Age-related macular degeneration (AMD) is one of the leading irreversible causes of blindness in China. The pathogenesis of AMD is not fully understood at present. Under various stress conditions, cellular senescence is activated, characterized by telomere shortening, mitochondrial dysfunction, DNA damage, and the release of various senescence-related secretory phenotype factors. Senescence is implicated in the pathogenesis of AMD through multiple pathways, contributing to chronic inflammation and the onset and progression of AMD. Mechanisms such as oxidative stress, lipofuscin, β amyloid protein and the membrane attack complex have become hotspots of study in the pathogenesis of AMD. The cyclic guanosine phosphate - adenosine synthase - interferon stimulating factor synthase-stimulator of interferon gene pathway has emerged as a critical signaling pathway in the early development of AMD, providing direction for further research on AMD. Currently, senolytics, selective agents targeting the induction of senescent cell apoptosis, show significant potential in the treatment of AMD. The integration of new technologies with cellular senescence may offer a novel approach to AMD treatment, and intervening in the AMD treatment through anti-cellular senescence pathways holds promising prospects.
Age-related macular degeneration (AMD) involves dysregulation of the innate immune response of complement and mononuclear phagocytes and abnormalities of local microglia. When microglia transition from a resting state to an active state, their metabolic pathway also changes, known as "metabolic reprogramming", and their glucose metabolic reprogramming is a key factor in the pathogenesis of AMD, involving multiple signaling pathways. Including phosphatidylinositol 3-kinase-serine threonine kinase-rapamycin target, adenylate activated protein kinase and hypoxia-inducing factor 1 pathway. These metabolic changes regulate the inflammatory response, energy supply, and neuroprotective functions of microglia. Therapeutic strategies to regulate the reprogramming of glucose metabolism in microglia have achieved initial results. Future studies should further explore the mechanisms of microglia metabolic regulation to develop new targeted drugs and intervene in the treatment of AMD through anti-cellular aging pathways.
The severe visual impairment caused by neovascular age-related macular degeneration (nAMD) is associated with macular neovascularization (MNV) invasion and subretinal fibrosis (SF). Excessive SF can lead to subretinal scarring, irreversible damage to photoreceptors, retinal pigment epithelium, and choroid tissue, resulting in permanent visual impairment in nAMD patients. The pathogenesis of SF is complex, involving many pathological processes such as tissue repair after injury, inflammation, and related signaling pathways and cytokine complex. Current experimental treatments for SF only target inhibition of a single cytokine. Timely and effective inhibition of the formation and progression of MNV and early identification of risk factors for SF are crucial to improving the prognosis of nAMD patients.
Vascular endothelial growth factor (VEGF) is a multifunctional factor that promotes blood vessel formation and increases vascular permeability. Its abnormal elevation plays a key role in common retinal diseases such as wet age-related macular degeneration and diabetic macular edema. Anti-VEGF therapy can inhibit angiogenesis, reduce vascular leakage and edema, thereby delaying disease progression and stabilizing or improving vision. Currently, the clinical application of anti-VEGF drugs has achieved satisfactory therapeutic effects, but there are also issues such as high injection frequency, heavy economy burden, potential systemic side effects, and non-responsiveness. To address these issues, current research and development mainly aim on biosimilars, multi-target drugs, drug delivery systems, oral anti-VEGF drugs, and gene therapy. Some drugs have shown great potential and are expected to turn over a new leaf for anti-VEGF treatment in ophthalmology.
Objective To observe the characteristics of indocyanine green angiography in exudative age-related macular degeneration. Methods Thirty one cases(36 eyes)were diagnosed as exudative age-related macular degeneration by ocular examination,fundus color photography,fundus fluorescein angiography(FFA)and indocyanine green angiography(ICGA).Their ages ranged from 50 to 82 years.The visual acuities were FC/30cm before eye to 0.7.We analyzed and compared the characteristics of ICGA and FFA in these patients. Results Of 26 eyes with occult choroidal neovascularization(CNV)by FFA,15(57.7%)had classic CNV.Of 4 eyes with serous retinal pigment epithelial detachment(PED)without CNV by FFA,l had serous PED with classic CNV.The hyperfluorescence of the scar stain was defected by ICGA. Conclusion ICGA adds clinically useful information and is important in laser treatment of patients with occult CNV in AMD. (Chin J Ocul Fundus Dis,1998,14:76-80)
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.
According to the best corrected visual acuity and the morphological changes of the macular fovea, responses to the neovascular age-related macular degeneration (nAMD) who receive anti-vascular endothelial growth factor (VEGF) therapy show large variability, including poor and non-responders. Various factors will be reviewed to account for poor and non-response to anti-VEGF therapy, such as the related susceptibility genes, factors related with the development of choroidal neovascularization and morphologic parameters, pharmacokinetics and tachyphylaxis. The future research should focus on comprehensive assessment of factors affecting the efficacy of anti-VEGF therapy to improve the therapeutic outcome of nAMD.
