OCT-Angiography and Glaucoma

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Article Summary

Glaucoma is the first cause of irreversible blindness in the world. Fifty percent of glaucomas are undiagnosed; consequently, we should develop new technologies to aid in glaucoma diagnosis. Angiography (OCTA) is a recent, non-invasive and fast technology that allows the visualization of retinal and papillary vessels. Studies have shown that OCTA detects decreased vascular density in glaucoma.

Disease Entity: Glaucoma

Glaucoma is an optic neuropathy with typical changes in the optic nerve head, retinal nerve fiber layer, and visual fields[1]. It is the second leading cause of blindness[2], which is unfortunately irreversible. Therefore, the diagnosis is critical to prevent blindness. The diagnosis depends on the clinical examination (optic disc, retinal fibers, gonioscopy, intraocular pressure) and complementary exams (visual fields and optical coherence tomography, OCT)[1]. Despite this, approximately 50% of glaucomas are undiagnosed[3][4].

Consequently, there is a need to develop technology to help diagnose glaucoma. OCTAngiography (OCTA) is a recent, non-invasive and fast technology that allows the visualization of retinal and papillary vessels, which can help to diagnose glaucoma[5]. However, before going into the details of OCTA, we should first focus on the vascular theory of glaucoma and vascularization of the optic nerve.

Vascular and Mechanical theories of glaucoma

The pathophysiology of glaucoma is not yet fully understood, but two theories try to explain the apoptosis of retinal ganglion cells[6].

A. Mechanical theory

The mechanical theory [7] explains apoptosis by disruption of the axonal transport of retinal ganglion cells (RGC) at the lamina cribrosa secondary to too high intraocular pressure (IOP). The lamina cribrosa becomes thinner and deformed, increasing the Cup / Disc ratio, impeding axoplasmic flow within the optic nerve fibers, ending with RGC apoptosis [8]. Many studies have shown IOP as a risk factor for developing glaucoma and its progression [9][10][11][12][13][14][15]. Nevertheless, this theory is insufficient to explain glaucoma because many glaucoma patients progress with normal IOP, and many patients have high IOP without developing glaucoma [13].

B. Vascular theory

The second theory is the vascular theory [12][16][17]: decreased ocular blood flow and optic nerve perfusion result in RGC apoptosis, secondary to mechanical effects such as IOP or systemic effects such as cardiovascular risk factors. The hypoperfusion and the loss of vascular autoregulation result in ischemia and oxidative stress [18].

Ocular perfusion pressure (OPP) can be defined[18] by the difference between arterial pressure (AP) and venous pressure (VP): OPP = AP –VP. Another equation is OPP = 2/3 mean arterial blood pressure – IOP. The intraocular arterial pressure is inaccessible directly, so we use the brachial mean arterial pressure (MAP): MAP = DBP + 1/3 (SBP − DBP), with SBP = systolic blood pressure and DBP = diastolic blood pressure.

The ocular arterial pressure has a nycthemeral variation, higher at night when lying down. For glaucomatous subjects, the difference between venous pressure and intraocular pressure is increased. Vascular resistance influences blood flow. The mathematical formula describing this resistance is R = (8 × n × l) / (π × r4) with n = blood viscosity, l = vascular length and r = vascular radius. Vascular length is constant in adult human beings; the diameter (radius * 2) remains the main factor controlling blood flow, increasing resistance reduce the blood flow. The loss of this regulatory mechanism can result in ischemia. For example, a 50% decrease in the vascular diameter reduces the flow by 94% [19]. Vasoregulators, either constrictors or dilators, control this diameter.

The primary vasodilator in the endothelium of the vessels is nitric oxide [20], which increases the level of cGMP, decreasing the level of intracellular calcium (Ca2 +) and reducing the phosphorylation of the loosening myosin chains. The two most effective mechanisms for creating vasodilation are hypoxia and hypercapnia. Vasodilation due to hypercapnia is seen in the choroid, retina, and optic nerve and is mediated by carbon monoxide and prostaglandins. Vasodilation secondary to hypoxia is observed in the retina. The aqueous humor of glaucomatous patients has increased nitric oxide concentration [21], probably by increased nitric oxide production by inducible NO synthetases in the optic nerve [22].

The main vasoconstrictor is endothelin-1 [22], which is secreted by the endothelium and mediates the two most potent vasoconstriction causes: hyperoxia and hypocapnia. Endothelin-1 is not involved in maintaining ocular basal blood flow in humans (in vitro comparison and measurement with Doppler ultrasound), according to one study [23].

Scientific evidence supports several aspects of the vascular theory. For example, arterial hypertension can correlate [24][25] with increased IOP, especially over 40 years. An increase in the mean arterial pressure of 10 mmHg was associated with an increase in IOP of 0.2-0.4 mmHg, according one study [17], but not in all. The nychthemeral variation of these two physiological variables also seems correlated [26]. Several studies have shown an association between arterial hypotension and primary open-angle glaucoma [17][27][28]. Intraocular pressure in glaucomatous patients is also associated with orthostatic arterial hypotension [29][30]. The visual fields in normal-pressure glaucoma have 2.6 times more relative risk of severity if associated with migraine [31]. Raynaud's syndrome is also observed more frequently in normal-pressure glaucoma than in primary open-angle glaucoma [32].

In conclusion, many studies support different aspects of each theory in glaucoma, but its pathogenesis is not fully understood.

Figure 1. Vascularization of the optic nerve.

Anatomy - Vascularization of the optic nerve

We present a brief anatomical review of the optic nerve to understand further how OCTA can aid in glaucoma diagnosis through visualizing blood flow. The optic nerve contains 1.2 million nerve fibers and is indirectly vascularized by the ophthalmic branch of the internal carotid artery. The optic nerve is 45-50 mm in length, including 1 mm intraocular, 25 mm intraorbital, 9 mm intra-canalicular, and 10-15 mm intracranial. In each of these paths, the vascularization is different[33][34][35]. Consequently, the intracranial optic nerve is supplied by the internal carotid artery, anterior cerebral and anterior communicating arteries. Pial branches from the ophthalmic artery and superior hypophyseal arteries[36] vascularize the intra-canalicular part. The ophthalmic artery and meningeal anastomoses perfuse the orbital region. The intraocular part further divides into four segments: retrolaminar, lamina cribrosa, prelaminar, and surface nerve fiber layer. Figure 1 shows the vascularization of the optic nerve. Pial arteries and sometimes an axial branch from the central retinal artery supply the retrolaminar part. Blood supply to the lamina cribrosa arises from short posterior ciliary arteries or by the circle of Zinn-Haller, in the sub-scleral space, when it exists. Anastomoses form the Zinn-Haller circle[37][38] from choroidal, pial, and perineural arteries and 4-8 posterior ciliary arteries. Peripapillary and choroid branches from posterior ciliary arteries vascularize the prelaminar region. Arterioles from the central retinal artery perfuse the surface nerve fiber layer of the optic disc.

All parts of the eye drain to the central retinal vein, which drains either into the cavernous sinus or the superior ophthalmic vein.

