Metrics of retinal vasculature detected on OCTA in carotid artery stenosis: a systematic review and meta-analysis.

BACKGROUND: Carotid artery stenosis (CAS) is a major cause of cerebral microcirculation dysfunction, contributing to 15-20% of ischemic strokes. Retinal vessel changes is associated with several systemic diseases, including CAS. This systematic review investigates retinal microvascular alterations measured using optical coherence tomography angiography (OCTA) in patients with CAS. METHODS: We comprehensively searched the electronic databases, namely PubMed, Cochrane Library, Embase, and Web of Science. Macular and optic nerve head vascular density (VD) in patients with CAS were compared to controls. Pooled data for each outcome were calculated as standardized mean difference (SMD) and 95% confidence interval. OCTA parameters were analyzed using Review Manager Version 5.4.1 software. RESULTS: Seven articles were included in this meta-analysis. Whole macular enface superficial and deep VD were significantly lower in patients with CAS than in controls (SMD = -0.97, P = 0.002; SMD = -1.05, P = 0.006, respectively). Additionally, the parafoveal superficial VD was significantly lower in the CAS group than in the healthy group (SMD= -0.71, P= 0.001). Radial peripapillary capillary (RPC) whole-image VD (SMD= -0.90, P< 0.0001), RPC inside disc VD (SMD= -0.49, P= 0.02), and RPC peripapillary VD (SMD= -0.64, P= 0.0003) were also significantly lower in patients with CAS compared to healthy individuals. CONCLUSION: These findings suggest that patients with CAS are prone to decreased VD in the macular and optic nerve head areas. Hence, OCTA shows potential as a promising tool for the early detection of cerebral microcirculation disorders due to CAS.

Optical coherence tomography angiography to assess for retinal vascular changes in Neuro-Sjögren.

Background: Sjögren's syndrome is an autoimmune disease characterized by sicca symptoms and various extraglandular manifestations including vasculitis. Neurological involvement occurs frequently (Neuro-Sjögren) and often mimics immune neuropathies such as chronic inflammatory demyelinating polyneuropathy (CIDP). Objectives: We aim to assess relevant differences in vessel density (VD) in Optical Coherence Tomography Angiography (OCTA) in those diseases to use it as an easily available diagnostic tool. Design: Prospective, monocentric pilot-study. Methods: OCTA (Heidelberg Engineering OCT SPECTRALIS) of the superficial vascular plexus, intermediate capillary plexus (ICP) and deep capillary plexus (DCP) of the retina was prospectively performed in Neuro-Sjögren, age-matched CIDP patients (n = 31, each), and healthy controls (n = 30). Vessel density (VD) and foveal avascular zone (FAZ) was measured with Erlangen Angio Tool. Results: Significantly lower VD were found for the DCP and ICP in Neuro-Sjögren and CIDP patients compared to healthy controls (p = 0.0002 and <0.0001). When group comparison was age-adjusted, these differences were not found anymore. Different frequencies of "low" retinal blood flow in each layer comparing Neuro-Sjögren and CIDP patients were not found. FAZ revealed no significant differences between patients with Neuro-Sjögren, CIDP and healthy controls. Conclusion: This study found no significant differences in VD or the foveal avascular zone between Neuro-Sjögren and CIDP patients using OCTA, suggesting that inflammatory vascular changes in the retina are uncommon in Neuro-Sjögren patients.

Sensitive optical coherence tomography angiography parameters detecting retinal vascular changes in Behcet's uveitis.

