Pachychoroid Diseases of the Macula

Advances in optical coherence tomography have enabled a better appreciation of the role of pathologic choroidal changes in a variety of retinal disease. A “pachychoroid†(pachy-[prefix]: thick) is defined as an abnormal and permanent increase in choroidal thickness often showing dilated choroidal vessels and other structural alterations of the normal choroidal architecture. Central serous chorioretinopathy is just one of several pachychoroid-related macular disorders. This review summarizes the current state of knowledge of the pachycoroid spectrum and the hallmark features seen with multimodal imaging analysis of these entitie

Pachychoroid Diseases of the Macula

Advances in optical coherence tomography have enabled a better appreciation of the role of pathologic choroidal changes in a variety of retinal disease. A “pachychoroid” (pachy-[prefix]: thick) is defined as an abnormal and permanent increase in choroidal thickness often showing dilated choroidal vessels and other structural alterations of the normal choroidal architecture. Central serous chorioretinopathy is just one of several pachychoroid-related macular disorders. This review summarizes the current state of knowledge of the pachycoroid spectrum and the hallmark features seen with multimodal imaging analysis of these entitie

Volume Rendering of Dense B-Scan Optical Coherence Tomography Angiography to Evaluate the Connectivity of Macular Blood Flow

Purpose: To characterize macular blood flow connectivity using volume rendering of dense B-scan (DB) optical coherence tomography angiography (OCTA) data. Methods: This was a prospective, cross-sectional, observational study. DB OCTA perifoveal scans were performed on healthy subjects using the Spectralis HRA+OCT2. A volumetric projection artifact removal algorithm and customized filters were applied to raw OCTA voxel data. Volume rendering was performed using a workflow on Imaris 9.5 software. Vascular graphs were obtained from angiographic data using the algorithm threshold-loops. Superficial arteries and veins were identified from color fundus photographs and connections between adjacent arteries and veins displayed using the shortest path algorithm. Connective pathway locations were analyzed with cross-sectional OCT and OCTA to determine their course through the superficial vascular complex (SVC) and the deep vascular complex (DVC). Results: Fourteen eyes from seven subjects (mean age: 28 ± 5 years; 3 women) were included in this analysis. One hundred and twenty-six vascular connections were analyzed. In all cases, the shortest path connections between superficial arteries and veins coursed through the DVC. We did not identify shortest path connections confined to the SVC. Conclusions: Volumetric analysis of vascular connectivity supports a predominantly in-series arrangement of blood flow between the SVC and DVC within the human perifoveal macula.publishersversionpublishe

Type 1 neovascularization may confer resistance to geographic atrophy amongst eyes treated for neovascular age-related macular degeneration

Background To report a series of age-related macular degeneration (AMD) patients in whom progression to geographic atrophy (GA) in one eye receiving frequent intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) therapy for type 1 neovascularization (NV) was slower than that of the fellow eye with non-neovascular AMD. Methods Retrospective, observational case series examining the clinical course and GA progression rate in four consecutive patients in which one eye harbored type 1 neovascular AMD and was receiving anti-VEGF therapy, while the fellow eye manifested signs of non-neovascular AMD only. Eligibility criteria included anti-VEGF therapy duration of over 4 years and over 50 injections. Lesion evolution was documented via multimodal imaging. GA at baseline and final visits was quantified and GA progression rate for each eye was determined. Results Four consecutive patients were followed for a mean interval of 94 months (range 62–120). One eye harbored type 1 NV while the fellow eye remained non-neovascular. The former received a mean of 65.5 ± 15.2 anti-VEGF injections. Mean rate of GA progression in non-neovascular eyes was 0.076 ± 0.024 mm2/month and in type 1 NV eyes was 0.004 ± 0.005 mm2/month. Difference in GA progression rate between type 1 and non-neovascular eyes was found to be statistically significant (P = 0.001). Conclusions These findings support previous hypotheses that, unlike type 2 and 3 lesions, type 1 NV may represent a neovascular AMD subtype more resilient to GA formation. This may have implications for anti-VEGF regimens in the management of type 1 NV

