Choroidal Capillaries Research Articles

Unveiling the hidden: a deep learning approach to unraveling subzone-specific changes in peripapillary atrophy in type 2 diabetes.

This study aimed to evaluate the optical coherence tomography angiography (OCTA) changes in subzones of peripapillary atrophy (PPA) among type 2 diabetic patients (T2DM) with or without diabetic retinopathy (DR) using well-designed deep learning models. A multi-task joint deep-learning model was trained and validated on 2,820 images to automate the determination and quantification of the microstructure and corresponding microcirculation of beta zone and gamma zone PPA. This model was then applied in the cross-sectional study encompassing 44 eyes affected by non-proliferative diabetic retinopathy (NPDR) and 46 eyes without DR (NDR). OCTA was utilized to image the peripapillary area in four layers: superficial capillary plexus (SCP), deep capillary plexus (DCP), choroidal capillary (CC) and middle-to-large choroidal vessel (MLCV). The patients in both groups were matched for age, sex, BMI, and axial length. The width and area of the gamma zone were significantly smaller in NPDR group compared to the NDR group. Multiple linear regression analysis revealed a negative association between the diagnosis of DR and the width and area of the gamma zone. The gamma zone exhibited higher SCP, DCP and MLCV density than the beta zone, while the beta zone showed higher CC density than the gamma zone. In comparison to the NDR group, the MLCV density of gamma zone was significantly lower in NPDR group, and this density was positively correlated with the width and area of the gamma zone. DR-induced peripapillary vascular changes primarily occur in gamma zone PPA. After eliminating the influence of axial length, our study demonstrated a negative correlation between DR and the gamma zone PPA. Longitudinal studies are required to further elucidate the role of the gamma zone in the development and progression of DR.

THE ORGANIZATION OF THE BASEMENT MEMBRANES IN THE CHOROID PLEXUS VILLI OF THE HUMAN BRAIN

THE ORGANIZATION OF THE BASEMENT MEMBRANES IN THE Choroid PLEXUS VILLI OF THE HUMAN BRAIN Authors O.V. Kirik 1*, O.S. Alekseeva 1,2, I.P. Grigorev 1, E.A. Fedorova 1, A.A. Beketova 1, D.E. Korzhevsky 1 Affiliation 1 Institute of Experimental Medicine, Saint Petersburg, Russian Federation 2 Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, Saint Petersburg, Russian Federation Abstract BACKGROUND: The choroid plexus of the brain is the main component of the blood-cerebrospinal fluid barrier, separating these two biological fluids. Basement membranes of the choroid plexus have a special role in the implementation of barrier functions: they underlie the choroidal epithelium and capillary endothelium, and serve as an additional filter for substances penetrating from the blood into the cerebrospinal fluid. AIM: The purpose of this work was to study the organization of basement membranes in the villi of the human telencephalon choroid plexus using immunohistochemical detection of type IV collagen. METHODS: The study was performed on archival material from the choroid plexus of the human brain (age 29-50 years, n=10) using the immunohistochemical method for detecting type IV collagen. RESULTS: An immunohistochemical reaction using antibodies to type IV collagen showed the distribution of this protein in the subepithelial area and in the stroma of the choroid plexus villi. All immunopositive structures had clear contours; there was no reaction in the cell cytoplasm or a nonspecific background. Contacts of subepithelial and subcapillary basement membranes labeled with antibodies to type IV collagen were not detected. CONCLUSION: The study showed that the basement membranes of the villi of the choroid plexus of the human brain in the subepithelial and perivascular areas have a different organization. In this case, the union of the subepithelial and perivascular components containing type IV collagen, as a rule, does not occur.

A preliminary study on the characteristics of refractive parameters and retinal blood flow in dominant eyes

