Publications by authors named "Xinghuai Sun"

291 Publications

Endogenous dual stimuli-activated NO generation in the conventional outflow pathway for precision glaucoma therapy.

Biomaterials 2021 Aug 17;277:121074. Epub 2021 Aug 17.

Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, Biomedical Engineering, Yong Loo Lin School of Medicine and Faculty of Engineering, National University of Singapore, Singapore, 119074, Singapore; Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117599, Singapore; Nanomedicine Translational Research Program, NUS Center for Nanomedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore. Electronic address:

High intraocular pressure (IOP) has been regarded as a predominant risk factor for glaucoma. Nitric oxide (NO) is shown to lower IOP, but the magnitude and duration of IOP reduction are not satisfying due to the poor cornea penetration of NO drugs and limited NO generation in the trabecular meshwork (TM)/Schlemm's canal (SC) area. Herein, we introduce deep cornea penetrating biodegradable hollow mesoporous organosilica (HOS) nanocapsules for the efficient co-delivery of hydrophobic JS-K (J) and hydrophilic l-Arginine (L). The resulting HOS-JL can be reduced and oxidized by the ascorbic acid (AA) and catalysis of endothelial nitric oxide synthase (eNOS) in the TM/SC microenvironment to release NO for inducing appreciable IOP reduction in various glaucoma mouse models. In addition to developing an endogenous stimuli-responsive NO nanotherapeutic, this study is also expected to establish a versatile, non-invasive, and efficacious treatment paradigm for precision glaucoma therapy.
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http://dx.doi.org/10.1016/j.biomaterials.2021.121074DOI Listing
August 2021

Inhibiting corneal neovascularization by sustainably releasing anti-VEGF and anti-inflammation drugs from silica-thermogel nanohybrids.

Mater Sci Eng C Mater Biol Appl 2021 Sep 26;128:112274. Epub 2021 Jun 26.

Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai 200031, China; NHC Key Laboratory of Myopia (Fudan University), Shanghai 200031, China; Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai 200031, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai 200031, China; State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China. Electronic address:

Corneal neovascularization (CNV) is one of the main factors that induce blindness worldwide. To effectively inhibit CNV, a novel nanohybrid has been developed by incorporating anti-VEGF bevacizumab (BEV)-loaded mesoporous silica nanoparticles ([email protected]) into the thermogel matrix with anti-inflammation cyclosporine A (CsA) ([email protected]@Thermogel). This nanohybrid regulates the in vitro release of both bevacizumab and cyclosporine A in a sustainable way for up to four weeks to enhance CNV inhibition through the synergistic anti-VEGF and anti-inflammation. The carrier materials (i.e. silica and thermogel) in this nanohybrid do not show any cytotoxicity to human Tenon's fibroblasts, corneal epithelial cells and corneal endothelial cells. [email protected]@Thermogel effectively prevents proliferation, migration, and tube-like structure formation of human umbilical vein endothelial cells. Moreover, subconjunctival injection of [email protected]@Thermogel significantly inhibits corneal neovascularization in terms of the CNV area, the new vessel length, the corneal opaque area, the corneal inflammation and abnormal fibrosis in a rabbit model. This nanohybrid is thus a promising alternative for effective CNV treatment.
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http://dx.doi.org/10.1016/j.msec.2021.112274DOI Listing
September 2021

Association of Ocular Surface Diseases With SARS-CoV-2 Infection in Six Districts of China: An Observational Cohort Study.

Front Immunol 2021 6;12:695428. Epub 2021 Aug 6.

Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses is mainly transmitted through respiratory droplets. Notably, some coronavirus disease 2019 (COVID-19) patients have ocular manifestations, including conjunctival hyperaemia, chemosis, epiphora, and increased secretions. However, the association between SARS-CoV-2 and ocular surface diseases is poorly described. Between May 2020 and March 2021, a total of 2, 0157 participants from six districts of China were enrolled. Serum samples were tested for immunoglobulin G and M (IgG and IgM) antibodies against the SARS-CoV-2 spike protein and nucleoprotein using magnetic chemiluminescence enzyme immunoassays. Throat swabs were tested for SARS-CoV-2 RNA using RT-PCR assays in a designated virology laboratory. Fisher exact, χ test, and logistic regression analysis were performed. Of 2, 0157 serum samples tested, 1, 755 (8.71%) were from ocular surface diseases, 1, 2550 (62.26%) from no-ocular surface diseases (ocular diseases except ocular surface diseases), 5, 852 (29.03%) from no-ocular diseases. SARS-CoV-2 prevalence for the combined measure was 0.90% (182/2, 0157). Seroprevalence of SARS-CoV-2 was significantly (p<0.05) higher in the population with ocular surface diseases (2.28%, 40/1755) compared with no-ocular surface diseases (0.70%, 88/1, 2550), and no-ocular diseases (0.92%, 54/5, 852). Similar results were also observed with respect to sex, age, time, and districts. Logistic regression analyses revealed that ocular surface diseases [ocular surface diseases no-ocular diseases (p=0.001, OR =1.467, 95% CI=1.174-1.834); ocular surface diseases no-ocular surface diseases (p<0.001, OR =2.170, 95% CI=1.434-3.284)] were associated with increased risk of susceptible to SARS-CoV-2 infection. In a word, there was a significant association between ocular surface disease and SARS-CoV-2 infection. Therefore, increasing awareness of eye protection during the pandemic is necessary, especially for individuals with ocular surface diseases.
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http://dx.doi.org/10.3389/fimmu.2021.695428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378230PMC
September 2021

Soluble tumor necrosis factor-alpha-induced hyperexcitability contributes to retinal ganglion cell apoptosis by enhancing Nav1.6 in experimental glaucoma.

J Neuroinflammation 2021 Aug 21;18(1):182. Epub 2021 Aug 21.

State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, 200032, China.

Background: Neuroinflammation plays an important role in the pathogenesis of glaucoma. Tumor necrosis factor-alpha (TNF-α) is a major pro-inflammatory cytokine released from activated retinal glial cells in glaucoma. Here, we investigated how TNF-α induces retinal ganglion cell (RGC) hyperexcitability and injury.

Methods: Whole-cell patch-clamp techniques were performed to explore changes in spontaneous firing and evoked action potentials, and Na currents in RGCs. Both intravitreal injection of TNF-α and chronic ocular hypertension (COH) models were used. Western blotting, immunofluorescence, quantitative real-time polymerase chain reaction (q-PCR), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) techniques were employed to investigate the molecular mechanisms of TNF-α effects on RGCs.

