Wet age-related macular degeneration (wAMD), characterized by pathological choroidal neovascularization (CNV), is a leading cause of irreversible vision loss in the elderly. The current standard treatment-anti-vascular endothelial growth factor (VEGF) therapy-effectively manages neovascularization in many patients. However, some experience suboptimal responses, and frequent intravitreal injections raise safety concerns. Photodynamic therapy is another effective option for treating wAMD, but it can lead to an increase in reactive VEGF after the procedure, resulting in CNV recurrence. In response to these challenges, we propose an integrated approach that combines a DNA nanoflower VEGF degrader with photodynamic therapy. The DNA nanoflower consists of numerous aptamer-based lysosome-targeted chimaera (LYTAC) units, which drive extracellular VEGF in the lesion area to the lysosome for degradation. Simultaneously, the DNA nanoflower acts as a carrier for verteporfin (VER), a clinically used photosensitizer. The resulting nanoflower, named NF@VER, generates reactive oxygen species under near-infrared light to induce endothelial cell death. These combined effects on endothelial cells effectively block VEGF-induced CNV in vivo, without causing noticeable side effects. Overall, this innovative approach presents a precise and effective strategy for treating wAMD, reducing the risk of VEGF reactivation-induced CNV recurrence, and minimizing the systemic side effects associated with photodynamic therapy.

Insulin resistance (IR) plays a critical role in shaping long-term outcomes in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Recent findings suggest that biological sex may influence the onset and progression of MASLD, yet it remains unclear whether sex modifies the link between IR and mortality in those with MASLD and advanced liver fibrosis. We analyzed data from 14,081 MASLD patients (7327 men and 6754 women) drawn from the 2001–2018 cycles of the National Health and Nutrition Examination Survey (NHANES). Participants were categorized based on sex-specific deciles of the Metabolic Score for Insulin Resistance (METS-IR). Kaplan–Meier survival analysis and Cox proportional hazards models were used to assess the association between METS-IR and all-cause mortality. Restricted cubic spline (RCS) modeling explored potential non-linear relationships. Marked sex-related disparities were identified in clinical and metabolic characteristics. Elevated METS-IR significantly predicted increased all-cause mortality in females with MASLD (log-rank p < 0.001), whereas this trend was not evident in males (p = 0.54). Multivariable Cox models showed that higher METS-IR independently correlated with mortality in women with MASLD and advanced fibrosis, but not in their male counterparts. The prognostic significance of METS-IR differs by sex in MASLD. Elevated METS-IR independently increases long-term mortality risk in females, supporting the need for sex-specific risk evaluation in managing metabolic liver disease.

AIM: To identify different metabolites, proteins and related pathways to elucidate the causes of proliferative diabetic retinopathy (PDR) and resistance to anti-vascular endothelial growth factor (VEGF) drugs, and to provide biomarkers for the diagnosis and treatment of PDR. METHODS: Vitreous specimens from patients with diabetic retinopathy were collected and analyzed by Liquid Chromatography-Mass Spectrometry (LC-MS/MS) analyses based on 4D label-free technology. Statistically differentially expressed proteins (DEPs), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway representation and protein interactions were analyzed. RESULTS: A total of 12 samples were analyzed. The proteomics results showed that a total of 58 proteins were identified as DEPs, of which 47 proteins were up-regulated and 11 proteins were down-regulated. We found that C1q and tumor necrosis factor related protein 5 (C1QTNF5), Clusterin (CLU), tissue inhibitor of metal protease 1 (TIMP1) and signal regulatory protein alpha (SIRPα) can all be specifically regulated after aflibercept treatment. GO functional analysis showed that some DEPs are related to changes in inflammatory regulatory pathways caused by PDR. In addition, protein-protein interaction (PPI) network evaluation revealed that TIMP1 plays a central role in neural regulation. In addition, CD47/SIRPα may become a key target to resolve anti-VEGF drug resistance in PDR. CONCLUSION: Proteomic analysis is an approach of choice to explore the molecular mechanisms of PDR. Our data show that multiple proteins are differentially changed in PDR patients after intravitreal injection of aflibercept, among which C1QTNF5, CLU, TIMP1 and SIRPα may become targets for future treatment of PDR and resolution of anti-VEGF resistance.