OCT, OCTA and glaucoma

Glaucomatous neuropathy can be assessed structurally using optical coherence tomography (OCT). OCT devices measure the thickness of several parameters associated with glaucoma, ranging from ganglion cells, retinal nerve fibers layer to the neuro-retinal rim [39]. The high resolution and reproducibility of this technology have been suggested to help in diagnosis and progression[40][41]. However, assessing a neurodegenerative disease by using neurons' thickness as a primary outcome is sub-optimal. Moreover, specificity and sensitivity vary significantly according to the glaucoma stage. Indeed, OCT can show differences in thickness before visual field changes in glaucoma (more valuable in mild glaucoma) while having a floor effect in more advanced stages of the disease (less helpful)[39].

Technology has therefore evolved further to capture a more dynamic component into these measurements. One example is retinal blood flow, which can provide additional information on the metabolic activity of these retinal cells and hopefully detect changes associated with disease before structural changes. Devices able to provide such information are called OCTA.

Historical considerations and functioning principles of OCT and OCTA

OCT is an imaging technique based on low-coherence interferometry, to scan tissues cross-sectionally, almost like a microscope. OCT bases on an analogous principle to ultrasound, but it measures the echo time delay and magnitude of light rather than sound, allowing better image resolution. Ultrasonography uses sound waves transmitted into the sample to perform the A-scan; the lag of waves reflected to the transductor determines the depth of the structures. Due to the high speed of the light in OCT, the lag time cannot be measured; hence indirect light assessment was developed: low coherence interferometry. The light reflected by the sample correlates with light that has traveled a known reference path with a translating mirror. Optical interference between both beams of light is demodulated to produce an assessment of ocular structures[42].

Fercher et al. presented low coherence interferometry for measurements of ocular structures [43]. In the early 90s, Fujimoto et al. further developed OCT in the Massachusetts Institute of Technology[44]. The first OCT was introduced to the ophthalmologic market in 1996 by Zeiss and used time-domain technology (TD-OCT). Moving the reference mirror allowed the detection of different depths in ophthalmic tissue and the establishment of an A-scan, but this moving mirror limited the scanning speed.

In 2002, spectral domain-OCT was developed. Based on a Fourier-transformation of the detected frequencies, this technic improved the signal analysis, noise, and sensitivity, compared with TD-OCT[45]. The imaging speed was increased, without compromising the signal quality, thanks to the absence of reference mirror movement. TD-OCT and the firsts SD-OCT used a wavelength of ≈800 nm. In 2005, a TD-OCT of 1040 nm enhanced choroid penetration. Then, Swept-source OCT (SS-OCT) was developed[46]. TD-OCT was too slow to assess retinal vasculature, but SD-OCT and SS-OCT revived this interest. For more information regarding OCT, visit the respective eyewiki page.

OCT-Angiography (OCTA) measured the reflection changes caused by moving particles (erythrocytes) flowing through vessels. Repeatedly capturing OCTs at the same retinal acquisition plane allowed the establishment of image contrast between the perfused vessels and the surrounding unmoving tissues [47]. OCTA, which enabled fast, non-invasive, high-resolution imaging of in vivo retinal and choroidal vasculature, was born. In 2015, the first OCTA was commercialized. Since then, several OCTA algorithms were proposed for OCTA image reconstruction and vessel density (VD) quantification.

Algorithms and devices

Commercial OCTA devices use different algorithms (ways of approaching the same technology). The first were the split-spectrum amplitude-decorrelation angiography (SAADA)[47][48] by the AngioVue® device (Optovue®), and the OCT-based microangiography (OMAG) by Angioplex® (Zeiss®) [49]. Meanwhile, other algorithms or techniques have been developed, such as the OCTA ratio analysis (OCTARA) in the swept-source OCTA by TopCon®. Different algorithms include a combined intensity and phase-decorrelation method used by AngioScan® (NIDEK®), intensity-decorrelation in SPECTRALIS® (Heidelberg Engineering®) and Canon®, which introduced the Angio Xephilio®. TopCon®(Triton™ DRI), Canon® (Angio Xephilio®) and Zeiss® (PLEX® Elite) provide swept-source OCTA solutions, thus providing higher speed and resolution and increased quality when studying the choroidal layers.

All of these devices lead to slightly different images and metrics [50]. Moreover, several of them have different depths to define each studied layer by default. As a result, direct comparisons are not equivalent across devices for the same patient.

Figure 2. OCTA terminology

Terminology in OCTA

For coherence, we present OCTA-related definitions [5] (figure 2):

·      Vessel density (VD): the percentage of area occupied by vessels, pictured by lighter tones of grey

·      Whole-image VD: the VD detected in the entire scan (whole-image optic disc, whole-image macular scan, etc.)

·      Peripapillary VD: the VD within a 750-µm-wide annulus extending from the optic disc boundary.

·      Parafoveal VD: the VD between two circles centered in the fovea with diameters of 1 mm and 3 mm

·      Perifoveal VD: the VD within diameters of 3 mm and 5 mm.

Technique description

As an example of performing OCTA in glaucoma, we used Triton (Topcon®, Japan), after pupillary dilatation if the pupil was smaller than 4 mm, with a scan size of 4.5 x 4.5 mm, centered on the optic disc. Triton provides a grayscale for each slab and a color image with the combination of all slabs [5] (figures in clinical cases below). This device presents a qualitative impression of vessel density (VD). We should exclude low-quality images with signal strength index (SSI) less than 40 (or 6 in Zeiss), motion artifacts, vessel segmentation, or media opacities. Video 1 shows one example of OCTA acquisition. Below (in clinical cases), we present several images as examples of OCTA.

Figure 3. OCTA of a healthy person, centered in the optic disc.

Figure 4. OCTA of a glaucomatous patient (darker greys and bluer color are appreciated compared to a healthy subject).

OCTA and diagnostics of glaucoma

OCTA helps in the diagnosis of glaucoma, providing both functional and structural information [5]. Our recent meta-analysis concluded that vessel density (VD) is lower in glaucoma eyes compared with controls in all macular and peripapillary regions assessed [5], as appreciated in figures 3 and 4. It seems that reduction in perfusion is more pronounced in superficial layers, both in the peripapillary [51] and macular [52] regions. This VD decrease was more pronounced in advanced glaucoma than moderate-mild glaucoma [52][53][54][55][56].

Microvascular dropout (MvD) is the choriocapillaris loss in regions of parapapillary atrophy [57][58], often inferotemporally within ß-zone[59] .  MvD was associated with structural (RNFL thinning and lamina cribrosa defects) and functional (VF loss) defects[57][60] and disc hemorrhages [61]. Similar to VD, the prevalence and size of MvD increase with glaucoma severity [57][62]. MvD also seemed to predict a faster rate of RNFL thinning and VF loss [63].

The diagnostic performance of OCTA was compared with OCT, namely with RNFL thickness and GCC thickness, was similar [53][64][65]. However, some studies reported a better sensitivity of RNFL (OCT) in early glaucoma [66]. Several other studies reported a better correlation between visual field (VF) and VD than between VF and OCT [5], being this correlation stronger in eyes with high myopia [67] and advanced glaucoma [68].

