Retinal Plexus Research Articles

112° field of view high-resolution swept-source OCT angiography for rat retinas.

This study introduces an ultra-wide field (UWF) and high-resolution swept-source optical coherence tomographic angiography (OCTA) system for rat retinal imaging. Using an asymmetrical optics design, the system achieves unprecedented details of retinal structures and vascular plexuses over a large field of view (112°) in a single-shot acquisition. Views of single-nerve fiber bundles and single capillary vessels are consistently visible over a 112° field of view. The system has a long imaging range and high penetration and allows a full view of vitreous hyaloid vessels, retina, choroid, sclera, and posterior ciliary arteries, down to sub-sclera connective tissues. In a longitudinal study of oxygen-induced retinopathy (OIR) in rats, the system successfully revealed the progression and regression of OIR-related vascular pathologies, such as ischemia, neovascularization, and tortuosity. To our knowledge, this novel UWF-OCT/OCTA prototype designed for rat retinal imaging will be a vital tool for monitoring disease progression and evaluating therapeutic interventions in preclinical models.

ATTRv-V30M amyloid fibrils from heart and nerves exhibit structural homogeneity.

Amyloidogenic transthyretin (ATTR) amyloidosis is a systemic disease characterized by the deposition of amyloid fibrils made of transthyretin. Transthyretin is primarily produced in tetrameric form by the liver, but also by retinal epithelium and choroid plexus. The deposition of these fibrils in the myocardium and peripheral nerves causes cardiomyopathies and neuropathies, respectively. Using cryoelectron microscopy (cryo-EM), we investigated fibrils extracted from cardiac and nerve tissues of an ATTRv-V30M patient. We found consistent fibril structures from both tissues, similar to cardiac fibrils previously described, but different from vitreous humor fibrils of the same genotype. Our findings, along with previous ATTR fibrils structural studies, suggest a uniform fibrillar architecture across different tissues when transthyretin originates from the liver. This study advances our understanding of how deposition and production sites influence fibril structure in ATTRv-V30M amyloidosis.

Associations between the Vessel Density in Deep Vascular Plexus and Macular Edema Recurrences in Patients with Retinal Vein Occlusion

Introduction: The aim of this study was to study the relationships between vessel density (VD) in different retinal vascular plexus and retinal vein occlusion-macular edema (RVO-ME) recurrence using wide-field swept source optical coherence tomography angiography (OCTA). Methods: Patients with a history of central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO) with macular edema in the Department of Ophthalmology, Shanghai General Hospital, from May 25, 2020, to January 12, 2023, were retrospectively reviewed and recruited. All patients were followed up for at least 6 months and divided in the release group and the recurrence group. The optical coherence tomography and OCTA examination were performed. Demographics, retinal structural, and angiographic data were collected and compared between two groups. The ordinal logistic regression was performed to assess the risk factors for RVO-ME. Results: A total of 85 patients were enrolled in this study. Among them, 30 patients had CRVO, while 55 had BRVO. The VD in the 6–9 mm ring in deep vascular plexus (DVP) was significantly higher in the recurrence group (25.414 ± 6.068% in the release group vs. 27.574 ± 7.767% in the recurrence group, p = 0.036). More patients with mean VD of the 6–9 mm ring in DVP no less than 30% were observed in the recurrence group (observed n = 20, expected n = 14.4, p = 0.043). The ordinal logistic regression reported that patients with mean VD of the 6–9 mm ring in DVP ≥30% had risk of RVO-ME increased to 11.508 (95% CI: 1.745–75.944, p = 0.011), when compared to the patients with mean VD of the 6–9 mm ring in DVP <20%, even with RVO type, baseline central macular thickness weighed. Conclusion: High vessel density of the 6–9 mm ring in DVP, especially those ≥30%, was associated with macular edema recurrences in patients with retinal vein occlusion.