Objective: To explore the characteristics of refractive parameters and retinal and choroidal blood flow in dominant and non-dominant eyes. Methods: A cross-sectional study. Students who were 18 to 32 years old and had emmetropia or myopia but no systemic diseases were recruited from universities in Wuhu, Anhui Province from April 2019 to August 2023. They were divided into 4 groups based on the difference in spherical equivalent between two eyes:<0.50 D (group A), 0.50 to 1.74 D (group B), 1.75 to 2.49 D (group C), and≥2.50 D (group D). The card hole method was used to determine the dominant eye. The refractive parameters of both eyes were recorded, including spherical equivalent, myopia degree, astigmatism degree, axial length, and corneal curvature difference (K2-K1). Optical coherence tomography angiography was performed to measure the blood flow density of the superficial retinal capillaries, deep retinal capillaries (DVC), avascular layer (AC), entire retina, choroidal capillaries, and choroidal vessels, as well as the retina and choroid as a whole. Statistical analysis was conducted using the paired sample t-test, chi square test, and variance analysis. Results: A total of 78 eligible subjects, aged (24.50±2.36) years old, 28 males and 50 females, were included. Fifty subjects had the right eye and 28 had the left eye as the dominant eye. Forty-two subjects had high myopia in the dominant eye, and 30 had high myopia in the non-dominant eye. There were statistically significant differences (all P<0.05) in the spherical equivalent [(-4.588±2.534) D vs. (-4.058±2.453) D], myopic spherical power [(-4.253±2.504) D vs. (-3.779±2.425) D], and axial length [(25.531±1.212) mm vs. (25.256±1.238) mm] between dominant and non-dominant eyes among all subjects, as well as in the astigmatism degree of groups A and C, spherical power of groups B to D, and spherical power and axial length of groups C and D. There were also statistically significant differences (all P<0.05) in the blood flow density of the DVC [(0.291±0.130) vs. (0.257±0.148)], AC [(0.347±0.118) vs. (0.326±0.126)], and overall retina and choroid [(0.385±0.102) vs. (0.349±0.084)] between dominant and non-dominant eyes among all subjects, as well as in the blood flow density of the superficial retinal capillaries, DVC, AC, choroidal capillaries, and overall retina and choroid of groups C and D, density of the choroidal vessels of group C, and density of the entire retina of group D. Conclusions: In young individuals with emmetropia or near vision, the degree of myopia in dominant eyes is higher than that in non-dominant eyes. When the difference in the spherical equivalent between two eyes is ≥1.75 D, the blood flow density of the retina and choroid in the dominant eye is greater than that in the non-dominant eye.

Assessment of the effects of myopic and hyperopic anisometropia on choroidal vascular structure in children using SS-OCTA.

To compare large- and medium-sized choroidal vascularity and the choriocapillaris (CC) flow area in children with different refractive errors using swept-source optical coherence tomography angiography (SS-OCTA). Forty-two anisometropic children were enrolled and divided into hyperopic anisometropia (HA) and myopic anisometropia (MA) groups. SS-OCTA was performed to analyse choroidal vascularity. Mean choroidal thickness (CT), choroidal vascularity volume (CVV), choroidal vascularity index (CVI) and CC flow area were compared between the two eyes. The inter-ocular differences between the two groups were also determined. Mean CT and CVV were highest in eyes with shorter axial lengths in both refractive groups, and the difference between the two eyes was positively correlated with the difference in axial length at the foveal region. Significant differences in the CVI in the MA group were only found in the parafoveal region. Inter-ocular differences in the CC were significantly reduced in eyes with longer axial lengths in the foveal and parafoveal regions of the HA and MA groups, respectively. Comparing inter-ocular differences, CC was significantly greater in the parafoveal region of the MA group than the HA group. All layers of choroidal vasculature were thinner in eyes with longer axial lengths in all groups. The inter-ocular CC difference was greater in the MA than in the HA group, with similar differences in axial length. This suggests that both medium-to-large choroidal vascular and choroidal capillaries may play a role in myopia development.

Investigation of the effectiveness of gelatin hydrolysate in human iPS-RPE cell suspension transplantation

IntroductionThe retinal pigment epithelium (RPE) plays essential roles in maintaining retinal functions as well as choroidal capillaries and can lead to visual disorders if dysfunctional. Transplantation of human-induced pluripotent stem cell-derived RPE (hiPSC-RPE) is a promising therapy for such RPE impaired conditions including age-related macular degeneration. The challenge with cell suspension transplantation is targeted delivery of graft cells and undesired cell reflux. Gelatin hydrolysate, a soluble variant with specific molecular weight distribution, is examined in this study for its potential use in hiPSC-RPE suspension transplantation, particularly in reducing cell reflux and enhancing RPE engraftment. MethodsA retinal bleb model was created using polydimethylsiloxane (PDMS) soft lithography to quantify cellular reflux. We examined the effects of gelatin hydrolysate on the hiPSC-RPE of various aspects of cell behavior and performance such as cell viability, hypoxia reaction, morphology, induction of inflammation and immune responses. ResultsGelatin hydrolysate at 5 % concentration effectively mitigated cell reflux in vitro mimic, improved cell viability, reduced cell aggregation, and had an inhibitory effect on hypoxic reactions due to cell deposition with hiPSC-RPE. Additionally, gelatin hydrolysate did not affect cell adhesion and morphology, and decreased the expression of major histocompatibility complex class II molecules, which suggests reduced immunogenicity of hiPSC-RPE. ConclusionGelatin hydrolysate is considered a valuable and useful candidate for future regenerative therapies in hiPSC-RPE suspension transplantation.

