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Abstract

We read with interest the letter by Borrelli et al concerning our work.1Couturier A. Rey P.-A. Erginay A. et al.Widefield OCT-angiography and fluorescein angiography assessments of nonperfusion in diabetic retinopathy and edema treated with anti-vascular endothelial growth factor.Ophthalmology. 2019; 126: 1685-1694Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar As mentioned, although anti–vascular endothelial growth factor (VEGF) injections are effective in diabetic macular edema, the existence of a retinal reperfusion after treatment remains controversial. The aim of our study was to assess the change in capillary and vessel perfusion in each nonperfusion (NP) area after 3 anti-VEGF injections using 2 imaging modalities, fluorescein angiography and OCT angiography (OCTA). Borrelli et al stated that they identified a few reperfused capillaries after treatment in our images. We performed a detailed analysis of each NP area to determine the reappearance or disappearance of vessel segment or capillaries. On early phase fluorescein angiography, the NP area was defined as an area of the fundus devoid of retinal arterioles, venules, and capillaries, with a pruned appearance of adjacent vessels. On OCTA, the NP area was defined as the absence of capillary bed between a terminal arteriole and a proximal venule or larger vessels. The analysis of capillary perfusion is complex for many reasons. First, each imaging modality has its disadvantages. Fluorescein angiography resolution does not allow visualizing capillaries and leakage of the dye may impair the visualization of some vessel segments at baseline. The change in leakage and choroidal background induced by anti-VEGF therapy may lead to a false interpretation of capillary reperfusion in some areas. Regarding OCTA imaging, capillaries with a low flow may not be detected and the detection of changes in small vessel segments may also be impaired by the change in signal strength, motion artifacts, or artifacts owing to the montage or boundaries of the images. Second, the retinal microcirculation is a complex and specific environment with a particular spatial and temporal heterogeneity and constant changes to meet the metabolic needs of this neuronal tissue. This has been nicely demonstrated by Yu et al,2Yu D.Y. Cringle S.J. Yu P.K. et al.Retinal capillary perfusion: spatial and temporal heterogeneity.Prog Retin Eye Res. 2019; 70: 23-54Crossref Scopus (57) Google Scholar who have taken multiple OCTA images from the macular region of a healthy subject and shown that the intensity of capillaries varied: most of the faint capillaries were only visible in 1 or 2 of the 31 frames. Owing to this temporal heterogeneity in the macular vascular network and the differences in capillary perfusion that could be found between each frame, we did not consider the minimal changes in capillary segments as an occlusion or reperfusion in our study. Similarly, we did not take into account the posttreatment nonflow seen in some arteriolar segments to assign the responsibility for these changes to anti-VEGF. Thus, it is true that there are several limitations with respect to the interpretation of the change in retinal microcirculation, and that the reappearance of some very small vessel or capillary segments may be difficult to attribute either to a real reperfusion, the physiologic and temporal heterogeneity of the retinal microcirculation, nonsignificant capillary remodeling, or to artifacts, as mentioned by Borelli et al in their letter. However, we believe our work remains relevant as we showed that the large NP areas were clearly unchanged after anti-VEGF therapy using 2 different imaging modalities despite the improvement in diabetic retinopathy severity score on color fundus photographs, as shown in all our figures. It seems important to us to highlight that wide NP areas persisted after 3 anti-VEGF injections, despite minor changes in microvascular segments, and therefore to draw attention to the need for carefully monitoring treated patients. Re: Couturier et al.: Widefield OCT-angiography and fluorescein angiography assessments of nonperfusion in diabetic retinopathy and edema treated with anti–vascular endothelial growth factor (Ophthalmology. 2019;126:1685–1694)OphthalmologyVol. 127Issue 5PreviewWe read the article by Couturier et al1 regarding the changes in retinal perfusion in eyes with diabetic retinopathy undergoing 3 monthly anti–vascular endothelial growth factor (VEGF) intravitreal injections for diabetic macular edema. The authors provided a fully integrated description of these changes employing both ultrawidefield fluorescein angiography (UWFA) and widefield OCT angiography (OCTA). Primary outcome measures include the number of nonperfusion areas and the quantity of arterioles or venules that disappeared or reappeared in each of these areas. Full-Text PDF