Role of OCT Angiography OCTA in the Diagnosis of Macular Diseases

Abstract

OCT becomes an indispensable tool in everyday practice. OCTA is the functional extension that provides cross-sectional information on retinal and choroidal circulations without dye injection. It allows visualization of abnormal flow in areas with no flow and abnormal vessels (like CNVM). In ARMD, it can detect active membranes before being leaky in FFA. In diabetic retinopathy, OCTA can diagnose abnormal areas of non-perfusion in the superficial plexus, deeper capillary structures, or neovascularization. OCTA can detect focal dilation and foveal capillaries alterations in macular telangiectasia. It is useful in the diagnosis of inherited retinal diseases such as retinitis pigmentosa. OCTA has many challenges including longer acquisition times and motion artifacts. Longer wavelength SS-OCT may provide a solution for imaging through media opacities and a wider field of view. OCTA does not give full details about the retinal periphery, also, it gives no information about blood-retinal barrier (no dye to leak); an important sign in many retinal diseases.

1. Introduction

With the introduction of OCTA, a new era of technological applications in the field of retinal pathologies has been opened. OCTA is a safe, fast imaging tool that allows better delineation of the retinal microvascular and choroidal vascular abnormalities without the risks of dye injection and morbidity hazards. It can show both blood flow and structural changes within the macular area. OCTA also helps to quantify vascular impairment according to the severity of the retinopathy. It is a useful modality for better understanding the real pathology of retinal diseases especially the retinal vascular occlusions, pathological myopia, inherited retinal disorders, and age-related macular degeneration, that opened the way for evaluating the effect of different treatment modalities, and monitoring of disease progression [1]. OCTA, in order to construct a blood flow, compares the differences in the backscattered signal intensity (decorrelation signal) between sequential OCT b-scans taken at a fixed point at a time (representing erythrocyte movement in retinal blood vessels). Incorporation of the split-spectrum amplitude-decorrelation angiography (SSADA) algorithm in flow detection, improves the signal-to-noise ratio. Although OCTA is a rapid three-dimensional scan with many advantages, it has also some limitations including the limited normative database, small field of view, more prone to image artifacts, obscuration by hemorrhage or fluid and the inability to show leakage (FA will remain the gold standard in this) [2]. However, FFA cannot separately visualize the major capillary networks; (superficial retinal, deep retinal, and choriocapillaris) or radial peripapillary network, with the possibility of systemic side effects and allergic reaction to the injected dye. OCTA vascular changes may be affected by the axial length and individuals’ systemic vascular risks [3].

NB: A detailed description of OCTA principles was mentioned in the first chapter “OCT from the Past to the Future.”

2. OCTA in age-related macular degeneration

Age-related macular degeneration (AMD) is the commonest cause of irreversible visual loss in the elder age group (above 65 years old and more). AMD is classified into two clinically distinct types, that is dry (non-neovascular) AMD and wet (neo-vascular) AMD. In the former, the clinical hallmark is drusen which are yellowish-white deposits within the RPE-Bruch’s membrane complex believed to be secondary to metabolic RPE dysfunction as well as impaired conductance of Bruch’s membrane. In the clinical course of the disease, dry AMD can either progress to advanced dry AMD with geographic macular atrophy or to wet AMD with the development of choroidal neovascularization which can be sub-RPE (type I), subretinal type II) or intraretinal (type III CNV; also called retinal angiomatous proliferation (RAP).

Different CNV-vessel patterns based on OCTA according to Sulzbacher et al. were assessed. The loose-net (LN) presented as large diameter vessels, well-defined and discernible with a low branching index showing no capillary sprouting. The dense-net (DN) appeared as a hyperreflective vascular net with dense capillary branching. Lesions with a ratio of approximately 50% of areas with large vessel diameter/low branching index and approximately 50% of areas with dense capillary branching were identified as the mixed type. Unidentifiable CNV pattern term was used when no neovascular vessels were detectable (neither in the choriocapillaris CC nor in the outer retina). Darwish classified AMD (according to OCTA lesions) into 2 patterns; pattern I requiring treatment and pattern II not requiring treatment. Pattern I showed all or at least three of the following five features; a well-defined CNV (tortuous lacy-wheel shaped), branching pattern (numerous tiny capillaries), presence of anastomoses and loops, the morphology of the vessel terminals (presence of a peripheral arcade) and perilesional hypo-intense halo. Coscas et al. provided these criteria as a basis for analysis and evaluation of CNV activity and the degree of CNV proliferation, persistence and/or recurrence; conversely, they provide for the stabilization and healing of vessels that become mature or quiescent. While a CNV lesion was considered as pattern II if it showed less than three of the previously reported OCTA features [4, 5, 6].

