Combined treatment of submacular hemorrhage with low-dose subretinal recombinant tissue plasminogen activator and intravitreal conbercept.

BACKGROUND: Pars Plana Vitrectomy (PPV) combined with subretinal injection of low-dose recombinant tissue plasminogen activator (rt-PA) and intravitreal injection of Conbercept as a novel therapy for submacular hemorrhage (SMH) requires evaluation. METHODS: In a retrospective interventional clinical study, 14 eyes of 14 patients with SMH underwent PPV along with rt-PA (subretinal) and Conbercept (intravitreal) injections. The main outcomes included best-corrected visual acuities (BCVAs), degrees of blood displacement, and adverse events. All patients completed at least 6-month follow-up visits. RESULTS: Mean BCVAs significantly improved at 7 days (22.29 ± 15.35), 1 month (30.71 ± 16.42), 3 months (38.29 ± 13.72), 4 months (38.86 ± 14.15), and 6 months (41.21 ± 14.91) post-treatment compared to baseline (16.36 ± 13.97) (F = 12.89, P = 0.004). The peak improvement in BCVAs occurred at 6 months postoperatively. The procedure effectively eliminated subfoveal hemorrhages in all eyes, with clots removal and absorption occurring within one month and complete regression by 3-month follow-up visits. Postoperatively, two cases of AMD resulted in discoid scars on the fundus. No instances of rt-PA-related retinal toxicity were observed during the follow-up period. CONCLUSION: The combined approach of PPV with low-dose rt-PA and anti-VEGF shows promise in enhancing both vision and anatomical structure in SMH therapy. Individualized treatment plans tailored to the primary disease should be developed to optimize visual prognoses. TRIAL REGISTRATION: Retrospectively registered No.ChiCTR2100053034. Registration date: 10/11/2021.

Retina as a potential biomarker for the early stage of Alzheimer's disease spectrum.

OBJECTIVE: To characterize the retinal microvasculature and structure in subjective cognitive decline (SCD) and identify the potential biomarker for the early stage of the Alzheimer's disease (AD) spectrum. METHODS: In this study, 35 patients with SCD, 36 with cognitive impairment, and 29 with normal cognition (NC) were enrolled. Optical coherence tomography angiography was employed to assess retinal vascular density, fovea avascular zone area, and retinal thickness. The parameters reflecting retinal perfusion and structure were compared among the three groups. In addition, the association between retinal parameters, cerebral blood flow (CBF), and peripheral blood biomarkers in the SCD stage was analyzed. RESULTS: The superficial vascular complex (SVC) vascular density in the macula and retinal nerve fiber layer thickness in the peripapillary were significantly reduced in individuals with SCD compared to NC. Furthermore, there was a positive correlation between macular ganglion cell complex thickness and CBF in SCD. INTERPRETATION: The retinal microvasculature and structure exhibit alterations in individuals with SCD. Macular ganglion cell complex thickness demonstrates correlations with cerebral perfusion. The retina holds potential as a novel biomarker for early detection of AD.

OCTA-based research on changes of retinal microcirculation in digestive tract malignancy.

PURPOSE: This cross-sectional study measured retinal vessel density (VD) in patients with digestive tract malignancy by optical coherence tomography angiography (OCTA), and compared them with healthy controls to explore the retinal microcirculation changes in patients with digestive tract malignancy. METHODS: 106 eligible participants were divided into three groups: gastric cancer (GC) group (36 individuals), colorectal cancer (CRC) group (34 individuals), and healthy control group (36 individuals). Angio 6 × 6 512 × 512 R4 and ONH Angio 6 × 6 512 × 512 R4 modes were performed to collect retinal vessel density data centered on fovea and papillary, respectively. The retina was automatically segmented into different layers (superficial vascular plexus (SVP), the inner retinal layer, radial peripapillary capillary plexus (RPCP), deep vascular plexus (DVP)) and areas to analyze. RESULTS: At the optic nerve head (ONH) region, the VD of the inner retinal layer increased in both GC and CRC groups in all quadrants and areas. In the papillary area, VD in the inner retinal layer, SVP, and RPCP increased in the GC and CRC groups. In the parapapillary area, VD in the inner retinal layer increased in the GC and the CRC groups. Significant increase in the global VD were found in the GC group of the RPCP and SVP. Regarding the macular region, no statistical differences were observed in each layer. CONCLUSIONS: The study suggested that retinal vessel density changed in patients with digestive tract malignancy, especially in the inner retinal layer of the ONH region, revealing the potential relevance of the relation between gastrointestinal cancer and retinal microcirculation.