OCTA and longitudinal studies

The majority of longitudinal OCTA studies in glaucoma with at least three months of follow-up found an association between OCTA changes and structural (OCT) and functional (VF) decline [69].  VD decline correlated with baseline values [70][71], the difference between control and glaucoma[72], and progression measured by OCT [73] and VF [71]. A faster loss of macular VD (OCTA) in POAG  than glaucoma-suspect or healthy eyes was observed, but not significantly in GCC (OCT)[73]. Software-assisted removal of large vessels [74] better allowed to identify VD decline.

Despite the lack of long-term follow-up studies to ascertain the role of OCTA in glaucoma progression, some studies demonstrated its ability to detect disease progression in superficial VD [74]. Moreover, lower baseline peripapillary and macular VD were associated with a faster rate of RNFL progression in mild to moderate glaucoma in a study with a mean follow-up over two years [75].  This association was independent of the baseline RNFL thickness, suggesting that OCTA may offer an additional contribution to assess glaucoma risk of progression [65]. However, VD is more sensitive than RNFL to IOP changes and variations in systemic perfusion and retinal oxygenation[65].

The current limitation to fully assess OCTA in glaucoma is the lack of standardization in protocol and devices and the scarcity of long-term longitudinal studies. Nevertheless, it was possible to detect a decrease in VD through glaucoma progression, according to a recent systematic review[70]. It was possible to show decreased VD with glaucoma aggravation, but is it possible to see VD improvement after surgery?

OCTA and glaucoma surgery

Currently, a few studies have evaluated the VD response to glaucoma surgery using OCTA [76][73][77][78]. Surgically-induced IOP-lowering causes changes in ocular hemodynamics[79], specifically an increase in ocular blood flow [80][81]. A significant increase in microvascular VD was noted after glaucoma surgery in several studies [76][82][83] (except one[73]). VD increase correlated with higher preoperative IOP, more significant IOP reduction, and reduced lamina cribrosa depth. The microvascular response seemed different between retinal territories. In particular, a study[78] showed that peripapillary VD was IOP-independent within the studied range of surgically controlled IOP, while macular VD revealed a delayed response followed by near-normal reperfusion after glaucoma surgery. OCTA may play a promising role in evaluating vascular recovery post-glaucoma surgery.

However, the available studies present limitations, including a short follow-up period (ranging from 3-months to 1-year)[70]. Also, few studies recorded the number of topical anti-glaucoma medications in the postoperative period, except for one study[78], the remainder evaluated only trabeculectomy. Nevertheless, it seems VD changes after glaucoma surgery, and OCTA could evaluate vascular recovery.

Figure 5. OCTA of iris versus iritis. On the left side of the figure, we present the normal iris vascularization. On the right side, iritis is visible, showing vessel dilation and irregularity.

OCTA of the anterior segment

Figure 6. OCTA of the anterior segment showing an avascular filtration bleb.

We have mentioned OCTA utilization in assessing papillary and retinal vascularization, but OCTA of the anterior segment can also be of value, namely for evaluating the filtration bleb.

Trabeculectomy is the most common glaucoma surgery[1]. Nonetheless, fibrosis (scar formation) is the primary cause of failure of glaucoma surgeries [84]. Angiogenesis is essential for the wound-healing process, and inflammation promotes bleb vascularization and fibrosis [85]. Thus, a meticulous clinical follow-up of the filtering bleb is necessary, and an avascular bleb is predictive of a functioning bleb. There are slit-lamp bleb evaluation scales, namely Indiana Bleb Appearance Grading Scale [86] or Moorfields Bleb Grading Scale[87] . Both scales focus on the vascularity of the bleb, but this clinical evaluation remains subjective and not reproductive.

OCTA of the anterior segment was used to evaluate corneal, iris, and conjunctival vessels [88] and for filtering bleb evaluation.  Figure 5 depicts the difference between normal iris and iritis distinguished by OCTA. Yin et al. found a peak in bleb vessel density (VD) one month after trabeculectomy using OCTA, identifying a correlation between the vessel area one month post-trabeculectomy and IOP six months post-surgery[89]. OCTA color and brightness density of the bleb-wall correlated with the clinical bleb scales in 92 patients who underwent trabeculectomy[90]. Hayek et al.[91] studied the conjunctiva before and after trabeculectomy and concluded that preoperative VD is a good indicator of surgical success. Poor conjunctival vascularization was associated with lower IOP and more intraepithelial microcysts on OCTA at six months of follow-up[91].

As for micro-invasive glaucoma surgeries (MIGS), filtration bleb after XEN surgery was evaluated with OCTA[92]. Successful filtration bleb after XEN gel implantation presented numerous and large areas of vessel displacement with the bleb-wall, along with a rarefied vascular network. Postoperative intraocular pressure correlated with low bleb-wall VD.

In conclusion, OCTA seems to gain a prominent role in postoperative bleb assessment. An avascular bleb is ideal, such as the one observed in figure 6. An OCTA classification could help clinicians in patient management.

OCTA and systemic and neuro-ophthalmological diseases

The possibility of direct viewing and quantifying ocular blood flow with OCTA gained the attention of several fields other than glaucoma and even outside ophthalmology.

OCTA and systemic pathologies

The application of this technology in disease detection and monitoring in cardiovascular diseases is flourishing. Microvascular vessel density (VD) decrease was found in hypertension, kidney disease, preeclampsia, coronary artery disease, and carotid artery stenosis [93].  Although vascular changes are a hallmark in diabetic retinopathy, diabetic patients show changes in the retinal vascular plexus in OCTA even before retinopathy [94]

Vascular abnormalities were further described in neurological conditions such as multiple sclerosis (MS), Alzheimer's disease, and Parkinson's disease with disease severity association in some studies[95]. Autoimmune diseases with vessel dysfunction such as systemic lupus erythematosus and rheumatoid arthritis likewise showed vessel rarefaction on OCTA[96]. Drug toxicity screening might be a novel use for OCTA, as abnormalities in hydroxychloroquine or tamoxifen users without retinopathy were detected[97]. In the wake of the COVID-19 pandemic, OCTA was used to analyze the retinal vasculature of patients with resolved SARS-COV-2 infection[98].

Multiple sclerosis

Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system leading to demyelination in cerebral regions. Optic neuritis (ON) represents the most common ocular manifestation of MS[99]. The macular vessel density (VD) is significantly reduced in patients with MS comparing to healthy subjects [100][101] independently of the previous ON (according to some studies[101][100], but not all[102]).

The optic nerve head (ONH) flow index was significantly lower for MS with a history of ON, compared to healthy subjects and MS without ON[103]. Similarly, a microvascular peripapillary VD decrease was found in MS. The rarefaction of retinal and optic nerve VD in MS is possibly due to reduced metabolic supply or inflammatory processes[95].

Anterior ischemic optic neuropathy

Anterior ischemic optic neuropathy (AION) affects the anterior portion of the optic nerve and divides into non-arteritic (NA-AION) and arteritic (A-AION). The NA-AION is the most common, occurring in middle-aged and elderly patients, and is associated with cardiovascular risk factors. The second often associates with giant cell arteritis. NA-AION might be related to transient hypoperfusion or non-perfusion of the optic nerve head[104]. One study found a macular VD decrease in the contralateral eye of NA-AION [105], but not another[106]. Peripapillary VD correlated with visual field defects[107].