Results: Intravitreal injection of soluble TNF-α significantly increased the spontaneous firing frequencies of RGCs in retinal slices. When the synaptic transmissions were blocked, more than 90% of RGCs still showed spontaneous firing; both the percentage of cells and firing frequency were higher than the controls. Furthermore, the frequency of evoked action potentials was also higher than the controls. Co-injection of the TNF-α receptor 1 (TNFR1) inhibitor R7050 eliminated the TNF-α-induced effects, suggesting that TNF-α may directly act on RGCs to induce cell hyperexcitability through activating TNFR1. In RGCs acutely isolated from TNF-α-injected retinas, Na current densities were upregulated. Perfusing TNF-α in RGCs of normal rats mimicked this effect, and the activation curve of Na currents shifted toward hyperpolarization direction, which was mediated through p38 MAPK and STAT3 signaling pathways. Further analysis revealed that TNF-α selectively upregulated Nav1.6 subtype of Na currents in RGCs. Similar to observations in retinas of rats with COH, intravitreal injection of TNF-α upregulated the expression of Nav1.6 proteins in both total cell and membrane components, which was reversed by the NF-κB inhibitor BAY 11-7082. Inhibition of TNFR1 blocked TNF-α-induced RGC apoptosis.

Conclusions: TNF-α/TNFR1 signaling induces RGC hyperexcitability by selectively upregulating Nav1.6 Na channels, thus contributing to RGC apoptosis in glaucoma.
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http://dx.doi.org/10.1186/s12974-021-02236-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380326PMC
August 2021

Effect of Nimodipine on Macular and Peripapillary Capillary Vessel Density in Patients with Normal-tension Glaucoma Using Optical Coherence Tomography Angiography.

Curr Eye Res 2021 Jul 30:1-6. Epub 2021 Jul 30.

Department of Ophthalmology & Visual Science, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China.

Purpose: This study aimed to investigate the effect of nimodipine on peripapillary and macular capillary vessel density (VD) in patients with normal-tension glaucoma (NTG) using optical coherence tomography angiography (OCTA).

Methods: Sixty mg nimodipine was administered to 20 enrolled NTG patients for 3 months. Patients were treated with glaucoma medication simultaneously. The macular and peripapillary VD were measured automatically by OCTA at baseline, 1.5 h after administering nimodipine, and after 3 months of administering the drug. The retinal nerve fibre layer (RNFL), ganglion cell complex thickness, visual field (VF) testing, intraocular pressure (IOP), blood pressure and pulse rate in each subject were assessed during each follow-up.

Results: Compared with the baseline, the parafovea VD was higher (50.89 ± 4.26 versus 46.80 ± 5.40, = .044) 1.5 h after administration of nimodipine. After administration of nimodipine for 3 months, the parafovea VD was obviously increased (51.14 ± 5.68 versus 46.80 ± 5.40, = .039), while IOP, systolic blood pressure, mean arterial pressure and mean ocular perfusion pressure were decreased compared to baseline (all < .05). No significant differences were found between the radial peripapillary capillary and disc VD. The parafovea VD was positively correlated with the administration of nimodipine (β = 0.39, = .004), RNFL thickness (β = 0.49, = .022), and VF mean deviation (β = 0.4, = .040) in the multivariate analysis.

Conclusions: Nimodipine effectively increased superficial macular capillary VD, but did not affect peripapillary capillary VD in patients with NTG. This finding indicates that patients with NTG may benefit from the administration of nimodipine.
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http://dx.doi.org/10.1080/02713683.2021.1944645DOI Listing
July 2021

Change of Retinal Vessels in Different Sectors of the Parapapillary Area in Primary Open-Angle Glaucoma.

Front Med (Lausanne) 2021 8;8:705829. Epub 2021 Jul 8.

Department of Ophthalmology and Visual Science, Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai, China.

To investigate the changes in the retinal vessels (RVs) in different sectors in patients with primary open-angle glaucoma (POAG), and their possible correlations with retinal nerve fiber layer thickness (RNFLT) and visual-field defects in the temporal parapapillary region. The RV diameters, RNFLTs, and visual-field parameters were measured. The temporal parapapillary region was divided into the temporal (T, 315°-45°), temporal superior (TS, 45°-90°), and temporal inferior sectors (TI, 270°-315°). The changes in the RV diameters in each sector were determined, and their relationships with RNFLT, the mean deviation (MD), and visual field sensitivity (VFS) were examined. Fifty POAG patients (50 eyes) and 50 healthy subjects (50 eyes) were included. Compared with the healthy subjects, the POAG group had a significantly smaller accumulated parapapillary RV diameter ( < 0.001), which was positively correlated with the MD and RNFLT. When the different temporal sectors were examined, the accumulated RV diameters were significantly smaller in the POAG group than in the healthy controls in the TI and T sectors, but not in the TS sector. The accumulated diameters in the TI and T sectors were correlated with the corresponding RNFLTs (all < 0.05), but only the accumulated diameter in the TI sector was correlated with the VFS. In POAG, the changes in the RVs differed between different temporal sectors, with the most prominent changes occurring in the TI and T sectors.
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http://dx.doi.org/10.3389/fmed.2021.705829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295556PMC
July 2021

Clinical characteristics of optic neuritis phenotypes in a 3-year follow-up Chinese cohort.

Sci Rep 2021 Jul 16;11(1):14603. Epub 2021 Jul 16.

Department of Ophthalmology, Eye Ear Nose and Throat Hospital of Fudan University, 83 Fenyang Road, Shanghai, 200031, China.

To evaluate the clinical characteristics of optic neuritis (ON) with different phenotypes. This prospective study recruited patients with new-onset ON between January 2015 and March 2017 who were followed-up for 3 years. They were divided into the myelin oligodendrocyte glycoprotein-seropositive (MOG-ON), aquaporin-4-seropositive (AQP4-ON), and double-seronegative (seronegative-ON) groups, and their clinical characteristics and imaging findings were evaluated and compared. Two-hundred-eighty patients (405 eyes) were included (MOG-ON: n = 57, 20.4%; AQP4-ON: n = 98, 35.0%; seronegative-ON: n = 125, 44.6%). The proportion of eyes with best-corrected visual acuity > 20/25 at the 3-year follow-up was similar between the MOG-ON and seronegative-ON groups; the proportion in both groups was higher than that in the AQP4-ON group (p < 0.001). Relapse rates were higher in the MOG-ON and AQP4-ON groups than in the seronegative-ON group (p < 0.001). Average retinal nerve fiber layer (RNFL) thickness at 3 years was similar between the MOG-ON and AQP4-ON groups (63.41 ± 13.39 and 59.40 ± 11.46 μm, p = 0.476) but both were thinner than the seronegative-ON group (74.06 ± 11.14 μm, p < 0.001). Macular ganglion cell-inner plexiform layer (GCIPL) revealed the same pattern. Despite RNFL and GCIPL thinning, the MOG-ON group's outcome was as favorable as that of the seronegative-ON group, whereas the AQP4-ON group showed unsatisfactory results.
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http://dx.doi.org/10.1038/s41598-021-93976-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285465PMC
July 2021

Role of amyloid β-peptide in the pathogenesis of age-related macular degeneration.

