Recalled age of myopia onset may predict risk of high adult myopia in Chinese adults.

INTRODUCTION: This study aimed to investigate the relationship between age of myopia onset and high myopia and to explore if age of onset mediated the associations of high myopia with parental myopia and time spent on electronics. METHODS: This cross-sectional study enrolled 1118 myopic patients aged 18 to 40. Information was obtained via a detailed questionnaire. Multivariable logistic regression and linear regression models were utilized to assess age of onset in relation to high myopia and spherical equivalent refractive error, respectively. Structural equation models examined the mediated effect of onset age on the association between parental myopia, time spent on electronics and high myopia. RESULTS: An early age at myopia onset was negatively correlated with spherical equivalent refractive power. Subjects who developed myopia before the age of 12 were more likely to suffer from high myopia than those who developed myopia after the age of 15. Age of myopia onset was the strongest predictor of high myopia, with an area under the curve (AUC) in Receiver Operator Characteristic (ROC) analysis of 0.80. Additionally, age of myopia onset served as a mediator in the relationships between parental myopia, electronic device usage duration, and the onset of high myopia in adulthood. CONCLUSIONS: Age of myopia onset might be the single best predictor for high myopia, and age at onset appeared to mediate the associations of high myopia with parental myopia and time spent on electronics.

Vitreous Olink proteomics reveals inflammatory biomarkers for diagnosis and prognosis of traumatic proliferative vitreoretinopathy.

Background: The aim of this study was to identify inflammatory biomarkers in traumatic proliferative vitreoretinopathy (TPVR) patients and further validate the expression curve of particular biomarkers in the rabbit TPVR model. Methods: The Olink Inflammation Panel was used to compare the differentially expressed proteins (DEPs) in the vitreous of TPVR patients 7-14 days after open globe injury (OGI) (N = 19) and macular hole patients (N = 22), followed by correlation analysis between DEPs and clinical signs, protein-protein interaction (PPI) analysis, area under the receiver operating characteristic curve (AUC) analysis, and function enrichment analysis. A TPVR rabbit model was established and expression levels of candidate interleukin family members (IL-6, IL-7, and IL-33) were measured by enzyme-linked immunosorbent assay (ELISA) at 0, 1, 3, 7, 10, 14, and 28 days after OGI. Results: Forty-eight DEPs were detected between the two groups. Correlation analysis showed that CXCL5, EN-RAGE, IL-7, ADA, CD5, CCL25, CASP8, TWEAK, and IL-33 were significantly correlated with clinical signs including ocular wound characteristics, PVR scoring, PVR recurrence, and final visual acuity (R = 0.467-0.699, p < 0.05), and all with optimal AUC values (0.7344-1). Correlations between DEP analysis and PPI analysis further verified that IL-6, IL-7, IL-8, IL-33, HGF, and CXCL5 were highly interactive (combined score: 0.669-0.983). These DEPs were enriched in novel pathways such as cancer signaling pathway (N = 14, p < 0.000). Vitreous levels of IL-6, IL-7, and IL-33 in the rabbit TPVR model displayed consistency with the trend in Olink data, all exhibiting marked differential expression 1 day following the OGI. Conclusion: IL-7, IL-33, EN-RAGE, TWEAK, CXCL5, and CD5 may be potential biomarkers for TPVR pathogenesis and prognosis, and early post-injury may be an ideal time for TPVR intervention targeting interleukin family biomarkers.

Relationship between visual acuity and OCT angiography parameters in diabetic retinopathy eyes after treatment.

