الفهرس 
? Physiology of blood-retinal barrier.Only 14 pages are availabe for public view
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Abstract
Diabetic macular edema (DME) is a general term defined as retinal thickening within two disc diameters of the foveal center; it can be either focal or diffuse in distribution. Cystic changes may appear within the macula, representing focal coalescence of exudative fluid giving rise to what is called cystoid macular edema.
Diabetic macular edema is a leading cause of visual loss and legal blindness in patients with diabetic retinopathy with an incidence between 13.9 and 25.4% over a 10-year period.
Hyperglycemia is the metabolic hallmark of diabetes and leads to widespread cellular damage. Malfunction of the blood-retinal barrier plays a central role in the disease and leads to retinal edema and secondary photoreceptor dysfunction. Diabetic vascular leakage and macular edema are regulated by a distinct combination of direct paracellular transport, alterations in endothelial intercellular junctions and endothelial cell death. The distribution and relevance of these three factors to diabetic maculopathy varies over the course of the disease.
VEGF is a potent angiogenic stimulus which is released in response to retinal hypoxia and leads to increased permeability and vascular leakage as a result of both vasodilation and an uncoupling of endothelial tight junctions and induction of fenestrations and vesiculo-vacuolar organelles. It induces vascular permeability up to 50,000 times more potent than that of histamine.
Symptoms of diabetic macular edema include diminution of visual acuity, psychophysical changes, metamorphopsia, contrast sensitivity changes. The diagnosis of DME requires a careful ocular retinal examination. The optimal examination technique is biomicroscopy under stereopsis with high magnification.
The fundus fluorescein angiogram and Optical coherence tomography are indicated and extremely useful in confirming the diagnosis, determining type of DME, helping guide the treatment pattern, delineating the FAZ and showing status of macular perfusion in early phase, measuring macular thickness and detecting presence of vitreomacular traction.
The ideal treatment for DME is primary prevention. However, prevention alone does not always work. Laser photocoagulation became the gold standard of care in the treatment of DME primarily as a result of the findings of the ETDRS and should be performed when a patient is first diagnosed with CSME. Laser treatment reduced the risk of vision loss due to diabetic macular edema by 50–70%. However, the limited efficacy of laser treatment has put forth the need for other lines of treatment in order to control cases with persistent or recurrent diabetic macular edema which do not respond well to laser photocoagulation.
IVTA has antiangiogenic, antifibrotic, and antipermeability properties that help to stabilize the blood retinal barrier, aid in exudation resorption. Several studies have investigated the efficacy of intravitreal 4mg triamcinolone acetonide for DME and proved its efficacy in improving VA and decreasing retinal thickness with minimal rise in IOP but unfortunately shorter duration.
Anti-VEGF therapy for DME shows promise in preliminary studies. Blockade of all involved growth factors will likely be necessary to completely suppress the detrimental effects of ischemia, but even isolated blockade of VEGF may have beneficial effects on DME. Anti-VEGF agents include Pegaptanib sodium (Macugen®), Ranibizumab (Lucentis™), Bevacizumab (Avastin®). Pegaptanib sodium is an anti-VEGF aptamer that binds to and blocks the effects of VEGF165, one isoform of the VEGF family of molecules. It was found that mean visual acuity has been improved to 20/50 after 36 weeks from intravitreal injection of 0.3 mg pegaptanib sodium; also mean central retinal thickness decreased to 267 μm. Bevacizumab is recombinant humanized monoclonal IgG1 antibody that inhibits all isoforms of VEGF. It was initially used for systemic treatment of metastatic colon cancer. Intravitreal 1.25 mg bevacizumab injection brought about significant macular thickness reduction. However, the response for bevacizumab was short-lived and visual acuity was essentially unchanged.
Ranibizumab is an antibody fragment derived from the full antibody molecule of Bevacizumab that also binds and blocks the effects of all isoforms of VEGF unlike pegaptanib. It was found that mean central retinal thickness was reduced by 198 μm after 3 months of intravitreal injection of FDA-approved 0.5-mg Ranibizumab.
Combined IVTA and grid laser treatment has proved to bring about better visual acuity improvement and greater macular thickness reduction for longer duration.
The additive effect of triamcinolone to bevacizumab has been shown in the stability of response to bevacizumab in comparison to the short lived response to bevacizumab alone.
Vitrectomy is indicated in diabetic macular edema in the case of persistent diabetic macular edema despite previous treatment modalities with presence of taut posterior hyaloid and vitreomacular traction on the macular area.