Which Theory of Cerebrospinal Fluid Production and Absorption Do Neurosurgeons Teach to Medical Students? Survey from Medical Universities in Japan, 2022.

Several new studies have been conducted on cerebrospinal fluid (CSF) dynamics. Our educational guidelines, the Model Core Curriculum for Medical University, recommend access to the best current information. However, we do not know whether or when to introduce changes to this concept.We surveyed which theory of CSF dynamics taught to students by neurosurgeons. The old theory is the bulk flow theory, and the new theory explains that CSF is produced from the choroid plexus and capillaries; CSF then pulsates and drains into the venous and lymphatic systems through newly discovered pathways.Old and new theories were taught to 64.8% and 27.0% of students, respectively. The reason for teaching the old theory was to help them understand the pathogenesis of noncommunicating hydrocephalus (77.1%), whereas the reason for teaching the new theory was to teach the latest knowledge (40.0%). Physicians who wished to teach the new theory in the near future accounted for 47.3%, which was higher than those who would teach the new theory in 2022 (27.0%), and those who still wished to teach the old theory in the near future accounted for 43.2%.An education policy on CSF dynamics will be established when we interpret ventricular enlargement and its improvement by third ventriculostomy in noncommunicating hydrocephalus based on the new theory. The distributed answers in the survey shared that it is difficult to teach about CSF dynamics and provided an opportunity to discuss these issues.

Conditional loss of Ube3d in the retinal pigment epithelium accelerates age-associated alterations in the retina of mice.

Several studies have suggested a correlation between the ubiquitin-proteasome system (UPS) and age-related macular degeneration (AMD), with its phenotypic severity ranging from mild visual impairment to blindness, but the mechanism for UPS dysfunction contributing to disease progression is unclear. In this study, we investigated the role of ubiquitin protein ligase E3D (UBE3D) in aging and degeneration in mouse retina. Conditional knockout of Ube3d in the retinal pigment epithelium (RPE) of mice led to progressive and irregular fundus lesions, attenuation of the retinal vascular system, and age-associated deterioration of rod and cone responses. Simultaneously, RPE-specific Ube3d knockout mice also presented morphological changes similar to the histopathological characteristics of human AMD, in which a defective UPS led to RPE abnormalities such as phagocytosis or degradation of metabolites, the interaction with photoreceptor outer segment, and the transport of nutrients or waste products with choroidal capillaries via Bruch's membrane. Moreover, conditional loss of Ube3d resulted in aberrant molecular characterizations associated with the autophagy-lysosomal pathway, oxidative stress damage, and cell-cycle regulation, which are implicated in AMD pathology. Thus, our findings strengthen and expand the impact of UPS dysfunction on retinal pathophysiology during aging, indicating that genetic Ube3d deficiency in the RPE could lead to the abnormal formation of pigment deposits and secondary fundus alterations. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Choroid vascular changes in hyperopic anisometropia amblyopia using SS-OCTA

