ObjectiveTo observe the clinical efficacy and safety of Tangning Tongluo tablets in the treatment of nonproliferative diabetic retinopathy （DR）. MethodsFourteen research centers participated in this study， which spanned a time interval from September 2021 to May 2023. A total of 240 patients with nonproliferative DR were included and randomly assigned into an observation group （120 cases） and a control group （120 cases）. The observation group was treated with Tangning Tongluo tablets， and the control group with calcium dobesilate capsules. Both groups were treated for 24 consecutive weeks. The vision， DR progression rate， retinal microhemangioma， hemorrhage area， exudation area， glycosylated hemoglobin （HbA1c） level， and TCM syndrome score were assessed before and after treatment， and the safety was observed. ResultsThe vision changed in both groups after treatment （P<0.05）， and the observation group showed higher best corrected visual acuity （BCVA） than the control group （P<0.05）. The DR progression was slow with similar rates in the two groups. The fundus hemorrhage area and exudation area did not change significantly after treatment in both groups， while the observation group outperformed the control group in reducing the fundus hemorrhage area and exudation area. There was no significant difference in the number of microhemangiomas between the two groups before treatment. After treatment， the number of microhemangiomas decreased in both the observation group （Z=-1.437， P<0.05） and the control group （Z=-2.238， P<0.05）， and it showed no significant difference between the two groups. As the treatment time prolonged， the number of microhemangiomas gradually decreased in both groups. There was no significant difference in the HbA1c level between the two groups before treatment. After treatment， the decline in the HbA1c level showed no significant difference between the two groups. The TCM syndrome score did not have a statistically significant difference between the two groups before treatment. After treatment， neither the TCM syndrome score nor the response rate had significant difference between the two groups. With the extension of the treatment time， both groups showed amelioration of TCM syndrome compared with the baseline. ConclusionTangning Tongluo tablets are safe and effective in the treatment of nonproliferative DR， being capable of improving vision and reducing hemorrhage and exudation in the fundus.

AIM: To investigate the global research status, hotspots, and trends of exosome studies in ophthalmology, providing a theoretical foundation and constructive references for future research, and promoting in-depth development in this field.METHODS: Relevant literature on exosomes in ophthalmology published up to May 20, 2024, was retrieved from the China National Knowledge Infrastructure(CNKI), Web of Science Core Collection, and PubMed databases. Visual analyses of publication countries, institutions, authors, high-frequency keywords, burst keywords, and timelines were performed using CiteSpace 6.3.R1 and VOSviewer software.RESULTS: A total of 37 Chinese articles and 548 English articles were included. The top five countries in terms of publication volume were the United States(130 articles), China(80 articles), South Korea(24 articles), the United Kingdom(20 articles), and Japan(19 articles). The leading foreign institutions were the University of California System, Duke University, and Harvard University, while the top domestic institutions were Qingdao University, the Department of Ophthalmology at the First Affiliated Hospital of Jinan University, and the School of Physical Education and Sports Science at Beijing Normal University. Analysis of Chinese and English high-frequency and burst keywords indicated that global research hotspots on exosomes in ophthalmology primarily focus on dry eye, extracellular vesicles, mesenchymal stem cells and their derived exosomes, ocular surface diseases, ocular surface inflammation, biomarkers, retinal protection, immune eye diseases, uveitis, degenerative eye diseases, macular degeneration, diabetic retinopathy, neovascularization, thyroid-associated ophthalmopathy, and glaucoma, while English high-frequency words mainly were dry eye, dry eye disease, delivery, regenerative medicine, uveal melanoma, protein, and transplantation. Research has evolved from initial basic biological studies to exploring the pathogenesis of ocular diseases and advancing toward novel diagnostic and therapeutic approaches.CONCLUSION: Over the past 5 a, research on exosomes in ophthalmology has grown rapidly. Exosomes, as novel biomarkers and potential therapeutic targets, have become central to studies on the pathogenesis and clinical applications of ophthalmic diseases. Their roles in the diagnosis, treatment, and prevention of these diseases represent promising directions for future research.