On-axis full-field swept-source optical coherence tomography for murine retinal imaging

A full-field swept-source optical coherence tomography (FF-SS-OCT) for in vivo murine retinal imaging is demonstrated. The on-axis FF-SS-OCT system was built in a Mach–Zehnder interferometer configuration employing a tunable laser source with an adjustable sweep rate and sweep range in conjunction with a fast 2D-CMOS camera. A large field retinal (coherent) illumination was accomplished using an imaging interface comprised of a short-focal length imaging lens and a contact lens. The magnification between the camera and retina (spatial sampling) was appropriately chosen to record the microscopic structural features of the retina in the image. A pupil stop was employed in the detection path to reject unwanted backscattering from the mouse eye and other sources and limit aberrations distorting the retinal images. In vivo mouse retinal imaging was performed at a sweep rate of 150 Hz to acquire volumes unaffected by the system vibrations, which predominated at lower frequencies. Operating the FF-SS-OCT at this speed yielded an effective axial scan rate of 20 million A-scans/s and a field of view of 820 × 410 µm (24.12° × 12.06°). High-quality retinal B-scans and enface images of the retina were obtained with the SS-FF-OCT, revealing all major retinal layers and vascular plexuses.

Multi-Plexus Nonperfusion Area Segmentation in Widefield OCT Angiography Using a Deep Convolutional Neural Network.

To train and validate a convolutional neural network to segment nonperfusion areas (NPAs) in multiple retinal vascular plexuses on widefield optical coherence tomography angiography (OCTA). This cross-sectional study included 202 participants with a full range of diabetic retinopathy (DR) severities (diabetes mellitus without retinopathy, mild to moderate non-proliferative DR, severe non-proliferative DR, and proliferative DR) and 39 healthy participants. Consecutive 6 × 6-mm OCTA scans at the central macula, optic disc, and temporal region in one eye from 202 participants in a clinical DR study were acquired with a 70-kHz OCT commercial system (RTVue-XR). Widefield OCTA en face images were generated by montaging the scans from these three regions. A projection-resolved OCTA algorithm was applied to remove projection artifacts at the voxel scale. A deep convolutional neural network with a parallel U-Net module was designed to detect NPAs and distinguish signal reduction artifacts from flow deficits in the superficial vascular complex (SVC), intermediate capillary plexus (ICP), and deep capillary plexus (DCP). Expert graders manually labeled NPAs and signal reduction artifacts for the ground truth. Sixfold cross-validation was used to evaluate the proposed algorithm on the entire dataset. The proposed algorithm showed high agreement with the manually delineated ground truth for NPA detection in three retinal vascular plexuses on widefield OCTA (mean ± SD F-score: SVC, 0.84 ± 0.05; ICP, 0.87 ± 0.04; DCP, 0.83 ± 0.07). The extrafoveal avascular area in the DCP showed the best sensitivity for differentiating eyes with diabetes but no retinopathy (77%) from healthy controls and for differentiating DR by severity: DR versus no DR, 77%; referable DR (rDR) versus non-referable DR (nrDR), 79%; vision-threatening DR (vtDR) versus non-vision-threatening DR (nvtDR), 60%. The DCP also showed the best area under the receiver operating characteristic curve for distinguishing diabetes from healthy controls (96%), DR versus no DR (95%), and rDR versus nrDR (96%). The three-plexus-combined OCTA achieved the best result in differentiating vtDR and nvtDR (81.0%). A deep learning network can accurately segment NPAs in individual retinal vascular plexuses and improve DR diagnostic accuracy. Using a deep learning method to segment nonperfusion areas in widefield OCTA can potentially improve the diagnostic accuracy of diabetic retinopathy by OCT/OCTA systems.

Changes in peripapillary and macular vasculature measured by optical coherence tomography angiography and their clinical correlation in patients with optic neuritis due to multiple sclerosis

Aim To document changes in the peripapillary vascular network and retinal vascular plexuses in patients with optic neuritis (ON) due to multiple sclerosis (MS) and compare it with healthy individuals. Settings and design A prospective comparative case–control study performed at the Ophthalmology Department of a tertiary-level university hospital, between November 2020 and November 2022. Patients and methods In all, 26 eyes of 26 patients with ON caused by MS and 26 eyes of 26 sex-matched and age-matched healthy controls. We used optical coherence tomography AngioVue Enhanced Microvascular Imaging System aiming to quantify and compare microvasculature changes in the macula and peripapillary region between the two groups. Results We found a statistically significant decrease in the superficial and deep vessel density in the macular area in patients with ON compared with the healthy controls. Superficial vessel density in the macular area in the healthy ones was 49.90±3.4, while in those with MS was 44.09±4.9 (P&lt;0.001). Deep vessel density in the macular area in patients without MS was 51.71±6.8 while in patients with MS was 45.51±5.7 (P&lt;0.001). Conclusion There is a decrease in superficial and deep vessel density and radial peripapillary vessel density in patients with ON caused by MS in comparison to healthy controls.