PURPOSE: To assess the relationship between visual acuity and OCT angiography parameters in diabetic retinopathy eyes after treatment, and to analyze the relative factors in PDR eyes. METHODS: A total of 89 eyes, including 42 eyes with non-PDR (NPDR), and 47 eyes after vitrectomy with PDR were included and underwent OCTA. All images were processed by Python or FIJI. Multivariable linear regression models were used to analyze the associations between postoperative BCVA and OCTA parameters in PDR patients. RESULTS: Postoperative OCTA parameters including deep capillary plexus (DCP) parafoveal and perifoveal vessel density (VD), DCP parafoveal and perifoveal vessel length density (VLD), DCP fractal dimension (FD), choriocapillaris plexus (CCP) VD, CCP VLD, were significantly lower in the PDR group than in the NPDR group. In the superficial capillary plexus (SCP), we found a negative correlation between the postoperative BCVA and VD (parafovea: ß coefficient = -0.351, p = 0.023; perifovea: ß coefficient = -0.338, p = 0.036). Perifoveal VLD (ß coefficient = -0.343, p = 0.031) and FD (ß coefficient = -0.375, p = 0.016) of the SCP were also negatively correlated with postoperative BCVA. Regarding the DCP, perifoveal VD (ß coefficient = -0.396, p = 0.008), perifoveal VLD (ß coefficient = -0.334, p = 0.025), vessel tortuosity (VT) (ß coefficient = -0.369, p = 0.015) were negatively correlated with postoperative BCVA. In CCP, VLD (ß coefficient = -0.373, p = 0.023) and number of flow voids (ß coefficient = -0.334, p = 0.036) exhibited a negative association with postoperative BCVA. CONCLUSIONS: Postoperative BCVA of PDR patients was related to OCTA parameters of the SCP (parafoveal and perifoveal VD, perifoveal VLD and FD), DCP (perifoveal VD, VLD, and VT) and CCP (VLD and number of flow voids).

An interpretable model predicts visual outcomes of no light perception eyes after open globe injury.

BACKGROUND: The visual outcome of open globe injury (OGI)-no light perception (NLP) eyes is unpredictable traditionally. This study aimed to develop a model to predict the visual outcomes of vitrectomy surgery in OGI-NLP eyes using a machine learning algorithm and to provide an interpretable system for the prediction results. METHODS: Clinical data of 459 OGI-NLP eyes were retrospectively collected from 19 medical centres across China to establish a training data set for developing a model, called 'VisionGo', which can predict the visual outcome of the patients involved and compare with the Ocular Trauma Score (OTS). Another 72 cases were retrospectively collected and used for human-machine comparison, and an additional 27 cases were prospectively collected for real-world validation of the model. The SHapley Additive exPlanations method was applied to analyse feature contribution to the model. An online platform was built for real-world application. RESULTS: The area under the receiver operating characteristic curve (AUC) of VisionGo was 0.75 and 0.90 in previtrectomy and intravitrectomy application scenarios, which was much higher than the OTS (AUC=0.49). VisionGo showed better performance than ophthalmologists in both previtrectomy and intravitrectomy application scenarios (AUC=0.73 vs 0.57 and 0.87 vs 0.64). In real-world validation, VisionGo achieved an AUC of 0.60 and 0.91 in previtrectomy and intravitrectomy application scenarios. Feature contribution analysis indicated that wound length-related indicators, vitreous status and retina-related indicators contributed highly to visual outcomes. CONCLUSIONS: VisionGo has achieved an accurate and reliable prediction in visual outcome after vitrectomy for OGI-NLP eyes.

Early use of intravitreal triamcinolone to inhibit traumatic proliferative vitreoretinopathy: a randomised clinical trial.

AIMS: To evaluate the efficacy and safety of intravitreal triamcinolone acetonide (TA) injection at the end of emergency surgery for open globe injury (OGI) to suppress traumatic proliferative vitreoretinopathy (TPVR). METHODS: A single-centre, participant-masked, prospective, randomised controlled clinical trial. A total of 68 globe rupture patients with zone III were randomised to the control group (n=34) or the TA group (n=34) in 1:1 allocation ratio. Patients were treated with 0.1 mL TA in the TA group and 0.1 mL balanced salt solution in the control group at the end of emergency surgery. The primary outcome was the assessment of TPVR during vitrectomy 10±3 days later. Secondary outcomes included visual acuity (VA), retinal attachment rate, macular attachment rate, proliferative vitreoretinopathy (PVR) recurrent rate, side effects 6 months after vitrectomy. RESULTS: During vitrectomy, the TPVR grade of the control group was significantly more severe than the TA group (p=0.028). The TPVR score was significantly better in the TA group (9.30±0.82) than in the control group (6.44±1.06) (p=0.036). The final VA improved in 23 eyes (92%) in the TA group and in 14 eyes (63.64%) in the control group (p=0.008). The retinal attachment rates were 88% and 63.64% in the TA and control group, respectively (p=0.049). The two groups showed no significant difference in macular repositioning and PVR recurrent rate (p=0.215, 0.191). Temporary intraocular pressure elevation occurred in one eye in the TA group after emergency surgery. CONCLUSIONS: Early intravitreal TA injection for OGI effectively reduces TPVR, increases surgical success and improves visual prognosis.