OBJECTIVE To evaluate the quality of evidence in the systematic evaluation/meta-analysis of traditional Chinese medicine （TCM） for diabetes retinopathy （DR） based on the GRADE system. METHODS Chinese and English databases were searched to obtain the relevant studies of systematic evaluation/meta-analysis of traditional Chinese medicine in the treatment of DR. The search time was from the establishment of each database to January 13th， 2024. According to the inclusion and exclusion criteria， literature screening was conducted. After extracting relevant information from the included literature， the GRADE system was used to evaluate the quality level of the evidence body in the included studies， and the evidence of the outcome indicators was integrated and summarized. RESULTS A total of 51 studies were ultimately included， encompassing 135 outcome indexes. Among these， 19 indicators （14.1%） were of high quality， 87 （64.4%） were of medium quality， 26 （19.3%） were of low quality， and 3 （2.2%） were of very low quality. Overall， the evidence quality of the outcome indicators in the included studies was medium to low quality. The integrated results of evidence on the efficacy of outcome indexes showed that compared with conventional Western medicine， calcium dobesilate or placebo， TCM had significant advantages in improving overall efficacy， reducing bleeding spot area， reducing macular foveal thickness， and increasing visual improvement rate. In addition，the combination of TCM and conventional Western medicine or calcium dobesilate was significantly more effective than using conventional Western medicine or calcium dobesilate alone. CONCLUSIONS The overall quality of the evidence in the systematic evaluation/meta-analysis study on the treatment of DR with TCM is medium to low quality. Based on existing research findings， TCM demonstrates good clinical efficacy in the treatment of DR.

AIM: To conduct a CiteSpace-based visualization analysis of the literature on traditional Chinese medicine(TCM)treatment of diabetic retinopathy(DR)from January 2014 to January 2024.METHODS: The literatures were retrieved from the China National Knowledge Infrastructure(CNKI)database. Co-occurrence, clustering, and emergence analyses of annual publications, authors, research institutions, and keywords were performed using Note Express and CiteSpace software to generate knowledge graph.RESULTS: A total of 643 Chinese-language articles were included. The annual publication trend was characterized by fluctuations. The primary research institutions were Liaoning University of Traditional Chinese Medical and Eye Hospital China Academy of Chinese Medical Sciences. Twenty high-frequency keywords were identified, including diabetes, TCM, and review, along with emergent terms such as Qiming granules and data mining. The research focus in 2014 was on exploring therapeutic methods and the efficacy of proprietary Chinese medicines. From 2016 to 2018, the research perspective expanded to include symptoms and multi-factorial analysis. Between 2018 and 2020, there was an in-depth investigation into evidence types and disease stages. After 2019, the emphasis shifted towards TCM-specific therapies and patient-centered concepts. From 2022 to 2024, innovation in research methods and the theory of TCM collaterals theory emerged as new hotspots.CONCLUSION: The research on TCM treatment for DR is still in an ascending phase. The primary research hotspot currently centers on Qiming granules. Future trends are likely to focus on the efficacy and mechanisms of action. The combined application of different therapies and long-term follow-up experimental research could provide a more robust basis for evidence-based medicine, unearth the potential of TCM, and promote its development in the prevention and treatment of DR.

