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Optical coherence tomography angiography was performed on a kHz SD-​OCT with a center wavelength of nm and axial resolution of 5 μm in tissue.
Table of contents

Structurally, this corresponded to pigment changes on infra-red imaging f and subretinal fluid next to a fibrovascular pigment epithelial detachment on OCT g. A prospective observational OCTA study including 74 eyes separated into five groups posterior uveitis with or without ME, anterior uveitis with or without ME, and healthy controls showed that, when compared to healthy controls, eyes with non-infectious posterior uveitis with or without ME had a significantly larger deep foveolar avascular zone, and eyes with anterior uveitis and ME had a significantly larger deep and superficial foveolar avascular zone [ 58 ].

A possible explanation for these findings might be a peripheral displacement of retinal capillaries as a result of the formation of cystoid spaces or cysts, preferentially leading to non-perfusion areas [ 58 ]. Uveitic ME was associated with significant changes in the deep retinal layer, regardless of projection artifacts, correlating well with the location of intraretinal cystoid spaces in the inner retina generally inner nuclear and plexiform layers , as shown by a cross-sectional, observational case series of eyes with anterior, posterior, or panuveitis and healthy controls but no cases of intermediate uveitis [ 36 ].

This is thought to represent an actual change in the capillary density owing to ME, but a physical displacement of retinal capillaries by the ME remains a plausible interpretation [ 36 ]. It was summarized that qualitative and quantitative changes in the parafoveal capillary density and morphology of subjects with uveitis can reliably be detected using OCTA [ 36 ].

There are multiple publications on OCTA in the clinical spectrum of so-called white dot syndromes, a heterogenous group of various forms of posterior or panuveitis having light fundus lesions as at least one common clinical distinguishing sign. APMPPE or multifocal ischemic choroidopathy is a rare type of uveitis, which is characterized by light yellow lesions localized in the outer retina, the retinal pigment epithelium RPE , and the choroid, due to inflamed choriocapillaris, RPE, and outer layers of the retina.

Typical FA findings in the acute phase of the disease are an early blockage of the choroidal background fluorescence under the active lesions, and late staining, whereas in ICGA, these lesions are hypocyanescent during early and late phases of the disease, interpretable as hypoperfusion of the choriocapillaris.

In the later course of the disease, late phase FA exhibits mottling hyperfluorescence, staining, and window defects due to scarring of RPE, whereas ICGA patterns remain the same. Early in the course of the disease, OCTA shows normal perfusion patterns of the superficial and deep layers of the retina, but reduced perfusion of the choriocapillaris and choroid like, not unexpectedly, in FA and ICGA, and also as areas of altered FAF [ 59 , 60 , 61 ].

Over time, the extent of the non-perfused areas decreases and signs of vascular reperfusion can be noted, but persistent flow void remains at the level of the choriocapillaries [ 62 , 63 ]. A multimodal imaging example comparing early and late stage of the disease is given in Fig. Disease-specific limitations of the method are its limited ability to give flow information of the peripheral retina and the limited resolution of the choroidal vasculature, due to the overlying thickened RPE and further inflammatory changes.

Multimodal imaging analysis of the macular and peripapillary area of the right eye showing multiple lesions at different stages of acute posterior multifocal placoid pigment epitheliopathy APMPPE. Serpiginous choroiditis is a rare ocular pathology that presents with binocular, but asymmetric grayish or yellow inflammatory lesions, which develop in an irregular serpentine pattern.

Optical Coherence Tomography | Department of Ophthalmology

These lesions develop into an atrophy of the outer retina, RPE, and the choriocapillaris. Older lesions present with window defect, and, in case of progress or relapse, with staining along the progressing edges. ICGA has been used for staging and detecting new activity during the course of the disease. The area of hypocyanescent choroidal non-perfusion is usually larger than expected by fundus examination, and OCTA can be used in serpiginous choroiditis to detect subclinical or persistent choroidal nonperfusion as lesion size on the OCTA choriocapillaris slabs shows a good correlation with lesions on ICGA [ 64 ].

As reported in another retrospective study with 22 eyes and case series of six eyes, there was no flow signal throughout the entire choroid in active lesions, whereas in inactive lesions, OCTA signals indicated some hyperintensity, which is interpreted as rarefaction of choroidal vessels and loss of choriocapillaris [ 60 , 66 ]. MEWDS is characterized by gray-white fundus lesions, which are the result of RPE lesions, typically located outside the fovea in a granular pattern. Rare findings can be sheathing of retinal veins and superficial retinal hemorrhages.

On FAF images, hyperautofluorescent dots can be appreciated even when funduscopy does not correlate with these dots. On ICGA, the early phase is unremarkable, but in the late phase, multifocal hypocyanescent lesions, even in clinically inconspicuous areas, with ill-defined margins, characterize the lesions of MEWDS.

However, in larger lesions of MEWDS, reduced flow of choriocapillaris had also been detected, thus ICGA hypocyanescence may be still interpreted as a reduction of choroidal blood flow [ 70 ]. However, altered flow information may be also due to a change in the optical property of the choroid due to blockage of invading inflammatory cells. Once again, the limitation of OCTA in detecting flow in the slow-flow system of the choriocapillaris with high enough sensitivity needs to be taken into account [ 71 ].