The essential role of N6-methyladenosine RNA methylation in complex eye diseases.

There are many complex eye diseases which are the leading causes of blindness, however, the pathogenesis of the complex eye diseases is not fully understood, especially the underlying molecular mechanisms of N6-methyladenosine (m6A) RNA methylation in the eye diseases have not been extensive clarified. Our review summarizes the latest advances in the studies of m6A modification in the pathogenesis of the complex eye diseases, including cornea disease, cataract, diabetic retinopathy, age-related macular degeneration, proliferative vitreoretinopathy, Graves' disease, uveal melanoma, retinoblastoma, and traumatic optic neuropathy. We further discuss the possibility of developing m6A modification signatures as biomarkers for the diagnosis of the eye diseases, as well as potential therapeutic approaches.

Long-term outcomes of administration of intravitreal triamcinolone acetonide after posterior vitreous detachment during pars plana vitrectomy for proliferative diabetic retinopathy.

AIM: To evaluate the long-term outcomes of intravitreal triamcinolone acetonide (TA) administration after posterior vitreous detachment (PVD) during pars plana vitrectomy (PPV) for patients with proliferative diabetic retinopathy (PDR). METHODS: A total of 189 eyes (152 patients) who underwent PPV for severe PDR were reviewed. Intravitreal injection of TA (IVTA) was administered during PPV in 118 eyes (PPV+IVTA group), and 71 eyes did not receive IVTA (PPV group). Immediately after PVD, when most of the vitreous and proliferative membranes were removed, 0.1 mL TA (40 mg/mL) was injected into the vitreous cavity in the PPV+IVTA group. All patients were followed-up for least 12 months. Visual outcomes and postoperative complications were recorded and compared between the two groups. RESULTS: IVTA was helpful for proliferative membrane peeling and haemostasis during PPV. In the PPV+IVTA group, best-corrected visual acuity had significantly improved and the intraocular pressure was controlled well during the follow-up. The incidence of early recurrent vitreous haemorrhage after PPV was significantly lower in the PPV+IVTA group (1.7%) than in the PPV group (9.9%) (p=0.028). CONCLUSION: The administration of IVTA after PVD during PPV can effectively improve the final visual outcomes and prevent postoperative complications in patients with severe PDR.

Association of Physical Activity with Retinal Thickness and Vascular Structure in Elderly Chinese Population.

INTRODUCTION: We aimed to assess the association of physical activity (PA) with retinal thickness and vascular structure in an elderly Chinese population. METHODS: This study enrolled 220 retirees aged 50 years and above from Tianjin University of Sport, China. PA data gathered through the International Physical Activity Questionnaires were computed for metabolic equivalent of task-minutes per week. All participants underwent full ophthalmic examination including optical coherence tomography angiography (OCTA). Multiple linear regression analyses were used to evaluate the association of PA with retinal thickness and vascular structure. RESULTS: A high amount of total PA was associated with smaller size of foveal avascular zone (FAZ) (high vs. low: area, ß=-0.04; circumference ß=-0.14) and greater central vessel (VD) (ß=1.04) and perfusion densities (PD) (ß=0.02). For domain-specific PA, participants with high and moderate recreational PA levels were found to have greater central VDs and PDs. Non-leisure activities demonstrated negative relationship with FAZ perimeter ratio (moderate vs. low: ß=-0.08; high vs. low: ß=-0.13) and, counter-intuitively, negative relation with VDs measured at the inner (high vs. low: ß=-0.98) and outer retinal layers (high vs. low: ß=-0.38). Additionally, higher levels of total PA were related to increased macular fovea thickness and average thickness of retinal nerve fiber layer. CONCLUSIONS: High PA level, particularly recreational PA, was associated with smaller FAZ and greater VD and PD in senior adults. Non-leisure time PA might not confer the same health benefits as leisure time PA. Our data supports a possible protective role of recreational PA in the retina against microvascular changes.

Guideline for the treatment of no light perception eyes induced by mechanical ocular trauma.

