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.
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.
ObjectiveTo observe the multi-modal fundus imaging features of subretinal drusenoid deposit (SDD) in age-related macular degeneration (AMD), and observe image features. MethodsA prospective clinical study. From December 2019 to December 2023, 65 patients (104 eyes) with a diagnosis of AMD-SDD by spectral domain optical coherence tomography (SD-OCT) examination in Shandong Eye Hospital were included. All eyes were examined by best corrected visual acuity (BCVA), traditional color fundus photography (CFP), ultra-wide-angle scanning laser fundus imaging (UWF), multicolor scanning laser fundus imaging (MC) and SD-OCT. The standard MC images were obtained by using Spectralis HRA+OCT for MC examination. The multi-mode image characteristics of SDD were analyzed retrospectively. Area under curve (AUC) was used to evaluate the sensitivity and specificity of CFP, MC and UWF in detecting SDD. ResultsAmong 65 patients with SDD, 29 cases of males (52 eyes) and 36 cases of females (52 eyes) was included. There were 26 patients with unilateral SDD and 39 patients with bilateral SDD. The average age was (71.74±10.97) years. The early, middle and late stages of AMD were 31 (29.8%, 31/104), 24 (23.1%, 24/104), 49 (47.1%, 49/104) eyes, respectively. The SDD detected by CFP, MC and UWF was 76 (73.1%, 76/104), 94 (90.4%, 94/104), 96 (92.3%, 96/104) eyes. CFP showed that the edge of SDD in the macular area was blurred. UWF showed that the dot and the ribbon SDD were light yellow pale discrete deposits and light yellow interlaced network deposits respectively. MC showed the dot SDD had a strong yellow-green circular reflection, while the edge of the ribbon SDD was surrounded by a weak reflection, and the boundary was clear. SD-OCT showed that SDD had strong reflection signal, which was located between the retinal pigment epithelium layer and the photoreceptor cell layer. The dot SDD could break through the ellipsoid zone and caused slight uplift or interruption of the external membrane, showing a cone-like strong reflection signal. While the ribbon SDD showed a continuous "hill-like" protrusion, which hardly broke through ellipsoid zone. The sensitivity and specificity of CFP, MC and UWF for SDD were 73.1%, 90.4%, 92.3% and 61.1%, 94.4% and 83.3%, respectively. ConclusionsMC and UWF show high sensitivity and specificity in diagnosing AMD-SDD, which is superior to CFP. SD-OCT can effectively reveal the location and morphoLogical characteristics of SDD under retina.
Age-related macular degeneration (AMD) represents a significant cause of visual impairment and blindness in individuals over 65 years old. In recent years, gene therapy has emerged as a research hotspot for wet AMD, with adeno-associated virus (AAV) vectors being widely utilized due to their non-pathogenic nature, low immunogenicity, broad tissue tropism, and capacity for sustained transgene expression. Several related studies have progressed to clinical trial stages. Although challenges persist, including immunogenicity concerns, limited vector capacity, and potential long-term adverse effects, the continuous advancement of research strategies and technologies holds promise. Future developments may employ AAV delivery systems to achieve gene supplementation, gene editing, or gene silencing of angiogenesis-related signaling molecules, thereby providing novel therapeutic approaches for wet AMD.
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.
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 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.
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)
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 DM 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 vision impairment and blindness in the elderly worldwide, with its prevalence increasing significantly with age. The pathogenesis of AMD is multifactorial, involving genetic predisposition, environmental risk factors, chronic inflammation, and mitochondrial dysfunction. In recent years, mitophagy has emerged as a critical mechanism for maintaining mitochondrial quality control, energy homeostasis, and cellular integrity in retinal pigment epithelium (RPE) and photoreceptor cells. Dysregulated mitophagy leads to the accumulation of damaged mitochondria, excessive reactive oxygen species, and metabolic imbalance, thereby triggering RPE dysfunction, inflammatory amplification, and choroidal neovascularization, which drive AMD progression. Both classical pathways (e.g., PINK1/Parkin) and non-classical pathways (e.g., BNIP3, FUNDC1) have been implicated in AMD pathophysiology. Molecules such as Parkin and p62, as well as multimodal imaging features, hold promise as early biomarkers for disease monitoring. Preclinical studies have shown that small-molecule activators (e.g., Urolithin A, Spermidine) and mitochondria-targeted antioxidants (e.g., MitoQ, SkQ1) can restore mitophagy and alleviate RPE damage. However, current evidence remains limited, as large-scale, long-term clinical trials are lacking. Challenges in drug delivery efficiency, safety, patient stratification, and clinical monitoring tools still hinder translation into practice. Future research should focus on biomarker-driven precision interventions, multicenter randomized controlled trials, and individualized therapeutic strategies. Overall, mitophagy research is transitioning from mechanistic exploration to clinical translation, with promising potential to enable early diagnosis, disease stratification, and precision management of AMD.