Research progress on the mechanism of subthreshold micropulse laser photocoagulation in central serous chorioretinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

Central serous chorioretinopathy(CSC)is a common macular degeneration that primarily affects young patients. While the disease may resolve on its own to some extent, delayed or inadequate treatment can result in recurrence and progression to chronic CSC. This can lead to complications such as retinal pigment epithelium(RPE)atrophy and choroidal neovascularization, ultimately causing irreversible damage to central vision. Subthreshold micropulse laser photocoagulation(SMLP)is a type of laser therapy that differs from traditional lasers in that it does not cause damage or thermal injury to RPE cells and photoreceptors. SMLP has become widely used in clinical treatment of CSC due to its effectiveness, safety, and reproducibility, particularly in cases where verteporfin is not available in photodynamic therapy(PDT). The purpose of this review is to explain the mechanism of SMLP in CSC and summarize the effector cells, cytokines, and mechanisms of action involved in its treatment. This will provide a theoretical basis for promoting and rationalizing the use of SMLP in clinical practice.

Research progress of microRNA in choroidal neovascularization signaling pathway / 国际眼科杂志(Guoji Yanke Zazhi)

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.

Choroidal lesions in varicella zoster virus uveitis

Purpose: To evaluate choroidal lesions with spectral domain optical coherence tomography (SD?OCT) scan in varicella zoster virus (VZV) uveitis. Methods: VZV?uveitis cases which underwent OCT scan for choroidal lesions were studied. SD?OCT scan passing through these lesions was studied in detail. Subfoveal choroidal thickness (SFCT) during active and resolved stages was studied. Angiogaphic features were studied where available. Results: Thirteen out of 15 cases had same?sided herpes zoster ophthalmicus skin rashes. All except three patients had old or active kerato?uveitis. All eyes demonstrated clear vitreous and a single or multiple hypopigmented orangish?yellow choroidal lesions. The number of lesions remained unchanged during the follow?up on clinical examination. SD?OCT over lesions (n = 11) showed choroidal thinning (n = 5), hyporeflective choroidal elevation during active inflammation (n = 3), transmission effects (n = 4), and ellipsoid zone disruption (n = 7). The mean change in SFCT (n = 9) after resolution of the inflammation was 26.3 ?m (range: 3–90 ?m). Fundus fluorescein angiography showed iso?fluorescence over lesions in all (n = 5), but indocyanine green angiography (n = 3) showed hypofluorescence at lesions. Mean follow?up was 1.38 years (range: 3 months–7 years). De?novo appearance of choroidal lesion during the first relapse of VZV?uveitis was captured in one case. Conclusion: VZV?uveitis can cause focal or multifocal hypopigmented choroidal lesions with thickening or scarring of choroidal tissue, depending on the disease activity.

Establishment of patient-derived xenografts of retinoblastoma and choroidal melanoma on the avian chorioallantoic membrane

Purpose: To develop a viable in vivo chorioallantoic membrane (CAM) model to study the growth and invasion of patient?derived retinoblastoma (RB) and choroidal melanoma (CM) xenografts (PDXs). The study utilizes primary tumor samples instead of cancer cell lines, which provides a more authentic representation of tumors due to conserved morphology and heterogeneity. Methods: Fertilized chicken eggs were procured, windowed, and their CAM layers were dropped. On embryonic development day (EDD) 10, freshly cut patient?derived CM and RB tumors were implanted on the CAM layer and the setup was incubated for 7 days. The tumor?embedded CAM layer was harvested on EDD 17, and the extracted tumor samples were subjected to hematoxylin and eosin staining and immunohistochemical analysis to evaluate the extent of tumor invasion. Results: Significant changes in the vascularity around the RB and CM PDXs were observed, indicating an angiogenic environment. The cross?sectional histological view of the tumor implant site revealed the invasion of both the tumors into the CAM mesoderm. Invasion of CM into CAM mesoderm was visualized in the form of pigmented nodules, and that of RB was indicated by synaptophysin and Ki?67 positivity in Immunohistochemistry (IHC). Conclusion: The CAM xenograft model was successfully able to support the growth of CM and RB PDXs and their invasion in CAM, thus presenting as a feasible alternative to mammalian models for studying tumorigenicity and invasiveness of ocular tumors. Moreover, this model can further be utilized to develop personalized medicine by inoculating patient?specific tumors for preclinical drug screening.