Deep Learning-Based Vascular Aging Prediction From Retinal Fundus Images.

Purpose: The purpose of this study was to establish and validate a deep learning model to screen vascular aging using retinal fundus images. Although vascular aging is considered a novel cardiovascular risk factor, the assessment methods are currently limited and often only available in developed regions. Methods: We used 8865 retinal fundus images and clinical parameters of 4376 patients from two independent datasets for training a deep learning algorithm. The gold standard for vascular aging was defined as a pulse wave velocity ≥1400 cm/s. The probability of the presence of vascular aging was defined as deep learning retinal vascular aging score, the Reti-aging score. We compared the performance of the deep learning model and clinical parameters by calculating the area under the receiver operating characteristics curve (AUC). We recruited clinical specialists, including ophthalmologists and geriatricians, to assess vascular aging in patients using retinal fundus images, aiming to compare the diagnostic performance between deep learning models and clinical specialists. Finally, the potential of Reti-aging score for identifying new-onset hypertension (NH) and new-onset carotid artery plaque (NCP) in the subsequent three years was examined. Results: The Reti-aging score model achieved an AUC of 0.826 (95% confidence interval [CI] = 0.793-0.855) and 0.779 (95% CI = 0.765-0.794) in the internal and external dataset. It showed better performance in predicting vascular aging compared with the prediction with clinical parameters. The average accuracy of ophthalmologists (66.3%) was lower than that of the Reti-aging score model, whereas geriatricians were unable to make predictions based on retinal fundus images. The Reti-aging score was associated with the risk of NH and NCP (P < 0.05). Conclusions: The Reti-aging score model might serve as a novel method to predict vascular aging through analysis of retinal fundus images. Reti-aging score provides a novel indicator to predict new-onset cardiovascular diseases. Translational Relevance: Given the robust performance of our model, it provides a new and reliable method for screening vascular aging, especially in undeveloped areas.

Safety of repeated low-level red-light therapy for children with myopia.

BACKGROUD: To investigate the safety of repetitive low-level red-light therapy (RLRLT) in children with myopia. METHODS: Children with myopia were assigned to the RLRL and control groups. Axial length (AL) and spherical equivalent refraction (SER) were followed up at 3-, 6-, and 12-month. To evaluate the safety of RLRLT, at 6 and 12 months in the RLRL group, multifocal electroretinography (mfERG) and contrast sensitivity were recorded. Furthermore, optical coherence tomography was used to measure the relative reflectance of the ellipsoid zone (rEZR), photoreceptor outer segment (rPOSR), and retinal pigment epithelium (rRPER). RESULTS: A total of 108 children completed the trial (55 in the RLRL group and 53 in the control group). After 3, 6, and 12 months, AL was shorter and SER less myopic in the RLRL group than in the control group. Regarding the safety of the RLRLT, the response density and amplitude of the P1 wave of the first ring of the mfERG increased significantly at 6 months (P = 0.001 and P = 0.017, respectively). At 6 and 12 months, contrast sensitivity at the high spatial frequency increased. Moreover, the rEZR increased significantly at 6 months (P = 0.029), the rPOSR increased significantly at 6 and 12 months (both P < 0.001), and the increase in rPOSR was greater with greater AL regression. CONCLUSIONS: Based on retinal function and structure follow-up, RLRLT was safe within 12 months. However, rEZR and rPOSR increased, the effects of this phenomenon requires further observation.