PURPOSE: To compare the retinal parameters in Behcet's uveitis (BU) patients with wide-field swept-source optical coherence tomography angiography (SS-OCTA) and find a sensitive OCTA parameter. METHODS: Fifty-two eyes from 52 quiescent BU patients and 50 healthy eyes were included. All subjects underwent SS-OCTA examinations with 12 × 12 mm region. Vessel density (VD) and flow area (FA) in nerve fiber layer (NFL), superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) were analyzed and compared in central, parafoveal, and peripheral regions with diameters of 1, 6 and 12 mm. Receiver operating characteristic curves (ROC), area under the curve (AUC), correlation analysis between OCTA metrics and best-corrected visual acuity (BCVA) were respectively evaluated. RESULTS: BU patients showed significantly lower peripheral VD and FA in NFL (P = 0.019 and 0.002), lower central and parafoveal VD-SVP (P = 0.006 and <0.001), and lower VD-ICP, VD-DCP, FA-SVP, FA-ICP and FA-DCP in all regions (all P < 0.05) as compared to healthy controls. The ROC analysis indicated that the parafoveal, peripheral FA-DCP-1, and a combination of the two metrics were sensitive parameters for identifying retinal vessel changes in BU (AUC=0.90, 0.90, 0.91, respectively). The parafoveal and peripheral FA-DCP were negatively associated with logMAR BCVA (r=-0.764, P < 0.0001; r=-0.641, P < 0.0001). CONCLUSION: The deep retinal layers were apt to be affected in BU patients. The parafoveal and peripheral FA values of DCP may be sensitive parameters for detecting retinal vasculature alterations in BU.

Retinal and Macular Changes in Pregnant Women of Advanced Maternal Age: A Retrospective Study.

Aims/Background Pregnancy may cause physiological and pathological changes in multiple organs in a woman's body, including the heart, liver, and eyes. With rapid advances in societies and economies, the proportion of advanced maternal age (AMA) women has significantly increased. Here, we aimed to investigate the changes in arteriole retinal diameter, venule diameter, macular layer thickness, and arteriole to venule ratio (AVR) in this population. Methods This retrospective case-control study included 523 pregnant women (1046 eyes) and was performed on both eyes. In total, 318 subjects were included in the AMA group, and 205 subjects were included in the non-AMA group. Nonmydriatic fundus photography and optical coherence tomography (OCT) were performed on the same day, and the results were analyzed for the central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), AVR, and macular thickness (9 subfields) by integrative vessel analysis and automatic OCT software. Results In both eyes, the CRAE was significantly lower in the AMA group than that in the non-AMA group (p < 0.05; respectively). The CRVE in the AMA group was higher than that in the non-AMA group (p < 0.001; respectively). Compared to the non-AMA group, the AMA group exhibited a significant reduction in macular thickness within the inner nasal, outer nasal, and inner temporal subfields of both eyes (p < 0.05; respectively). Age was significantly correlated with CRVE and AVR in both eyes of pregnant women (CRVE: p < 0.0001; AVR: p < 0.01). Conclusion This study reports variations in the diameter of the retinal vasculature and the thickness of the macula in women of AMA. It is important to consider these changes when interpreting the adverse eye outcomes experienced by women of AMA.

Investigation of optical coherence tomography angiography findings in patients with bipolar disorder.

OBJECTIVES: Bipolar Disorder (BD) is an important psychiatric disease that progresses with attacks, can be chronic and causes serious mental problems. In this study, we aimed to identify the retinal vascular pathologies in BD patients by optical coherence tomography angiography (OCTA) imaging. METHODS: Retinal vascular analysis from 35 BD patients and 30 healthy controls (HCs) were scanned using the OCTA machine. In addition, psychometric tests such as the Young Mania Rating Scale (YMRS) and Clinical Global Impression Scale (CGI-S) were applied to BD patients to assess the severity of the disease and determine the patient's level of functionality. RESULTS: As a result of OCTA scans, there were significant differences between the groups as following; Deep retinal vessel density (VD) in the total, parafoveal and perifoveal area, Macular thickness in the inner parafoveal area, VD of retinal capillary plexuses in the inside disk and the Choroidal thickness (p < 0.05). Furthermore, according to the results of Pearson correlation analysis between OCTA scans and YMRS and CGI-S scores, it was determined that there was no significant relationship in any measurement (p > 0.05). CONCLUSION: In our study, it was determined that there were general differences in deep retinal vascular density and inner macular thickness in BD patients. These findings demonstrate that the deep and inner zone of the retina is affected in BD patients.

Retinal vascular reactivity in carriers of X-linked inherited retinal disease - a study using optical coherence tomography angiography.