Research progress on the correlation between choroidal blood flow perfusion and myopia in children / 国际眼科杂志(Guoji Yanke Zazhi)

Myopia is the most common type of refractive error. At present, the characteristics of the low age and rapid growth of myopia in our country are obvious, and the myopia of adolescents and children has become a public health problem of concern to the whole society. Visual experience guides the development of children's refractive state and emmetropization. The occurrence and development of myopia is accompanied by changes in the structure of the eyeball, and the choroid has a thinning trend. The thickness change of the choroid may be determined by blood flow perfusion. Decreased choroidal blood flow perfusion may lead to scleral ischemia and hypoxia, and hypoxia induces scleral matrix remodeling and axial length growth. This article reviews the relationship between choroidal blood flow and myopia, and suggests the significance of paying attention to choroidal changes in the prevention and control of myopia.

Correlation analysis of vision and changes of macular structure and microcirculation in myopic maculopathy / 国际眼科杂志(Guoji Yanke Zazhi)

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.

Influencing factors of poor response to anti-vascular endothelial growth factor drug therapy for wet age-related macular degeneration and therapeutic strategy of targeting pericytes / 国际眼科杂志(Guoji Yanke Zazhi)

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.

Research progress on the application of deep learning in choroidal segmentation / 国际眼科杂志(Guoji Yanke Zazhi)

In recent years, ophthalmology, as one of the medical fields highly dependent on auxiliary imaging, has been at the forefront of the application of deep learning algorithm. The morphological changes of the choroid are closely related to the occurrence, development, treatment and prognosis of fundus diseases. The rapid development of optical coherence tomography has greatly promoted the accurate analysis of choroidal morphology and structure. Choroidal segmentation and related analysis are crucial for determining the pathogenesis and treatment strategies of eye diseases. However, currently, choroidal mainly relies on tedious, time-consuming, and low-reproducibility manual segmentation. To overcome these difficulties, deep learning methods for choroidal segmentation have been developed in recent years, greatly improving the accuracy and efficiency of choroidal segmentation. The purpose of this paper is to review the features of choroidal thickness in different eye diseases, explore the latest applications and advantages of deep learning models in measuring choroidal thickness, and focus on the challenges faced by deep learning models.

Observation of vortex venous anastomosis in central serous chorioretinopathy / 中华眼底病杂志

Objective:To observe the anastomotic status of the vortex veins in patients with central serous chorioretinopathy (CSC).Methods:A cross-sectional study of clinical practice. From July 2021 to July 2022, 50 cases (50 eyes) of monocular CSC patients diagnosed through ophthalmic examination at the First Affiliated Hospital of Zhengzhou University were included in the study. Among them, there were 37 males (74.0%, 37/50) and 13 females (26.0%, 13/50), with the mean age of (44.30±9.59) years old. The course of disease from the onset of symptoms to the time of treatment was less than 3 months. The affected eye and contralateral eye of CSC patients were divided into the affected eye group and contralateral eye group, respectively. Fifty healthy volunteers of the same age and gender were selected as the normal control group with 50 eyes. The macular area scanning source optical coherence tomography (OCT) vascular imaging examination was performed with Visual Microimaging (Henan) Technology Co., Ltd. VG200D. Horizontal watershed vortex veins anastomosis rate and asymmetric vortex-venous dilation rate were observed by en face OCT. The device comes with software to calculate the central foveal choroidal thickness (SFCT), mean choroidal thickness (MCT), and choroidal vascular index (CVI). One-way analysis of variance and χ2 test were used to compare the three groups. When variances were unequal between groups, nonparametric tests were performed. Results:The SFCT values of the affected eye group, contralateral eye group, and normal control group were (567.12±129.02), (513.26±133.17), (327.64±97.40) μm, respectively; MCT were (407.38±97.54), (388.24±94.13), (275.46±60.55) μm, respectively; CVI were 0.34±0.05, 0.32±0.04, and 0.27±0.04, respectively; anastomosis rates of vortex veins were 98% (49/50), 78% (39/50), and 40% (20/50), respectively; asymmetric dilation rates of vortex veins were 96% (48/50), 88% (44/50), and 48% (24/50), respectively. The differences of SFCT ( F=53.974), MCT ( Z=51.415), CVI ( F=28.082), vortex vein anastomosis rate ( χ2=43.056), asymmetric dilation rate of vortex veins ( χ2=37.728) among three groups were statistically significant ( P<0.001). Compared with the contralateral eye group, the SFCT, MCT, CVI, vortex vein anastomosis rate, and vortex vein asymmetric dilation rate in the affected eye group were significantly higher than those in the contralateral eye group. Among them, the differences of SFCT ( t=2.054), CVI ( t=2.211), and vortex vein anastomosis rate ( χ2=9.470) were statistically significant ( P<0.05); the differences of MCT ( Z=7.490), asymmetric dilation rate of vortex veins ( χ2=2.714) were not statistically significant ( P=1.000, 0.140). Conclusions:SFCT, MCT, and CVI in the affected and contralateral eyes of monocular CSC patients significantly increase. The anastomotic rate and asymmetric dilation rate of the vortex vein in the opposite eye were lower than those in the affected eye.

