Proteomic analysis of aqueous humor reveals novel regulators of diabetic macular edema.

Diabetic macular edema (DME) is the most common cause of blindness in patients with diabetic retinopathy. To investigate the proteomic profiles of the aqueous humor (AH) of individuals with diabetic macular edema (DME), AH samples were collected from patients with non-diabetes mellitus (NDM), DM, nonproliferative diabetic retinopathy (NPDR), and DME. We performed comparative proteomic analyses using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and bioinformatics analyses. We identified 425 proteins in these AH samples, of which 113 showed changes in expression in DME compared with NDM, 95 showed changes in expression in DME vs. DM, and 84 showed changes in expression in DME compared with NPDR. The bioinformatics analysis suggested that DME is closely associated with platelet degranulation, oxidative stress-related pathway, and vascular-related pathways. Upregulation of haptoglobin (HP) and downregulation of fibrillin 1 (FBN1) were validated by ELISA. Receiver operating characteristic (ROC) analysis showed that HP and FBN1 could distinguish DME from NPDR with areas under the curve of 0.987 (p = 0.00608) and 0.791 (p = 0.00629), respectively. The findings provide potential clues for further analysis of the molecular mechanisms and the development of new treatments for DME. HP and FBN1 may be potential key proteins and therapeutic targets in human DME. The proteomics dataset generated has been deposited to the ProteomeXchange/iProX Consortium with Identifier: PXD033404/IPX0004353001.

Deep learning-based postoperative visual acuity prediction in idiopathic epiretinal membrane.

BACKGROUND: To develop a deep learning (DL) model based on preoperative optical coherence tomography (OCT) training to automatically predict the 6-month postoperative visual outcomes in patients with idiopathic epiretinal membrane (iERM). METHODS: In this retrospective cohort study, a total of 442 eyes (5304 images in total) were enrolled for the development of the DL and multimodal deep fusion network (MDFN) models. All eyes were randomized into a training dataset with 265 eyes (60.0%), a validation dataset with 89 eyes (20.1%), and an internal testing dataset with the remaining 88 eyes (19.9%). The input variables for prediction consisted of macular OCT images and diverse clinical data. Inception-Resnet-v2 network was utilized to estimate the 6-month postoperative best-corrected visual acuity (BCVA). Concurrently, a regression model was developed using the clinical data and OCT parameters in the training data set for predicting postoperative BCVA. The reliability of the models was subsequently evaluated using the testing dataset. RESULTS: The prediction DL algorithm exhibited a mean absolute error (MAE) of 0.070 logMAR and root mean square error (RMSE) of 0.11 logMAR in the testing dataset. The DL model demonstrated a robust promising performance with R2 = 0.80, notably superior to R2 = 0.49 of the regression model. The percentages of BCVA prediction errors within ± 0.20 logMAR amounted to 94.32% in the testing dataset. CONCLUSIONS: The OCT-based DL model demonstrated sensitivity and accuracy in predicting postoperative BCVA in iERM patients. This innovative DL model exhibits substantial potential for integration into surgical planning protocols.

Low expression of RBP4 in the vitreous humour of patients with proliferative diabetic retinopathy who underwent Conbercept intravitreal injection.

Intravitreal injection of anti-VEGF antibodies has been widely used in the treatment of proliferative diabetic retinopathy (PDR). However, anti-VEGF drugs can exacerbate fibrosis and eventually lead to retinal detachment. To explore proteins closely related to fibrosis, we conducted proteomic analysis of human vitreous humour collected from PDR patients who have or have not intravitreal Conbercept (IVC) injection. Sixteen vitreous humour samples from PDR patients with preoperative IVC and 20 samples from those without preoperative IVC were examined. An immunodepletion kit was used to remove high-abundance vitreous proteins. Conbercept-induced changes were determined using a tandem mass tag-based quantitative proteomic strategy. Enzyme-linked immunosorbent assays were performed to confirm the concentrations of selected proteins and validate the proteomic results. Based on a false discovery rate between 0.05% and -0.05% and a fold-change > 1.5, 97 proteins were altered (49 higher levels and 48 lower levels) in response to IVC. Differentially expressed proteins were found in the extracellular and intracellular regions and were found to be involved in VEGF binding and VEGF-activated receptor activity. Protein-protein interactions indicated associations with fibrosis, neovascularisation and inflammatory signalling pathways. We found the low levels of RBP4 in the vitreous humour of PDR patients with IVC injection, as revealed by ELISA and proteomic profiling. Moreover, RBP4 significantly restored the mitochondrial function of HRMECs induced by AGEs and down regulated the level of glycolysis. Our study is the first to report that RBP4 decreases in the vitreous humour of PDR patients who underwent Conbercept treatment, thereby verifying the role of RBP4 in glucose metabolism. Results provide evidence for the potential mechanism underlying Conbercept-related fibrosis.