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: β coefficient = -0.351, p = 0.023; perifovea: β coefficient = -0.338, p = 0.036). Perifoveal VLD (β coefficient = -0.343, p = 0.031) and FD (β coefficient = -0.375, p = 0.016) of the SCP were also negatively correlated with postoperative BCVA. Regarding the DCP, perifoveal VD (β coefficient = -0.396, p = 0.008), perifoveal VLD (β coefficient = -0.334, p = 0.025), vessel tortuosity (VT) (β coefficient = -0.369, p = 0.015) were negatively correlated with postoperative BCVA. In CCP, VLD (β coefficient = -0.373, p = 0.023) and number of flow voids (β 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).

BACKGROUND:The dysregulation of the innate immune system plays a crucial role in the development of Diabetic Retinopathy (DR). To gain an insight into the underlying mechanism of DR, it is essential to identify specific biomarkers associated with immune cell infiltration. METHODS:In this study, we retrieved the GSE94019 and GSE60436 datasets from the Gene Expression Omnibus (GEO) database. By utilizing CIBERSORT, MCPcounter, and xCell algorithms, we conducted a comprehensive analysis of the immune cell infiltration landscape in DR. The limma package was employed to identify Differentially Expressed Necroptosis-related Genes (DENRGs). Subsequently, enrichment analysis was performed to investigate the potential functions of the DENRGs. To identify the core DENRGs, the CytoHubba plug-in in Cytoscape software was utilized. The expression levels of these core DENRGs were verified in an independent dataset. RESULTS:Our analysis identified 213 DENRGs, and among them, Platelet-derived Growth Factor subunit A (PDGFA) was identified as a core DENRG. Notably, the expression of PDGFA was found to be upregulated in DR, and this finding was further validated in the GSE102485 dataset. Additionally, the results of GSVA and GSEA revealed that in the high PDGFA group, there was activation of pathways related to inflammation and the immune system. Moreover, analysis of immune infiltration demonstrated a significant association between PDGFA gene expression and the infiltration levels of specific immune cells, including basophils, macrophages M1, macrophages, neutrophils, monocytes, NK cells, and B cells. CONCLUSION:The involvement of neutrophils in the development and progression of DR is suggested. PDGFA has emerged as a potential marker and is linked to the infiltration of immune cells in DR. These findings shed new light on the underlying mechanisms of DR.

AIM: To observe the retinal and choroidal circulations in patients with non-arteritic permanent central retinal artery occlusion (NA-CRAO) via optical coherence tomography angiography (OCTA) and analyze their correlation with visual acuity. METHODS: Sixty-two eyes with clinically confirmed acute NA-CRAO were included in the study and divided into: A type (mild n=29), B type (moderate n=27) and C type (severe n=6) based on the degree of visual loss, retinal edema, and arterial blood flow delay in fundus fluorescence angiography (FFA). Contralateral healthy eyes were used as the control group. Best-corrected visual acuity (BCVA), slit lamp microscopy, indirect ophthalmoscopy, fundus color photography, OCTA, and FFA were performed. Spearman's correlation analysis was used to determine the correlations between retinal and choroidal vessels and visual acuity. RESULTS: There were no statistically significant differences in age, gender, and intraocular pressure among the three types and the control group (P>0.05). Vessel density in deep capillary plexus (VD-DCP) significantly decreased (P<0.05) in all three types of NA-CRAO patients compared to the control group. Vessel density in superficial vascular plexus (VD-SVP) significantly decreased (P<0.05) in type A patients and choriocapillaris flow area significantly decreased (P<0.05) in type B and type C patients compared to the control group; while outer retinal flow areas significantly increased in the type A (P<0.05) and decreased in type C patients (P<0.05). The retinal thickness significantly increased in type C group (P<0.05). The VD-SVP at fovea in the type A was significantly lower than both of type B and C. The VD-SVP at nasal parafovea in type A and B was significantly lower than type C (P<0.05). The logMAR BCVA of type A was significantly better than that of type B and C groups (P<0.05). Spearman's correlation analysis showed that the logMAR BCVA was positively correlated with VD-SVP at fovea (r=0.679, P=0.031) and nasal parafovea (r=0.826, P=0.013). CONCLUSION: OCTA is valuable for assessing retinal ischemia, and evaluating visual impairment. Deep retinal vasculature is commonly affected in all NA-CRAO types. VD-SVPs at fovea and nasal parafovea can serve as reliable markers of visual impairment in NA-CRAO.