Severe mechanical ocular trauma with no light perception (NLP) predicts a poor prognosis of visual acuity and enucleation of the eyeball. Since the innovative treatment concept of exploratory vitreoretinal surgery has developed and treatment technology has advanced, the outcomes of severe ocular trauma treatment in NLP patients have greatly improved. However, there remains a lack of unified standards for the determination, surgical indication, and timing of vitrectomy in NLP eye treatment. To address these problems, we aimed to create evidence-based medical guidelines for the diagnosis, treatment, and prognosis of mechanical ocular trauma with NLP. Sixteen relevant recommendations for mechanical ocular trauma with NLP were obtained, and a consensus was reached. Each recommendation was explained in detail to guide the treatment of mechanical ocular trauma associated with NLP.

Potential Impact of N6-Methyladenosine RNA Methylation on Vision Function and the Pathological Processes of Ocular Diseases: New Discoveries and Future Perspectives.

N6-methyladenosine (m6A) methylation/modification plays a critical role in various biological processes through post-transcriptional ribonucleic acid (RNA) modification, which involves RNA processing, nuclear export, translation and decay. Functionally, m6A modification may be involved in ocular cell growth and differentiation, stem cell identity, development, haemostasis and innate versus adaptive immunity. Aberrations in m6A methylation may mediate numerous pathological conditions in the eye, including microorganism infection, inflammation, autoimmune disease, senescence, degeneration, epithelial-mesenchymal transition, fibrosis, angiogenesis, tumorigenesis and complex eye diseases. In this review, we have discussed the relevance of m6A modification to precision medicine, stem cell directional differentiation, biomarkers of eye diseases and m6A methylation activators and inhibitors. In addition, we summarised the challenges and future research directions in the field related to visual function and eye diseases.

Timely vitrectomy without intraocular lens removal for acute endophthalmitis after cataract surgery.

AIM: To investigate the clinical features, causative organisms and effects of timely vitrectomy and silicone oil tamponade without intraocular lens (IOL) removal in the treatment of acute-onset endophthalmitis after cataract surgery (APCE). METHODS: We retrospectively analyzed the clinical features and microbiological factors in 10 eyes of 10 patients with APCE at Tianjin Medical University General Hospital from January 2010 to December 2018. Data on the clinical features, causative organisms, visual acuity, intraocular pressure (IOP) and complications were collected. The mean follow-up period was 25.5mo. RESULTS: The mean age of the patients was 71.4y. The mean time between cataract surgery and the onset of endophthalmitis was 2.0d. Preoperative visual acuity ranged from no light perception to hand motion. After vitrectomy, the visual acuity increased in nine eyes (90%), and was unchanged in one eye (10%). A significant difference was observed between the mean preoperative (36.3±7.1 mm Hg) and postoperative IOP (14.9±4.3 mm Hg, P<0.05). Staphylococcus epidermidis was isolated in 5 eyes, S. aureus in 2 eyes, and Enterococcus in 1 eye. Postoperative complications mainly included fibrin exudates in the anterior chamber at the early stages in all eyes and temporary IOP elevation in one eye. No retinal detachment or ocular atrophy was observed during the follow-up period. CONCLUSION: Under systemic antibiotic treatment and timely diagnosis, vitrectomy and silicone oil tamponade without IOL removal is a safe and effective method for APCE.

Lysozyme Protects Against Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Inflammation in Human Corneal Epithelial Cells.

Purpose: The purpose of this study was to investigate the effects of lysozyme, an antimicrobial enzyme found in tears that protects the eye against pathogens, on pseudotyped severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection through corneal epithelial cells. Methods: The expression of the angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease (TMPRSS2) in human corneal epithelial cells (HCECs) was measured by RT-PCR and Western blotting. The altered expression of the pro-inflammatory molecules induced by spike protein and lysozyme was analyzed by RT-PCR. Cell toxicity was tested by CCK8 assay. The cell entry of SAR-CoV-2 in HCECs and primary rabbit corneal epithelial cells (RbCECs) was detected by luciferase assay. Results: ACE2 and TMPRSS2 were highly expressed in HCECs. The spike proteins of SARS-CoV-2 stimulated a robust inflammatory response in HCECs, characterized by increased secretion of pro-inflammatory molecules, including IL-6, TNF-α, iNOS, and MCP-1, and pretreatment with lysozyme in HCECs markedly decreased the production of proinflammatory molecules induced by spike proteins. In addition, the inflammatory cytokine TNF-α enhanced the entry of SARS-CoV-2 into HCECs, which can be mitigated by pretreatment with lysozyme. Conclusions: In this study, we analyzed the susceptibility of human corneal epithelial cells to SARS-CoV-2 infection and suggested the protective effects of lysozyme on SARS-CoV-2 infection.