PurposeTo observe and understand the structural changes in choroidal vessels in eyes with hyperopic anisometropic amblyopia using swept-source optical coherence tomography angiography (SS-OCTA).MethodsA total of 44 patients were enrolled in this study: 22 children with hyperopic anisometropic amblyopia and 22 age-matched controls. SS-OCTA was used to scan the 6*6 mm macular area of their eyes. The average choroidal thickness (CT) and choroidal capillary flow area (CC) in a 3 mm diameter area centered on the macular area were obtained. The choroidal vascularity volume (CVV) was automatically extracted and 3D reconstructed by inbuild software, and the three-dimensional choroidal vascularity index (3D-CVI) was calculated. The effect of amblyopia on the choroidal vessel structure was assessed using generalized linear estimating equations (GEEs) corrected for axial length, sex, age, and best-corrected visual acuity.ResultsThe CC was greater in amblyopic eyes than in fellow eyes (P = 0.014) but was not significantly different from that in control eyes (P = 0.963). After correcting for sex, age, axial length, and visual acuity using GEEs, the mean CT in the amblyopic eyes was greater than that in the fellow eyes (P = 0.030) but was not significantly different from that in the control eyes (P = 0.160). The 3D-CVI in amblyopic eyes was higher than that in control eyes (P = 0.038) but was not significantly different from that in fellow eyes (P = 0.407). The three-dimensional choroidal vascularity volume (3D-CVV) was higher in amblyopic eyes than in fellow eyes (P = 0.046) and control eyes (P = 0.023).ConclusionsWe found that eyes with hyperopic anisometropic amblyopia demonstrated higher CT, CC and 3D-CVV values than the contralateral eyes after correction, while the 3D-CVI was unchanged. Compared with control eyes, amblyopic eyes had higher 3D-CVV and 3D-CVI values but similar CT and CC values. Amblyopic eyes may have different choroidal vascular structures from fellow and control eyes.

LipidUNet-Machine Learning-Based Method of Characterization and Quantification of Lipid Deposits Using iPSC-Derived Retinal Pigment Epithelium.

The retinal pigment epithelium (RPE) is a monolayer of hexagonal cells located at the back of the eye. It provides nourishment and support to photoreceptors and choroidal capillaries, performs phagocytosis of photoreceptor outer segments (POS), and secretes cytokines in a polarized manner for maintaining the homeostasis of the outer retina. Dysfunctional RPE, caused by mutations, aging, and environmental factors, results in the degeneration of other retinal layers and causes vision loss. A hallmark phenotypic feature of degenerating RPE is intra and sub-cellular lipid-rich deposits. These deposits are a common phenotype across different retinal degenerative diseases. To reproduce the lipid deposit phenotype of monogenic retinal degenerations in vitro, induced pluripotent stem cell-derived RPE (iRPE) was generated from patients' fibroblasts. Cell lines generated from patients with Stargardt and Late-onset retinal degeneration (L-ORD) disease were fed with POS for 7 days to replicate RPE physiological function, which caused POS phagocytosis-induced pathology in these diseases. To generate a model for age-related macular degeneration (AMD), a polygenic disease associated with alternate complement activation, iRPE was challenged with alternate complement anaphylatoxins. The intra and sub-cellular lipid deposits were characterized using Nile Red, boron-dipyrromethene (BODIPY), and apolipoprotein E (APOE). To quantify the density of lipid deposits, a machine learning-based software, LipidUNet, was developed. The software was trained on maximum-intensity projection images of iRPE on culture surfaces. In the future, it will be trained to analyze three-dimensional (3D) images and quantify the volume of lipid droplets. The LipidUNet software will be a valuable resource for discovering drugs that decrease lipid accumulation in disease models.

Optical coherence tomography angiography–guided vs indocyanine green angiography–guided half-dose photodynamic therapy for acute central serous chorioretinopathy: 6-month randomized trial results

PurposeThis study aimed to compare the anatomic and functional results of optical coherence tomography angiography (OCTA)-guided half-dose photodynamic therapy (PDT) versus indocyanine green angiography (ICGA)-guided PDT in eyes with acute central serous chorioretinopathy (CSC).MethodsOne hundred and thirty-one eyes of 131 patients with acute central serous chorioretinopathy (CSC) were recruited, and randomly assigned to the OCTA-guided group and ICGA-guided group. The primary outcome measures were the rates of complete subretinal fluid (SRF) resolution at 1 month, 3 months, and 6 months. The secondary outcomes included best-corrected visual acuity (BCVA), central retinal thickness (CRT), choroidal capillary flow deficit density at each scheduled visit, and recurrence rate of SRF at 3 months and 6 months.ResultsThere were 110 eyes that finished the follow-up, with 56 eyes in the OCTA-guided group and 54 eyes in the ICGA guided group. OCTA-guided PDT was demonstrated to be noninferior to ICGA-guided PDT for SRF resolution rate at 1 months and 6 months (P = 0.021 and P = 0.037), but not at 3 months for acute CSC (P = 0.247). The average CRT of the ICGA-guided group was significantly lower than that of the OCTA-guided group at 3-month visit (P = 0.046), but no significant difference was found between them at the 1-month and 6-month visits (P = 0.891 and 0.527). There was no significant difference between the two groups for BCVA (P = 0.359, 0.700, and 0.143, respectively) and the deficit area on CC (P = 0.537, 0.744,and 0.604, respectively) at 1, 3, and 6 months.ConclusionOCTA may replace ICGA to guide PDT for the treatment of acute CSC and their follow-up.

