Objective:To observe and analyze the short-term effects of intravitreal injection of Conbercept (IVC) on the expression levels of matrix metalloproteinase (MMP)-2 and MMP inhibitor-2 (TIMP-2) in the aqueous humor of eyes with proliferative diabetic retinopathy (PDR).Methods:A prospective clinical study. From March 2024 to June 2024, 30 consecutive patients with 30 eyes with PDR (PDR group) undergoing IVC combined with pars plana vitrectomy (PPV) at Department of Ophthalmology of The First Affiliated Hospital of University of Science and Technology were included in the study, along with 20 patients with 20 eyes undergoing cataract surgery (control group) during the same period. In the PDR group, IVC treatment was performed 3 to 7 days before PPV, and 0.05-0.10 ml aqueous humor was collected before IVC and before PPV. In the control group, 0.05-0.10 ml aqueous humor was collected before cataract surgery. The levels of vascular endothelial growth factor (VEGF), MMP-2, and TIMP-2 in the aqueous humor were measured using enzyme-linked immunosorbent assay. For normally distributed data, independent samples t-test were used for comparison between two groups; for non-normally distributed data, the Mann-Whitney U test was used. The correlation analysis of VEGF, MMP-2, TIMP-2 concentrations in aqueous humor of PDR patients was performed using Pearson's correlation coefficient. Results:There were no statistically significant differences in age ( Z=-1.810) and gender composition ( χ2=3.450) between the PDR group and the control group ( P>0.05). Before IVC, VEGF and MMP-2 expression levels were (0.23±0.10), (2.11±1.32) ng/ml and (0.12±0.03), (0.53±0.26) ng/ml in patients' aqueous fluid in PDR group and control group, respectively. The expression level of TIMP-2 and the ratio of MMP-2/TIMP-2 were (0.99±0.26), (1.76±0.11) ng/ml and 2.04 (1.19, 2.98), 0.36 (0.15, 0.39), respectively. Compared with the control group, the expression levels of VEGF and MMP-2 in aqueous humor in PDR group ( t=-5.030, -5.260) and the ratio of MMP-2/TIMP-2 ( Z=-5.740) were significantly increased, with statistical significance ( P<0.01). The expression level of TIMP-2 was significantly lower than that of control group, the difference was statistically significant ( t=12.120, P<0.01). After IVC, the expression levels of VEGF and MMP-2 in aqueous humor of PDR patients were (0.13±0.03) and (2.11±1.32) ng/ml, respectively. The expression level of TIMP-2 and the ratio of MMP-2/TIMP-2 were (0.95±0.28) ng/ml and 1.57 (1.02, 3.13), respectively. Compared with before IVC, the expression level of VEGF in aqueous humor in PDR group after IVC was significantly decreased, and the difference was statistically significant ( t=6.080, P<0.01). The expression levels of MMP-2 ( t=1.220), TIMP-2 ( t=0.290) and the ratio of MMP-2/TIMP-2 ( Z=-0.260) were not significantly different ( P=0.270, 0.780, 0.800). After IVC, there was no significant difference in VEGF expression level between PDR group and control group ( t=-1.200, P=0.240). The expression level of MMP-2 was still significantly increased ( t=-5.880), the expression level of TIMP-2 was still significantly decreased ( t=11.520), and the ratio of MMP-2/TIMP-2 was still significantly increased ( Z=-5.780), with statistical significance ( P<0.01). Correlation analysis showed that VEGF was positively correlated with MMP-2 in aqueous humor of PDR patients before IVC ( r=0.590, P<0.01). Conclusions:IVC can effectively reduce the level of VEGF in the aqueous humor of eyes with PDR in the short term, but it has no significant effect on the levels of MMP-2 and TIMP-2.

Diabetic retinopathy (DR) has become an important cause of irreversible vision loss worldwide. Intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs is an important method to the treatment of DR. However, the current anti-VEGF treatment regimen is not uniform. Anti-VEGF injection was preferred and then delayed combined with laser had better prognostic effect. The best time for operation was 5-7 days after injection of anti-VEGF drugs. Pars plana vitrectomy, intraoperative and postoperative on-demand anti-VEGF drugs injection can significantly improve patient prognosis and reduce complications, but further research is needed to strike a balance between the economic burden and the number of injections. Various anti-VEGF drugs have their own advantages for different diseases and should be selected according to the characteristics of the diseases and drugs. Anti-VEGF drugs combined with antioxidants may further improve DR outcomes. Future studies should pay more attention to the optimization and personalization of anti-VEGF drugs application programs to meet the therapeutic needs of different patients.