In AMD, OCTA has the advantage of dual appraisal of structural RPE and photoreceptor changes as well as vascular changes of choriocapillaris either choriocapillaris loss in dry AMD or the advent of choroidal neovascular membrane which is the defining feature of wet AMD. The longitudinal correlation between outer retinal and RPE structural changes and choriocapillaris vascular alterations in the clinical context of AMD constitutes the basis for OCTA utility in AMD which serves not only diagnosis but also follow-up and appraisal of response to treatment, for example anti-VEGF (Figures 1 and 2). However, OCTA choriocapillaris slabs must be assessed cautiously because they are liable to projection and masking artifacts of overlying structures given their deep anatomical location. Therefore, OCTA choriocapillaris slabs must always be correlated with the structural en-face images. OCTA can also show the early subclinical CNV before the signs of activity in the conventional FFA or SD-OCT [7, 8].

Figure 1.

A: Active type 2 CNVM lesion imaged by Optovue Angiovue OCTA. A: At the choriocapillaris level, there is a densely packed vascular net formed of loops, and peripheral anastomoses and surrounded by a hypointense halo. The lesion is seen invading the RPE. The B-scan showed accumulated subretinal fluid. B: After injection, the CNVM shows inactivity. Large mature vessels are seen in a “dead tree” appearance showing no peripheral anastomosis or loops. No fluid accumulation is visible on SD-OCT with macular thinning (atrophy).

Figure 2.

A: Active type 2 CNVM lesion imaged by Optovue Angiovue OCTA, A: With a mixed net configuration at choriocapillaris showing minimal activity and increased central thickness in B-scan. B: After repeated injections, the vascular tree in OCTA gets mature with decreased CMT in SD-OCT scan.

3. OCTA in myopic macular-related conditions

Pathological/degenerative myopia is characterized by progressive anteroposterior elongation of the globe with resulting morphological, structural and functional consequences. Ocular pathologies associated with degenerative myopia include myopic traction maculopathy e.g. myopic retinoschisis, posterior staphyloma, parapapillary atrophy, and myopic choroidal neovascular membrane among others. Myopic CNVM has a poor prognosis for central vision preservation and is a major cause of visual morbidity in myopic patients. Since OCTA combines both high-resolution structural B-scans and angiography, it can be useful to demonstrate structural and morphological alterations of myopia like retinoschisis, parapapillary atrophy, dome-shaped macula as well as to detect the development of CNVM (Figures 3 and 4). However, the anatomical derangement of the posterior segment in degenerative myopia can pose an obstacle to retrieving high-quality OCTA images with OCTA segmentation artifacts being very common in eyes with degenerative myopia. Therefore, myopic OCTA images have to be examined cautiously and frequently require manual segmentation by an expert to lessen the impact of segmentation artifacts [9, 10].

Figure 3.

A myopic CNVM case: A branching tree with peripheral anastomoses and looping as well as dark halo around the edges conforming activity. The B-scan showed subretinal fluid accumulation denoting activity.

Figure 4.

End-stage myopic CNVM; a dead tree configuration at the level of choriocapillaris with a lack of branching, anastomoses, and looping.

4. OCTA in macular oedema of different pathologies

Macular oedema is a pathological component of myriad ocular conditions and is a major cause of visual morbidity. Macular oedema can be due to inflammatory cause (as in uveitis), vascular, diabetes mellitus, retinal vein occlusion, CNV, metabolic, or in cases of retinal dystrophies. The high-resolution OCT B-scans allow for accurate description of macular oedema in terms of thickness, morphological pattern (cystoid, spongy or associated neurosensory detachment), and the anatomical involvement of selected retinal layers, the outer plexiform layer (OPL) (Figure 5). Such details can be useful not only for disease diagnosis but also for follow-up of treatment response. An advantage of OCTA over the traditional OCT B-scans is the ability to simultaneously correlate macular oedema with the underlying aetiological vascular process, for example ischemia and vascular drop-outs.

Figure 5.

Optical coherence tomography angiography (OCTA) of mild NPDR with diabetic maculopathy, the SCP (b, e) showed well-defined perifoveal and parafoveal vessels with areas void of flow representing area of capillary drop-outs, more than those seen with the conventional FFA (a). SAME findings in the DCP (c, f) but more advanced regarding the areas of ischemia there is significant decrease in the perfusion as measured by the vessels density and flow index (d) more evident in the DCP.

In diabetic eyes, OCTA can delineate successfully the enlarged FAZ with underlying non-perfusion that increases according to the severity of diabetic retinopathy, quantitative measurement of vascular density (mainly perfusion density and vessel density), reduced capillary density in the superficial and deep capillary plexuses, microaneurysms (appear as focally dilated saccular or fusiform capillaries), choriocapillaris flow voids changes and increased vessel tortuosity. Moreover, OCTA may show DR before it is clinically detectable.