Alterations of choroidal vasculature after submacular fluid absorption in central serous chorioretinopathy using ultra-widefield swept-source optical coherence tomography angiography / 中华眼底病杂志

Objective:To analyze the associations between the choroidal vasculature and submacular fluid (SMF) in central serous chorioretinopathy (CSC).Methods:A retrospective study. A total of 29 CSC patients (31 eyes) with complete records who visited the Department of Ophthalmology in Peking University People's Hospital from August 1, 2021 to March 1, 2023 were included in this study. The patients were divided into complete absorption and incomplete absorption groups according to the status of SMF in the last visit. All the patients underwent ultra-widefield swept-source optical coherence tomography angiography (UWF SS-OCTA) with a scanning range of 24 mm × 20 mm. The UWF SS-OCTA images were automatically analyzed in 9 regions (superotemporal, superior, superonasal, temporal, central, nasal, inferotemporal, inferior, and inferonasal). Alterations of choroidal vasculature in the nine subfields after SMF absorption were described, including choroidal thickness (CT), flow density of choriocapillaris layer, vessel density of large choroidal vessel layer, three-dimensional choroidal vascularity index (CVI), the mean choroidal vessel volume (mCVV), and the mean choroidal stroma volume (mCSV). The relevant factors affecting the complete absorption of SMF were additionally evaluated.Results:At baseline, CT ( Z=2.859, P=0.004), mCVV ( t=2.514, P=0.018), and mCSV ( Z=2.958, P=0.003) in the superotemporal region of the affected eyes in the incomplete absorption group were significantly higher than those in the complete absorption group. Compared with baseline, at the last visit, the proportion of asymmetric vortex veins in the complete absorption group was significantly decreased ( χ2=6.000, P=0.014), CVI in the superotemporal, superonasal, temporal, central, nasal, inferotemporal, and inferonasal regions ( t=-4.125, t=-3.247, Z=-3.213, t=-2.994, t=-3.417, t=-3.733, t=-3.795; P=0.001, 0.006, 0.001, 0.010, 0.005, 0.003, 0.002), the mCVV of 9 regions ( t=-2.959, t=-2.537, t=-2.235, t=-3.260, t=-3.022, t=-2.796, t=-2.747, Z=-2.107, t=-2.935; P=0.011, 0.025, 0.044, 0.006, 0.010, 0.015, 0.017, 0.035, 0.012) were significantly decreased. Compared to the complete absorption group, the choroidal blood flow changes in the non-complete absorption group were more limited, and CT in the upper region increased significantly at the last follow-up ( t=2.272, P=0.037). Multivariate logistic regression analysis revealed that baseline CT in the superotemporal region may be an independent risk factor affecting the complete absorption of SMF (odds ratio=0.981, 95% confidential interval 0.965-0.997, P=0.021). Conclusions:In the process of SMF absorption in CSC, significant reductions of choroidal blood flow were found in the large choroidal vessel layer, and there may be a locally compensatory increase in CT. In addition, baseline CT in superotemporal region is an independent risk factor affecting SMF absorption.