Purpose: Female carriers of X-linked inherited retinal diseases (IRDs) can show highly variable phenotypes and disease progression. Vascular reactivity, a potential disease biomarker, has not been investigated in female IRD carriers. In this study, functional optical coherence tomography angiography (OCT-A) was used to dynamically assess the retinal microvasculature of X-linked IRD carriers. Methods: Genetically confirmed female carriers of IRDs (choroideremia or X-linked retinitis pigmentosa), and healthy women were recruited. Macular angiograms (3x3mm, Zeiss Plex Elite 9000) were obtained in 36 eyes of 15 X-linked IRD female carriers and 21 age-matched control women. Two tests were applied to test vascular reactivity: (i) mild hypoxia and (ii) handgrip test, to induce a vasodilatory or vasoconstrictive response, respectively. Changes to vessel density (VD) and vessel length density (VLD) were independently evaluated during each of the tests for both the superficial and deep capillary plexuses. Results: In the control group, the superficial and deep VD decreased during the handgrip test (p<0.001 and p=0.037, respectively). Mean superficial VLD also decreased during the handgrip test (p=0.025), while the deep plexus did not change significantly (p=0.108). During hypoxia, VD and VLD increased in the deep plexus (p=0.027 and p=0.052, respectively) but not in the superficial plexus. In carriers, the physiologic vascular responses seen in controls were not observed in either plexus during either test, with no difference in VD or VLD noted (all p>0.05). Conclusions: Functional OCT-A is a useful tool to assess dynamic retinal microvascular changes. Subclinical impairment of the physiological vascular responses seen in carriers of X-linked IRDs may serve as a valuable clinical biomarker.

Retinal vascular changes and arterial stiffness during 8-month isolation and confinement: the SIRIUS-21 space analog mission.

Introduction: Isolation and confinement are significant stressors during space travel that can impact crewmembers' physical and mental health. Space travel has been shown to accelerate vascular aging and increase the risk of cardiovascular and cerebrovascular disorders. However, the effect of prolonged isolation and confinement on microvascular function has not yet been thoroughly investigated. Methods: Retinal vascular imaging was conducted on four crewmembers during- and post-8-month SIRIUS-21 space analog mission. Central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), and arteriovenous ratio (AVR) were measured. Pulse wave velocity (PWV), an indicator of arterial stiffness, was also measured. Results: Data from 4 participants was analyzed. These participants had a mean age of 34.75 ± 5.44 years, height of 170.00 ± 2.00 cm, weight of 74.50 ± 12.53 kg, and average BMI of 25.47 ± 3.94 kg/m2. During- and post-isolation, average CRVE showed an upward trend (Pearson's r 0.784, R-square 0.62), suggesting a dilation of retinal venules, while AVR showed a downward trend (Pearson's r -0.238, R-square 0.057), which is suggestive of a higher risk of cardiovascular and cerebrovascular dysfunctions. But neither of these trends were statistically significant. Additionally, the average PWV showed an upward trend during- and after-isolation across all crew members. Conclusion: Isolation and confinement appear to contribute towards retinal vascular damage and arterial stiffness. This cautiously suggests an increased risk of cardiovascular and cerebrovascular disorders due to the contribution of the isolation in space flight. Further studies are needed to confirm and expand on these results as we prepare for future manned missions to the Moon and Mars.

Analysis of the Retinal and Choroidal Vasculature Using Ultrawidefield Fundus Imaging in Mild Cognitive Impairment and Normal Cognition.

Purpose: To utilize ultrawidefield (UWF) imaging to evaluate retinal and choroidal vasculature and structure in individuals with mild cognitive impairment (MCI) compared with that of controls with normal cognition. Design: Prospective cross sectional study. Participants: One hundred thirty-one eyes of 82 MCI patients and 230 eyes of 133 cognitively normal participants from the Eye Multimodal Imaging in Neurodegenerative Disease Study. Methods: A scanning laser ophthalmoscope (California, Optos Inc) was used to obtain UWF fundus color images. Images were analyzed with the Vasculature Assessment Platform for Images of the Retina UWF (VAMPIRE-UWF 2.0, Universities of Edinburgh and Dundee) software. Main outcome measures: Imaging parameters included vessel width gradient, vessel width intercept, large vessel choroidal vascular density, vessel tortuosity, and vessel fractal dimension. Results: Both retinal artery and vein width gradients were less negative in MCI patients compared with controls, demonstrating decreased rates of vessel thinning at the periphery (P < 0.001; P = 0.027). Retinal artery and vein width intercepts, a metric that extrapolates the width of the vessel at the center of the optic disc, were smaller in MCI patients compared with that of controls (P < 0.001; P = 0.017). The large vessel choroidal vascular density, which quantifies the vascular area versus the total choroidal area, was greater in MCI patients compared with controls (P = 0.025). Conclusions: When compared with controls with normal cognition, MCI patients had thinner retinal vasculature manifested in both the retinal arteries and the veins. In MCI, these thinner arteries and veins attenuated at a lower rate when traveling toward the periphery. MCI patients also had increased choroidal vascular density. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Optical coherence tomography angiography measurements in systemic lupus erythematosus: A systematic review and meta-analysis.