Mechanistic study of silica nanoparticles on the size-dependent retinal toxicity in vitro and in vivo.

BACKGROUND: Silica nanoparticles (SiO2 NPs) are extensively applied in the biomedical field. The increasing medical application of SiO2 NPs has raised concerns about their safety. However, studies on SiO2 NP-induced retinal toxicity are lacking. METHODS: We investigated the retinal toxicity of SiO2 NPs with different sizes (15 and 50 nm) in vitro and in vivo along with the underlying mechanisms. The cytotoxicity of SiO2 NPs with different sizes was assessed in R28 human retinal precursor cells by determining the ATP content and LDH release. The cell morphologies and nanoparticle distributions in the cells were analyzed by phase-contrast microscopy and transmission electron microscopy, respectively. The mitochondrial membrane potential was examined by confocal laser scanning microscopy. The retinal toxicity induced by SiO2 NPs in vivo was examined by immunohistochemical analysis. To further investigate the mechanism of retinal toxicity induced by SiO2 NPs, reactive oxygen species (ROS) generation, glial cell activation and inflammation were monitored. RESULTS: The 15-nm SiO2 NPs were found to have higher cytotoxicity than the larger NPs. Notably, the 15-nm SiO2 NPs induced retinal toxicity in vivo, as demonstrated by increased cell death in the retina, TUNEL-stained retinal cells, retinal ganglion cell degeneration, glial cell activation, and inflammation. In addition, The SiO2 NPs caused oxidative stress, as demonstrated by the increase in the ROS indicator H2DCF-DA. Furthermore, the pretreatment of R28 cells with N-acetylcysteine, an ROS scavenger, attenuated the ROS production and cytotoxicity induced by SiO2 NPs. CONCLUSIONS: These results provide evidence that SiO2 NPs induce size-dependent retinal toxicity and suggest that glial cell activation and ROS generation contribute to this toxicity.

Case series: Two cases of severe retinal cicatricial contraction after vitrectomy for open-globe injury in patients with skin keloid.

PURPOSE: To report two cases of severe retinal cicatricial contraction after vitrectomy for open-globe injury in patients with skin keloid. OBSERVATIONS: One was a 33-year-old male patient who developed severe retinal cicatricial contraction 6.5 months post-operatively, and his skin wound was observed with keloid simultaneously. The second case was a 36-year-old male patient who developed recurrent retinal detachment 1 week after the two operations, and keloid was also found on his skin. CONCLUSIONS AND IMPORTANCE: Retinal detachment is a vision-threatening complication of open-globe injury. Besides most of the already known factors, skin keloid should be concerned.

Patients with unilateral retinal vein occlusion show reduced radial peripapillary capillary density in their fellow eyes.

BACKGROUND: To evaluate the radial peripapillary capillary (RPC) density in the fellow eyes of unilateral retinal vein occlusion (RVO) patients using optical coherence tomography angiography (OCTA), and further analyze the correlation between RPC density and peripapillary retinal nerve fiber layer (RNFL) thickness. METHODS: Seventy-eight unilateral RVO patients and 70 normal controls were included in the study. OCTA was conducted with the 4.5 × 4.5-mm scan pattern centered on the optic nerve head, and the RPC density and peripapillary RNFL thickness were quantified. RESULTS: The peripapillary RNFL in the RVO fellow eyes was significantly thinner than in normal controls in the average, inferior-hemisphere, inferior quadrant, and temporal quadrant (P < 0.05, respectively). The RPC density in the fellow eyes was also significantly lower in the average, inferior-hemisphere, nasal quadrant, and temporal quadrant ((P < 0.05, respectively). There were no significant differences in RNFL thickness and RPC density between branch RVO fellow eyes and central RVO fellow eyes. Pearson's correlation analysis showed significant positive correlations between the RPC density and RNFL thickness in all measurements (P < 0.001, respectively). CONCLUSIONS: The regional RPC density was reduced in the RVO fellow eyes, which might contribute to peripapillary RNFL thinning in the corresponding region, suggesting the influence of systemic risk factors on RVO. OCTA may offer new insights into the pathophysiology of RVO.

