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AIM: To compare the efficacy of different dosing regimens of conbercept in the treatment of pathological myopic choroidal neovascularization(CNV).METHODS: Prospective clinical study. Totally 42 patients(42 eyes)who were diagnosed with pathological myopic CNV in our hospital from January 2019 to January 2022 were selected in the study. According to two different initial dosing regimens, the patients were divided into 1+pro re nata(PRN)group, with 20 patients(20 eyes), and 3+PRN group with 22 patients(22 eyes). The patients in the 1+PRN group were given one intravitreal injection and then given PRN, the patients in the 3+PRN group were given intravitreal injection once a month for 3 mo and then given PRN. Followed-up for 12 mo after initial treatment, the best corrected visual acuity(BCVA), central macular thickness(CMT), CNV area and injection times were compared between the two groups.RESULTS: The BCVA was improved, CMT was decreased, and CNV area was reduced at 1, 3, 6, and 12 mo after the initial treatment(P<0.01). However, there was no statistically significant difference in BCVA, CMT and CNV area between two groups(P>0.05). The average injection in the 1+PRN group was significantly less than that of the 3+PRN group [2(1, 3)times vs 3(3, 4)times, P<0.05], but the average reinjection in the 1+PRN group was more than that of the 3+PRN group [1(0, 2)times vs 0(0, 1)times, P<0.05].CONCLUSION: Two regimens were both safe and effective in the treatment of pathological myopic CNV by Conbercept, which can improve BCVA, decrease CMT, and reduce CNV area, with less total times of injection in the 1+PRN regimen, and less times of reinjection in the 3+PRN regimen.
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Age-related macular degeneration(ARMD)is the leading cause of blindness in the elderly. Studies have shown that the regulation disorder of extracellular matrix(ECM)is one of the important characteristics of ARMD, and its damage can be sustained throughout the disease course. Additionally, various cell types participate in the formation and abnormal deposition of ECM under the control of multiple signals. Subsequently, they transmit signals that regulate adhesion, migration, proliferation, apoptosis, survival or differentiation, which lead to the destruction of the retinal and choroidal microenvironment, immune dysfunction, infiltrative inflammatory cell differentiation, neovascularization and epithelial mesenchymal transformation, and ultimately lead to subretinal fibrosis, scarring and severe visual impairment in advanced ARMD. Therefore, increasing attention has been paid to the role of ECM in ARMD in recent years. This article reviews the relationship between retinal ECM and ARMD and the role between ECM and various types of cells in ARMD, hoping to provide guidance for the research direction of ARMD treatment.
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AIM: To observe the multimodal imaging characteristics of Best vitelliform macular dystrophy(BVMD).METHODS:The clinical data of 30 patients(60 eyes)diagnosed as BVMD at stage Ⅰ to Ⅳ in Nanjing Medical University Affiliated Eye Hospital from June 2016 to October 2022 were collected for a retrospective analysis, and all patients are binocular involved. All patients underwent best corrected visual acuity(BCVA), slit lamp microscopy, indirect ophthalmoscopy, intraocular pressure, fundus photography, spectral-domain optical coherence tomography(SD-OCT), fundus autofluorescence(FAF), fundus fluorescein angiography(FFA), electro-oculogram(EOG)and optical coherence tomography angiography(OCTA).RESULTS: A total of 30 patients(60 eyes)were included, with 8 eyes at stage Ⅰ, 24 eyes at stage Ⅱ, 22 eyes at stage Ⅲ and 6 eyes at stage Ⅵ. The imaging characteristics of fundus photography, FAF, FFA and SD-OCT were basically consistent with previous literature reports. EOG showed Arden ratio <1.55. OCTA could detect early lesions, observe the location of vitelliform substance, external segment of photoreceptor, fluid and choroidal neovascularization(CNV).CONCLUSION: Multimodal imaging assisted in diagnosing BVMD, reducing missed diagnosis and misdiagnosis, among which OCTA had significant advantages over other examinations, and fast and non-invasive were its biggest advantages.
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Choroidal neovascularization(CNV)is the ultimate pathological manifestation of various ocular diseases. Its pathogenesis is extremely complex and involves multiple cells, cytokines, and signaling pathways. MicroRNA(miRNA), as a kind of small biological molecules, is a non-coding RNA composed of 22 nucleotides that regulates gene expression by degrading or inhibiting mRNA translation of target genes. Having been increasingly studied and their involvement in the development of various diseases through miRNA-mediated signaling pathways have been revealed. In the field of ophthalmology, miRNA target specific protein genes through various signaling pathways to promote or inhibit CNV. Therefore, revealing the role and mechanism of miRNA in the pathogenesis of CNV is an important direction of future research on the pathogenesis of CNV. This article aims to review on phosphatidylinositol 3 kinase- protein kinase B(PI3K-Akt), transforming growth factor-beta(TGF-β), nuclear factor-kappa B(NF-κB), Notch and Wnt signaling pathways in miRNA regulation of CNV, providing new insights into the pathogenesis of CNV and targeted therapy for CNV.
