Kunal K. Dansingani

EN FACE IMAGING OF PACHYCHOROID SPECTRUM DISORDERS WITH SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY.

Purpose: To correlate clinical manifestations with choroidal morphology in pachychoroid disorders, including central serous chorioretinopathy, pachychoroid pigment epitheliopathy, pachychoroid neovasculopathy, and polypoidal choroidal vasculopathy, using en face swept-source optical coherence tomography (OCT). Methods: Patients with pachychoroid spectrum diagnoses were identified nonconsecutively through a review of charts and multimodal imaging. Each eye was categorized as uncomplicated pachychoroid, pachychoroid pigment epitheliopathy, central serous chorioretinopathy, pachychoroid neovasculopathy, or polypoidal choroidal vasculopathy. All patients included in this series then underwent bilateral swept-source OCT. Results: Sixty-six eyes of 33 patients were included. Numbers assigned to diagnostic categories were 8 uncomplicated pachychoroid, 13 pachychoroid pigment epitheliopathy, 27 central serous chorioretinopathy, 15 pachychoroid neovasculopathy, and 3 polypoidal choroidal vasculopathy. One eye was classified as normal. Swept-source OCT choroidal thickness maps confirmed increased thickness under the areas of pachychoroid pigment epitheliopathy, central serous chorioretinopathy, type 1 NV (pachychoroid neovasculopathy), or polyps (polypoidal choroidal vasculopathy). En face swept-source OCT showed dilated outer choroidal vessels in all eyes. In several eyes with a chronic disease, focal choriocapillaris atrophy with inward displacement of deep choroidal vessels was noted. Conclusion: Although clinical manifestations of pachychoroid spectrum disorders vary considerably, these entities share morphologic findings in the choroid, including increased thickness and dilated outer choroidal vessels. En face swept-source OCT localizes these changes to disease foci and shows additional findings that may unify our understanding of disease pathogenesis.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF TYPE 3 NEOVASCULARIZATION SECONDARY TO AGE-RELATED MACULAR DEGENERATION.

Purpose: To characterize the vascular structure of Type 3 neovascularization secondary to age-related macular degeneration using optical coherence tomography angiography. Methods: Optical coherence tomography angiography cube scans (3 mm × 3 mm) were acquired in 29 eyes of 24 patients with Type 3 lesions secondary to age-related macular degeneration using the RTVue XR Avanti with AngioVue, Split-spectrum amplitude-decorrelation, and motion correction technology. Automated layer segmentation boundaries were adjusted to best visualize the neovascular complex on en face projection images. Results: A distinct neovascular complex could be identified in 10 (34%) eyes, all of which were active on optical coherence tomography imaging. In all 10 eyes, the neovascular complex appeared as a small tuft of bright, high-flow tiny vessels with curvilinear morphology located in the outer retinal layers with a feeder vessel communicating with the inner retinal circulation (i.e., deep retinal capillary plexus). The mean (SD) size of the neovascular complex measured 0.07 (± 0.07) mm2. Conclusion: With optical coherence tomography angiography, it is possible to identify small intraretinal neovascular complexes communicating with the deep retinal capillary plexus in eyes with Type 3 neovascularization secondary to age-related macular degeneration. Qualitative and quantitative analyses of Type 3 neovascular complexes can be performed using optical coherence tomography angiography.

Polypoidal choroidal vasculopathy a distinct disease or manifestation of many

A Distinct Disease or Manifestation of Many? Polypoidal choroidal vasculopathy (PCV) is a term coined by Yannuzzi et al more than 30 years ago (Yannuzzi LA, Idiopathic PCV, Presented at Macula Society Meeting 1982; Miami, FL). As originally described, the term PCV was used to distinguish a particular form of exudative maculopathy that appeared distinct from other disorders associated with serosanguineous complications, such as age-related macular degeneration (AMD), angioid streaks, and myopic choroidal neovascularization (CNV). Polypoidal choroidal vasculopathy was characterized by the occurrence of polypoidal lesions or “polyps” that commonly progressed to hemorrhagic complications in the subretinal pigment epithelial (RPE) compartment. At the time, dye angiography and clinical observations were used to document the findings of PCV, and it was speculated that the polyps arose directly from the inner choroidal circulation. Since the original report describing PCV, the advent of multimodal imaging (MMI) has permitted phenotypic characterization of choroidal diseases at an unprecedented level. Integration of fundus autofluorescence, spectral domain optical coherence tomography, and, more recently, optical coherence tomography angiography findings have facilitated greater understanding of the structural features and natural course of neovascular diseases. It has also clarified previously held misconceptions about disease pathophysiology that were drawn from inferences made using technology with limited anatomical resolution. Finally, MMI has allowed redefinition of diseases using nomenclature that has greater utility with respect to natural course, treatment, and visual prognosis. The diagnostic criteria for PCV remain poorly defined, thus there is some degree of inconsistency in the application of this term within the ophthalmic literature. Some authors have used the term PCV to refer to a distinct clinical entity, whereas others have used it to describe a focal morphological manifestation within a broader neovascular process. Polypoidal changes within the neovascular process have been documented in a range of diseases including AMD, central serous chorioretinopathy, peripheral exudative hemorrhagic chorioretinopathy, and choroidal nevi (Figure 1). Applying the diagnosis of PCV to describe all of these diseases is erroneous because it implies a common pathogenic mechanism. We propose that the clinical definition for PCV should be revised using MMI criteria and outline our rationale below.