AIM: To observe the effect of human umbilical cord mesenchymal stem cells (hUCMSCs) secretions on the relevant factors in mouse retinal astrocytes, and to investigate the effect of hUCMSCs on the expression of vascular endothelial growth factor-A (VEGF-A) and to observe the therapeutic effect on the mouse model of retinopathy of prematurity (ROP). METHODS: Cultured hUCMSCs and extracted exosomes from them and then retinal astrocytes were divided into control group and hypoxia group. MTT assay, flow cytometry, reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to detect related indicators. Possible mechanisms by which hUCMSCs exosomes affect VEGF-A expression in hypoxia-induced mouse retinal astrocytes were explored. At last, the efficacy of exosomes of UCMSCs in a mouse ROP model was explored. Graphpad6 was used to comprehensively process data information. RESULTS: The secretion was successfully extracted from the culture supernatant of hUCMSCs by gradient ultracentrifugation. Reactive oxygen species (ROS) and hypoxia inducible factor-1α (HIF-1α) of mice retinal astrocytes under different hypoxia time and the expression level of VEGF-A protein and VEGF-A mRNA increased, and the ROP cell model was established after 6h of hypoxia. The secretions of medium and high concentrations of hUCMSCs can reduce ROS and HIF-1α, the expression levels of VEGF-A protein and VEGF-A mRNA are statistically significant and concentration dependent. Compared with the ROP cell model group, the expression of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signal pathway related factors in the hUCMSCs exocrine group is significantly decreased. The intravitreal injection of the secretions of medium and high concentrations of hUCMSCs can reduce VEGF-A and HIF-1α in ROP model tissues. HE staining shows that the number of retinal neovascularization in ROP mice decreases with the increase of the dose of hUCMSCs secretion. CONCLUSION: In a hypoxia induced mouse retinal astrocyte model, hUCMSCs exosomes are found to effectively reduce the expression of HIF-1α and VEGF-A, which are positively correlated with the concentration of hUCMSCs exosomes. HUCMSCs exosomes can effectively reduce the number of retinal neovascularization and the expression of HIF-1α and VEGF-A proteins in ROP mice, and are positively correlated with drug dosage. Besides, they can reduce the related factors on the PI3K/AKT/mTOR signaling pathway.

BackgroundThe 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. MethodsClinical 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. ResultsThe 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. ConclusionsVisionGo has achieved an accurate and reliable prediction in visual outcome after vitrectomy for OGI-NLP eyes.

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.

? AIM: To investigate the association of ganglion cell complex thickness (GCCt), global loss volume percentage (GLV%), and focal loss volume percentage (FLV%) with structural and functional findings among patients with chronic central serous chorioretinopathy (CCSC) and recurrent central serous chorioretinopathy (RCSC) by optical coherence tomography (OCT). ? METHODS: Among 29 patients with monocular affected central serous chorioretinopathy (CSC), 15 had CCSC, and 14 had RCSC. The GCCt, FLV%, GLV%, and subfoveal choroidal thickness (SFCT) and sublesional choroidal thickness (SLCT) values were determined using OCT, and the association of these characteristics with neural structure parameters, choroidal morphology, features and functional alterations were estimated for the CCSC and RCSC patients. ? RESULTS: In CCSC, the affected eyes had significantly lower GCCt values than the fellow eyes in the macular regions (all P<0.05), with the highest GCCt observed in the inferior area. A significant association was found between the GCCt in different regions and the change in best corrected visual acuity (BCVA; r=-0.696;-0.695;-0.694, P<0.05) in CCSC patients. A statistically significant moderate negative correlation indicated that long-term CCSC was associated with greater differences in the GCCt in different regions between affected and fellow eyes (r=-0.562; r=-0.556; r=0.525, P<0.05). Additionally, observation of thickened SFCT was associated with a worse FLV% (r=0.599; r=0.546, P<0.05) in both groups. Similarly, thickened SLCT was associated with FLV% in RCSC patients (r=0.544, P<0.05). ? CONCLUSION: The distribution and GCCt are associated with the duration and visual outcomes of CCSC, whereas there is no correlation among RCSC patients. FLV% may be instrumental in differentiating the various outer choroidal vessels (pachyvessels) in long-term CSC. These results suggest that neural structure parameters may aid in estimating and predicting the recovery of altered morphology and function in CCSC and RCSC patients.