ObjectiveTo explore the multimorbidity of age-related macular degeneration (AMD) and diabetic retinopathy (DR) in diabetic patients, and observe the association between AMD and the two-year progression of DR. MethodsA prospective cohort study. The data were obtained from the Phase Ⅰ baseline and Phase Ⅱ follow-up of the Beichen Eye Study, which was conducted from June 2020 to August 2023, and the data from participants with diabetes were extracted for analysis. The baseline study included demographic data, anthropometric indices, ocular biometry, visual acuity, fundus imaging, Lens Opacities Classification System Ⅲ grade, questionnaires and laboratory information, etc., and follow-up was performed after two years. DR diagnosis and grading was performed based on the DR International Classification Criteria, and the eye with the heavier DR classification was taken as the affected eye. According to whether there was new-onset DR or DR progression at the follow-up visit, patients were divided into DR non-progressing group and progressing group. The Wisconsin AMD grading standard was used for AMD diagnosis and grading. Quantitative data were compared using the Mann-Whitney U test, and categorical variables were compared using the χ2 test or Fisher's exact test. Logistic regression models were used to estimate the odds ratio (OR) and 95% confidence interval. Sub-group analysis would be executed if the primary analysis had no significant results. Sensitivity analysis was conducted after the application of multiple imputation for missing data. ResultsA total of 1 190 eligible diabetic patients were included at baseline. The observed prevalence rates were 22.69% (270/1 190) for DR, 25.97% (309/1 190) for AMD, and 6.64% (79/1 190) for DR-AMD co-morbidity. Among the 741 patients who completed the 2-year follow-up, 95 cases (12.82%) were in the DR progression group and 646 cases (87.18%) were in the non-progression group. Compared with those without AMD, the prevalence of DR in patients with early (24.44%, 66/270), middle (4.07%, 11/270), late atrophic AMD (0.37%, 1/270), and exudative AMD (0.37%, 1/270) showed an increasing trend. However, the differences were not statistically significant (P＞0.05). The results of logistic regression analysis showed that having AMD at baseline was an independent risk factor for DR (OR=1.532, P=0.026). During the follow-up period, subgroup analysis revealed that in AMD patients with an axial length of 22.9-23.5 mm (OR=4.507, P=0.028) or a platelet-lymphocyte ratio of 99.5-122.0 (OR=4.107, P=0.015), the risk of DR progression was significantly increased. The results of the sensitivity analysis after multiple imputation of the missing data remained stable. ConclusionAMD in diabetic patients over 50 years of age is an independent risk factor for DR prevalence and progression.
Age-related macular degeneration (AMD) is one of the leading causes of irreversible vision loss. There are two primary forms of AMD: exudative age-related macular degeneration (WAMD) and atrophic AMD (DAMD). While numerous medications are currently available for the treatment of WAMD, yielding significant therapeutic outcomes, effective treatments for DAMD remain scarce. Various animal studies and clinical trials on DAMD treatment have been conducted, focusing primarily on antioxidants, complement pathway inhibitors, mitochondrial protectors, visual cycle inhibitors, neuroprotectants, amphiphilic polymer-based drug delivery systems, cell therapy, photobiomodulation therapy, gene therapy, surgical interventions, and traditional Chinese medicine. Among these, antioxidant supplementation with vitamins and complement pathway inhibitor APL-2 and ACP have received Food and Drug Administration approval for the treatment of DAMD. With the continuous development of the medical field, the future will explore the treatment methods with little trauma, good efficacy and good patient compliance, and successfully achieve clinical transformation.
Purpose To decribe the prevalence of age related macular degeneration (AMD) in the population aged 50 and over in Doumen County of Gunagdong Province. Methods After randomized clustering sampling,all selected individuals were enumerated according to village residence register.Visual acuity were measured by illuminated EDTRS chart. The examination of eyelid,cornea,lens and fundus were also carried out.The diagnosis of AMD was made according to the criteria of National Academic Group of Fundus Diseases combining with the visual criteria of Framingham Eye Study. Results 5 324 indivduals were axamined with participating rate of 92.8%.The ove rall prevalence of AMD was 8.4%.The prevalence of 2.9%,7.8% and 12.9% was found in the age groups of 50-,60-,70- respectively.The prevalence of male and female was 8.5% and 8.4% respctively.5% of AMD eyes were blind and 49% were low vision. Conclusion The prevalence of AMD is hight and increased with aging,but not correlated with sex.AMD can cause severe visual impairment. (Chin J Ocul Fundus Dis,1998,14:122-124)