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Objective To analyze the influencing factors of choroidopathy(choroidal atrophy and choroidal neovas-cularization)secondary to high myopia based on Logistic regression analysis and to construct a Nomogram risk prediction model based on the related factors,so as to provide guidance for clinical treatment.Methods A total of 340 patients(680 eyes)with high myopia admitted to Beijing Jishuitan Hospital from January 2021 to January 2023 were selected and di-vided into group A(170 patients,340 eyes)and group B(170 patients,340 eyes).The incidence of choroidopathy in the two groups was compared.The groups A and B were divided into two subgroups,subgroup a and subgroup b,according to whether choroidopathy occurred or not.Multivariate Logistic regression analysis was carried out to explore the influencing factors of choroidopathy secondary to high myopia.A Nomogram risk prediction model for choroidopathy secondary to high myopia was constructed based on the influencing factors and externally validated.Results In groups A and B,the age,proportion of diabetes mellitus,axial length,and level of seruim transforming growth factor β1(TGF-β1)of patients in subgroup a were higher than those in the subgroup b,and the diopter was lower than that in the subgroup b(all P＜0.05).The Logistic regression analysis showed that age,diabetes mellitus,axial length and serum TGF-β1 level were independent risk factors for choroidopathy secondary to high myopia,and diopter was a protective factor(all P＜0.05).Age,diabetes mellitus,axial length and serum TGF-β1 level were positively correlated risk factors for choroidopathy secondary to high myopia,and diopter was a negatively correlated risk factor(all P＜0.05).The area under the curve of the Nomogram risk prediction model for predicting choroidopathy secondary to high myopia was 0.818,and the calibration was good.Con-clusion Age,diabetes mellitus,axial length,diopter and serum TGF-β1 level are the influential factors for choroidopa-thy secondary to high myopia.The Nomogram risk prediction model established based on these factors has a certain value for predicting choroidopathy secondary to high myopia.The clinical therapeutic schedules should be made based on this model to reduce the risk of secondary choroidopathy.
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Objective To investigate the effect of the HtrA serine peptidase 3(HTRA3)gene on choroidal neovascu-larization(CNV)and M2 macrophage polarization.Methods Fasting venous blood was collected from 30 patients with wet age-related macular degeneration(wAMD group)and 30 healthy subjects(normal group).The serum HTRA3 messen-ger ribonucleic acid(mRNA)level was detected by quantitative reverse transcription polymerase chain reaction(qRT-PCR).RF/6A cells were randomly divided into the control group,NC-sh group and HTRA3-sh group.Lentiviral vectors of NC-shRNA and HTRA3-shRNA were transfected into RF/6A cells in the NC-sh group and HTRA3-sh group by Lipo-fectamine2000.HTRA3 transfection was detected by qRT-PCR and Western blot.Then,the RF/6A cells were randomly di-vided into the N group,H group,H+NC-sh group and H+HTRA3-sh group.After cell transfection,RF/6A cells in the N group were cultured in a RPMI 1640 complete medium at a normoxia state,and cells in other groups were cultured in a RP-MI 1640 medium with 200 mmol·L-1 CoCl2 at a hypoxia state.Tubule formation was measured by Matrigel.The C57BL/6J mice were divided into the control group,CNV group,CNV+NC-sh group and CNV+HTRA3-sh group,with 12 mice in each group.Mice in the control group were unmodeled mice,and mice in the other groups were laser-induced CNV model mice.NC-shRNA and HTRA3-shRNA lentiviral vectors with a titer of 1 × 1011 TU·mL-1 were administered to mice in the CNV+NC-sh group and CNV+HTRA3-sh group via intravitreal injection.Mice in the control group and CNV group were in-jected with phosphate buffered saline.After 7 days of treatment,the mice were examined by fundus fluorescein angiogra-phy,and the eyeballs received hematoxylin & eosin staining.The mRNA levels of HTRA3,chitinase-like protein 3(Ym-1),arginase 1(Arg-1),inducible nitric oxide synthase(iNOS),cyclooxygenase-2(COX-2)and vascular endothelial growth factor(VEGF)in RF/6A cells or choroidal tissues were detected by qRT-PCR.The protein expression levels of HTRA3,VEGF and nuclear factor kappa B(NF-κB)p65 in RF/6A cells or choroidal tissues were detected by Western blot.Re-sults Compared with the normal group,serum HTRA3 mRNA level of patients in the wAMD group increased(t=11.804,P＜0.001).Compared with the control group and NC-sh group,the expressions of HTRA3 mRNA and protein in RF/6A cells in the HTRA3-sh group decreased(all P＜0.05).Compared with the N group,the number of closed lumen and the mRNA and protein expressions of HTRA3 and VEGF in RF/6A cells in the H group increased(all P＜0.05).Compared with the H+NC-sh group,the number of closed lumen and the mRNA and protein expressions of HTRA3 and VEGF decreased in RF/6A cells in the H+HTRA3-sh group(all P＜0.05).Compared with the control group,the mRNA and protein expression levels of HTRA3 increased,the relative fluorescence intensity of CNV increased,the mRNA levels of Ym-1 and Arg-1 in-creased,the iNOS and COX-2 mRNA levels decreased,and the NF-κB p65 protein expression level increased in mice of the CNV group(all P＜0.05).Compared with the CNV+NC-sh group,the mRNA and protein expression levels of HTRA3 de-creased,the relative fluorescence intensity of CNV decreased,the mRNA levels of Ym-1 and Arg-1 decreased,the mRNA levels of iNOS and COX-2 increased,and the NF-κB p65 protein expression level decreased in mice of the CNV+HTRA3-sh group(all P＜0.05).Conclusion Down-regulation of HTRA3 can inhibit the formation of CNV and the polarization of M2 macrophages.HTRA3 may be an important potential target for the prevention and treatment of wAMD.