AIM:To evaluate effects of endogenous dopamine induced by low concentration atropine eye drops on choroidal neovascularization (CNV) in high myopia mice.METHODS:The C57BL/6J mice were deprived of the right eye for 4wk, and the high myopia was diagnosed by optometry, the diopter was less than -6.00 D, and CNV was induced by 532 nm laser. The changes of dopamine D1 receptor (DRD1), dopamine D2 receptor (DRD2), and vascular endothelial growth factor A (VEGFA) were detected by Western blot technology at 0.5, 1, 2h, and 7d after 0.01%, 0.05%, and 0.1% atropine eye drops, respectively, the area of CNV was measured.RESULTS:Significant increases were observed on the expression of DRD2 in mouse high myopia model at 0.5, 1, 2h, 7d with 0.05% and 0.1% atropine eye drops (P<0.05). Significant decreases were observed on the expression of DRD1 and VEGFA in mouse high myopia model at 0.5, 1, 2h, 7d with 0.05% and 0.1% atropine eye drops (P<0.05). The area of CNV induced by laser in the drug-treated group was significantly smaller than that in the control group, and the higher the concentration, the more significant the inhibitory effect (P<0.05).CONCLUSION:The 0.01%, 0.05%, 0.1% atropine eye drops can decrease the level of VEGFA and inhibit high myopia CNV indirectly by up-regulating the level of DRD2 and down-regulating the level of DRD1, and the effect of 0.05% and 0.1% atropine eye drops is more significant.

目的 比较合并糖尿病黄斑水肿(DME)的白内障患者,行超声乳化术(Phaco)联合地塞米松玻璃体腔植入物(Ozurdex;DEX-I)与单纯行超声乳化术后,其黄斑部形态与功能的变化.方法 回顾性病例对照研究.纳入对象为我院就诊的合并DME的46 例(46 只眼)白内障患者,其中行伴有DEX-I的超声乳化术的 23 例(23 只眼)患者为Phaco-Dex组,行单纯超声乳化术的23 例(23 只眼)患者为单纯Phaco组.比较其术前及术后不同阶段黄斑部形态与功能的变化.结果 Phaco-Dex组,与术前相比,从术后第 1 个月开始BCVA(logMAR)均显著提高(P＜0.05);黄斑中心凹视网膜厚度(CMT)和黄斑体积(MV)自第2 个月起显著下降(P＜0.05);与单纯Phaco组相比较,Phaco-Dex组在每个随访点CMT和MV均显著降低.随访期间单纯Phaco组眼压显著升高(P＜0.05).单纯Phaco-alone组,CMT和MV从第2 个月开始增加(P＜0.05).结论 对合并DME视力显著性下降的白内障患者,超声乳化吸除联合DEX-I治疗是有效、安全的,不管是黄斑部形态和功能的改善方面都要优于单纯白内障超声乳化手术.

? AIM: To identify metabolites, proteins, and related pathways involved in the etiology of rhegmatogenous retinal detachment (RRD) for use as biomarkers in diagnosing and treating RRD.? METHODS: Vitreous specimens were collected and liquid chromatography-tandem mass spectrometry analysis was performed using the four-dimensional label-free technique. Statistically significant differentially expressed proteins, gene ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway representations, and protein interactions were analyzed.? RESULTS: Nine specimens were subjected to proteomic analysis. In total, 161 proteins were identified as differentially expressed proteins (DEPs), including 53 upregulated proteins and 108 downregulated proteins. GO functional analysis revealed that some DEPs were enriched in neuron-related terms and membrane protein terms. Moreover, KEGG analysis indicated that the cell adhesion molecule metabolic pathway was associated with the greatest number of DEPs. Finally, the evaluation of protein-protein interaction network revealed that DEPs were clustered in neuronal adhesion, apoptosis, inflammation and immune responses, correct protein folding, and glycolysis.? CONCLUSION: Proteomic profiling is useful for the exploration of molecular mechanisms that underlie RRD. This study reveals increased expression levels of proteins related to heat shock protein content, glycolysis, and inflammatory responses in RRD. Knowledge regarding biomarkers of RRD pathogenesis may help to prevent the occurrence of RRD in the future.