Notch signaling regulates UNC5B to suppress endothelial proliferation, migration, junction activity, and retinal plexus branching

Notch signaling guides vascular development and function by regulating diverse endothelial cell behaviors, including migration, proliferation, vascular density, endothelial junctions, and polarization in response to flow. Notch proteins form transcriptional activation complexes that regulate endothelial gene expression, but few of the downstream effectors that enable these phenotypic changes have been characterized in endothelial cells, limiting our understanding of vascular Notch activities. Using an unbiased screen of translated mRNA rapidly regulated by Notch signaling, we identified novel in vivo targets of Notch signaling in neonatal mouse brain endothelium, including UNC5B, a member of the netrin family of angiogenic-regulatory receptors. Endothelial Notch signaling rapidly upregulates UNC5B in multiple endothelial cell types. Loss or gain of UNC5B recapitulated specific Notch-regulated phenotypes. UNC5B expression inhibited endothelial migration and proliferation and was required for stabilization of endothelial junctions in response to shear stress. Loss of UNC5B partially or wholly blocked the ability of Notch activation to regulate these endothelial cell behaviors. In the developing mouse retina, endothelial-specific loss of UNC5B led to excessive vascularization, including increased vascular outgrowth, density, and branchpoint count. These data indicate that Notch signaling upregulates UNC5B as an effector protein to control specific endothelial cell behaviors and inhibit angiogenic growth.

Characteristics of Retinal Vascular Degeneration and the Expression of Vessel-Related Claudin Proteins in Retinal Degeneration Mouse.

This study aimed to investigate the characteristics of retinal vascular degeneration and the expression of vessel-related claudin (CLD) proteins in retinal degeneration mouse (Pde6βrd1/rd1 rd1 mouse). Retinas from wild-type (WT) mice and rd1 mice at postnatal day 3 (P3), P5, P8, P11, P13, P15, P18, and P21 were collected. Immunofluorescence staining was used to assess the retinal vascular plexus, cell proliferation, CLD expression, and retinal ganglion cells (RGCs). The distribution of retinal superficial and deep vessels was determined by isolectin B4 fluorescence staining of retinal flat mounts and frozen sections. Hematoxylin and eosin staining and terminal deoxynucleotidyl transferase-mediated dNTP nick-end labeling were used to investigate retinal histological degeneration and apoptosis in rd1 mice, respectively. Quantitative real-time PCR and Western blot were used to measure the expression of vessel-related CLD-1, -2, -3, and -5, vascular endothelial growth factor A (VEGFA), and vascular endothelial growth factor receptor 2 (VEGFR2) in the retinas. Compared to the WT mice, the rd1 mice displayed delayed but completed progressive development in the retinal superficial vascular plexuses (SVPs) and deep vascular plexuses (DVPs). In the rd1 mice, the thickness of retinal layers gradually decreased and the retinas underwent progressive atrophy and degeneration. The deterioration got worse at the late developmental stage. The declined vessel density of SVP and DVP correlated with the decreased thickness of the full and inner parts of the retina and the reduced number of RGCs. DVP degeneration and the thinning of the outer nuclear layer exhibited an obvious reduction at P15. The expression levels of CLD-1, CLD-2, CLD-3, CLD-5, VEGFA, and VEGFR2 decreased and were consistently lower in the rd1 mice than in WT mice since P15. Rd1 mice exhibited progressive vascular degeneration of retinal SVP and DVP, the thinning and atrophy of retinal ONL and RGC, and the downregulation of vessel-related CLD proteins during the late developmental period. Thus, the rd1 mouse is a useful model of not only retinal neuro-degeneration but also retinal vascular degeneration.

