Multimodal Imaging of Waldenstrom Macroglobulinemia-Associated Hyperviscosity-Related Retinopathy Treated with Plasmapheresis.

While plasmapheresis is well known to significantly improve both retinal findings and systemic manifestations associated with Waldenstrom macroglobulinemia, few reports exist documenting changes in optical coherence tomography angiography (OCT-A). The authors present a case of a patient with Waldenstrom macroglobulinemia who had resolution of white-centered peripheral retinal lesions and parafoveal outer nuclear layer hyperreflective material following plasmapheresis. Applying image analysis software to before and after OCT-A images, the authors were able to show an objective decrease in retinal capillary and large vessel density following plasmapheresis. This technique can be used to guide treatment and surveillance for patients with hyperviscosity-related retinopathy.

Vascular Patterning as Integrative Readout of Complex Molecular and Physiological Signaling by VESsel GENeration Analysis.

The molecular signaling cascades that regulate angiogenesis and microvascular remodeling are fundamental to normal development, healthy physiology, and pathologies such as inflammation and cancer. Yet quantifying such complex, fractally branching vascular patterns remains difficult. We review application of NASA's globally available, freely downloadable VESsel GENeration (VESGEN) Analysis software to numerous examples of 2D vascular trees, networks, and tree-network composites. Upon input of a binary vascular image, automated output includes informative vascular maps and quantification of parameters such as tortuosity, fractal dimension, vessel diameter, area, length, number, and branch point. Previous research has demonstrated that cytokines and therapeutics such as vascular endothelial growth factor, basic fibroblast growth factor (fibroblast growth factor-2), transforming growth factor-beta-1, and steroid triamcinolone acetonide specify unique "fingerprint" or "biomarker" vascular patterns that integrate dominant signaling with physiological response. In vivo experimental examples described here include vascular response to keratinocyte growth factor, a novel vessel tortuosity factor; angiogenic inhibition in humanized tumor xenografts by the anti-angiogenesis drug leronlimab; intestinal vascular inflammation with probiotic protection by Saccharomyces boulardii, and a workflow programming of vascular architecture for 3D bioprinting of regenerative tissues from 2D images. Microvascular remodeling in the human retina is described for astronaut risks in microgravity, vessel tortuosity in diabetic retinopathy, and venous occlusive disease.

Imaging of Macrophage-Like Cells in Living Human Retina Using Clinical OCT.

Purpose: To image retinal macrophages at the vitreoretinal interface in the living human retina using a clinical optical coherence tomography (OCT) device. Methods: Eighteen healthy controls and three patients with retinopathies were imaged using a clinical spectral-domain OCT. In controls, 10 sequential scans were collected at three different locations: (1) ∼9 degrees temporal to the fovea, (2) the macula, and (3) the optic nerve head (ONH). Intervisit repeatability was evaluated by imaging the temporal retina twice on the same day and 3 days later. Only 10 scans at the temporal retina were obtained from each patient. A 3-µm OCT reflectance (OCT-R) slab located above the inner limiting membrane (ILM) surface was averaged. Results: In controls, ramified macrophage-like cells with regular spatial separation were visualized in the temporal and ONH OCT-R images; however, cell structures were not resolvable at the macula. Interim changes in cell position suggestive of cell translocation were observed between images collected on the same day and those collected 3 days later. There was considerable variation in cell density and nearest-neighbor distance (NND) across controls. Mean ± SD cell densities measured at the temporal and ONH were 78 ± 23 cells/mm2 and 57 ± 16 cells/mm2, respectively. Similarly, mean ± SD NNDs measured at the temporal and ONH were 74.3 ± 13.3 µm and 93.3 ± 20.0 µm, respectively. Nonuniform spatial distribution and altered morphology of the cells were identified in patients with retinopathies. Conclusions: Our findings showed regular spatial separation and ramified morphology of macrophage-like cells on the ILM surface with cell translocation over time in controls. Their distribution and morphology suggest an origin of macrophage-like cells such as microglia or hyalocytes.

ACUTE MACULAR AND PERIPAPILLARY ANGIOGRAPHIC CHANGES WITH INTRAVITREAL INJECTIONS.

PURPOSE: Intravitreal injections acutely and temporarily increase intraocular pressure (IOP), and this may have cumulative long-term effects including an increased risk for glaucoma surgery. This study was designed to measure retinal perfusion density changes on optical coherence tomography (OCT) angiography and OCT thickness alterations associated with acutely increased IOP after intravitreal injections. METHODS: Retrospective observational clinical study of 40 eyes (39 patients) with various retinopathies from October 2016 to June 2017 at a tertiary care retina clinic in NYC. Patients were older than 18 years, with vision >20/100, able to fixate and without media opacities precluding OCT angiography, receiving intravitreal bevacizumab or aflibercept for diabetic retinopathy, retinal vein occlusion, macular degeneration, retinal neovascularization, or radiation retinopathy. The 3-mm × 3-mm macular and 4.5-mm × 4.5-mm peripapillary OCT angiography perfusion density, macular OCT thickness, and IOP were measured before and immediately after intravitreal injections. Paired t-test was used to compare preinjection and postinjection values for perfusion density and OCT thickness. Regression analysis was performed for potential effects of baseline IOP, IOP change, and age. RESULTS: Statistically significant decreases in angiographic perfusion density (P < 0.05) were found in most areas of the superficial and deep layer macular OCT angiography, and the overall optic nerve head and the radial peripapillary capillary layer, preferentially temporal. Macular OCT thickness was significantly decreased in the temporal region and increased in the nasal region. Regression analysis showed relationships between age and decreased superficial macular perfusion. Preinjection IOP was only related to OCT thickness in the fovea. Intraocular pressure change was related only to decreased superficial macular perfusion density. CONCLUSION: Intravitreal injections produce acute IOP changes that are associated with reduced macular and peripapillary perfusion density. Therefore, it is possible that patients receiving regular intravitreal injections may be sustaining perfusion-related injury to ocular structures that may produce glaucomatous damage to the macula and optic nerve.