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AIM:To investigate the mechanism of curcumin inhibiting the choroidal neovascularization(CNV)of brown Norway(BN)rats.METHODS: CNV model of 36 BN rats was established through laser photocoagulation induction, and they were divided into 6 groups with 6 rats in each group. Normal group was fed normally with no intervention, while 532nm laser photocoagulation was used to establish a experimental CNV model in BN rats. Rats after modeling were respectively intervened for 14d and divided into model group, ranibizumab group, curcumin low [100mg/(kg·d)], medium [200mg/(kg·d)], and high [400mg/(kg·d)] dose group. The model group was given intragastric administration of saline for 14d, ranibizumab(10mg/mL, 0.2mL/dose)was injected at 2d after photocoagulation with 5μL once for rats in ranibizumab group, and different concentrations of curcumin were intragastrically administrated to the rats in low, medium and high groups for 14d. Fundus photography, fundus fluorescein angiography(FFA)and indocyanine green angiography(ICGA)examination were performed at 14d after photocoagulation. Ocular histopathological specimens of rats with CNV were made, and the central thickness of CNV were observed by HE staining. Ocular histopathological specimens were made, and the expressions of AKT/p-AKT/HIF-1α/VEGF signaling pathway-related proteins were observed by immunohistochemistry. The mRNA relative expressions of AKT/HIF-1α/VEGF factor in CNV tissues were detected by RT-qPCR, and the protein expressions of AKT/p-AKT/HIF-1α/VEGF factor in CNV tissues were detected by Western-blot.RESULTS: CNV generation rates in the model group, the ranibizumab group, and the low, medium and high-dose curcumin groups were 78.18%, 73.21%, 77.19%, 75.86%, 74.55%, respectively, which were higher than 70%. The average absorbance were 182.12±6.59, 119.22±8.03, 166.45±8.33, 164.34±5.69, 149.22±6.45, respectively; the ranibizumab group was significantly lower than the model group(P&#x003C;0.05); the low-dose, medium-dose and high-dose groups were significantly higher than the ranibizumab group(P&#x003C;0.05), and the curcumin high-dose group was significantly lower than the model group(P&#x003C;0.05). HE staining showed that the retinal tissue structure of BN rats in normal group was clear and neatly arranged. The central thickness of CNV in the ranibizumab group was significantly reduced at 14d after photocoagulation compared with the model group(P&#x003C;0.05); While the curcumin high-dose group was significantly reduced compared with the model group(P&#x003C;0.05), but increased when compared with ranibizumab group(P&#x003C;0.05). Immunohistochemistry results showed that AKT, p-AKT, HIF-1α, and VEGF factors were negatively expressed in the retinal tissue structure of BN rats in the normal group, and no brown-yellow reactants were found. The expression of AKT, p-AKT, HIF-1α, and VEGF factors in the model group were higher than that in the normal group at 14d after photocoagulation(P&#x003C;0.05); the ranibizumab group was lower than the model group(P&#x003C;0.05). While the expression of the curcumin high-dose group was significantly decreased compared with the model group(P&#x003C;0.05), but significantly increased when compared with ranibizumab group(P&#x003C;0.05). The mRNA results showed that the relative expression levels of AKT, HIF-1α and VEGF mRNA in the model group at 14d after photocoagulation were higher than those of the normal group(P&#x003C;0.05); the ranibizumab group was lower than the model group(P&#x003C;0.05). While curcumin high-dose group was significantly decreased compared with the model group(P&#x003C;0.05), but significantly increased when compared with ranibizumab group(P&#x003C;0.05). Western-blot results showed that there was no significant difference in the relative expression of AKT protein among each experimental groups at 14d after photocoagulation. The relative expression of p-AKT protein in the model group was significantly higher than that in the normal group(P&#x003C;0.05); the ranibizumab group was significantly lower than the model group(P&#x003C;0.05); the curcumin high-dose group was significantly lower than the model group(P&#x003C;0.05). The relative expression levels of HIF-1α protein were significantly higher in the model group than in the normal group(P&#x003C;0.05), and the ranibizumab group was lower than in the model group(P&#x003C;0.05). The relative expression levels of HIF-1α protein was lower in the curcumin high-dose group than in the model group(P&#x003C;0.05)but higher than ranibizumab group(P&#x003C;0.05). The relative expression level of VEGF protein was significantly lower in the curcumin medium/high-dose group than in the model group(P&#x003C;0.05).CONCLUSION: Curcumin at 400mg/(kg·d)has an inhibitory effect on CNV in BN rats. The mechanism may be closely related to inhibiting the activation of AKT/p-AKT/HIF-1α/VEGF signaling pathways.