Systemic lupus erythematosus (SLE) is an autoimmune disease affecting various organs. Ocular involvement, particularly retinopathy, is common, emphasizing the significance of early detection. Optical coherence tomography angiography (OCTA), a non-invasive imaging technique, reveals microvascular changes, aiding SLE diagnosis and monitoring. This study evaluates OCTA's effectiveness in detecting SLE-related retinal alterations. A systemic search was undertaken across PubMed, Embase, and Scopus databases to identify studies presenting OCTA measurements in SLE patients compared to healthy controls. The meta-analysis, employing either fixed-effects or random-effects models based on heterogeneity levels, was conducted. Additionally, subgroup and sensitivity analyses, meta-regression, and quality assessments were carried out. Thirteen studies of 565 eyes in the SLE group and 560 eyes in the control group were included. The meta-analyses revealed that SLE patients had a significantly lower retinal vessel density in the superficial and deep capillary plexus layers, choriocapillaris flow area, and foveal avascular zone (FAZ) circularity index compared to healthy controls, but that there were no significant differences in the FAZ area and perimeter. These findings highlight how OCTA can provide a noninvasive assessment of SLE effects on the retinal microvasculature, potentially presenting a reliable biomarker for more precise detection of SLE and disease activity monitoring.

Clinical and genetic studies for a cohort of patients with Leber congenital amaurosis.

PURPOSE: Leber congenital amaurosis (LCA) is a group of early-onset retinal degenerative disorders, resulting in blindness in children. This study aimed to describe the clinical and genetic characteristics of a cohort of patients with LCA and to investigate the retinal vascular characteristics in LCA patients. METHODS: Fifty-two children with LCA were included in the study. All patients underwent detailed ocular examinations. Electroretinography (ERG) was used to evaluate the retinal function. Optical coherence tomography (OCT) was used to assess the structure change of the retina for those patients who were able to cooperate very well. Panel-based next-generation sequencing was performed to identify pathogenic variants in genes associated with LCA. Diameters of the retinal vessels were measured using the EVision AI screening system with an artificial intelligence (AI) technique. An ultrasound Doppler was used to evaluate hemodynamic parameters, including peak systolic velocity (PSV), resistive index (RI), and pulsatility index (PI), in the ophthalmic, central retinal, posterior ciliary, carotid, and internal carotid as well as external carotid arteries in 12 patients aged from 3 to 14 years. RESULTS: We detected 75 pathogenic variants from ten genes of RPGRIP1, CEP290, GUCY2D, LCA5, AIPL1, CRB1, RPE65, CRX, RDH12, and TULP1, including 29 novel and 36 previously reported variants in 52 affected children with LCA, with the highest detective rate in RPGRIP1 (26.9%). Fundus appearance is diverse in patients with LCA, ranging from normal to severe peripheral or central retinopathy. Retinal vasculature was evaluated in 12 patients with different gene variants, showing narrowed arteries with an average diameter of 43.6 ± 3.8 µm compared to that of 51.7 ± 2.6 µm in the normal controls (P < 0.001, n = 12). Meanwhile, their hemodynamic parameters were changed as well in the ophthalmic artery (OA), with a decreased PSV (P = 0.0132, n = 12) and slightly increased PI (P = 0.0488, n = 12) compared to the normal controls. However, the hemodynamic parameters did not change significantly in the other vessels. CONCLUSIONS: Blood supply to the eyeball is predicted to be reduced in patients with LCA, presumably due to photoreceptor cell degeneration. The novel identified variants will expand the spectrum of variants in LCA-related genes and be useful for studying the molecular mechanisms of LCA.

