Pro-permeability Factors in Diabetic Macular Edema; The Diabetic Macular Edema Treated With Ozurdex Trial

We would like to address several issues arising from the interesting and comprehensive study by Campochiaro and associates, who measured aqueous pro-permeability factors (PPFs) in patients with diabetic macular edema (DME) before and after injection of dexamethasone (Ozurdex; Allergan, Inc, Irvine, California, USA) implant or vascular endothelial growth factor (VEGF)-neutralizing protein and correlated them with changes in excess foveal thickness (EFT).

There were no data on the anatomic types of DME (cystic changes within neurosensory retina/subretinal fluid) as well as the details regarding vitreoretinal interface abnormalities (vitreomacular adhesion/traction and epiretinal membranes) before and after treatment.

There were no comparative data referring to the demographics and baseline ocular characteristics of patients treated with dexamethasone implant and injections of VEGF-neutralizing protein.

Initially, a comparison had to be carried out between the 2 groups of patients to establish whether or not they are comparable. Accordingly, this comparison should have been conducted only if there were no significant differences between all variables of these 2 groups.

Implementation of the 2-sequence, 2-period, 2-treatment crossover design, in which each patient was randomly assigned to a sequence of treatment, brought no real benefits in this study. On the contrary, the disadvantages of such a study could not be avoided. Thus, the washout period, which is essential between periods of a crossover study in terms of aliased effects, has not been precisely delimited and the impact of the significant carryover effects may be confounded with direct treatment effects, in the sense that these effects could not be estimated separately being able to bias the interpretation of data analysis.

The patients in the present study suffered from persistent DME of 48.1 months’ duration, and had previously been treated with anti-VEGF and/or corticosteroid intraocular injections and grid and scatter laser photocoagulation with insufficient macular deturgescence. Most likely, there was a chronic retinal capillaropathy due to permanent breakdown of the inner and outer blood-retinal barriers (pigmentary changes in the fovea, poorly controlled severe recurrent macular edema, telangiectatic vessels with leakage, and epiretinal membrane formation). This permanent retinal capillaropathy caused by longstanding duration of macular edema was temporarily relieved by reduction of the edematous component with treatment. However, the pathology was incurable owing to irreversible ischemic changes to the macular ganglion cell complex, close to the foveola, with macular edema being a minor factor. VEGF is one proven contributor to macular edema in patients with diabetic retinopathy. Besides, a lot of proinflammatory and proangiogenic cytokines, chemokines, and growth factors may be associated with pathophysiology of DME, suggesting that the pathogenesis of DME is not only related to VEGF dependency. The whole panoply of PPFs, comprehensively highlighted by Campochiaro and associates, could be included in this latter group of possible contributors to DME in addition to VEGF, which were maximally expressed in the ischemic lesions of the longstanding DME and which exacerbated the deterioration primarily caused by VEGF in the initially damaged macular ganglion cell complex.

Altogether, regardless of the therapeutic agents used (anti-VEGF agents/corticosteroids), the efficacy of therapy depends primarily on the promptness of the treatment after DME diagnosis. Any delay in treatment adversely influences the restoration of visual function, which is difficult to correct even with subsequent treatment.

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Jan 5, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on Pro-permeability Factors in Diabetic Macular Edema; The Diabetic Macular Edema Treated With Ozurdex Trial

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