Effects of mesenchymal stem cells and their exosomes on the healing of large and refractory macular holes.

PURPOSE: To assess the efficacy of mesenchymal stem cells (MSCs) and MSC-derived exosomes (MSC-Exos) to promote the healing of large and refractory macular holes (MHs). METHODS: Seven patients (age 51-75 years old) with large and long-standing idiopathic MHs underwent vitrectomy, internal limiting membrane peeling, MSC (two patients) or MSC-Exo (five patients) intravitreal injection, and heavy silicon oil, air, 20% SF6, or 14% C3F8 tamponade. The MSCs were isolated from human umbilical cord tissue, and MSC-Exos were isolated from the supernatants of cultured MSCs using sequential ultracentrifugation. RESULTS: Five eyes underwent pars plana vitrectomy (PPV) only, while two underwent PPV combined with cataract surgery. Six MHs were closed, while one remained in a flat-open state. The best-corrected visual acuity (BCVA) was improved in five patients with MH closure and remained unchanged in one patient with MH closure who had a 4-year history of MH. A fibrotic membrane was observed on the surface of the retina in one patient who underwent MSC therapy. One patient who received a higher dose of MSC-Exos exhibited an inflammatory reaction. CONCLUSIONS: MSC and MSC-Exo therapy may promote functional and anatomic recovery from MH. MSC-Exo therapy may be a useful and safe method for improving the visual outcomes after surgery for refractory MHs.

A meta-analysis of the effect of a dexamethasone intravitreal implant versus intravitreal anti-vascular endothelial growth factor treatment for diabetic macular edema.

BACKGROUND: This meta-analysis evaluated the effectiveness and safety of dexamethasone (DEX) implant and intravitreal anti-vascular endothelial growth factor (VEGF) treatment for diabetic macular edema (DME). METHODS: The PubMed, Embase, clinicaltrials.gov website and Cochrane Library databases were comprehensively searched for studies comparing DEX implant with anti-VEGF in patients with DME. Best-corrected visual acuity (BCVA), central subfield thickness (CST) and adverse events were extracted from the final eligible studies. Review Manager (RevMan) 5.3 for Mac was used to analyze the data and GRADE profiler were used to access the quality of outcomes. RESULTS: Based on four randomized clinical trials assessing a total of 521 eyes, the DEX implant can achieve visual acuity improvement for DME at rates similar to those achieved via anti-VEGF treatment (mean difference [MD] = - 0.43, P = 0.35), with superior anatomic outcomes at 6 months (MD = - 86.71 µm, P = 0.02), while requiring fewer injections, in comparison to anti-VEGF treatment. Although the mean reduction in CST did not showed significant difference at 12 months (MD = - 33.77 µm, P = 0.21), the significant in BCVA from baseline to 12 months supported the anti-VEGF treatment (MD = - 3.26, P < 0.00001). No statistically significant differences in terms of the serious adverse events. However, use of the DEX implant has higher risk of intraocular pressure elevation and cataract than anti-VEGF treatment. CONCLUSIONS: Compared with anti-VEGF, DEX implant improved anatomical outcomes significantly. However, this did not translate to improved visual acuity, which may be due to the progression of cataract. Therefore, the DEX implant may be recommended as a first chioce for select cases, such as for pseudophakic eyes, anti-VEGF-resistant eyes, or patients reluctant to receive intravitreal injections frequently.

