OCT-Angiography in Neuro-Ophthalmology
Optical Coherence Tomography (OCT) has become one of the most important imaging modalities in ophthalmology, since its invention in 1990's. OCT is a noninvasive technique based on the principle of low-coherence interferometry, which generates high-resolution, cross-sectional images from backscattered light, and helps to assess the structural changes in different retinal diseases. Low contrast between capillaries and retinal tissue hinders OCT to be used to monitor vascular changes.
Fluorescein angiography (FA) and indocyanine green angiography (ICGA) are conventionally used for qualitative clinical assessment of retinal and choroidal circulations, but both techniques require intravenous (IV) injection of contrast agents. Contrast administration is time-consuming and can have potentially serious side effects. FA and ICGA provide two-dimensional (2D) images of ocular circulations, but do not give information regarding the depth of involvement. OCT-Angiography (OCT-A) is a noninvasive method which gives a three dimensional visualization of blood vessels present at different levels.
OCT-A identifies blood vessels by detecting blood flow-induced change in the OCT reflectance signal. Flowing red blood cells causes more variation in the OCT signal between repeated scans than static tissue. Multiple approaches have been described for quantifying this change through assessment of the intensity and phase of the OCT signal. Intensity-based technique was later introduced to visualize retinal and choroidal microvasculature called split-spectrum amplitude-decorrelation angiography (SSADA). The SSADA algorithm divides the OCT spectrum into narrower bands and then averages the intensity decorrelation detected in each band. This method significantly improved the signal-to-noise ratio. OCT-A employs two methods for motion detection: amplitude decorrelation or phase variance. The former detects differences in amplitude between two different OCT B-scans. Phase variance is related to the emitted light wave properties, and the variation of phase when it intercepts moving objects. In order to improve visualization and to reduce background noise from normal small eye movements, two averaging methods (split spectrum amplitude decorrelation technique and volume averaging) were developed. These OCT-A algorithms produce an image (3mm2 to 12mm2) that is segmented, into four zones: the superficial retinal plexus, the deep retinal plexus, the outer retina, and the choriocapillaries.
Indications of OCT-A in neuro-ophthalmology
- Multiple Sclerosis
- Non arteritic anterior ischemic optic neuropathy (NAION)
- Anterior arteritic ischemic optic neuropathy (AAION)
- Hereditary optic neuropathy (Leber Hereditary Optic Neuropathy)
In the setting of Multiple Sclerosis (MS), OCT allows for visualization of the thickness of the retinal nerve fiber layer (RNFL). RNF loss is a well-documented parameter in MS patients with or without optic neuritis and is also predictive of the clinical visual outcome. OCT-A measurements in MS patients can help to detect retinal vascular impairment. The optic nerve head flow index (ONH-FI) is measured by OCT-A and allows for visualization of the density and caliber of retinal vessels and flow velocity. Studies have reported a significant decrease in ONH-FI in MS patients with a history of optic neuritis as compared to healthy controls or MS patients without ON but no significant changes were observed in the parafoveal region. Detecting optic nerve damage in MS patients with optic neuritis is most accurate when ONH-FI and structural OCT parameters are considered in combination. These findings have demonstrated the usefulness of OCT-A in studying vascular abnormalities associated with MS.
Rougier et al, found that in inflammatory optic disc edema, no vascular drop out was present. A significant peripapillary edema can hide the underlying capillaries, but capillaries were visible above the edematous area. The radial distribution of peripapillary capillaries is usually preserved.
In patients with papilledema, radial peripapillary network remains unchanged, capillaries present at the surface of optic nerve head are dilated and tortuous and appear like a tangled ball of vessels, with no associated areas of vascular dropout. OCT-A may have the potential to differentiate between papilledema and pseudopapilledema. In contrast to papilledema where peripapillary capillary density is similar to control eyes, pseudopapilledema demonstrated decreased vessel density compared to control eyes. This distinction is important because papilledema may represent life-threatening conditions such as meningitis or a brain tumor resulting in increased intracranial pressure.
Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common acute optic neuropathy among patients older than 50 years. It is the consequence of an acute ischemic event of the optic nerve head. The pathophysiology of NAION is believed to be the result of occlusion of the posterior ciliary artery, resulting in hypoperfusion of optic disc microcirculation. NAION is also known to be associated with structural crowding of the optic disc, hypertension, diabetes, and hyperlipidemia and hypercoagulable disorders, sleep apnea, and nocturnal hypotension.
Choroidal thinning and pachychoroid have been reported in association with NAION, suggesting choroidal vasculature may be involved in the pathophysiology. Because fluorescein angiography does not provide adequate information about the deeper vasculature, OCT-A may be useful in this setting.
Wright Mayes et al, demonstrated flow impairment of the retinal peripapillary capillaries, especially in the temporal sector on OCT-A in patients with NAION. This finding corresponded to the structural OCT deficits of retinal nerve fiber layer (RNFL) and ganglion cell layer complex (GCC) as well as the automated visual field deficits. Another study showed vascular dropout with associated tortuosity of the peripapillary capillary network.
Partial recovery of peripapillary vascular flow with improvement in visual function has been reported, suggesting a possible clinical application of OCT-A to monitor visual recovery in NAION patients.
Superficial peripapillary capillary dilation has been reported in eyes with acute AAION and the contralateral eye. The cause of dilation can be explained by two mechanisms: short posterior ciliary arterial compromise resulting in luxury perfusion or hyperperfusion, or decreased optic nerve perfusion leading to centrally-mediated autoregulatory mechanisms. Superficial peripapillary capillary dilation is a nonspecific sign of AAION and has been reported in other disease processes, such as Leber Hereditary Optic Neuropathy.
Focal non-perfusion of superficial and deep retinal capillaries has also been reported in AAION. These defects manifest as cotton-wool spots in the retinal or optic disc edema. The finding of focal non-perfusion coupled with superficial peripapillary capillary dilation on OCT-A may be a useful tool when evaluating for AAION.
Hereditary optic neuropathy
Microangiopathy is a well-known feature of eyes with LHON. The telangiectatic vessels with focal tortuosity are visible on OCT-A in patients with pseudoedema of the optic disk secondary to LHON. Moreover, temporal optic atrophy and NFL thinning in the papillomacular bundle is a general feature for LHON.
Different patterns of loss of choriocapilaries have been reported in different stages of LHON. In the early subacute stage of LHON, vascular density is reduced chiefly in the temporal sector and progresses to involve the temporal, supertemporal, and inferotemporal sectures in the late subacute stages. In chronic stages of LHON, vessel density is reduced in all sectors, but is limited to the RNFL and retinal ganglion cell layers. OCT-A may be useful in monitoring retinal ganglion cell apoptosis and disease progression.
In cases of optic atrophy, a decrease in peripapillary microvasculature has been noted. A possible explanation for decreased visibility of microvasculature in optic atrophy is a smaller number of nerve fibers in the peripapillary area which reduces the metabolic activity and in turn, lowers the blood flow via autoregulatory mechanisms.
Findings on OCT-A vary with the subtypes of glaucoma. In primary open angle glaucoma (POAG), both vessel density and flow indices within the optic nerve head, macula, and peripapillary retina were reduced compared to normal control eyes. Eyes with normal tension glaucoma have similar findings on OCT-A of decreased peripapillary capillary density, but to a lesser degree than POAG. In primary angle closure glaucoma, OCT-A has demonstrated significant reduction in peripapillary vessel density when compared to control eyes. Circumpapillary vessel density reduction has also been reported after acute angle closure.