OCTA shows a reduction in peripapillary VD, macular capillary VD, and choroidal VD in the atrophic stage of NA-AION[107]. At the acute phase, edema hinders the assessment of the peripapillary plexus; hence, RNFL segmentation allows better visualization due to reduced edema-related darkening [108]. Peripapillary VD was lower for patients with NA-AION than in the fellow eye and the affected eye of patients with other diseases[109]. OCTA cannot differentiate the two types of AION. Nevertheless, there seems to be a significantly worse optic nerve hypoperfusion for A-AION compared to NA-AION[106].

Leber hereditary optic neuropathy

Leber hereditary optic neuropathy is a rare genetic disorder inherited by the maternal mitochondrial DNA, affecting young males. At the acute stage, tortuosity and swelling of the peripapillary capillaries were described[110]. OCTA studies showed a gradual reduction of peripapillary capillary VD, beginning temporally [111] even before RNFL thinning. Parafoveal VD was also decreased, mainly in nasal and inferior regions, reflecting damage of the papillomacular bundle[112].

Dominant optic atrophy

Dominant optic atrophy is a mitochondrial inherited optic neuropathy affecting children. It is characterized by bilateral degeneration of retinal ganglion cells and their axons with optic disc atrophy and pallor, causing insidious visual loss. Most cases are associated with mutations in the OPA1 gene, with incomplete penetrance and variable expression[113].

OCTA shows a diffuse decrease of peripapillary and parafoveal VD. VD reduction correlates with RNFL and GCC thickening and visual field loss[114].

Optic disc swelling

Bilateral optic disc edema is often related to papilledema and requires magnetic resonance imaging of the brain. Fluorescein angiography can help diagnose AION if there is perfusion delay or hypoperfusion of the optic nerve head. Otherwise, diffuse dye leakage hides optic microvasculature.

A study assessed peripapillary vascular changes in acute optic disc swelling due to different etiologies[115]. The peripapillary VD was significantly lower in NA-AION than papilledema. However, the distinction between other diseases was less clear (optic neuritis, papilledema, and A-AION). Peripapillary VD tended to decrease in idiopathic intracranial hypertension (IIC) compared to healthy subjects, but not in regressed papilledema[116]. Another study identified no difference in IIC after excluding the large vessels[117]. Further research is required to clarify the vascular changes in patients with acute optic disc swelling.

OCTA was also studied to distinguish papilledema from pseudopapilledema[117]. This can be exciting due to the underlying condition of papilledema that can threaten the life's patient. Whole and nasal peripapillary capillary VD were reduced for pseudopapilledema compared to papilledema. This difference was not statistically significant in severe papilledema but was in low-grade papilledema. OCTA could be promising to help differentiate mild papilledema from pseudopapilledema.

Optic disc drusen

Optic disc drusen (ODD) are acellular deposits within the optic nerve head, well diagnosed by autofluorescence, echography, and enhanced depth-OCT[118]. These deposits are often bilateral and lead to progressive visual field loss due to degenerative optic neuropathy[118]. Mechanical compression of retinal nerve fibers by drusen in the optic disc or vascular theory are potential explanations.

Peripapillary microvascular density is reduced in ODD compared to healthy subjects[119]. Low peripapillary VD was associated with visual field loss[120]. One study of macular microvasculature supply found no difference between ODD and healthy subjects[119]. Moreover, macular vessel diameter and flux increased in patients with ODD and visual field loss, without changes in RNFL, GCC, and peripapillary VD. Increased macular vessel diameter could be an early marker for visual field loss.

Compressive optic neuropathy

Compressive optic neuropathy results from mechanical compression secondary to a tumor or benign lesions. The compression can occur in the anterior visual pathway (optic nerve) or posteriorly.

A study of optic pathway gliomas identified a decrease in RNFL and GCC thickness (OCT) and in peripapillary VD (OCTA). Macular VD was decreased compared to healthy subjects, but not optic disc VD[121]. Studies of chiasmatic compressive optic neuropathy linked to pituitary adenomas found reduced peripapillary VD and superficial capillary (SCP) perfusion, but normal deep capillary perfusion compared to healthy eyes[122]. Peripapillary VD loss affected temporal and nasal sectors, with sparing of superior and inferior areas, which is consistent with several studies relating severe temporal RNFL thinning[123][124]. VD loss was associated with OCT and visual field defects. In a unilateral postgeniculate visual pathway lesion, a similar pattern distribution for GCC thinning (OCT) and reduction of macular superficial density and peripapillary VD (OCTA)were observed[125].

Radiation optic neuropathy

Radiation retinopathy and radiation optic neuropathy are complications of radiation treatment. In eyes treated with brachytherapy for uveal melanoma and with radiation retinopathy or optic neuropathy, the decrease of peripapillary VD correlated with the radiation dose to the optic disc and the visual acuity[126]. Recently, a prospective study confirmed peripapillary and macular ischemia induced by brachytherapy, and a grading system based on OCTA VD was proposed[127].

Clinical cases and images of OCTA and glaucoma

Figure 7. Macular OCTA of healthy versus glaucomatous patient.

We present some examples of OCTA application in clinical practice.

Healthy patient - optic nerve OCTA

Figure 3 (above) shows the OCTA scan of the optic nerve of a healthy patient with Triton device. Triton scans the optic disc using a long-wavelength scanning light of 1050nm at a speed of 100000 A-scans per second. This device analyses different retinal slabs (or retinal depths): optic nerve, radial peripapillary capillary (RPC), vitreous, choroid, as seen in the figure. It provides a grayscale for each slab and a color image (density map) with the combination of all slabs. It also shows an eye fundus image and OCT B-scan. At the moment, this device presents only qualitative VD for the optic disc. This healthy subject has light grays in all slabs and a predominance of red colors, showing high VD.

Glaucomatous patient - whole-image optic nerve OCTA

Figure 4 (above) shows the OCTA of a glaucomatous patient with Triton. We can appreciate darker gray shadows in each slab. A whole-image optic nerve VD decrease is visible in the density map, illustrated by darker and bluer colors, more pronounced in the inferior hemifield.

Glaucomatous versus healthy patient – whole-image macular OCTA

Figure 7 illustrates the whole-image macular OCTA of a glaucomatous patient (above) and compares it to a healthy patient (below). We can appreciate located darker zones in nearly all OCTA slabs (depths) in glaucoma (blue arrows), more evident in the color image. There were minor movement artifacts in the glaucoma OCTA (stars).

Figure 8. OCTA of asymmetric glaucoma and respective visual fields.

Advanced asymmetric glaucoma and myopia

We depict a patient with myopia and advanced asymmetric glaucoma. The visual field of the left eye (left-side of figure 8, "OS") is almost lost (mean deviation of -28dB), and the respective whole-image optic nerve OCTA is very dark (the "colour map" is blue, showing an extremely decreased VD). The right visual field shows a less severe but advanced loss, and the right OCTA is less altered. Notice that the OCTA of the right eye has movement artifacts and has an SSI of 48, less than recommended. The peripapillary atrophy shown in the retinography is consistent with myopia.

