**1. Introduction**

Optical coherence tomography angiography (OCT-A) is a novel imaging technique that relies on the intrinsic movement of red blood cells (RBCs), allowing non-invasive, motion-contrast, high-resolution images of both retinal and choroidal vascular networks [1].

The retina is supplied by up to 4 layers of vessels: (1) the radial peripapillary capillary network, within the nerve fiber layer and located around the optic nerve head; (2) the superficial vascular plexus, within the ganglion cells layer; (3) the deep capillary complex, which comprises 2 capillary beds on both sides of the inner nuclear layer [2].

The choroid, conversely, consists of 3 layers of vessels: (1) the Haller layer, the outer, large-caliber layer of vessels; (2) the Sattler layer, the middle, smaller-diameter layer of vessels; (3) the choriocapillaris, which is the innermost and smallest layer of vessels [2].

OCT-A is able to clearly display several vascular alterations, including, among others, areas of macular telangiectasia, impaired perfusion, microaneurysms, capillary remodeling and neovascularization [3]. In contrast with conventional imaging modalities, the dye-free image acquisition of this method avoids the onset of typical side effects of fluorescein and indocyanine green angiography (FA and ICGA) [4,5].

More importantly, OCT-A allows depth-resolved analysis of retinal tissue that has never been available before [3]. OCT-A has been adopted to investigate a broad spectrum of retinal vascular diseases, ranging from diabetic retinopathy and retinal venous occlusion, up to age-related macular degeneration, and inflammatory and ocular oncology disorders [3]. Over the past 15 years, the retinal and choroidal imaging capabilities of OCT-A have been applied to further characterize primary and secondary alterations in inherited retinal diseases (IRDs). In this review of the literature, we aim to analyze and summarize all

**Citation:** Iovino, C.; Iodice, C.M.; Pisani, D.; Damiano, L.; Di Iorio, V.; Testa, F.; Simonelli, F. Clinical Applications of Optical Coherence Tomography Angiography in Inherited Retinal Diseases: An Up-to-Date Review of the Literature. *J. Clin. Med.* **2023**, *12*, 3170. https://doi.org/10.3390/ jcm12093170

Academic Editor: Masayuki Akimoto

Received: 21 March 2023 Revised: 14 April 2023 Accepted: 26 April 2023 Published: 28 April 2023

**Copyright:** © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

clinical applications of OCT-A in the diagnosis and management of IRDs and to discuss advantages and limitations of this imaging technique.

## **2. Optical Coherence Tomography Angiography Technical Aspects**

OCT-A is an optical coherence tomography (OCT)-based imaging technique that enables the visualization of blood vessels within the eye, and it is built on the principle of OCT signal variation generated by the moving RBCs within the vessels [6–8]. Multiple scans are performed at the same location and the subsequent temporal changes of the OCT signal caused by the constant motion of the RBCs generate angiographic contrast, allowing visualization of the microvasculature [3].

Barton et al., in 2005, laid the foundation for this relatively new technology, which has only been commercially available since 2016 [9]. The authors adjusted analysis of speckles to produce an amplitude-based angiogram [9]. The speckle pattern stays relatively constant over time for static objects, while it changes for moving scatterers (i.e., erythrocytes) [9]. In 2009, Wang et al. introduced optical microangiography (OMAG), an imaging technique in which spatial frequency analysis of time-varying spectral interferograms was used to distinguish the signals backscattered by particles in motion from those backscattered by static objects, creating a high-resolution angiogram image [10]. Subsequently, in 2012, Jia et al. developed a more refined signal processing algorithm, named split-spectrum amplitudedecorrelation angiography (SSADA), which enhanced the signal-to-noise ratio of flow detection while reducing the pulsatile bulk-motion noise [11].

OCT-A may be captured with spectral domain OCT (SD-OCT), which, in commercial devices, employs a wavelength of ~840 nm, or with swept-source OCT (SS-OCT), which uses a longer wavelength of ~1050 nm [12].