Comparative evaluation of trypsin and elastase digestion techniques for isolation of murine retinal vasculature.

Dysfunctional pericytes and disruption of adherens or tight junctions are related to many microvascular diseases, including diabetic retinopathy. In this context, visualizing retinal vascular architecture becomes essential for understanding retinal vascular disease pathophysiology. Although flat mounts provide a demonstration of the retinal blood vasculature, they often lack a clear view of microaneurysms and capillary architecture. Trypsin and elastase digestion are the two techniques for isolating retinal vasculatures in rats, mice, and other animal models. Our observations in the present study reveal that trypsin digestion impacts the association between pericytes and endothelial cells. In contrast, elastase digestion effectively preserves these features in the blood vessels. Furthermore, trypsin digestion disrupts endothelial adherens and tight junctions that elastase digestion does not. Therefore, elastase digestion emerges as a superior technique for isolating retinal vessels, which can be utilized to collect reliable and consistent data to comprehend the pathophysiology of disorders involving microvascular structures.

Progress in clinical research and applications of retinal vessel quantification technology based on fundus imaging.

Retinal blood vessels are the only directly observed blood vessels in the body; changes in them can help effective assess the occurrence and development of ocular and systemic diseases. The specificity and efficiency of retinal vessel quantification technology has improved with the advancement of retinal imaging technologies and artificial intelligence (AI) algorithms; it has garnered attention in clinical research and applications for the diagnosis and treatment of common eye and related systemic diseases. A few articles have reviewed this topic; however, a summary of recent research progress in the field is still needed. This article aimed to provide a comprehensive review of the research and applications of retinal vessel quantification technology in ocular and systemic diseases, which could update clinicians and researchers on the recent progress in this field.

Quantitative Analysis of the Vasculature and Cone Photoreceptors in Subjects With Diabetes Without Diabetic Retinopathy.

PURPOSE: To characterize any differences in the vasculature and cone photoreceptor packing geometry (CPG) between subjects with diabetes without/no diabetic retinopathy (NDR) and healthy controls. METHODS: Eight NDR and five controls were enrolled. Optical coherence tomography angiography (OCTA) taken at the macula was used to measure vessel density, vessel length density, and vessel density index (VDI) in three vascular plexuses, namely, the superficial vascular plexus, intermediate capillary plexus, and deep capillary plexus (DCP). The choriocapillaris (CC) flow deficit (FD) was also measured. OCTA images were binarized and processed to extrapolate the parafovea and parafoveal quadrants and the OCTA indices mentioned above. The CC was processed with six different radii to quantify FD. Adaptive optics - scanning laser ophthalmoscopy images were acquired and processed to extract CPG indices, i.e., cone density (CD), cone-to-cone spacing (CS), linear dispersion index, heterogeneity packing index and percent of cells with six neighbors at 3.6° in the temporal retina. RESULTS: In all eyes, statistically significant differences were found (i) in parafoveal FD across the six radii (p < 0.001) and (ii) in the correlation between the parafoveal temporal quadrant (PTQ) DCP VDI and CS (r = 0.606, p = 0.048). No other significant correlations were found. For OCTA or CPG indices, no significant differences were found between the cohorts in the parafovea or parafoveal quadrants. CONCLUSIONS: CS is the most sensitive CPG index for detecting alterations in the cone mosaic. The DCP and the cone photoreceptors are significantly correlated, indicating that alterations in the DCP can affect the cones. Future work elucidating the vascular alterations and neurodegeneration present in diabetic eyes should focus on the DCP and multiple CPG indices, not solely CD. Moreover, such alterations are highly localized, hence using larger regions e.g. parafovea versus smaller areas, such as the PTQ, will potentially mask significant correlations.

Retinal Vascular Changes in Response to Hypoxia: A High-Altitude Expedition Study.