OCTA VD increase after glaucoma surgery

Figure 9 shows two patients who had laser suture lysis to further decrease IOP during the first month after a trabeculectomy. An OCTA was performed before and 15 minutes after laser suture lysis. This maneuver allowed an IOP decrease and a VD increase in localized regions (red ovals), possibly reflecting vascularization improvement.

Figure 9. VD increase after IOP decrease during the postoperative period.

Figure 10. Macular OCTA of the same patient with 2 devices.

Figure 11. Optic nerve OCTA of the same patient with two devices.

Two OCTA devices with the same patient

Figures 10 and 11 depict the same patient with two different OCTA devices (Triton on the right and Angiovue on the left). Figure 10 illustrates a macular OCTA scan, while figure 11 shows an optic nerve scan.


In conclusion, OCTA is a non-invasive, rapid, and evolving technology that has shown to be valuable in the diagnosis and follow-up of glaucoma, among other ophthalmic pathologies.

Additional Resources

Below are some informative OCTA books:

  • Practical Handbook of OCT Angiography Bruno Lumbroso Jaypee Brothers Medical Publishers (P) Ltd; ISBN : 9789385999970. 2006
  • Atlas d'Angiographie OCT Clinique B.Lumbroso, D. Huang, C.J. Chen, Y.Jia, M.Rispoli, A.Romano, N.K.Waheed. 2006.