Central Serous Chorioretinopathy: An Update on the Current State of Management.

Central serous chorioretinopathy (CSCR) is a relatively common retinal disorder that leads to central vision impairment, often with a high recurrence rate. The exact etiology and pathogenetic mechanisms have not been fully elucidated but are likely to be associated with hyperpermeability of the choroidal capillaries and failure of the retinal pigment epithelium (RPE), leading to serous detachment of the neurosensory retina. Multimodal imaging plays a critical role in the diagnostic approach and monitoring of CSCR. Fortunately, the natural course of the disease is usually self-limiting, with spontaneous resolution and total fluid reabsorption. However, some patients may exhibit recurrences or persistent subretinal fluid (chronic CSCR), leading to progressive and irreversible RPE atrophy or photoreceptor damage. Thus, to prevent permanent visual loss, individualized treatment should be considered. Recent developments in the diagnostic and therapeutic approach have contributed to better outcomes in patients with CSCR. More studies are required to improve our understanding of epidemiology, pathogenesis, diagnosis, and treatment, with a significant impact on the management of this challenging clinical entity. The purpose of this review is to summarize the current knowledge about the clinical features, diagnostic workup, and therapeutic approach of CSCR.

Polyunsaturated Lipids in the Light-Exposed and Prooxidant Retinal Environment.

The retina is an oxidative stress-prone tissue due to high content of polyunsaturated lipids, exposure to visible light stimuli in the 400-480 nm range, and high oxygen availability provided by choroidal capillaries to support oxidative metabolism. Indeed, lipids' peroxidation and their conversion into reactive species promoting inflammation have been reported and connected to retinal degenerations. Here, we review recent evidence showing how retinal polyunsaturated lipids, in addition to oxidative stress and damage, may counteract the inflammatory response triggered by blue light-activated carotenoid derivatives, enabling long-term retina operation despite its prooxidant environment. These two aspects of retinal polyunsaturated lipids require tight control over their synthesis to avoid overcoming their protective actions by an increase in lipid peroxidation due to oxidative stress. We review emerging evidence on different transcriptional control mechanisms operating in retinal cells to modulate polyunsaturated lipid synthesis over the life span, from the immature to the ageing retina. Finally, we discuss the antioxidant role of food nutrients such as xanthophylls and carotenoids that have been shown to empower retinal cells' antioxidant responses and counteract the adverse impact of prooxidant stimuli on sight.

Transcriptome Analysis of Retinal and Choroidal Pathologies in Aged BALB/c Mice Following Systemic Neonatal Murine Cytomegalovirus Infection.

Our previous studies have shown that systemic neonatal murine cytomegalovirus (MCMV) infection of BALB/c mice spread to the eye with subsequent establishment of latency in choroid/RPE. In this study, RNA sequencing (RNA-Seq) analysis was used to determine the molecular genetic changes and pathways affected by ocular MCMV latency. MCMV (50 pfu per mouse) or medium as control were injected intra-peritoneally (i.p.) into BALB/c mice at <3 days after birth. At 18 months post injection, the mice were euthanized, and the eyes were collected and prepared for RNA-Seq. Compared to three uninfected control eyes, we identified 321 differentially expressed genes (DEGs) in six infected eyes. Using the QIAGEN Ingenuity Pathway Analysis (QIAGEN IPA), we identified 17 affected canonical pathways, 10 of which function in neuroretinal signaling, with the majority of DEGs being downregulated, while 7 pathways function in upregulated immune/inflammatory responses. Retinal and epithelial cell death pathways involving both apoptosis and necroptosis were also activated. MCMV ocular latency is associated with upregulation of immune and inflammatory responses and downregulation of multiple neuroretinal signaling pathways. Cell death signaling pathways are also activated and contribute to the degeneration of photoreceptors, RPE, and choroidal capillaries.