Study of the retina macular region microvascular bed parameters in healthy people of the older age group according to optical coherence tomography with angiography function

BACKGROUND: To date, there is insufficient data on normal blood flow indicators in the retinal choroid plexuses in healthy people of the older age group. AIM: To create a normative basis for average indicators of vessel density in the superficial and deep plexuses of the retina, parameters of the foveal avascular zone and retinal thickness in the macular region in healthy people of the older age group according to optical coherence tomography with angiography. MATERIAL AND METHODS: The retrospective study included 73 people (146 eyes) aged from 58 to 79 years with preserved visual functions and somatic parameters corresponding to the age norm. Optical coherence tomography with angiography function analyzed the density of vessels in the superficial and deep retinal plexuses, the area and perimeter of the foveal avascular zone, the density of vessels in the area up to 300 μm from the foveal avascular zone, and the thickness of the retina. Statistical processing of the data was performed in MS Office Excel 2016. The data was presented in the format M±σ, where M was the average value of the indicator, σ was the standard deviation. RESULTS: In the study group, the overall average retinal thickness in the macular area was 279.9±14.8 µm. The overall average density of vessels of the superficial retinal plexus in the macular zone of the retina was 48.7±2.5%. The overall average density of vessels in the deep retinal plexus in the macular area was 51.9±3.7%. The area of the foveal avascular zone in healthy people was on average 0.322±0.123 mm2; the density of vessels within 300 µm from the foveal avascular zone was 53.8±3.3%. CONCLUSION: The age-related physiological norm for blood flow indicators in the retinal choroid plexuses in healthy people of the older age group has been established.

ZO-1 interacts with YB-1 in endothelial cells to regulate stress granule formation during angiogenesis

Zonula occludens-1 (ZO-1) is involved in the regulation of cell-cell junctions between endothelial cells (ECs). Here we identify the ZO-1 protein interactome and uncover ZO-1 interactions with RNA-binding proteins that are part of stress granules (SGs). Downregulation of ZO-1 increased SG formation in response to stress and protected ECs from cellular insults. The ZO-1 interactome uncovered an association between ZO-1 and Y-box binding protein 1 (YB-1), a constituent of SGs. Arsenite treatment of ECs decreased the interaction between ZO-1 and YB-1, and drove SG assembly. YB-1 expression is essential for SG formation and for the cytoprotective effects induced by ZO-1 downregulation. In the developing retinal vascular plexus of newborn mice, ECs at the front of growing vessels express less ZO-1 but display more YB-1-positive granules than ECs located in the vascular plexus. Endothelial-specific deletion of ZO-1 in mice at post-natal day 7 markedly increased the presence of YB-1-positive granules in ECs of retinal blood vessels, altered tip EC morphology and vascular patterning, resulting in aberrant endothelial proliferation, and arrest in the expansion of the retinal vasculature. Our findings suggest that, through its interaction with YB-1, ZO-1 controls SG formation and the response of ECs to stress during angiogenesis.

The neurovascular retinal involvement in a large population of patients recovered from COVID-19: an OCT and OCT angiography study.

This study aimed to assess the neuronal and microvascular retinal and choroidal involvement in COVID-19 recovered patients using optical coherence tomography (OCT) and OCT angiography (OCTA). This observational cross-sectional study recruited patients recovered from COVID-19 and a group of healthy controls for comparisons. OCT (peripapillary scan and macular map) and OCTA (macular map) were performed to obtain: the central subfield thickness (CST), the macular volume (MV), the peripapillary retinal nerve fibre layer (pRNFL) thickness, the vessel area density (VAD), vessel length fraction (VLF), vessel diameter index (VDI) and fractal dimension (FD) of the superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP), and the vessel density (VD), stromal density (SD) and vascular/stromal (V/S) ratio of the choriocapillaris (CC) and choroid (Ch). Data regarding disease severity, administered therapy and prior comorbidities were collected. We recruited 676 eyes from 338 patients and 98 eyes from 49 healthy controls. VAD of all the three retinal plexuses, VLF and VDI of ICP and DCP and VD of CC were significantly reduced in patients versus controls. No differences were found in CST, MV and pRNFL. A multivariate analysis showed that oxygen therapy, previous cardio/cerebrovascular events and hypertension negatively influenced vascular parameters. A microvascular retinal and choriocapillaris damage may be identified secondary to SARS-CoV-2 infection, even after recovery. OCTA may represent a reproducible and non-invasive tool to assess microangiopathy in these patients, with particular regard to those with previous cardio/cerebrovascular events, hypertension and those who received oxygen therapy.