Volume-Rendering Optical Coherence Tomography Angiography of Macular Telangiectasia Type 2

PURPOSE To evaluate the vascular structure of eyes with macular telangiectasia type 2 (MacTel2) using volume-rendered optical coherence tomography angiography (OCTA). DESIGN Retrospective cross-sectional study. PARTICIPANTS A total of 14 consecutive patients (20 eyes) with MacTel2 who had a signal strength score ≥55 and could maintain fixation during the scan process. METHODS The eyes were scanned using optical coherence tomography with split-spectrum amplitude decorrelation techniques to derive flow information. Data were extracted and used to create volume-rendered images of the retinal vasculature that could be rotated about 3 different axes for evaluation. MAIN OUTCOME MEASURES Descriptive appraisal of the vascular abnormalities associated with MacTel2. RESULTS Vessels posterior to the outer boundary of the deep retinal plexus were secondary to retinal thinning, vascular invasion, or a combination of both. These vessels had the same shape and distribution as the late staining seen during conventional fluorescein angiography. Lateral contraction in the temporal macula in 5 eyes created an appearance of vessels radiating from a central locus, which was the site of a right angle vein. Loss of macular tissue as part of the disease process led to a central amalgamation of the inner vascular plexus and the deep vascular plexus, which appeared to be in a state of decline. Subretinal neovascularization originated from the retinal circulation but involved not only the subretinal space but also could infiltrate the remaining, thinned, retina. CONCLUSIONS Volume rendering of OCTA information preserves the 3-dimensional relationships among retinal vascular layers and provides opportunities to visualize retinal vascular abnormalities in unprecedented detail. The retinal vascular leakage and invasion in MacTel2 may arise as a consequence of loss of control with depletion of Müller cells and exposure of the remaining retinal vessels to the more hypoxic environment near the inner segments of the photoreceptors.

A Comparison Between Optical Coherence Tomography Angiography and Fluorescein Angiography for the Imaging of Type 1 Neovascularization

PURPOSE To determine the sensitivity of the combination of optical coherence tomography angiography (OCTA) and structural optical coherence tomography (OCT) for detecting type 1 neovascularization (NV) and to determine significant factors that preclude visualization of type 1 NV using OCTA. METHODS Multicenter, retrospective cohort study of 115 eyes from 100 patients with type 1 NV. A retrospective review of fluorescein (FA), OCT, and OCTA imaging was performed on a consecutive series of eyes with type 1 NV from five institutions. Unmasked graders utilized FA and structural OCT data to determine the diagnosis of type 1 NV. Masked graders evaluated FA data alone, en face OCTA data alone and combined en face OCTA and structural OCT data to determine the presence of type 1 NV. Sensitivity analyses were performed using combined FA and OCT data as the reference standard. RESULTS A total of 105 eyes were diagnosed with type 1 NV using the reference. Of these, 90 (85.7%) could be detected using en face OCTA and structural OCT. The sensitivities of FA data alone and en face OCTA data alone for visualizing type 1 NV were the same (66.7%). Significant factors that precluded visualization of NV using en face OCTA included the height of pigment epithelial detachment, low signal strength, and treatment-naïve disease (P < 0.05, respectively). CONCLUSIONS En face OCTA and structural OCT showed better detection of type 1 NV than either FA alone or en face OCTA alone. Combining en face OCTA and structural OCT information may therefore be a useful way to noninvasively diagnose and monitor the treatment of type 1 NV.