Characteristics and Classification of Choroidal Caverns in Patients with Various Retinal and Chorioretinal Diseases

To investigate the features of choroidal caverns in diverse retinal diseases with swept-source optical coherence tomography (SS-OCT). Subjects with normal eyes, retinitis pigmentosa (RP), wet age-related macular degeneration (wAMD), acute central serous chorioretinopathy (CSC), or chronic CSC were enrolled. The characteristics of choroidal caverns were evaluated with SS-OCT. The prevalence of choroidal caverns in retinal diseases and the correlations between the number, width and depth of choroidal caverns with the thickness of choroid were analyzed. Among 315 eyes of 220 subjects, choroidal caverns were found in 110 eyes (34.9%). Choroidal caverns were divided into two categories based on their location and size. Type I was small and usually lobulated, presented in the choroidal capillary and Sattler's layers. Type II was larger, usually isolated, and presented in the Sattler's and Haller's layers. The prevalence of type I in subjects with normal eyes, RP, wAMD, acute CSC, or chronic CSC was 17.4%, 19.6%, 1.6%, 32.8%, and 85.2%, respectively, while that of type II was 0%, 0%, 21.3%, 13.8%, and 53.7%, respectively. The number, width, and thickness of type II choroidal caverns correlated positively with macular choroidal thickness. Choroidal caverns could be divided into two categories. Type II choroidal caverns appeared associated with the pachychoroid spectrum and RPE atrophic diseases.

Changes in retinal and choroidal capillary dynamics in patients with multisystem inflammatory syndrome in children.

PurposeTo evaluate patients with multisystemic inflammatory syndrome in children (MIS-C) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using optical coherence tomography angiography (OCTA) during and after resolution of inflammation to investigate the effect of this entity on the retinal and choroidal circulation.MethodsThe study included 38 eyes of 19 patients diagnosed as having MIS-C between March 2021 and June 2021. OCTA measurements of choroidal thickness and vessel density in the radial peripapillary capillary plexus (RPCP), superficial capillary plexus (SCP), and deep capillary plexus (DCP) obtained at time of diagnosis and 60 days later were compared. Correlations between C-reactive protein (CRP) levels at diagnosis and retinochoroidal involvement were investigated.ResultsCompared to post-recovery follow-up examinations, patients with active MIS-C showed foveal avascular zone enlargement (p = 0.031), decreased vessel density in the temporal parafoveal SCP (p = 0.047) and all parafoveal areas of the DCP (p < 0.05 for all), and increased choroidal thickness (p = 0.021). Correlation analysis between CRP levels and OCTA changes during MIS-C revealed significant negative correlations with all parafoveal sectors of the SCP and DCP and a significant positive correlation with CT.ConclusionThere were especially marked effects on the DCP and choroid in MIS-C patients. Our findings also correlate with CRP levels. The use of optical coherence tomography angiography in patients with multisystemic inflammatory syndrome may have potential future implications for detecting ocular microvascular changes that occur before permanent damage develops.Clinical Trial Registration Number and Date: 77/1340; March 1, 2021.

Reduced choroidal peripapillary capillaries in thyroid-associated ophthalmopathy with early stage of dysthyroid optic neuropathy.

To investigate whether the subtle change of choroidal/retinal vessel densities and volumes in thyroid-associated ophthalmopathy (TAO) could be an early sign to detect dysthyroid optic neuropathy (DON). This was a retrospective cross-sectional study, and a total of 98 eyes from 50 subjects were enrolled under certain criteria. Thirty-four eyes of normal controls and 64 eyes of TAO, including 39 eyes of DON and 25 eyes of TAO without DON, underwent optical coherence tomography angiography (OCTA) scanning. All the tested parameters of OCTA scanning including choroid radial peripapillary capillaries (RPC), retinal nerve fiber layer (RNFL), and macular ganglion cell complex (GCC) were compared among groups, and the correlation between OCTA parameters and visual function parameters was also investigated. Whole choroidal RPC was significantly reduced in DON (48.24%±0.4978%) compared to normal (50.33%±0.3173%) and TAO without DON (49.16%±0.5463%; P=0.0041). The reduction of whole choroidal RPC was also correlated with visual field (VF) defect in DON (r=0.5422, n=39). Although vision acuity and VF were improved in all the patients with DON after being treated with medical and surgical decompression, the reduction of RPC density were not reversed. There is a notable reduction in choroidal RPC in DON, which is correlated with VF defect. The reduction of RPC density could not be reversed immediately by medical and surgical decompression even when vision and VF were improved. These findings suggest that choroidal RPC could be a useful parameter to diagnose and monitor early stage of DON.

