Optical Coherence Tomography Angiography of Shallow Irregular Pigment Epithelial Detachments In Pachychoroid Spectrum Disease


To determine the proportion of shallow irregular pigment epithelial detachments in eyes with pachychoroid features that harbor neovascular tissue and to study the morphology of this tissue with optical coherence tomography (OCT) angiography.


Prospective consecutive cohort study.


Patients with pachychoroid spectrum diagnoses and shallow irregular pigment epithelial detachment in at least 1 eye (study eye) were included. Charts and multimodal imaging were reviewed to determine a dye angiography detection rate for type 1 neovascularization in study eyes. All patients then underwent OCT angiography prospectively, followed by masked segmentation and grading.


Twenty-two eyes of 16 patients were included. Mean age was 71 (range 57–95) years. Mean subfoveal choroidal thickness was 381 μm (standard deviation: 141 μm). Four out of 22 study eyes (18%) exhibited polypoidal lesions. Dye angiography demonstrated specific features of neovascularization in 5 out of 17 eyes (29%) with suspected nonpolypoidal pachychoroid neovasculopathy. With OCT angiography, type 1 neovascular tissue was visualized in 21 out of 22 study eyes (95%).


Our data suggest that, in eyes with pachychoroid features, the finding of a shallow irregular pigment epithelial detachment on OCT has greater diagnostic value for type 1 neovascularization than previously thought and that dye angiography may underestimate the prevalence of neovascularization compared to OCT angiography.

Retinal pigment epithelial detachments (PEDs) are seen most commonly in age-related macular degeneration. They also occur in 70%–100% of eyes with central serous chorioretinopathy with various morphologies and reflectivity characteristics, some of which may resemble those of neovascular age-related macular degeneration.

Type 1 neovascularization is defined by the presence of a vascularized PED. Diagnosis of active neovascularization relies on cross-sectional optical coherence tomography (OCT) to image the PED and fluorescein angiography to demonstrate “poorly defined” stippled hyperfluorescence with late leakage and/or staining at the site of the PED. Type 1 neovascularization may also occur in a more benign or “quiescent” form in which fluid and leakage are not detectable by OCT or fluorescein angiography, but a shallow irregular PED is seen with a corresponding plaque in the late phase of an indocyanine green angiogram. Shallow irregular PEDs were previously described in the polypoidal literature in terms of a “double-layer sign” resolved by OCT. These PEDs were shown by Sato and associates to contain the type 1 neovascular tissue representing branching vascular networks that feed polypoidal lesions.

The term “pachychoroid” describes a set of choroidal characteristics shared by a group of related diseases. These features, which include focal or diffuse increase in choroidal thickness, choroidal hyperpermeability, and dilated choroidal vessels, were first described using indocyanine green angiography and enhanced depth imaging OCT in patients with chronic central serous chorioretinopathy. Recently, en face imaging with swept-source OCT has revealed new findings that refine the definition of the pachychoroid phenotype to emphasize the morphologic characteristics of pathologically dilated choroidal vessels (“pachyvessels”) over absolute choroidal thickness.

Pachychoroid neovasculopathy refers to type 1 neovascularization in patients who do not have drusen or other risk factors for neovascularization but who exhibit pachychoroid features. Although type 1 neovascularization is a well-recognized complication of chronic central serous chorioretinopathy, it can also arise in pachychoroid eyes that have not yet manifested frank subretinal fluid. Pigment epithelial detachments in these eyes often have a shallow irregular morphology with moderate internal reflectivity on OCT that closely resembles the “double-layer sign.” However, in the setting of pachychoroid, choroidal hyperpermeability and chronic alterations of the retinal pigment epithelium (RPE) and outer retina can compromise the diagnostic specificity of dye-based angiography for type 1 neovascularization, leaving the clinician with some uncertainty as to the vascularity of these PEDs.

Optical coherence tomographic angiography images microvascular circulation in vivo without the need for intravenous dye or contrast injection. Spaide and Kuehlewein and associates have described the distinctive OCT angiography appearance of type 1 neovessels in age-related macular degeneration treated with anti–vascular endothelial growth factor (anti-VEGF) agents and have presented explanations to account for their large caliber and de-arborized appearance.