BMJ Open Ophthalmol 2021 29;6(1):e000774. Epub 2021 Jun 29.

Shenzhen Eye Hospital, Shenzhen, Guangdong, China.

Age-related macular degeneration (AMD) is the most common eye disease in elderly patients, which could lead to irreversible vision loss and blindness. Increasing evidence indicates that amyloid β-peptide (Aβ) might be associated with the pathogenesis of AMD. In this review, we would like to summarise the current findings in this field. The literature search was done from 1995 to Feb, 2021 with following keywords, 'Amyloid β-peptide and age-related macular degeneration', 'Inflammation and age-related macular degeneration', 'Angiogenesis and age-related macular degeneration', 'Actin cytoskeleton and amyloid β-peptide', 'Mitochondrial dysfunction and amyloid β-peptide', 'Ribosomal dysregulation and amyloid β-peptide' using search engines Pubmed, Google Scholar and Web of Science. Aβ congregates in subretinal drusen of patients with AMD and participates in the pathogenesis of AMD through enhancing inflammatory activity, inducing mitochondrial dysfunction, altering ribosomal function, regulating the lysosomal pathway, affecting RNA splicing, modulating angiogenesis and modifying cell structure in AMD. The methods targeting Aβ are shown to inhibit inflammatory signalling pathway and restore the function of retinal pigment epithelium cells and photoreceptor cells in the subretinal region. Targeting Aβ may provide a novel therapeutic strategy for AMD.
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http://dx.doi.org/10.1136/bmjophth-2021-000774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245440PMC
June 2021

Correction to: Etiologies and clinical characteristics of young patients with angle-closure glaucoma: a 15-year single-center retrospective study.

Graefes Arch Clin Exp Ophthalmol 2021 Aug;259(8):2389-2390

Department of Ophthalmology & Visual Science, Eye & ENT Hospital, Shanghai Medical College, Fudan University, 83 Fenyang Road, Shanghai, 200031, China.

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http://dx.doi.org/10.1007/s00417-021-05260-7DOI Listing
August 2021

A Novel Hierarchical Deep Learning Framework for Diagnosing Multiple Visual Impairment Diseases in the Clinical Environment.

Front Med (Lausanne) 2021 7;8:654696. Epub 2021 Jun 7.

Complete Genomics Inc., San Jose, CA, United States.

Early detection and treatment of visual impairment diseases are critical and integral to combating avoidable blindness. To enable this, artificial intelligence-based disease identification approaches are vital for visual impairment diseases, especially for people living in areas with a few ophthalmologists. In this study, we demonstrated the identification of a large variety of visual impairment diseases using a coarse-to-fine approach. We designed a hierarchical deep learning network, which is composed of a family of multi-task & multi-label learning classifiers representing different levels of eye diseases derived from a predefined hierarchical eye disease taxonomy. A multi-level disease-guided loss function was proposed to learn the fine-grained variability of eye disease features. The proposed framework was trained for both ocular surface and retinal images, independently. The training dataset comprised 7,100 clinical images from 1,600 patients with 100 diseases. To show the feasibility of the proposed framework, we demonstrated eye disease identification on the first two levels of the eye disease taxonomy, namely 7 ocular diseases with 4 ocular surface diseases and 3 retinal fundus diseases in level 1 and 17 subclasses with 9 ocular surface diseases and 8 retinal fundus diseases in level 2. The proposed framework is flexible and extensible, which can be inherently trained on more levels with sufficient training data for each subtype diseases (e.g., the 17 classes of level 2 include 100 subtype diseases defined as level 3 diseases). The performance of the proposed framework was evaluated against 40 board-certified ophthalmologists on clinical cases with various visual impairment diseases and showed that the proposed framework had high sensitivity and specificity with the area under the receiver operating characteristic curve ranging from 0.743 to 0.989 in identifying all identified major causes of blindness. Further assessment of 4,670 cases in a tertiary eye center also demonstrated that the proposed framework achieved a high identification accuracy rate for different visual impairment diseases compared with that of human graders in a clinical setting. The proposed hierarchical deep learning framework would improve clinical practice in ophthalmology and broaden the scope of service available, especially for people living in areas with a few ophthalmologists.
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http://dx.doi.org/10.3389/fmed.2021.654696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215208PMC
June 2021

Automatic Anterior Chamber Angle Classification Using Deep Learning System and Anterior Segment Optical Coherence Tomography Images.

Transl Vis Sci Technol 2021 05;10(6):19

Eye Institute and Department of Ophthalmology, Eye and ENT Hospital, Fudan University, Shanghai, China.

Purpose: The purpose of this study was to develop a software package for the automatic classification of anterior chamber angle using anterior segment optical coherence tomography (AS-OCT).

Methods: AS-OCT images were collected from subjects with open, narrow, and closure anterior chamber angles, which were graded based on ultrasound biomicroscopy (UBM) results. The Inception version 3 network and the transfer learning technique were applied in the design of an algorithm for anterior chamber angle classification. The classification performance was evaluated by fivefold cross-validation and on an independent test dataset.

Results: The proposed algorithm reached a sensitivity of 0.999 and specificity of 1.000 in the judgment of closed and nonclosed angles. The overall classification of the proposed method in open angle, narrow angle, and angle-closure classifications reached a sensitivity of 0.989 and specificity of 0.995. Additionally, the sensitivity and specificity reached 1.000 and 1.000 for angle-closure, 0.983 and 0.993 for narrow angle, and 0.985 and 0.991 for open angle.

Conclusions: The experimental results showed that the proposed method can achieve a high accuracy of anterior chamber angle classification using AS-OCT images, and could be of value in future practice.

Translational Relevance: The proposed deep learning-based method that automate the classification of anterior chamber angle can facilitate clinical assessment of glaucoma.
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http://dx.doi.org/10.1167/tvst.10.6.19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142723PMC
May 2021

Measurement of Iris Thickness at Different Regions in Healthy Chinese Adults.

J Ophthalmol 2021 11;2021:2653564. Epub 2021 May 11.

Department of Ophthalmology and Vision Science, Eye and ENT Hospital, Fudan University, Shanghai 200031, China.

Purpose: To study the variation of iris thicknesses in different regions and explore the possible correlations with age and gender.

Methods: Healthy Chinese adults were recruited; the anterior segment of their eyes was imaged by swept-source optical coherence tomography (SS-OCT). The horizontal scan of the right eye was selected, and the thicknesses of both the nasal and temporal irises were measured at 199 evenly spaced points.

