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Optical Coherence Tomography Angiography in Neuro-Ophthalmology

Hagag, Ahmed M. MD; Huang, David MD, PhD

doi: 10.1097/WNO.0000000000000584

Department of Ophthalmology, Casey Eye Institute, Oregon Health and Science University, Portland, Oregon.

Address correspondence to David Huang, MD, PhD, Casey Eye Institute, Oregon Health and Science University, Portland, OR 97239; E-mail:

Supported by Grants R01 EY023285 and P30 EY010572 from the National Institutes of Health (Bethesda, MD), unrestricted departmental funding from Research to Prevent Blindness (New York, NY), and the Champalimaud Foundation (Lisbon, Portugal).

Oregon Health & Science University (OHSU) and D. Huang have a significant financial interest in Optovue, Inc, a company that may have a commercial interest in the results of this research and technology. These potential conflicts of interest have been reviewed and managed by OHSU. D. Huang receives patent royalties from Carl Zeiss Meditec, Inc. The remaining author reports no conflicts of interest.

Optical coherence tomography (OCT) has become the most commonly performed imaging procedure in ophthalmology (1,2). Conventional OCT provides high-resolution structural information of the retina and optic nerve. More recent functional extensions such as Doppler OCT (3) and OCT angiography (OCTA) (4) have emerged as useful tools for vascular evaluation of eye diseases, including optic neuropathies. This issue of the Journal of Neuro-Ophthalmology has 2 articles (5,6) demonstrating the utilization of OCTA in the evaluation of 2 different types of optic neuropathy. Here, we put these reports in the context of overall applications of OCT and OCTA in neuro-ophthalmology.

Structural OCT has been widely used for diagnosis and monitoring of both glaucomatous optic neuropathy (GON) and nonglaucomatous optic neuropathy (NON). OCT can reliably detect thinning of retinal nerve fiber layer (NFL) and ganglion cell–inner plexiform layer, which strongly correlates with visual field (VF) deficits (7). In glaucoma, the early damage preferentially affects the inferior and superior disc quadrants with relative sparing of the temporal quadrant (8). By contrast, many NON primarily involve the papillomacular nerve fiber bundle, producing more damage in the temporal quadrant (temporal optic disc pallor). These OCT changes sometimes occur before any detectable VF change (9). In disorders with optic disc edema, OCT measurements of retinal and/or NFL thickness can be of great value in detecting and monitoring the swelling (10). Moreover, enhanced depth imaging OCT has the ability to investigate the characteristics of optic disc of drusen and their relationship with the lamina cribrosa (11). OCT also has been used in many neurodegenerative diseases. The retina of patients with Alzheimer disease has reduced the thickness of NFL and GCC (12). These findings also have been demonstrated in patients with mild cognitive impairment (MCI) (13), as well as patients with Parkinson disease and multiple sclerosis (with and without optic neuritis) (14,15).

Doppler OCT measures the Doppler shift of the reflected light because of the axial component of blood flow velocity. It has been used to measure total retinal blood flow (16,17). Both GON and NON showed decreased retinal blood flow rate and velocity (18).

Although Doppler OCT is able to measure flow in large retinal vessels, it is not sensitive to the slow transverse flow in retinal, choroidal, and optic disc capillary networks. OCTA is able to image slow transverse flow in capillaries by detecting the variation or decorrelation of OCT signal between cross-sectional images. Because it uses the intrinsic contrast of moving blood cells, no dye injection is needed (4). Furthermore, because OCTA is 3 dimensional, retinal and choroidal vascular plexuses can be separated into slabs for en face visualization and quantification (4). Using OCTA, glaucomatous reduction in vessel density has been detected in the optic disc (19), peripapillary retina (20), peripapillary choriocapillaris (PCC) (21), and the macula (22). OCTA parameters have been found to have strong correlation with VF parameters, more so than structural parameters such as NFL thickness (23). Projection-resolved OCTA (24) can visualize up to 4 vascular plexuses in the retina, depending on location (25). Glaucoma had been found to primarily affect the superficial vascular complex, which supplies the ganglion cell complex (22). This pattern should be true for NON as well.

Aside from GON, OCTA has been used to investigate several neurodegenerative and NON diseases with vascular components (26). In multiple sclerosis (MS), OCTA of the optic disc has shown reduced flow index and vessel density in eyes with optic neuritis compared with normal subjects, as well as MS eyes without a history of optic neuritis (27,28). Meanwhile, inconsistent macular OCTA results have been published by different groups. Wang et al (27) reported statistically equivalent parafoveal flow index in MS and control groups (27). By contrast, Higashiyama et al (29) detected significant decrease in macular vessel density in eyes recently treated for optic neuritis. These differing results can be explained by the differences in OCTA machines used, patient characteristics, and the OCTA parameters reported by the 2 groups. In Leber hereditary optic neuropathy, OCTA has been able to detect peripapillary telangiectatic blood vessels (30,31), which were not visible on fluorescein angiography (30). In addition, OCTA has been able to detect decreased retinal perfusion in other entities, including chiasmal compression (32), optic disc drusen, and ischemic optic neuropathy (33).

In this issue of the Journal of Neuro-Ophthalmology, Wright Mayes et al (5) observed both retinal peripapillary capillaries (RPC) and PCC defects in a series of patients with nonarteritic anterior ischemic optic neuropathy (NAION). These microvascular changes were highly correlated with structural OCT changes (peripapillary NFL and macular GCC) and VF loss. A novel contribution of this study was the demonstration of the correspondence between PCC flow impairment and VF defects in NAION subjects. This observation supports the hypothesis that the primary insult involves the posterior ciliary arteries (34). This new information could only have been obtained by OCTA, as the choroidal circulation is poorly observed in traditional dye-based angiography.

Also in this issue of the journal, Gaier et al (6) reported OCTA imaging in a patient with bilateral optic disc drusen. OCT angiograms detected focal microvascular attenuation in the optic disc and the RPC at the locations of superficial drusen. Moreover, areas of decreased perfusion correlated with the structural (NFL thinning) and functional (VF defects) parameters.

These reports, along with previous literature, illustrate the ability of OCTA to detect focal microcirculatory defects in optic neuropathy. The ability of OCTA to separately view retinal and choroidal plexuses provides insight into pathophysiologic mechanisms that were previously unavailable. OCTA provides both angiographic and structural information and allows the correlation between neural tissue and its blood supply. OCTA may be to provide better indication of optic neuropathy in situations where the structure is complicated by swelling, exudates, or drusen (35). However, OCTA has limitations because it was only recently introduced commercially in 2014 (36). Quantitative analysis of vessel density and flow index has been limited to a few research laboratories until very recently. Available clinical studies on NON have been cross-sectional and based on small samples of patients. In addition, OCTA image artifacts such as bulk motion, shadowing, and flow projection interfere with interpretation and clinical evaluation (37,38). Better software tools for artifact removal and education of clinicians are needed to improve the reliability of clinical interpretation (39–41). Quantitative analysis of flow impairment in different sectors of peripapillary and macular regions could provide more objective assessment of the pattern and severity of optic nerve damage and aid in differential diagnosis and disease staging (22,23,42,43).

In conclusion, OCTA is a new imaging technique able to assess microvascular changes associated with both GON and NON. Its use in the neuro-ophthalmological literature is still sparse. We anticipate that this will be an active area of research in the clinical evaluation of various types of NON and provide pathophysiological insight into a variety of optic nerve disorders.

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