Reply

Abstract

We very much appreciate the interest of Patel and Kim in our recent publication “Intravitreal Aflibercept Injection in Patients with Myopic Choroidal Neovascularization: the MYRROR Study.”1Ikuno Y. Ohno-Matsui K. Wong T.Y. et al.Intravitreal aflibercept injection in patients with myopic choroidal neovascularization: the MYRROR study.Ophthalmology. 2015; 122: 1220-1227Abstract Full Text Full Text PDF PubMed Scopus (151) Google Scholar Patel and Kim raise concerns regarding the choice of therapy for controls in the MYRROR study.1Ikuno Y. Ohno-Matsui K. Wong T.Y. et al.Intravitreal aflibercept injection in patients with myopic choroidal neovascularization: the MYRROR study.Ophthalmology. 2015; 122: 1220-1227Abstract Full Text Full Text PDF PubMed Scopus (151) Google Scholar First, they asked whether verteporfin photodynamic therapy (PDT) could be used for the control group. At the time of study enrollment, in the principal study country of investigation (Japan), PDT was not approved for myopic choroidal neovascularization (CNV). Furthermore, a prospective, randomized, placebo-controlled trial (Verteporfin in Photodynamic Therapy) has demonstrated that there is no difference in visual outcomes between PDT and placebo treatment over 2 years in patients with myopic CNV.2Verteporfin in Photodynamic Therapy (VIP) Study GroupVerteporfin therapy of subfoveal choroidal neovascularization in pathologic myopia: 2-year results of a randomized clinical trial VIP report no. 3.Ophthalmology. 2003; 110: 667-673Abstract Full Text Full Text PDF PubMed Scopus (351) Google Scholar Finally, there is increasing evidence of risk of chorioretinal atrophy in PDT-treated eyes with myopic CNV compared with those treated with an anti-vascular endothelial growth factor therapy.3Hayashi K. Ohno-Matsui K. Teramukai S. et al.Comparison of visual outcome and regression pattern of myopic choroidal neovascularization after intravitreal bevacizumab or after photodynamic therapy.Am J Ophthalmol. 2009; 148: 396-408Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar Based on these findings, the investigators believed that PDT was not a suitable alternative, “effective” treatment for patients with myopic CNV and thus did not use PDT in the control arm. The choice of the comparator was further discussed in detail with various regulatory agencies as well as with ethics committees, all of whom supported the use of a sham control arm in the MYRROR study.1Ikuno Y. Ohno-Matsui K. Wong T.Y. et al.Intravitreal aflibercept injection in patients with myopic choroidal neovascularization: the MYRROR study.Ophthalmology. 2015; 122: 1220-1227Abstract Full Text Full Text PDF PubMed Scopus (151) Google Scholar Patel and Kim also query the use of bevacizumab (Avastin) as a control. Although bevacizumab was being used off-label in clinical care, at the time of study enrollment there were limited prospective clinical data on its use in this specific patient population. Thus, the investigators did not feel bevacizumab was an appropriate comparator in this trial. We would agree that, based on the known findings and with hindsight, 3 months would have been a sufficient time scale to see an improvement in visual outcomes with intravitreal aflibercept injection; however, at the time of the study we did not know this to be the case and 6 months was therefore chosen as the cutoff. Finally, we had sufficient safety mechanisms in the trial; investigators were free to withdraw any patient from the study who experienced poor outcomes at any time. A total of 7 (7.7%) and 6 (19.4%) patients discontinued treatment (before 6 months) from the intravitreal aflibercept and sham treatment groups, respectively; no patients were withdrawn from the intravitreal aflibercept group owing to treatment failure, but 1 patient (3.2%) was withdrawn from the sham treatment group owing to treatment failure. Two patients (6.5%) in the placebo group switched treatment. The treatment for myopic CNV is evolving and future trials should take into account new evidence of alternative treatments for control arms. Re: Ikuno et al.: Intravitreal aflibercept injection in patients with myopic choroidal neovascularization: the MYRROR study (Ophthalmology 2015;122:1220-7)OphthalmologyVol. 123Issue 2PreviewWe read with some concern the recent article by Ikuno at al1 on intravitreal aflibercept in patients with myopic choroidal neovascularization (CNV). The authors report a 3:1 randomization of intravitreal aflibercept and sham in patients with sight-threatening CNV owing to myopia. Patients in the sham (control) group “were given 1 sham injection followed by repeated sham injections every 4 weeks through week 24 regardless of whether re-treatment criteria were fulfilled or not.” Control patients were only offered treatment at week 24. Full-Text PDF