Changes of choroidal biomarkers in patients with central serous chorioretinopathy / 中华眼底病杂志

Objective:To quantitatively evaluate the changes of choroidal biomarkers in patients with central serous chorioretinopathy (CSC) and preliminarily explore its pathogenesis.Methods:Clinical cross-sectional study. From July 2021 to December 2022, 74 eyes of 65 patients with CSC (CSC group) confirmed by ophthalmic examination at the First Affiliated Hospital of Zhengzhou University were included in the study. Among them, 46 patients (51 eyes) were male, 19 patients (23 eyes) were female. The duration from the onset of symptoms to the time of treatment was less than or equal to 3 months. A control group consisted of 40 healthy volunteers (74 eyes) matched in age and gender. Among them, 26 patients (50 eyes) were male, and 14 patients (24 eyes) were female. Using VG200D from Microimaging (Henan) Technology Co., Ltd., macular scanning source light coherence tomography angiography was performed, with scanning range 6 mm × 6 mm. According to the division of the diabetes retinopathy treatment research group, the choroid within 6 mm of the macular fovea was divided into three concentric circles centered on the macular fovea, namely, the central area with a diameter of 1 mm, the macular area with a diameter of 1-3 mm, and the surrounding area of the fovea with a diameter of 3-6 mm. The device comes with software to record the three-dimensional choroidal vascular index (CVI), choroidal vascular volume (CVV), perfusion area of the choroidal capillary layer (CFA), choroidal thickness (CT), and three-dimensional CVI, CVV, and CT in the upper, temporal, lower, and subnasal quadrants within 6 mm of the fovea. Quantitative data between the two groups were compared using an independent sample t-test. Qualitative data comparison line χ2 inspection. The value of receiver operating curve (ROC) analysis in predicting the occurrence of CSC, including CVI, CVV, CFA, and CT. Results:Compared with the control group, the CVI ( t=3.133, 4.814), CVV ( t=7.504, 9.248), and CT ( t=10.557, 10.760) in the central and macular regions of the affected eyes in the CSC group significantly increased, while the CFA ( t=-8.206, -5.065) significantly decreased, with statistically significant differences ( P<0.05); CVI ( t=7.129), CVV ( t=10.020), and CT ( t=10.488) significantly increased within 6 mm of the central fovea, while CFA ( t=-2.548) significantly decreased, with statistically significant differences ( P<0.05). The CVI ( t=4.980, 4.201, 4.716, 8.491), CVV ( t=9.014, 7.156, 7.719, 10.730), and CT ( t=10.077, 8.700, 8.960, 11.704) in the upper, temporal, lower, and lower nasal quadrants within 6 mm of the central fovea were significantly increased, with statistically significant differences ( P<0.05). In the CSC group, the maximum CVI and CVV were (0.39±0.10)% and (1.09±0.42) mm 3, respectively, on the nasal side of the affected eye. Upper CT was (476.02±100.89) μm. The nasal side CVI, CVV, and CT have the largest changes. The ROC curve analysis results showed that the area under the curve of CT, CVV, and CVI within 6 mm of the central region, macular region, and fovea was over than 0.5. Subcentral CT was the most specific for the diagnosis of CSC. Conclusion:Choroidal biomarkers CVI, CVV, and CT in CSC patients increase, while CFA decreases. Central CT is the most specific for the diagnosis of CSC.

The efficacy of triamcinolone acetonide peribulbar injection combined with vitrectomy for rhegmatogenous retinal detachment associated with choroidal detachment / 中国医师杂志

Objective:To investigate the clinical efficacy of triamcinolone acetonide peribulbar injection combined with vitrectomy for rhegmatogenous retinal detachment associated with choroidal detachment (RRD-CD).Methods:This study was a retrospective case series study. Nineteen cases (19 eyes) with RRD-CD who had undergone pars plana vitrectomy at the Dalian No.3 People′s Hospital were analyzed. All the cases received 20 mg triamcinolone acetonide peribulbar injection within 3 to 7 days before surgery. The severity of patient′s uveitis was assessed before and after peribulbar injection of triamcinolone acetonide. Best corrected visual acuity (BCVA) and intra ocular pressure (IOP) before and after surgery, the area of retinal detachment, the rate of retinal reattachment, the rate of recurrent retinal detachment and surgical complications were analyzed. Patients′ blood pressure and blood glucose levels were also monitored.Results:19 patients were followed up for (13.1±1.5)months. The severity of uveitis reduced to different extents compared with preoperative condition. The IOP was (8.73±3.38)mmHg before injection and (10.95±2.46)mmHg after injection, and the difference was statistically significant ( t=-7.571, P=0.027). The choroid detachment range was 4-12(9.37±2.69)sites before injection, and 0-11(4.63±4.10)sites after injection, and the difference was statistically significant ( Z=-3.834, P=0.001). Compared with the preoperative results, the BCVA increased in 12 patients, unchanged in 5 cases and decreased in 2 cases. In the final follow-up of 18 patients with retinal reattachment, 17 eyes underwent a single operation, 2 eyes had recurrent retinal detachment, and 1 eye had retinal reattachment after a second operation. There were no significant difference in blood glucose and blood pressure before and after injection (all P>0.05). There were no other complications besides temporarily elevated IOP and cataract. Conclusions:Vitrectomy combined with triamcinolone acetonide peribulbar injection is effective and safe for patients with RRD-CD.