Objective:To observe the changes of retinal and choroidal blood flow density and thickness in macula of different myopic dioptre eyes, and to analyze the correlation between retinal and choroidal blood flow density and axial length (AL).Methods:A retrospective clinical study. From October 2022 to May 2023, 86 eyes of 56 myopic patients scheduled for refractive surgery in Department of Ophthalmology, PLA Central Theater CommandGeneral were included into the study. According to the equivalent spherical specular degree (SE), 19, 21, 27 and 19 eyes of low myopia group (group A), moderate myopia group (group B), high myopia group (group C) and super high myopia group (group D) were observed. Optical coherence tomography angiography (OCTA) and AL measurement were performed in all patients. The diopter was expressed in SE. AL was measured by ultrasonic bio-meter. OCTA scanner was used to scan the macular region in the range of 3 mm × 3 mm. The software automatically divided the macular region into two concentric circles with the fovea as the center, which were 1 mm in diameter respectively, the paracentric fovea of 1-3 mm was divided into 5 regions: superior, nasal, inferior and temporal. The superficial capillary plexus (SCP), deep capillary plexus (DCP), choroidal capillary plexus (CC), choroidal blood flow density, retinal and choroidal thickness were measured. The correlation between AL and blood flow density and thickness was analyzed by Pearson correlation analysis.Results:There was no significant difference in SCP blood density and DCP blood density in the fovea in groups A, B, C and D ( P>0.05) .There were significant differences in DCP flow density among superior, nasal, inferior and temporal areas ( P<0.05), the difference was significant ( P<0.05). There was no significant difference in the fovea area between the four groups ( P>0.05), but there was significant difference in the superior, nasal, inferior and temporal areas ( P<0.05). Different macular regions: there were statistically significant among group A, group B, and group C, group D ( P<0.05). Results of correlation analysis, AL was negatively correlated with DCP blood flow density ( r=-0.504, -0.500, -0.460, -0.465), retinal thickness ( r=-0.348, -0.338, -0.312, -0.230), macular subarea CC ( r=-0.633, -0.666, -0.667, -0.710, -6.82), choroidal layer ( r=-0.635, -0.687, -0.659, -0.703, -0.680) and choroidal thickness ( r=-0.665, -0.605, -0.656, -0.648,-0.643) ( P<0.05). Conclusions:AL is negatively correlated with DCP, CC, CDF, retinal and choroidal thickness in the eyes with myopia. SCP, DCP and retinal thickness in fovea did not change significantly, and temporal choroidal thickness changed earlier than other areas.

