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

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

Multimodal imaging documentation of rapid evolution of retinal changes in handheld laser-induced maculopathy

Purpose To use multimodal imaging to document the relatively rapid clinical evolution of handheld laser-induced maculopathy (HLIM). To demonstrate that inadvertent ocular injury can result from devices mislabeled with respect to their power specifications. Methods The clinical course of a 17-year-old male who sustained self-inflicted, central macular damage from a 20–25 s direct stare at a red-spectrum, handheld laser pointer ordered from an internet retailer is provided. Retrospective review of multimodal imaging that includes fundus photography, fluorescein angiography, MultiColor reflectance, eye-tracked spectral domain optical coherence tomography (SD-OCT), fundus autofluorescence, and microperimetry is used to describe the evolving clinical manifestations of HLIM in the first 3 months. Results Curvilinear bands of dense hyperreflectivity extending from the outer retina and following the Henle fibers were seen on SD-OCT immediately after injury. This characteristic appearance had largely resolved by 2 weeks. There was significant non-uniformity in the morphological characteristics of HLIM lesions between autofluorescence and reflectance images. The pattern of lesion evolution was also significantly different between imaging modalities. Analysis of the laser device showed its wavelength to be correctly listed, but the power was found to be 102.5–105 mW, as opposed to the <5 mW described on the label. Conclusion While the immediate SD-OCT characteristics are highly specific for handheld laser -induced maculopathy, this finding can undergo rapid resolution in the span of several days. In the absence of this finding, other multimodal imaging clues and a careful history may aid in recognizing this diagnosis. A greater awareness regarding inaccurate labeling on some of these devices could help reduce the frequency of this preventable entity

Label-Free Density Measurements of Radial Peripapillary Capillaries in the Human Retina

Radial peripapillary capillaries (RPCs) comprise a unique network of capillary beds within the retinal nerve fibre layer (RNFL) and play a critical role in satisfying the nutritional requirements of retinal ganglion cell (RGC) axons. Understanding the topographical and morphological characteristics of these networks through in vivo techniques may improve our understanding about the role of RPCs in RGC axonal health and disease. This study utilizes a novel, non-invasive and label-free optical imaging technique, speckle variance optical coherence tomography (svOCT), for quantitatively studying RPC networks in the human retina. Six different retinal eccentricities from 16 healthy eyes were imaged using svOCT. The same eccentricities were histologically imaged in 9 healthy donor eyes with a confocal scanning laser microscope. Donor eyes were subject to perfusion-based labeling techniques prior to retinal dissection, flat mounting and visualization with the microscope. Capillary density and diameter measurements from each eccentricity in svOCT and histological images were compared. Data from svOCT images were also analysed to determine if there was a correlation between RNFL thickness and RPC density. The results are as follows: (1) The morphological characteristics of RPC networks on svOCT images are comparable to histological images; (2) With the exception of the nasal peripapillary region, there were no significant differences in RPC density measurements between svOCT and histological images; (3) Capillary diameter measurements were significantly greater in svOCT images compared to histology; (4) There is a positive correlation between RPC density and RNFL thickness. The findings in this study suggest that svOCT is a reliable modality for analyzing RPC networks in the human retina. It may therefore be a valuable tool for aiding our understanding about vasculogenic mechanisms that are involved in RGC axonopathies. Further work is required to explore the reason for some of the quantitative differences between svOCT and histology

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 \u3c 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

Microstructure and Network Organization of the Microvasculature in the Human Macula

PURPOSE. To characterize the topography and cellular structure of the macular microvasculature using a recently developed technique of arterial cannulation, perfusion, fixation, and staining of human donor eyes. METHODS. Sixteen human donor eyes were used. The central retinal artery was cannulated and perfused with Ringer's, then fixative, membrane permeabilizing, and selected labeling solutions. The eyes were immersion fixed, and the retina was flat mounted for confocal microscopy. The macular area, including the foveola, fovea, and parafovea, was sampled. The intracellular cytoskeleton of vascular endothelial and smooth muscle cells was studied in different orders of arterioles and venules and in the capillaries. To evaluate the degree of asymmetry within vascular networks, the distribution of generation numbers and the Horton-Strahler approach to vessel naming were compared. RESULTS. The distribution of the microvascular network in the macular region was complex but followed a general theme. The parafoveal region was supplied by dense vasculature with approximately nine closely arranged pairs of arterioles and venules. Each arteriole had abundant branches and a high degree of asymmetry (~10 generations and 3.5 orders within 1.2-mm length). Only a few arterioles (average ~2.9) supplied the terminal capillary ring. Very long spindle endothelial cells were seen in the superficial and deep capillaries. Significant heterogeneity of distribution and shape of the endothelial and smooth muscle cells was evident in different orders of the macular vasculature. CONCLUSIONS. The authors have demonstrated for the first time the cellular structure and topographic features of the macular microvasculature in human donor eyes

An assessment of microvascular hemodynamics in human macula

Abstract An adequate blood supply to meet the energy demands is essential for any tissue, particularly for high energy demand tissues such as the retina. A critical question is: How is the dynamic match between neuronal demands and blood supply achieved? We present a quantitative assessment of temporal and spatial variations in perfusion in the macular capillary network in 10 healthy human subjects using a non-invasive and label-free imaging technique. The assessment is based on the calculation of the coefficient of variation (CoV) of the perfusion signal from arterioles, venules and capillaries from a sequence of optical coherence tomography angiography images centred on the fovea. Significant heterogeneity of the spatial and temporal variation was found within arterioles, venules and capillary networks. The CoV values of the capillaries and smallest vessels were significantly higher than that in the larger vessels. Our results demonstrate the presence of significant heterogeneity of spatial and temporal variation within each element of the macular microvasculature, particularly in the capillaries and finer vessels. Our findings suggest that the dynamic match between neuronal demands and blood supply is achieved by frequent alteration of local blood flow evidenced by capillary perfusion variations both spatially and temporally in the macular region