Results: A total of 233 subjects with an average age of 36.79 ± 10.04 years (range 19 to 62) were included in the final analysis. The mean iris thicknesses of the temporal and nasal sides were 364.79 ± 47.58 m and 372.44 ± 43.75 m, respectively. The mean nasal iris thickness was positively correlated with age ( = 0.9 m/year;  = 0.002), but the temporal one was not ( = 0.077 m/year;  = 0.806). At 139 points of the nasal iris and 146 points of the temporal iris, the iris thickness was significantly correlated with age ( < 0.05). The thicknesses of the peripheral and pupillary parts were positively correlated with age, while the middle part was negatively correlated with age. No significant difference was observed in the mean iris thickness between genders (temporal:  = 1.597,  = 0.112; nasal:  = 1.870,  = 0.063), but females had a thicker iris than males at 50 points in the temporal side and 49 points in the nasal side ( < 0.05); no point in males was observed to have thicker iris compared to females.

Conclusion: Using SS-OCT and the novel method, thicknesses of the iris at different regions were measured. The thicknesses of the peripheral and pupillary irises increase with age, while the thicknesses of the middle part decrease.
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http://dx.doi.org/10.1155/2021/2653564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131156PMC
May 2021

Agreement of Optic Nerve Head Evaluation of Primary Open-Angle Glaucoma Between General Ophthalmologists and Glaucoma Specialists.

Risk Manag Healthc Policy 2021 6;14:1815-1822. Epub 2021 May 6.

Department of Ophthalmology and Vision Science, Eye and ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.

Purpose: To investigate the agreement of optic nerve head evaluations and initial diagnoses of primary open-angle glaucoma (POAG) by general ophthalmologists and glaucoma specialists in Shanghai, China.

Methods: This multicenter, cross-sectional study involved the outpatients from the general ophthalmology departments of four top eye hospitals in Shanghai. The participants underwent ocular examinations, including intraocular pressure, fundus photography, corneal thickness, refractometry, visual acuity, visual field and gonioscopy. General ophthalmologists and glaucoma specialists performed the diagnoses and classified them as non-glaucoma, POAG suspects, and POAG. The consistency of initial diagnosis between general ophthalmologists and glaucoma specialists was measured using the weighted kappa coefficient. Logistic regression analysis was used to detect the risk factors for the reliability of POAG diagnosis.

Results: In 922 participants, the initial diagnosis rates of POAG and non-glaucoma were much higher in the glaucoma specialist group than in the general ophthalmologist group, while the initial diagnosis rates of POAG suspects were higher in the general ophthalmologist group. The weighted kappa coefficient between the two groups was 0.831±0.027 (95% confidence interval, 0.779-0.884). Logistic regression analysis of the risk factors for the reliability of POAG diagnosis showed that the independent risk factors were intraocular pressure (OR 8.363, 95% CI: 4.27-16.37) and vertical cup-to-disc ratio (OR 3.459, 95% CI: 1.54-7.76).

Conclusion: The diagnosis consistency between the general ophthalmologists and the glaucoma specialists was similar among outpatients in the area of Shanghai. However, general ophthalmologists tended to classify the indefinite subjects as POAG suspects, and their accuracy in diagnosing POAG was low. By paying more attention to the risk factors of POAG diagnosis, general ophthalmologists could improve the diagnosis accuracy.
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http://dx.doi.org/10.2147/RMHP.S307527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110282PMC
May 2021

Metabolomic Profiling of Aqueous Humor and Plasma in Primary Open Angle Glaucoma Patients Points Towards Novel Diagnostic and Therapeutic Strategy.

Front Pharmacol 2021 14;12:621146. Epub 2021 Apr 14.

Department of Ophthalmology and Visual Science, Eye and ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China.

Glaucoma is the second leading cause of blindness globally characterized by progressive loss of retinal ganglion cells (RGCs) and irreversible visual deficiency. As the most common type of glaucoma, primary open angle glaucoma (POAG) is currently an unmet medical need with limited therapy by lowering intraocular pressure (IOP). However, some patients continue to progress even though their IOP are controlled. Although early diagnosis and prompt treatment are crucial in preventing irreversible visual impairment, there are currently no biomarkers for screening POAG. Metabolomics has the advantages of illustrating the final downstream products of the genome and establishing the closest link to the phenotype. So far, there is no study investigating the metabolomic profiles in both aqueous humor and plasma of POAG patients. Therefore, to explore diagnostic biomarkers, unveil underlying pathophysiology and potential therapeutic strategies, a widely targeted metabolomic approach was applied using ultrahigh-resolution mass spectrometry with C18 liquid chromatography to characterize the metabolomic profiles in both aqueous humor and plasma of 28 POAG patients and 25 controls in our study. Partial least squares-discriminant analysis (PLS-DA) was performed to determine differentially expressed metabolites (DEMs) between POAG and age-matched controls. The area under the receiver operating characteristic curve (AUC) was calculated to assess the prediction accuracy of the DEMs. The correlation of DEMs with the clinical parameters was determined by Pearson correlation, and the metabolic pathways were analyzed using MetaboAnalyst 4.0. PLS-DA significantly separated POAG from controls with 22 DEMs in the aqueous humor and 11 DEMs in the plasma. Additionally, univariate ROC analysis and correlation analysis with clinical parameters revealed cyclic AMP (AUC = 0.87), 2-methylbenzoic acid (AUC = 0.75), 3'-sialyllactose (AUC = 0.73) in the aqueous humor and N-lac-phe (AUC = 0.76) in the plasma as potential biomarkers for POAG. Moreover, the metabolic profiles pointed towards the alteration in the purine metabolism pathway. In conclusion, the study identified potential and novel biomarkers for POAG by crosslinking the metabolomic profiles in aqueous humor and plasma and correlating with the clinical parameters. These findings have important clinical implications given that no biomarkers are currently available for glaucoma in the clinic, and the study provided new insights in exploring diagnostic biomarkers and potential therapeutic strategies of POAG by targeting metabolic pathways.
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http://dx.doi.org/10.3389/fphar.2021.621146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080440PMC
April 2021

24-h intraocular pressure patterns measured by Icare PRO rebound in habitual position of open-angle glaucoma eyes.

Graefes Arch Clin Exp Ophthalmol 2021 Aug 29;259(8):2327-2335. Epub 2021 Apr 29.

Department of Ophthalmology, Shanghai Jing'an District Bei Zhan Hospital, Shanghai, 200070, China.

Purpose: To measure the 24-h intraocular pressure (IOP) by Icare PRO rebound in healthy and primary open-angle glaucoma (POAG) eyes and compare it with non-contact tonometry (NCT).

Methods: Thirty POAG patients, who were under IOP-lowering treatment, and 30 healthy subjects were included. Participants were hospitalized overnight for the 24-h IOP measurement. IOPs were measured by Icare PRO and NCT according to a standard protocol every 2 h during 24 h. The 24-h IOP curve and IOP-related parameters were compared between Icare PRO and NCT groups in POAG and healthy eyes.

Results: The IOPs measured by Icare PRO in habitual position increased notably at 22:00 in the normal group and at 20:00 in the POAG group, reached peak at 0:00, stayed high until 4:00, and then decreased in both groups (all p < 0.05). The POAG patients had higher mean 24-h IOP, peak IOP, IOP fluctuation, and greater IOP change from supine to sitting position in the nocturnal period than those in the normal subjects even after adjusting for eyes, age, gender, CCT, and axial length (all p < 0.05).