Efficacy of conbercept in the treatment of polypoidal choroidal vasculopathy based on EDI-OCT and OCTA / 中国医师杂志

Objective:To evaluate the changes of retinal thickness, choroid thickness and choroid vascular polypoid lesions (polyps) before and after the treatment of conbercept in polypoidal choroidal vasculopathy (PCV) with conbercept based on enhanced-depth imaging optical coherence tomography (EDI-OCT) and OCT angiography (OCTA).Methods:Twenty patients with PCV admitted to the ophthalmology department of the Affiliated Hospital of Traditional Chinese Medicine of Xinjiang Medical University from January 2019 to December 2020 (who had not received intravitreous injection before) were selected and given intravitreous injection of conbercept with 3+ pro re nata (PRN) treatment. The changes of visual acuity, intraocular pressure, central macular thickness (CMT), subfoveal choroidal thickness (SFCT), peripapillary choroid thickness (PCT), polyps height, and maximum cross-sectional area of polyps were observed before and after treatment.Results:There were significant difference in the best corrected visual acuity (BCVA), CMT, SFCT, PCT, polyps height and maximum polyps cross-sectional area before and after treatment in 20 patients (all P<0.05). BCVA was significantly improved at 1 week and 1 month after treatment (all P<0.05), and still improved at 6 months after treatment, but the difference was not statistically significant compared with 3 months after treatment ( P>0.05), and slightly fluctuated at 6 to 12 months after treatment, but basically stable. CMT, SFCT and PCT decreased significantly after 3 months of treatment, and were basically stable from 6 to 12 months after treatment. One month after treatment, polyps height was (251.30±57.49)μm, with a decrease of 11.3 μm; the polyps height decreased at 3, 6 and 12 months after treatment, and the difference was statistically significant (all P<0.05). The maximum cross-sectional area of polyps at 3 and 12 months after treatment was (2.10±0.44)μm 2 and (1.98±0.44)μm 2, respectively, with a certain degree of decrease, and the difference was statistically significant (all P<0.05). Conclusions:Intraocular injection of conbercept can effectively reduce CMT, SFCT, PCT, polyps height, maximum cross-sectional area of polyps and increase BCVA in PCV patients 3 months after treatment. EDI-OCT and OCTA were used to quantitatively detect the changes of PCV indexes and observe the curative effect and prognosis.

Application and problems of optical coherence tomography in clinical diagnosis and treatment of polypoidal choroidal vasculopathy / 中国医师杂志

Polypoidal choroidal vasculopathy (PCV) is a fundus disease that can cause severe visual impairment. At present, the gold standard for the diagnosis of PCV is indocyanine green angiography (ICGA). Due to its invasiveness and inconvenience in clinical application, researchers are exploring the use of non-invasive optical coherence tomography (OCT) in clinical diagnosis and follow-up of PCV, and non-invasive diagnostic criteria based on OCT are gradually emerging. However, in the clinical application of this technology, there are still some problems, such as poor imaging effect, unclear diagnosis, over-reliance on OCT technology, complex follow-up situations and so on. This paper intends to review the current situation, new diagnostic criteria and related problems of OCT in the clinical diagnosis and treatment of PCV, in order to provide reference for ophthalmologists.

The role of NLRP3/GATA-4/VEGF signal pathway in neovascular age-related macular degeneration / 中国医师杂志

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.