AIM: To explore the current status, research hotspots, and trends of global uveitis research to provide a theoretical basis and references for researchers in the field of uveitis, and promote further development in this area.METHODS: Relevant literatures on uveitis were retrieved from the China National Knowledge Infrastructure(CNKI)database, Wanfang database, and Web of Science core collection database since their establishment until 24 August 2023. The country/publishing institutions, research authors, high-frequency keywords, and burst keywords were visual analyzed by using software such as GraphPad Prism 9, CiteSpace 6.2. R2, and VOSviewer.RESULTS: Research teams for uveitis have been formed in various countries globally. The top three countries in terms of publications are the United States of America(7 585 papers), the United Kingdom(2 412 papers)and Germany(1 679 papers). The top three foreign institutions in terms of publications are Harvard University, Oregon Health & Science University, and Moorfields Eye Hospital, while the top three domestic institutions are Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine, Chongqing Medical University, and Zhongshan Ophthalmic Center, Sun Yat-sen University. The analysis of high-frequency keywords and burst keywords in Chinese and English shows that research hotspots mainly focus on exploring pathogenesis and different treatment methods for uveitis. The research hotspots related to uveitis treatment are transitioning to molecular biology-related research topics, such as molecular biological signaling pathways(NF-κB signaling pathway with a strength value of 22.89), biological agents(adalimumab with a strength value of 32.21), and tumor necrosis factor(with a strength value of 48.44). Related research is also expanding to basic experiments on relevant rats.CONCLUSIONS: In recent years, the research hotspots and trends of global uveitis mainly focus on precise diagnosis, pathogenesis, and more effective treatment methods. It is important for more scholars to dedicate themselves to uveitis-related research in the future to make breakthroughs and progress in the field. More large-scale and multicenter clinical studies on uveitis can provide high-quality research evidence.

Diabetes retinopathy (DR) is a blinding ocular complication of diabetes, and its pathological mechanism is complex. The damage to the retinal neurovascular unit (NVU) and the imbalance of its coupling mechanism are important pathological foundations. Autophagy plays an important role in the progression of DR. Oxidative stress, endoplasmic reticulum stress, hypoxia, and competitive endogenous RNA regulatory networks can affect the occurrence of autophagy, and autophagy induced cell death is crucial in NVU dysfunction. Retinal neurocyte are non-renewable cells, and adaptive autophagy targeting neuronal cells may provide a new direction for early vision rescue in patients with DR. It is necessary that exploring the possible autophagy interrelationships between ganglion cells, glial cells, and vascular constituent cells, searching for targeted specific cell autophagy inhibitors or activators, and exploring the impact of autophagy on the NVU complex more comprehensively at the overall level. Adopting different autophagy intervention methods at different stages of DR may be one promising research directions for future DR.

Diabetic retinal neurodegeneration is a serious complication of diabetes mellitus, manifested by apoptosis and gliosis, and its pathogenesis is closely related to the oxidative stress induced by high glucose levels. The increase in blood glucose in the body leads to excessive production of reactive oxygen species and the downregulation of antioxidant defense signaling pathways, which leads to oxidative stress in the body, which in turn induces apoptosis, mitochondrial damage and autophagy, resulting in diabetic retinal neurodegeneration. Antioxidant stress therapy with gene therapy, flavonoids, recombinant Ad-β-catenin carriers, and autophagy inducers to exert neuroprotective effects. In the future, more clinical trials are needed to explore the effective dosage and side effects of drugs, and to develop new drugs and treatment strategies for oxidative stress to prevent and treat diabetic retinal neurodegeneration and protect retinal nerve function.