However, OCTA has certain limitations in the assessment of vascular retinal diseases associated with macular oedema. It is incapable of testing the structural and functional integrity of vessel walls and hence cannot demonstrate leakage (reflecting the breakdown of the blood-retinal barrier) as in FFA or ICGA. FFA has the advantage of showing abnormal blood vessels, such as retinal neovascularization or intraretinal microvascular abnormalities. In addition, OCTA has so far, a limited imaging field missing most of the peripheral retina which is the main site of pathology in a number of retinal diseases (the developing widefield OCTA technology). Therefore, for DR, fluorescein angiography will remain an essential vital diagnostic modality and OCTA will be the alternative or complementary method of angiography that can be safely (in risky patients especially with impaired kidney functions) and more frequently performed to assess the effectiveness of treatment in DR [11, 12, 13, 14].

Macular telangiectasia Type 2 (MacTel2) is a neurodegenerative change affecting the Muller cells in the macular area. SD-OCT abnormalities in MacTel include; cyst formation in the inner retina, disruption of the external limiting membrane, loss of inner/outer segment, parafoveal venular dilation, hyporeflective cavitation of the outer retina, perifoveal capillary leakage, and subretinal neovascularization. In OCTA, Zeimer et al. noted vascular changes in the deep capillary network (enlargement of vessels, larger intervascular spaces, dilated, dendritic appearance of vessels, telangiectasis, reduction and/or loss of capillary density), and the extension of anastomoses toward the superficial capillary network with progression of the disease. RPE-proliferations were often associated with “contraction” of surrounding vessels [14, 15] (Figures 6 and 7).

Figure 6.

Mac Tel type 2 OCT-angiography shows temporal flow voids areas in the superficial and deep capillary plexuses, spacing between the vessels with increased vascular diameter, and minimal vascular invasion of the FAZ at the deep capillary plexus. The B scan shows multiple hyporeflective cavitations, focal loss of the inner/outer segment with no evidence of external limiting membrane disruption.

Figure 7.

Advanced mac Tel type 2 OCT-angiography showed temporal flow voids areas in the superficial and deep capillary plexuses. Telangiectatic vessels are seen among the superficial and deep plexuses with increased vascular diameter as well as rarefied vessels; temporal and superior to the FAZ with right-angled configuration and, vascular invasion of the FAZ at the superficial and deep capillary plexuses. The B scan showed multiple hyporeflective cavitations with focal and diffuse loss of the inner outer segment as well as external limiting membrane disruption.

5. OCTA in challenging macular disorders

5.1 Vaso-occlusive disorders

Retinal vein occlusions (RVOs) are one of the visually disabling pathologies that lead to impaired capillary perfusion and retinal ischemia. OCTA has the ability to view the retinal vasculature in details as seen in FFA and SD-OCT, which allows accurate evaluation of the microvascular abnormalities including areas of capillary non-perfusion, shunt vessels, vascular dilatation, enlarged the FAZ size, foveal atrophy, intraretinal oedema, and multiple hyporeflective spaces in the inner retinal layers. Bonini Filho et al. reported that OCTA in retinal artery occlusion (RAOs) can accurately delineate retinal capillary plexuses at different levels with the extent of macular ischemia and monitoring vascular flow changes during the disease course [14, 16] (Figures 8 and 9).

Figure 8.

A case of branch retinal vein occlusion BRVO, OCT-A showed enlarged FAZ with parafoveal flow voids areas in the superficial and deep capillary plexus, more evident in the deep plexus. The b-scan showed interrupted epiretinal membrane with foveal atrophy and multiple hyporeflective spaces in the inner retinal layers. Also, the inner outer photoreceptors segment shows focal disruption up to the ELM.

Figure 9.

A case of central retinal vein occlusion CRVO with the OCTA showed asymmetry between the affected and healthy retina. Both superficial and deep network showed rarefied appearance with small telangiectatic vessels at the level of the deep capillary plexus. The RPE and the choriocapillaris showed multiple dark areas representing areas void of flow caused by the shadow casted by the subretinal fluid.

Figure 10.

Adult Vitelliform dystrophy, SD-OCT showed a hyper-reflective material lies between the RPE/Bruch’s membrane complex and the photoreceptors layer (ellipsoid zone). In OCTA, there is displacement of blood vessels at the level of the superficial and deep capillary plexus caused by the accumulation of the subretinal material with rarefaction of the choriocapillaris layer.

Figure 11.

Stargardt’s disease, OCTA showed rarefied superficial and deep capillary plexus with decreased vessel density, decreased flow index, and more exposure of the choroidal blood vessels.

Figure 12.