INTRAVITREAL CONBERCEPT (KH902) FOR SURGICAL TREATMENT OF SEVERE PROLIFERATIVE DIABETIC RETINOPATHY.

PURPOSE: To evaluate the role, safety, and effectiveness of intravitreal conbercept (KH902) injections as an adjunct to vitrectomy in the management of severe proliferative diabetic retinopathy. METHODS: A randomized controlled trial was performed on 36 eyes of 36 patients affected by vitreous hemorrhage and tractional retinal detachment, which occurred as a consequence of active proliferative diabetic retinopathy. The patients were randomly assigned to two groups. The patients in one of the groups received an intravitreal injection of conbercept in the inferior temporal sector 4 mm from the sclerocorneal limbus with a sterile technique 1 week before vitrectomy. RESULTS: In the group without conbercept, intraoperative bleeding occurred in 14 patients (77.8%), and in five of these cases, bleeding was significant. The use of endodiathermy was necessary in 8 patients (44.4%). In 3 patients (16.6%), iatrogenic retinal breaks occurred, and in 1 patient (5.5%), a relaxing retinotomy was performed. Endotamponade with silicone oil was performed in 12 patients (66.6%). In the group treated with conbercept, intraoperative bleeding occurred in 2 cases (11.1%). The use of endodiathermy was necessary in 1 patient (5.5%). No patients experienced iatrogenic breaks or relaxing retinotomy during the surgery. Endotamponade with silicone oil was performed in 2 patients (11.1%). CONCLUSION: Preoperative intravitreal injection of conbercept could reduce the chances of intraoperative bleeding, which are beneficial in the management of proliferative diabetic retinopathy.

Primary orbital melanoma combined with giant divided nevus of the eyelid.

The authors report a rare case of primary orbital melanoma (POM) combined with giant divided nevus of the eyelid. An 8-year-old Chinese girl is referred for evaluation of 2-month duration of exophthalmos with decreased vision, epiphora, and pain on her right eye. His presentation, imaging, biopsy, histopathology, and management are presented. The possible cellular origin of the POM and the relationship of POM and divided nevus are discussed. We presume that divided nevus may be one of rarely preexisting lesions of POM.

Construction and validation of a neovascular glaucoma nomogram in patients with diabetic retinopathy after pars plana vitrectomy.

BACKGROUND: Neovascular glaucoma (NVG) is likely to occur after pars plana vitrectomy (PPV) for diabetic retinopathy (DR) in some patients, thus reducing the expected benefit. Understanding the risk factors for NVG occurrence and building effective risk prediction models are currently required for clinical research. AIM: To develop a visual risk profile model to explore factors influencing DR after surgery. METHODS: We retrospectively selected 151 patients with DR undergoing PPV. The patients were divided into the NVG (NVG occurrence) and No-NVG (No NVG occurrence) groups according to the occurrence of NVG within 6 months after surgery. Independent risk factors for postoperative NVG were screened by logistic regression. A nomogram prediction model was established using R software, and the model's prediction accuracy was verified internally and externally, involving the receiver operator characteristic curve and correction curve. RESULTS: After importing the data into a logistic regression model, we concluded that a posterior capsular defect, preoperative vascular endothelial growth factor ≥ 302.90 pg/mL, glycosylated hemoglobin ≥ 9.05%, aqueous fluid interleukin 6 (IL-6) ≥ 53.27 pg/mL, and aqueous fluid IL-10 ≥ 9.11 pg/mL were independent risk factors for postoperative NVG in patients with DR (P < 0.05). A nomogram model was established based on the aforementioned independent risk factors, and a computer simulation repeated sampling method was used to internally and externally verify the nomogram model. The area under the curve (AUC), sensitivity, and specificity of the model were 0.962 [95% confidence interval (95%CI): 0.932-0.991], 91.5%, and 82.3%, respectively. The AUC, sensitivity, and specificity of the external validation were 0.878 (95%CI: 0.746-0.982), 66.7%, and 95.7%, respectively. CONCLUSION: A nomogram constructed based on the risk factors for postoperative NVG in patients with DR has a high prediction accuracy. This study can help formulate relevant preventive and treatment measures.