Choroidal blood flow and visual function in idiopathic macular hole

Objective: To investigate the choroidal blood flow and visual function in idiopathic macular hole. Methods: In this prospective study, fundus structure and visual function in 22 eyes with macular hole and their fellow eyes and 16 normal eyes were assessed. The best corrected visual acuity and retinal sensitivity were detected by the EDTRS visual chart and MP1. The choroidal blood flow was observed by optical coherence tomography angiography. The choriocapillary blood flow density was measured using MatLab. The thickness of the choroid and the aperture size of macular hole were measured using enhanced depth imaging mode of Heidelberg optical coherence tomography. Results: The best corrected visual acuity and retinal sensitivity of macular hole eyes [1.02±0.20 and (13.03±2.91) dB] were significantly lower than fellow eyes [0.15±0.11, t=17.019, P<0.001 and (17.25±2.03) dB, t=-4.085, P<0.001] and normal eyes [0.04±0.05, t=21.736, P=0.001 and (16.63±2.89) dB, t=-3.134, P=0.004]. The blood flow area of choroidal capillaries in macular hole eyes [(1.33±0.29) mm2] was significantly lower than fellow eyes [(1.98±0.13) mm2; t=-9.424, P<0.001] and normal eyes [(1.93±0.12) mm2; t=-8.707, P<0.001]. The paracentral blood vessel density of the choroid capillary layer in macular hole eyes (48.91%±10.12%) was significantly lower than fellow eyes (58.27%±6.18%; t=-3.502, P=0.001) and normal eyes (55.20%±2.12%; t=-2.830, P=0.020). The subfoveal choroidal thickness of macular hole eyes [(188±21) μm] was significantly lower than fellow eyes [(217±36) μm; t=-3.672, P=0.002] and normal eyes [(229±25) μm; t=-3.304, P<0.001]. The basic diameter of macular hole eyes was correlated with the blood vessel density (r=-0.584, P=0.004), the subfoveal choroidal thickness (r=-0.511, P=0.015) and the retinal sensitivity (r=-0.432, P=0.044). The retinal sensitivity was correlated with the blood vessel density (r=0.450, P=0.035) and the subfoveal choroidal thickness (r=0.429, P=0.046). Conclusions: The retinal sensitivity and fundus blood perfusion of idiopathic macular hole was decreased, and the thickness of paracentral choroid in the contralateral eye tended to become thinner. The reduced visual function in eyes with macular hole may be associated with the decreased choroidal thickness and worse blood flow of fundus microcirculation.

Distribution characteristics of retinal nerve fiber layer thickness in macular area and its relationship with vessel density in highly myopic eyes

AIM: To investigate the distribution characteristics of retinal nerve fiber layer thickness and vessel density in macular area of eyes with high myopia, using optical coherence tomography angiography (OCTA). METHODS: Forty eyes in 20 patients diagnosed with high myopia, age 29.90±7.92 years old, with a spherical equivalent of -8.95±2.01 D, were recruited. The retinal nerve fiber layer (RNFL) thickness and the vessel density of the superficial retinal capillary plexus, deep retinal capillary plexus, and choroidal capillary were measured by OCTA. Macular regions within a 6-mm diameter circle were divided into 9 subfields: the central subfield, and the pericentral and peripheral regions of superior, inferior, nasal, and temporal quadrants. The retinal nerve fiber layer thicknesses of different subfields were compared, and their relationships with spherical equivalent, axial length, and vessel density were analyzed. RESULTS: In the pericentral region, the retinal nerve fiber layer thickness of the superior quadrant was the lowest, whereas thickness was highest in the inferior quadrant (all P&lt;0.05). In the peripheral region, the retinal nerve fiber layer thickness of the temporal quadrant was the lowest (all P&lt;0.05). A negative correlation was found between the retinal nerve fiber layer thickness and spherical equivalent (r=-0.356, P=0.024) in the peripheral superior subfield. The vessel density of superficial retinal capillary plexus was positively correlated with retinal nerve fiber layer thickness in the nasal and inferior quadrants of the pericentral region and in the superior, nasal, and inferior quadrants of the peripheral region (r=0.314, 0.408, 0.467, 0.655, and 0.737 respectively; and all P&lt;0.05), whereas the vessel density of choroidal capillary was negatively correlated with retinal nerve fiber layer thickness in the peripheral superior subfield (r= -0.356, P=0.024). CONCLUSION: The RNFL of macular areas is not uniformly distributed in high myopia (HM). As the spherical equivalent (SE) increases, the RNFL thickness decreases in certain areas, which correlates with the vessel density(VD) of superficial retinal capillary plexus (SCP) and choroidal capillary (CC) layers.