Westwood, Jessica, India Mayhook-Walker, Ciaran Simpkins, Andrew Darby-Smith, Dan Morris, and Eduardo Normando. Retinal vascular changes in response to hypoxia: a high-altitude expedition study. High Alt Med Biol. 25:49-59, 2024. Background: Increased tortuosity and engorgement of retinal vasculature are recognized physiological responses to hypoxia. This can lead to high-altitude retinopathy (HAR), but incidence reports are highly variable, and our understanding of the etiological mechanisms remains incomplete. This study quantitatively evaluated retinal vascular changes during an expedition to 4,167 m. Methods: Ten healthy participants summited Mount Toubkal, Morocco. Fundus images were taken predeparture, daily throughout the expedition, and 1 month postreturn. Diameter and tortuosity of four vessels were assessed, in addition to vessel density and features of HAR. Results: Significant (p ≤ 0.05) increases in tortuosity and diameter were observed in several vessels on high-altitude exposure days. There was a strong correlation between altitude and supratemporal retinal artery diameter on days 2, 3, and 6 of the expedition (r = 0.7707, 0.7951, 0.7401, respectively; p < 0.05). There was a significant increase in median vessel density from 6.7% at baseline to 10.0% on summit day. Notably there were no incidences of HAR. Conclusion: Physiological but not pathological changes were seen in this cohort, which gives insight into the state of the cerebral vasculature throughout this expedition. These results are likely attributable to relatively low altitude exposure, a conservative ascent profile, and the cohort's demographic. Future study must include daily retinal images at higher altitudes and take steps to mitigate environmental confounders. This study is relevant to altitude tourists, patients with diabetic retinopathy or retinal vein occlusion, and critically ill patients.

Non-Invasive Evaluation of Retinal Vascular Alterations in a Mouse Model of Optic Neuritis Using Laser Speckle Flowgraphy and Optical Coherence Tomography Angiography.

Optic neuritis, a characteristic feature of multiple sclerosis (MS), involves the inflammation of the optic nerve and the degeneration of retinal ganglion cells (RGCs). Although previous studies suggest that retinal blood flow alterations occur during optic neuritis, the precise location, the degree of impairment, and the underlying mechanisms remain unclear. In this study, we utilized two emerging non-invasive imaging techniques, laser speckle flowgraphy (LSFG) and optical coherence tomography angiography (OCTA), to investigate retinal vascular changes in a mouse model of MS, known as experimental autoimmune encephalomyelitis (EAE). We associated these changes with leukostasis, RGC injury, and the overall progression of EAE. LSFG imaging revealed a progressive reduction in retinal blood flow velocity and increased vascular resistance near the optic nerve head in the EAE model, indicating impaired ocular blood flow. OCTA imaging demonstrated significant decreases in vessel density, number of junctions, and total vessel length in the intermediate and deep capillary plexus of the EAE mice. Furthermore, our analysis of leukostasis revealed a significant increase in adherent leukocytes in the retinal vasculature of the EAE mice, suggesting the occurrence of vascular inflammation in the early development of EAE pathology. The abovechanges preceded or were accompanied by the characteristic hallmarks of optic neuritis, such as RGC loss and reduced visual acuity. Overall, our study sheds light on the intricate relationship between retinal vascular alterations and the progression of optic neuritis as well as MS clinical score. It also highlights the potential for the development of image-based biomarkers for the diagnosis and monitoring of optic neuritis as well as MS, particularly in response to emerging treatments.

Mechanisms Underlying Rare Inherited Pediatric Retinal Vascular Diseases: FEVR, Norrie Disease, Persistent Fetal Vascular Syndrome.

Familial Exudative Vitreoretinopathy (FEVR), Norrie disease, and persistent fetal vascular syndrome (PFVS) are extremely rare retinopathies that are clinically distinct but are unified by abnormal retinal endothelial cell function, and subsequent irregular retinal vascular development and/or aberrant inner blood-retinal-barrier (iBRB) function. The early angiogenesis of the retina and its iBRB is a delicate process that is mediated by the canonical Norrin Wnt-signaling pathway in retinal endothelial cells. Pathogenic variants in genes that play key roles within this pathway, such as NDP, FZD4, TSPAN12, and LRP5, have been associated with the incidence of these retinal diseases. Recent efforts to further elucidate the etiology of these conditions have not only highlighted their multigenic nature but have also resulted in the discovery of pathological variants in additional genes such as CTNNB1, KIF11, and ZNF408, some of which operate outside of the Norrin Wnt-signaling pathway. Recent discoveries of FEVR-linked variants in two other Catenin genes (CTNND1, CTNNA1) and the Endoplasmic Reticulum Membrane Complex Subunit-1 gene (EMC1) suggest that we will continue to find additional genes that impact the neural retinal vasculature, especially in multi-syndromic conditions. The goal of this review is to briefly highlight the current understanding of the roles of their encoded proteins in retinal endothelial cells to understand the essential functional mechanisms that can be altered to cause these very rare pediatric retinal vascular diseases.