Novel Insights Based on the Anatomy of Henle Fiber Layer

Purpose: The purpose of this study was to identify a precise location of deep capillary plexus (DCP) injury in acute macular neuroretinopathy (AMN) lesions using multimodal imaging. Methods: En face structural optical coherence tomography (OCT) images were manually segmented to delineate outer retinal AMN lesions involving the ellipsoid zone and interdigitation zone. AMN lesion centroid was calculated, and image distortion was applied to correct for Henle fiber layer (HFL) length and orientation. The resulting image was registered with the corresponding en face OCT angiography (OCTA) image segmented at the DCP and structural OCT volume before grading for vascular and structural features, respectively. Results: Thirty-nine AMN lesions from 16 eyes (11 female patients, mean age 34 ± 4 years) were analyzed. After correcting for HFL anatomy, in 62% of AMN lesions, the centroid co-localized with a capillary vortex (pattern 1); flow defects were detected in 33% of lesions (pattern 2); and in 5% of lesions no specific pattern could be identified (pattern 3). The detection of a specific pattern increased after correcting the projection of AMN lesion for HFL anatomy (28% vs. 5%, P = 0.04). Outer nuclear layer thickness was lower in the centroid area in 10 (29%) AMN lesions from 6 patients, all corresponding to lesions fitting pattern 2 (r = 0.78, P < 0.001). Conclusions: AMN lesions might be a result of DCP impairment at the level of the capillary vortex or draining venule. In eyes with AMN, the location of outer retinal changes associated with DCP ischemia appears to be influenced by the length and orientation of HFL.publishersversionpublishe

Quantitative shadow compensated optical coherence tomography of choroidal vasculature

Conventionally rendered optical coherence tomography (OCT) images of the posterior segment contain shadows which influence the visualization of deep structures such as the choroid. The purpose of this study was to determine whether OCT shadow compensation (SC) alters the appearance of the choroid and the apparent choroidal vascularity index (CVI), an OCT-derived estimated ratio of luminal to total choroidal volume. All scans were shadow compensated using a previously published algorithm, binarized using a novel validated algorithm and extracted binarized choroid to estimate CVI. On 27 raw swept-source OCT volume-scans of healthy subjects, the effect of SC on CVI was established both qualitatively and quantitatively. In shadow compensated scans, the choroid was visualized with greater brightness than the neurosensory retina and the masking of deep tissues by retinal blood vessels was greatly reduced. Among study subjects, significant mean difference in CVI of -0.13 was observed between raw and shadow compensated scans. Conventionally acquired OCT underestimates both choroidal reflectivity and calculated CVI. Quantitative analysis based on subjective grading demonstrated that SC increased the contrast between stromal and luminal regions and are in agreement with true tissue regions. This study is warranted to determine the effects of SC on CVI in diseased eyes

Presumed Pyogenic Granuloma Associated with Intravitreal Anti-Vascular Endothelial Growth Factor Therapy

To report a case of a presumed pyogenic granuloma at the site of multiple intravitreal anti-Vascular Endothelial Growth Factor (VEGF) injections. Intravitreal anti-VEGF injections can be complicated by a localized reaction of the conjunctiva

Quantitative Analysis of Outer Retinal Tubulation in Age-Related Macular Degeneration From Spectral-Domain Optical Coherence Tomography and Histology

Purpose: To assess outer retinal tubulation (ORT) morphology from spectral-domain optical coherence tomography (SD-OCT) volumes and donor eye histology, analyze ORT reflectivity, and estimate the number of cones surviving in ORT. Methods: In SD-OCT volumes from nine patients with advanced AMD, ORT was analyzed en face and in B-scans. The hyperreflective ORT border in cross-section was delineated and surface area calculated. Reflectivity was compared between ORT types (Closed, Open, Forming, and Branching). A flatmount retina from a donor with neovascular AMD was labeled to visualize the external limiting membrane that delimits ORT and allow measurements of cross-sectional cone area, center-to-center cone spacing, and cone density. The number of cones surviving in ORT was estimated. Results: By en face SD-OCT, ORT varies in complexity and shape. Outer retinal tubulation networks almost always contain Closed cross-sections. Spectral-domain OCT volumes containing almost exclusively Closed ORTs showed no significant direction-dependent differences in hyperreflective ORT border intensity. The surface areas of partial ORT assessed by SD-OCT volumes ranged from 0.16 to 1.76 mm2. From the flatmount retina, the average cross-sectional area of cone inner segments was 49.1 ± 7.9 μm2. The average cone spacing was 7.5 ± 0.6 μm. Outer retinal tubulation cone density was 20,351 cones/mm2. The estimated number of cones in ORT in a macula ranged from 26,399 to 186,833 cones, which is 6% to 44% of the cones present in a healthy macula. Conclusions: These first estimates for cone density and number of cones surviving in ORT suggest that ORT formation considerably distorts the photoreceptor mosaic. Results provide additional insight into the reflectivity characteristics and number of ORT cones observable in living patients by SD-OCT, as cones persist and disease progresses