Emerging role of ferroptosis in diabetic retinopathy: a review.

BACKGROUND: Diabetic retinopathy (DR) is a significant complication of diabetes and the primary cause of blindness among working age adults globally. The development of DR is accompanied by oxidative stress, characterised by an overproduction of reactive oxygen species (ROS) and a compromised antioxidant system. Clinical interventions aimed at mitigating oxidative stress through ROS scavenging or elimination are currently available. Nevertheless, these treatments merely provide limited management over the advanced stage of the illness. Ferroptosis is a distinctive form of cell death induced by oxidative stress, which is characterised by irondependent phospholipid peroxidation. PURPOSE: This review aims to synthesise recent experimental evidence to examine the involvement of ferroptosis in the pathological processes of DR, as well as to explicate the regulatory pathways governing oxidative stress and ferroptosis in retina. METHODS: We systematically reviewed literature available up to 2023. RESULTS: This review included 12 studies investigating the involvement of ferroptosis in DR.

Performance of deep learning for detection of chronic kidney disease from retinal fundus photographs: A systematic review and meta-analysis.

OBJECTIVE: Deep learning has been used to detect chronic kidney disease (CKD) from retinal fundus photographs. We aim to evaluate the performance of deep learning for CKD detection. METHODS: The original studies in CKD patients detected by deep learning from retinal fundus photographs were eligible for inclusion. PubMed, Embase, the Cochrane Library, and Web of Science were searched up to October 31, 2022. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was used to assess the risk of bias. RESULTS: Four studies enrolled 114,860 subjects were included. The pooled sensitivity and specificity were 87.8% (95% confidence interval (CI): 61.6% to 98.3%), and 62.4% (95% CI: 44.9% to 78.7%). The area under the curve (AUC) was 0.864 (95%CI: 0.769, 0.986). CONCLUSION: Deep learning based on retinal fundus photographs has the ability to detect CKD, but it currently has a lot of room for improvement. It is still a long way from clinical application.

Insights into myopic choroidal neovascularization based on quantitative proteomics analysis of the aqueous humor.

BACKGROUND: Previous studies on the biomarkers of pathologic myopia choroidal neovascularization (pmCNV) development merely detected limited types of proteins and provide a meagre illustration of the underlying pathways. Hence, a landscape of protein changes in the aqueous humor (AH) of pmCNV patients is lacking. Here, to explore the potential mechanisms and biomarkers of pmCNV, we analyzed the clinical data and protein profile among atrophic (A) lesions, tractional lesions (T) and neovascular (N) lesions in myopic patients based on the ATN grading system for myopic maculopathy (MM). RESULTS: After investigating demographic data of our patients, a correlation was found between A and N lesions (R = 0.5753, P < 0.0001). Accordingly, groups were divided into patients without MM, patients with myopic atrophic maculopathy (MAM), and patients with pmCNV (N2a lesion). In proteomics analysis, the increased protein level of GFAP and complement-associated molecules in AH samples of the 3 groups also indicated that MAM and pmCNV shared similar characteristics. The GO enrichment and KEGG pathway analysis were performed, which mapped that differential expressed proteins mainly engaged in JAK-STAT pathway between the pmCNV group and two controls. Furthermore, we identified several potential biomarkers for pmCNV, including FCN3, GFAP, EGFR, SFRP3, PPP2R1A, SLIT2, and CD248. CONCLUSIONS: Atrophic lesions under pathologic myopic conditions demonstrated similarities to neovascularization development. Potential biomarkers including GFAP were associated with the pathogenesis of pmCNV. In summary, our study provides new insights for further research on pmCNV development.

Low-Dose Trans-Resveratrol Ameliorates Diabetes-Induced Retinal Ganglion Cell Degeneration via TyrRS/c-Jun Pathway.

