**1. Introduction**

Inherited retinal dystrophies (IRD) represent a group of extremely heterogeneous retinal disorders. In recent years, several steps forward in the understanding of IRD pathogeneses and clinical courses have been provided by the use of quantitative multimodal retinal imaging, namely a set of noninvasive diagnostic techniques allowing to reach a very high, histology-like level of details. The main multimodal retinal imaging technologies are based on fundus autofluorescence (FAF), optical coherence tomography (OCT), and OCT angiography (OCTA), although many other ancillary techniques are even more employed both in research and clinical contexts [1]. The combined use of these imaging modalities allows to obtain highly detailed information regarding the morphological and biochemical properties of retinal diseases.

The even larger use of multimodal retinal imaging provided undoubted advantages in retinal diagnostics, and IRD highly benefitted from this, watching the increasing interest of research groups and companies in developing new treatment strategies [2]. From this point of view, the next years will provide meaningful changes regarding the management of IRD, providing new potential treatments and changing the clinical course of these genetically determined retinal diseases. These are the reason why ophthalmologists and retinal specialists should be more focused on reaching a good level of knowledge regarding IRD imaging findings, especially looking at OCT and OCTA ones. The main goal of this chapter is to provide an updated and complete scenario regarding OCT and OCTA characteristics of the most common IRD, namely retinitis pigmentosa (RP), Stargardt disease (STGD), and Best vitelliform macular dystrophy (BVMD). In addition, we dedicated a section to pigmented paravenous retinochoroidal atrophy (PPCRA), a rare retinal disorder characterized by still unknown pathogenesis, which is currently an object of very high research interest. A brief description regarding the current literature findings in pattern dystrophies is also provided.

## **2. Retinitis pigmentosa**

RP is the most common IRD form, characterized by very high genotypical and phenotypical heterogeneity [3]. RP is a progressive, centripetal disease characterized by primary damage of rod photoreceptors followed by cone photoreceptors involvement in later stages [3]. The clinical presentation is mainly characterized by night blindness and peripheral visual field alterations; central vision impairment occurs in more advanced stages of the disease. The classic fundoscopic triad is made by optic disc pallor, attenuated retinal vessels, and "bone-spicule" peripheral retinal pigment deposits. A complete noninvasive multimodal retinal imaging RP case is shown in **Figure 1**.

FAF examination is characterized by peripheral diffuse hypoautofluorescence. The central retina is surrounded by the typical Robson-Holder hyperautofluorescence ring, interpreted as RPE reactive phenomenon correlating with the integrity of the outer retinal bands and the progression of the disease [4, 5]. The central retina may be characterized by different amount of FAF alterations, depending on the status of the outer retina and the occurrence of macular edema. FAF deterioration was found strictly related with the electrophysiology evidence of retinal functional decline [4].

OCT provided undoubtedly advantages in detecting the changes occurring at the level both of inner and outer retinal layers. It offers the most detailed representation of the status of outer retinal bands, correlating with visual acuity, retinal sensitivity, and RP progression [6]. In particular, the status of an external limiting membrane (ELM), ellipsoid zone (EZ), outer nuclear layer (ONL), and outer hyperreflective bands ruled the central vision and peripheral visual field [7, 8]. Electrophysiology investigations also highlighted a relationship between the integrity and thickness of inner retinal layers and the functionality of the central retina [9]. Many times, myopia-related alterations coexist with typical signs of retinal degeneration related to RP [10]. In advanced stages, outer retinal tubulations (ORT) can be identified on structural OCT [10]. ORT is defined as round outer retinal structures with hyperreflective borders surrounding a mixed reflectivity core, usually located at the borders of, or centrally within, regions of outer retinal atrophy [11]. ORT formation is made by the gradual remodeling and invagination of the ELM-photoreceptors complex and is commonly interpreted as a degenerative sign. Although RP is mainly considered an outer retinal disorder, even growing evidence are suggesting a major involvement

*New OCT and OCTA Insights in Inherited Retinal Dystrophies DOI: http://dx.doi.org/10.5772/intechopen.109953*