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AIM: To investigate the role and mechanism of methyltransferase-like 3(METTL3)-mediated N6-methyladenosine(m6A)methylation modification in regulating biological activity of vascular endothelial cells in the pathogenesis of choroidal neovascularization.METHODS: Human umbilical vein endothelial cells(HUVEC)cultured in vitro were divided into the following groups: control group(normal culture), low density lipoprotein(LDL)group, fluorescence-labelled LDL(Dil-LDL)group, 12.5μg/mL and 25μg/mL oxidized LDL(ox-LDL)groups, 12.5μg/mL and 25μg/mL fluorescence-labelled ox-LDL(Dil-ox-LDL)groups, DMSO group, STM2457(METTL3 inhibitor)group, DAPT group; and monkey retina-choroidal endothelial cells(RF/6A)cultured in vitro were divided into control group, DMSO group, 12.5 μg/mL ox-LDL group, and DAPT group. Endocytosed lipoprotein level was examined through fluorescence microscopy. RNA m6A methylation level was detected through a dot blot assay. Protein and RNA levels of METTL3 or angiogenesis-related markers were measured through Western blot assays and real-time quantitative polymerase chain reaction(RT-qPCR), respectively. METTL3 expression and localization were investigated through immunofluorescence. Cell migratory and tube formation capacities were assessed through transwell migration and tube formation assays, respectively.RESULTS: Endocytosed lipoprotein levels in HUVECs exposed to Dil-LDL, 12.5μg/mL and 25μg/mL Dil-ox-LDL groups were significantly higher than those in the control group. 12.5μg/mL and 25μg/mL ox-LDL groups significantly increased m6A methylation(all P<0.05), METTL3 protein expression(all P<0.01), and cell migration and angiogenesis capacities(all P<0.01). METTL3 mRNA level was significantly unregulated in the 12.5μg/mL ox-LDL group(P<0.05). In comparison to the DMSO group, the addition of STM2457 caused significant decrease in m6A methylation level(P<0.05), expression of VEGF and other angiogenesis-related markers(all P<0.05), cell migration and angiogenesis capacities(all P<0.01)and the expression of NICD(P<0.05). However, there were no significant differences in METTL3 protein and mRNA levels(all P>0.05). The expression of VEGF and NICD(all P<0.05), as well as the ability of cell migration and angiogenesis of RF/6A, was all significantly decreased in the DAPT group compared to the DMSO group(all P<0.01).CONCLUSION: METTL3-mediated m6A methylation modification promotes angiogenesis in vascular endothelial cells via the Notch signaling pathway in the pathogenesis of choroidal neovascularization.
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Objective:To investigate the molecular expression and pathological features of endothelial cell (EC) in a murine model of choroidal neovascularization (CNV) based on single-cell RNA sequencing (scRNA-seq).Methods:Six C57BL/6 mice aged 6-8 weeks were randomly divided into two groups, with 3 mice in each group.Bilateral eyeballs were enucleated.The choroidal tissues from the two groups were isolated by shearing the complex and scraping the choroid, respectively.Single-cell suspension was prepared by continuous digestion with trypsin/type Ⅰ collagenase at 37 ℃, and the cell viability and EC ratio were detected by flow cytometry to determine the preparation method of single-cell suspension.Another 6 mice were randomly assigned into the control group and the CNV group, with 3 mice in each group.The CNV model was induced by laser photocoagulation and single-cell suspensions were prepared 7 days after modeling.Gene expression library construction was performed using the Chromi-um (10x Genomics) instrument.High throughput sequencing was performed using the Illumina Novaseq6000 to obtain the expression matrix.The EC subpopulations were classified according to previous researches and the Cellmarker database.Pseudo-time analysis was performed in EC, revealing the gene expression matrix of different states.CNV-EC were further selected with preliminary analysis of the expression characteristics.Another 6 mice were selected to establish the CNV model and eyeball frozen sections were prepared 7 days after modeling.Expression and distribution as well as the area percentage of EC marker Pecam1, mitochondrial outer membrane proteins Tomm20 and mt-Co1, and capillary markers Kdr and Plvap were observed by immunofluorescence staining, and the vascular diameter was calculated.The use and care of animals followed the ARVO statement.This study protocol was approved by the Experimental Animal Welfare and Ethics Committee of Air Force Military Medical University (No.20200181).Results:The cell viability of the single-cell suspension prepared from choroidal-scleral fragments and choroidal scrapings was 99.4% and 99.1%, respectively, both of which met the sequencing requirements.The percentage of EC detected by flow cytometry was approximately 1.58%.The scRNA-seq result revealed that both the normal control and CNV groups contained 13 choroidal cell clusters.Compared with the normal control group, the proportions of rod/cone photoreceptor cells, EC and hematopoietic cells all increased, while the retinal pigment epithelium (RPE) and Schwan cells reduced in the CNV group.Among all clusters, EC constituted 18.4%.The pseudo-time analysis demonstrated that EC could be further divided into 4 states.The percentage of state 2 EC was 29.1% in the CNV group, which was significantly higher than 9.5% in the normal control group.Differentially expressed gene analysis showed that the expression of mitochondrion-related genes, including mt-Nd4 and mt-Atp6, were upregulated in state 2 EC, while capillary-related genes, including Kdr and Esm1, were downregulated.Immunofluorescent staining revealed that the area of Tomm20 and mt-Co1 in Pecam1-positive EC in the CNV area was (19.50±4.68)% and (4.64±2.82)%, respectively, which were both higher than (3.00±2.09)% and (0.18±0.34)% in normal area ( t=7.88, 3.84; both at P<0.01). The area of Kdr and Plvap in Pecam1-positive EC in the CNV area was (1.50±0.29)% and (0.79±0.97)%, respectively, which were both lower than (31.30±5.44)% and (10.43±2.28)% in the normal area ( t=13.40, 9.48; both at P<0.01). The vascular diameter in the CNV area was (5.52±1.85)μm, which was larger than (4.21±1.84)μm in the normal area ( t=9.57, P<0.001). Conclusions:When CNV occurs, the proportion of EC in choroid increases, and CNV-EC shows pathologic features of mitochondrial metabolic activation and loss of capillary properties, suggesting the mitochondrial activation of EC may play a role in the formation of CNV.