AIM To describe the clinical characteristics of eyes using multimodal imaging features with acute macular neuroretinopathy (AMN) lesions following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS Retrospective case series study. From December 18, 2022 to February 14, 2023, previously healthy cases within 1-week infection with SARS-CoV-2 and examined at Tianjin Eye Hospital to confirm the diagnosis of AMN were included in the study. Totally 5 males and 9 females [mean age: 29.93±10.32 (16-49)y] were presented for reduced vision, with or without blurred vision. All patients underwent best corrected visual acuity (BCVA), intraocular pressure, slit lamp microscopy, indirect fundoscopy. Simultaneously, multimodal imagings fundus photography (45° or 200° field of view) was performed in 7 cases (14 eyes). Near infrared (NIR) fundus photography was performed in 9 cases (18 eyes), optical coherence tomography (OCT) in 5 cases (10 eyes), optical coherence tomography angiography (OCTA) in 9 cases (18 eyes), and fundus fluorescence angiography (FFA) in 3 cases (6 eyes). Visual field was performed in 1 case (2 eyes). RESULTS Multimodal imaging findings data from 14 patients with AMN were reviewed. All eyes demonstrated different extent hyperreflective lesions at the level of the inner nuclear layer and/or outer plexus layer on OCT or OCTA. Fundus photography (45° or 200° field of view) showed irregular hypo-reflective lesion around the fovea in 7 cases (14 eyes). OCTA demonstrated that the superficial retinal capillary plexus (SCP) vascular density, deep capillary plexus (DCP) vascular density and choriocapillaris (CC) vascular density was reduced in 9 case (18 eyes). Among the follow-up cases (2 cases), vascular density increased in 1 case with elevated BCVA; another case has vascular density decrease in one eye and basically unchanged in other eye. En face images of the ellipsoidal zone and interdigitation zone injury showed a low wedge-shaped reflection contour appearance. NIR image mainly show the absence of the outer retinal interdigitation zone in AMN. No abnormal fluorescence was observed in FFA. Corresponding partial defect of the visual field were visualized via perimeter in one case. CONCLUSION The morbidity of SARS-CoV-2 infection with AMN is increased. Ophthalmologists should be aware of the possible, albeit rare, AMN after SARS-CoV-2 infection and focus on multimodal imaging features. OCT, OCTA, and infrared fundus phase are proved to be valuable tools for detection of AMN in patients with SARS-CoV-2.

Abstract AIM: To evaluate the changes of choroid thickness in adolescence with different types of high myopia. METHODS: From January to November 2021, 134 eyes of 78 adolescents with myopia in Liaocheng Aier Eye Hospital were collected and analyzed. According to the Mean Spherical Equivalent(MSE) and Corneal Curvature(CC), subjects are divided into mild myopia or emmetical eye group (ME group), high myopia group (HM group), occult high myopia group(OHM group) and super high myopia group(SHM group). The macular foveal choroidal thickness(CT) of the four groups was analyzed by Using Zeiss frequecy domain optical coherence tomography (Cirrus HD OCT), acquire horizontal and vertical cross-sectional images of macular. The CT values were measured manually subfoveal choroidal thickness(SFCT) and 1mm,3mm from the fovea at 9 sites, including the superior, nasal, inferior, temporal. The same operator completed the measurement 3 times ,and took the average numerical value as the final reference data.RESULTS:. There were significant differences in choroid thickness at 1mm and 3mm in macular fovea (P < 0.05). Compared with the ME group, SFCT, 1mm and 3mm in the HM group, OHM group and SHM group were significantly thinner than those in ME group (P < 0.05). Compared with SHM, HM and OHM group were significant differences in CT (P < 0.05). There was no statistical significance in CT of each point in HM group and OHM group (P > 0.05). CONCLUSION: The CT of SHM is significantly lower than that of HM and OHM. Although OHM has a lower degree of myopia, the CT has become significantly thinner, and the degree of choroid thinning is almost the same as that of OHM.