#### **Figure 1.**

*Multimodal retinal imaging in RP. Confocal multicolor image (A) shows changes in the peripheral pigment with some bone spicule, attenuated retinal vasculature, and central pigment rarefaction. FAF image (B) shows extensive peripheral hypoautofluorescent signal, the perifoveal hyperautofluorescent Robson-Holder ring, and the preserved central physiological hypoautofluorescence. Structural OCT (C) shows the disappearance of the peripheral outer retinal bands, with preservation limited to the foveal region. Moreover, OCT shows myopic signs, such as the increased curvature of the eye and thin choroid. OCTA shows preserved SCP (D), markedly altered DCP (E) with some projections artifacts, and increased CC flow voids (F).*

also of the inner retina [12]. Previous studies showed either thickening or thinning of inner retinal layers, and no consensus has been reached regarding the precise inner retinal changes occurring in RP yet [10, 12, 13]. It is likely to hypothesize that inner retinal involvement may vary as different phenotypic profiles of different RP subgroups. On the other side, all the studies agreed on correlating the inner retinal

status with central retina function [10, 12–17]. Moreover, cystoid macular edema is a common structural OCT finding, occurring in approximately 10–50% of cases. The pathogenesis is still poorly understood; the current hypotheses include the breakdown of the inner blood-retinal barrier, the dysfunction of RPE pumps, the macular Müller cells impairment, possible autoimmune-related phenomena, and vitreomacular anomalies and traction [18, 19]. Other structural OCT-described findings include vitreoretinal interface alterations, epiretinal membrane, and macular hole [20]. Moreover, hyperreflective foci have been described in RP, correlating their number with the severity of the disease and the rate of progression [21, 22].

It is known that choroidal perfusion is impaired in RP; OCT-based imaging modalities may offer a detailed detection of choroidal features, improving the diagnostic workup of RP patients [23–26]. The choroid is not simply thinner than controls; a recent study highlighted how quantitative-based approaches can unveil specific RP choroidal patterns, characterized by different baseline features as well as the rate of progression. By combining the measure of choroidal thickness, Sattler layer thickness, Haller layer thickness, and choroidal vascularity index (CVI), it was possible to find three different RP choroidal patterns [27]. Pattern 1 is characterized by normal-appearing choroid, whereas Pattern 2 shows reduced Haller and Sattler layers. Moreover, Pattern 3 is characterized by reduced Haller and Sattler layers and choroidal caverns [27]. Pattern 1 was associated with better visual acuity and imaging parameters, and lower progression. Pattern 3 showed the worst baseline conditions and the fastest progression. Pattern 2 showed intermediate characteristics, since the morpho-functional status resulted worse than Pattern 1, although the 1-year progression resulted in unremarkable.

OCTA provided noninvasive evidence both of intraretinal and choroidal perfusion impairment in RP. Indeed, intraretinal vascular network impairment has been clearly shown by OCTA, together with degenerative changes occurring at the level of the choriocapillaris [28–31]. DCP represents the most altered plexus, as usually occurs almost in all retinal diseases. The main reason is related to the fact that DCP is a low-pressure network, thus earlier suffering from perfusion reductions associated with the disease-related pathological changes [1]. Hence, DCP alterations can be considered very sensitive to disease-related degenerative processes, although poorly specific. The use of quantitative OCTA metrics allowed us to distinguish two different RP vascular patterns, the first one characterized by better perfusion status and lower amount of vascular network disorganization, associated with lower progression and better visual outcome, than the second RP vascular pattern [32]. Vascular changes in RP occur as a consequence of progressive retinal homeostasis loss. However, the overall improvement of quantitative imaging techniques will allow us to better categorize different RP subtypes, also optimizing the diagnostic workup for future clinical trials.

### **3. Stargardt disease**

STGD is one of the most common IRD associated with both recessive and dominant autosomal transmittance. Most of the patients show pathogenic variants of *ABCA4* gene, whose transmission is autosomal recessively inherited, while the remaining ones have autosomal dominant transmission mainly involving *PROM1* gene or *EVLOV4* [33–35]. The clinical presentation is usually characterized by bilateral central vision loss due to the macular involvement and fundoscopy-detectable

*New OCT and OCTA Insights in Inherited Retinal Dystrophies DOI: http://dx.doi.org/10.5772/intechopen.109953*

#### **Figure 2.**

*Multimodal retinal imaging in STGD. Confocal multicolor image (A) shows hypopigmentation interesting the entire macular region. FAF image (B) confirms the presence of complete macular atrophy, with a thin line of partially preserved autofluorescent signal, together with sparse hyper- and hypoautofluorescence flecks over the entire posterior pole. Structural OCT (C) shows the complete disappearance of the central outer retinal bands, with choroidal hypertransmission and evident thinning of inner retinal layers. OCTA shows rarefied SCP (D), almost absent DCP (E) with some projections artifacts, and disappeared central CC with exposure of choroidal vessels, associated with markedly altered CC in the rest of the posterior pole (F).*

flecks, namely sparse lipofuscin accumulations localized within the posterior pole and outside the vascular arcades. Age presentation follows two main peaks; the first is around 20 years of age with a more severe progression and worse prognosis, while the second one is around 40 years of age, typically presenting in a milder form [36]. A complete noninvasive multimodal retinal imaging STGD case is shown in **Figure 2**.