Anatomy of the complete mouse eye vasculature explored by light-sheet fluorescence microscopy exposes subvascular-specific remodeling in development and pathology.

Eye development and function rely on precise establishment, regression and maintenance of its many sub-vasculatures. These crucial vascular properties have been extensively investigated in eye development and disease utilizing genetic and experimental mouse models. However, due to technical limitations, individual studies have often restricted their focus to one specific sub-vasculature. Here, we apply a workflow that allows for visualization of complete vasculatures of mouse eyes of various developmental stages. Through tissue depigmentation, immunostaining, clearing and light-sheet fluorescence microscopy (LSFM) entire vasculatures of the retina, vitreous (hyaloids) and uvea were simultaneously imaged at high resolution. In silico dissection provided detailed information on their 3D architecture and interconnections. By this method we describe successive remodeling of the postnatal iris vasculature, involving sprouting and pruning, following its disconnection from the embryonic feeding hyaloid vasculature. In addition, we demonstrate examples of conventional and LSFM-mediated analysis of choroidal neovascularization after laser-induced wounding, showing added value of the presented workflow in analysis of modelled eye disease. These advancements in visualization and analysis of the respective eye vasculatures in development and complex eye disease open for novel observations of their functional interplay at a whole-organ level.

Acrolein Induces Retinal Abnormalities of Alzheimer's Disease in Mice.

It is reported that retinal abnormities are related to Alzheimer's disease (AD) in patients and animal models. However, it is unclear whether the retinal abnormities appear in the mouse model of sporadic Alzheimer's disease (sAD) induced by acrolein. We investigated the alterations of retinal function and structure, the levels of ß-amyloid (Aß) and phosphorylated Tau (p-Tau) in the retina, and the changes in the retinal vascular system in this mouse model. We demonstrated that the levels of Aß and p-Tau were increased in the retinas of mice from the acrolein groups. Subsequently, a decreased amplitudes of b-waves in the scotopic and photopic electroretinogram (ERG), decreased thicknesses of the retinal nerve fiber layer (RNFL) in the retina, and slight retinal venous beading were found in the mice induced by acrolein. We propose that sAD mice induced by acrolein showed abnormalities in the retina, which may provide a valuable reference for the study of the retina in sAD.

The Effect of Post-Coronavirus Disease 2019 Infection on the Retinal Microvasculature.

Purpose: To evaluate the short-term microvasculature changes of the macula and optic disc following coronavirus disease 2019 (COVID-19). Methods: This study included 150 eyes (50 eyes of healthy controls and 100 eyes of patients) during the 1st month following COVID-19 recovery, as evidenced by two negative polymerase chain reactions. A complete ophthalmic examination and optical coherence tomography angiography were performed to detect the deep and superficial macular vessel density (VD). In addition, the VD of the optic disc was evaluated. Results: Deep VD (DVD) showed a statistically significant decrease in post-COVID-19 patients, particularly those with severe COVID-19. This reduction occurred in the whole image, parafoveal, and perifoveal VD (P = 0.002, P = 0.002, and P < 0.001, respectively). Concerning the superficial VD (SVD), only the superior hemisphere of the whole image density was statistically significantly reduced (P = 0.037). There was no statistically significant difference in foveal VD (both deep and superficial vessel) among the study groups (P = 0.148 and P = 0.322, respectively). Regarding the foveal avascular zone (FAZ), there was no statistically significant among groups (P = 0.548). Regarding the optic disc, the whole image VD and redial peripapillary capillary VD demonstrated a highly significant decrease, particularly in cases of severe COVID-19. Conversely, inside disc VD showed a nonsignificant change among the study groups. Conclusions: According to the findings of the current study, retinal microvasculature was affected in the 1st month following recovery from COVID-19. DVD was significantly reduced more than SVD. In addition, peripapillary VD decreased, whereas the FAZ was unaffected.