  1. 1.0 1.1 1.2 European Glaucoma Society Terminology and Guidelines for Glaucoma, 4th Edition - Chapter 2: Classification and terminology. British Journal of Ophthalmology (2017;101:80-85).
  2. Quigley, H.A. and A.T. Broman, The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol, 2006. 90(3): p. 262-7.
  3. Mitchell, P., et al., prevalence of open-angle glaucoma in Australia. The Blue Mountains Eye Study. Ophthalmology, 1996. 103(10): p. 1661-9.
  4. Keel, S., et al., Prevalence of glaucoma in the Australian National Eye Health Survey. Br J Ophthalmol, 2019. 103(2): p. 191-195.
  5. 5.0 5.1 5.2 5.3 5.4 5.5 Miguel, A.I.M., A.B. Silva, and L.F. Azevedo, Diagnostic performance of optical coherence tomography angiography in glaucoma: a systematic review and meta-analysis. Br J Ophthalmol, 2019.
  6. Fechtner, R.D. and R.N. Weinreb, Mechanisms of optic nerve damage in primary open angle glaucoma. Surv Ophthalmol, 1994. 39(1): p. 23-42.
  7. Yan, D.B., et al., Deformation of the lamina cribrosa by elevated intraocular pressure. Br J Ophthalmol, 1994. 78(8): p. 643-8.
  8. Quigley, H.A., et al., Morphologic changes in the lamina cribrosa correlated with neural loss in open-angle glaucoma. Am J Ophthalmol, 1983. 95(5): p. 673-91.
  9. Sommer, A., et al., Relationship between intraocular pressure and primary open angle glaucoma among white and black Americans. The Baltimore Eye Survey. Arch Ophthalmol, 1991. 109(8): p. 1090-5.
  10. Investigators, A., The Advanced Glaucoma Intervention Study (AGIS): 11. Risk factors for failure of trabeculectomy and argon laser trabeculoplasty. Am J Ophthalmol, 2002. 134(4): p. 481-98.
  11. Gordon, M.O., et al., The Ocular Hypertension Treatment Study: baseline factors that predict the onset of primary open-angle glaucoma. Arch Ophthalmol, 2002. 120(6): p. 714-20; discussion 829-30.
  12. 12.0 12.1 Leske, M.C., et al., Predictors of long-term progression in the early manifest glaucoma trial. Ophthalmology, 2007. 114(11): p. 1965-72.
  13. 13.0 13.1 Varma, R., et al., Four-year incidence of open-angle glaucoma and ocular hypertension: the Los Angeles Latino Eye Study. Am J Ophthalmol, 2012. 154(2): p. 315-325 e1.
  14. Jampel, H.D., et al., Perioperative complications of trabeculectomy in the collaborative initial glaucoma treatment study (CIGTS). Am J Ophthalmol, 2005. 140(1): p. 16-22.
  15. Robert N. Weinreb, T.A., Felipe A. Medeiros. , The Pathophysiology and Treatment of Glaucoma: A Review. JAMA - Journal of the American Medical Association, 2014 311(18): 1901–1911. doi:  10.1001/jama.2014.3192
  16. Flammer, J., The vascular concept of glaucoma. Surv Ophthalmol, 1994. 38 Suppl: p. S3-6.
  17. 17.0 17.1 17.2 Bonomi, L., et al., Vascular risk factors for primary open angle glaucoma: the Egna-Neumarkt Study. Ophthalmology, 2000. 107(7): p. 1287-93.
  18. 18.0 18.1 Schmidl, D., G. Garhofer, and L. Schmetterer, The complex interaction between ocular perfusion pressure and ocular blood flow - relevance for glaucoma. Exp Eye Res, 2011. 93(2): p. 141-55.
  19. Mottet, B., et al., Vascular factors in glaucoma. Journal Francais d'Ophtalmologie, 2015. 38(10): p. 983-995.
  20. Schmetterer, L. and K. Polak, Role of nitric oxide in the control of ocular blood flow. Prog Retin Eye Res, 2001. 20(6): p. 823-47.
  21. Ghanem, A.A., A.M. Elewa, and L.F. Arafa, Endothelin-1 and nitric oxide levels in patients with glaucoma. Ophthalmic Res, 2011. 46(2): p. 98-102.
  22. 22.0 22.1 Toda, N. and M. Nakanishi-Toda, Nitric oxide: ocular blood flow, glaucoma, and diabetic retinopathy. Prog Retin Eye Res, 2007. 26(3): p. 205-38.
  23. Polak, K., et al., Regulation of human retinal blood flow by endothelin-1. Exp Eye Res, 2003. 76(5): p. 633-40.
  24. Dielemans, I., et al., Primary open-angle glaucoma, intraocular pressure, and systemic blood pressure in the general elderly population. The Rotterdam Study. Ophthalmology, 1995. 102(1): p. 54-60.
  25. Bulpitt, C.J., C. Hodes, and M.G. Everitt, Intraocular pressure and systemic blood pressure in the elderly. Br J Ophthalmol, 1975. 59(12): p. 717-20.
  26. Bulpitt, C.J., C. Hodes, and M.G. Everitt, Intraocular pressure and systemic blood pressure in the elderly. Br J Ophthalmol, 1975. 59(12): p. 717-20.
  27. Tielsch, J.M., et al., Hypertension, perfusion pressure, and primary open-angle glaucoma. A population-based assessment. Arch Ophthalmol, 1995. 113(2): p. 216-21.
  28. Tokunaga, T., et al., Association between nocturnal blood pressure reduction and progression of visual field defect in patients with primary open-angle glaucoma or normal-tension glaucoma. Jpn J Ophthalmol, 2004. 48(4): p. 380-5.
  29. Tokunaga, T., et al., Association between nocturnal blood pressure reduction and progression of visual field defect in patients with primary open-angle glaucoma or normal-tension glaucoma. Jpn J Ophthalmol, 2004. 48(4): p. 380-5.
  30. Kaiser, H.J., et al., Systemic blood pressure in glaucoma patients. Graefes Arch Clin Exp Ophthalmol, 1993. 231(12): p. 677-80.
  31. Drance, S., et al., Risk factors for progression of visual field abnormalities in normal-tension glaucoma. Am J Ophthalmol, 2001. 131(6): p. 699-708.
  32. Gasser, P. and J. Flammer, Blood-cell velocity in the nailfold capillaries of patients with normal-tension and high-tension glaucoma. Am J Ophthalmol, 1991. 111(5): p. 585-8.
  33. Francois, J. and A. Fryczkowski, The blood supply of the optic nerve. Adv Ophthalmol, 1978. 36: p. 164-73.
  34. Potts, A.M., The blood supply of the optic nerve and optic papilla. Trans Am Acad Ophthalmol Otolaryngol, 1969. 73(5): p. 886-9.
  35. Vail, D., The blood supply of the optic nerve and its clinical significance. Am J Ophthalmol, 1948. 31(1): p. 1-12.
  36. van Overbeeke, J. and L. Sekhar, Microanatomy of the blood supply to the optic nerve. Orbit, 2003. 22(2): p. 81-8.
  37. Hollo, G., Peripapillary circle of Zinn-Haller revealed by fundus fluorescein angiography. Br J Ophthalmol, 1998. 82(3): p. 332-3.
  38. Park, K.H., et al., In vivo detection of perineural circular arterial anastomosis (circle of Zinn-Haller) in a patient with large peripapillary chorioretinal atrophy. Am J Ophthalmol, 1996. 122(6): p. 905-7.
  39. 39.0 39.1 Bussel, II, G. Wollstein, and J.S. Schuman, OCT for glaucoma diagnosis, screening and detection of glaucoma progression. Br J Ophthalmol, 2014. 98 Suppl 2: p. ii15-9.
  40. Bockova, M., et al., Sensitivity and specificity of spectral OCT in patients with early glaucoma. Cesk Slov Oftalmol, 2019. 75(5): p. 260-264.
  41. Vidotti, V.G., et al., Sensitivity and specificity of machine learning classifiers and spectral domain OCT for the diagnosis of glaucoma. Eur J Ophthalmol, 2012: p. 125.
  42. Fujimoto, J.G., Optical coherence tomography for ultrahigh resolution in vivo imaging. Nature Biotechnology, 2003. 21(11): p. 1361-1367.
  43. Fercher, A.F., K. Mengedoht, and W. Werner, Eye-length measurement by interferometry with partially coherent light. Opt Lett, 1988. 13(3): p. 186-8.
  44. Huang, D., et al., Optical coherence tomography. Science, 1991. 254(5035): p. 1178-81.
  45. Leitgeb, R., C. Hitzenberger, and A. Fercher, Performance of fourier domain vs. time domain optical coherence tomography. Opt Express, 2003. 11(8): p. 889-94.
  46. Zheng, K., et al., Experimental confirmation of potential swept source optical coherence tomography performance limitations. Appl Opt, 2008. 47(33): p. 6151-8.
  47. 47.0 47.1 Jia, Y., et al., Split-spectrum amplitude-decorrelation angiography with optical coherence tomography. Opt Express, 2012. 20(4): p. 4710-25.