Repeatability of swept-source optical coherence tomography angiography automated macular vessel density.

Optical Coherence Tomography Angiography Ratio Analysis (OCTARA) is capable of visualizing inner and outer retinal vascular plexuses, choriocapillaris, and larger choroidal vasculature in vivo without contrast injection. The aim of this study was to assess the intrasession repeatability of automated vessel density measurements using Triton Swept-Source Optical Coherence Tomography Angiography (OCTA) innovative algorithm OCTARA in retinal and choroidal vasculature. To study population between 65-90 years old with no eye diseases. For each subject measurements were performed four times. The intraclass correlation coefficient and the coefficient of variation were calculated to analyze repeatability of the OCTARA automatically generated vessel density measurements. A total of 35 eyes were included in the study. The intraclass correlation coefficient of the global vessel density in the superficial capillary plexus and the deep capillary plexus were 0.963 and 0.975, respectively, and the coefficient of variation were 5.4% and 4.4%, respectively. The intraclass correlation coefficient of the rest of the global measurements was indicative of good reliability with the exception of the deep choroid layer with an intraclass correlation coefficient of 0.6 indicative of moderate reliability. Our results proved excellent repeatability of automated vessel density measurements in the superficial and deep capillary plexus layers in our cohort using a OCTARA algorithm indicating that it may be a reliable diagnostic tool. It also showed good reliability in choriocapillary and mid choroid layer. These findings may be of value in assessing the significance of differences in capillary density measurements over time and across different settings.

Clinical features of three-layer’s impairment of capillary plexuses’ perfusion at follow-up in patients with Purcher retinopathy and Purcher-like retinopathy

In Purcher retinopathy and Purcher-like retinopathy, ischemic lesions occur at the level of all three retina capillary plexuses. Recognition of characteristic ischemic patterns by optical coherence tomography helps to predict the degree of visual functions’ recovery. The aim of this study is to present clinical cases of patients with Purcher retinopathy and Purcher-like retinopathy and to observe the dynamics of visual rehabilitation of patients with retinal vascular conditions. Two patients with complaints of central vision loss and skotomata in the visual field were examined. The complex of multimodal visualization included fundus photoregistration with fundus camera, optical coherence tomography and optical coherence tomography-angiography, and microperimetry. Paracentral acute middle maculopathy and acute macular neuroretinopathy are the manifestations of the same ischemic process on different levels of retinal vascular plexuses. The “diffuse” pattern damages in paracentral acute middle maculopathy lead to more permanent structural and functional impairments opposed to the “skip” pattern. The optical coherence tomography allows to predict the possibilities of visual and functional rehabilitation in patients with ischemic damage of retinal vessels.

Retinal and Choroidal Vascularity Evaluation in Pediatric Radiologically Isolated Syndrome and Multiple Sclerosis

