**1. Introduction**

Recent advances in biomedical imaging have led several imaging modalities to improve our understanding of various ophthalmological and/or neurological diseases. First developed by Fujimoto's group at the Massachusetts Institute of Technology (MIT) in 1991, Optical Coherence Tomography (OCT) works based on tissue

backscattering properties [1]. OCT utilizes the short coherence length of broadspectrum light sources to obtain cross-sectional images of biological tissue samples on a microscopic scale. Since its inception in the 1990s, it has rapidly become a crucial imaging technique in various biomedical fields, particularly in ophthalmology, where it can be used to visualize the anterior eye and retina through transparent media. As the brain and retina originate from the same embryologic origin, the retina provides a unique "window" into the central nervous system (CNS) because of having unmyelinated axons and a low concentration of glial cells. That is why retina is called "a relative vacuum" while studying neurons and axons and it can serve as a valuable surrogate marker of neurodegeneration, neuroprotection, and neurorestoration [2].

The major users of OCT technology over the last 20 years have been mostly ophthalmologists, but in these days, it is also being used widely by more specifically neuro-ophthalmologists and neurologists on patients with ocular and/or neurologic disorders. We previously summarized the updates on OCT's applications in neuroscience and interested readers may refer to it [2]. Besides, one of the modern-day OCT successors, OCT Angiography (OCT-A) has drawn significant attention from biomedical communities for its unique capabilities in imaging microvasculature in different neuro-ophthalmological and neurological conditions. Some purely neuroophthalmological conditions (e.g., optic neuropathies, papilledema, glaucoma) and some neurologic conditions with ocular manifestations (e.g., multiple sclerosis, Parkinson's disease, Alzheimer's disease, stroke) show changes in eye vasculature that can be detected, studied and monitored using OCT-A, are discussed together in this chapter due to their significant inter-relations [3–9].

In neuro-ophthalmology, OCT-A has been used in different types of optic nerve head (ONH) edema (e.g., ischemic, inflammatory, papilledema) and optic neuropathies (e.g., ischemic, inflammatory, hereditary) [10, 11]. There has been recent attention to implementing OCT-A in diabetic retinopathy as well [12, 13]. The key advantage OCT-A provides in addition to conventional structural OCT images, it can capture the microvascular architecture in unprecedented detail which can synergize the clinical diagnosis, monitoring disease progression and prognosis [14, 15]. Again, some central nervous system (CNS) diseases have retinal microvasculature involvement. For instance, neurodegenerative diseases like Alzheimer's disease (AD) affects retina as well. The mechanism behind the reduced retinal vessel density in AD is not clear, but it has been proposed that decreased angiogenesis due to sequestration of vascular endothelial growth factor (VEGF) by Aβ plaques and competition between Aβ and VEGF receptor 2 is a factor. Studies have found Aβ plaques in the retinas of postmortem AD patients and in mice with AD. These findings suggest that Optical Coherence Tomography Angiography (OCT-A) could be used to detect microvascular abnormalities in even pre-clinical AD pathology [8]. Recent applications of OCT-A have shed light on acute stroke diagnosis even from retina though it requires further research [7]. In this chapter, we will explore the potential applications of OCT-A in these fields, their challenges, and future directions.

### **2. Basic concepts of OCT-A**

OCT-A is an imaging tool for visualizing the retinal vasculature in the eye based on the traditional OCT but allows for high-speed imaging acquisition of the retinal blood vessels. OCT-A uses algorithms such as Ultrahigh-sensitive optical microangiography, split-spectrum amplitude-decorrelation angiography, full spectrum amplitude
