Moataz F ElsawyOphthalmology Department, Faculty of Medicine, Menofia University, Menofia, EgyptObjectives: To evaluate the outcome of vitreolysis using intravitreal autologous plasmin (IAP) injection as a sole therapeutic modality for patients with diffuse diabetic macular edema in comparison to triamcinolone acetonide (TA).Patients and methods: The study included 50 diabetic patients, 18 males and 32 females, with a mean age of 66.4 ± 7.8 years and a mean duration of diabetes of 14 ± 2.4 years. All patients underwent full ophthalmologic examination and were allocated randomly into two groups: the TA group received 4 mg TA and the IAP group received 0.2 mL freshly home-prepared autologous plasmin. Outcome measures included determination of central macular thickness (CMT), best-corrected visual acuity (BCVA), and intraocular pressure (IOP) at 1, 3, and 6 months.Results: Both TA and plasmin induced significant decrease of CMT compared to baseline thickness with nonsignificant difference between both groups. The extent of decrease of CMT reached a peak at 1 month after injection and then started to decline until the sixth month, but was significantly thinner when compared to baseline thickness. However, the extent of deterioration was less evident with plasmin as the difference between follow-up measures at 3 and 6 months were nonsignificant compared to the 1-month measure and to each other. BCVA was significantly improved compared to baseline BCVA with a nonsignificant difference between both groups at 1 and 3 months, but at 6 months, mean BCVA significantly deteriorated in TA group compared to that recorded at 3 months, but not in the IAP group. At 3 and 6 months after injection, IOP was significantly lower in both groups compared to IOP at 1 month despite being significantly higher in the TA group, but IOP was nonsignificantly lower in the IAP group compared to baseline. Moreover, mean IOP estimated at 3 and 6 months was significantly higher in the TA group compared to the IAP group.Conclusion: Vitreolysis using IAP injection provided effective diminution of CMT with improvement of BCVA and this effect was longer lasting and safer than intravitreal injection of TA without concomitant increase of IOP.Keywords: intravitreal injection, autologous plasmin, triamcinolone, diabetic macular edema