BackgroundTo assess vessel density (VD) and flow of retinal plexuses and peripapillary region related with the pediatric radiologically isolated syndrome (RIS) and multiple sclerosis (MS). MethodsWe analyzed 24 eyes of 12 participants with the diagnosis of RIS, 24 eyes of 12 participants with the diagnosis of MS, and 26 eyes of 13 age- and sex-matched healthy controls in this prospective, cross-sectional study. The superficial capillary plexus (SCP) and deep capillary plexus, foveal avascular zone, and the flow of choriocapillaris were investigated using optical coherence tomography angiography. ResultsParafoveal VD and all subregion parameters in SCP were significantly decreased in the MS group compared with the controls, whereas only nasal and inferior VD were significantly decreased in the pediatric RIS group compared with the controls. Ganglion cell layer (GCL) thickness of all subregions of the inner ring was significantly decreased in the pediatric MS group compared with the control group. No significant difference was observed between the pediatric RIS group and the control group regarding thickness. ConclusionsWe showed lower parafoveal VD in all subregions of SCP in pediatric MS, whereas only parafoveal nasal and inferior VD were decreased in pediatric RIS. GCL thickness of inner ring was significantly decreased in the pediatric MS, whereas GCL thickness did not change in pediatric RIS. Therefore, a decrease of parafoveal nasal and inferior VD without a decrease in thickness implies an early impairment of microvasculature in the RIS before impairment of thickness and that microvascular alterations begin from highly vascular superficial parafovea.

The characteristics of acute macular neuroretinopathy following COVID-19 infection

BackgroundIn this study, we report a case series of acute macular neuroretinopathy (AMN) associated with COVID-19 infection.MethodsThis retrospective observational study was conducted at Beijing Tongren Hospital. We reviewed patients who were diagnosed with AMN within one month of testing positive for COVID-19 using real-time reverse transcription-polymerase chain reaction (RT-PCR).ResultsA total of 11 AMN patients (20 eyes) were included in the study. The mean age was 33.8 ± 12.6 years. The average interval between a positive COVID-19 PCR test and the onset of ocular symptoms was 2.8 ± 2.5 days. The mean follow-up period for the patients was 12.5 ± 3.8 weeks. Imaging characteristics of AMN patients following COVID-19 infection included areas of low reflectivity on near-infrared reflectance (NIR) imaging, hyperreflective lesions at the level of the outer plexiform layer (OPL) and outer nuclear layer (ONL) and disruption of the ellipsoid zone (EZ) on spectral domain optical coherence tomography (SD-OCT) B-scans. Visual field examinations revealed parafoveal scotomas that closely corresponded to the clinical lesions. Optical coherence tomography angiography (OCT-A) demonstrated impaired perfusion in the deep retinal vascular plexus. Fluorescein angiography (FA), indocyanine green angiography (ICGA), and spontaneous fundus autofluorescence showed no significant abnormalities. During follow-up, partial improvement in retinal lesions was observed in NIR imaging and SD-OCT in some patients, but a proportion of patients still exhibited persistent retinal damage and no improvement in visual field scotomas.ConclusionCOVID-19-related AMN share similar clinical and imaging features with AMN due to other causes, as evidenced by the persistent presence of visual field scotomas over a longer duration.Trail registrationhttps://www.chictr.org.cn/; identifier: ChiCTR2100044365

Retina hypoperfusion in multiple sclerosis: Is it only a consequence of atrophy?

Aims/Purpose: To study if there are vascular changes in patients with multiple sclerosis (MS) when compared healthy controls, analysing oct and OCT‐angiography findings (choroidal thickness and retinal vascular density) at the macular level.Methods: The study compared two groups (controls and patients) and it analysed whether there were statistically significant differences in the different parameters studied using OCT: choroidal thickness and in the vascular macular plexuses, using OCT‐angiography. Any patient has an optic neuritis history. It was also studied whether there was a statistically significant correlation between anatomical parameters (radial nerve fibre layer, RNFL and ganglion cell layer, GCL) and vascular parameters matching cases and controls by age and sex.Results: We found a statistically significant reduction in macular choroidal thickness in patients when compared to controls. The study of retinal vascular plexuses showed that the superficial and deep retinal vascular plexuses and the choriocapillaris plexus showed significantly lower vascular density in the patients group. Variations in anatomical parameters between anatomical parameters and in vascular parameters between vascular parameters pairing cases and controls show direct correlations. Regarding the correlation between the differences in anatomical versus vascular parameters, we only observed a low direct correlation between the difference in the papillary RFNL and that of the superficial macular vascular plexus between case and control group.Conclusions: The density of macular vascular plexus and choroidal thickness proved to be significantly lower in MS patients than in healthy subjects. To date, it is not known to what extent hypoperfusion in MS is a cause or consequence of the brain disease or whether it is a simply association. Vascular parameters could be used as useful markers in the diagnosis and follow‐up of MS.

