Optical Coherence Tomography Angiography (OCTA) is an imaging technique that non-invasively visualizes the blood vessels of the retina and optic nerve head. It repeatedly scans the same cross-section and detects changes in reflection caused by the movement of red blood cells flowing within the vessels. This creates image contrast between perfused vessels and surrounding static tissue, allowing vascular structures to be depicted without contrast agents. The first commercial OCTA was introduced in 2015.
Glaucoma is the leading cause of irreversible blindness worldwide2), with approximately 50% of cases undiagnosed. OCTA can detect reduced vessel density in glaucomatous eyes and is expected to be applied to diagnosis and progression assessment. OCTA allows non-invasive observation of the loss of intra- and peripapillary vessels and the reduction of the macular capillary network. According to glaucoma practice guidelines, OCTA can evaluate superficial and deep retinal blood flow, and it is known that superficial retinal blood flow decreases more in advanced glaucoma1).
QHow is OCTA different from regular OCT?
A
Regular OCT statically measures the structure (thickness) of the retina. OCTA additionally acquires dynamic blood flow information, allowing assessment of vessel density and changes in blood flow. Its feature is that it provides both structural and functional information.
In glaucomatous eyes, vessel density (VD) is reduced compared to control eyes. In both the peripapillary and macular regions, VD reduction is more pronounced in the superficial layer. The decrease in VD is more prominent in end-stage glaucoma than in early to moderate glaucoma. In glaucomatous eyes, intra-papillary capillaries disappear as cupping progresses, and radial peripapillary capillaries are lost in correspondence with retinal nerve fiber layer defects. In the macula, enlargement and deformation of the foveal avascular zone (FAZ) are also observed.
Microvascular dropout (MvD) is the loss of choriocapillaris in the peripapillary atrophy area. It is often observed in the inferotemporal region within the beta zone. MvD is associated with RNFL thinning, lamina cribrosa defects, visual field defects, and optic disc hemorrhage. The prevalence and size of MvD increase with glaucoma severity. MvD is a predictor of faster progression of RNFL thinning and visual field defects.
It has also been noted that deep-layer blood flow dropout around the optic nerve head is related to glaucoma progression1).
The diagnostic ability of OCTA is generally equivalent to that of OCT (RNFL thickness, GCC thickness). However, some reports indicate that OCT-measured RNFL thickness has better sensitivity in early glaucoma. On the other hand, in advanced glaucoma, OCTA may be advantageous as it is less susceptible to the floor effect of OCT1).
3. Background: Vascular Theory and Mechanical Theory of Glaucoma
The reason OCTA is attracting attention in glaucoma care is the involvement of vascular factors in the pathophysiology of glaucoma.
Mechanical Theory
Elevated intraocular pressure and lamina cribrosa deformation: Relative elevation of intraocular pressure causes deformation and thinning of the lamina cribrosa, disrupting axonal transport of retinal ganglion cells (RGCs) and leading to apoptosis.
Basis for intraocular pressure-lowering treatment: Many large-scale studies identify intraocular pressure as the greatest risk factor for the onset and progression of glaucoma5).
Limitations: It cannot fully explain normal-tension glaucoma or cases that progress despite intraocular pressure reduction3).
Vascular Theory
Decreased ocular blood flow and ischemia: Reduced ocular perfusion pressure and loss of vascular autoregulation expose the optic nerve to ischemia and oxidative stress3).
Involvement of arteriosclerosis: It is suggested that arteriosclerosis creates high pulsatility, causing damage to ocular microvessels3).
Significance of OCTA: OCTA, which can quantitatively assess vessel density, is a powerful tool for verifying the vascular theory.
In recent years, the “mechanical theory” and “vascular theory” are not considered independent; rather, the mainstream view integrates them as a biomechanical theory of the optic nerve head. It is thought that intraocular pressure-dependent and intraocular pressure-independent factors (circulatory disorders, autoimmunity, oxidative stress, etc.) interact in a complex manner to constitute glaucomatous optic neuropathy.
OCTA is based on SD-OCT or SS-OCT. Repeated B-scans are acquired at the same retinal location, and decorrelation (signal change) between consecutive images is detected. Red blood cells flowing in blood vessels alter the reflected signal, while surrounding stationary tissue does not. This difference is visualized as a blood flow map.
SSADA: Split-spectrum amplitude-decorrelation angiography. Used in AngioVue® (Optovue®)
OMAG: OCT-based microangiography. Used in Angioplex® (Zeiss®)
OCTARA: OCT angiography ratio analysis. Used in Triton® (TopCon®) SS-OCTA
Others: Intensity and phase decorrelation combination method in AngioScan® (NIDEK®), intensity decorrelation method in SPECTRALIS® (Heidelberg®)
Device Selection Considerations
Inter-device incompatibility: Due to differences in algorithms and default slab depths, direct comparison between devices is not possible even in the same patient.
SS-OCTA: TopCon®, Canon®, and Zeiss® offer swept-source OCTA, which improves speed and resolution for evaluating the choroidal layer.
Image quality criteria: Low-quality images with a signal strength index (SSI) below 40 (below 6 for Zeiss) should be excluded.
