**1. Introduction**

In the general cascade of events leading to irreversible changes in the optic nerve, damage to the nerve fiber layer, and the retinal ganglion cell complex (GCC) are important factors contributing to the optical neuropathy pathogenesis of any genesis [1–7]. The possibility of retrograde trans-synaptic degeneration of visual fibers in visual pathway central neuron damage [8] opens up new prospects for visualizing morphological changes in the central nervous system (CNS) at the retinal level, since the retina being a part of the central nervous system, has much in common with the physiological characteristics of the brain.

The organization of visual pathway neural links is quite complex. Within the retina of every eye, it is a layer of photoreceptors (I neuron), then bipolar (II neuron) and ganglion cells with their long axons (III neuron). Together, they form the peripheral part of the visual pathway, represented by the optic nerves, chiasm and visual tracts. The visual tracts end in the cells of the corpus geniculatum laterale (CGL), which is the primary visual center. Central neuron fibers of the visual pathway (radiatio optica Gratiolet) originate from them and reach the area striate of the occipital lobe of the brain, where the primary cortical center of the visual analyzer is localized (**Figure 1**) [9].

The uniqueness of the visual pathway organization is that there is only one synapse between the retina and the visual cortex. Thus, any damage to the optic nerve head (ONH) will lead to trans-synaptic (trans-neuronal) degeneration in both anterograde and retrograde directions. Trans-synaptic anterograde degeneration leads to changes in the CGL, radiatio optica, and visual cortex, and trans-synaptic retrograde degeneration leads to changes in the retinal ganglion cell complex (GCC) (**Figure 1**) [10, 11].

Ophthalmoscopic manifestations of neurodegenerative diseases often precede the symptoms of CNS disorders and are used for their diagnosis. In turn, retinal visualization is much simpler and more economical than the available methods of CNS visualization.

The most technologically advanced and dynamically developing imaging method in ophthalmology is optical coherence tomography (OCT). Qualitative assessment

**Figure 1.** *The structure of the visual pathway.*

*Morphofunctional Changes of the Retina and Optic Nerve in Optical Neuropathy of Various… DOI: http://dx.doi.org/10.5772/intechopen.109850*

and quantitative analysis, integrated into the tomography software, allow identifying pathological changes in the studied structures with high repeatability and specificity.

When evaluating OCT images, it is necessary to understand the factors that determine the structural changes' range. The topography of the retinal nerve fibers layer (RNFL) is characterized by strict regularity. Ganglion cell axons extending from the central retinal region, as a part of the papillomacular bundle, form the temporal part of the ONH. Fibers extending from the superior-temporal and inferior-temporal retinal quadrants form the superior-temporal and inferior-temporal segments, respectively. Axons extending from ganglion cells located nasally and along the retinal periphery penetrate into the optic nerve disc from the nasal side. From the periphery of the temporal part of the retina, axons are directed to the superior and inferior parts of the ONH (**Figure 2**) [12].

Various patterns of damage to the RNFL and GCC are caused by the pathogenesis of neurons' primary damage. These differences can be used as differential diagnostic criteria for glaucomatous and non-glaucomatous optical neuropathies in routine clinical practice.

### **2. Glaucoma optic neuropathy**

Primary open-angle glaucoma is a chronic progressive optical neuropathy resulting from damage to retinal ganglion cells [13, 14]. Damage to the GCC axons in glaucoma is initialized in the optic nerve head by various mechanisms, such as mechanical

compression of intraocular pressure, vascular disorders, immunological influence, and oxidative stress. This can lead to direct retrograde damage to the GCC, followed by thinning of the RNFL and visual field defects [15].

A comprehensive assessment of early-onset glaucoma and its subsequent monitoring is achieved by combining the results of "structure-function." The key diagnostic methods for glaucoma are OCT and static automated perimetry (SAP). Each of the methods has its advantages and limitations.

Structural and functional relationships reach their peak at the advanced stage of the disease [16]. At early and late stages of glaucoma, there may be contradictions between OCT and SAP [17–20].

OCT allows for obtaining objective information about the retinal layers' thickness with high repeatability and reproducibility. Diagnostic OCT markers of POAG are the width of the rim area, RNFL, and GCC thickness [21, 22].

The temporal half of the superior and inferior quadrants of the optic nerve head are the most vulnerable areas of peripapillary RNFL loss—the superior and inferior vulnerable zones (superior vulnerable zone—SVZ & inferior vulnerable zone—IVZ) [23–25]. In severe glaucoma, the values reach a "floor effect" level [26].

With the progression of glaucoma, the defects area increases. With a decrease in the thickness of the RNFL and GCC to the "floor" level (50–70% of the nerve fiber layer thickness of healthy eyes), the existence of functional axons in the remaining layer is assumed, but the total number of these axons does not significantly contribute to the thickness of the layer [16, 27].

