Our second finding was that the NPAs in eyes with RVOs decreased 6 months after therapy, especially in the retinal deep capillary layer. Interestingly, more frequent injections of anti-VEGF agents resulted in smaller NPAs and improved flow area, while fewer injections did not do so, suggesting that frequent blockade of VEGF might result in reperfusion of NPAs and improved retinal vessel flow. It has been recognized for many years that in some patients with RVOs the NPAs increase in size over time.
22 Therefore, the current result was surprising. Also, it is still controversial whether VEGF inhibition worsens retinal ischemia. Because VEGF is a survival factor for vascular endothelial cells, its blockade might result in worse progression of the retinal ischemia.
23 In fact, several studies have reported such an effect.
9–11 However, Campochiaro et al.
22 reported that blockade of VEGF not only prevented worsening of NPAs but also might have improved the retinal perfusion status. That report supports our current results. However, in the study of Campochiaro et al., the NPAs were assessed on FA images and the size was expressed in disc areas. In addition, retinal hemorrhages usually result in hypofluorescence on FA images because both excitation and emission lights are blocked but minimally impair the OCTA images obtained using a longer wavelength light (840 nanometers).
15 We previously reported that OCTA visualizes NPAs better than FA.
15 Moreover, OCTA enables quantification of the size as an absolute value. Taken together, OCTA is superior for evaluating NPA size compared with FA. Intraocular injections of VEGF drugs in primates resulted in leukostasis and progressing NPAs.
23 Miyamoto et al.
24 also reported that VEGF-induced capillary nonperfusion occurred downstream from the area of leukocyte adhesion. Later, after the disappearance of the leukocytes, the capillaries reopened because neutrophil and monocyte diameters can exceed those of retinal capillary lumens.
24 Vascular endothelial growth factor blockade might halt leukocyte adhesion and lead to retinal reperfusion. If VEGF inhibition actually reduces the size of the NPA in RVOs, it might suppress the incidence of retinal and iris neovascularization and neovascular complications.
25 In fact, in the current study, only one eye (patient 6 with BRVO) underwent laser photocoagulation because of retinal neovascularization, although the follow-up period was just 6 months.