Objective:To observe the effects of RasGRP4 gene deletion on the structure and function of the retina in diabetic mice, and to explore the mechanism of RasGRP4 in diabetic retinopathy (DR) by transcriptome sequencing in conjunction with bioinformatics analysis. Methods:A total of 12 male C57BL/6J mice were divided into normal group, diabetic group (DM group), with 6 mice in each group. Six male RasGRP4 knockout mice were uesd as RasGRP4 knockout diabetic group (DM-KO group). Mice in the DM group and DM-KO group were fed with high-fat diet combined with intraperitoneal injection of streptozotocin to establish diabetic model and body weight and blood glucose were monitored regularly. Three months after modeling, optical coherence tomography was used to detect the retinal thickness and ganglion cell layer thickness. Electroretinography was used to detect the function of the retina in mice under dark-adapted conditions. Total RNA was extracted from the retinas of mice in DM group and DM-KO group, and transcriptomic sequencing was performed to screen differentially expressed genes (DEG). Core genes were screened using MCODE and Cytohubba plug-ins of Cytoscape v3.8.2 software. At the same time, the functional enrichment analysis of gene samples (GO) of the selected DEG was performed. The mRNA relative expression levels of interleukin-8, transforming growth factor-β (TGF-β), interferon-γ (IFN-γ), NOd-like receptor thermal protein domain protein 3 (NLRP3), Caspase-1 and IL-1β in each group were detected by real-time quantitative polymerase chain reaction. t test was used to compare the two groups. One-way analysis of variance was used to compare the three groups. Results:Compared with the DM group, there was no significant difference in blood glucose and body weight in the DM-KO group with the extension of high-fat diet ( t=0.12, 2.02, 0.22, 0.10, 0.59, 0.41, 1.35, 0.31, 1.12, 1.58, 1.47, 1.20, 1.24, 0.39, 0.66, 0.14; P>0.05). The retinal thickness and ganglion cell layer thickness of mice in the three groups were significantly reduced in the DM group compared with the normal group, while DM-KO was significantly increased compared with the DM group, and the differences were statistically significant ( F=30.43, 7.81; P<0.000 1, 0.01). Comparison of a-wave and b-wave amplitudes among the three groups showed that the DM group was significantly lower than the normal group, while the DM-KO was significantly higher than the DM group, and the differences were statistically significant ( F=16.46, 35.58; P<0.001, 0.000 1). Compared with the DM group, 184 differential genes (DEG) were screened in the DM-KO group, among which 39 up-regulated and 145 down-regulated genes were detected, respectively. The results of the MCODE plug-in analysis showed that Col1a2, Fbln1, Fbn1, Col6a3, Fmod, Ogn, Tgfb, Mfap4, Vcan, Nid2, and Col18a1 were core genes in the DEG. Cytohubba plug-in analysis showed that Col1a2, Mrc1, Cd47, Fbn1, Cybb, Cd163, Fbln1, Fmod, Adgre1, and Col6a3 were the core genes in DEG. The results of the GO functional enrichment analysis showed that DEG was mainly involved in hemoglobin complexes, MHC class Ⅱ protein complex, apical plasma membrane, inflammasome complex, immunological synapse, response to bacterium, inflammatory response, immune system processe, response to hypoxia, and cell adhesion were significantly enriched. Comparison of mRNA relative expression levels of IL-8, TGF-β, IFN-γ, NLRP3, Caspase-1 and IL-1β in the three groups showed that the DM group was significantly higher than the normal group, while the DM-KO was significantly lower than the DM group, with statistical significance ( F=12.43, 15.41, 70.09, 29.04, 11.79, 41.28; P<0.01). Conclusion:RasGRP4 deficiency plays a therapeutic role in the development of DR through inhibition of inflammatory factor secretion and NLRP 3 inflammasome pathway activation.

Objective:To observe the effect of mild anemia on prognosis of hyperplastic diabetic retinopathy (PDR) treated by pars plana vitrectomy (PPV).Methods:A retrospective case-control study. From January 2021 to December 2022, 147 PDR patients with 147 eyes who received PPV treatment at Shenyang He Eye Hospital were included in the study. There were 147 eyes in 147 cases, 82 eyes in 82 males and 65 eyes in 65 females. Age was 25-79 (53.54±12.74) years old. A hemoglobin (Hb) of 90 to 120 g/L in men and 90 to 110 g/L in women was defined as mild anemia. According to Hb results, the patients were divided into mild anemia group and non-anemia group, with 39 cases (39 eyes) and 108 cases (108 eyes), respectively. The best corrected visual acuity (BCVA) test was performed using the international standard logarithmic visual acuity scale before and after the surgery, which was statistically converted to minimum resolved logarithmic (logMAR) visual acuity. The logMAR BCVA of the affected eye was 0.2-2.5 (1.60±0.62) before surgery. According to whether the BCVA improved by more than 3 lines 6 months after surgery, the affected eyes were divided into BCVA improved by more than 3 lines and BCVA improved by less than 3 lines, 117 eyes and 30 eyes, respectively. The patient's body mass index (BMI), BCVA at 6 months after surgery, and the occurrence of neovascular glaucoma (NVG) and recurrence of vitreous hemorrhage (RVH) were recorded. Independent sample t test was used for comparison between groups. Multivariate logistic regression analysis was performed to analyze the influencing factors of increased BCVA ≥3 rows after surgery. Results:Six months after surgery, the logMAR BCVA of patients in mild anemia group and non-anemia group were 0.97±0.87 and 0.68±0.63, respectively. BCVA increased ≥3 in 26 (66.7%, 26/39) and 91 (84.3%, 91/108) eyes, respectively. logMAR BCVA ( t=2.234) and BCVA increased by ≥3 rows of eyes ( χ2=5.460) between the two groups, the differences were statistically significant ( P=0.027, 0.019). Logistic regression analysis showed that baseline logMAR BCVA [odds ratio ( OR) = 4.291, 95% confidence interval ( CI) 1.918-9.600, P<0.001)], BMI ( OR=1.248, 95% CI 1.057-1.472, P=0.009), the number of retinal laser photocoagulation during surgery ( OR=1.001, 95% CI 1.000-1.002, P=0.038), mild anemia ( OR=0.360, 95 % CI 0.131-0.993, P=0.048), postoperative NVG ( OR=0.156, 95% CI 0.033-0.726, P=0.018) and RVH ( OR=0.264, 95% CI 0.086-0.808, P=0.020) were independent factors for BCVA improvement ≥3 lines after PPV. Conclusions:Mild anemia has a certain effect on BCVA improvement after PPV of PDR. Mild anemia, post-operative NVG and RVH were independent risk factors for increasing BCVA ≥3 lines after PPV in PDR patients.