Probable Treatment Targets for Diabetic Retinopathy Based on an Integrated Proteomic and Genomic Analysis.

Purpose: Using previously approved medications for new indications can expedite the lengthy and expensive drug development process. We describe a bioinformatics pipeline that integrates genomics and proteomics platforms to identify already-approved drugs that might be useful to treat diabetic retinopathy (DR). Methods: Proteomics analysis of vitreous humor samples from 12 patients undergoing pars plana vitrectomy for DR and a whole genome dataset (UKBiobank TOPMed-imputed) from 1330 individuals with DR and 395,155 controls were analyzed independently to identify biological pathways associated with DR. Common biological pathways shared between both datasets were further analyzed (STRING and REACTOME analyses) to identify target proteins for probable drug modulation. Curated target proteins were subsequently analyzed by the BindingDB database to identify chemical compounds they interact with. Identified chemical compounds were further curated through the Expasy SwissSimilarity database for already-approved drugs that interact with target proteins. Results: The pathways in each dataset (proteomics and genomics) converged in the upregulation of a previously unknown pathway involved in DR (RUNX2 signaling; constituents MMP-13 and LGALS3), with an emphasis on its role in angiogenesis and blood-retina barrier. Bioinformatics analysis identified U.S. Food and Drug Administration (FDA)-approved medications (raltitrexed, pemetrexed, glyburide, probenecid, clindamycin hydrochloride, and ticagrelor) that, in theory, may modulate this pathway. Conclusions: The bioinformatics pipeline described here identifies FDA-approved drugs that can be used for new alternative indications. These theoretical candidate drugs should be validated with experimental studies. Translational Relevance: Our study suggests possible drugs for DR treatment based on an integrated proteomics and genomics pipeline. This approach can potentially expedite the drug discovery process by identifying already-approved drugs that might be used for new indications.

Immunomodulatory effects of mesenchymal stem cells in a rat corneal allograft rejection model.

Mesenchymal stem cells (MSCs) are promising candidates for immunomodulatory therapy that are currently being tested in several organ transplant rejection models. In this study, we tested the immunomodulatory effects of MSC injection in a rat model of corneal allograft rejection. MSCs were isolated and cultured from bone marrow of Wistar rats. A rat corneal allograft rejection model was established using Wistar rats as donors and Lewis rats as recipients. Lewis rats were randomly separated into 12 groups and treated with MSCs alone or MSCs combined with Cyclosporin A (CsA) at different doses. In MSC-treated rats, the T cell response to ConA was evaluated, Th1/Th2 cytokines produced by T lymphocytes were measured, and the number of CD4+CD25+Foxp3+ regulatory T cells (Treg) was assessed. Results demonstrated that postoperative injection of MSCs prolonged graft survival time. MSCs significantly inhibited proliferation of pathogenic T cells in vitro and prevented T cell response in vivo (p < 0.05). Postoperative injection also reduced Th1 pro-inflammatory cytokines and elevated IL-4 cytokine secretion from T lymphocytes derived from cornea-transplanted rats. In addition, Tregs were upregulated by MSC treatment. Unexpectedly, the application of MSCs combined with low dose CsA therapy (1 mg/kg) accelerated graft rejection compared with postoperative MSC therapy alone. However, when 2 mg/kg CsA was given together with MSCs, graft survival was significantly prolonged. These results suggested that MSCs could exert therapeutic effect against corneal allograft rejection, and further investigation of combined MSC and CsA treatment be required as opposite effects were observed depending on CsA dose.

[Investigation of the role of mesenchymal stem cells on keratoplasty rejection].

