Eyeworld

EW RETINA 36 April 2015 by Michelle Dalton EyeWorld Contributing Writer Long-awaited Protocol T results published The first head-to-head-to- head comparison of the common anti-VEGFs for the treatment of DME reveals some surprises P atients with diabetes will likely develop ocular com- plications; macular edema is one of the common causes of vision loss in this patient population. For decades, focal laser photocoagulation was the primary treatment, but results were not as stellar as clinicians would have liked. The introduction of the antivascular endothelial growth factors (anti-VEGF) has changed the treatment paradigm drastically whereby intravitreal injections are favored heavily as a first-line treat- ment. Aflibercept (Eylea, Regeneron, Tarrytown, N.Y.) and ranibizumab (Lucentis, Genentech, South San Francisco) are 2 approved therapies for the treatment of diabetic macular edema (DME). Another anti-VEGF, bevacizumab (Avastin, Genentech), is often used off-label. The Diabetic Retinopathy Clinical Research Net- work has released results from the first head-to-head-to-head compari- son of the 3 anti-VEGFs, commonly referred to as "Protocol T," 1 and found in some patients aflibercept yielded a greater improvement in visual acuity than did the other 2 compounds. Funding for the study was through the National Insti- tutes of Health, which has a vested interest in the outcomes not only for safety and efficacy, but for cost evaluations: The approximate costs to Medicare for a single injection is $1,950 for aflibercept (2.0 mg dose), $50 for bevacizumab (presuming the aliquot is 1.25 mg), and $1,200 for ranibizumab (0.3 mg). DME is often bilateral and chronic. Study protocol A total of 660 participants complet- ed the study, randomized as follows: 224 participants in the aflibercept arm, 218 in the bevacizumab arm, and 218 in the ranibizumab arm. Mean letter score at baseline was 64.8 (roughly a 20/50 Snellen equiv- alent), and mean central subfield thickness was 412 µm. Study drugs were injected every 4 weeks after an initial baseline dose, unless visual acuity (VA) was 20/20 or better with a central subfield thickness below the eligibility threshold and there was no improvement or worsening in response to the past 2 injections, according to the treatment proto- col. For the purposes of this study, improvement was defined as a line gain or a decrease in central subfield thickness of 10% or more. Wors- ening was defined as a minimum 5-letter loss or an increase in central subfield thickness of 10% or more. Regardless of visual or anatomic results at week 24, injections were withheld if there was no improve- ment or if the patient worsened after 2 consecutive visits; treatment was reinitiated if either visual or anatom- ic outcomes worsened. Study results Each of the 3 drugs improved visual acuity at 1 year, and each of the ap- proved formulations produced better visual outcomes than bevacizumab. All eyes underwent a mean of 9–10 injections. In eyes with visual acuity of 20/40 or better, there was no difference among the drugs in improvement in the visual acuity letter score (mean improvement, 8 for each drug) or the number of injections (median, 9 for each drug) required to achieve this result. Study authors noted "the relative effect varied according to initial visual acuity." In patients with an initial base- line acuity of 20/50 or worse, there was a statistically significant advan- tage to aflibercept over ranibizumab and bevacizumab in mean letter score improvements (19 letters, 14 letters, and 12 letters, respectively). All groups started to show improve- ment in visual acuity by 4 weeks; in eyes with 20/50 or worse baseline VA, "the greater efficacy of afliber- cept started to become apparent as early as 4 weeks after the initiation of treatment," the study authors said. 1 However, they also noted the "magnitude of the greater effect of aflibercept lacked clinical applicabili- ty" because baseline acuity drove the results. " This study found no significant differences among the 3 drugs when baseline vision was 20/40 or better, meaning cost is likely to be a consideration when planning first-line therapies. " "There haven't been any pub- lished cases, but there have been reports of migration," Dr. Khurana said. "The package insert discuss- es the contraindication without specifying if it's limited to Iluvien or if it's fluocinolone in any implant. Retisert, which has fluocinolone, has been shown to cause corneal problems if it comes forward." The original phase 3 studies on Ozurdex reported no incidents Retinal continued from page 34 of migration, but exclusion crite- ria included aphakia and anterior chamber IOLs. 2 A smaller study of vitrectomized eyes (n=17) found one case (6%), and that was in an aphakic eye. 3 As a result, in September 2012, the Food and Drug Administration changed the Ozurdex package insert to contraindicate aphakic patients with rupture of lens capsule or ante- rior chamber IOL patients who have had a lens capsule rupture. EW References 1. Khurana RN, Appa SN, McCannel CA, et al. Dexamethasone implant anterior chamber migration: risk factors, complications, and management strategies. Ophthalmology. 2014;121:67–71. 2. Haller JA, Bendello F, Belfort R Jr., et al for the OZURDEX GENEVA study group. Random- ized, sham-controlled trial of dexamethasone intravitreal implant in patients with macular edema due to retinal vein occlusion. Ophthal- mology. 2010 Jun;117(6):1134–1146. 3. Adan A, Pelegrin L, Rey A, Llorens V, Mesquida M, Molins B, Rios J, Keller J. Dexamethasone intravitreal implant for treatment of uveitic persistent cystoid macular edema in vitrectomized patients. Retina. 2013; 33(7):1435–40. Editors' note: Dr. Khurana has financial interests with Allergan. Contact information Khurana: rnkhurana@gmail.com

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