Retinal vein occlusion (RVO) is a serious retinal vascular disease, often accompanied by systemic cardiovascular and cerebrovascular diseases, the eye changes include macular edema, retinal ischemia, and even neovascularization, etc. As a common chronic disease of the fundus, it seriously affects patients' vision and quality of life. With the development of optical coherence tomography, the role of choroid in the occurrence and development of RVO has become a research hotspot. The research on the changes of the choroid layer of the eye with RVO has expanded from a simple two-dimensional thickness analysis to a more comprehensive multidimensional observation index such as three-dimensional volume, blood flow density and velocity. In addition, some cutting-edge research combines artificial intelligence algorithm techniques to improve the accuracy and depth of analysis. In the future, it is still necessary to further improve the data of the choroid layer of the eye with RVO, enhance the overall understanding of RVO, and provide new ideas for clinical prevention and treatment of RVO.

Age-related macular degeneration (AMD) is an age-related neurodegenerative eye disease characterized by degeneration and progressive death of retinal pigment epithelium (RPE) and photoreceptor cells. In recent years, as a new treatment for AMD, stem cell therapy has attracted wide attention in the field of AMD, and has become a current research hotspot. Although stem cell therapy carries risks such as increased incidence of cancer and immune rejection, it significantly promotes damaged photoreceptor cells and retinal cells by differentiating into RPE cells and other retinal cell types, as well as secreting neurotrophic factors and extracellular vesicles. In particular, the development of embryonic stem cell-derived RPE cells, its cryopreservation technology and the advancement of plasmid, adeno-associated virus, Sendai virus and other delivery technologies have laid a solid foundation for stem cell therapy of AMD. As a new method to prevent retinal damage and photoreceptor degeneration, stem cell neuroprotective therapy has shown great potential, and with the continuous maturity and improvement of these technologies, stem cell therapy is expected to provide new ideas for the prevention and treatment of AMD in the future.

Bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) are common and critically important diseases of preterm infants. The common feature of both conditions is altered angiogenesis and pathological changes in the case of incomplete organ development. The interaction of multiple factors leads to abnormal angiogenesis, which not only increases the possibility of comorbidity of BPO and ROP, but also reveals the potential co-pathogenesis between the two. However, the specific mechanism of this angiogenic balance in the occurrence and development of BPD or ROP is still unclear, and there are no animal models to explore the pathogenesis of both diseases. At present, effective prevention measures for BPO and ROP are still lacking, and treatment methods mainly rely on drug therapy and surgery. In the future, more studies should be conducted to find common therapeutic targets for factors affecting angiogenesis, so as to provide better treatment options for BPD and ROP and improve the effectiveness of treatment.