The purpose of this paper is to determine the proportion of shallow irregular PEDs in pachychoroid eyes that contain neovascular tissue and to study their morphology with OCT angiography.


This prospective cohort study was approved by the Western Institutional Review Board (Olympia, Washington, USA). It complies with the Health Insurance Portability and Accountability Act of 1996 and follows the tenets of the Declaration of Helsinki.

Patients were recruited consecutively from the practice of a single retina specialist (K.B.F.) if they manifested a shallow irregular PED in the macula of at least 1 eye in the presence of pachychoroid characteristics, defined as any of the following: (1) choroidal thickness in excess of 270 μm, (2) the presence of pachyvessels, (3) history of central serous chorioretinopathy. In order to maintain a consistent phenotype, patients were excluded if they exhibited macular drusen, if they had any history of inflammatory eye disease, if they were highly myopic, or if image quality was too poor for grading.

Clinical charts and previous multimodal imaging data were reviewed. Patients had previously undergone fundus photography, fluorescein and/or indocyanine green angiography, fundus autofluorescence, and OCT as clinically indicated for their ongoing care. Some patients had also had swept-source OCT. Instruments used were the TRC-50IX flood-illuminated fundus camera (Topcon Corp, Tokyo, Japan), the OCT Stratus 3000 (Carl Zeiss Meditec Inc, Dublin, California, USA), the HRA-OCT scanning laser ophthalmoscope with OCT (Heidelberg Engineering, Heidelberg, Germany), and the DRI OCT-1 (“Atlantis,” Topcon Medical Inc, Oakland, New Jersey, USA). Choroidal thickness measurements were taken using the software caliper tool of the Heidelberg Eye Examination software on enhanced depth scans.

All patients underwent OCT angiography (RTVue XR “Avanti,” Optovue, Fremont, California, USA). The RTVue XR is a spectral-domain OCT device that performs 70,000 A-scans per second and employs a split-spectrum amplitude decorrelation algorithm to produce depth-resolved 3-dimensional microvascular volume maps of the posterior pole. The OCT angiography volume scans were segmented manually using the viewing software accompanying the RTVue XR and were examined by a masked grader (C.B.) for the presence or absence of type 1 neovascular tissue with tangled vascular morphology, as previously described. The en face area of neovascular complexes was determined by manual border tracing using analysis tools in the Fiji distribution (“Fiji is just ImageJ,” http://fiji.sc ).

Since dye angiography had been performed only when clinically indicated, the time interval between dye angiography and OCT angiography was not controlled. Where dye angiograms were available for multiple historic time points for any given patient, the angiogram contemporary with the onset of the shallow irregular PED was graded. Owing to the relatively recent availability of OCT angiography in our practice (approximately 1 year), it was not possible to obtain OCT angiographic data contemporary with the onset of shallow irregular PED for several patients in this cohort.


Baseline Demographics

A total of 22 eyes of 16 patients met the selection criteria. The mean age of the patients was 71 years (range 54–95 years). Eight patients were male and 8 were female. Shallow irregular PEDs were noted in all eyes and were bilateral in 6 out of 16 patients. The Table includes a list of patients with demographic data and visual acuities at final follow-up.


Summary of Patients, Study Eyes, and Demographic Data With Findings on Fluorescein Angiography, Indocyanine Green Angiography, and Optical Coherence Tomography Angiography