OBJECTIVE: To investigate the effect of mesenchymal stem cells (MSC) on keratoplasty rejection in a rat mode. METHODS: MSC from bone marrow of Wistar rats was cultured. Corneas of Wistar rats (donors) were transplanted to Lewis rats (recipients). Transplanted rats were randomly divided into A, B, C three groups. Rats in group B were injected with MSC suspended in PBS via the tail vein continually for three days before the surgery, while rats in group C accepted similar MSC transplantation after the surgery. The rats in group A were given the same volume of PBS. Grafts were scored for corneal transparency, edema and extent of neovascularization by slit lamp observation. Expressions of CD(4), CD(8), CD(25) and CD(45) in corneas 10 days after transplantation were examined by immunohistochemistry. RESULTS: The survival time of the corneal grafts in group C [(9.9 ± 0.69) d] was significantly prolonged compared with that of the group A and group B [(11.83 ± 0.54), (16.89 ± 1.91) d] (F = 5.732, P = 0.001, 0.019). Expression level of CD(4), CD(8), CD(25) of the corneal grafts in group C was lower than that of group A and group B (t = 2.477, 2.359, 2.445, P = 0.024, 0.042, 0.030). CONCLUSION: Post-operative injection of MSCs could inhibit keratoplasty rejection and prolong the corneal allografts survival in a rat model.

Application and observation of artificial intelligence in clinical practice of fundus screening for diabetic retinopathy with non-mydriatic fundus photography: a retrospective observational study of T2DM patients in Tianjin, China.

Objective: To observe the consistency of a preliminary report of artificial intelligence (AI) in the clinical practice of fundus screening for diabetic retinopathy (DR) using non-mydriatic fundus photography. Methods: Patients who underwent DR screening in the Metabolic Disease Management Center (MMC) of our hospital were selected as research participants. The degree of coincidence of the AI preliminary report and the ophthalmic diagnosis was compared and analyzed, and the kappa value was calculated. Fundus fluorescein angiography (FFA) was performed in patients referred to the out-of-hospital ophthalmology department, and the consistency between fluorescein angiography and AI diagnosis was evaluated. Results: In total, 6146 patients (12,263 eyes) completed the non-mydriasis fundus examination. The positive DR screening rate was 24.3%. When considering moderate nonproliferative retinopathy as the cut-off point, the kappa coefficient was 0.75 (p < 0.001), the sensitivity was 0.973, and the precision was 0.642, which was shown in the precision-recall curve. Fifty-nine patients referred to receive FFA were compared with non-mydriatic AI diagnoses. The kappa coefficient was 0.53, and the coincidence rate was 66.9%. Conclusion: Non-mydriasis fundus examination combined with AI has a medium-high consistency with ophthalmologists in DR diagnosis, conducive to early DR screening. Combining diagnosis and treatment modes with the Internet can promote the development of telemedicine, alleviate the shortage of ophthalmology resources, and promote the process of blindness prevention and treatment projects.

Biocompatibility and Efficacy of a Linearly Cross-Linked Sodium Hyaluronic Acid Hydrogel as a Retinal Patch in Rhegmatogenous Retinal Detachment Repairment.

To prevent the migration of retinal pigment epithelium (RPE) cells into the vitreous cavity through retinal breaks after the pars plana vitrectomy for the repair of rhegmatogenous retinal detachment (RRD), sealing retinal breaks with an appropriate material appears to be a logical approach. According to a review of ocular experiments or clinical trials, the procedure for covering retinal breaks with adhesives is complex. A commercially available cross-linked sodium hyaluronic acid (HA) hydrogel (Healaflow®) with the injectable property was demonstrated to be a perfect retinal patch in RRD clinical trials by our team. Based on the properties of Healaflow®, a linearly cross-linked sodium HA hydrogel (HA-engineered hydrogel) (Qisheng Biological Preparation Co. Ltd. Shanghai, China) with the injectable property was designed, whose cross-linker and cross-linking method was improved. The purpose of this study is to report the characteristics of an HA-engineered hydrogel using Healaflow® as a reference, and the biocompatibility and efficacy of the HA-engineered hydrogel as a retinal patch in the rabbit RRD model. The HA-engineered hydrogel exhibited similar dynamic viscosity and cohesiveness and G' compared with Healaflow®. The G' of the HA-engineered hydrogel varied from 80 to 160 Pa at 2% strain under 25°C, and remained constantly higher than G″ over the range of frequency from 0.1 to 10 Hz. In the animal experiment, clinical examinations, electroretinograms, and histology suggested no adverse effects of the HA-engineered hydrogel on retinal function and morphology, confirming its favorable biocompatibility. Simultaneously, our results demonstrated the efficacy of the HA-engineered hydrogel as a retinal patch in the RRD model of rabbit eyes, which can aid in the complete reattachment of the retina without the need for expansile gas or silicone oil endotamponade. The HA-engineered hydrogel could play the role of an ophthalmologic sealant due to its high viscosity and cohesiveness. This pilot study of a small series of RRD models with a short-term follow-up provides preliminary evidence to support the favorable biocompatibility and efficacy of the HA-engineered hydrogel as a promising retinal patch for sealing retinal breaks in retinal detachment repair. More cases and longer follow-up studies are needed to assess its safety and long-term effects.