Paying close attention to the therapeutic effect of brolucizumab on polypoidal choroidal vasculopathy and its clinical application / 中华实验眼科杂志

Polypoidal choroidal vasculopathy (PCV) occurs in the middle-aged and elderly population and is characterized by abnormal intrachoroidal vascular patterns such as branching choroidal vascular networks and polypoidal dilatation of vessel terminals, subretinal orange nodular lesions and hemorrhagic or plasma retinal pigment epithelial detachment (PED), which can cause retinal hemorrhage or vitreous hematopoiesis and is one of the major blinding fundus lesions.Intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs is currently the main method of PCV treatment, and has certain advantages in eliminating abnormal vascular networks and removing polypoidal lesions, reducing vascular exudation and promoting exudate absorption, and improving visual prognosis.However, frequent intravitreal drug injections increase the risk of infection and the treatment burden for patients.In addition, the high recurrence rate after treatment poses a significant challenge to clinical practice, so the search for new therapeutic agents that are durable and less costly is a focus of clinical research in PCV.The literature from abroad suggests that brolucizumab is a novel small-molecule anti-VEGF humanized monoclonal antibody with the advantages of high tissue penetration, high local drug concentration and bioavailability, small injectable dose, long-lasting efficacy and long injection interval, which brings new hope for the clinical treatment of PCV and improving the prognosis of affected eyes.Although the efficacy and safety of brolucizumab in the treatment of PCV have been well documented, the literature is mainly from Japan, India and Korea, and clinical practice data from China are still lacking.With the approval of the drug in several countries, it is believed that more PCV patients could benefit from this treatment in the near future.Ophthalmologists and researchers in China should closely follow the progress of brolucizumab in the treatment of PCV.

Analysis of choroidal vascularity index distribution and influencing factors in normal children / 中华实验眼科杂志

Objective:To evaluate the distribution characteristics of choroidal vascularity index (CVI) in macula among normal children using swept-source optical coherence tomography (SS-OCT), and to investigate the influencing factors.Methods:A cross-sectional study was conducted.Sixty-three children aged 6 to 12 years were enrolled in The First Affiliated Hospital of Zhengzhou University from May 2021 to November 2021.Spherical equivalent refraction, axial length (AL) and other ocular biological parameters were measured.Macula-centered CVI and choroidal thickness (ChT) were measured by SS-OCT angiography.According to the ETDRS partition, the obtained image was divided into macular central fovea (0-1 mm diameter), inner ring (1-3 mm diameter) and outer ring (3-6 mm diameter) zones.Data from the right eye were selected for statistical analysis.CVI in the three rings and four zones (superior, temporal, inferior and nasal zones) of the inner and outer rings were compared.Univariate and multiple linear regression analyses were used to analyze the correlation between CVI and sex, AL, anterior chamber depth (ACD), ChT and pupil diameter.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of The First Affiliated Hospital of Zhengzhou University (No.2021-KY-0399-003). Written informed consent was obtained from each guardian.Results:The average CVI in the macular central fovea, inner ring and outer ring were 0.35±0.12, 0.32±0.10 and 0.27±0.08, respectively, with a significant difference ( F=10.96, P<0.001), and significant differences in CVI were found in pairwise comparisons of the three ring zones (all at P<0.05). Significant differences in CVI were found among superior, temporal, inferior and nasal zones in inner and outer rings ( Fring=11.60, P=0.001; Fzone=12.02, P<0.05). The CVI was smaller in superior and nasal zones in inner ring than in temporal zone, greater in superior, temporal and inferior zones in outer ring than in nasal zone, smaller in superior zone of outer ring than that of the inner ring, and the differences were statistically significant (all at P<0.001). The single factor linear regression analysis showed that ChT in the fovea, inner ring and outer ring were the influencing factors of CVI in the three ring zones (all at β=0.001, P<0.001). Pupil diameter ( β=0.034, P=0.038; β=0.040, P=0.003; β=0.024, P=0.011) and ACD ( β=0.097, P=0.034; β=0.097, P=0.013; β=0.061, P=0.032) were the influencing factors of CVI in fovea, inner ring and outer ring.After multiple linear regression analysis, the regression equations were established as follows: CVI in the macular fovea=0.001×ChT in the macular fovea + 0.001×ChT in the inner ring+ 0.001×ChT in the outer ring-0.301 ( R2=0.514, F=6.875, P<0.001); CVI in the inner ring=0.001×ChT in the macular fovea+ 0.001×ChT in the inner ring+ 0.001×ChT in the outer ring+ 0.088×AL-0.307 ( R2=0.603, F=9.870, P<0.001); CVI in the outer ring=0.001×ChT in the macular fovea+ 0.001×ChT in the inner ring+ 0.001×ChT in the outer ring-0.135 ( R2=0.601, F=9.781, P<0.001). Conclusions:In children aged 6-12 years old, the CVI is higher in the macular central fovea than in inner and outer rings, and the CVI in nasal zone is the smallest in both inner and outer rings.The thicker the ChT, the higher the CVI in all zones in the macular area; the deeper the anterior chamber, the higher the CVI in the inner ring.