Conclusions: The Icare PRO provides a well-tolerated approach for 24-h IOP monitoring in habitual position. Twenty-four-hour IOP in habitual position is more sensitive for detecting high nocturnal IOP peaks and greater IOP fluctuation for POAG patients.
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http://dx.doi.org/10.1007/s00417-021-05192-2DOI Listing
August 2021

Correction: A miRNA stabilizing polydopamine nano-platform for intraocular delivery of miR-21-5p in glaucoma therapy.

J Mater Chem B 2021 Apr;9(16):3595

Department of Ophthalmology & Visual Science, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai 200031, China and NHC Key Laboratory of Myopia, Chinese Academy of Medical Sciences, and Shanghai Key Laboratory of Visual Impairment and Restoration (Fudan University), Shanghai 200031, China.

Correction for 'A miRNA stabilizing polydopamine nano-platform for intraocular delivery of miR-21-5p in glaucoma therapy' by Chen Tan et al., J. Mater. Chem. B, 2021, DOI: 10.1039/d0tb02881a.
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http://dx.doi.org/10.1039/d1tb90052hDOI Listing
April 2021

A miRNA stabilizing polydopamine nano-platform for intraocular delivery of miR-21-5p in glaucoma therapy.

J Mater Chem B 2021 04 30;9(15):3335-3345. Epub 2021 Mar 30.

Department of Ophthalmology & Visual Science, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai 200031, China.

The elevation of intraocular pressure (IOP) is an important risk factor in the development of primary open angle glaucoma (POAG), which is the main cause of irreversible vision loss. miRNAs are promising new anti-glaucoma therapeutic agents. However, the low stability and cellular transfection of miRNA in vivo hinder its further application. This study aims to investigate the use of polydopamine-polyethylenimine nanoparticles (PDA/PEI NPs) as miRNA carriers in the treatment of ocular hypertension and glaucoma. The in vitro study proves that the carrier preserves the activity of nucleic acid for a long period. Besides, it has comparable transfection efficiency with commercially available vehicles, while having lower cytotoxicity. It has been demonstrated in the animal model that PDA/PEI NPs successfully reach the target tissues without an obvious inflammatory response. PDA/PEI NPs/miR-21-5p increases the permeability of porcine angular aqueous plexus cells, thereby reducing IOP by facilitating the conventional outflow pathway at least partially through the pathway involving endothelial nitric oxide synthase. Our results indicate that PDA/PEI NPs/miR-21-5p is a promising anti-glaucoma drug for treating POAG. And the delivery strategy may be extended to other gene therapy in treating intraocular diseases.
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http://dx.doi.org/10.1039/d0tb02881aDOI Listing
April 2021

Etiologies and clinical characteristics of young patients with angle-closure glaucoma: a 15-year single-center retrospective study.

Graefes Arch Clin Exp Ophthalmol 2021 Aug 19;259(8):2379-2387. Epub 2021 Apr 19.

Department of Ophthalmology & Visual Science, Eye & ENT Hospital, Shanghai Medical College, Fudan University, 83 Fenyang Road, Shanghai, 200031, China.

Purpose: To investigate the etiologies and the clinical characteristics of angle-closure glaucoma (ACG) patients younger than 40 years old in Chinese.

Methods: Inpatients with diagnosis of ACG and diagnosed age younger than or equal to 40 years old, who were admitted in Eye, Ear, Nose, and Throat Hospital Fudan University from 2002 to 2017, were included in this retrospective non-comparative case series. The underlying causes and clinical features for all the patients were analyzed by comprehensive review of medical charts.

Results: A total of 298 patients (463 eyes) met the criteria, including 153 females (51.3%) and 145 males (48.7%); the mean age was 25.6 ± 13.0 years. Primary angle-closure glaucoma (PACG), uveitis, and anterior segment dysgenesis (ASD) were the top three etiologies in our patients, which accounted for 32.6%, 20.3%, and 15.1% of the total patients respectively. PACG mainly occurs after 30 years of age and ASD is the top reason of ACG in patients younger than 20 years old. Other known etiologies include iridocorneal endothelial syndrome, neovascular glaucoma, nanophthalmos, retinitis pigmentosa, spherophakia, bestrophinopathy, persistent fetal vasculature, iridociliary cysts, congenital retinoschisis, Marfan's syndrome, retinopathy of prematurity, familial exudative vitreoretinopathy, congenital retinal folds, Coat's disease, and neurofibromatosis.

Conclusions: We described the uncommon presentation of ACG in Chinese young patients. Although unusual, most of the etiologies could be identified. Therefore, more careful and comprehensive examinations are needed for early detection and timely treatment for young ACG patients.
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http://dx.doi.org/10.1007/s00417-021-05172-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8352827PMC
August 2021

Polymorphisms of the cytomegalovirus glycoprotein B genotype in patients with Posner-Schlossman syndrome.

Br J Ophthalmol 2021 Mar 22. Epub 2021 Mar 22.

Department of Ophthalmology and Vision Science, Eye & ENT Hospital, Fudan University, Shanghai, China.

Aims: The aim of this observational study was to report the distribution of glycoprotein B (gB) genotypes in the eyes of cytomegalovirus (CMV) positive patients with Posner-Schlossman syndrome (PSS), and to investigate their clinical characteristics and outcomes.

Methods: We collected aqueous humour samples from 165 patients clinically diagnosed with PSS between 2017 and 2019. PCR was performed to analyse the CMV DNA and identify the gB genotypes in the samples. Clinical characteristics and responses to antiviral treatment were compared among patients with different gB genotypes.

Results: CMV DNA was detected in 94 (56.97%) of the 165 aqueous humour specimens analysed. Owing to the quantity requirement for CMV gB genotype analysis, results could be obtained from only 14 specimens. CMV gB type 1 was detected in 11 samples (78.6%), whereas CMV gB type 3 was detected in three samples (21.4%). No other gB genotypes or mixed genotypes were detected. Overall, 9.1% (1/11) of the patients in the gB type 1 group and 66.7% (2/3) of the patients in the gB type 3 group had bilateral attacks (p=0.093). The concentration of anti-CMV immunoglobulin G (IgG) in the type 1 group was 0.94±0.79 s/co (ratio of aqueous humour CMV IgG/serum CMV IgG to aqueous humour albumin concentration/serum albumin concentration), whereas that in the type 3 group was 0.67±0.71 s/co.

Conclusion: Genotype 1 was the most prevalent genotype in the aqueous humour of CMV-infected patients with PSS. Bilateral attack was predominant among patients with gB genotype 3. CMV gB gene may be related to the pathogenicity of CMV virus strain in patients with PSS.
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http://dx.doi.org/10.1136/bjophthalmol-2020-318284DOI Listing
March 2021

Airborne particulate matter (PM) triggers ocular hypertension and glaucoma through pyroptosis.