Retinal biomarkers in vascular occlusion

Objective: To clarify the diagnostic and prognostic values of the biomarkers detected by multimodal imaging procedures as coloured fundus imaging, fluorescein angiography, near infra‐red imaging, fundus Autofluorescence, SD‐OCT, and OCT angiography to predict the prognosis and the response to therapy in retinal vascular occlusions (artery or vein).Recently, there has been an interest in determining the prognostic value of changes on optical coherence tomography (OCT) in retinal vein occlusion as it allows both quantitative and qualitative analysis of imaging biomarkers such as central retinal thickness, choroidal thickness, intraretinal hyper‐reflective foci (HRF), disorganization of the inner retinal layers (DRIL), external limiting membrane (ELM) disruption, ellipsoid zone (EZ) disruption. Also classifying the intraretinal edema if sponge‐like or cystoid or serous retinal detachment (and detecting its height). Also signs of ischemia can be detected such as prominent middle limiting membrane (p‐MLM), paracentral acute middle maculopathy (PAMM), as well as hyperreflectivity of the inner retinal layers (HIRL) which is commonly seen in cases of acute retinal artery occlusion. Internal limiting membrane detachment (ILMD) which is a novel biomarker that can be detected in some cases of acute CRAO.OCT Angiography has added more information about the assessment of microvascular alterations, especially vessel density in the deep retinal vascular plexus, the foveal avascular zone and of areas with no capillary perfusion. Biomarkers of ultra‐widefield angiography, such as peripheral ischemia (ischemic index) and neovascularization are essential for retinal laser treatment decision.Finally, FAF has been a very useful tool in monitoring the disease progression and response to treatment.The speaker will present examples of multimodal imaging of different retinal biomarkers in retinal vascular occlusion that help in predicting the prognosis.

Endothelial Jagged1 levels and distribution are post-transcriptionally controlled by ZFP36 decay proteins

Vascular morphogenesis requires a delicate gradient of Notch signaling controlled, in part, by the distribution of ligands (Dll4 and Jagged1). How Jagged1 (JAG1) expression is compartmentalized in the vascular plexus remains unclear. Here, we show that Jag1 mRNA is a direct target of zinc-finger protein 36 (ZFP36), an RNA-binding protein involved in mRNA decay that we find robustly induced by vascular endothelial growth factor (VEGF). Endothelial cells lacking ZFP36 display high levels of JAG1 and increase angiogenic sprouting invitro. Furthermore, mice lacking Zfp36 in endothelial cells display mispatterned and increased levels of JAG1 in the developing retinal vascular plexus. Abnormal levels of JAG1 at the sprouting front alters NOTCH1 signaling, increasing the number of tip cells, a phenotype that is rescued by imposing haploinsufficiency of Jag1. Our findings reveal an important feedforward loop whereby VEGF stimulates ZFP36, consequently suppressing Jag1 to enable adequate levels of Notch signaling during sprouting angiogenesis.

Optical coherence tomography angiography features of the chorioretinal complex and choriocapillaris perfusion before and after vitrectomy with conventional versus fovea-sparing internal limiting membrane peeling for idiopathic macular hole