  48. Zhang, A., et al., Methods and algorithms for optical coherence tomography-based angiography: A review and comparison. Journal of Biomedical Optics, 2015. 20(10).
  49. An, L., M. Johnstone, and R.K. Wang, Optical microangiography provides correlation between microstructure and microvasculature of optic nerve head in human subjects. J Biomed Opt, 2012. 17(11): p. 116018.
  50. Zhang, A., et al., Methods and algorithms for optical coherence tomography-based angiography: a review and comparison. J Biomed Opt, 2015. 20(10): p. 100901.
  51. Liu, L., et al., Projection-Resolved Optical Coherence Tomography Angiography of the Peripapillary Retina in Glaucoma. Am J Ophthalmol, 2019. 207: p. 99-109.
  52. 52.0 52.1 Takusagawa, H.L., et al., Projection-Resolved Optical Coherence Tomography Angiography of Macular Retinal Circulation in Glaucoma. Ophthalmology, 2017. 124(11): p. 1589-1599.
  53. 53.0 53.1 Mansoori, T., et al., Radial Peripapillary Capillary Density Measurement Using Optical Coherence Tomography Angiography in Early Glaucoma. J Glaucoma, 2017. 26(5): p. 438-443.
  54. Liu, L., et al., Optical Coherence Tomography Angiography of the Peripapillary Retina in Glaucoma. JAMA Ophthalmol, 2015. 133(9): p. 1045-52.
  55. Shin, J.W., et al., Regional vascular density-visual field sensitivity relationship in glaucoma according to disease severity. Br J Ophthalmol, 2017. 101(12): p. 1666-1672.
  56. Yarmohammadi, A., et al., Peripapillary and Macular Vessel Density in Patients with Primary Open-Angle Glaucoma and Unilateral Visual Field Loss. Ophthalmology, 2018. 125(4): p. 578-587.
  57. 57.0 57.1 57.2 Suh, M.H., et al., Deep Retinal Layer Microvasculature Dropout Detected by the Optical Coherence Tomography Angiography in Glaucoma. Ophthalmology, 2016. 123(12): p. 2509-2518.
  58. Lee, E.J., et al., Underlying Microstructure of Parapapillary Deep-Layer Capillary Dropout Identified by Optical Coherence Tomography Angiography. Invest Ophthalmol Vis Sci, 2017. 58(3): p. 1621-1627.
  59. Bojikian, K.D., P.P. Chen, and J.C. Wen, Optical coherence tomography angiography in glaucoma. Curr Opin Ophthalmol, 2019. 30(2): p. 110-116.
  60. Lee, E.J., et al., Parapapillary Deep-Layer Microvasculature Dropout in Glaucoma: Topographic Association With Glaucomatous Damage. Invest Ophthalmol Vis Sci, 2017. 58(7): p. 3004-3010.
  61. Park, H.L., J.W. Kim, and C.K. Park, Choroidal Microvasculature Dropout Is Associated with Progressive Retinal Nerve Fiber Layer Thinning in Glaucoma with Disc Hemorrhage. Ophthalmology, 2018. 125(7): p. 1003-1013.
  62. Shin, J.W., et al., Choroidal Microvasculature Dropout is Not Associated With Myopia, But is Associated With Glaucoma. J Glaucoma, 2018. 27(2): p. 189-196.
  63. Kwon, J.M., et al., Parapapillary Deep-Layer Microvasculature Dropout and Visual Field Progression in Glaucoma. Am J Ophthalmol, 2019. 200: p. 65-75.
  64. Chen, H.S., et al., Optical Coherence Tomography Angiography of the Superficial Microvasculature in the Macular and Peripapillary Areas in Glaucomatous and Healthy Eyes. Invest Ophthalmol Vis Sci, 2017. 58(9): p. 3637-3645.
  65. 65.0 65.1 65.2 Rao, H.L., et al., Diagnostic ability of peripapillary vessel density measurements of optical coherence tomography angiography in primary open-angle and angle-closure glaucoma. Br J Ophthalmol, 2017. 101(8): p. 1066-1070.
  66. Chung, J.K., et al., Glaucoma Diagnostic Ability of the Optical Coherence Tomography Angiography Vessel Density Parameters. Curr Eye Res, 2017. 42(11): p. 1458-1467.
  67. Shin, J.W., et al., Relationship between vessel density and visual field sensitivity in glaucomatous eyes with high myopia. Br J Ophthalmol, 2018.
  68. Ghahari, E., et al., Association of Macular and Circumpapillary Microvasculature with Visual Field Sensitivity in Advanced Glaucoma. Am J Ophthalmol, 2019. 204: p. 51-61.
  69. Werner, A.C. and L.Q. Shen, A Review of OCT Angiography in Glaucoma. Semin Ophthalmol, 2019. 34(4): p. 279-286.
  70. 70.0 70.1 70.2 Miguel, A., et al., OCT-angiography detects longitudinal microvascular changes in glaucoma: a systematic review. Br J Ophthalmol, 2021.
  71. 71.0 71.1 Park, H.Y., et al., Association Between Parapapillary Choroidal Vessel Density Measured With Optical Coherence Tomography Angiography and Future Visual Field Progression in Patients With Glaucoma. JAMA Ophthalmol, 2019. 137(6): p. 681-688.
  72. Shin, J.W., et al., Peripapillary Microvascular Improvement and Lamina Cribrosa Depth Reduction After Trabeculectomy in Primary Open-Angle Glaucoma. Invest Ophthalmol Vis Sci, 2017. 58(13): p. 5993-5999.
  73. 73.0 73.1 73.2 73.3 Lommatzsch, C., et al., Retinal perfusion 6 months after trabeculectomy as measured by optical coherence tomography angiography. 2019.
  74. 74.0 74.1 Hollo, G., Influence of Removing the Large Retinal Vessels-related Effect on Peripapillary Vessel Density Progression Analysis in Glaucoma. J Glaucoma, 2018. 27(8): p. e137-e139.
  75. Moghimi, S., et al., Macular and Optic Nerve Head Vessel Density and Progressive Retinal Nerve Fiber Layer Loss in Glaucoma. Ophthalmology, 2018. 125(11): p. 1720-1728.
  76. 76.0 76.1 Shin, J.W., et al., Peripapillary Microvascular Improvement and Lamina Cribrosa Depth Reduction After Trabeculectomy in Primary Open-Angle Glaucoma. Invest Ophthalmol Vis Sci, 2017. 58(13): p. 5993-5999.
  77. Shoji, T., et al., Progressive Macula Vessel Density Loss in Primary Open-Angle Glaucoma: A Longitudinal Study. Am J Ophthalmol, 2017. 182: p. 107-117.
  78. 78.0 78.1 78.2 Ch’ng, T.W., et al., - Effect of surgical intraocular pressure lowering on retinal structures-nerve fibre layer, foveal avascular zone, peripapillary and macular vessel density: 1 year results. 2019: p. 110.
  79. Trible, J.R., et al., Trabeculectomy is associated with retrobulbar hemodynamic changes. A color Doppler analysis. Ophthalmology, 1994. 101(2): p. 340-51.
  80. Kuerten, D., et al., Long term effect of trabeculectomy on retrobulbar haemodynamics in glaucoma. Ophthalmic Physiol Opt, 2015. 35(2): p. 194-200.
  81. Berisha, F., et al., Effect of trabeculectomy on ocular blood flow. Br J Ophthalmol, 2005. 89(2): p. 185-8.
  82. In, J.H., et al., Peripapillary Vessel Density Reversal after Trabeculectomy in Glaucoma. J Ophthalmol, 2018. 2018: p. 8909714.
  83. Kim, J.A., et al., Microvascular Changes in Peripapillary and Optic Nerve Head Tissues After Trabeculectomy in Primary Open-Angle Glaucoma. Investigative Ophthalmology & Visual Science, 2018. 59(11): p. 4614-4621.
  84. Landers, J., et al., A twenty-year follow-up study of trabeculectomy: risk factors and outcomes. Ophthalmology, 2012. 119(4): p. 694-702.
  85. Joseph, J.P., M.H. Miller, and R.A. Hitchings, Wound healing as a barrier to successful filtration surgery. Eye (Lond), 1988. 2 Suppl: p. S113-23.
  86. Cantor, L.B., et al., Morphologic classification of filtering blebs after glaucoma filtration surgery: the Indiana Bleb Appearance Grading Scale. J Glaucoma, 2003. 12(3): p. 266-71.
  87. Wen, J.C., S.S. Stinnett, and S. Asrani, Comparison of Anterior Segment Optical Coherence Tomography Bleb Grading, Moorfields Bleb Grading System, and Intraocular Pressure After Trabeculectomy. J Glaucoma, 2017. 26(5): p. 403-408.
  88. Richter, G.M., The Promise of Optical Coherence Tomography Angiography in Glaucoma. Ophthalmology, 2017. 124(11): p. 1577-1578.
