Faculty Bibliography

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.

To investigate associations and predictive factors between macular neovascularization (MNV) lesion variants and drusen types in patients with treatment-naïve neovascular age-related macular degeneration (AMD).

The Henle fiber layer (HFL) is comprised of bundles of unmyelinated photoreceptor axons intermingled with outer Müller cell processes. The photoreceptor axons extend from the cell bodies located in the outer nuclear layer and radially project toward the outer plexiform layer, the inner third of which includes the synaptic junctional complexes and the outer two-thirds of which includes the HFL. The oblique path of the HFL provides unique structural and reflectance properties and this radial anatomy is highlighted in many macular disorders including those with macular star exudation and HFL hemorrhage. Recent investigations using multimodal imaging techniques, especially cross sectional and en face optical coherence tomography (OCT), have provided new perspectives regarding HFL disruption in retinal diseases. The aim of this review is to highlight the pathoanatomy and multimodal imaging, especially OCT, associated with HFL disruption that is present in various macular diseases. After describing the current knowledge of the embryology, anatomy, and physiology of the HFL, we review the existing imaging modalities that allow in vivo visualization of the HFL in the healthy and diseased retina. Finally, we report the clinical and imaging findings of acute HFL alteration in various macular disorders, including degenerative, inflammatory, and vascular conditions. Also, we propose a novel and signature OCT biomarker indicative of acute photoreceptor disruption involving the HFL, termed the "angular sign of HFL hyperreflectivity" (ASHH) of macular disease, to unify the pathoanatomy common to these various macular disorders and to provide clarity regarding the underlying pathogenesis.

Non-exudative macular and choroidal neovascularization (MNV and CNV) usually refers to the entity of treatment-naïve type 1 neovascularization in the absence of associated signs of exudation. Histopathological studies, dating back in the early 70s, identified the presence of non-exudative MNV, but the first clinical report of this finding was in the late 90s using indocyanine green angiography in eyes with age-related macular degeneration (AMD). With more advanced retinal imaging, there has been an ever increasing appreciation of non-exudative MNV associated with AMD and CNV with other macular disorders. However, consensus regarding the exact definition and the clinical management of this entity is lacking. Furthermore, there may be variation in the imaging features and clinical course suggesting that a spectrum of disease may exist. Herein, we review the large body of published work that has provided a better understanding of non-exudative MNV and CNV in the last decade. The prevalence, multimodal imaging features, clinical course, and response to treatment are discussed to elucidate further key insights about this entity. Based on these observations, this review also proposes a new theory about the origin and course of different sub-types of non-exudative MNV/CNV which can have different etiologies and pathways according to the clinical context of disease.

PURPOSE/OBJECTIVE:To characterize and distinguish non-neovascular deep retinal age-related microvascular anomalies (DRAMA) from type 3 macular neovascularization (MNV) using volume rendering of optical coherence tomography (OCT) and OCT angiography (OCTA). DESIGN/METHODS:Retrospective, consecutive case series. SUBJECTS/METHODS:Consecutive patients with age-related macular degeneration (AMD) exhibiting de novo non-neovascular abnormalities within the deep vascular plexus (DCP) on high-resolution (High-Res) spectral domain and swept-source OCT/OCTA. Patients with retinal vascular alterations attributable to other disease entities were excluded. METHODS:Complete ophthalmologic examination and multimodal imaging including confocal fundus photography (CFP), spectral domain OCT (SD-OCT), High-Res SD-OCT and OCTA, and volume-averaged swept-source OCTA (SS-OCTA). Volume rendering of High-Res OCTA and averaged SS-OCTA were used to analyze capillary abnormalities and inflow/outflow connectivity pathways. MAIN OUTCOME MEASURES/METHODS:The primary outcomes were the characteristics of capillary abnormalities (number, size, shape, reflectivity, and location) and inflow/outflow connectivity pathways. Secondary outcomes were nearby changes in CFP and structural OCT (hyperreflective foci, outer retinal atrophy, and retinal pigment epithelium (RPE) atrophy). RESULTS:From 8 eyes of 8 patients, 2 DRAMA subtypes were identified: small diameter perifoveal capillary dilations with hyperreflective walls within the inner nuclear layer (type 1, n=4) and vascular outpouchings, typically multiple, extending posteriorly into Henle's fiber layer with reflectivity similar to adjacent normal retinal capillaries (type 2, n=10). Four eyes had both DRAMA subtypes. Three-dimensional visualization of OCTA data demonstrated DRAMA corresponding to dilations of DCP capillaries without direct inflow or outflow connections to the superficial plexus. Fundus photographs showed circular red dots in 3 eyes, all corresponding to type 1 DRAMA. DRAMA co-localized with hyperreflective foci in all cases. No lesions were found anterior to areas of retinal pigment epithelium or outer retina atrophy. Asymptomatic intraretinal exudation varied through a follow-up of up to 6 years, with no lesions progressing to type 3 MNV. CONCLUSIONS:In eyes with non-neovascular AMD, DRAMA includes two types of capillary dilations occurring without remodeling of the surrounding vascular network. DRAMA can resemble microvascular changes due to other causes and can masquerade as type 3 MNV. Mild intraretinal exudation can vary during follow up without progression to type 3 MNV.