Purpose: The purpose of this study was to investigate the protective effect of low-dose trans-resveratrol (trans-RSV) on diabetes-induced retinal ganglion cell (RGC) degeneration and its possible mechanism. Methods: A streptozotocin-induced diabetic mouse model was established and treated with or without trans-RSV intragastric administration (10 mg/kg body weight/day) for 12 weeks. Oscillatory potentials (Ops) of the dark-adapted electroretinogram (ERG) were recorded. The number of RGCs was detected by Tuj1 and TUNEL staining. The apoptosis markers in the retina were analyzed by Western blot. The cross sections of optic nerves were observed by transmission electron microscopy. In addition, mouse neuroblastoma N2a cells were injured by high-glucose (HG) treatment. Cell viability and apoptosis were measured with or without low-dose trans-RSV treatment. The intracellular localization of tyrosyl transfer-RNA synthetase (TyrRS) was observed in both mouse retinas and N2a cells. The effects of low-dose trans-RSV on the binding of TyrRS to the transcription factor c-Jun and the binding of c-Jun to pro-apoptotic genes were analyzed by co-IP and ChIP assays in HEK 293 cells. Results: Trans-RSV relieved electrophysiological injury of retinas and inhibited RGC apoptosis in diabetic mice. It also protected N2a cells from HG-induced apoptosis. Additionally, it promoted TyrRS nuclear translocation in both diabetic mouse retinas and HG-treated N2a cells. Trans-RSV promoted TyrRS binding to c-Jun, inhibited the phosphorylation of Ser-63 of c-Jun, and downregulated pro-apoptotic gene transcription. Conclusions: Low-dose trans-RSV can ameliorate diabetes-induced RGC degeneration via the TyrRS/c-Jun pathway. It can promote TyrRS nuclear translocation and bind to c-Jun, downregulating c-Jun phosphorylation and downstream pro-apoptotic genes.

Detection of Choroidal Neovascularization Using Optical Tissue Transparency.

Purpose: Optical tissue transparency (OTT) provides a tool for visualizing the entire tissue block. This study provides insights into the potential value of OTT with light-sheet fluorescence microscopy (LSFM) in detecting choroidal neovascularization (CNV) lesions. Methods: OTT with LSFM, hematoxylin and eosin (H&E) staining of paraffin sections, choroidal flatmount immunofluorescence, and optical coherence tomography angiography (OCTA) were used to obtain images of CNV. We determined the rate of change as (Data of week 1 - Data of week 2)/Data of week 1 × 100%. Finally, we compared the rate of change acquired from OTT with LSFM and the other methodologies. Results: We found that OTT with LSFM can realize three-dimensional (3D) visualizations of the entire CNV. The results showed that the decline in the rate of change from week 1 to week 2 after laser photocoagulation was 33.05% with OTT, 53.01% with H&E staining, 48.11% with choroidal flatmount, 24.06% with OCTA (B-scan), 18.08% with OCTA (en face), 10.98% with OCTA (3D reconstruction), and 7.74% with OCTA (vessel diameter index). Conclusions: OTT with LSFM will continue to be an invaluable resource for investigators to detect more visualized and quantified information regarding CNV. Translational Relevance: OTT with LSFM now serves as a tool for detecting CNV in mice, and it may undergo human clinical trials in the future.

Ocular images-based artificial intelligence on systemic diseases.

PURPOSE: To provide a summary of the research advances on ocular images-based artificial intelligence on systemic diseases. METHODS: Narrative literature review. RESULTS: Ocular images-based artificial intelligence has been used in a variety of systemic diseases, including endocrine, cardiovascular, neurological, renal, autoimmune, and hematological diseases, and many others. However, the studies are still at an early stage. The majority of studies have used AI only for diseases diagnosis, and the specific mechanisms linking systemic diseases to ocular images are still unclear. In addition, there are many limitations to the research, such as the number of images, the interpretability of artificial intelligence, rare diseases, and ethical and legal issues. CONCLUSION: While ocular images-based artificial intelligence is widely used, the relationship between the eye and the whole body should be more clearly elucidated.

Compartmental analysis of three-dimensional choroidal vascularity and thickness of myopic eyes in young adults using SS-OCTA.

