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The purpose of this study was to compare the effectiveness of intravitreal injection (IVT) versus posterior subtenon infusion (STI) of triamcinolone acetonide performed during phacoemulsification cataract surgery in eyes with refractory diffuse diabetic macular edema.Twenty-four eyes of 24 patients with refractory diffuse diabetic macular edema scheduled to undergo phacoemulsification cataract surgery were randomly assigned to receive either a 4-mg IVT (n = 12) or a 40-mg STI (n = 12) of triamcinolone acetonide during cataract surgery. Comprehensive ophthalmic evaluation, including best-corrected visual acuity, intraocular pressure, and central macular thickness measured with optical coherence tomography, was performed at baseline and at 1, 4, 8 ± 1, 12 ± 2, and 24 ± 2 weeks postoperatively.Ten patients from the IVT group and 9 patients from the STI group completed the 24-week study visit. Mean baseline best-corrected visual acuity (logarithm of the minimum angle of resolution) was 20/259 and 20/222 in the IVT and STI groups, respectively (t = 0.41; P = 0.3407). A significant improvement in best-corrected visual acuity was observed only in the IVT group at 4 weeks (mean difference ± standard error, improved to 20/116; P = 0.0437), 8 weeks (20/110; P = 0.0355), and 12 weeks (20/121; P = 0.0471) postoperatively. There was no significant change from baseline in mean intraocular pressure in either group. Mean ± standard error baseline central macular thickness was 474.1 ± 42.4 μm and 490.8 ± 70.8 μm in the IVT and STI groups, respectively (t = 0.21; P = 0.5807). The central macular thickness reductions after surgery at all study follow-up visits were significantly greater in the IVT group than in the STI group (P < 0.05).These data suggest that IVT is more effective than STI of triamcinolone acetonide for the management of refractory diffuse diabetic macular edema in eyes undergoing phacoemulsification. Further investigation of a larger number of patients with longer follow-up is necessary to confirm these findings.