While OCT is considered a cross-sectional imaging modality, OCT-A images are mainly studied with en face visualization. Currently, all commercially available OCT-A platforms allow the segmentation of the volumetric scans at specific depths through the definition of "slabs" [12].

FA and ICGA have been considered, so far, the gold standard for the evaluation of retinal and choroidal vasculature in vivo. Nevertheless, although dye injection is generally safe, serious allergic reactions may occur and these techniques are therefore considered invasive [12]. Moreover, the use of dyes in pregnant or breastfeeding women appears to be controversial [13,14].

OCT-A provides a non-invasive and fast analysis of choroidal and retinal microvascular circulation without the need for any dye injection. Moreover, it has the additional advantage of depth-resolution with better visualization of the deeper vascular layers [12].

#### **3. Clinical Applications**

#### *3.1. OCT-A in Retinitis Pigmentosa*

Most of the literature about the findings of OCT-A in retinitis pigmentosa (RP) converged to a common demonstration of retinal and choroidal vascular impairment. A summary of the data collected is reported in Table 1.

The mean follow-up ranged between 2 months and 36 months [12–31]. Overall, significant reductions in both the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were observed in all the affected patients of the evaluated cohorts over time [12–31]. In addition, all the studies that explored the involvement of choriocapillaris (CC) demonstrated its significant impairment in RP patients [12,15–17,21–23,25,30,31]. Several authors focused on the variation of the foveal avascular zone (FAZ) area in RP patients, two-thirds of which described an increased avascular area [12,15,19,20,26,31], while the remaining third demonstrated its significant reduction [16,17,29]. Nakajima et al. and Alnawaiseh et al. explored an interesting association between the reduction in optic nerve head (ONH) vessel density (VD) in RP patients and the deterioration of the visual field mean deviation (MD) [15,27]. The authors demonstrated that the VD in both the radial peripapillary capillary network and ONH layers was significantly lower in patients rather

than controls, significantly correlating with the MD and the cup/disc area ratio [15,27]. Mastropasqua et al. investigated the mean microperimetry (MP) retinal sensitivity between RP patients and healthy subjects and explored possible correlations with retinal perfusion density [25]. The authors found a significant reduction in retinal sensitivity in RP patients, compared to healthy controls, at 4◦, 8◦ and 20◦ [25]. A significant positive correlation was also observed in RP patients between the perfusion density of the central 1.5 mm retina in either DCP and CC and microperimetry at 4◦ and 8◦, meaning that a reduction in the perfusion density would be associated with a retinal sensitivity decrease [25]. Toto et al. demonstrated instead that parafoveal SCP and DCP VD were significantly correlated with mfERG values, while parafoveal CC VD correlated directly with the P1R2 amplitude, highlighting that vessel impairment may affect macular function [33].

A representative case of RP patient examined with OCT-A is shown in Figure 1.

**Table 1.** Optical coherence tomography angiography features in patients with retinitis pigmentosa.


CC: choriocapillaris; CVI: choroidal vascularity index; CH: choroid; DCP: deep capillary plexus; F-UP: followup; FAZ: foveal avascular zone; MO: months; NA: not applicable; N.: number of; ONH: optic nerve head; P: prospective; R: retrospective; RPL: radial peripapillary layer; SCP: superficial capillary plexus; VD: vessel density. Results were significant for *p* < 0.05.

**Figure 1. Multimodal imaging features in a patient with genetically confirmed retinitis pigmentosa**. (**A**) Color fundus image displays pallor of the optic disc, attenuation of retinal vessels, extensive retinal atrophy, and pigmentary clumping in mid-periphery. (**B**) Blue-light autofluorescence (BAF) shows a granular hypoautofluorescence extending from the perifoveal region to the midperiphery. En face 6 × 6 optical coherence tomography angiography with corresponding B scan angio flow of superficial capillary plexus (**C**), deep capillary plexus (**D**), and choriocapillaris (**E**) with automatic segmentation. Flow voids areas are denoted in all retinal plexuses, and especially in the choriocapillaris, possibly related to either segmentation artifacts, outer retinal atrophy, or extremely reduced blood flow which fails to produce a signal (see corresponding B scans angio flow).