Purpose: We aimed to investigate the change of three-dimensional (3D) choroidal thickness (ChT), choroidal vessel volume (CVV), and choroidal vessel index (CVI) in young myopic adults using swept-source optical coherence tomography angiography (SS-OCTA) and compare the difference of these indicators in different quadrants of the macula and optic disc. Methods: A total of 248 eye samples from 135 participants were used in this cross-sectional study. Each participant underwent detailed history taking and ocular examinations. Based on axial length (AL), patients were divided into the emmetropia (EM) group, mild-myopia (MIM) group, moderate-myopia (MOM) group, and high-myopia (HM) group. 6 mm × 6 mm (1,024 × 1024 B-scans) SS-OCTA scans were performed centered on the fovea and optic disc. 3D ChT, CVV, and CVI were measured based on a built-in deep learning algorithm. Differences in ChT, CVV, and CVI were analyzed in different regions and different myopic groups. Results: Significant reduction in the global CVV were found in the HM group (1.930 ± 0.865) in comparison with the EM (3.486 ± 0.992), MIM (3.238 ± 1.033), and MOM (2.589 ± 1.083) groups (p < 0.001). The global CVI was also lower in the HM group (0.258 ± 0.061) than in the EM (0.320 ± 0.055), MIM (0.320 ± 0.051), and MOM (0.286 ± 0.066) groups (p < 0.001). The ChT was thinner in eyes with HM (242.753 ± 65.641) than in eyes with EM (377.532 ± 80.593), MIM (348.367 ± 78.191), or MOM (300.197 ± 87.175) (p < 0.001). Compartmental analysis revealed that ChT, CVV, and CVI in the nasal quadrant of the macula and temporal and inferior quadrants of the optic disc were much lower than those in other quadrants (p < 0.05). Correlation analyses found that ChT, CVV, and CVI were negatively correlated with AL and spherical equivalence. Conclusion: 3D ChT, CVV, and CVI gradually decreased as the degree of myopia increased. The changes were more dramatic on the nasal side of the macula and the temporal and inferior sides of the optic disc. These findings demonstrated the 3D choroidal change and highlighted the papillo-macular bundle as a sensitive region in myopic development.

Comparative study of a modified double-lumen tube ventilation control connector and traditional connector in clinical use: a randomised-controlled trial.

BACKGROUND: A Y-shaped rotatable connector (YRC) for double-lumen tubes (DLT) is invented and compared with the traditional connector (Y-shaped connector, YC). METHODS: Sixty patients with ASA grade I-III, aged ≥ 18 years, who needed to insert a DLT for thoracic surgery were recruited and assigned into the YRC group (n = 30) and the YC group (n = 30) randomly. The primary endpoints included the inhaled air concentration (Fi) and the exhaled air concentration (Et) of sevoflurane before and after the switch between two-lung ventilation and one-lung ventilation at different times, positioning time, and switching time. The secondary endpoints were the internal gas volume of the two connectors, airway pressure, and the sputum suction time. RESULTS: The Et and Fi of the YRC group and the YC group were significantly different (all p < 0.05) at 5s, 10s, and 30s after the patient switched from two-lung ventilation to one-lung ventilation. The positioning time of the YRC group was less than YC group (89.75 ± 14.28 s vs 107.80 ± 14.96 s, p < 0.05), as well as the switching time (3.60 ± 1.20 s vs 9.05 ± 2.53 s, p < 0.05) and the internal gas volume (17.20 ml vs 24.12 ml). There was no difference in airway pressure and the sputum suction time in two groups. CONCLUSION: Compared with YC, YRC was beneficial for maintaining depth of anesthesia, improves efficiency for the switch between one-lung and two-lung ventilation, and shortens the tube positioning time.

Analysis of White and Dark without Pressure in a Young Myopic Group Based on Ultra-Wide Swept-Source Optical Coherence Tomography Angiography.