Nevertheless, the papillomacular bundle and high central vision in glaucoma patients persist until the later stages of the disease. The inferior macular zone associated with arcuate defects of peripapillary nerve fibers is more vulnerable, therefore, in the late stage of the disease, asymmetric preservation of the macula is often observed.

At the same time, in early glaucoma, SAP may not be informative, because statistically significant visual field defects are detected with 25–35% loss of retinal ganglion cells [28]. Visual field defects are not detected in the early stages due to the inability of the SAP to detect small functional losses as a result of the redundancy of the visual system and the overlap of receptive fields [29]. In addition, the SAP method is subjective, high concentration is required from the patient during the study, which can reduce the repeatability and reproducibility of testing.

The software of modern computer perimeters provides wide opportunities for analyzing threshold values of retinal photosensitivity. Thus, sensitivity to early glaucoma changes increases with cluster analysis, when the test points of the visual field are located and grouped along the course of a single bundle of retinal nerve fibers (clusters). The mean cluster photosensitivity defect is calculated for every cluster (**Figure 3**) [30, 31].

In addition to cluster analysis, anatomically oriented polar analysis is carried out in the Octopus perimeter [32]. It provides information about the expected location of morphological lesions of the rim area in the optic nerve head. Each visual field defect is combined with a nerve fibers bundle that hypothetically corresponds to it. Then, a vector is applied to the diagram of the optic nerve head at a certain angle corresponding to the localization of the defect, the length of which reflects the loss of photosensitivity in dB (**Figure 3**).

The addition of central test points to Protocol 24-2, 30-2, and macular area testing (Protocol 10-2) increases the effectiveness of testing [33].

To compare structural and functional defects, RNFL and GCC thickness maps can be superimposed on the test points of the visual field (24-2 location on the FNFL thickness map and 10-2 on the GCC thickness maps) (**Figure 4**).

*Morphofunctional Changes of the Retina and Optic Nerve in Optical Neuropathy of Various… DOI: http://dx.doi.org/10.5772/intechopen.109850*

#### **Figure 3.**

*54-year-old man with glaucoma. A—fundus-image. B—grayscale of values. The color scale indicates the absolute values of the light sensitivity thresholds in the form of a color map. C—cluster analysis. The degree of background darkening reflects the degree of deviation of clusters from the norm. D—polar analysis. The gray sector is in the normal range. The red vector is the radial coordinate. The length of the vector indicates the length of the defect. The angular coordinate is determined by the entry angle of nerve fibers bundles connected to each test point in the optic nerve disk.*

#### **Figure 4.**

*Spatial correspondence of structural-functional indicators. A 48-year-old man with glaucoma. BCVA 1.0. A—superposition of abnormal points of the visual field on RNFL and GCC probability maps (Revo NX, Optopol). B—NSTIN-RNFL profile color-coded. C—polar analysis. D—cluster analysis.*

A better understanding of the spatial correspondence of structural-functional indicators is facilitated by the representation of the profile of the peripapillary nerve fibers layer in the form of a scan graph NSTIN (nasal, N; superior, S; temporal, T; inferior, I; nasal, N), when the indicators of the RNFL thickness from the temporal half of the disk are presented in the middle of the graph (**Figure 4**) [34].

The evolution of OCT in ophthalmology has led to the emergence of a fundamentally new research method—OCT angiography (OCTA). OCTA is a new method of noninvasive visualization of blood vessels in the ONH and retina *in vivo* [35, 36].

Localized RNFL defects are spatially associated with density reduction of peripapillary vessels, even in early and preperimetric glaucoma. The most pronounced differences in OCTA indices between groups of healthy individuals and glaucoma patients were found in the inferior-temporal and superior-temporal quadrants of the peripapillary retina. Thus, the relationship between structural and functional, and hemodynamic changes in patients with POAG is obvious (**Figure 5**) [37, 38].

At the same time, multifunctional correlations are stronger than structuralfunctional ones [39].

Thus, the OCTA method is promising and, along with structural OCT and visual field testing, can become part of everyday routine practice. Today, OCTA is successfully used in the primary diagnosis of glaucoma, differential diagnosis of glaucoma in combined pathology, disease monitoring, and hemodynamic shifts assessment in IOP fluctuations [40, 41].

The characteristic pattern of RNFL and GCC damage in glaucoma is asymmetric paracentral macular defects associated with arcuate defects of the peripapillary RNFL, corresponding to them a density reduction of the peripapillary and parafoveolar capillaries, and perimetric defects.

#### **Figure 5.**

*54-year-old man with advanced glaucoma. BCVA 1.0. A—OCT probability map of RNFL and GCC. B—grayscale of values. C—OCTA, capillary density of the radial peripapillary plexus and the superficial plexus. A significant decrease in the peripapillary and parafoveolar capillaries density, corresponds to the thinning of GCC and RNFL.*

*Morphofunctional Changes of the Retina and Optic Nerve in Optical Neuropathy of Various… DOI: http://dx.doi.org/10.5772/intechopen.109850*