Advances in biomaterials as a retinal patch for the repair of rhegmatogenous retinal detachment.

Rhegmatogenous retinal detachment (RRD) is the most common retinological emergency that can cause blindness without surgical treatment. RRD occurs when liquefied vitreous accumulates between the neurosensory retina and the retinal pigment epithelium via retinal breaks, which are caused by the separation of the vitreous from the retina with aging. Currently, the main treatment option is pars plana vitrectomy, which involves surgical removal of the vitreous and laser photocoagulation around retinal breaks to generate firm chorioretinal adhesion, as well as subsequent filling of the vitreous cavity with long-lasting substitutes (expansile gas or silocone oil) to prevent the connection between the subretinal space and the vitreous cavity via the breaks before the chorioretinal adhesion firm enough. However, the postoperative face-down position and the not very satisfactory first retinal reattachment rate place a heavy burden on patients. With the development of technology and materials engineering, researchers have developed biomaterials that can be used as a retinal patch to seal retinal breaks and prevent the connection of subretinal space and vitreous cavity via breaks, thus replacing the long-lasting vitreous substitutes and eliminating the postoperative face-down position. Preclinical studies have demonstrated that biomaterial sealants have enough biocompatibility and efficacy in the in vitro and in vivo experiments. Some sealants have been used in clinical trials on a small scale, and the results indicate promising application prospects of the biomaterial sealants as retinal patches in the repair of RRD. Herein, we review the recent advances in biomaterials as retinal patches for the repair of RRD, focusing on the biomaterial categories, methods, and procedures for sealing retinal breaks, as well as their biocompatibility and efficacy, current limitations, and development perspectives.

Effect of small extracellular vesicles derived from IL-10-overexpressing mesenchymal stem cells on experimental autoimmune uveitis.

BACKGROUND: Autoimmune uveitis is a sight-threatening intraocular inflammation mainly caused by immune dysregulation. The development of safe and effective therapeutic approaches is urgently needed. Small extracellular vesicles (sEVs) derived from mesenchymal stem cells (MSCs) have been demonstrated to inhibit autoimmune responses; however, the immunosuppressive effect of MSC-sEVs is too weak for clinical transfer. In the current study, we investigated the therapeutic effect of IL-10-overexpressing MSC-sEVs (sEV-IL10) on experimental autoimmune uveitis (EAU) and studied the underlying mechanism. METHODS: Mice were randomly grouped and received a single tail vein injection of different sEVs (50 µg) or PBS on day 11 post-immunization. The clinical and histological scores were graded, and the percentage of T helper cell was measured. To investigate the effect of sEVs on the proliferation of T-cells and the differentiation of Th1, Th17 and Treg cells, T-cells were cocultured with sEVs under the corresponding culture conditions. After labeled with PKH-26, sEVs were traced both in vivo and in vitro. RESULTS: Compared with normal or vector sEV-treated groups, mice in the sEV-IL10-treated group had lower clinical and histological scores with lower percentages of Th1 and Th17 cells in the eyes and higher percentages of Treg cells in the spleen and draining lymph nodes (LN). Furthermore, sEV-IL10 enhanced the suppressive effect of MSC-sEVs on the proliferation of T-cells and differentiation of Th1 and Th17 cells, whereas upregulated the differentiation of Treg cells. Both in vivo and in vitro experiments demonstrated that MSC-sEVs were rapidly enriched in target tissues and internalized by T-cells. CONCLUSION: These results suggested that sEV-IL10 effectively ameliorates EAU by regulating the proliferation and differentiation of T-cells, indicating sEVs as a potential novel therapy for autoimmune uveitis or other autoimmune diseases.