Purpose: This study aimed to investigate the incidence of white without pressure (WWOP) and dark without pressure (DWOP) in a young myopic group based on multimode imaging and to explore the quantitative changes in DWOP based on ultra-wide swept-source optical coherence tomography angiography (SS-OCTA). Methods: A total of 138 patients with high myopia (SE < −6.00 D) were recruited. Examinations, including indirect ophthalmoscope, ultra-wide color fundus photograph, and ultra-wide SS-OCTA, were conducted for each eye. A total of 50 of the 138 patients were selected for further analysis since their DWOP lesions in SS-OCTA could be well quantified. Results: The incidence rates of WWOP and DWOP in the young myopic group were 35.24% and 29.96%, respectively. The patients with a lower spherical equivalent (SE) showed a tendency to have a higher axial length (AL) and higher prevalence of WWOP. Multivariate regression analysis illustrated that a more serious SE and a longer AL were risk factors for both WWOP and DWOP. Eyes with DWOP lesions had lower vessel density (VD) in the whole retina (p < 0.001) and a deep vascular complex (DVC) (p < 0.001), and lower thickness of the outer retina (p < 0.001) compared with healthy counterparts. Conclusion: Ultra-wide SS-OCTA provided new insights into myopic-related peripheral retinal degenerations. DWOP was characterized by thinning of the outer retina and lower perfusion in DVC.

Clinical Features and Vitreous Biomarkers of Early-Onset Type 2 Diabetes Mellitus Complicated with Proliferative Diabetic Retinopathy.

Purpose: To compare the clinical features and vitreous biomarkers of proliferative diabetic retinopathy (PDR) between patients with early-onset and late-onset type 2 diabetes mellitus (T2DM). Materials and Methods: This case-control study analyzed the clinical data of 74 patients with PDR who underwent vitrectomy. The patients were divided into the early-onset (T2DM diagnosis age ≤ 40 years, n = 39) and late-onset (T2DM diagnosis age > 40 years, n = 35) groups. Thirty-six specimens were collected, and the liquid chip technology was used to detect the content of 27 types of cytokines in the vitreous. Differences in clinical features and cytokine levels between the two groups were evaluated. Bonferroni correction was applied for multiple comparisons. Results: Compared with the late-onset group, the levels of hemoglobin A1c (HbA1c) and total cholesterol were significantly higher in the early-onset group (P < 0.001 and P = 0.009, respectively). Patients with early-onset T2DM PDR had worse visual prognoses and a higher rate of postoperative recurrent vitreous hemorrhage. The results of cytokine detection showed that the levels of interleukin-4 (IL-4), IL-6, IL-8, IL-9, granulocyte colony-stimulating factor, interferon-γ, interferon-inducible 10 kDa, monocyte chemotactic protein 1, macrophage inflammatory protein (MIP)-1α, and MIP-1ß in the early-onset group were significantly higher than those in the late-onset group (p < 0.0026). Age at diabetes diagnosis and HbA1c, IL-4, and regulated upon activation, normal T cell expressed and secreted levels were independent risk factors for visual acuity after undergoing vitrectomy. Conclusion: Early-onset T2DM PDR patients had poor blood glucose and lipid metabolism, higher levels of inflammatory factors, and worse visual prognosis. Stricter metabolic management and earlier anti-inflammatory interventions may be required for patients with early-onset T2DM.

Preparation of a novel tacrolimus ion sensitive ocular in situ gel and in vivo evaluation of curative effect of immune conjunctivitis.

BACKGROUND: The aim of this study was to formulate a novel TAC preparation into an in situ gel for ocular drug delivery, in order to prolong the residence time on mucosal surfaces and increase patient compliance. METHODS: The optimal formulation was characterized by surface morphology, gelling capacity, viscosity, stability and in vitro release. In vivo studies were also conducted to evaluate the precorneal retention and pharmacodynamic results. RESULTS: In this study, the TAC in situ gel can be prepared by a simple solvent stirring method, and the optimized formulation exhibited good stability within 3 months. During storage, the initial viscosity of the formula had little change. The results of viscosity measurement showed that TAC in situ gel was typical of pseudo plastic systems and exhibited a marked increase in viscosity stimulated with STF. In vitro and in vivo studies illustrated that TAC in situ gel administration facilitated the retention and sustained release of TAC. CONCLUSIONS: TAC combined with in situ gelling agents demonstrates an efficient topical drug delivery platform.