A Case Study

OK Publisher Copyright: © 2023 American Academy of OphthalmologyPurpose: To investigate intraretinal neovascularization and microvascular anomalies by correlating in vivo multimodal imaging with corresponding ex vivo histology in a single patient. Design: A case study comprising clinical imaging from a community-based practice, and histologic analysis at a university-based research laboratory (clinicopathologic correlation). Participants: A White woman in her 90s treated with numerous intravitreal anti-VEGF injections for bilateral type 3 macular neovascularization (MNV) secondary to age-related macular degeneration (AMD). Methods: Clinical imaging comprised serial infrared reflectance, eye-tracked spectral-domain OCT, OCT angiography, and fluorescein angiography. Eye tracking, applied to the 2 preserved donor eyes, enabled the correlation of clinical imaging signatures with high-resolution histology and transmission electron microscopy. Main Outcome Measures: Histologic/ultrastructural descriptions and diameters of vessels seen in clinical imaging. Results: Six vascular lesions were histologically confirmed (type 3 MNV, n = 3; deep retinal age-related microvascular anomalies [DRAMAs], n = 3). Pyramidal (n = 2) or tangled (n = 1) morphologies of type 3 MNV originated at the deep capillary plexus (DCP) and extended posteriorly to approach without penetrating persistent basal laminar deposit. They did not enter the subretinal pigment epithelium (RPE)–basal laminar space or cross the Bruch membrane. Choroidal contributions were not found. The neovascular complexes included pericytes and nonfenestrated endothelial cells, within a collagenous sheath covered by dysmorphic RPE cells. Deep retinal age-related microvascular anomaly lesions extended posteriorly from the DCP into the Henle fiber and the outer nuclear layers without evidence of atrophy, exudation, or anti-VEGF responsiveness. Two DRAMAs lacked collagenous sheaths. External and internal diameters of type 3 MNV and DRAMA vessels were larger than comparison vessels in the index eyes and in aged normal and intermediate AMD eyes. Conclusions: Type 3 MNV vessels reflect specializations of source capillaries and persist during anti-VEGF therapy. The collagenous sheath of type 3 MNV lesions may provide structural stabilization. If so, vascular characteristics may be useful in disease monitoring in addition to fluid and flow signal detection. Further investigation with longitudinal imaging before exudation onset will help determine if DRAMAs are part of the type 3 MNV progression sequence. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.publishersversionpublishe

Amplitude-scan classification using artificial neural networks

Optical coherence tomography (OCT) images semi-transparent tissues noninvasively. Relying on backscatter and interferometry to calculate spatial relationships, OCT shares similarities with other pulse-echo modalities. There is considerable interest in using machine learning techniques for automated image classifcation, particularly among ophthalmologists who rely heavily on diagnostic OCT.Artifcial neural networks (ANN) consist of interconnected nodes and can be employed as classifers after training on large datasets. Conventionally, OCT scans are rendered as 2D or 3D humanreadable images of which the smallest depth-resolved unit is the amplitude-scan refectivity-function profle which is difcult for humans to interpret. We set out to determine whether amplitude-scan refectivity-function profles representing disease signatures could be distinguished and classifed by a feed-forward ANN. Our classifer achieved high accuracies after training on only 24 eyes, with evidence of good generalization on unseen data. The repertoire of our classifer can now be expanded to include rare and unseen diseases and can be extended to other disciplines and industries