**3. Neuro-ophthalmological conditions**

## **3.1 Papilledema and pseudopapilledema**

Papilledema is swelling of the optic nerve head (ONH) caused by increased intracranial pressure (ICP) eventually causing stasis in axonal transport. Distinguishing it from pseudopapilledema, caused by a congenital optic disc elevation (crowded optic disc) or optic disc drusen, can be difficult based on ophthalmoscopic features alone [16]. Studies have suggested that the shape and thickness of the retinal nerve fiber layer (RNFL) around the ONH as seen on spectral-domain OCT (SD-OCT) can distinguish between ONH drusen and edema. However, SD-OCT can only show the presence of ONH drusen and cannot determine if there is also swelling present. In such cases, fluorescein dye tests can be used to determine if there is true edema present [3]. Fard *et al.* demonstrated that whole image and nasal peripapillary sector capillary densities using OCT-A had diagnostic accuracy for differentiating true and pseudo-disc swelling [16]. They showed there was a significantly lower whole image and nasal sector peripapillary capillary density of the inner retina in pseudopapilledema eyes than papilledema eyes. The peripapillary vasculature values were found to be lower in both papilledema and pseudopapilledema eyes compared to healthy eyes when analyzed using commercial machine software. However, when using their customized software, the peripapillary capillary density in papilledema eyes was not significantly different from healthy eyes (**Figure 3**). On the other hand, the peripapillary capillary density in pseudopapilledema eyes was found to be significantly lower compared to healthy eyes.

Again, the main differentiating characteristic of papilledema from other pseudo edemas (e.g., non-arteritic anterior ischemic optic neuropathy (NAION)) on ONH OCT-A is the vascular dropout observed in NAION [3]. Rougier *et al.* [10] examined the changes in the blood vessels in eyes with disc edema and found that there were changes in the capillary network around the ONH in cases of non-arteritic NAION and papillitis, while in cases of papilledema, there were dilated and tortuous superficial blood vessels without any changes in the capillary network. The study suggests that the decreased visibility of the capillary network in cases of papilledema is likely due to the swelling of the optic disc, rather than an actual lack of blood flow, and that this may be related to changes in blood flow regulation. The cases are highlighted in **Table 2** for the enhancement of clinical knowledge of the readership and the author's observation of the retrospective analysis of all such related cases are highlighted too.

#### **Figure 3.**

*Disc photograph (a) of an eye with NAION and OCT-A (b) showing superior focal loss of microvasculature (yellow arrows) and a corresponding inferior visual field defect (c). Reprinted with permission from ref. [17].*


healthy eye (a). OCT-B images (c and d) matching a and b]

*Optical Coherence Tomography Angiography (OCT-A): Emerging Landscapes in Neuro… DOI: http://dx.doi.org/10.5772/intechopen.110810*


**Table 2.**

*OCT-A of different kinds of optic nerve head (ONH) edema and corresponding example clinical cases.*

*Optical Coherence Tomography Angiography (OCT-A): Emerging Landscapes in Neuro… DOI: http://dx.doi.org/10.5772/intechopen.110810*

The authors concluded that the morphological analysis of OCT-A appeared to be more beneficial than the quantification analysis in the acute phase, enabling the differentiation between the three kinds of ONH edema: ischemic, inflammatory, and papilledema [10].

Another significant application of OCT-A is in glaucoma. Studies have shown that changes in the blood vessels in the eyes, seen through OCT angiography (OCT-A), can be useful in diagnosing primary open-angle glaucoma. This is because these changes are consistent with the pathophysiology of the disease and can provide complementary information to traditional diagnostic methods. Vessel density loss associated with glaucoma can be detected by OCT-A. Peripapillary, macular, and choroidal vessel density parameters may complement visual field and structural OCT measurements in the diagnosis of glaucoma. Interested authors may refer to a separate chapter on this topic in this book [18]. OCT-A may be particularly useful in evaluating patients who are suspected of having glaucoma and in monitoring advanced cases [19, 20].


*Reprinted with permission from ref. [11].*

#### **Table 3.**

*Different types of optic neuropathies.*

#### **3.2 Optic neuropathies**

Optic neuropathies refer to a spectrum of disorders with abnormalities and dysfunction of the optic nerve [11]. **Table 3** summarizes different types of optic neuropathies and their pathology and epidemiology.

Anterior ischemic optic neuropathies (AAION) can be divided into two types: arteritic (AAION) and nonarteritic (NAION). AAION is commonly linked to giant cell arteritis, a severe form of vasculitis that affects vision. NAION, on the other hand, mainly affects individuals with cardiovascular risk factors and those with crowded optic discs [3]. NAION is the most common optic neuropathy (other than glaucoma) beyond the age of 50 years. The pathogenesis of NAION is related to vascular dysfunction and is thought to be a result of the occlusion of the short posterior ciliary arteries [17].

Studies using quantitative analysis in OCT-A (Optical Coherence Tomography Angiography) have shown that AAION has more abnormal blood vessels compared to NAION. This may be justified by the fact that AAION is characterized by more swelling of the optic disk [3]. Though there is no definite quantitative cut-off value for differentiating AAION from NAION, clinical applications of OCT-A in NAION are reported in several studies investigating the retinal vessels, choroidal vasculature, and optic disc perfusion. Karrabi *et al.* summarized different studies comparing NAION, fellow eyes, and normal eyes and interested readers may refer to it [3].