Effects of the Pars Plana Vitrectomy on the Chronic Total Rhegmatogenous Retinal Detachment in the Young Adults.

Objective: To observe the characteristics and evaluate the efficacy and safety of the chronic total rhegmatogenous retinal detachment (RRD) treatment by the 23-gauge pars plana vitrectomy (PPV) in young adults and to analyze the related factors. Methods: A retrospective chart review was performed for the young adults who underwent the 23-gauge PPV for the chronic total RRD at the Tianjin Medical University General Hospital from 2011 to 2018. A total of 54 eyes of 48 patients were included in this study. The preoperative vision ranged from 2.00 to 1.00. The mean duration of RRD was 9 ± 0.6 months with a range from 4 to 18 months. The proliferative vitreoretinopathy (PVR) grade D1 and grade D2 was diagnosed in 48 eyes and 6 eyes, respectively. About 37 eyes were filled with C3F8 and 17 eyes were filled with silicone oil tamponade. The follow-up ranged from 9 to 78 months with a mean of 23 ± 2.2 months. Results: The postoperative visual acuity increased in all the eyes at the final observation. The retinal attachment was achieved in 49 eyes (90.7%) in the primary PPV. Five eyes (9.3%) with the failed retinal attachment finally achieved the attachment after the second procedure. The postoperative complications mainly included temporary intraocular pressure (IOP) elevation, hyphema, and retinal redetachment. Conclusion: Chronic total RRD can be treated via the 23-gauge PPV with a great anatomical and visual prognosis in the young adult. The successful treatment of the chronic total RRD in young adults is mainly associated with the complete dissection of the severe vitreoretinopathy, especially for the epiretinal membrane at the retinal breaks and degenerations and the subretinal proliferation during surgery.

Creation of a New Explosive Injury Equipment to Induce a Rabbit Animal Model of Closed Globe Blast Injury via Gas Shock.

To establish a rabbit animal model of closed globe blast injury with an application of self-developed explosive injury equipment, we tend to explore the anatomic and pathological changes of eyes under different gas pressure. The device comprises of high-pressure air source compression pump, air channel, and gas shock. There were 36 healthy bluish blue rabbits exposed to one of five blast pressures (500, 1,000, 1,500, 2,000, and 5,000 Kpa). Slit lamp microscope, B-mode ultrasonography, fundus photography, optical coherence tomography (OCT), and intraocular pressure (IOP) examination were performed at 0-, 1-, 3-, and 7-days post exposure, while gross histopathology was assessed with H&E stain at 7 days. The contralateral eyes and non-blast exposed rabbits were used as controls. Definitive evidence of closed globe blast injury was obtained. Corneal edema and hyphema were observed in the models under all pressures with no full-thickness globe injury, or lens rupture, as the severity was pressure independent. There was no obvious retinal abnormality on B ultrasound or OCT scan, while light vitreous hemorrhage, commotio retinae, and heavy retinal pigmentation presented on one eye, respectively, in the eyes exposed to 5,000 Kpa. Increased retinal thickness with disorganizations on the retinal ganglion cell (RGC) layer and RGC apoptosis in groups under higher pressure (>500 Kpa). IOP of injured eyes were statistically decreased at day 1 and 7 post injury (p < 0.05). Conclusively, the rabbit animal model induced by self-developed equipment could mimic the clinical features of closed ocular blast injury successfully that was feasible and easy to operate. This will be a new rabbit animal model for investigating mechanisms and new therapeutic interventions of closed globe blast injury in the future.

Tumor necrosis factor ligand-related molecule 1A maintains blood-retinal barrier via modulating SHP-1-Src-VE-cadherin signaling in diabetic retinopathy.