Objective:To establish a rat model of diabetic microangiopathopathy and simulate the biochemical and pathological changes of diabetic retinal and renal microangiopathopathy.Methods:Forty healthy male Sprague-Dawley rats were randomly divided into blank group and model group (10 and 30 rats, respectively). After the rats in blank group and model group were fed ordinary diet and high-fat and high-sugar diet for 5 weeks, respectively, the rats in model group were injected with 1% streptozotocin (STZ) through the abdominal cavity at the dose of 35 mg/kg to establish a type 2 diabetes model. After modeling, the rats were continuously fed until the 10th week (4 weeks after modeling), the general conditions of the rats were observed, and samples were collected for follow-up experiments. Serum creatinine (CREA), triglyceride (TG), total cholesterol (TC), high density lipoprotein (HDL-C), low density lipoprotein (LDL-C), microalbuminuria, urinary creatinine (UCr) and urine sugar were detected. Calculate the kidney index and microalbumin/urinary creatinine ratio (UACR). Optical coherence tomography angiography (OCTA) was used to observe the vascular changes and non-perfusion area of retinal superficial capillary plexus. The morphological and structural changes of kidney and retina were observed by hematoxylin-eosin and periodate Scheff staining. The expression of nerve fibers and nucleus of Müller cells in rat retina was observed by immunofluorescence staining. Ultrastructural results of retina were observed by transmission electron microscope. Independent sample t test was used for comparison between groups. Results:Four weeks after modeling, compared with blank group, the body weight of rats in model group was significantly decreased, and random glucose was significantly increased, with statistical significance ( t=5.755, -51.291; P<0.05). Renal index, urinary glucose and UACR were significantly increased, while UCr was significantly decreased, with statistical significance ( t=10.878, 137.273, 3.482,-6.110; P<0.05). CREA decreased, TG, TC, HDL-C, LDL-C increased, and the differences were statistically significant ( t=-28.012, 33.018, 118.018, 13.585, 16.480; P<0.05). OCTA examination showed that there was no perfusion area of shallow retinal capillaries. The optical microscope showed that the inner boundary membrane of retina in model group was swollen and thickened, the surface was uneven, the inner and outer nuclear layer cells were disordered and the density decreased. Glomerular congestion was accompanied by cortical tubular epithelial swelling, widening of the mesangial area, and thickening of the basement membrane. The results of immunostaining showed that the inner and outer plexiform layers of the retina showed lamellar strong green fluorescence expression, and the inner and outer nuclear layers showed scattered dot green fluorescence expression. Transmission electron microscopy showed that the basal membrane of retinal microvessels in model group was slightly thickened, vascular endothelial cells edema, endothelial nucleus and perinucleus contraction, nuclear membrane contraction, mild mitochondrial swelling, vacuolation. Conclusion:High-glucose and high-fat feeding plus a single intraperitoneal injection of STZ 35 mg/kg can successfully establish a microangiopathic model of type 2 diabetes.

Diabetic retinopathy (DR) is one of the main cause of severe visual impairment in diabetic patients. Most of the existing treatments are aimed at patients with intermediate and advanced stages of vision impairment, and are invasive treatments with limited effects. Therefore, it is urgent for non-invasive new therapies and new targets to prevent the risk of DR or delay the progress of DR. Early optimization of metabolic therapies, which are strict control of blood glucose, blood pressure and blood lipid in the early stage of diabetes, may prevent or improve potential and reversible microangiopathy, however, there is still a lack of comprehensive and effective drug targeted therapy and unified clinical application standards. Therefore, this study summarizes the application of new hypoglycemic drugs and some antihypertensive and lipid-lowering drugs in the prevention and treatment of DR in recent years, in order to provide some reference for the clinical early prevention and treatment of this disease.

Microvascular dysfunction is a key pathological mechanism of diabetic retinopathy (DR). In recent years, it has been found that the phenomenon of "metabolic memory" is prevalent in diabetic patients, and diabetic microangiopaplasia cannot be avoided even if patients' blood glucose is well controlled. Therefore, it is necessary to explore DR from a genetic perspective. miR-126 is the unique microRNA specifically expressed in vascular endothelial cells, which is closely related to the formation of neovascularization and can affect the stability of DR microvessels as well as the germination and migration of endothelial cells, and its gene level is significantly negatively correlated with the expression of vascular endothelial cell growth factor. The potential value of intracellular and circulating miR-126 in the regulation of DR microvascular homeostasis, early diagnosis and treatment, and monitoring of disease course has attracted great attention. However, studies in this area are mostly hypothesis-driven and still have some limitations. It is believed that with the rapid development of genomics, the miRNA spectrum and its molecular mechanism in eye development and eye diseases will gradually become clear, which may lead to a breakthrough in the intervention of individual refractory retinal diseases and establish a new miRNA diagnosis and treatment method in the future.