Investigation of endothelial cell pathological characteristics in murine choroidal neovascularization model based on single-cell RNA sequencing / 中华实验眼科杂志

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.

Evaluation of choroidal vascularity index and subfoveal choroidal thickness in eyes with chronic central serous chorioretinopathy and their normal fellow eyes / 中华实验眼科杂志

Objective:To observe the choroidal vascular changes of chronic central serous chorioretinopathy (cCSC), and analyze their correlations with central macular thickness (CMT).Methods:A cross-sectional study was adopted.Seventy-six eyes of 38 patients with monocular cCSC who were treated in Renmin Hospital of Wuhan University from March 2018 to December 2019 were enrolled, and 30 eyes of 30 normal control matched with age, gender, and spherical equivalent (SE) were included.Choroidal images of all subjects, and the CMT, subfoveal choroidal thickness (SFCT), choroidal vascularity index (CVI), total choroidal area (TCA), choroidal stromal area (SA), and choroidal luminal area (LA) were measured by Heidelberg enhanced depth imaging optical coherence tomography.The differences in SFCT, LA, SA, TCA, CMT and CVI between the cCSC eye, fellow eye and normal eye, as well as the correlation between SFCT and CVI, SFCT and CMT, and CVI and CMT were analyzed.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Renmin Hospital of Wuhan University (No.WDRY2020-K234).Results:The CVI and the SFCT of the cCSC eyes, fellow eyes and normal eyes were (71.67±5.60)% and 483.82(409.01, 550.87)μm, (68.33±3.85)% and 444.66(351.25, 505.15)μm, (64.70±1.88)% and 373.46(327.98, 405.48)μm, respectively.The CMT, SFCT, TCA, LA, CVI in cCSC eyes were significantly higher than those in the contralateral eyes and normal control eyes, while SFCT, TCA, LA, CVI in the contralateral eyes were higher than those in normal control eyes (all at P<0.05). Pairwise comparison among the three groups showed no significant difference in SA (all at P>0.05). Correlation analysis showed that in cCSC eyes, SFCT was strongly positively correlated with CVI ( rs=0.703, P<0.001), and there was no correlation between CMT and SFCT ( rs=0.181, P=0.278), or CMT and CVI ( r=0.231, P=0.164). Conclusions:The SFCT and CVI are higher in cCSC and the fellow eyes compared with normal eyes, and the choroidal vessels are significantly dilated in cCSC patients.The SFCT and CVI of the cCSC eye are slightly higher in comparison with the fellow eye.CMT is not correlated with SFCT or CVI in cCSC eyes.

Differential Analysis of Macular Structure and Microcirculation in Both Eyes of Patients With Myopic Anisometropia / 中国医学科学院学报

Objective To compare the macular structure and microcirculation in both eyes of the patients with myopic anisometropia.Methods Optical coherence tomography angiography(OCTA)was employed to scan the macular areas in both eyes of 44 patients with myopic anisometropia.The patients were assigned into high and low groups based on the refractive diopter,and the parameters such as retinal thickness,choroidal thickness,vascular density,and perfusion density in the macular areas of both eyes were compared between the two groups.Results Other macular areas except the central and external nasal areas and the choroid of the fovea in the high group were thinner than those in the low group(all P<0.05).There was no statistically significant difference in retinal vascular density or perfusion density in different areas between the two groups(all P>0.05).Conclusion In the patients with myopic anisometropia,most areas of the retina in the case of high myopia is thinner than that in the case of low myopia,while there is no difference in retinal vascular density or perfusion density in both eyes.