PURPOSE To assess the impact of two iron chelation modalities in thalassemic patients on foveal and subfoveal choroidal thickness. METHODS The study included 60 β-thalassemia major patients. They included 30 patients on oral deferasirox after a period of subcutaneous deferoxamine (Group 2) and 30 patients on subcutaneous deferoxamine (Group 3). Thirty age- and sex-matched healthy children were included as a control group (Group 1). All participants underwent a complete ophthalmologic evaluation and Spectral Domain Optical Coherence Tomography. RESULTS Age, gender, intraocular pressure, best-corrected visual acuity, and refraction were not statistically different between the three studied groups. Ferritin level, pretransfusion hemoglobin, serum iron, and duration of thalassemia were not statistically different between the two thalassemic groups. Foveal thickness in Group 1 (225.15 ± 17.35 μm) was statistically higher than in Group 2 (210.53 ± 21.73 μm) (P < 0.001) and Group 3 (200.15 ± 7.34 μm) (P < 0.001). It was statistically higher in Group 2 than in Group 3 (P = 0.001). Subfoveal choroidal thickness in Group 1 (279.70 ± 32.54 μm) was statistically higher than in Group 2 (255.80 ± 19.20 μm) (P < 0.001) and Group 3 (248.28 ± 20.43 μm) (P < 0.001). It was statistically higher in Group 2 than in Group 3 (P < 0.05). CONCLUSION Thalassemic patients can develop a significant decrease in foveal thickness because of the inevitable use of chelation therapy. Deferoxamine as a chelating agent can affect foveal thickness more than the oral form (deferasirox).