FAF examination is extremely useful in monitoring STGD progression by delineating atrophic regions, typically presenting as a central hypoautofluorescent area surrounded by a hyperautofluorescent ring [37, 38]. It is important to deeply assess two different sources of hypoautofluorescent signals. In particular, FAF can discriminate definitely decreased autofluorescence (DDAF), defined as a signal more than 90% black in Ref. to the optic nerve head, and questionably decreased autofluorescence (QDAF), defined as a signal included between 50% and 90% of reference black [39]. If DDAF corresponds to complete retinal atrophy, DDAF is more associated with the activity of the disease and the expansion of the atrophic margins. Near-infrared autofluorescence (NIR-AF) is a noninvasive modality focused on the assessment of melanin distribution. It is useful to describe the composition of flecks, which may disclose melanin content over lipofuscin, as well as to clearly detect the sparing of the fovea [40, 41]. If STGD has been mainly considered central dystrophy, the introduction of ultra-wide-field approaches expanded the knowledge regarding peripheral retinal involvement. In particular, different ultra-wide-field FAF patterns have been described, including Type I showing only central alterations without peripheral FAF changes; Type II is characterized by central atrophy and peripheral flecks; Type III presenting macular atrophy, peripheral FAF changes secondary to flecks, and progressively increasing extension of peripheral atrophy, further subclassified as IIIa, IIIb, and IIIc [42]. The peripheral extension of STGD-related alterations significantly correlated with the amount of central morpho-functional involvement, thus configurating completely different STGD phenotypes [43].

OCT is a mandatory investigation in STGD. Flecks are categorized into five different types (A, B, C, D, and E), based on their localization and their stage [44, 45]. In particular, Type A flecks resulted limited to the outer photoreceptors segment. Type B flecks showed protrusions through the interface of the inner photoreceptors segment. Type C flecks protrude up to the lower margin of the outer nuclear layer. Type D flecks lesions were characterized much more involved the thickness of the outer nuclear layer. Type E lesions appeared as drusen-like lesions. Structural OCT provides highly detailed pictures of the amount of outer and inner retinal degeneration, and of the number of hyperreflective foci [46–49]. The outer retinal bands are completely absent in the central part of the retina when atrophic changes occur, with typical choroidal hypertransmission. As previously described for RP, also in STGD it was possible to detect different clinically relevant choroidal patterns. In particular, Pattern 1 had a normal-appearing choroid, whereas Pattern 2 was characterized by alterations of Sattler or Haller choroidal layers. Pattern 3 showed significant alterations in both of the Sattler and Haller choroidal layers, whereas Pattern 4 was characterized by significant alterations in both of the Sattler and Haller choroidal layers and choroidal caverns [50]. The higher the choroidal pattern, the worse result of morpho-functional retinal status [50]. Moreover, choroidal patterns significantly correlated with the rate of STGD progression, resulting in the fastest in the Pattern 4 subtypes [50].

OCTA highlighted the significant vascular involvement of the intraretinal vascular network in STGD, showing a relationship between the amount of vascular impairment and both visual function, FAF, and structural OCT alterations [51–53]. In particular, DCP results highly altered already in early STGD stages, whereas the alterations at the level of the SCP occurs in later stages. The contribution of OCTA was improved by quantitative metrics segregating two different vascular patterns of STGD eyes [54]. Remarkably, the prevalence of foveal sparing was similar between the two OCTA subgroups, suggesting that the pathogenesis of foveal involvement might be even more complex, showing vascular supply impairment as a minor

pathogenic element [54]. In addition, OCTA provided further support to the hypothesis of greater choriocapillaris involvement in STGD, compared with geographic atrophy secondary to age-related macular degeneration, providing the basis for a reliable differential diagnosis [55].