Part Fibre Toxicol 2021 03 4;18(1):10. Epub 2021 Mar 4.

Department of Ophthalmology & Visual Science, Eye Institute, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, 200031, China.

Background: Particulate matter (PM) is strongly linked to human health and has detrimental effects on the eye. Studies have, however, focused on the ocular surface, with limited research on the impact of PM on intraocular pressure (IOP).

Methods: To investigate the impact of PM on IOP and the associated mechanism, C57BL/6 mouse eyes were topically exposed to a PM suspension for 3 months, and human trabecular meshwork (HTM) cells were subjected to various PM concentrations in vitro. Cell viability, NLRP3/caspase-1, IL-1β, and GSDMD expression, reactive oxygen species (ROS) production and cell contractility were measured by western blot, ELISA, cell counting kit-8, ROS assay kit or a cell contractility assay. ROS scavenger N-acetyl-L-cysteine (NAC) and caspase-1 inhibitor VX-765 were used to intervene in PM-induced damages.

Results: The results revealed that the IOP increased gradually after PM exposure, and upregulations of the NLRP3 inflammasome, caspase-1, IL-1β, and GSDMD protein levels were observed in outflow tissues. PM exposure decreased HTM cell viability and affected contraction. Furthermore, elevated ROS levels were observed as well as an activation of the NLRP3 inflammasome and downstream inflammatory factors caspase-1 and IL-1β. NAC improved HTM cell viability, inhibited the activation of the NLRP3 inflammasome axis, and HTM cell contraction by scavenging ROS. VX-765 showed similar protection against the PM induced adverse effects.

Conclusion: This study provides novel evidence that PM has a direct toxic effect on intraocular tissues and may contribute to the initiation and development of ocular hypertension and glaucoma. This occurs as a result of increased oxidative stress and the subsequent induction of NLRP3 inflammasome mediated pyroptosis in trabecular meshwork cells.
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http://dx.doi.org/10.1186/s12989-021-00403-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934500PMC
March 2021

Feasibility of microscope-integrated swept-source optical coherence tomography in canaloplasty.

Ann Transl Med 2020 Dec;8(23):1577

Department of Ophthalmology and Visual Science, Eye, Ear, Nose and Throat Hospital, Shanghai Medical College of Fudan University, Shanghai, China.

Background: Several researchers have used commercial microscope-integrated optical coherence tomography (OCT) systems in glaucoma surgery, including trabeculectomy and canaloplasty. However, the 840 nm wavelength light source of the OCT systems is not ideal for imaging the anterior chamber angle structures because of its limited penetration. We evaluated the potential value of a microscope-integrated swept-source OCT system with a 1,310 nm center-wavelength light in canaloplasty for glaucoma.

Methods: Sixteen porcine eyes were used to simulate canaloplasty. The critical surgical steps were monitored using a prototype microscope-integrated OCT system with a 1,310 nm light source and a high axial scan rate of 100 kHz. The images from swept-source OCT and three-dimensional images from the microscope were projected simultaneously onto a liquid crystal display three-dimensional monitor (LMD-4251TD, Sony, Japan). The changes in the collector vessel (aqueous drainage structure in the porcine eye, similar to Schlemm's canal in humans) were measured using Image J software. Histological sections stained with hematoxylin and eosin were used to assess surgical efficacy.

Results: High-resolution real-time images of the anterior segment were acquired during canaloplasty using the microscope-integrated OCT system. With the real-time OCT images, the position of the collector vessel was identified and the scleral flap could be created at the ideal location. The expansion of the collector vessel after viscoelastic injection was also visualized in real time. Compared with baseline, there was a significant increase in the cross-sectional area (from 14,502.98±9,242.55 to 59,499.04±20,506.41 µm, P<0.001) of the collector vessel.

Conclusions: Using the microscope-integrated OCT system, real-time images of the anterior segment were successfully acquired during the operation. The microscope-integrated OCT system might be useful in future anti-glaucoma surgery.
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http://dx.doi.org/10.21037/atm-20-3469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791249PMC
December 2020

Nicotinamide ameliorates energy deficiency and improves retinal function in Cav-1 mice.

J Neurochem 2021 05 30;157(3):550-560. Epub 2020 Dec 30.

Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China.

Caveolin-1(Cav-1) is involved in lipid metabolism and energy homeostasis, which is important for the energetically demanding retina. Although retinal function deficits were noted in Cav-1 knockout (Cav-1 ) mice, the underlying causes remain largely unknown. Here, we investigate if the disruption in energy homeostasis presents a potential mechanism for retinal function deficits in Cav-1 retina and if it can be ameliorated by nicotinamide (NAM). In this study, NAM was administrated orally for 2 weeks in Cav-1 mice before experiments. Oxidative lipidomics was conducted to detect the oxylipin changes, the retinal energy flux was measured by seahorse assay, and the retinal function was assessed by electroretinogram (ERG). Cav-1 deficiency induced the dysregulation of oxidative lipidomics and reduction in energy consumption/production in the retina by decreasing Na /K -ATPase, oxidative phosphorylation CII, cytochrome c, and oxygen consumption rate (OCR). A decrease in Sirt1 was also detected. Therapeutic administration of NAM significantly increased Sirt1 expression and improved energy deficiency by increasing Na /K -ATPase, cytochrome c, and OCR. The dysregulation of oxidative lipidomics was partially recovered, and the retinal function was improved as assessed by ERG compared to Cav-1 mice. Our study demonstrated the dysregulation of oxidative lipidomics in Cav-1 retina and established a link between energy deficiency and retinal function deficits in Cav-1 mice. Administration of NAM ameliorated energy deficiency, increased the expression of Sirt1, and improved retinal function, which presents a potential therapeutic strategy for Cav-1 deficiency-induced retinal function deficits.
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http://dx.doi.org/10.1111/jnc.15266DOI Listing
May 2021

Therapeutic Targeting of Retinal Immune Microenvironment With CSF-1 Receptor Antibody Promotes Visual Function Recovery After Ischemic Optic Neuropathy.

Front Immunol 2020 13;11:585918. Epub 2020 Nov 13.

Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, United States.