Patient # Age Sex Eye Eye # Snellen VA Polypoidal Lesions Fluorescein Angiography Indocyanine Green Angiography Neovascular Detection by Dye Angiography Dye-Angiography → OCT Angiography Interval (Months) Neovascularization on OCT Angiography
Scan Area (mm 2 ) Morphology Trunk Diameter (μm) Neovascular Complex Area (mm 2 )
1 63 F OD 1 20/25 Nonspecific Nonspecific Negative 1 9 Tangle 84 0.594
OS 2 20/20 Nonspecific Not available Negative 1 9 Loop Not identified 0.087
2 86 M OD 3 20/70 Nonspecific Not available Negative 84 9 Tangle 86 2.968
OS 4 20/40 Not available Not available Not available 9 Placoid Not identified 0.303
3 70 F OD 5 20/70 Present Polypoidal + masking of choroidal neovascularization Branching vascular network + polypoidal Positive 108 9 + 36 (36 mm 2 montage) Tangle Not identified >4.51
4 63 F OD 6 20/100 Present Nonspecific Polypoidal Positive 4 36 + 36 (58 mm 2 montage) Tangle 146 >20.0
OS 7 20/25 Present Nonspecific Choroidal neovascularization + polypoidal Positive 4 9 Tangle 129 >4.53
5 60 M OD 8 20/60 Normal Nonspecific Negative 26 9 Tangle Not identified 0.729
OS 9 20/60 Choroidal neovascularization Plaque Positive 26 9 Tangle 46 >3.728
6 70 F OS 10 20/25 Not available Plaque Positive 9 9 Tangle 57 0.669
7 76 M OS 11 20/40 Atrophy Not available Negative 39 9 Tangle 69 3.719
8 67 M OD 12 20/30 Choroidal neovascularization Plaque Positive 60 9 Tangle 60 1.415
9 58 F OS 13 20/25 Present Not available Choroidal neovascularization + polypoidal Positive 45 9 Tangle 36 3.480
10 57 M OD 14 20/20 Nonspecific Nonspecific Negative 34 9 Tangle 117 >6.44
OS 15 20/30 Nonspecific Nonspecific Negative 49 9 Tangle Not identified >6.85
11 70 F OS 16 20/50 Choroidal neovascularization Plaque Positive 19 9 Tangle 48 3.76
12 54 F OS 17 20/25 Choroidal neovascularization Nonspecific Positive 19 9 Tangle 87 0.512
13 95 M OD 18 20/70 Nonspecific Not available Negative 79 9 Tangle Not identified 0.463
OS 19 20/30 Nonspecific Not available Negative 79 9 Tangle 49 0.544
14 74 M OD 20 20/40 Nonspecific Not available Negative 19 9 Not detected Not identified
15 70 F OS 21 20/30 Nonspecific Nonspecific Negative 27 9 Tangle 50 0.777
16 82 M OS 22 20/50 Atrophy Not available Negative 20 9 Tangle Not identified 1.479

OCT = optical coherence tomography; VA = visual acuity.

Areal dimensions are for the measurable portion of each neovascular lesion, and where the lesion extended beyond the scan field, dimensions are expressed as being greater than the specified measurable value.

Nineteen study eyes had a history of prior treatment. Eighteen eyes had received intravitreal anti-VEGF treatment (mean 31.3 injections per eye; standard deviation [SD]: 22.7) and 6 eyes had received verteporfin photodynamic therapy (mean 2.6 treatments per eye; SD: 1.5).

Choroidal Features

Mean subfoveal choroidal thickness for study eyes was 381 μm (SD: 141 μm). Seven of the study eyes had choroidal thicknesses less than 270 μm (mean: 212 μm; range: 176–248 μm; SD: 28.8 μm), but each of these qualified as pachychoroid (as opposed to age-related macular degeneration) on the basis of one or more previously described criteria : (1) an extrafoveal focus of maximal choroidal thickness exceeding subfoveal choroidal thickness by at least 60 μm (2 standard deviations) (2 eyes); (2) pachyvessels with distinctive en face OCT morphology (7 eyes). Four of these eyes had previously had photodynamic therapy.

Dye Angiography

Fluorescein angiography was available for 19 study eyes and revealed features of type 1 neovascularization in 4 eyes. In 14 study eyes the pattern of hyperfluorescence could not be distinguished from that seen in chronic central serous chorioretinopathy, and type 1 neovascularization could not be diagnosed specifically. Fluorescein angiography was normal in 1 study eye. Indocyanine green angiography was available for 14 study eyes and revealed hyperfluorescent plaques in 4 eyes and polypoidal lesions with branching vascular networks in 4 eyes. In the 4 eyes with polypoidal lesions, grading for the presence or absence of type 1 plaques on indocyanine green angiography was difficult to perform objectively because the grader could not be masked to the presence of polypoidal lesions. For study eyes with nonpolypoidal pachychoroid neovasculopathy that had at least one form of dye-based angiography, the combined detection rate for type 1 neovascularization was 5 out of 17 eyes (29%). Dye angiographic findings are listed in the Table .