[Prevalence survey of visual impairment in a multiethnic rural district in the high altitude area of Yunnan Province, China].

OBJECTIVE: To estimate the prevalence and causes of visual impairment by a population-based survey conducted in Gongshan County of Yunnan Province. METHODS: Cluster sampling method was used for sample selection. In person interview, pilot study, visual acuity (VA) check, intraocular pressure, slit lamp microscopy and fundus examination were performed. The diagnoses of blindness (VA<0.05) and visual impairment (VA<0.3 to ≥0.05) were based on best-corrected visual acuity in the better eye. The prevalence of visual impairment was calculated as to age, gender, education, ethnic group and altitude of living area. The dominant causes of blindness and visual impairment were then identified. The comparison of prevalence among different group examined by four-fold table Chi-square test, R×2 Chi-square test and trend Chi-square test. RESULTS: Among 3070 eligible residents, 2460 (80.1%) were finally enrolled in the present study. The total prevalence of visual impairment was 6.46%. The bilateral blindness and unilateral blindness was 19 and 46 respectively. The bilateral and unilateral low vision was 49 and 45 respectively. There was no statistical significant difference of prevalence of visual impairment among different ethnic groups (χ2=0.75, P=0.388). There was significantly statistical difference of prevalence of visual impairment among groups who lives in different altitude area (χ2=18.34, P=0.000). High prevalence were also observed in the elder (≥70 years), illiterate and outdoor-workers, which was 2.24%, 4.19%, 5.65% respectively. The leading causes of bilateral blindness was cataract (42.1%, 8/19), corneal opacity (26.3%, 5/19), and retinal abnormality (21.1%, 4/19). The leading cause of bilateral low vision was also cataract (42.9%, 21/49). CONCLUSIONS: Cataract was the dominant cause of visual impairment in Gongshan County of Yunnan Province. The study highlights an urgent need of visual impairment prevention program conducted by local public heath intervention, especially focusing on cataract treatment.

Clinical experience of using the NGENUITY three-dimensional surgery system in ophthalmic surgical procedures.

PURPOSE: To assess the clinical experience of using a three-dimensional (3D) system for ophthalmic surgical procedures. METHODS: We retrospectively analysed video recordings of patients who underwent 3D ophthalmic surgery, using the NGENUITY® 3D visualization system, or traditional microsurgery at our hospital, from August 2017 to February 2018. Patients underwent phacoemulsification or phacoemulsification combined with vitrectomy. Diagnoses, operation type, duration of continuous curvilinear capsulorhexis (CCC), number of forceps nips during CCC and capsulorhexis complications were recorded. Five surgeons and four assistants answered a 3D surgery questionnaire. RESULTS: Twenty-six of 46 patients who underwent 3D surgery, and 31 of 51 patients who underwent traditional microsurgery (control group) were enrolled. The mean CCC duration in the study and control groups was 31.2 ± 10.8 and 28.7 ± 13.2 seconds (p = 0.071), and the mean number of forceps nips was 5 ± 2 and 5 ± 2 (p = 0.634), respectively. The anterior capsular rupture rate of phacoemulsification under 3D and traditional conditions was 3.85% (1/26 cases) and 3.23% (1/31 cases), respectively. The complication rate was similar between the two groups (p > 0.999). Four of five surgeons and two of four assistants believed the clarity of 3D surgery was similar or better than that of traditional microsurgery. The occurrence of dizziness (p > 0.999), shoulder and neck pain (p = 0.262), backache (p = 0.471) and visual fatigue (p = 0.347) did not differ significantly between the two methods. CONCLUSION: The 3D surgical system facilitated similar operation speed and stability as the traditional microscope and provided reliable support for ophthalmic surgery.

Human embryonic stem cell-derived extracellular vesicles alleviate retinal degeneration by upregulating Oct4 to promote retinal Müller cell retrodifferentiation via HSP90.

