Much of our understanding on the relationship between visual function and macular ischemia in patients with RVO is derived from FFA. The conclusion that visual dysfunction is in lockstep with ischemic changes of the FAZ as reflected by FFA is at most a conjecture, with discrepant reports describing the relationship between the grade of visual dysfunction and status of the FAZ following RVO [
25‐
27]. The reason is that FFA, due to its inherent limitations, fails to include critical information on structural changes of the retinal micro-structure and of the DCP, which are cardinal determinants of the visual outcome in patients with RVO [
28‐
31]. Accordingly, absolute reliance on FFA for evaluation of macular ischemia following RVO episode could pose major compromise of our perception of the perfusion profile of the macula. In the present study, we focused on quantifying the pathological changes in the retinal vascular plexuses secondary to RVO using SS-OCTA and to devise a perfusion profile of the macula that would accurately represent the ischemic insult inflicted. Furthermore, we correlated our findings with the anatomic changes evident on SS-OCT and FFA and their relation to the visual function. Our results showed a statistically significant discrepancy between the grade of ischemia in SCP and DCP on SS-OCTA, in the sense that more ischemic quadrants were present at the level of the DCP relative to the SCP, which showed less ischemic damage. Moreover, perifoveal capillary ischemia and reduced vessel density per quadrant were more pronounced in the DCP relative to the SCP. These results confirm reports from several authors that ischemic damage in RVO is preferentially main-seated in the DCP and often precedes SCP ischemia [
4,
7,
10,
29‐
33]. In comparison with our results, Coscas et al. [
6] reported in a series of 54 patients with RVO, more extensive ischemic damage in the DCP relative to the SCP (84.3% vs. 58.8%, respectively). Cardoso et al. [
13], demonstrated in a reliability analysis of 81 eyes with RVO that capillary changes associated with ischemia were primarily located in the DCP. Chung et al. [
34], reported in a study recruiting 12 patients with RVO, patchy CNP areas involving the DCP that were not detected on the SCP using OCTA. Further corroborating evidence of more selective DCP affection in RVO was demonstrated in a retrospective series including 17 eyes by Samara et al. [
8], and in two series by Suzuki et al. [
35,
36] that included 12 eyes with BRVO and CRVO and 28 eyes with BRVO, respectively. These studies detected abnormally enlarged FAZ that was more pronounced in the DCP in eyes with RVO compared to the fellow unaffected eye. Moreover, Suzuki et al. [
35], detected reduced retinal flow area that was most marked in the DCP in eyes with RVO compared to the unaffected fellow eye. Similarly, Adhi et al. [
9], reported in a prospective case series of 23 patients with RVO, decreased vascular perfusion in the DCP that surpassed in frequency of occurrence and severity of involvement that of the SCP. Another important aspect of the present study, is the analysis of the correlation between SS-OCT anatomical features with ischemic changes revealed on SS-OCTA. Increased CMT and DROL were the most sensitive SS-OCT indices for DCP ischemia. On the other hand, DRIL was the least reliable SS-OCT index for SCP or DCP, though it had a direct proportional correlation with the severity of perifoveal capillary ischemia. Henceforth, we could propose a high-risk SS-OCT profile that includes increased CMT, DROL and DRIL and that portends significant ischemia in the DCP and in the perifoveal capillary arcade, respectively. Our conclusion on the positive correlation between increased CMT and DCP ischemia is ratified by Spaide’s theory on the cause-effect relationship between compromised blood flow within the DCP and reduced clearance of interstitial fluid from the retina and that eventually leads to macular edema [
37]. Further corroborating evidence is provided from the work of Tsuboi et al. [
38], who demonstrated a statistically significant positive correlation between flow-voids; equivalent to diminished vessel density in the SCP and the DCP and persistent macular edema in BRVO patients. In comparison, our results revealed that FFA was not reliable in assessment of ischemia. FFA representation of macular perfusion was significantly proportionate to SCP perfusion on SS-OCTA but in most cases it could not reveal the entire extent of macular ischemia as revealed by SS-OCTA depiction of DCP. Our findings are in line with two studies of the retinal vascular layers by Mendis et al. [
39], and Spaide et al. [
10], who compared FFA versus confocal laser scanning microscopy, and FFA versus OCTA respectively in evaluating the retinal vascular layers. Both studies concluded that FFA was unable to provide complete information on the DCP. In accordance with our findings, Chung et al. [
34], reported poor agreement between FFA and OCTA in revealing CNP following RVO with clear superiority of OCTA over FFA (91.67% vs. 58.33%), particularly in DCP non-perfusion and in detection of perifoveal capillary ischemia. Similarly, two case series including 28 eyes and 10 eyes with BRVO by Suzuki et al. [
36], and Rispoli et al. [
40], respectively, and one case report of ischemic BRVO by Kuehlewein et al. [
41], found that OCTA was superior to FFA in detection of CNP areas and in delineating them with higher-resolution, and in detection of microvascular abnormalities and FAZ dimensions. It is worthy of note that the latter authors used the SS-OCTA technology in their study. In terms of versatility of the studied imaging modalities in predicting visual outcome after RVO, our findings revealed that increased CMT, DRIL, and DROL on SS-OCT, and SCP and DCP ischemia on SS-OCTA were significant predictors of poor visual outcome; whereas FFA features that included macular edema and macular ischemia did not correlate with the visual outcome of those patients. These findings are in line with Wakabayashi et al. [
7], who studied the correlation between OCTA and BCVA in a series of 85 eyes with BRVO. These authors found that DCP ischemia is the most significant determinant of BCVA. Furthermore, the authors reported significant correlation between DCP ischemia on OCTA and worsening macular edema and disrupted photoreceptors layer on OCT. Our results are congruous with those of Samara et al. [
8], who detected that logMAR BCVA correlated positively with foveal thickness on OCT, and negatively with vascular density in DCP on OCTA. The present study has several confounding factors, of which the most salient is its retrospective design, which allowed entry of patients with important epidemiologic and phenotypic variation of RVO. This uneven stratification might have posed an information bias that could affect our interpretation of the correlation between the tested parameters in more than one aspect. Firstly, almost 50% of recruited patients had CRVO and HRVO, which implicate more extensive DCP ischemia on SS-OCTA, more diffuse structural changes on SS-OCT and worse impact on visual acuity than BRVO. Secondly, recruited patients had different stages of RVO whether acute or chronic. Accordingly, those patients were going through different stages of microvascular remodeling following the retinal venous occlusive event with fairly wide-variation in time course and quantity. Thirdly, patients were allowed to enroll in the study regardless of whether they were treatment-naïve or had received single or multiple lines of therapy, which could have important impact on the vessel density in the SCP and DCP, and on the structural changes on SS-OCT. Finally, the current study lacked concurrent evaluation of the perfusion of the peripheral retina, which has an important impact on macular edema. Rather the study focused on grading the perfusion in the macular area and the posterior pole. A more comprehensive evaluation of RVO would include correlation between the current findings and the grade of non-perfusion in the retinal periphery using wide-field OCTA or a montage of multiple 9 × 9 mm or 12 × 12 mm scans.