An understanding of hemodynamic changes in the optic disc area may yield valuable insights into the pathogenesis of NTG and BRVO. OCTA enables noninvasive visualization of vessels in the retina and optic disc, as well as quantification of vessel parameters, thus imparting detailed information regarding hemodynamic changes associated with disease. Here, we quantitatively analyzed the VDs of optic disc vessels evident on OCTA images of eyes with NTG, according to BRVO status; we compared these findings between and among groups. We found differences in the VDs of the optic disc and peripapillary area between eyes with NTG, according to BRVO status; we also found correlations between the VDs of large and small vessels in the disc and peripapillary area. Our principal findings were that BRVO was associated with enhanced large vessel VD and reduced small vessel VD in the optic disc. This was evident in both eyes with NTG + BRVO and fellow eyes with NTG alone. Furthermore, the large vessel and small vessel VDs differed significantly between fellow eyes with NTG alone and control eyes, suggesting that such changes may contribute to NTG development in patients with BRVO. Peripapillary VD was significantly reduced only in eyes with NTG + BRVO, suggesting that the change may be attributable to BRVO.
The contributions of large and small vessels to the disc VD differed between eyes with NTG, according to BRVO status. The mean VD of large vessels was higher, whereas the mean VD of small vessels was lower, in patients with NTG + BRVO. Because factors that might affect disc vasculature (e.g., age, comorbid diabetes, refractive error, and axial length; Table 4) were comparable among the groups, our interpretation may be valid. Engorgement of large vessels (especially veins) may be followed by attenuation of small vessels in eyes with BRVO. The peripapillary VDs were also lower in eyes with BRVO. The negative apparent correlation between large and small vessel VDs supports this notion. The optic disc head occupies a limited space; enhanced large vessel volume caused by congestion may trigger mechanical compression of small vessels. However, the detailed underlying mechanism requires further investigation.
The fellow eyes in patients with BRVO exhibited a greater large vessel VD and a lower small vessel VD, compared to the control eyes, suggesting that underlying systemic factors affect both eyes in patients with BRVO. Hypertension is a possible contributing factor; this demographic differed between patients with BRVO and controls. In a previous study, we showed that patients with BRVO exhibited more rapid glaucoma progression in their fellow eyes, compared to patients with glaucoma who did not develop BRVO.18 The difference in fellow eye hemodynamics between patients with BRVO and controls, observed in the present study, might be relevant in this context.
Here, we also found that the NTG fellow eyes in patients with BRVO exhibited a significantly lower small vessel VD in the optic disc, compared with NTG control eyes. The peripapillary VD parameters did not differ between the NTG fellow eyes in patients with BRVO and NTG controls, suggesting that a small vessel VD change in the optic disc may accelerate glaucoma progression in the glaucomatous fellow eyes in patients with BRVO.18 Systemic factors may trigger changes in the disc VDs of both eyes, thereby increasing the proportion of large vessels in patients who develop BRVO, followed by more prominent changes. Because this was a cross-sectional study, we could not determine whether the phenomenon was a cause or a result of BRVO.
Blood flows from two principal sources to the optic disc. The superficial layers of the optic nerve head (i.e., the RNFL) are supplied by the central retinal artery; the deeper layers (i.e., the prelaminar, lamina cribrosa, and retrolaminar regions) are supplied by the posterior ciliary artery.19 Analysis of respective layers would yield detailed information regarding whether the observed changes reflect alterations in branches of the central retinal or posterior ciliary arteries. However, the resolution of current OCTA systems is inadequate for such analysis; it may be achieved in the future by using more powerful angiographic imaging systems.
The peripapillary VDs of the entire region and all four quadrants were lower in eyes with BRVO than in fellow eyes and controls, consistent with the results of a previous study by Shin et al.20 Notably, Shin et al. reported that various peripapillary microvascular parameters were lower in fellow eyes in patients with RVO. Most vessels visible on OCTA scans of the peripapillary area are retinal, radial peripapillary capillaries.21 These radial peripapillary capillaries branch from the central retinal artery; thus, lower peripapillary VD can be largely explained by reduction of perfusion from the central retinal artery, perhaps attributable to the venous engorgement of eyes with BRVO and the negative correlation between the large vessel VD of the optic disc and the peripapillary VD, despite the weak correlation. However, this may be less important than in the optic disc area, as the peripapillary area is not a limited space. Other possible causes of reduced central retinal artery perfusion include capillary attenuation attributable to vasospasm, atherosclerosis, or shunting.
Our study had limitations inherent to all cross-sectional retrospective analyses. As mentioned above, we could not investigate causal relationships between vessel changes and disease development; we showed only that hemodynamic changes are evident. However, to the best of our knowledge, this study was the first to quantitatively analyze disc vessel morphology in eyes with NTG, according to BRVO status. Because hemodynamic factors play important pathophysiological roles in both NTG and BRVO, we believe that the results deepen our understanding of the pathogenesis of both diseases.
In conclusion, we measured VDs of the optic disc area of eyes with NTG, according to BRVO status; we revealed enhancement of large vessel VD and reduction of small vessel VD, as well as reduction of peripapillary VD, in eyes with BRVO. The large vessel VD was significantly enhanced and the small vessel VD was significantly reduced in fellow eyes (with NTG alone) in patients with BRVO, suggesting that hemodynamic changes may contribute to NTG development in patients with BRVO. Our results suggest that the hemodynamics around the disc area differ in eyes with NTG, according to BRVO status, and may be associated with disease development or progression. Prospective follow-up studies with larger samples are required to confirm our findings.