The mean interval between dye angiography and OCT angiography for nonpolypoidal study eyes was 36 months (SD: 30.5 months) and any further analysis to compare these modalities directly on the basis of data in this cohort was therefore felt to be inappropriate.

Optical Coherence Tomography Angiography

Type 1 neovascular networks were detected in 21 out of 22 study eyes (95%) by OCT angiography. In 18 of these eyes, en face segments taken through the PEDs showed tangled networks of large-caliber “trunk vessels” with identifiable feeder vessels (eg, Figure 1 , bottom row, first image); in 2 eyes, the type 1 networks were small and localized (eg, Figure 1 , bottom row, third image); in 1 eye, the flow signature of the type 1 lesion had a more consolidated or placoid morphology ( Figure 2 , second row, fourth image). In the 4 eyes with polypoidal lesions, the polypoidal lesions themselves did not exhibit a detectable flow signature. One of the study eyes did not exhibit neovascularization on OCT angiography. (One eye of 1 patient had an ungradeable OCT angiogram owing to poor fixation and motion artifact and is neither shown nor represented in any figures or analyses.)

Figure 1

Multimodal imaging of both eyes of a 63-year-old female patient with pachychoroid neovasculopathy. (Top row, first and second images) Color photograph and fundus autofluorescence of the right eye show nonspecific retinal pigment epithelial changes with dependant morphology. (Second row, first and second images) Fluorescein angiography shows poorly defined hyperfluorescence with minimal late leakage. (Third row, first and second images) Indocyanine green angiography shows dilated choroidal pachyvessels with focal choroidal hyperpermeability, but a late-phase plaque is not definitively visible. (Fourth row, first image) Spectral-domain optical coherence tomography (OCT) of the right eye shows subretinal fluid, subfoveal debris, and pachyvessels (p) with overlying choriocapillaris thinning (yellow arrowhead) and a shallow irregular pigment epithelial detachment (PED). (Bottom row, first image) En face OCT angiography (3 × 3 mm) through the PED shows a tangled network of type 1 neovascular tissue. (Top row, third and fourth images) Color photograph and fundus autofluorescence of the left eye show geographic atrophy at the fovea. (Second row, third and fourth images) Fluorescein angiography shows a corresponding hyperfluorescent transmission defect. (Third row, third and fourth images) Findings on indocyanine green angiography are similar to those of the right eye and inconclusive for diagnosing neovascularization. (Fourth row, second image) Spectral-domain OCT of the left eye shows debris in the subfoveal space and choroidal findings similar to the right eye; a very small PED with irregular contour is noted and a double-layer sign is seen with magnification. (Bottom row, second image) En face OCT angiography (3 × 3 mm) through the choriocapillaris shows a type 1 neovascular loop (yellow arrowhead). (Bottom row, third image) Anterior displacement of the en face segmentation window isolates this loop from the surrounding choriocapillaris and localizes it within the boundaries of the foveal avascular zone; the retinal circulation is seen as a projection artifact.

Figure 2

Multimodal imaging of the right and left eyes, respectively, of an 86-year-old male patient with pachychoroid neovasculopathy. (Top row, first and third images) Color photographs show retinal pigment epithelial changes, more so in the right eye, in which subfoveal choroidal vascular markings are also more prominent. An absence of drusen is noted. (Second row, first image) Horizontal raster swept-source optical coherence tomography (SS OCT) shows a shallow irregular pigment epithelial detachment (PED) in the right eye and a smaller, shallow PED in the left eye. Subfoveal pachyvessels (p) are noted with overlying loss of choriocapillaris and Sattler layers. (Top row, second and fourth images) En face SS OCT (12 × 9 mm) segmented c. 150 μm below the Bruch’s membrane shows the extent and morphology of the pachyvessels (p), which account for increased extrafoveal choroidal thickness, superotemoral to the fovea where they are most densely located. (Second row, second and fourth images) En face OCT angiography through the PEDs shows high-flow signatures from type 1 neovascular networks with a tangled morphology in the right eye and a more placoid morphology in the left eye.