AIM: To assess the effects of intravitreal ranibizumab (IVR) on angiogenesis and glial activity of the fibrovascular membrane (FVM) in patients with proliferative diabetic retinopathy (PDR). METHODS: Forty-two eyes from 42 patients with PDR requiring vitrectomy were included and divided into two groups: control group (n=16) did not receive IVR, while IVR group (n=26) underwent IVR 5d before vitrectomy. FVM specimens were collected by the same surgeon during the interventions. Histopathological morphology was examined by hematoxylin-eosin (H-E) staining and cell densities in the FVM was assessed. Microvessels were outlined by immunohistochemical staining of CD31 and microvessel density (MVD) assessed as an index of FVM angiogenesis. Dual-color immunofluorescence staining, and confocal microscopy was used to detect co-localization and relative expression levels of glial fibrillary acidic protein (GFAP) and α-smooth muscle actin (α-SMA) as markers of glial-mesenchymal transition (GMT). The GMT index (GI; ratio of relative GFAP/α-SMA expression) was used to semi-quantify the degree of GMT or glial activity of FVMs. RESULTS: H-E staining showed similar vascularization in both groups, with microvessels and scattered stromal cells in the matrix. Infiltrated cell densities did not differ significantly between the two groups (P>0.05). The MVD of the IVR group (130.62±15.46/mm2) was significantly lower than that of the controls (142.25±19.16/mm2, P<0.05). In both groups, all sections were strongly immunostained for GFAP and α-SMA. The Pearson's correlation coefficients (PCC) of intensity of automated pixel count of two markers indicated GFAP and α-SMA co-stained well and GMT participated in the remolding of FVMs in PDR. The mean relative GFAP expression in the IVR group was significantly lower, whereas that of α-SMA was significantly higher than in controls (P<0.05). GI in the IVR group (1.10±0.10) was significantly lower than in the controls (1.21±0.12, P<0.05). CONCLUSION: IVR can reduce angiogenesis, glial activity of FVM and promote glial-fibrotic transformation by reducing MVD and promoting GMT but does not decrease the cell density in patients with PDR.

AIM To investigate the binocular intraocular lens (IOL) power difference in eyes with short, normal, and long axial lengths (AL) using Lenstar LS 900 optical biometry. METHODS A total of 716 (1432 eyes) participants were included. The groups were categorized into short (group A: AL<22 mm), normal (group B: 22 mm≤AL≤25 mm), and long AL groups (group C: AL>25 mm). The central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT), AL, anterior corneal keratometry, white-to-white (WTW), pupil diameter (PD), as well as IOL power calculated using embedded Barrett formula were assessed. Bland-Altman plots were used to test the agreement of the binocular parameters. RESULTS In group A, the CCT of the right eye was significantly thinner than that of the left eye (P=0.044) with a difference of -2±8 µm [95% limits of agreement (LoA), -17.8 to 13.2 µm]. For group B, the PD and IOL power in the right eye were significantly lower than those of the left eye (P=0.001, <0.001) with a difference of -0.05±0.32 mm (95%LoA, -0.68 to 0.58 mm) and -0.18±1.01 D (95%LoA, -2.2 to 1.8 D). The AL of right eye was longer than that of the left eye (P=0.002) with a difference of 0.04±0.25 mm (95%LoA, -0.45 to 0.52 mm). No significant difference was observed for all the binocular parameters in group C. The percentage of participants with binocular IOL power difference within ±0.5 D were 62% (31/50), 68.3% (339/496), and 38.8% (66/170) in groups A, B, and C, respectively. CONCLUSION The binocular parameters related to IOL power are in good agreement, but the binocular IOL power difference of more than half of participants with long AL is more than 0.50 D.

AIM: To assess the protective effect of human umbilical cord mesenchymal stem cell exosomes (hucMSC-Exs) in a diabetic rat model by using a variety of retinal bioassays. METHODS: hucMSCs were subjected to differential ultracentrifugation for the collection of exosomes, and transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) using a NanoSight analysis system and Western blotting (WB) were used to analyze the expression of surface marker proteins such as CD63, CD9 and Calnexin. Streptozotocin (STZ) was injected into the intraperitoneal cavity to establish a diabetic model. Rats were divided into a normal group, diabetic group and hucMSC-Ex group. Fundus fluorescein angiography (FFA), optical coherence tomography (OCT) and other live imaging methods were used to observe the fundus of the rats. Finally, the eyeballs of rats from each group were collected for hematoxylin-eosin (HE) staining to further analyze the retinal structure. RESULTS: Through TEM, NTA and WB, we successfully isolated hucMSC-Exs. Subsequent FFA and OCT confirmed that hucMSC-Exs effectively prevented early retinal vascular damage and thickening of the retina. Finally, HE staining of rat retinal sections revealed that exosomes effectively alleviated retinal structure disruption caused by diabetes. CONCLUSION: hucMSC-Exs have a protective effect on the retina in diabetic rat through FFA, OCT and HE staining.