  89. Yin, X., et al., Relationship between filtering bleb vascularization and surgical outcomes after trabeculectomy: an optical coherence tomography angiography study. Graefes Arch Clin Exp Ophthalmol, 2018. 256(12): p. 2399-2405.
  90. Seo, J.H., et al., Evaluation of Functional Filtering Bleb Using Optical Coherence Tomography Angiography. Translational Vision Science & Technology, 2019. 8(3).
  91. 91.0 91.1 Hayek, S., et al., Optical Coherence Tomography Angiography Evaluation of Conjunctival Vessels During Filtering Surgery. Transl Vis Sci Technol, 2019. 8(4): p. 4.
  92. Mastropasqua, R., et al., Angiographic biomarkers of filtering bleb function after XEN gel implantation for glaucoma: an optical coherence tomography-angiography study. Acta Ophthalmol, 2020. 98(6): p. e761-e767.
  93. Monteiro-Henriques, I., A. Rocha-Sousa, and J. Barbosa-Breda, Optical coherence tomography angiography changes in cardiovascular systemic diseases and risk factors: A Review. Acta Ophthalmol, 2021, p95
  94. Zhang, B., et al., Early Detection of Microvascular Impairments With Optical Coherence Tomography Angiography in Diabetic Patients Without Clinical Retinopathy: A Meta-analysis. Am J Ophthalmol, 2021. 222: p. 226-237.
  95. 95.0 95.1 Tsokolas, G., et al., Optical Coherence Tomography Angiography in Neurodegenerative Diseases: A Review. Eye Brain, 2020. 12: p. 73-87.
  96. Ayar, K., et al., Evaluation of retinal vascularization by optical coherence tomography angiography (OCTA) in rheumatoid arthritis, and its relationship with disease activity. Mod Rheumatol, 2020: p. 1-10.
  97. Crisostomo, S., et al., TAMOXIFEN-INDUCED CHORIORETINAL CHANGES: An Optical Coherence Tomography and Optical Coherence Tomography Angiography Study. Retina, 2020. 40(6): p. 1185-1190.
  98. Cennamo, G., et al., Optical Coherence Tomography Angiography Features in Post-COVID-19 Pneumonia Patients: A Pilot Study. Am J Ophthalmol, 2021. 227: p. 182-190.
  99. Garcia-Martin, E., et al., Retinal and Optic Nerve Degeneration in Patients with Multiple Sclerosis Followed up for 5 Years. Ophthalmology, 2017. 124(5): p. 688-696.
  100. 100.0 100.1 Lanzillo, R., et al., Optical coherence tomography angiography retinal vascular network assessment in multiple sclerosis. Mult Scler, 2018. 24(13): p. 1706-1714.
  101. 101.0 101.1 Farci, R., et al., Optical coherence tomography angiography in multiple sclerosis: A cross-sectional study. PLoS One, 2020. 15(7): p. e0236090.
  102. Feucht, N., et al., Optical coherence tomography angiography indicates associations of the retinal vascular network and disease activity in multiple sclerosis. Mult Scler, 2019. 25(2): p. 224-234.
  103. Wang, X., et al., Optical coherence tomography angiography of optic nerve head and parafovea in multiple sclerosis. Br J Ophthalmol, 2014. 98(10): p. 1368-73.
  104. Hayreh, S.S., Ischemic optic neuropathies - where are we now? Graefes Arch Clin Exp Ophthalmol, 2013. 251(8): p. 1873-84.
  105. Wang, H., et al., Macular evaluation of the retinal and choroidal vasculature changes in anterior ischemic optic neuropathy-a case control study. BMC Ophthalmol, 2018. 18(1): p. 341.
  106. 106.0 106.1 Pierro, L., et al., Vessel Density and Vessel Tortuosity Quantitative Analysis of Arteritic and Non-arteritic Anterior Ischemic Optic Neuropathies: An Optical Coherence Tomography Angiography Study. J Clin Med, 2020. 9(4).
  107. 107.0 107.1 Augstburger, E., et al., Retinal and Choroidal Microvasculature in Nonarteritic Anterior Ischemic Optic Neuropathy: An Optical Coherence Tomography Angiography Study. Invest Ophthalmol Vis Sci, 2018. 59(2): p. 870-877.
  108. Rougier, M.B., et al., OCT angiography analysis in acute non-arteritic anterior ischemic optic neuropathy: The importance of segmentation. Eur J Ophthalmol, 2020: p. 1120672120978358.
  109. Chuang, J.C., et al., Comparison of Peripapillary Vessel Density of Acute Nonarteritic Anterior Ischemic Optic Neuropathy and Other Optic Neuropathies With Disc Swelling Using Optical Coherence Tomography Angiography: A Pilot Study. J Neuroophthalmol, 2020.
  110. Smith, J.L., W.F. Hoyt, and J.O. Susac, Ocular fundus in acute Leber optic neuropathy. Arch Ophthalmol, 1973. 90(5): p. 349-54.
  111. Balducci, N., et al., Peripapillary vessel density changes in Leber's hereditary optic neuropathy: a new biomarker. Clin Exp Ophthalmol, 2018. 46(9): p. 1055-1062.
  112. Borrelli, E., et al., Topographic Macular Microvascular Changes and Correlation With Visual Loss in Chronic Leber Hereditary Optic Neuropathy. Am J Ophthalmol, 2018. 192: p. 217-228.
  113. Chun, B.Y. and J.F. Rizzo, 3rd, Dominant Optic Atrophy and Leber's Hereditary Optic Neuropathy: Update on Clinical Features and Current Therapeutic Approaches. Semin Pediatr Neurol, 2017. 24(2): p. 129-134.
  114. Martins, A., et al., Peripapillary and macular morpho-vascular changes in patients with genetic or clinical diagnosis of autosomal dominant optic atrophy: a case-control study. Graefes Arch Clin Exp Ophthalmol, 2019. 257(5): p. 1019-1027.
  115. Fard, M.A., et al., Optical Coherence Tomography Angiography in Optic Disc Swelling. Am J Ophthalmol, 2018. 191: p. 116-123.
  116. Tuntas Bilen, F. and H. Atilla, Peripapillary Vessel Density Measured by Optical Coherence Tomography Angiography in Idiopathic Intracranial Hypertension. J Neuroophthalmol, 2019. 39(3): p. 319-323.
  117. 117.0 117.1 Fard, M.A., et al., Optical Coherence Tomography Angiography in Papilledema Compared With Pseudopapilledema. Invest Ophthalmol Vis Sci, 2019. 60(1): p. 168-175.
  118. 118.0 118.1 Malmqvist, L., et al., The Optic Disc Drusen Studies Consortium Recommendations for Diagnosis of Optic Disc Drusen Using Optical Coherence Tomography. J Neuroophthalmol, 2018. 38(3): p. 299-307.
  119. 119.0 119.1 Yan, Y., et al., Vision Loss in Optic Disc Drusen Correlates With Increased Macular Vessel Diameter and Flux and Reduced Peripapillary Vascular Density. Am J Ophthalmol, 2020. 218: p. 214-224.
  120. Kim, M.S., et al., Morphologic Features of Buried Optic Disc Drusen on En Face Optical Coherence Tomography and Optical Coherence Tomography Angiography. Am J Ophthalmol, 2020. 213: p. 125-133.
  121. Parrozzani, R., et al., Retinal Vascular and Neural Remodeling Secondary to Optic Nerve Axonal Degeneration: A Study Using OCT Angiography. Ophthalmol Retina, 2018. 2(8): p. 827-835.
  122. Suzuki, A.C.F., et al., Circumpapillary and macular vessel density assessment by optical coherence tomography angiography in eyes with temporal hemianopia from chiasmal compression. Correlation with retinal neural and visual field loss. Eye (Lond), 2020. 34(4): p. 695-703.
  123. Kanamori, A., et al., Optical coherence tomography detects characteristic retinal nerve fiber layer thickness corresponding to band atrophy of the optic discs. Ophthalmology, 2004. 111(12): p. 2278-83.
  124. Lee, G.I., et al., Analysis of Optic Chiasmal Compression Caused by Brain Tumors Using Optical Coherence Tomography Angiography. Sci Rep, 2020. 10(1): p. 2088.
  125. Jaumandreu, L., et al., Reduced Peripapillary and Macular Vessel Density in Unilateral Postgeniculate Lesions With Retrograde Transsynaptic Degeneration. J Neuroophthalmol, 2019. 39(4): p. 462-469.
  126. Skalet, A.H., et al., Quantitative OCT Angiography Evaluation of Peripapillary Retinal Circulation after Plaque Brachytherapy. Ophthalmol Retina, 2018. 2(3): p. 244-250.
  127. Parrozzani, R., et al., Peripapillary vascular changes in radiation optic neuropathy: an optical coherence tomography angiography grading. Br J Ophthalmol, 2018. 102(9): p. 1238-1243.