OBJECTIVE: Retinal degenerative diseases remain the dominant causes of blindness worldwide, and cell replacement is viewed as a promising therapeutic direction. However, the resources of seed cells are hard to obtain. To further explore this therapeutic approach, human embryonic stem extracellular vesicles (hESEVs) were extracted from human embryonic stem cells (hESCs) to inspect its effect and the possible mechanism on retinal Müller cells and retinal function. METHODS: hESEVs were extracted by multi-step differential centrifugation, whose morphologies and specific biomarkers (TSG101, CD9, CD63, and CD81) were observed and measured. After hESEVs were injected into the vitreous cavity of RCS rats, the retinal tissues and retinal functions of rats were assessed. The alteration of Müller cells and retinal progenitor cells was also recorded. Microvesicles (MVs) or exosomes (EXOs) were extracted from hESCs transfected with sh-HSP90 or pcDNA3.1-HSP9, and then incubated with Müller cells to measure the uptake of EVs, MVs, or EXOs in Müller cells by immunofluorescence. The retrodifferentiation of Müller cells was determined by measuring Vimentin and CHX10. qRT-PCR and western blot were used to detect HSP90 expression in MVs and evaluate Oct4 level in Müller cells, and Co-IP to inspect the interaction of HSP90 and Oct4. RESULTS: RCS rats at the postnatal 30 days had increased retinal progenitor cells which were dedifferentiated from Müller cells. hESEVs were successfully extracted from hESCs, evidenced by morphology observation and positive expressions of specific biomarkers (TSG101, CD9, CD63, and CD81). hESEVs promoted Müller cells dedifferentiated and retrodifferentiated into retinal progenitor cells evidenced by the existence of a large amount of CHX10-positive cells in the retinal inner layer of RCS rats in response to hESEV injection. The promotive role of hESEVs was exerted by MVs demonstrated by elevated fluorescence intensity of CHX10 and suppressed Vimentin fluorescence intensity in MVs rather than in EXOs. HSP90 in MVs inhibited the retrodifferentiation of Müller cells and suppressed the expression level of Oct4 in Müller cells. Co-IP revealed that HSP90 can target Oct4 in Müller cells. CONCLUSION: hESEVs could promote the retrodifferentiation of Müller cells into retinal progenitor cells by regulating the expression of Oct4 in Müller cells by HSP90 mediation in MVs.

Proteomic analysis of aqueous humor in patients with pathologic myopia.

Complications from pathologic myopia (PM) are a major cause of visual impairment and blindness. However, an efficient clinical therapeutic strategy for PM is still lacking. The aim of this study was to quantitatively compare the proteomic profiles of aqueous humor between PM and non-PM cataract patients. Twenty aqueous humor samples from each group were analyzed with label-free quantitative proteomic analysis to identify the differentially expressed proteins for function enrichment analyses and protein-protein interaction network construction. Hub protein was validated with ELISA using an independent cohort consisting of 20 samples from each group and its receiver operating characteristic (ROC) curve analysis was conducted. A total of 583 proteins were identified and 101 proteins were found to be differentially expressed, including 63 up-regulated proteins and 38 down-regulated proteins. The bioinformatics analysis suggested that PM is closely associated with immunity and inflammation interactions, and remodeling of extracellular matrix. Apolipoprotein A-I (ApoA1) was enriched as the hub protein of the network with the highest score, degree and centrality. ROC analysis showed that ApoA1 could distinguish PM from controls with an area under the curve of 0.963 (p < 0.001). The findings could provide potential clues for further study on the molecular mechanisms and developing new treatments for PM, especially related to immunity and inflammation interactions. ApoA1 may be a potential key protein and therapeutic target in human PM. SIGNIFICANCE: It is important and urgent to discover the mechanisms of pathologic myopia (PM) to inhibit its progression. This study applied the quantitative proteomic analysis to study aqueous humor from patients with or without PM, aiming to discover dysregulated proteins related to PM. Our results suggested that those dysregulated proteins are closely associated with immunity and inflammation interactions, and remodeling of extracellular matrix. The findings from this study could provide potential clues for further research on the molecular mechanisms and developing new treatments for PM, especially related to immunity and inflammation. ApoA1 may be a potential key protein and therapeutic target in human PM.