AIM: To determine the effect of exosomes derived from human umbilical cord blood mesenchymal stem cells (hUCMSCs) on the expression of vascular endothelial growth factor A (VEGF-A) in human retinal vascular endothelial cells (HRECs). METHODS: Exosomes were isolated from hUCMSCs using cryogenic ultracentrifugation and characterized by transmission electron microscopy, Western blotting and nanoparticle tracking analysis. HRECs were randomly divided into a normal control group (group A), a high glucose model group (group B), a high glucose group with 25 μg/mL (group C), 50 μg/mL (group D), and 100 μg/mL exosomes (group E). Twenty-four hours after coculture, the cell proliferation rate was detected using flow cytometry, and the VEGF-A level was detected using immunofluorescence. After coculture 8, 16, and 24h, the expression levels of VEGF-A in each group were detected using PCR and Western blots. RESULTS: The characteristic morphology (membrane structured vesicles) and size (diameter between 50 and 200 nm) were observed under transmission electron microscopy. The average diameter of 122.7 nm was discovered by nanoparticle tracking analysis (NTA). The exosomal markers CD9, CD63, and HSP70 were strongly detected. The proliferation rate of the cells in group B increased after 24h of coculture. Immunofluorescence analyses revealed that the upregulation of VEGF-A expression in HRECs stimulated by high glucose could be downregulated by cocultured hUCMSC-derived exosomes (F=39.03, P<0.01). The upregulation of VEGF-A protein (group C: F=7.96; group D: F=17.29; group E: F=11.89; 8h: F=9.45; 16h: F=12.86; 24h: F=42.28, P<0.05) and mRNA (group C: F=4.137; group D: F=13.64; group E: F=22.19; 8h: F=7.253; 16h: F=16.98; 24h: F=22.62, P<0.05) in HRECs stimulated by high glucose was downregulated by cocultured hUCMSC-derived exosomes (P<0.05). CONCLUSION: hUCMSC-derived exosomes downregulate VEGF-A expression in HRECs stimulated by high glucose in time and concentration dependent manner.

Background To compare the accuracy of low-frequency ultrasound biomicroscopy (LFUBM) and 14-MHz ultrasonography with tissue harmonic imaging (14-MHz + THI) in the assessment of posterior capsule (PC) integrity in patients with traumatic cataracts (TCs). Methods From January 2019 to October 2020, 51 patients (51 eyes) with TCs who were scheduled for cataract extraction and for whom the PC of the lens could not be observed by the slit lamp visited Tianjin Eye Hospital, including 47 patients (47 eyes) with a penetrating injury of the eyeball and 4 patients (4 eyes) with a blunt injury of the eyeball. All eyes underwent LFUBM and 14-MHz + THI examinations before cataract extraction to determine the integrity of the PC. The integrity of the PC observed in surgery was the actual findings, and the consistency between the 2 methods was assessed in terms of the preoperative examination and intraoperative findings. Fisher’s exact test was used for consistency analysis, and P < 0.05 was considered statistically significant. Results Thirty-two eyes with ruptured PCs and 19 eyes with intact PCs were actual findings in surgery. Thirty eyes with ruptured PCs and 21 eyes with intact PCs were examined by LFUBM. Thirty-two eyes with ruptured PCs and 19 eyes with intact PCs were examined by 14-MHz + THI. There were no significant differences between the 2 methods and the intraoperative findings (P = 0.293 LFUBM, P = 0.623 14-MHz + THI). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of LFUBM and 14-MHz + THI were 91 and 94%, 95 and 89%, 97 and 94%, 86 and 89% and 92 and 92%, respectively. Conclusions Both LFUBM and 14-MHz + THI were proved to have high levels sensitivity and specificity in diagnosing the status of the PC in TC and they can be used as accurate diagnostic tool in these cases.