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Objective:To explore the potential role of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)/GATA-binding protein 4 (GATA-4)/vascular endothelial growth factor (VEGF) signal pathway in neovascular age-related macular degeneration (nAMD).Methods:We applied the TRANSFAC Public database to search the human and mouse VEGF promoters and upstream transcription factors, analyzed the transcription factors that may influence the transcriptional activity of VEGF. The RAW264.7 cells were divided into control group and lipopolysaccharide (LPS) stimulated group (LPS group). Real time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the activation of NLRP3 inflammasome, and the mRNA levels of GATA-4 and VEGFA. Thus, we applied the specific small molecular NLRP3 inhibitor MCC950 pretreated RAW264.7 cells (LPS+ MCC950 group), and detected the gene expression of NLRP3, Caspase-1, interleukin 1β( IL-1β), GATA-4 and VEGFA.Results:There were multiple GATA transcription factor binding sites upstream of human and mouse VEGF promoters. Compared with the control group, mRNA expression of NLRP3, Caspase-1, IL-1β, GATA-4 and VEGFA in LPS group were increased (all P<0.05). Compared with LPS group, mRNA expression of NLRP3, Caspase-1, IL-1β, GATA-4 and VEGFA in LPS+ MCC950 group were significantly decreased (all P<0.05). Conclusions:NLRP3/GATA-4/VEGF signal pathway may play a significant role in the pathologic processes of nAMD.
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With the increasing aging population, the incidence of wet age-related macular degeneration(wARMD)is gradually rising. The formation of neovascularization leads to recurrent hemorrhage in the macular region, which is one of the main causes of blindness in the elderly. Currently, the primary clinical treatment for wARMD is intravitreal injection of anti-vascular endothelial growth factor(VEGF)drugs. However, there are still some patients who have poor or no response to anti-VEGF drugs, resulting in suboptimal or ineffective clinical outcomes. Analyzing the specific influencing factors will be beneficial in guiding clinical decision-making. This article reviews the impact of factors such as advanced age, treatment duration, number of injections, characteristics of neovascular lesions, macular structure, intraocular cytokine levels, and genetics on the response to anti-VEGF therapy. In addition, recent studies have found that pericytes, as cellular components of microvascular walls, can influence the sensitivity to anti-VEGF therapy. This review summarizes the current research on the mechanisms of pericytes in poor or non-response to anti-VEGF therapy and discusses targeted strategies focusing on pericytes.
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AIM:To observe the changes of macular morphology and microcirculation in myopic maculopathy(MM), and investigate theirs correlation and effects on vision.METHODS: Case-control study. A total of 165 patients(189 eyes)with high myopia and 154 healthy volunteers(154 eyes)from October 2016 to December 2018 were selected. According to the classification of Meta-analysis for pathologic myopia(META-PM), participants were divided into M0 group(category 0, 41 eyes), M1 group(category 1, 53 eyes), M2 group(category 2 and 3, 52 eyes), and myopic choroidal neovascularization(mCNV)group(43 eyes). All participants underwent optical coherence tomography angiography(OCTA)examination. Morphological and microcirculation parameters of retina at different layers were compared between groups. Pearson correlation was used to assess the correlation between morphological and microcirculation parameters. Correlations between vision and other parameters were analyzed using multiple linear regression analysis.RESULTS:Foveal full retinal thickness(FRT)and outer retinal thickness(ORT)were all lower in M0, M1 and M2 groups than those of control group(all P<0.01). Foveal superficial capillary plexus vessel density(SVD)and deep capillary plexus vessel density(DVD)were all lower in M2 and mCNV groups than those of the control group(all P<0.01). Parafoveal FRT and ORT were all lower in M0, M1, M2 and mCNV groups than those of the control group(all P<0.01). Parafoveal inner retinal thickness(IRT), SVD and DVD were all lower in M2 and mCNV groups than those of the control group(all P<0.01). Subfoveal choroidal thickness(SFCT)and choroid capillaries vessel density(CVD)were all lower in M0, M1, M2 and mCNV groups than those of the control group(all P<0.01). Foveal vessel density of retina and choroid were positively correlated with its thickness in patients with MM without CNV(all P<0.05). Multivariate analysis showed that axial length(AL), diffuse or patchy chorioretinal atrophy were influencing foctors of best corrected visual acuity(BCVA; all P<0.01).CONCLUSION:Retinal morphological changes precede microcirculation changes in MM. Most of all, ORT changes precede IRT changes. Foveal vessel density of retina and choroid were positively correlated with its thickness. The main influencing factors of BCVA were AL and types of MM.
