**6. Spectral domain OCT (SD-OCT) and OCTA features of selected macular dystrophies**

#### **6.1. Stargardt's disease**

Stargardt's disease is considered the most common inherited childhood dystrophy. The pattern of inheritance is an autosomal-recessive one and represents the mildest form of ABCA4 gene mutation. The mutated gene causes malfunction of the ATP-binding cassette proteins that have key role in cell transport processes within the photoreceptors layer. The resultant disruption of photoreceptors visual cycle leads to over-accumulation of a metabolic byproduct, namely lipofuscin in the RPE cell layer. Clinically, patients present with bilateral and symmetrical involvement of the posterior pole by characteristic yellowish flecks at the level of the RPE resembling fish scales. Occasionally, two adjacent flecks join in an obtuse angle reminiscent of a fish tail, hence the term pisciform. The end stage is characterized by resorption of flecks and ensuing atrophic maculopathy with a substantial visual loss. To date, no known treatment exists for Stargardt's disease [1, 2].

SD-OCT in Stargardt's disease demonstrates thinning of the outer retina including the photoreceptor layer and the RPE, and altered choroidal morphology in which the normal bowlshaped contour of the choroidoscleral interface, with maximum thickness at the sub-foveal area, is replaced by an abnormal S-shaped contour due to a marked reduction of sub-foveal choroidal thickness and displacement of the thickest point of the choroid away from the fovea [13]. On the other hand, OCTA imaging reveals generalized attenuation of the vascular layers of the ocular fundus, though the most significant vascular changes are located in the choriocapillaris, which exhibit generalized loss of the normal homogeneous hyperintense texture with the development of vascular rarefaction and flow-void areas. These morphological changes are attributed to the patchy loss of choriocapillaris or to the masking effect of the pisciform flecks [15, 29]. In some cases, there is enhanced visualization of the underlying Sattler's layer [16]. In terms of retinal capillary plexuses, vascular alterations of the SCP layer include rarefaction of the peri-foveal arcade with the enlargement of the foveal avascular zone (FAZ), and generalized reduction of vessel density in the SCP and the DCP layers, though these changes are most pronounced in the DCP layer [15, 28, 29].

#### **6.2. Best's disease (vitelliform macular dystrophy)**

In this map, vessel density in a given area is inferred from the decorrelation motion contrast signal provided by SS-OCTA, where high flow is represented by an increased vessel density and vice versa. Different vessel densities are then given color codes and numeric percentage values that reflect the percentage area occupied by blood vessels, where bright red color represents areas of highest density and hence a high numeric percentage, whereas dark blue represents areas of no detectable vessels and hence low or zero numeric percentage. Intermediate

Normally, the retinal superficial capillary plexus (SCP) appears on SS-OCTA as an interlacing network of horizontal arterioles and venules connected by transverse capillaries and anastomosing together to form the peri-foveal capillary circle. Arterioles are surrounded by a wider capillary-free zone compared to venules. The retinal deep capillary plexus (DCP) appears as polygonal lobules or vortices composed of capillaries converging radially on an epicenter. The choriocapillaris appears as a homogeneous hyperintense layer composed of densely

**6. Spectral domain OCT (SD-OCT) and OCTA features of selected** 

Stargardt's disease is considered the most common inherited childhood dystrophy. The pattern of inheritance is an autosomal-recessive one and represents the mildest form of ABCA4 gene mutation. The mutated gene causes malfunction of the ATP-binding cassette proteins that have key role in cell transport processes within the photoreceptors layer. The resultant disruption of photoreceptors visual cycle leads to over-accumulation of a metabolic byproduct, namely lipofuscin in the RPE cell layer. Clinically, patients present with bilateral and symmetrical involvement of the posterior pole by characteristic yellowish flecks at the level of the RPE resembling fish scales. Occasionally, two adjacent flecks join in an obtuse angle reminiscent of a fish tail, hence the term pisciform. The end stage is characterized by resorption of flecks and ensuing atrophic maculopathy with a substantial visual loss. To date, no

SD-OCT in Stargardt's disease demonstrates thinning of the outer retina including the photoreceptor layer and the RPE, and altered choroidal morphology in which the normal bowlshaped contour of the choroidoscleral interface, with maximum thickness at the sub-foveal area, is replaced by an abnormal S-shaped contour due to a marked reduction of sub-foveal choroidal thickness and displacement of the thickest point of the choroid away from the

color shades represent variable grades of vessel density [26, 27].

packed capillaries with no intervening dark spaces [21, 27, 28].

known treatment exists for Stargardt's disease [1, 2].

**choriocapillaris in normal individuals**

**macular dystrophies**

6 OCT - Applications in Ophthalmology

**6.1. Stargardt's disease**

**5. SS-OCTA depiction of retinal vascular plexuses and the** 

Best's disease is an autosomal-dominant disorder whose primary target tissue is the RPE cell layer. The condition is caused by mutation in the BEST1 gene which causes the production of abnormal bestrophin protein. Normally located in the RPE plasma membrane, bestrophin acts as a calcium-dependent chloride channel and is responsible for normal ionic conduction across the RPE cell. Abnormal bestrophin formation causes the disruption of the ionic conduction within the RPE and interferes with the normal calcium metabolism that is essential for adhesiveness between interphotoreceptor matrix and the RPE layer. The end result is the deposition of abnormal amorphous vitelliform or egg yolk-like material in the photoreceptors' outer segments, within the RPE and sub-RPE. Though considered the hallmark of Best's disease, the origin of the vitelliform material remains uncertain. One plausible theory is that it is derived from the accumulation of lipofuscin material within over-shed photoreceptors' outer segments due to abnormal phagocytosis by RPE cell layer. Clinically, the disease is characterized by a solitary sub-retinal vitelliform lesion occupying the macular area. Less commonly, lesions may be multiple or eccentric in location. With time, the vitelliform lesion undergoes degeneration and may even get resorbed completely, with ensuing atrophic changes and scarring. Vision remains unaffected in early stages with most individuals maintaining reading and driving vision well into adult life until the atrophic or cicatricial stages develop. The abnormal ionic conduction in Best's disease is responsible for the characteristic loss of light response and abnormal Arden ratio on electro-oculogram (EOG) examination [1, 2].

