Retinal Physician

JAN-FEB 2017

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46 R E T I N A L P H Y S I C I A N . C O M | N O V E M B E R / D E C E M B E R 2 0 1 6 showed that eyes with PDR at randomization that were treated with intravitreal ranibizumab had a lower rate of PDR progression, compared to eyes treated with PRP. 11 ese results persisted through two years of follow-up. Aflibercept e VISTA and VIVID studies compared aflibercept (Eylea, Regeneron, Tarrytown, NY ) to macular laser for DME. 5 ese studies definitively showed the superiority of aflibercept in terms of VA gains and ≥2-step improve- ment in DRSS score. Patients receiving intravitreal aflibercept either monthly or every two months after five monthly loading doses were approximately three times more likely to achieve a ≥2-step improvement in DRSS score, compared to patients receiv- ing laser photocoagulation. Patients were not subdivided into those with NPDR vs those with PDR, and no data were reported regarding rates of progression to PDR between the two groups. Baseline DRSS score was the only factor significantly associated with ≥2-step improvement in DRSS score. 12 Aflibercept is FDA approved as a treatment for patients with DR and DME, but it is not approved for use to stop DR progression. Bevacizumab e BOLT study investigated bevacizumab (Avastin, Genentech, South San Francisco, CA) vs laser therapy for DME and found that eyes treated with bevacizumab had a statistically significant improvement in BCVA. 13 ETDRS retinopathy levels were also reported, and the bevacizumab arm demonstrated a trend toward a reduction in DR severity, although statistical significance was not attained, perhaps because only 80 patients were included in the analysis (42 receiving bevacizumab and 38 receiving focal laser). Recent studies comparing all three anti-VEGF agents currently used in the United States have shown that they all have efficacy in the treatment of DR, and these results have been confirmed with two-year follow-up data. 14 More data are needed to fully ascertain the effect of bevacizumab on DR progression. Anti-VEGF Summary Several large, randomized, multicenter clinical trials have definitively shown the protective effect of early anti-VEGF for stopping and, in some cases reversing, DR progression. e reason for DR reversal with anti-VEGF is not fully known, although it has been postulated that capillary non- perfusion is a primary contributor to DR progression in patients with more advanced DR at baseline. 9 In patients with DME, there is a time-dependent increase in retinal nonperfusion (RNP), and anti-VEGF therapy blocks the feedback loop responsible for this phenomenon. In RIDE and RISE, secondary analysis of fluores- R E T I N A L P H Y S I C I A N | J A N U A R Y / F E B R U A R Y 2 0 1 7 46 cein angiograms was performed by masked graders, using a modified ETDRS FA grading protocol. Once patients previously in the sham treatment group were treated with ranibizumab, RNP growth halted and was reversed in many cases. 15 is finding suggests that blocking the downstream effects of VEGF is key to halting and reversing DR pro- gression. Recent OCT angiography data have suggested that patients with deep capillary plexus damage are more likely to respond poorly to anti-VEGF treatment, and this imag- ing modality could play a role in helping to predict treat- ment response. 16 LOCAL CORTICOSTEROID THERAPY Steroid therapy exerts a treatment effect in DR through the inhibition of leukostasis, enhancement of the barrier function of vascular endothelial-cell tight junctions, and mitigation of inflammatory factors including VEGF. 7 e place of steroids in DR treatment regimens has been confirmed in several large, multicenter trials, and ongoing research is focusing on continued optimization of appro- priate patient selection. Triamcinolone DRCRnet Protocol B compared intravitreal triamcinolone acetonide injections to macular laser for the treatment of DME. e primary outcome measurements were changes in VA and central retinal thickness, and triamcinolone was not found to be superior to macular laser. Side effects in the triamcinolone groups were more common than those in the laser treatment group. However, additional analysis of the data obtained in this study focused on DR progression, and high-dose intravitreal tri- amcinolone (0.4 mg) was found to result in a statistically significant reduction in DR progression, compared to laser alone. is result persisted through three years of follow- up. Due to the side effects experienced by patients receiv- ing intravitreal triamcinolone, the authors cautioned that a reduction in DR progression alone should not be used to change treatment protocols. DRCRnet Protocol I showed that triamcinolone was effective in reducing DR progres- sion, particularly in patients with pre-existing PDR. Subgroup analysis of eyes that were pseudophakic showed better VA gains, as would be expected given the elimination of cataracts as a potential side effect. e dif- ference in efficacy of triamcinolone between Protocols B and I might be due to patients in Protocol I receiving prompt focal laser following intravitreal triamcinolone. 4 Dexamethasone Implant e pivotal MEAD study investigated a dexamethasone implant (Ozurdex, Allergan, Irvine, CA) compared to sham in the treatment of DME. 7 e group treated with the implant had a statistically significant improvement in DIABETIC RETINOPATHY: HALTING AND REVERSING PROGRESSION

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