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Purpose: To analyze the structural features of subretinal hyper-reflective material (SHRM) in posterior uveitis using swept-source optical coherence tomography (SS-OCT) and optical coherence tomography angiography (SS-OCTA). Methods: In this observational study, subjects with quiescent posterior uveitis and the presence of SHRM on SS-OCT were subjected to SS-OCTA to identify the presence of an intrinsic choroidal neovascular (CNV) network. OCT features were compared for SHRM harboring CNV (vascular SHRM) with those without CNV network (avascular SHRM) to identify clinical signs pointing toward the presence of CNVM inside SHRM. Results: Forty-two eyes of 33 subjects (18 males; mean age: 29.52 ± 12.56 years) were evaluated. Two-thirds (28/42) of eyes having SHRM on SS-OCT harbored intrinsic neovascular network (vascular SHRM). Increased reflectivity of SHRM (P < 0.001) and increased transmission of OCT signal underlying SHRM (P = 0.03) were suggestive of the absence of CNVM. The presence of intra/subretinal fluid (P = 0.08) and pitchfork sign (P = 0.017) were important markers of vascular SHRM. Conclusion: SHRM is an important OCT finding in eyes with posterior uveitis. Meticulous assessment of SHRM characteristics on SS-OCT can aid in identifying the underlying intrinsic neovascular network.
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The pathogenesis of neovascular age-related macular degeneration (nAMD) is complex and macular neovascularization (MNV), a key pathogenic factor in nAMD, is prone to recurrence.Vitreous injection of anti-VEGF drugs is the main therapy of nAMD.In recent years, a lot of progress has been made in fundus imaging techniques and optical coherence tomography angiography (OCTA) with non-invasive, rapid, stratified and high-definition functions has shown strong advantages in diagnosis, differential diagnosis, disease dynamic monitoring and follow-up of nAMD.Clinicians have had a certain understanding of the important role of OCTA in the diagnosis of nAMD and other diseases, and its clinical application value has been recognized gradually.However, its application value in follow-up of patients with nAMD and polypoid choroidal vasculopathy (PCV) is still not well understood.By reviewing a large number of recent relevant literature on OCTA, and combining the clinical practice of our research team in monitoring the course of AMD and PCV disease by OCTA, we have gained new knowledge and understanding of the pathological mechanism of AMD and PCV.In this paper, we elucidated the latest understanding of the diagnostic value of OCTA in AMD based on long-term series of OCTA studies, the new findings of OCTA in AMD management of our team, as well as its impact on ophthalmology clinical practice.Then we forecasted the role of OCTA in the prediction of recurrence and anti-VEGF treatment response, as well as the clinical value of OCTA in the optimization of nAMD treatment and follow-up plan.It is recommended that clinicians pay more attention to the clinical value and guiding role of OCTA in long-term treatment monitoring and follow-up of AMD.
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Objective:To evaluate the effectiveness and safety of intravitreal injection of different doses of aflibercept for polypoidal choroidal vasculopathy (PCV) with serous pigment epithelial detachment (PED) resistant to ranibizumab.Methods:A non-randomized controlled clinical study was conducted.Seventy-three eyes of 73 patients with PCV and serous PED resistant to ranibizumab were enrolled at the First Affiliated Hospital of Zhengzhou University from January 2019 to December 2020.All patients were treated by intravitreal injection of 2 mg or 4 mg aflibercept according to patients' willingness.2 mg aflibercept or 4 mg aflibercept was intravitreally injected monthly for three consecutive months following pro re nata (PRN) regimen in 2 mg aflibercept group (38 eyes) and 4 mg aflibercept group (35 eyes), respectively.PED height and central macular thickness (CMT) were measured by optical coherence tomography, and the best corrected visual acuity (BCVA) was examined with a visual acuity chart and converted to logarithm of the minimum angle of resolution (LogMAR) unit before injection and 1 month, 2, 3, 6 months from the first injection.Intraocular pressure and treatment-related adverse events were recorded.This study adhered to the Declaration of Helsinki and was approved by an Ethics Committee of The First Affiliated Hospital of Zhengzhou University (No.2021-KY-1252).Written informed consent was obtained from each patient prior to entering study cohort.Results:Thirty-three patients (86.84%) in 2 mg aflibercept group and 30 patients (85.71%) in 4 mg aflibercept group finished the treatment and follow-up, respectively. The PED, BCVA and CMT before treatment and at the end of follow-up were (379.24±95.50) and (280.09±120.50)μm, 0.68±0.27 and 0.51±0.19, (393.96±100.81) and (291.70±44.09)μm in 2 mg aflibercept group, respectively, showing statistically significant differences (all at P<0.05).The PED, BCVA and CMT before treatment and at the end of follow-up were (393.07±93.76) and (278.63±145.07)μm, 0.66±0.31 and 0.48±0.22, (377.43±79.61) and (284.67±84.88)μm in 4 mg aflibercept group, respectively, with statistically significant differences (all at P<0.05).The CMT value in 4 mg aflibercept group was significantly lower than that in the 2 mg aflibercept group in one month after injection ( P<0.05).No severe ocular and systemic adverse events were found during the follow-up, such as retinal detachment, endophthalmitis, cataract, and persistent high intraocular pressure. Conclusions:Both 2 mg and 4 mg aflibercept can effectively treat ranibizumab-resistant PCV with serous PED, and improve the anatomical structure of retina and BCVA.4 mg aflibercept can accelerate the recovery of PED and CMT.