Remarkably, in the light of OCTA findings in this uveitis type, the discussion about the pathogenesis of MEWDS was recently risen up and mainly questions the primary focus of inflammation, be it in the RPE or the choriocapillaris [ 70 ]. MCP, a chronic, recurrent disease, typically affects female patients in their fourth decade of life. Multiple yellow or yellowish gray lesions of various size, primarily at the level of the RPE and inner choroid, in association with vitreous cells, can be seen on funduscopy.

In their inactive form, these lesions appear punched out, possibly with pigmented fraction and scarring. A common complication in MCP is an inflammatory CNV of type 2 and, as already noted above, OCTA can be very helpful in these cases to define and detect inflammatory CNVs, which is essential for further treatment decisions [ 15 , 19 , 54 , 55 , 57 , 72 ] Fig. Optical coherence tomography angiography OCTA for differentiating acute inflammatory lesions from choroidal neovascularization in a myopic eye with idiopathic multifocal choroiditis.

The flow overlying the RPE layer represents the projection of the flow signal from the more superficial retinal circulation projection artifact. It looks like vascular branches of a choroidal neovascularization, but scrolling the slap through the retina represents a projection artifact. But OCTA has also been shown to have limitations in differentiating active neovascularization versus an inactive scar [ 57 ].

In contrast to MCP, PIC rarely is associated with vitritis and lesions are less commonly seen anterior to the posterior pole and are rather scattered than arranged in a particular pattern. It may be associated with CNV. Sixty percent of the cases are bilateral. POHS lesions correspond to areas of focal flow loss in the choriocapillaris and deeper choroidal layers on OCTA, which is consistent with the theory that choroidal seeding of Histoplasma capsulatum spores leads to the destruction of choroidal blood vessels [ 70 ].

In contrast to most other white dot syndromes, the lesions are more focal than widespread. The name BSR was given to this form of white dot lesion due to its shotgun pattern of creamy whitish lesions scattered throughout the fundus. It is strongly associated with HLA and presents with moderate vitritis and phlebitis, and the lesions affect the choroid and the retina.

In a prospective observational review of four patients with BSR, OCTA visualized telangiectasia, capillary dilatations and loops, and an increased intercapillary space in the retinal vasculature [ 75 ]. Furthermore, as central retinal thinning in birdshot patients correlates with these areas displaying a decreased capillary perfusion on OCTA, it was postulated that thinning of the macula could be due to an ischemic insult to ganglion cells and their axons, although macular thinning on OCT scans show mainly a thinning of outer retinal layers [ 19 ].

Looking at the DCP, even more reduction of flow could be detected, which was proposed to be, besides inflammatory reasons, a possible explanation for the development of retinal neovascularization in BSR [ 76 ] Fig. OCTA demonstrates multifocal hypoperfusion within the choriocapillaris and even larger areas of hypoperfusion when looking at deeper choroidal layers [ 70 , 75 ]. Early active lesions are found in near vicinity of the larger vessels of the Haller layer [ 68 ].

While early active lesions may only involve the deeper choroidal layers and may regress under treatment, chronic birdshot lesions will reveal full thickness choroidal flow void also affecting the choriocapillaris. These lesions will not regress under appropriate treatment [ 77 ].

The Clinical Utility of OCT Angiography

Based on these findings, OCTA may be a reliable additional tool to follow birdshot patients and to identify disease progression and insufficient treatment [ 77 ]. AMN is characterized as wedge-shaped superficial retinal defects in the macula, resulting in paracentral scotomas and are associated with vasoconstrictors and sympathomimetics. The fact that a majority of patients are young females and a lot report flu-like symptoms prior onset of eye symptoms has prompted the conclusion that AMN belongs to the spectrum of white dot syndromes.

On OCT, AMN starts with hyperreflectivity of the outer plexiform layer with subsequent thinning of the outer nuclear layer and a significant attenuation of the interdigitation zone IZ and ellipsoid zone and external limiting membrane. Changes resolve over time; however, usually, sequelae of IZ attenuation, photoreceptor layer thinning, and corresponding scotomas remain.

However, some case series also found persistent flow attenuation in the choriocapillaris [ 78 , 80 , 81 ]. While paracentral acute middle maculopathy PAMM shows consistently flow changes in the DCP as well as the middle capillary plexus and occasionally also in the SCP throughout the literature, the changes found in AMN are more inconsistent [ 82 , 83 , 84 , 85 ].

In contrast to AMN, PAMM is often associated with cardiovascular diseases and cardiovascular risk factors and should therefore not be restricted to the white dot spectrum [ 81 , 86 ]. AZOOR is a rare retinopathy that, in some cases with preceding viral infection, affects one eye, but may also progress to involvement of the second eye. Intraocular cells are rare and the fundus in the early phase appears normal.