In each of the 4 eyes that manifested polypoidal lesions, the appearance of the associated type 1 neovascular network on spectral-domain OCT closely resembled that of branching vascular networks of polypoidal choroidal vasculopathy as described by Sato and associates. Type 2 and type 3 neovascularization were not detected in any of the study eyes by any of the imaging modalities employed.

Representative Case Descriptions

In each of the following cases, en face OCT angiography through the shallow irregular PED showed a flow signature compatible with type 1 neovascularization.

Patient 1 was a 63-year-old woman referred for a second opinion with a history of nonspecific visual disturbance and a diagnosis of chronic central serous chorioretinopathy complicated by type 1 neovascularization in both eyes. She had received 1 intravitreal injection of aflibercept to the right eye prior to referral. Visual acuities were 20/25 in the right eye and 20/20 in the left eye. Multimodal imaging findings of both eyes are summarized in Figure 1 . Pachychoroid features were seen on indocyanine green angiography and spectral-domain OCT and both fluorescein and indocyanine green angiography were noncontributory for diagnosing neovascularization.

Patient 2 was an 86-year-old white man with pachychoroid neovasculopathy. His right eye had undergone 3 sessions of photodynamic therapy and received 59 anti-VEGF injections; the left eye had received 69 anti-VEGF injections. Visual acuities were 20/70 in the right eye and 20/40 in the left eye and imaging findings are summarized in Figure 2 . Although subfoveal choroidal thickness appeared to be within normal limits, pachyvessels were seen on cross-sectional and en face OCT with thinning and loss of the overlying choriocapillaris and Sattler layers. Extrafoveal choroidal thickness measurements were significantly greater where pachyvessels were most densely located. Dye angiography (not shown) was noncontributory.

Patient 3 was a 70-year-old African-American woman with polypoidal choroidal vasculopathy. Findings are summarized in Figure 3 . She had presented at baseline with acute visual loss and was found to have extensive subretinal and sub-RPE hemorrhage with a recent subfoveal bleed. She had subsequently undergone 3 sessions of photodynamic therapy and received 62 anti-VEGF injections in the right eye. By year 6, corrected visual acuity of the study eye was 20/70, improving to 20/30 with pinhole, and remained stable thereafter. At that time spectral-domain OCT showed a shallow irregular PED. At the last follow-up in year 8, clinical and OCT findings were unchanged and OCT angiography through the PED showed subfoveal type 1 neovascularization with mature feeder vessels extending from the fovea toward the peripapillary site of the polypoidal lesions.

Figure 3

Fundus imaging of the right eye of a 70-year-old African-American female patient with pachychoroid features, presenting with polypoidal choroidal vasculopathy. (Baseline, first image) Color photograph shows widespread subretinal and subretinal pigment epithelial hemorrhage, some of which is relatively new and some of which is longstanding. Foveal involvement is noted. (Baseline, second image) Baseline indocyanine green angiography shows several peripapillary polypoidal lesions (red arrowheads) and dilated choroidal vessels with choroidal hyperpermeability superior and inferior to the fovea (asterisks). (Year 6, upper image) Color photograph at year 6 shows that the hemorrhage has reabsorbed, leaving subretinal fibrosis inferior to the fovea and superonasal to the optic disc. (Year 6, lower image) Spectral-domain optical coherence tomography (OCT) shows a shallow irregular pigment epithelial detachment (PED) overlying an area of pachyvessels. (Year 8) En face OCT angiography (3 × 3 mm overlaid on 6 × 6 mm scan) through the PED shows type 1 neovascularization (yellow circle) under the fovea with a bundle of mature, large-caliber type 1 feeder vessels (yellow arrowhead) coursing nasally toward the site of the polypoidal lesions; red-green crosshairs localize the foveal center; inferior to the fovea, retinal vessels are visualized by their projection artifacts.

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Jan 6, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on Optical Coherence Tomography Angiography of Shallow Irregular Pigment Epithelial Detachments In Pachychoroid Spectrum Disease

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