OCTA provides both functional and structural information in the diagnosis of glaucoma. Meta-analyses have concluded that VD in all evaluated regions is lower in glaucomatous eyes compared to controls. The diagnostic ability of OCTA is considered equivalent to that of OCT (RNFL thickness, GCC thickness). Some reports indicate that the correlation between visual field (VF) and VD is better than that between VF and OCT, and this correlation becomes stronger in highly myopic eyes and end-stage glaucoma.
Most longitudinal studies with follow-up of 3 months or longer have found associations between VD changes and structural (OCT) and functional (VF) deterioration. Lower baseline peripapillary and macular VD is associated with faster rates of RNFL progression in early to moderate glaucoma. This association is independent of baseline RNFL thickness, suggesting that OCTA may provide additional contribution to progression risk assessment.
Progression assessment by OCTA is considered less affected by the floor effect of structural OCT, and may be more advantageous in advanced glaucomatous eyes compared to OCT1). However, at present, a standardized method for clinical use has not been established1).
Intraocular pressure reduction by surgery induces changes in ocular hemodynamics, leading to increased ocular blood flow. Multiple studies have reported a significant increase in microvascular VD after glaucoma surgery. The increase in VD correlates with higher preoperative IOP, greater IOP reduction, and decreased lamina cribrosa depth.
Peripapillary VD is independent of IOP within the postoperative IOP range, while macular VD shows a delayed response and continues to exhibit near-normal reperfusion. However, many studies have short follow-up periods of 3 months to 1 year, and long-term validation is needed.
QCan OCTA be used to evaluate after glaucoma surgery?
A
It may be possible. Multiple studies have reported a significant increase in VD after surgery, showing promise for assessing vascular recovery. However, long-term follow-up studies are lacking, and further validation is needed.
6. Pathophysiology: Vascular damage captured by OCTA
Ocular perfusion pressure (OPP) is defined as the difference between arterial and venous pressure. The formula is OPP = 2/3 MAP − IOP (MAP = mean arterial pressure). Blood flow is affected by vascular resistance; a 50% reduction in vessel diameter reduces blood flow by approximately 94%. Loss of this regulatory mechanism leads to ischemia.
The main vasodilator is nitric oxide (NO), which relaxes vascular smooth muscle via increased cGMP. Hypoxia and hypercapnia also induce vasodilation. The main vasoconstrictor is endothelin-1 (ET-1). In glaucomatous eyes, NO concentration is elevated in the aqueous humor, which is thought to reflect increased activity of inducible NO synthase in the optic nerve.
Increased pulsatility due to arteriosclerosis may cause smooth muscle hypertrophy, arteriolar narrowing, increased vascular resistance, and decreased VD in ocular microvessels 3). Cross-sectional studies have shown a positive association between pulse wave velocity (PWV) and glaucoma, with participants having higher PWV tending to have lower macular VD 3). Prospective studies have linked pulse pressure >70 mmHg with increased risk of POAG3).
The decreased VD and MvD observed on OCTA are considered consequences of the above vascular damage mechanisms. Peripapillary radial capillary dropout corresponds to RNFL defects, and microchoroidal vessel dropout within the PPA area reflects deep vascular atrophy at the choroidal level. The clinical value of OCTA lies in its ability to quantitatively capture these findings.
Beros et al. (2024) examined whether arterial pulse wave velocity (aPWV), aortic pulse pressure (aPP), and estimated PWV (ePWV) measured by an oscillometric device predict the onset of glaucoma in a large New Zealand cohort (ViDA Study) 3). Increased PWV was associated with a higher risk of primary open-angle glaucoma, suggesting that high arterial stiffness may contribute to glaucoma development through ocular microvascular damage 3).
Stangos et al. (2025) conducted an umbrella review of ocular and systemic risk factors and biomarkers associated with glaucoma4). They evaluated 87 risk factors and 46 biomarkers, and three ocular factors (intraocular pressure, myopia, corneal hysteresis) and one peripheral biomarker (total antioxidant status) were rated as having “highly suggestive evidence” 4). It is suggested that vascular density assessment by OCTA may play a role as a biomarker in the future.
For the full-scale clinical application of OCTA in glaucoma management, standardization across devices and protocols and accumulation of long-term longitudinal studies are essential. Since VD measurements are susceptible to fluctuations in intraocular pressure, systemic perfusion, and retinal oxygenation, analyses that account for these confounding factors are required. Automated analysis of OCTA images using artificial intelligence (AI) is also an area expected to develop in the future.
European Glaucoma Society. European Glaucoma Society Terminology and Guidelines for Glaucoma, 6th Edition. Br J Ophthalmol. 2025.
Beros AL, Sluyter JD, Hughes AD, et al. Arterial Stiffness and Incident Glaucoma: A Large Population-Based Cohort Study. Am J Ophthalmol. 2024;266:68-76. doi:10.1016/j.ajo.2024.05.015. PMID:38754800.
Stangos A, et al. Ocular and Systemic Risk Factors and Biomarkers for Glaucoma: An Umbrella Review of Systematic Reviews and Meta-Analyses. Invest Ophthalmol Vis Sci. 2025;66(12):35.
Stamer WD, Bhatt K. Intraocular Pressure. Annu Rev Vis Sci. 2024.
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