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Objective:To systematically evaluate the diagnostic value of optical coherence tomography angiography (OCTA) and fluorescein fundus angiography (FFA) for choroidal neovascularization (CNV) in central serous chorioretinopathy (CSC).Methods:PubMed, Cochrane Library, Web of Science, Embase, China National Knowledge Internet (CNKI), VIP database and Wanfang Database were searched for literature published from January 1991 to March 2020 with CSC patients as subjects and OCTA and FFA as diagnostic methods of CNV.The quality of the included literature was evaluated with Australian JBI tool.A meta-analysis was performed using Review Manager 5.3 software.The source of heterogeneity was identified by age and total number of samples subgroup analysis.Results:Nine studies with a total sample size of 374 eyes were enrolled.The quality score of 8 studies was greater than 14.The detection rate of CNV in CSC by OCTA was higher than that by FFA [odds ratio( OR)=3.99, 95% confidence interval( CI): 1.44-11.07, P<0.001].Studies with sample size >40 showed no heterogeneity ( I2=49%, P=0.14), suggesting that sample size might be a source of heterogeneity.Publication bias was found by funnel plot. Conclusions:OCTA has a higher detection rate of CNV secondary to CSC than FFA, and it can be used as a routine inspection method.
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Objective:To conduct a systematic review of clinical manifestations, treatment, and associated genotyping of Sorsby fundus dystrophy (SFD).Methods:An evidence-based medicine study. Sorsby fundus dystrophy, anti-vascular endothelial growth factor therapy, choroidal neovascularization, macular neovascularization, and TIMP3 gene were hereby used as search terms. Relevant literature was searched in CNKI, Wanfang, PubMed of the National Library of Medicine, and Embase of the Netherlands. The time span for literature searching ranged from the establishment of the database to April 2022, and two reviewers independently screened the literature and extracted relevant data, with duplicates, incomplete or irrelevant articles, and review articles excluded. SPSS26.0 software was used for analysis. The 95% confidence interval ( CI) was used as an estimate of the effect size. The clinical manifestations, treatment and related pathogenic genes of SFD were counted and recorded. Results:According to the search strategy, 157 pieces of literature were initially retrieved, and 49 eyes of 35 patients from 16 articles were finally included for analysis, among which, 17 patients were male, 13 patients were female, and 5 patients were unknown gender; 16 involved left eyes, 19 involved right eyes, and 14 involved unidentified eyes. The age of the disease onset was 42.33±2.19 years (28-59) years old. There were 19 cases with a positive family history, and the total positive rate was 54.3% (19/35, 95% CI 36%-72%). There were 31 cases of gene mutation, all of which were TIMP3. In the included literature, there were 2 and 2 cases with no mutation and unreported loci, respectively, with a total positive rate of 93.9% (31/33, 95% CI 85%-100%). Among the 31 cases with gene mutation, 22, 4, 1, and 4 cases were in the UK, Germany, Switzerland, and Chinese, respectively, and the detection rates were all 100% (22/22, 4/4, 1/1, 4/4). The clinical manifestations of SFD were mainly yellow-white deposits in the fundus and choroidal neovascularization (CNV) in the macula, thereby leading to a decrease in central vision, followed by the expansion of the deposits to the periphery, the further development of CNV, and a severe decline in vision caused by peripheral retinal and choroidal atrophy. The treatment methods for SFD include photodymatic therapy, anti-VEGF drugs, glucocorticoids, vitamin A, etc., among which, anti-VEGF drugs were considered the first-line treatment, and the combined treatment was provided with a better prognosis than a single treatment. Conclusions:Variations in the TIMP3 gene cause SFD, the fundus characteristic manifestations of which, are yellowish-white deposits and CNV, which develop from the center to the periphery, thus resulting in progressive decline of visual acuity. Current studies have shown that combined therapy presents a better prognosis than monotherapy.
