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Abstract

We read with interest the letter by Călugăru and Călugăru in response to our paper published in the journal.1Bailey C. Scott L. Rogers C. et al.Intralesional macular atrophy in antiVEGF therapy for age-related macular degeneration in the IVAN trial.Ophthalmology. 2019; 126: 75-86Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar The authors raise the issue of angiographic type at baseline and make some useful points about the complexity of baseline diagnosis. We agree that the interpretation of imaging in neovascular age-related macular degeneration (AMD) remains challenging. We devoted considerable amounts of time in the setting of our network of reading centers in further developing our classifications from the original ones used in IVAN and CATT (references 1–6 in our article). Contrary to the authors’ statement, we did in fact consider the proportions of classic vs occult choroidal neovascularization at baseline (at least in a categorical manner) as shown in Table 2 (in the original article). Moreover, we investigated the effect of the proportion of classic choroidal neovascularization at baseline, and the presence of subretinal fluid and pigment epithelial detachment both at baseline and at final visit, in our primary analyses of predictors of the development of macular atrophy (MA; Figs 3 and 4 in the original article). We recognize that there continues to be a significant debate amongst the research and clinical community about the subclassification of polypoidal choroidal vasculopathy (PCV). We did not have access to indocyanine green angiography in the IVAN study. The points about the response to subtypes of treatment are interesting but were outside the scope of our study. However, we are in agreement that indocyanine green angiography is an important adjunct in the diagnosis in neovascular AMD in the clinic and particularly when PCV is suspected. One study from the UK reported PCV in 9.1% of white people presenting with neovascular AMD.2Yadav S. Parry D.G. Beare N.A.V. et al.Polypoidal choroidal vasculopathy: a common type of neovascular age-related macular degeneration in Caucasians.Br J Ophthalmol. 2017; 101: 1377-1380Crossref PubMed Scopus (24) Google Scholar Because OCT angiography becomes increasingly used in clinical practice, this may also prove useful in improving the identification of PCV. The authors comment on the OCT definition of MA. In our study, we used OCT as supporting evidence only, requiring the MA to be visible on color photography or fluorescein angiography. The authors speculate on the possible effects of anti-vascular endothelial growth factor therapy on the function of the choriocapillaris. We agree that this may prove important but we did not have data to explore this further. Finally, the authors make the point that we “found no significant associations between development of intralesional MA [ILMA] and drug or treatment frequency as well as any other morphologic or visual function measure” and argue that we should have investigated a much wider set of baseline covariates in our analyses. They list a number of other features visible on current OCT images as potential covariates, which we recognize may prove informative in the future. In responding to their statement, we have preferred to describe associations with the predictor first and the outcome second and to separate out the associations (i) between drug or treatment frequency or other morphological measure and incident ILMA (Fig 3 in the original article) from (ii) between visual function and ILMA. With respect to (i), the outcome was binary and so fitting lots of covariates runs the risk of the logistic model not fitting. We restricted covariates in this analysis to a number appropriate for the sample size and for which there was an a priori biologically plausible relationship. With respect to (ii), we believe that it is appropriate to adjust only for covariates that are not associated with the development of ILMA. Otherwise, adjustment runs the risk of removing any effect of the groups being compared. In this context, our finding of no association of visual acuity (without adjustment) with ILMA seems robust, because the direction of our hypothesis was that ILMA should decrease visual acuity. Re: Bailey et al: Intralesional macular atrophy in anti-vascular endothelial growth factor therapy for age-related macular degeneration in the IVAN trial (Ophthalmology. 2019;126:75–86)OphthalmologyVol. 126Issue 9PreviewWe would like to address several issues with the study by Bailey et al.1 Of the 6 angiographic types of choroidal neovascularization (CNV) existing in patients with neovascular age-related macular degeneration (AMD), the study analyzed at presentation only 1 of them, namely, occult CNV. The other 5 angiographic types (e.g., predominantly and minimally classic CNVs, mixed CNV, retinal angiomatous proliferation, and polypoidal choroidal vasculopathy [PCV]) were not screened and investigated in the study populations as potential predictive factors influencing the occurrence and progression of intralesional macular atrophy (MA). Full-Text PDF