Purpose:To characterize macular blood flow connectivity in vivo using high-resolution optical coherence tomography (HighRes OCT). Methods:Cross-sectional, observational study. Dense (6-µm interscan distance) perifoveal HighRes OCT raster scans were performed on healthy participants. To mitigate the limitations of projection-resolved OCT-angiography, flow and structural data were used to observe the vascular structures of the superficial vascular complex (SVC) and the deep vascular complex. Vascular segmentation and rendering were performed using Imaris 9.5 software. Inflow and outflow patterns were classified according to vascular diameter and branching order from superficial arteries and veins, respectively. Results:Eight eyes from eight participants were included in this analysis, from which 422 inflow and 459 outflow connections were characterized. Arteries had direct arteriolar connections to the SVC (78%) and to the intermediate capillary plexus (ICP, 22%). Deep capillary plexus (DCP) inflow derived from small-diameter vessels succeeding ICP arterioles. The most prevalent outflow pathways coursed through superficial draining venules (74%). DCP draining venules ordinarily merged with ICP draining venules and drained independently of superficial venules in 21% of cases. The morphology of DCP draining venules in structural HighRes OCT is distinct from other vessels crossing the inner nuclear layer and can be used to identify superficial veins. Conclusions:Vascular connectivity analysis supports a hybrid circuitry of blood flow within the human parafoveal macula. Translational Relevance:Characterization of parafoveal macular blood flow connectivity in vivo using a precise segmentation of HighRes OCT is consistent with ground-truth microscopy studies and shows a hybrid circuitry.

PURPOSE/OBJECTIVE:To report a case of branch retinal artery occlusion associated with paracentral acute middle maculopathy on spectral-domain optical coherence tomography presumably related to heavy cannabis consumption. METHODS:Retrospective case report. Spectral-domain optical coherence tomography, fluorescein angiography, and optical coherence tomography angiography were performed. RESULTS:A 21-year-old healthy man described the acute onset of superior visual field loss in his right eye. He admitted smoking approximately 15 g daily of cannabis for several weeks during COVID-19 confinement. Ophthalmoscopic examination of the right eye showed inferotemporal retinal whitening. Spectral-domain optical coherence tomography illustrated evidence of the ischemic cascade with diffuse hyperreflectivity of the inner and middle retinal layers within the central region of the retinal infarct and paracentral acute middle maculopathy at the border of the infarct. Optical coherence tomography angiography demonstrated predominant flow signal loss at the level of the deep retinal capillary plexus. Fluorescein angiography and complete systemic workup were unremarkable. CONCLUSION/CONCLUSIONS:Branch retinal artery occlusion and paracentral acute middle maculopathy may be related to heavy cannabis use as the result of transient arterial vasospasm.

Purpose/UNASSIGNED:To develop a machine-learning image processing model for three-dimensional (3D) reconstruction of vitreous anatomy visualized with swept-source optical coherence tomography (SS-OCT). Methods/UNASSIGNED:Healthy subjects were imaged with SS-OCT. Scans of sufficient quality were transferred into the Fiji is just ImageJ image processing toolkit, and proportions of the resulting stacks were adjusted to form cubic voxels. Image-averaging and Trainable Weka Segmentation using Sobel and variance edge detection and directional membrane projections filters were used to enhance and interpret the signals from vitreous gel, liquid spaces within the vitreous, and interfaces between the former. Two classes were defined: "Septa" and "Other." Pixels were selected and added to each class to train the classifier. Results were generated as a probability map. Thresholding was performed to remove pixels that were classified with low confidence. Volume rendering was performed with TomViz. Results/UNASSIGNED:Forty-seven eyes of 34 healthy subjects were imaged with SS-OCT. Thirty-four cube scans from 25 subjects were of sufficient quality for volume rendering. Clinically relevant vitreous features including the premacular bursa, area of Martegiani, and prevascular vitreous fissures and cisterns, as well as varying degrees of vitreous degeneration were visualized in 3D. Conclusions/UNASSIGNED:A machine-learning model for 3D vitreous reconstruction of SS-OCT cube scans was developed. The resultant high-resolution 3D movies illustrated vitreous anatomy in a manner like triamcinolone-assisted vitrectomy or postmortem dye injection. Translational Relevance/UNASSIGNED:This machine learning model now allows for comprehensive examination of the vitreous structure beyond the vitreoretinal interface in 3D with potential applications for common disease states such as the vitreomacular traction and Macular Hole spectrum of diseases or proliferative diabetic retinopathy.