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Objective:To establish an artificial intelligence robot-assisted diagnosis system for fundus diseases based on deep learning optical coherence tomography (OCT) and evaluate its application value.Methods:Diagnostic test studies. From 2016 to 2019, 25 000 OCT images of 25 000 patients treated at the Eye Center of the Second Affiliated Hospital of Zhejiang University School of Medicine were used as training sets and validation sets for the fundus intelligent assisted diagnosis system. Among them, macular epiretinal membrane (MERM), macular edema, macular hole, choroidal neovascularization (CNV), and age-related macular degeneration (AMD) were 5 000 sheets each. The training set and the verification set are 18 124 and 6 876 sheets, respectively. Through the transfer learning Attention ResNet structure algorithm, the OCT image was characterized by lesion identification, the disease feature was extracted by a specific procedure, and the given image was distinguished from other types of disease according to the statistical characteristics of the target lesion. The model algorithms of MERM, macular edema, macular hole, CNV and AMD were initially formed, and the fundus intelligent auxiliary diagnosis system of five models was established. The performance of each model-assisted diagnosis in the fundus intelligent auxiliary diagnostic system was evaluated by applying the subject working characteristic curve, area under the curve (AUC), sensitivity, and specificity.Results:With the intelligent auxiliary diagnosis system, the diagnostic sensitivity of the MERM was 93.5%, the specificity was 99.23%, and AUC was 0.983 7; the diagnostic sensitivity of macular edema was 99.02%, the specificity was 98.17%, and AUC was 0.994 6; the diagnostic sensitivity of macular hole was 98.91%, the specificity was 99.91%, AUC was 0.996 2; the diagnostic sensitivity of CNV was 97.54%, the specificity was 94.71%, AUC was 0.987 5; the diagnostic sensitivity of AMD was 95.12%, the specificity was 97.09%, AUC was 0.985 3.Conclusions:The artificial intelligence robot-assisted diagnosis system for fundus diseases based on deep learning for OCT images has accurate and efficient diagnostic performance for assisting the diagnosis of MERM, macular edema, macular hole, CNV, and AMD.
الملخص
Ocular neovascularization is a pathological change in various ocular diseases such as diabetic retinopathy, retinopathy of prematurity, central retinal vein occlusion and age-related macular degeneration, which seriously affects patient's vision. β receptors are expressed in conjunctiva, corneal epithelial cells, corneal endothelial cells, extraocular muscles, trabecular meshwork, ciliary muscle, lens and retina. β adrenergic receptor antagonists bind to β receptors to exert anti-angiogenic effects by inhibiting the expression of vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1, interleukin-6 and other angiogenic cytokines; reducing macrophage-related inflammatory response; increasing the expression of anti-angiogenic factors. In the treatment of corneal neovascularization, choroidal neovascularization, and retinopathy of prematurity, it can significantly reduce the area of neovascularization and delay disease progression. Co-administration of anti-VEGF drugs can reduce the frequency of administration of anti-VEGF drugs. At effective therapeutic concentrations, β-adrenergic receptor antagonists are well tolerated; they have broader targets than anti-VEGF drugs, which offers new treatment strategies for ocular neovascularization such as corneal, choroidal and retinal neovascularization.
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Objective:To observe the multimodal image features of inflammatory lesions and choroidal neovascularization (CNV) in multifocal choroiditis (MFC).Methods:A retrospective clinical analysis. A total of 90 eyes of 46 patients with MFC diagnosed in the Department of Ophthalmology of Yunnan University Affiliated Hospital from May 2017 to April 2021 were included in the study. Among them, there were 21 males and 25 females; the average age was 38.30±8.97 years old. Twenty-nine cases of MFC were diagnosed in the past, and they visited the doctor again due to new symptoms; 17 cases without a clear past medical history were the first visits. All eyes underwent color fundus photography, fluorescein fundus angiography (FFA), optical coherence tomography (OCT), and OCT angiography (OCTA). With reference to the literature and the results of multimodal fundus imaging examinations, MFC lesions were divided into active CNV lesions, inactive CNV lesions, active inflammatory lesions, and inactive inflammatory lesions, with 31 (34.4%, 31/90), 12 (13.3%, 12/90), 26 (28.9%, 26/90), 90 (100.0%, 90/90) eyes. Nineteen eyes were treated with anti-vascular endothelial growth factor drugs. To summarize and analyze the manifestations of inflammatory lesions and CNV lesions in different imaging examinations. The Wilcoxon rank test was used to compare the detection rate of CNV lesions between FFA and OCTA.Results:In eyes with active inflammatory lesions and active CNV lesions, yellow-white lesions, retinal hemorrhage and exudation were seen on fundus color photography; FFA examination showed fluorescein leakage in the lesions; OCT examination showed retinal pigment epithelium (RPE) layer in the lesions was uplifted, the boundary was unclear, combined with subretinal and intraretinal fluid; OCTA examination showed that there was no blood flow signal in each layer of vascular tissue in active inflammatory lesions, and blood flow signals were seen in active CNV lesions. In the eyes of inactive inflammatory lesions and inactive CNV lesions, the fundus color photography showed that the lesions had clear boundaries without bleeding or exudation; FFA examination, the lesions were fluorescently stained, and there was no fluorescein leakage; OCT examination, inactive CNV lesions manifested as raised lesions with clear boundaries, and inactive inflammation manifested as scars formed by mild RPE hyperplasia or depressions in outer structures formed by atrophy; OCTA examination, inactive inflammatory lesions showed patchy loss of blood flow signal or penetrating blood flow signal below, blood flow signal can be seen in inactive CNV lesions.Conclusion:MFC active inflammatory lesions and active CNV lesions are often accompanied by retinal hemorrhage and exudation; FFA shows fluorescein leakage; OCT shows that the boundary of raised lesions is unclear; OCTA can identify the nature of CNV or inflammatory lesions.