LECT2 Ameliorates Blood-Retinal Barrier Impairment Secondary to Diabetes Via Activation of the Tie2/Akt/mTOR Signaling Pathway.

Purpose: Current treatments for diabetic retinopathy (DR) have considerable limitations, emphasizing the need for new therapeutic options. The effect of leukocyte cell-derived chemotaxin 2 (LECT2) on diabetes-induced blood-retinal barrier impairment and the possible underlying mechanism were investigated both in vivo and in vitro. Methods: Twenty diabetic and 22 nondiabetic eyes were included in this study. Additionally, we established a streptozotocin-induced diabetic mouse model and observed vascular leakage in mice treated with or without recombinant LECT2 (rLECT2) intravitreal injection (40 µg/mL, 1 µL). The levels of LECT2 and interendothelial junction proteins (ZO1, VE-cadherin, and occludin) were analyzed by western blot and/or immunofluorescence. Endothelial junctions in mouse retinas were observed by transmission electron microscopy (TEM). Moreover, confluent human retinal microvascular endothelial cells (HRMECs) and human umbilical vein endothelial cells (HUVECs) were treated (0-72 hours) with glucose (0 or 30 mM) in the presence or absence of rLECT2 (40-360 ng/mL). After treatment, intact cell monolayers were monitored for permeability to 40-kD FITC-dextran. Interendothelial junction targets and Tie2/Akt/mTOR signaling pathway components were investigated by western blot. Results: In diabetic human and mouse retinas and high-glucose (30 mM)-treated HRMECs and HUVECs, the levels of LECT2 and interendothelial junction proteins were decreased. rLECT2 treatment (80 ng/mL) significantly attenuated the hyperglycemia-induced reduction in endothelial cell barrier function and inhibited the migration and tube formation of HRMECs and HUVECs. In addition, rLECT2 increased the levels of interendothelial junction proteins via activation of the Tie2/Akt/mTOR signaling pathway. Furthermore, intravitreal rLECT2 injections increased the levels of interendothelial junction proteins and reversed diabetes-induced junction disruption. Conclusions: rLECT2 can increase the levels of interendothelial tight junction proteins through activation of the Tie2/Akt/mTOR signaling pathway and can ameliorate inner blood-retinal barrier impairment secondary to diabetes. LECT2 might be a potential target to prevent the progression of DR.

Investigation of SARS-CoV-2 on Ocular Surface of Coronavirus Disease 2019 Patients Using One-Step Reverse-Transcription Droplet Digital PCR.

PURPOSE: This study detects SARS-CoV-2 in the ocular surface through one-step reverse-transcription droplet digital PCR (one-step RT-ddPCR) and evaluates the possibility of the ocular surface as a possible transmission route. METHODS: A single-center prospective observational study was designed to investigate the viral loads in ocular surface. Specimens including the conjunctival swabs, nasopharyngeal swabs and blood were synchronously collected at a single time point for all COVID-19 patients. SARS-CoV-2 loads in nasopharyngeal swabs were tested by real-time polymerase chain reaction (PCR); the blood samples and conjunctival swabs were tested by real-time PCR and one-step RT-ddPCR. RESULTS: Sixty-eight COVID-19 patients confirmed by nasopharyngeal real-time PCR were recruited. In the single time point test, 40 cases showed positive SARS-CoV-2 detection in either the blood, tears, or nasopharynx, of which four cases were triple-positive, 10 were dual-positive, and 26 were single-positive. The positive rate of nasopharyngeal swab real-time PCR test was 22.1% (15/68). The positive rate of blood and conjunctival swabs by one-step RT-ddPCR was 38.2% (26/68) and 25% (17/68), respectively, whereas real-time PCR was all negative. Positive conjunctival swabs were significantly correlated with positive nasopharyngeal swabs (P = 0.028). The sampling lags from illness onset to sampling day in 3 out of 4 triple-positive patients and in 9 out of 10 dual-positive patients were respectively less than 9 days and less than 20 days. CONCLUSION: Our results indicate that the positive rate of SARS-CoV-2 on the ocular surface is much higher than expected. Transmission possibility through the ocular surface may be greatly underestimated.