Fractal dimensional analysis of optical coherence tomography angiography in eyes with diabetic retinopathy

Purpose We used fractal dimensional analysis to analyze retinal vascular disease burden in eyes with diabetic retinopathy using spectral-domain optical coherence tomography angiography (OCTA). Methods A retrospective study was performed of 13 eyes with diabetic retinopathy without diabetic macular edema and 56 control eyes. Optical coherence tomography angiography images were acquired using the RTVue XR Avanti. Automated segmentation was obtained through the superficial and deep capillary plexuses for each eye. Grayscale OCTA images were standardized and binarized using ImageJ. Fractal box-counting analyses were performed using Fractalyse. Fractal dimensions (FD) as well as software-generated vascular density analyses of the superficial and deep capillary plexuses were compared between diabetic and control eyes using 2-tailed t-tests and 1-way multivariate ANOVA (MANOVA) analyses. Results The superficial and deep plexuses from diabetic and control eyes were analyzed. The average FD for diabetic eyes was significantly lower than control eyes for the superficial (P = 4.513 × 10-3) and deep (P = 2.653 × 10-3) capillary plexuses. In diabetic eyes, the vascular density also was significantly reduced in the superficial (P = 8.068 × 10-5) and deep (P = 3.120 × 10-6) capillary plexuses. One-way MANOVA showed a significant difference between diabetic and control eyes. Conclusions The OCTA FD is significantly reduced in the superficial and deep capillary plexuses in eyes with diabetic retinopathy. Applying fractal analysis to OCTA imaging holds the potential to establish quantitative parameters for microvascular pathology.

TYPE 3 NEOVASCULARIZATION IMAGED WITH CROSS-SECTIONAL AND EN FACE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

Purpose: To study the cross-sectional and en face optical coherence tomography angiography (OCTA) findings in Type 3 neovascularization (NV). Methods: Optical coherence tomography angiography imaging of 27 eyes of 23 patients with Type 3 NV was analyzed with 9 eyes having consecutive follow-up OCTA studies. Results: Type 3 NV appeared as a linear high-flow structure on cross-sectional OCTA corresponding to a high-flow tuft of vessels seen on en face OCTA. Cross-sectional OCTA seemed to enable the distinction between vascular and nonvascular intraretinal hyperreflective foci. Two patterns of flow were observed; Pattern 1 (11%): a flow signal confined to the neurosensory retina and Pattern 2 (74%): a flow signal extending through the retinal pigment epithelium. No definitive retinal–choroidal anastomosis was observed; however, projection artifacts confounded the interpretation of deeper structures. An increase in the intensity of the high-flow tuft was seen during the progression or recurrence of Type 3 NV. Intravitreal anti–vascular endothelial growth factor therapy caused a reduction in the intensity of the high-flow tuft which was not sustained. Conclusion: Compared with conventional imaging, OCTA may improve detection and delineation of vascular changes occurring in Type 3 NV. Cross-sectional and en face OCTA may prove useful in studying the pathogenesis and guiding the management of these lesions.

The Evolution of the Plateau, an Optical Coherence Tomography Signature Seen in Geographic Atrophy

Purpose Histologic details of progression routes to geographic atrophy (GA) in AMD are becoming available through optical coherence tomography (OCT). We studied the origins and evolution of an OCT signature called plateau in eyes with GA and suggested a histologic correlate. Methods Serial eye-tracked OCT scans and multimodal imaging were acquired from eight eyes of seven patients with GA and plateau signatures over a mean follow-up of 7.7 years (range, 3.7–11.6). The histology of unrelated donor eyes with AMD was reviewed. Results Drusenoid pigment epithelial detachment (PED) on OCT imaging progressed into wide-based mound-like signatures with flattened apices characterized by a hyporeflective yet heterogeneous interior and an overlying hyperreflective exterior, similar to outer retinal corrugations previously ascribed to persistent basal laminar deposit (BLamD) but larger. These new signatures are described as “plateaus.” An initial increase of the PED volume and hyporeflectivity of its contents was followed by a decrease in PED volume and thinning of an overlying hyperreflective band attributable to the loss of the overlying RPE leaving persistent BLamD. Both imaging and histology revealed persistent BLamD with defects through which gliotic Müller cell processes pass. Conclusions Plateaus can be traced back to drusenoid PEDs on OCT imaging. We hypothesize that during progressive RPE atrophy, Müller cell extension through focal defects in the residual persistent BLamD may contribute to the heterogeneous internal reflectivity of these entities. The role of Müller cell activation and extension in the pathogenesis of AMD should be explored in future studies.

CHOROIDAL MORPHOLOGY IN EYES WITH POLYPOIDAL CHOROIDAL VASCULOPATHY AND NORMAL OR SUBNORMAL SUBFOVEAL CHOROIDAL THICKNESS.

