Pro-permeability Factors After Dexamethasone Implant in Retinal Vein Occlusion; The Ozurdex for Retinal Vein Occlusion (ORVO) Study

We read with great interest the excellently illustrated and comprehensive article by Campochiaro and associates, which correlated aqueous vasoactive protein changes with macular edema after dexamethasone implant in retinal vein occlusion (RVO). The authors explained the poor visual results of the RETAIN study (ie, unresolved macular edema observed after 4 years of anti–vascular endothelial growth factor [VEGF] injections, with active disease in 50% of branch retinal vein occlusion [BRVO] patients and in 56% of the central retinal vein occlusion [CRVO] patients) by evolution or changes in the underlying disease process over time, indicating that pro-permeability factors other than VEGF may play a more important role. Of course, the vasoactive proteins detected in the aqueous might contribute to the pathogenesis of macular edema; however, other factors should be specifically considered and accounted for. The patients with RVO were eligible for the RETAIN study if they completed the BRAVO and CRUISE trials and had subsequent follow-up in the HORIZON study. The worsening of the visual function of the patients in the RETAIN study may have been caused by the reduced frequency of injections as well as the 2 periods of time during which the patients went without treatment. The first period occurred prior to the initiation of the BRAVO and CRUISE trials; that is, the BRVO and CRVO diagnoses were made within 12 months (mean 3.3 months) before study initiation, when VEGF was maximally expressed with subsequent progression of the ocular disease. The second period was the time elapsed from HORIZON study exit to entry in the RETAIN study (mean 92.7 days). These facts favored the delayed occurrence of a permanent retinal capillaropathy (eg, pigmentary changes in the fovea, poorly controlled severe recurrent macular edema, telangiectatic vessels with leakage, and epiretinal membrane formation). However, the condition is incurable owing to the ischemic and irreversible damage to the macular ganglion cell complex (consisting of a retinal nerve fiber layer, ganglion cell layer, and inner plexiform layer), close to the foveola, with macular edema being a minor factor. The pro-permeability factors mentioned by Campochiaro and associates are maximally expressed in the ischemic lesions. These factors in turn amplify, through a vicious circle, the deterioration primarily caused by VEGF in the initially damaged macular ganglion cell complex.

In 2015, we published a prospective clinical study on the 3-year outcomes of bevacizumab treatment at a dose of 2.5 mg per injection in patients with acute (≤1 month after the occlusion was diagnosed) central/hemicentral RVOs. Of these patients, 50% had ischemic central/hemicentral RVOs. The results of this study were the first evidence suggesting that early treatment, administered immediately after clinical onset of the venous occlusion, provides significant and sustained improvements in visual acuity and foveal thickness with inactive disease (dry retina and stable visual acuity for at least 6 months after the last injection) in most phakic patients with acute central/hemicentral RVOs. Therefore, this treatment option is a rational and viable therapeutic strategy. The sooner the treatment is started after RVO onset, the sooner the patient is likely to have gains in visual acuity and foveal thickness. Any delay in initiating therapy will adversely affect the restoration of visual functions, which are difficult to recover even with subsequent treatment.

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Jan 6, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on Pro-permeability Factors After Dexamethasone Implant in Retinal Vein Occlusion; The Ozurdex for Retinal Vein Occlusion (ORVO) Study

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