An impaired blood-retinal barrier (BRB) leads to diabetic macular edema (DME), which is a major complication of Diabetic retinopathy (DR). Mediators such as inflammation cause BRB breakdown. However, the explicit mechanism of its disruption is largely unknown. In this study, we identified tumor necrosis factor ligand-related molecule 1A (TL1A) as a crucial factor which protect retinal endothelial cells integrity in DR. By providing both human and mouse data, we show that TL1A is significantly decreased in the retinas of DME patients and diabetic rodents. We further demonstrate that the loss of TL1A accelerated diabetes-induced retinal barrier breakdown. TL1A supplementation protects the diabetic retina against BRB breakdown. Mechanistically, TL1A stabilize intracellular junctions and protect vascular integrity by blocking SHP1-Src-regulated VE-cadherin phosphorylation. Collectively, our findings reveal that loss of TL1A in the retina leads to increased vascular permeability in DR, and that TL1A treatment is of potential therapeutic interest for the treatment of DME.

Size-Dependent Cytotoxicity and Reactive Oxygen Species of Cerium Oxide Nanoparticles in Human Retinal Pigment Epithelia Cells.

PURPOSE: The use of cerium oxide nanoparticles (CeO2 NPs), a lanthanide element oxide and bivalent compound, has been growing continuously in industry and biomedicine. Due to their wide application, the potential human health problems of CeO2 NPs have attracted attention, but studies on the toxicity of this compound to human eyes are lacking. This study investigated the cytotoxicity and reactive oxygen species (ROS) of CeO2 NPs in human retinal pigment epithelial cells (ARPE-19 cells). METHODS: Using the transmission electron microscope (TEM), the size distribution and shape of CeO2 NPs were characterized. To explore the effect of CeO2 NP size on ophthalmic toxicity in vitro, three sizes (15, 30 and 45 nm) of CeO2 NPs were investigated using ATP content measurement, LDH release measurement and cell proliferation assay in ARPE-19 cells. ROS values and mitochondrial membrane potential depolarization were evaluated by H2DCF-DA staining and JC-1 staining. Morphology changes were detected using a phase-contrast microscope. RESULTS: The cytotoxicity of 15 nm CeO2 NPs was found to be the highest and hence was further explored. Treatment with 15 nm CeO2 NPs caused the morphology of ARPE-19 cells to change in a dose- and time-dependent manner. Moreover, the treatment induced excessive ROS generation and mitochondrial membrane potential depolarization. In addition, cytotoxicity was attenuated by the application of a ROS scavenger N-acetyl-L- cysteine (NAC). CONCLUSION: CeO2 NPs induced cytotoxicity in ARPE-19 cells and excessive production of ROS and decreasing mitochondrial membrane potential. The Overproduction of ROS partially contributes to CeO2 NP-induced cytotoxicity.

Repair of unilateral combined orbital floor and medial wall fracture using two titanium mesh plates: a modified technique.

BACKGROUND: Compared to isolated orbital wall fracture, combined orbital floor and medial wall fractures are more likely to be required surgical correction due to a higher possibility of complications. However, it remains a challenge to repair concomitant orbital fracture using a one-piece implant due to the complex anatomic structures of the orbit. Aiming to reduce surgical difficulties and enhance therapeutic effects, we repaired unilateral combined orbital floor and medial wall fractures using two separated modified titanium mesh plates in this study. METHODS: A retrospective study was conducted on 21 consecutive patients who presented with unilateral combined orbital floor and medial wall fractures in Tianjin Medical University General Hospital between November 2010 and January 2016. The orbital fractures were repaired with two separated titanium mesh plates. The corner at the transition zone area between the orbital floor and the medial wall was reconstructed simultaneously through a combined transcaruncular and inferior subciliary approach with lateral canthotomy. The pre- and post-operative functions and aesthetic results were evaluated. RESULTS: Preoperatively, all patients presented with 3.5-6.5 mm enophthalmos, five patients presented with diplopia with ocular motility limitation in injured eyes, and six patients presented with hypoglobus ranging from 1.5 to 3.5 mm. Orbital floor and medial wall fractures of all patients were successfully repaired with two separated titanium mesh plates. Postoperatively, enophthalmos was improved in all patients, which was less than 2 mm on the last follow-up day. Hypoglobus was disappeared in all six patients postoperatively. Diplopia was resolved in five patients within 3 months post operation, and was reduced in one patient. CONCLUSIONS: In cases of unilateral concomitant orbital floor and medial wall fractures, two titanium mesh plates implantation is a safe and effective procedure. It is worthwhile to take the technique into account when the key points to consider when applying this method include reconstruction of the special orbital shape and the complete return reposition of prolapsed intraorbital soft tissues were intended.