Purpose: To subsegment the choroid in patients with polypoidal choroidal vasculopathy and to determine whether the ratio of choriocapillaris/Sattler layer thickness to total choroidal thickness is decreased at sites of polypoidal pathology. Methods: Retrospective, observational, cross-sectional study. A total of 320 eyes of 305 patients with polypoidal choroidal vasculopathy were studied with optical coherence tomography and dye angiography. The ratio of choriocapillaris/Sattler layer thickness to total choroidal thickness was calculated at polypoidal lesion sites in eyes with subfoveal choroidal thickness (SFCT) ⩽200 &mgr;m. Results: Mean SFCT was 267.7 ± 118.5 &mgr;m for the entire cohort. Mean SFCT was 151.2 ± 35.0 &mgr;m in eyes with SFCT ⩽200 &mgr;m (n = 124, 39%). In this subgroup, dilated Haller vessels (pachyvessels) were identified under the site of neovascular ingrowth in 117 eyes (94%). Choroidal thickness in the pachyvessel zone was greater (213.3 ± 52.2 &mgr;m) than SFCT (P < 0.001) with a significantly lower choriocapillaris/Sattler layer to total thickness ratio (P < 0.001). Qualitative alterations of the retinal pigment epithelium were observed in 60 eyes (51%). Conclusion: Eyes with normal or subnormal SFCT exhibited extrafoveal choroidal thickening at sites of polypoidal disease. The choriocapillaris and Sattler layers were attenuated at these locations, but Haller vessels were markedly dilated. These changes were topographically associated with sites of neovascular ingrowth and support the classification of polypoidal choroidal vasculopathy as a pachychoroid disorder.PURPOSE To subsegment the choroid in patients with polypoidal choroidal vasculopathy and to determine whether the ratio of choriocapillaris/Sattler layer thickness to total choroidal thickness is decreased at sites of polypoidal pathology. METHODS Retrospective, observational, cross-sectional study. A total of 320 eyes of 305 patients with polypoidal choroidal vasculopathy were studied with optical coherence tomography and dye angiography. The ratio of choriocapillaris/Sattler layer thickness to total choroidal thickness was calculated at polypoidal lesion sites in eyes with subfoveal choroidal thickness (SFCT) ≤200 μm. RESULTS Mean SFCT was 267.7 ± 118.5 μm for the entire cohort. Mean SFCT was 151.2 ± 35.0 μm in eyes with SFCT ≤200 μm (n = 124, 39%). In this subgroup, dilated Haller vessels (pachyvessels) were identified under the site of neovascular ingrowth in 117 eyes (94%). Choroidal thickness in the pachyvessel zone was greater (213.3 ± 52.2 μm) than SFCT (P < 0.001) with a significantly lower choriocapillaris/Sattler layer to total thickness ratio (P < 0.001). Qualitative alterations of the retinal pigment epithelium were observed in 60 eyes (51%). CONCLUSION Eyes with normal or subnormal SFCT exhibited extrafoveal choroidal thickening at sites of polypoidal disease. The choriocapillaris and Sattler layers were attenuated at these locations, but Haller vessels were markedly dilated. These changes were topographically associated with sites of neovascular ingrowth and support the classification of polypoidal choroidal vasculopathy as a pachychoroid disorder.

A Perspective on the Nature and Frequency of Pigment Epithelial Detachments

PURPOSE To describe and compare the clinical and imaging characteristics of pigment epithelial detachments (PEDs) in age-related macular degeneration (AMD), polypoidal choroidal vasculopathy (PCV), and central serous chorioretinopathy (CSC) as seen in a clinical setting of a tertiary retinal practice. DESIGN A perspective supported by clinical and imaging characteristics of a consecutive cohort of patients with strictly defined PEDs. RESULTS One hundred seventy-four eyes of 113 patients with PEDs were studied with comprehensive clinical retinal examination and multimodal imaging; PEDs were differentiated into nonvascularized and vascularized forms with 3 main underlying etiologies: AMD (76%), PCV (9%), and CSC (3%). AMD was the most common diagnosis, with both nonvascularized PEDs (drusenoid and serous) and vascularized PEDs (type 1 and type 3 neovascularization) associated with drusen and a thin choroid. PCV patients had large, vascularized, peaked PEDs associated with polyps and a variable choroidal thickness, while CSC patients had a thick choroid and predominantly nonvascularized, serous PEDs with an overlying neurosensory detachment. The combined clinical and imaging characteristics form a profile for each PED subtype related to their underlying disease. However, atypical features noted in 11% of patients may complicate the underlying diagnosis. CONCLUSION Typical phenotypic manifestations of PEDs and other features seen with multimodal imaging were associated with specific underlying etiologies. As suggested by our study, identification of these features help clinicians to determine the precise underlying etiology and manage both vascularized PEDs, where evidence-based treatment exists, and nonvascularized PEDs, where current treatment is not supported by convincing evidence.