The purpose of this study is to evaluate the safety end efficacy of combined phakoemulsification and vitrectomy with retinal endophotocoagulation and intraoperative use of bevacizumab in patients with diffuse diabetic macular edema (DDME), to determine the possible preoperative and intraoperative factors that might influence surgical outcomes.

The pathogenesis of the diabetic macular edema is multiple. Therefore treatment of this disease should be combined too. VEGF is involved in pathogenesis of diabetic macular edema and recently anti-VEGF agents such as bevacizumab have been shown to be beneficial in the treatment of this retinal disorder. However, endogenous VEGF is required for visual function. Growing body evidence indicates that VEGF acts also on nonvascular cells, it plays survival role on Muller cells and photoreceptors. Therefore anti-VEGF therapies should be administered with caution and not persistent. Photocoagulation in nonperfused areas eliminate increased production of VEGF, proliferation of RPE and increased production of PEDF in surrounded impact laser area. Vitrectomy with ILM peeling reliefs traction on the macula, improve oxygenation of the macula leading to decreased vascular permeability with subsequent resolution or decrease in DME. Removed ILM contains a part of the Müller cell endfeet and the horizontal gliosis. It is likely that the proliferation of GFAP-stained gliofibrils, observed in microdamaged Müller cells, preserves the blood-retinal barrier, reinforces architectural cohesion, and opposes the installation of the edema. Therefore, we made hypothesis that combined triple therapy was effective for decreasing macular thickness and improvement of vision for eyes with diffuse diabetic macular edema.

It is important for the surgeon to determine the factors that might influence surgical outcome so that patients are chosen for the procedure that they can get benefit from. Therefore, we evaluated the possible preoperative and intraoperative factors that might influence surgical outcomes

Inclusion Criteria:

1. diagnosis of DDME on clinical exam, definite retinal thickening involving the center of the macula, confirmed by fluorescein angiography, with or without PVD,
2. BCVA of 0,3 or worse in log MAR units (<=70 ETDRS letter) and 1,5 or better in log MAR units (>=10 ETRDS letter),
3. mean central macular thickness greater than 250 μm on optic coherence tomography (OCT),
4. presence of vitreomacular traction or a thickened and taut posterior hyaloid or presence of an epimacular membrane.

Exclusion Criteria:

1. significant macular ischemia defined as enlarged perifoveal capillary loss (>1000 µm) by fluorescein angiography,
2. the focal macular edema due to focal leakage from microaneurysm,
3. ophthalmic disorders associated with macular edema, such as uveitis, branch or central retinal vein occlusion and pseudophakic cystoid macular edema,
4. vitreous hemorrhage or tractional retinal detachment secondary to diabetic retinopathy,
5. an ocular condition is present such that, visual acuity would not improve from resolution of macular edema (e.g., foveal atrophy, pigmentary abnormalities, dense subfoveal hard exudates),
6. history of retinal macular photocoagulation, intravitreal corticosteroids, or other treatment for DME within 3 months prior to enrollment,
7. history of any intraocular surgery within prior 6 months.