A Comparison of Vessel Density in Primary Open-Angle Glaucoma and Normal-Tension Glaucoma Patients Using OCT Angiography [Letter]

We read with interest the article by Zehavi-Dorin et al 1 comparing vessel density in Primary Open-Angle Glaucoma (POAG) and Normal-Tension Glaucoma (NTG).We commend the authors for their rigorous severity-matching using Hodapp-Parrish-Anderson criteria and thoughtful study design.We write to offer several methodological considerations that may warrant further discussion and help contextualize their conclusion that "vascular factors may play a more prominent role in the early stages of NTG". 1 Statistical Significance and the Vascular HypothesisThe authors report a "trend toward significance" (p = 0.058) for lower peripapillary vessel density in early NTG.While this is an intriguing observation, we note that after adjustment for multiple comparisons, this difference was not statistically significant (p = 0.301). 1 We respectfully suggest that this non-significant finding might alternatively indicate that global vessel density metrics are not sufficiently sensitive to distinguish between POAG and NTG when severity is matched.We would be interested to know the authors' perspective on the statistical basis for their conclusion regarding vascular factors in early NTG given the adjusted p-value of 0.301.The authors note that "the RNFL thickness appeared to follow a similar trend to vessel density".1 Given the wellestablished correlation between vessel density and RNFL thickness in both healthy 2,3 and glaucomatous eyes, 4 we wonder whether the observed patterns in vessel density might reflect parallel structural changes.We would be interested to learn whether a multivariate analysis adjusting for RNFL thickness was performed, as this could help clarify if the microvascular changes represent an independent finding. Additional Data That May Inform InterpretationThe authors report similar IOPs on the day of OCTA (13.9 ± 3.4 mmHg for POAG vs 13.3 ± 2.4 mmHg for NTG), 1 suggesting patients were on treatment.Since Holló 5 demonstrated that significant IOP reduction can increase peripapillary vessel density, we wonder whether information on baseline untreated IOP, treatment regimens, and disease duration might be available.This additional context could help readers better understand whether the observed vessel density reflects underlying disease pathophysiology or potential treatment effects.The authors acknowledge that "systemic hypertension, cardiovascular status, or topical and systemic medications" were not collected.1 We appreciate this transparent acknowledgment.Given that NTG is associated with systemic vascular dysregulation 6,7 and that conditions such as hypertension, sleep apnoea, and carotid stenosis can affect retinal vessel density, [8][9][10] future studies incorporating these variables might help further elucidate the relationship between vessel density and NTG pathophysiology.