SD-OCT in early stages of the disease shows a sub-retinal smooth dome-shaped amorphous optically opaque material. As the disease progresses, degenerative changes ensue on the vitelliform structure causing it to break down. The corresponding SD-OCT features consist of irregular optically—opaque amorphous deposits alternating with optically—translucent areas that correspond to the resorbed vitelliform material. In addition, RPE irregularities could be detected including irregular thickened RPE layer, and solitary or multiple RPE detachment(s) (PED). The atrophic stage of the disease is marked by diffuse disruption of the outer retinal layers including the external limiting membrane (ELM), inner segment/outer segment (IS/OS) photoreceptor junction, and marked atrophy or even disappearance of RPE cell layer [30, 31].

OCTA in Best's disease demonstrates generalized rarefaction of the SCP and the DCP layers along with a reduced vessel density. The mechanism of vascular rarefaction in Best's disease is controversial. One explanation is that the vitelliform material causes centrifugal displacement of blood vessels in the macular area with resultant progressive atrophy due to mechanical compression. Occasionally, the DCP layer shows a central area of hypointense signal caused by vascular rarefaction and a reduced vessel density surrounded by an annulus of hyperintense signal. This peculiar configuration could be due to overcrowding of vessels being displaced by the vitelliform lesion, or due to compensatory dilatation of the para-macular vascular bed secondary to vessel rarefaction in the macula, with consequent increased blood flow. Likewise, the choriocapillaris shows vascular rarefaction with multiple hypointense flow-void areas, which could be explained by vascular impairment due to degenerative changes induced by mechanical compression or due to masking effect by the accumulating vitelliform material [30–35].

revealed bilateral numerous yellowish discrete flecks in the macular area at the level of the RPE. The lesions were identical in appearance though more numerous in the RE. SS-OCT examination revealed bilateral foveal thinning, disrupted ELM and IS/OS photoreceptor junction, and thinning of the choriocapillaris with enhanced visualization of the larger choroidal vessels. SS-OCTA revealed bilateral rarefaction of the SCP and the DCP layers. Affection was more pronounced in the DCP layer. The choriocapillaris showed a moth-eaten appearance instead of the normal hyperintense homogeneous texture, due to the presence of multiple black areas that could correspond to areas of flow void or masking effect by the pisciform lesions. The corresponding flow density maps showed a reduced vessel density that corresponded to vascular rarefaction in the SCP, the DCP, and the choriocapillaris

Novel Insight into Morphological Features and Vascular Profile of Selected Macular Dystrophies…

http://dx.doi.org/10.5772/intechopen.78679

9

Case 2. Late stage of Stargardt's disease. A 58-year-old female who was a known case of Stargardt's disease presented for follow-up with complaints of defective vision in both eyes of approximately 2-year duration. Her BCVA was 20/400 and 20/200 in the RE and the LE, respectively. Fundus examination of the RE revealed a sharply circumscribed area of geographic atrophy occupying the macula, approximately of 4 disc diameters (DD) in size. On

**Figure 1.** Case 1. Top left, color photograph of the RE of a 26-year-old male in early stage of Stargardt's disease. Note the numerous subretinal pisciform yellowish flecks occupying the macular area. Bottom left, radial scan SS-OCT shows foveal thinning (168 μ), disrupted ELM and IS/OS photoreceptor junction, and thinning of the choriocapillaris with enhanced visualization of the larger choroidal vessels. Right, en face SS-OCTA projection of the SCP, the DCP, and the choriocapillaris in a 6 × 6 mm field (upper row), and the corresponding flow density maps (lower row). The SCP and the DCP layers show vascular rarefaction. Affection is more pronounced in the DCP layer. The choriocapillaris shows a moth-eaten appearance instead of the normal homogeneous hyperintense texture, due to the presence of multiple black areas of flow voids. The corresponding flow density maps show a reduced vessel density that corresponds to vascular

rarefaction in the SCP, the DCP, and the choriocapillaris.

(**Figures 1** and **2**).

#### **6.3. Choroidal neovascularization secondary to Best's disease: a diagnostic predicament**

The most dreadful complication of Best's disease is CNV formation, which could develop in some cases secondary to compromised RPE/Bruch's complex [30, 32–34]. The advent of CNV on top of Best's disease could pose a diagnostic challenge due to overlapping fluorescein patterns of the vitelliform material and PEDs in Best's disease and the fibrovascular and neovascular components of CNV. Likewise, SD-OCT could yield inconclusive results, even when deploying the ultrahigh-definition versions, due to similar backscattering light intensity properties between the amorphous vitelliform and the CNV. OCTA helps disentangle this overlap by its ability to separate erythrocytes from the surrounding static tissue, hence displaying flow in a vascular network that is pathognomonic of CVN formation. In addition, OCTA integrates light-scattering reduction technology (reduced sensitivity roll-off) that preserves the integrity of the incident infra-red laser beam, hence allowing deeper penetration, layer segmentation, and delineation of the neovascular network of CNV from the surrounding vitelliform material [20, 27, 36–40].