Fingolimod (FTY720), a Sphinogosine-1-Phosphate Receptor Agonist, Mitigates Choroidal Endothelial Proangiogenic Properties and Choroidal Neovascularization.

Neovascular or wet age-related macular degeneration (nAMD) causes vision loss due to inflammatory and vascular endothelial growth factor (VEGF)-driven neovascularization processes in the choroid. Due to the excess in VEGF levels associated with nAMD, anti-VEGF therapies are utilized for treatment. Unfortunately, not all patients have a sufficient response to such therapies, leaving few if any other treatment options for these patients. Sphingosine-1-phosphate (S1P) is a bioactive lipid mediator found in endothelial cells that participates in modulating barrier function, angiogenesis, and inflammation. S1P, through its receptor (S1PR1) in endothelial cells, prevents illegitimate sprouting angiogenesis during vascular development. In the present paper, we show that, in choroidal endothelial cells, S1PR1 is the most abundantly expressed S1P receptor and agonism of S1PR1-prevented choroidal endothelial cell capillary morphogenesis in culture. Given that nAMD pathogenesis draws from enhanced inflammation and angiogenesis as well as a loss of barrier function, we assessed the impact of S1PR agonism on choroidal neovascularization in vivo. Using laser photocoagulation rupture of Bruch’s membrane to induce choroidal neovascularization, we show that S1PR non-selective (FTY720) and S1PR1 selective (CYM5442) agonists significantly inhibit choroidal neovascularization in this model. Thus, utilizing S1PR agonists to temper choroidal neovascularization presents an additional novel use for these agonists presently in clinical use for multiple sclerosis as well as other inflammatory diseases.

Optical Coherence Tomography Angiography Predicts Visual Outcomes for Craniopharyngioma in Children by Quantifying Choroidal Capillaries.

Purpose: To predict the prognosis of craniopharyngioma in children by optical coherence tomography angiography (OCTA).Methods: We evaluated if the relationship between preoperative OCTA of the choroidal capillary density (CCD) and visual outcome continued over long-term visual recovery in 38 patients undergoing craniopharyngioma resection. Patients were evaluated 3 times: 1 week before surgery (Visit1), followed-up at 6–10 weeks (Visit2), and 9–15 months (Visit3) after surgery.Results: In total 38 patients (70 eyes) with craniopharyngiomas, which included 20 (52.6%) boys and 18 (47.4%)girls, the mean age was 11.8 ± 2.7 years (range: 6–18 years). The age (p = 0.71), gender (p = 1.00), mean refractive error (p = 0.55), and axial length (p = 0.23) of 38 normal volunteers (76 eyes) were matched. After surgery, the cross-compression of patients was relieved. The average visual acuity change in the normal CCD group was 0.07 ± 0.02; the average visual acuity change in the low CCD group was 0.01 ± 0.01, p < 0.001. Preoperative CCD value is related to the preoperative BCVA (p < 0.001), and the visual function after the long-term follow-up (9–15 months) (p < 0.001). The prognosis of CCD has the same trend as the BCVA. Further correlation analysis shows that CCD and BCVA are significantly correlated (r = 0.878; p < 0.001). CCD has a weak but significant correlation both with MD (r = 0.19; p < 0.001) and PSD (r = −0.21; p <0.001). A natural cutoff of CCD is approximately 38%. With the normal CCD group the maximum improvement of BCVA exceeds 0.3 post-operatively, compared to eyes in the low CCD group that improve by <0.03, and worse after surgery.Conclusions: Long-term vision recovery after surgical decompression of craniopharyngiomas in children can be predicted by preoperative by OCTA. Patients with normal CCD before surgery showed a tendency to improve vision; this trend of improvement persisted in subsequent follow-ups. The CCD baseline natural cutoff value for predicting visual prognosis before and after surgery is about 38%.