Objective:To observe and analyze the pathogenic genes and clinical phenotype characteristics of retinitis pigmentosa sinepigmento(RPSP).Methods:A retrospective clinical study. Two patients (proband) and five family members from two RPSP families admitted to Xiamen Eye Center of Xiamen University in December 2022 and Shenzhen Eye Hospital in July 2023 were included in the study. Two families have no blood relationship and were both Han Chinese. Detailed ocular and systemic medical history and specialized examinations were performed for all members, including color fundus photography, fundus autofluorescence (FAF), and full field electroretinogram (ff-ERG) examination. The peripheral venous blood of all members was collected, and genomic DNA was extracted. Pathogenic genes and their loci were screened using whole exome high-throughput sequencing technology. Sanger sequencing was used to verify the pathogenic genes in the two pedigrees. The pathogenicity of candidate variants was evaluated according to the American Society for American College of Medical Genetics and Genomics (ACMG) classification criteria and guidelines for genetic variants.Results:The two probands were male, aged 9 and 7 years, respectively. The main complaint was poor binocular vision for 6 and 3 years and poor treatment effect of amblyopia. The proband (Ⅱ2) in family 1 had a pale red color on the optic disc, with leopard-like changes in the posterior pole and thinner retinal arteries. FAF showed mottled fluorescence attenuation outside the macular vascular arch. There was no significant waveform in both bright and dark visual responses of ff-ERG. He also had 6-toed deformity of both feet, renal cysts, and a slightly overweight body. The clinical diagnosis was non-pigmentary retinitis pigmentosa. The proband of family 2 (Ⅱ1) had poor binocular vision in a dark environment and had atrophy lesions on the nasal side of the optic disc and leopard print like changes in the fundus. FAF showed uneven enhancement in the fovea. ff-ERG showed severe abnormalities in dark and light response, with significant decrease and delay in b-wave amplitude and latency. He had no other systemic abnormalities. The clinical diagnosis was binocular RPSP. There were no abnormal ocular and systemic manifestations in the two family members. Gene sequencing revealed a homozygous mutation (c.534+1G>T) of BBS2 gene, which was inherited from the mother and father respectively. Based on clinical manifestations and genetic testing results, the final diagnosis was Bardet Biedl syndrome. The genetic sequencing results confirmed a novel compound heterozygous mutation (c.950T>G: p. Leu317Arg missense mutation and c.849+1G>C splicing mutation) of BBS7 gene. His father (Ⅰ1) and mother (Ⅰ2) carried M1 heterozygous variants. Combined with the clinical manifestations and genetic testing results, the final diagnosis was Bardet-Biedl syndrome (BBS). Family 2 proband (Ⅱ1) carried the BBS7 gene C.950T>G (p.Leu317Arg) (M2) missense variation and C.849 +1G>C (M3) splice site variation. His father (Ⅰ1) and mother (Ⅰ2) carried M3 shear site variation and M2 missense variation, respectively. The two families all fit the autosomal recessive inheritance pattern, and the genotype and clinical phenotype were coseparated. According to ACMG guidelines, M1, M2 and M3 were all identified as possible pathogenic variants. Conclusions:BBS2 gene M1 homozygous variation and BBS7 gene M2, M3 complex heterozygous variation are the possible pathogenic genes in family 1 and family 2, respectively. Two families are affected by BBS and RPSP, respectively.

Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes, which seriously threatens the vision of patients. The pathogenesis of DR Is complex and involves many pathophysiological processes. At present, the treatment methods for DR Mainly include panretinal laser photocoagulation, vitrectomy and vitreous cavity injection, etc. However, each treatment method has certain limitations. In recent years, remarkable progress has been made in the field of drug treatment of DR, especially in anti-vascular endothelial growth factor drugs, anti-inflammatory drugs, anti-oxidative stress damage drugs, neuroprotective agents, gene therapy and stem cell therapy. These drugs not only improve the effectiveness of treatment, but also expand the range of treatment options. In addition, by carrying DR Treatment drugs on carriers such as nanoparticles, hydrogels and photosensitive materials, continuous and efficient release of drugs in the eye is achieved, thereby extending the time interval of administration and reducing the need for frequent treatment of patients. In the future, based on biomarker detection technology, it is expected to promote the development of personalized and precise treatment, which can develop more accurate treatment plans for patients and improve the efficacy.