Retinal ischemia/reperfusion injury (RI) is a common cause of irreversible visual impairment and blindness in elderly and critical unmet medical need. While no effective treatment is available for RI, microglial activation and local immune responses in the retina are thought to play important roles in the pathophysiology of neurodegeneration. While survival and activation of microglia depend critically on colony-stimulating factor receptor (CSF-1R) signaling, it remains unclear if targeting the retinal immune microenvironments by CSF-1RAb after RI is sufficient to rescue vision and present a potentially effective therapy. Here we used rodent models of RI and showed that retinal ischemia induced by acute elevation of intraocular pressure triggered an early activation of microglia and macrophages in the retina within 12 h. This was followed by lymphocyte infiltration and increased production of pro-inflammatory cytokines. Intravitreal injection of CSF-1R neutralizing antibody (CSF-1RAb) after RI significantly blocked microglial activation and the subsequent T cell recruitment. This also led to improved retinal ganglion cell survival and function measured by cell quantification and electroretinogram positive scotopic threshold responses, as well as increased visual acuity and contrast sensitivity as assessed by optomotor reflex-based assays, when compared to the isotype-treated control group. Moreover, the administration of CSF-1RAb efficiently attenuated inflammatory responses and activation of human microglia in culture, suggesting a therapeutic target with human relevance. These results, together with the existing clinical safety profiles, support that CSF-1RAb may present a promising therapeutic avenue for RI, a currently untreatable condition, by targeting microglia and the immune microenvironment in the retina to facilitate neural survival and visual function recovery.
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http://dx.doi.org/10.3389/fimmu.2020.585918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691249PMC
June 2021

Association of 24-Hour Intraocular Pressure Fluctuation With Corneal Hysteresis and Axial Length in Untreated Chinese Primary Open-Angle Glaucoma Patients.

Transl Vis Sci Technol 2020 11 19;9(12):25. Epub 2020 Nov 19.

Department of Ophthalmology and Visual Science, Eye and Ear Nose Throat Hospital, Shanghai Medical College, Fudan University, Shanghai, China.

Purpose: The purpose of this study was to evaluate the association of 24-hour intraocular pressure (IOP) fluctuation with corneal biomechanics and ocular biometric parameters in Chinese patients with primary open angle glaucoma (POAG) before initial treatment.

Methods: Forty-nine Chinese patients with POAG (98 eyes) were recruited in this study before start of any POAG treatment. The 24-hour IOP was measured with a 2-hour interval by a noncontact tonometer. Corneal biomechanical properties and biometric parameters were measured once during 8 AM to 6 PM before 24-hour IOP measurement.

Results: The 24-hour IOP fluctuation was defined as the differences between the peak and trough IOP measurement and was significantly associated with axial length (AL) in the multivariate analysis. The POAG subjects with AL ≤ 26 mm had significantly larger 24-hour IOP fluctuation but lower corneal hysteresis, compared to those with AL > 26 mm. In addition, subgroup analysis showed that high tension glaucoma subjects had larger 24-hour IOP fluctuation and higher corneal resistance factor than patients with normal tension glaucoma.

Conclusions: This study revealed the association of 24-hour IOP fluctuation with office hour corneal biomechanical properties and AL in patients with POAG. Their contributions to IOP fluctuation should be considered in the risk analysis of glaucoma development and progression.

Translational Relevance: Ocular biometric parameters are related with 24-hour IOP fluctuation in patients with POAG, which is potentially helpful in explaining different progression patterns in different types of patients.
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http://dx.doi.org/10.1167/tvst.9.12.25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683862PMC
November 2020

Consistency between optical coherence tomography and humphrey visual field for evaluating glaucomatous defects in high myopic eyes.

BMC Ophthalmol 2020 Nov 20;20(1):460. Epub 2020 Nov 20.

Department of Ophthalmology & Visual Science, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China.

Background: The study is to investigate the influence of high myopia on the consistency between optical coherence tomography (OCT) and visual field in primary open-angle glaucoma (POAG).

Methods: We enrolled 37 patients with POAG with high myopia (POAG-HM group), 27 patients with POAG without high myopia (POAG group), and 29 controls with high myopia (HM group). All subjects underwent Humphrey perimetry (30-2 and 10-2 algorithms). The peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell-inner plexiform layer (GCIPL) thicknesses were measured using Cirrus HD-OCT. Spearman's rank correlation analysis was used to determine correlations between OCT and perimetric parameters. Agreement was analyzed by cross-classification and weighted κ statistics.

Results: In POAG group, the cross-classification analysis showed strong agreement between the inferior temporal GCIPL thickness and the mean sensitivity (MS) of 10-2 algorithms (κ = 0.5447, P = 0.0048), and good agreement between the superior and inferior RNFL thicknesses and 30-2 MS (κ = 0.4407 and 0.4815; P < 0.05). In the POAG-HM group, only the inferior temporal GCIPL thickness showed good agreement with 10-2 MS (κ = 0.3155, P = 0.0289) and none of the RNFL sectors were in good agreement with the corresponding MS.

Conclusions: In POAG patients with high myopia, changes in macular measurements were in accordance with visual field defects, and RNFL thickness did not consistently decline with visual field defects due to the effects of high myopia. This study suggests that during diagnosis and follow-up of glaucoma with high myopia, more attention need to be focused on structure and functional defects in macular areas.
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http://dx.doi.org/10.1186/s12886-020-01724-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678135PMC
November 2020

TNFα activates MAPK and Jak-Stat pathways to promote mouse Müller cell proliferation.

Exp Eye Res 2021 01 7;202:108353. Epub 2020 Nov 7.

Department of Ophthalmology & Visual Science, Eye Institute, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai 200031, China; Key Laboratory of Myopia, Chinese Academy of Medical Sciences (Fudan University), and Shanghai Key Laboratory of Visual Impairment and Restoration (Fudan University), Shanghai 200031, China; State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China. Electronic address:

Mouse Müller cells, considered as dormant retinal progenitors, often respond to retinal injury by undergoing reactive gliosis rather than displaying neural regenerative responses. Tumor necrosis factor alpha (TNFα) is a key cytokines induced after injury and implicated in mediating inflammatory and neural regenerative responses in zebrafish. To investigate the involvement of TNFα in mouse retinal injury, adult C57BL/6J mice were subjected to light damage for 14 consecutive days. TNFα was elevated in the retina of mice exposed to light damage, which induced Müller cell proliferation in vitro. Affymetrix microarray showed that, in Müller cells, TNFα induces up-regulation of inflammatory and proliferation-related genes, including NFKB2, leukemia inhibitory factor, interleukin-6, janus kinase (Jak) 1, Jak2, signal transducer and activator of transcription (Stat) 1, Stat2, mitogen-activated protein kinase (MAPK) 7, and MAP4K4 but down-regulation of neuroprogenitor genes, including Sox9, Ascl1, Wnt2 and Hes1. Blocking the Jak/Stat and MAPK pathways attenuated TNFα-induced Müller cell proliferation. These results suggest that TNFα may drive the proliferation and inflammatory response, rather than the neural regenerative potential, of mouse Müller cells.
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http://dx.doi.org/10.1016/j.exer.2020.108353DOI Listing
January 2021

Quantification of Retinal Microvascular Density Using Optic Coherence Tomography Angiography in Primary Angle Closure Disease.

Curr Eye Res 2021 Jul 26;46(7):1018-1024. Epub 2020 Nov 26.