As the disease progresses, decreased vision and photopsia is realized by the patient, and a scotoma coinciding with the affected zone of outer retinal dysfunction, often an enlargement of the blind spot, is detectable. The typical finding in progressing AZOOR lesions is retinal atrophy and mottling of the RPE leading to typical fundus changes with grayish or yellowish lines along the atrophy area of the RPE, outer retina, and choroid.

FAF illustrates a characteristic trizonal sign with the increased autofluorescence of active lesions and decreased autofluorescence of damaged RPE cells and normal autofluorescence of the unaffected retina. ICGA may be normal or show hypocyanescence. FA shows, later in the course of the disease, window defects.

OCTA findings may show increased decorrelation signal at the DCP at the watershed zone [ 87 ], but at early presentation, a case report demonstrated normal OCTA imaging of the retinal and choroidal vasculature, whereas en face OCTA structural analysis revealed hyper-reflective dots at the level of ellipsoid zone of different patterns in both affected eyes of one patient [ 88 ]. Furthermore, there are some reports on toxoplasmosis, acute retinal necrosis ARN , and more infrequent conditions such as dengue fever, Bartonella cat-scratch disease and West Nile virus infection, which will be summarized below.

Introduction

TB has various forms of appearance: granulomatous anterior uveitis, intermediate uveitis, panuveitis or posterior uveitis, the latter being the most common presentation. Diverse clinical findings can be seen in TB, e.


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In TB, OCTA has proven to be useful in the detection of CNV in a patient with tubercular serpiginous-like choroiditis and showed an involvement of various retinochoroidal layers by an abnormal vascular network [ 90 ]. In serpiginous-like TB chorioretinitis, OCTA showed a more precise picture of choroidal hypoperfusion as compared with ICGA [ 89 ] and was useful in the follow-up of patients with tubercular multifocal serpiginoid choroiditis [ 91 ].

In a case report of choroidal granuloma caused by TB, a type 2 CNV could be detected in its early stage, and growth was documented with the help of OCTA, although secondary complications like intraretinal fluid were not yet found [ 52 ]. In a sample of nine eyes with different forms of posterior tuberculous uveitis, OCTA showed neovascular flow assigned to type 1 CNV [ 53 ]. For longitudinal choriocapillaris flow evaluation in a TB patient with serpiginous-like choroiditis, OCTA showed progressive restoration of the choroidal circulation over time, with reduction of the lesion size and reduction in hypoperfusion, suggesting vascular remodeling during the recovery phase [ 92 ].

Understanding OCT Angiography

The choriocapillaris flow appeared to progressively restore centrally from the lesion edges under treatment, correlating with FAF signal changes over time, which is an interesting and similar finding as in APMPPE and in idiopathic serpiginous chorioretinopathy [ 92 ]. These findings were confirmed in a larger prospective case series of 32 eyes using a panoramic OCTA device [ 93 ]. The parasite Toxoplasma gondii , an intracellular protozoan, causes necrotizing retinochoroiditis and can cause severe vision loss.

Another, less recent case report focused on the advantage of volume rendering on OCTA of such lesions, which allows visualization of all OCTA scans simultaneously [ 95 ]. A new case report used OCTA for longitudinal follow-up of a toxoplasmic lesion and showed vascular obliteration of the retina and choroid in the acute stage with only partial restoration in the periphery of the lesion during the quiescent stage, but with persistence of destruction in the choriocapillaris texture [ 96 ].

Acute retinal necrosis ARN , mainly caused by varicella zoster virus and herpes simplex virus types 1 and 2, is characterized by vitreal and anterior chamber inflammatory reaction, retinal necrotic lesions, circumferential progression, and evidence of occlusive vasculopathy. A recent case report suggested that OCTA could be used in ARN cases to evaluate the therapeutic response and anatomical improvement as macular vascular density has been observed to decrease until normal density is restored within one month in the SCP and DCP during therapy, supplied by capillary branches of the vessel embedded in a necrotizing retinal lesion [ 97 ].

Dengue fever, an arthropod-borne disease, caused by four serotypes of Dengue virus, can manifest various ophthalmologic symptoms, such as subconjunctival hemorrhage, keratitis, anterior uveitis, angle-closure glaucoma as for anterior segment and, more commonly, ME, retinal hemorrhages, foveolitis, cotton wool spots, AMN lesions, and microaneurysms as for posterior segment involvement [ 98 ]. Deduced from case reports, OCTA has proven to be a worthy diagnostic tool for detecting flow deficits in the perifoveal region within the DCP and SCP in ischemic inflammatory foveolitis and outer maculopathy, even when fundus lesions were not detectable [ 98 , 99 , ].

Bartonella henselae causes focal retinochoroiditis, Parinaud oculoglandular syndrome and neuroretinitis. Bartonella bacteria tend to colonize endothelial cells which seem to have vasoproliferative effects and local CNV-development [ ].

The case of one patient with Bartonella-associated CNV was investigated with OCTA, which proved to be helpful, since dye-based angiographies could not be interpreted conclusively as the hyperfluorescence of the inflammatory lesion did not allow the differentiation of a local neovascular complex [ ]. West Nile virus WNV infection of the eye is mostly associated with bilateral multifocal chorioretinitis.