OCT-A studies have consistently shown changes in the blood vessels of patients with NAION. The most common changes include tortuous capillaries, irregularity, and loss of the peripapillary vessels, particularly in the temporal and superior sectors. Disc edema or hemorrhage can affect the signal and cause a decrease in blood flow density, which may not necessarily indicate an ischemic process but rather be a result of compressive edema or imaging artifacts. Two patterns of vasculature loss in NAION have been observed, a diffuse loss of the microvasculature network and additional sectoral choroidal vascular dropout. Decreased vessel density, which is the proportion of the measured area occupied by vessels, has been found in patients with NAION compared to healthy individuals. This reduction can be reversed and may also have prognostic values. However, it should be kept in mind that part of this vascular density reduction and its reversibility can be a result of the artifact caused by optic disc edema during the acute phase of the disease [3].

Though macular OCT-A findings in NAION are debated and controversial, there is a good correlation between perfusion and visual acuity, visual field defect, and structural changes in the ONH. The decrease in peripapillary vessel density and the location of visual field defects as well as peripapillary retinal nerve fiber layer (RNFL) thinning has been reported. The whole and temporal peripapillary vessel density was strongly correlated with visual acuity, and the dropout of the temporal peripapillary superficial retinal microvasculature was associated with visual acuity loss. OCT-A revealed hypoperfusion in the retinal pigment epithelium (RPE) and peripapillary capillaries (PPC) following NAION, especially at the level of the choroid, corresponding to both functional and structural impairments. Irreversible vascular damage can lead to a decrease in perfusion, which can negatively affect visual outcomes in selective quadrants. The temporal and superior quadrants had the most reduction in vessel density, which is consistent with the commonly identified inferonasal field defect (**Figure 3**) [3, 17].

In other types of optic neuropathy, toxic and traumatic optic neuropathy, OCT-A might not be useful and structural assessment is still superior to vascular parameters in differentiating toxic and traumatic optic neuropathies [3]. Apart from it, Montorio *et al.* [21] found that OCT-A can provide a detailed and quantitative analysis of early retinal

*Optical Coherence Tomography Angiography (OCT-A): Emerging Landscapes in Neuro… DOI: http://dx.doi.org/10.5772/intechopen.110810*

vascular perfusion alterations over time after traumatic retinopathy, demonstrating that the impairment of the retinal microvasculature and its progressive changes over time occurred even in the absence of compromised visual acuity. Hence, OCT-A may be useful for monitoring the course of vascular changes in traumatic optic neuropathy [21].

OCT-A has been used in studying hereditary optic neuropathies (e.g., Leber's hereditary optic neuropathy or LHON) as well. First described in 1871 by Leber, LHON is a maternally inherited mitochondrial disease caused by mutations in the mitochondrial DNA that affects complex I of the oxidative phosphorylation chain [3, 22]. Yu *et al.* demonstrated that the retinal structure and the perfusion of the macular and peripapillary areas are reduced in subacute LHON, and the retinal structure and the perfusion of the peripapillary area are further reduced in chronic LHON [22].

Recently there has been growing interest in implementing OCT-A in diabetic retinopathy (DR). OCT-A has a potential role as an objective tool for evaluating diabetic retinopathy (DR) and its impact on the retina. It has been shown to visualize features associated with DR, including microaneurysms and neovascularization, and quantify changes in retinal capillaries and choriocapillaris (**Figures 4** and **5**). Additionally, OCT-A can potentially detect DR earlier than what is visible on traditional fundus examination. It is a promising technology for accurately classifying DR

#### **Figure 4.**

*A healthy control subject's optical coherence tomography angiography (OCT-A; 3 mm 3 mm region) is shown in the top panel (A, B) and reveals a dense network of capillaries in the superficial vascular plexus, which surrounds the foveal avascular zone. A diabetic patient's OCT-A pictures (bottom panel; C, D) display vascular abnormalities in both the superficial and deep plexus layers, including microaneurysms (red arrows), capillary nonperfusion, and other vascular anomalies. (green arrows). A larger foveal avascular zone is shown. (FAZ). After the projection artifacts were eliminated, (B,D) were produced. Reprinted from ref. [12].*

#### **Figure 5.**

*Widefield optical coherence tomography angiography (OCT-A; 15 9 mm area; A,B) and color-coded maps showing low- or non-perfusion regions of a superficial vascular plexus in a diabetic (Right panel; C,D) and a healthy control individual (Left panel; A-C) (Right panel; B-D). In a diabetic eye, there are more areas of retinal nonperfusion, especially in the temporal regions. (D; labelled as yellow). It's imperative to keep in mind that the typical person has occasional yellow spots in the periphery. (C; labelled as yellow). Reprinted from ref. [12].*

and for identifying eyes that have experienced vision loss due to diabetic macular ischemia [12, 13].

Furthermore, implementing Deep Learning (DL) in OCT-A image analysis for DR has highlighted several benefits such as early detection and progression assessment [23]. The capability of OCT-A to detect the clinical onset of DR and prediction for its progression may become valuable for the personalized management of diabetic eye disease and arguably open a new horizon of research owing to the silent epidemic of diabetes around the globe.