OCT-A has been reported to be a useful tool for evaluating optic disc perfusion in glaucomatous eyes; however, vessel density and flow indices do not reliably correlate with disease stage. It may be useful in evaluating glaucoma suspects or early glaucoma, before decline in vision occurs. One study demonstrated a decrease in blood flux index (similar to flow index) in glaucoma suspects with normal RNFL thickness, normal visual field, and normal vessel density. Moreover, the quantitative data from these retinal vessels may prove useful in analyzing metabolic activity from the inner layers of the retina and thus provide further advances in monitoring function and progression in this disease.
- Petzold A, de Boer JF, Schippling S, Vermersch P, Kardon R, Green A, et al. Optical coherence tomography in multiple sclerosis: A systematic review and meta-analysis. Lancet Neurol. 2010;9:921–32.
- Spain RI, Liu L, Zhang X, et al. Optical coherence tomography angiography enhances the detection of optic nerve damage in multiple sclerosis. Br J Ophthalmol. 2018;102(4):520–524. doi:10.1136/bjophthalmol-2017-310477
- Wang X, Jia Y, Spain R, et al. Optical coherence tomography angiography of optic nerve head and parafovea in multiple sclerosis. Br J Ophthalmol 2014;98:1368–1373
- Rougier MB et al Optical coherence tomography angiography at the acute phase of optic disc edema Eye Vis (Lond). 2018 Jun 23;5:15
- Fard MA, Sahraiyan A, Jalili J, et al. Optical Coherence Tomography Angiography in Papilledema Compared With Pseudopapilledema. Invest Ophthalmol Vis Sci. 2019;60(1):168–175. doi:10.1167/iovs.18-25453
- Arnold AC. Pathogenesis of nonarteritic anterior ischemic optic neuropathy. J Neuroophthalmol. 2003;23:157–163.
- Gandhi U, Chhablani J, Badakere A, et al. Optical coherence tomography angiography in acute unilateral nonarteritic anterior ischemic optic neuropathy: A comparison with the fellow eye and with eyes with papilledema. Indian J Ophthalmol. 2018;66(8):1144–1148. doi:10.4103/ijo.IJO_179_18
- Wright Mayes E, Cole ED, et al. Optical coherence tomography angiography in nonarteritic anterior ischemic optic neuropathy.J Neuroophthalmol 2017;37:358‑64
- Sharma S, Ang M, Najjar RP et al. Optical coherence tomography angiography in acute non‑arteritic anterior ischaemic optic neuropathy. Br J Ophthalmol 2017;101:1045‑51.
- Gaier ED, Gilbert AL Optical coherence tomographic angiography identifies peripapillary microvascular dilation and focal non-perfusion in giant cell arteritis Br J Ophthalmol.2018 Aug;102(8):1141-1146.
- Balducci N et al Peripapillary vessel density changes in Leber's hereditary optic neuropathy: a new biomarker. Clin Exp Ophthalmol. 2018 Dec;46(9):1055-1062.
- Kousal B, Kolarova H, Meliska M, Bydzovsky J, Diblik P, Kulhanek J, Votruba M, Honzik T, Liskova P. Peripapillary microcirculation in Leber hereditary optic neuropathy. Acta Ophthalmol. 2019 Feb;97(1):e71-e76. doi: 10.1111/aos.13817. Epub 2018 Sep 26. PubMed PMID: 30259673.
- Ghasemi Falavarjani K, Tian JJ, Akil H, Garcia GA, Sadda SR, Sadun AA. Swept source optical coherence tomography angiography of the optic disk in optic neuropathy. Retina. 2016;36(Suppl 1):S168–S177.
- Werner AC, Shen LQ. A Review of OCT Angiography in Glaucoma. Semin Ophthalmol. 2019 Jun 3:1-8. doi: 10.1080/08820538.2019.1620807. [Epub ahead of print] PubMed PMID: 31158045.
- Yarmohammadi A, Zangwill LM, Diniz-Filho A, et al. Peripapillary and Macular Vessel Density in Patients with Glaucoma and Single-Hemifield Visual Field Defect. Ophthalmology. 2017;124(5):709-719.