Markers of the sympathetic, parasympathetic and sensory nervous system are altered in the human diabetic choroid.

BACKGROUND: We sought to evaluate alterations in markers of the autonomic nervous system in human diabetic choroid. METHODS: Eighteen eyeballs from subjects with diabetes and 22 eyeballs from subjects without diabetes were evaluated in this study. Synaptophysin, tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DßH), neuronal nitric oxide synthase (nNOS), choline acetyltransferase (ChAT), vesicular monoamine transporter II (VMAT-2), vesicular acetylcholine transporter (VAChT), vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), and calcitonin gene-related peptide (CGRP) levels were detected by western blot analysis and immunofluorescence was performed in some cases. Furthermore, differences in adrenergic (α1- and ß2-subtypes) and cholinergic (M1 and M3) receptor levels between diabetic subjects and controls were noted. RESULTS: Decreased synaptophysin levels were found in diabetic choroids by western blot analysis and a reduction of synaptophysin-immunoreactive nerves was also found by immunofluorescence. Furthermore, a decrease of the levels of the key enzyme (TH) and transporter (VMAT2) of norepinephrine was evident both by western blot analysis and immunofluorescence. Additionally, increased NPY, VAChT, nNOS, and CGRP levels were observed in diabetic choroids. The levels of adrenergic (ß2 subtype) and acetylcholine (M1 subtype) receptors decreased in diabetic choroids, as shown by western blotting and although the differences in α1 and M3 were not significant, there was a downward trend. CONCLUSIONS: In the diabetic choroid, the levels of neurotransmitters, enzymes, and receptors associated with choroidal blood flow regulation are altered. These changes may affect the regulation of choroidal blood flow and may be associated with impaired retinal function and retinal pathology.

Multimodal Imaging Characteristics and Presumed Cause of Intrapapillary Hemorrhage with Adjacent Peripapillary Subretinal Hemorrhage.

PURPOSE: To describe the multimodal imaging findings of intrapapillary hemorrhage with adjacent peripapillary subretinal hemorrhage (IHAPSH) and reveal the possible mechanism of this rare benign disease. PATIENTS AND METHODS: Observational study. Three eyes in three patients with intrapapillary hemorrhage with adjacent peripapillary subretinal hemorrhage were evaluated at the retina division of our institution. We describe the multimodal imaging findings including visual field examination, fundus photography, fluorescein and indocyanine green angiography (FFA&ICGA), spectral-domain optical coherence tomography (OCT), and ultrasonography. RESULTS: Three myopic patients with IHAPSH shared a similar clinical course and multimodal imaging appearance. The symptom was sudden dark shadows floating in the affected eye with mild visual blurring. Fundus photography showed hemorrhage in intrapapillary and subretinal, as well as optic disc bulges on the nasal side with local vitreoretinal separation in the affected eyes. OCT confirmed intrapapillary and subretinal hemorrhage with obviously elevated optic papilla in the affected eye and local vitreoretinal separation at the temporal side of optic disc together with vitreoretinal adhesion at the superonasal edge. FFA&ICGA ruled out optic drusen and neovascularization. B-ultrasonography in one case revealed optic disc bulge in the affected eye with tight traction by local detached vitreous posterior limiting membrane at the edge. The overall visual prognosis was excellent and the bleeding could be completely absorbed. CONCLUSION: IHAPSH tends to appear in young women with myopia. The mechanism may be attributed to an incomplete posterior vitreous detachment (PVD), followed by a tightly vitreous-papilla adhesion and concentrated traction to the superonasal part of the tilted small optic disc.