OCT-Angiography in Neuro-Ophthalmology
Article summary goes here.
OCT has become one of the most important imaging modalities in ophthalmology, since its invention in 1990's. OCT is a noninvasive technology based on principle of low-coherence interferometry, thus generating high-resolution, cross-sectional images from backscattered light, thus helps in assessing the structural changes in different retinal diseases. But due to low contrast between capillaries and retinal tissue, structural OCT cannot 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 require intravenous injection of contrast agents, which is time-consuming and can have potentially serious side effects. FA and ICGA provide two-dimensional (2D) images of ocular circulations, and do not give information regarding the depth of involvement. OCT- Angiography is a non invasive method which gives a three dimensional visualisation of blood vessels present at different levels.
OCTA 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, phase, or intensity and phase of the OCT signal. Studies also showed that the derived OCTA signal is related to the speed of flowing red blood cells, where faster flow results in greater flow signal, up to a saturation limit. Later intensity-based technique was 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, at the expense of axial resolution. 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. To improve visualization and 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, by standard, into four zones: the superficial retinal plexus, the deep retinal plexus, the outer retina and the choriocapillaris. Applied to the optic disc it includes its full depth.
Indications of OCT-A in neuro-ophthalmology
Multiple Sclerosis Papillitis Papilledema Non arteritic anterior ischemic optic neuropathy (NAION) Anterior arteritic ischemic optic neuropathy (AAION) Hereditary optic neuropathy (Leber Hereditary Optic Neuropathy)
NFL loss in OCT in patients of multiple sclerosis with or without optic neuritis is a well-documented structural parameter.  OCT findings have shown a high correlation with functional measurements and have also proved to be predictive of the clinical visual outcome. Furthermore, OCTA measurements in MS patients has detected retinal vascular impairment. Wang et al. reported significant decrease of ONH flow index in MS patients with a history of optic neuritis compared to healthy controls or MS patients without ON. No significant changes were observed in the parafoveal region. These findings demonstrate the usefulness of OCTA 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 sometimes disappeared in the edema, but they were visible above the edematous area. Radial distribution of peripapillary capillaries usually remains preserved, global aspect was a moderate alteration of the peripapillary regular pattern.
In patients with papilledema, radial peripapillary network remains unchanged, capillaries present at the surface of optic nerve head are dilated and tortuous like a tangled ball of vessels and there is no associated vascular dropout. 
Nonarteritic anterior ischemic optic neuropathy (NAION) is the consequence of an acute ischemic event of the optic nerve head. The pathophysiology of NAION is believed to be the result of hypoperfusion of optic disc microcirculation, which is chiefly contributed by short posterior ciliary arteries. NAION is known to be associated with structural crowding of the optic disc, hypertension, diabetes, and hyperlipidemia and hypercoagulable disorders, sleep apnea, and nocturnal hypotension.  It is the most common acute optic neuropathy among patients older than 50 years.
Wright Mayes et al,  in their retrospective study in NAION patients have demonstrated, flow impairment in OCTA in the retinal peripapillary capillaries which corresponds to structural OCT deficits of the retinal nerve fiber layer (RNFL) and ganglion cell layer complex (GCC) and automated visual field deficits, similarly flow impairment seen on OCTA in the peripapillary choriocapillaries correspond to structural OCT deficits of the RNFL and GCC . A potential clinical application of OCT-A in NAION is monitoring recovery, early OCT-A study has revealed partial recovery of peripapillary vascular flow with improvement in visual function.  Rougier MB et al , have shown that in NAION patients peripapillary network is less visible and there are vascular dropout areas associated with tortousity. 
Superficial peripapillary capillary dilation has been reported in eyes with acute AAION and also in fellow eyes The cause of dilation can be explained by luxury perfusion in setting of short posterior ciliary arterial compromise. Alternatively, the dilation may represent centrally mediated autoregulatory mechanisms in the setting of reduced perfusion of the optic nerve These retinal capillary perfusion defects also correspond to visual field loss. 
Hereditary optic neuropathy
Microangiopathy is a well-known feature of eyes with LHON. The telangiectatic vessels with focal tortuosity can be clearly made visible by OCTA 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, by Balduci et al.
In early sub acute stage of LHON, vascular density was reduced in the temporal sector, in late sub-acute stages of LHON-l, vessel density was reduced in whole, temporal, superotemporal and inferotemporal sectors and in chronic stages of LHON, vessel density is reduced in all sectors , further it was found that vessel density changes occur earlier than RNFL thickness changes, suggesting that OCT-A can be a useful biomarker to monitor the disease progression and treatment
In cases of optic atrophy a decrease in peripapillary microvascularture has been noted, A possible explanation for decreased visibility of microvasculature in optic atrophy is
smaller number of nerve fibers in the peripapillary area which reduces metabolic activity and in turn, results in lower blood flow via autoregulatory mechanisms. 
OCT-A has been reported as a useful tool for evaluating optic disc perfusion in glaucomatous eyes, as attenuated peripapillary and macular vessel density has been detected in pre-perimetric glaucoma patients. Therefore, OCT-A can help in early detection of glaucomatous damage. Moreover, the quantitative data from these retinal vessels may prove useful in analysing metabolic activity from the inner layers of the retina and thus provide further advances in monitoring function and progression in this disease. 
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