Purpose: To assess optical coherence tomography angiography (OCTA)-measured changes in the chorioretinal complex and choriocapillaris perfusion density in the macula before and after vitrectomy with fovea-sparing versus conventional internal limiting membrane (ILM) peeling for idiopathic macular hole (IMH). Material and Methods: Eyes with stage-2 to stage-4 holes as per the classification by Gass received 25-G vitrectomy with conventional or fovea-sparing ILM peeling and gas tamponade with 20% SF6 or 15% С3F8. IMH diameter, foveal avascular zone (FAZ) area in the deep retinal plexus and choriocapillaris perfusion density (CPD) were assessed before and 1 month after surgery. Results: Totally, 70 patients had an IMH surgery in 71 eyes. The mean age ± standard deviation (SD) was 65.7 ± 6.8 years, median IMH duration (interquartile range or IQR), 3.0 (1.0-6.0) months, median best-corrected visual acuity or BCVA (IQR), 0.19 (0.1-0.25), and median maximum IMH diameter (IQR), 673.5 (549.5–1010.5) µm. In eyes with IMH and fellow eyes, the median FAZ area (IQR) was 0.51 (0.15–0.53) mm2, and 0.46 (0.10–0.74) mm2, respectively (р = 0.49), and mean CPD ± SD, 0.11 ± 0.06, and 0.29 ± 0.13 (р = 0.0001), respectively. Thirty-four eyes received conventional ILM peeling and 37 eyes, fovea-sparing ILM peeling, and there was no significant intergroup difference in baseline characteristics. One month after surgery, IMH closure was achieved in 63/71 eyes (i.e., the closure rate was 88.7% for total operated eyes, and 88.2% and 89.2%, respectively, for eyes in conventional ILM peeling and fovea-sparing ILM peeling groups), and median BCVA (IQR) improved to 0.60 (0.4–0.8) (р = 0.00001). After IMH closure, in operated eyes, median FAZ area (IQR) decreased to 0.30 (0.12–0.6) mm2, but the difference was not significant, whereas mean CPD ± SD increased significantly from 0.11 ± 0.06 to 0.25 ± 0.10 (р = 0.0001). No significant difference in OCTA-based retinal microcirculation and choriocappillaris characteristics was observed between the conventional ILM peeling and fovea-sparing ILM peeling groups. Conclusion: The presence of macular hole is accompanied by abnormal perfusion in the choriocapillaris, but the CPD recovers after IMH closure. Postoperative CPD recovery is not influenced by the type (conventional or fovea-sparing) of ILM peeling.

Evaluation of Structural Retinal Layer Alterations in Retinitis Pigmentosa.

Objective: This study aimed to analyze retinal layers in the macular region using spectral-domain optical coherence tomography (SD-OCT). Additionally, we examined the retinal vascular plexus densities of the eyes using optical coherence tomography angiography (OCT-A), specifically in patients with retinitis pigmentosa (RP). Methods: In the study, 36 eyes from patients with retinitis pigmentosa (RP) and 36 eyes from healthy controls were included. Measurements involved assessing the thicknesses of each retinal layer at the central fovea, parafoveal, and perifovea using spectral domain optical coherence tomography (SD-OCT). Moreover, the study involved the evaluation of retinal capillary plexus densities (RCPD), encompassing deep capillary plexus density values, superficial capillary plexus, and radial peripapillary capillary plexus. This assessment was performed using optical coherence tomography angiography (OCT-A). Results: No statistically significant difference in retinal thickness was found in the central fovea between the two groups. The thicknesses of the INL, OPL, and PRL in the parafoveal regions as well as the RPE in the perifoveal regions increased in the RP group. Nonetheless, the ONL, IPL, GCL, and RNFL demonstrated reduced thickness in both the perifoveal and parafoveal areas. The OCT-A findings indicated that patients with RP exhibited lower values for all RCPD. Conclusion: The retinal layers and RCPD were significantly impacted at varying rates of RP. It is essential to acknowledge that this alteration may be significant in the context of the retinal findings in patients with RP. Abbreviations: SD-OCT = Spectral-domain optical coherence tomography, OCT-A = Optical coherence tomography angiography, RP = Retinitis pigmentosa, ETDRS = Early Treatment Diabetic Retinopathy Study, SD = standard deviation, TRT = Total Retinal Thickness, IRT = Inner Retinal Thickness, ORT = Outer Retinal Thickness, RNFL = Retinal Nerve Fiber Layer, GCL = Ganglion Cell Layer, IPL = Inner Plexiform Layer, INL = inner nuclear layer, OPL = Outer Plexiform Layer, ONL = Outer Nuclear Layer, PRL = Photoreceptor layer, RPE = Retinal Pigment Epithelium, µm = micrometer, PaFoSu = parafovea superior, PeFoSu = perifovea superior, PaFoNa = parafovea nasal, PeFoNa = perifovea nasal, PaFoTe = parafovea temporal, PeFoTe = perifovea temporal, PaFoIn = parafovea inferior, PeFoIn = perifovea inferior.