Department of Ophthalmology and Visual Science, Eye, Ear, Nose and Throat Hospital, Shanghai Medical College of Fudan University, Shanghai, China.

: To evaluate the microvascular density of the peripapillary and parafoveal areas of the eyes with primary angle closure disease (PACD) using optical coherence tomography angiography (OCTA).: An observational study was conducted with 76 PACD patients (29 eyes with primary angle closure suspect, 22 eyes with primary angle closure [PAC], and 25 eyes with primary angle closure glaucoma [PACG]) and 27 control eyes. OCTA was performed for all subjects to acquire a 4.5 × 4.5 mm scanning area centered on the optic discs and a 3 × 3 mm parafoveal cubes. Peripapillary and parafoveal vessel density (VD) were compared between these four groups, and the relationship between VD values and structural and functional changes was evaluated.: Among all four groups, the peripapillary VD of the PACG eyes was the lowest in all six sections (all < .01), while the parafoveal VD was lower than that of the normal group only in the average, superior, and inferior areas (all < .05). The PAC group had lower peripapillary VD than the normal group (62.6[55.2-67.4] vs. 66.7[54.7-69.3], = .01), while their retinal nerve fiber layer (RNFL) and ganglion cell complex thickness were not significantly different than those of the control group (all > .05). In addition, the stages of PACD, visual field mean deviation, and RNFL thickness were shown to be predictors of the peripapillary VD in the multiple linear regression analysis.: The PAC eyes had lower peripapillary VD than normal eyes when their RNFL and GCC thickness did not differ. This suggests that a reduction in retinal VD may occur before structural loss in PAC eyes. Retinal VD measurement may be a useful tool for the assessment of PACD.
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http://dx.doi.org/10.1080/02713683.2020.1849728DOI Listing
July 2021

Circular RNA Expression Profiling Identifies Glaucoma-Related Circular RNAs in Various Chronic Ocular Hypertension Rat Models.

Front Genet 2020 7;11:556712. Epub 2020 Oct 7.

Department of Ophthalmology and Visual Science, Eye, Ear, Nose and Throat Hospital, Shanghai Medical College of Fudan University, Shanghai, China.

Circular RNAs are characterized as a class of covalently closed circular RNA transcripts and are associated with a variety of cellular processes and neurological diseases by sponging microRNAs. Expression profiling of circular RNAs in glaucoma, which is a form of optic neuropathy, has not been performed to date. The most common characteristic of all forms of glaucoma is the loss of retinal ganglion cells. While the pathogenesis of glaucoma is not fully understood, intraocular pressure is unquestionably the only proven modifiable factor which makes chronic ocular hypertension (COH) animals the classical glaucoma models. Based on these findings, we completed the first in-depth study of rat retinal circular RNA expression profiling to identify probable biomarkers for the diagnosis of glaucoma. Two ocular hypertension models were induced by episcleral vein ligation (EVL) and microbead injection in rats. Overall, 15,819 circular RNA were detected. Furthermore, 3,502 differentially expressed circular RNAs verified in both COH rats were identified, of which 691 were upregulated and 2,811 were downregulated. Seven significantly downregulated (both logFoldChange < -2.5 and adjusted < 0.001) and seven significantly upregulated (both logFoldChange > 2.5 and adjusted < 0.001) circular RNAs were shown. Six target microRNAs aligned with the top 14 circular RNAs were identified. According to the construction of the circular RNA-microRNA network and circBase information, only RNO_CIRCpedia_1775 had the homologous hsa_circ_0023826 in the human genome. The hsa_circ_0023826 and mRNA of the host gene TENM4 (teneurin transmembrane protein 4) were validated in aqueous humor samples of five glaucoma patients and five cataract control patients. The expression of hsa_circ_0023826 showed a significant decrease in glaucoma patients, while TENM4 mRNA showed no significant difference compared to cataract patients ( = 0.024 and = 0.294, respectively). The results of this study comprehensively characterized the expression profiles of circular RNA in glaucoma-affected eyes, as verified by two different ocular hypertension rat models. Together with the target microRNAs underlying the top differentially expressed circular RNAs, a new target of hsa_circ_0023826 and its host gene TENM4 were identified and further verified in the aqueous humor of glaucoma patients, indicating a promising biomarker for the disease.
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http://dx.doi.org/10.3389/fgene.2020.556712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575816PMC
October 2020

The evaluation of juvenile ocular hypertension by optical coherence tomography angiography.

BMC Ophthalmol 2020 Oct 21;20(1):423. Epub 2020 Oct 21.

Department of Ophthalmology & Visual Science, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Fenyang Road. 83, Shanghai, 200031, China.

Background: Vessel density (VD) of the elderly ocular hypertension patients measured by optical coherence tomography angiography (OCTA) have been reported. However, the studies of VD in juvenile ocular hypertension (JOHT) are limited. We wished to evaluate VD changes using OCTA in JOHT. We also investigated the potential risk parameters of intraocular pressure (IOP) and vertical cup/disc ratio (CDR) with OCTA for observing the development of JOHT.

Methods: We examined 86 eyes in 45 control (Ctrl) subjects and 65 eyes in 34 patients with JOHT using OCTA at the glaucoma clinic of the Eye, Ear, Nose, and Throat Hospital of Fudan University. The VD of radial peripapillary capillaries (RPC) and the perifoveal superficial vascular plexus (SVP) was compared between the Ctrl and JOHT groups. Other basic study factors such as age, sex, blood pressure, best-corrected visual acuity, central corneal thickness, IOP, CDR, the thickness of the retinal nerve fiber layer, ganglion cell complex, visual field mean deviation, and pattern standard deviation were also recorded.

Results: Bare difference was found in the nasal-inferior and temporal RPC-VD between the Ctrl and JOHT groups (P = 0.042 and P = 0.033, respectively) while SVP-VD was not (all P > 0.05). In the mixed linear regression model analysis, temporal RPC-VD was marginally negatively associated with high IOP (r = - 1.379, P = 0.043). Five additional sections of nasal, inferior-nasal, inferior-temporal, superior-temporal, and superior-nasal RPC-VD showed positive correlation with large CDR (all P <  0.05). SVP-VD in the superior and nasal regions was marginally negatively correlated with high IOP (r = - 1.877, P = 0.023; r = - 1.693, P = 0.049). No other regions were found statistical different of relationship between IOP, CDR and VD.

Conclusions: Nasal-inferior and temporal peripapillary VD was marginally lower in JOHT subjects. Regarding parameters of IOP and CDR, peripapillary temporal VD had a borderline level of negative correlation with IOP more than 21 mmHg while additional five regions were strongly positively correlated with large CDR. Some macular regions only found marginal positive correlation with parameter of high IOP. We conclude that OCTA can be used as a potential technique to evaluate the VD in JOHT and peripapillary scans should be analyzed individually based on different levels of CDR.
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http://dx.doi.org/10.1186/s12886-020-01641-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576766PMC
October 2020
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