol only, and three reached target IOP by both drugs. OCT was done for all patients after achieving target IOP and was repeated after 6 months of medical control. Results The mean IOP before treatment was 29.89 mmHg and decreased significantly (P<0.001) after treatment to 12.17 mmHg. There was a significant (P<0.05) difference regarding the superior RNFL thickness before and after treatment (100.31 vs. 101.15). There was also a significant (P<0.05) difference in the nasal RNFL thickness before and after treatment (73.37 vs. 74.34). The cup-to-disc area ratio (CDR) mean had decreased significantly (P<0.01) after treatment (0.51 before treatment vs. 0.47 after treatment). Vertical CDR and cup volume had the same trend (0.69 vs. 0.66 for vertical CDR and 0.42 vs. 0.39 for cup volume). There was a highly significant (P<0.01) strong positive correlation between IOP changes and rim volume (r=0.81). Conclusion Achieving target IOP in patients with glaucoma results in a significant change in the RNFL and ganglion cell complexes layer as shown by spectral-domain OCT.