Blood Flow in Glaucoma
Brent Siesky
Alon Harris
Katie Hutchins
Josh Gross
INTRODUCTION
Glaucoma is a multifactorial and progressive optic neuropathy with strong evidence of vascular influences in many individuals. Numerous cross-sectional and longitudinal studies have identified low ocular perfusion pressure (calculated from blood pressure – intraocular pressure [IOP]) is an independent risk factor for the prevalence, incidence, and progression of glaucoma. Important anatomic vascular beds of interest in glaucoma include the retrobulbar vessels, peripapillary choroid, pre- and intra-laminar optic nerve head, and the capillary plexus of the superficial retinal nerve fiber layer (RNFL). Recent longitudinal studies have identified vascular factors as predictors of open-angle glaucoma (OAG) progression. In addition, ocular vascular health may be a more influential contributing factor in the pathophysiology of OAG in patients of African descent compared to European descent.
Advancements in imaging modalities of ocular blood flow have increased the understanding of ocular vascular dynamics, and have helped describe its role in glaucoma pathophysiology. Historically, evaluation of ocular and optic nerve blood flow in glaucoma has presented many challenges, and, therefore, many techniques focus on vascular regions accessible by ultrasound, laser, or other principles. It is important to acknowledge that no single technology is capable of assessing all significant vascular beds. Herein, clinically impactful and emerging ocular blood flow measurement techniques are presented and discussed (Fig. 9-1).
BIBLIOGRAPHY
Abegao Pinto L, Willekens K, Van Keer K, et al. Ocular blood flow in glaucoma—the Leuven Eye Study. Acta Ophthalmol. 2016;94(6):592-598.
Costa VP, Harris A, Anderson D, et al. Ocular perfusion pressure in glaucoma. Acta Ophthalmol. 2014;92(4):e252-e266.
Kanakamedala P, Harris A, Siesky B, et al. Optic nerve head morphology in glaucoma patients of African descent is strongly correlated to retinal blood flow. Br J Ophthalmol. 2014;98(11):1551-1554.
Moore NA, Harris A, Wentz S, et al. Baseline retrobulbar blood flow is associated with both functional and structural glaucomatous progression after 4 years. Br J Ophthalmol. 2017;101(3):305-308.
Siesky B, Harris A, Carr J, et al. Reductions in retrobulbar and retinal capillary blood flow strongly correlate with changes in optic nerve head and retinal morphology over 4 years in open-angle glaucoma patients of African descent compared with patients of European descent. J Glaucoma. 2016;25(9):750-757.
Tobe LA, Harris A, Hussain RM, et al. The role of retrobulbar and retinal circulation on optic nerve head and retinal nerve fibre layer structure in patients with open-angle glaucoma over an 18-month period. Br J Ophthalmol. 2015;99(5):609-612.
OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY
Purpose
• Evaluation of retinal, optic nerve, and choroidal hemodynamics
Description
Optical coherence tomography angiography (OCT-A) is a novel and noninvasive imaging modality that builds on existing OCT technology and offers the promise of highly specialized outcomes of optic nerve vascularity. OCT-A utilizes the differences in amplitude between subsequent beams of reflected infrared light to analyze both cross-sectional structural information and compute the quantity of retinal and choroidal blood flow (dimensionless units), providing vessel density percentage in the retina and optic nerve in 3 to 4 seconds. Two algorithms, split-spectrum amplitude-decorrelation angiography (SSADA) and optical microangiography (OMAG), have been widely used in research and are commercially available for clinical application. The SSADA algorithm utilizes the reflected amplitude of an infrared laser to find the decorrelation between consecutive B-scans (Fig. 9-2). OMAG utilizes a Hilbert transformation to assess scattering light reflections as either static or in motion. These calculations are used to generate high-resolution 3D (18 µm in coronal plane) images of the optic disc vasculature with segmentation of vascular layers (Fig. 9-3), including deep into the lamina cribrosa (2- to 3-mm penetration depth), and provide simultaneous structural and vascular assessments.
• Specialized angiography SSADA algorithm provides a reduction of artifacts from saccadic eye movements, high signal-to-noise ratio and vessel continuity, as well as vessel quantification in terms of density and flow index. OMAG allows for highly sensitive capillary images, and detection of blood flow as slow as 4 µm/s3.
• Vessel density (%) demonstrated similar diagnostic accuracy compared to RNFL thickness measurement for differentiating between healthy subjects and those with glaucoma (Fig. 9-4).
• Current cross-sectional studies in glaucoma patients show correlations between lower peripapillary vessel density and visual field defects, and correlation of visual field deficits to be stronger with vessel density deficits than with RNFL thinning (Fig. 9-5).
• Current limitations include difficulty imaging deep vasculature of the optic disc because of shadow interference from the larger and overlying central retinal vessels, flow index of the optic disc may include retinal microvasculature, difficulty distinguishing between decreased vascularity because of tissue loss versus ischemia, vascular leakage cannot be assessed, and no longitudinal studies of glaucoma progression have been performed, thus resulting in unknown prognostic ability.
• It does not provide a comprehensive assessment of all significant vascular beds in glaucoma; therefore, reductions in vascularity may represent a consequence of decreased upstream blood flow.
BIBLIOGRAPHY
Koustenis A, Harris A, Gross J, et al. Optical coherence tomography angiography: an overview of the technology and an assessment of applications for clinical research. Br J Ophthalmol. 2017;101(1):16-20.
Yarmohammadi A, Zangwill LM, Diniz-Filho A, et al. Optical coherence tomography angiography vessel density in healthy, glaucoma suspects, and glaucoma eyes. Invest Ophthalmol Vis Sci. 2016;57(9):OCT451-OCT459.
Yarmohammadi A, Zangwill LM, Diniz-Filho A, et al. Relationship between optical coherence tomography angiography vessel density and severity of visual field loss in glaucoma. Ophthalmology. 2016;123(12):2498-2508.
Zhang A, Zhang Q, Chen CL, et al. Methods and algorithms for optical coherence tomography-based angiography: a review and comparison. J Biomed Opt. 2015;20(10):100901.
FIGURE 9-2. Optical coherence tomography angiography split-spectrum amplitude-decorrelation angiography in a healthy subject. (Courtesy of Optovue Inc., Fremont, CA.) |
FIGURE 9-5. Optical coherence tomography angiography (OCT-A) glaucoma disease severity with corresponding visual fields: Correlation between vessel densities measured with OCT-A and visual field results, in both healthy controls and glaucomatous patients. Glaucomatous patients of differing disease severity have progressive peripapillary vessel deficits that correspond to greater relative visual field loss. This demonstrates a relationship between structural changes and functional changes. (Yarmohammadi A, Zangwill LM, Diniz-Filho A, et al. Relationship between optical coherence tomography angiography vessel density and severity of visual field loss in glaucoma. Ophthalmology. 2016;123(12):2498-2508.)
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