Retinitis pigmentosa case showed an irregular widened FAZ at the level of the superficial and deep plexus with areas void of flow mainly in the superficial plexus. Diffuse loss at the level of the RPE and the choriocapillaris with exposure of the large choroidal blood vessels findings confirmed by the B-scan showing cystoid oedema and loss of the inner/outer segment as well as the affection of the RPE/choriocapillaris complex.

5.2 Inherited retinal dystrophies

Inherited retinal dystrophies are a heterogenous group of diseases that result from mutations in various genes with consequent changes in retinal metabolism that result in photoreceptor loss. The most common retinal dystrophies include vitelliform dystrophy (Figure 10), Stargardt’s disease (Figure 11), and retinitis pigmentosa (Figure 12). In Stargardt disease, mutations and subsequent decrease in ABCA4 gene activity results in excessive lipofuscin deposition in RPE. The characteristic dark choroid appearance in FFA of Stargardt results from absorption of the blue excitation light by the lipofuscin pigment in RPE. B-scan OCT in Stargardt disease demonstrates the outer retinal changes of RPE irregularities and shaggy photoreceptor layer with outer retinal loss in the advanced stages. Recently, OCTA showed severe choriocapillaris atrophy coinciding with the areas of RPE and photoreceptor loss that were previously undetectable by FFA due to RPE lipofuscin deposits. Vitelliform dystrophy is due to a mutation in the BEST gene and hence the other name, that is Best disease. In the early stages of the disease, there is progressive deposition of subretinal vitelliform, egg-yolk-colored material, that is vitelliform stage, which then starts to resolve leaving behind variable degrees of photoreceptor loss and may become complicated by CNV. Therefore, OCTA can be very useful to detect the CNV complication of vitelliform dystrophy which is mostly undetectable by either FFA or B-scan OCT due to masking and projection artifacts respectively. Retinitis pigmentosa is an umbrella term for a group of hereditary retinal diseases that share some common clinical and pathological features. Retinitis pigmentosa is historically characterized by the clinical triad of retinal arteriolar attenuation, waxy optic disc pallor, and RPE proliferation and intraretinal migration, which manifest as bone spicule retinal pigmentations. While the main cause of visual impairment in retinitis pigmentosa is photoreceptor loss, other complications may concur and contribute to visual morbidity, for example macular oedema. Consequently, OCTA can prove useful in detecting macular oedema as well as retinal vascular plexus changes in retinitis pigmentosa [17, 18].

The B-scan showed diffuse foveal atrophy with hyperreflective external limiting membrane, loss of the ellipsoid zone, and invariance of retinal tissue through Bruch’s membrane.

6. OCTA in inflammatory retinal and uveal diseases

Uveitis is inflammation of the uveal tract, which is the middle vascular coat of the eye. It is classified into anterior, middle, and posterior uveitis according to the anatomical portion involved being the iris and anterior ciliary body, pars plana, and posterior uvea, respectively. While anterior uveitis causes predominantly anterior segment complications, for example cataract, synechia, corneal opacities, and glaucoma; intermediate and posterior uveitis cause posterior segment complications that are the culprits in visual morbidity. Posterior segment complications of uveitis include macular oedema, exudative retinal detachment, CNVM, occlusive retinal vasculitis, and ischemia. Given the major contribution of posterior segment complications in myriad types of uveitis, B-scan OCT and OCTA can be of help in the detection and follow-up of such complications with an accurate characterization of macular oedema, areas of vascular drop-outs, for example ischemia at the different ocular vascular beds, such as the superficial and deep macular vascular plexuses and choriocapillaris. A significant limitation of OCTA in posterior uveitis and retinal vasculitis is the small field of imaging which may not appreciate peripheral retinal involvement which is not only common but also important in proper management like delineating peripheral ischemic retinal zones for subsequent retinal photocoagulation. Therefore, a multimodal imaging approach including wide-field dye-based angiography combined with B-scan OCT and OCTA is a must for proper and comprehensive management of uveitis which mirrors the multidisciplinary approach to uveitis diagnosis [19, 20, 21].

7. OCTA in retinal and choroidal tumors

OCTA is an evolving technology that can be useful in the study of posterior segment tumors. The choroidal nevi are mainly seen as heterogenic and hyperreflective lesions. When studying melanocytic tumors, the higher risk of malignancy (choroidal melanoma) is associated with the presence of parilesional hyporeflective plexus or hyperreflective ring (in the choriocapillaris layer) [22] (Figure 13).

Figure 13.

OCTA of choroidal metastasis, choriocapillaris slab shows significant loss of its’ classically mottled appearance, there are areas void of signal indicating tumor invasion of the blood vessel. The b scan showed a classic bumpy appearance with smooth elevation and visible subretinal fluid.

Acknowledgments

Ahmed Ameen Ismail, M.B.B.Ch.

Department of Ophthalmology, Faculty of Medicine, Fayoum University, Al Fayoum, Egypt.