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.
Lipid globules in retina and choroid are new definitions based on pathology and high-resolution optical coherence tomography (OCT). OCT examination shows that the lipid globules are low reflective circular cavities in the choroid and retina, without strong reflective boundaries around them, followed by a characteristic superreflective tail. It occurs in healthy human eyes and in age-related macular degeneration characterized by retinal pigment epithelium (RPE) atrophy. Its characteristic superreflective tail is the key to distinguishing it from other diseases. At present, the understanding of lipid globules is still in the initial stage. Although lipid globules can be observed in healthy human eyes, a certain prevalence rate indicates that they are associated with choroidal hypoperfusion and RPE atrophy. In the future, larger randomized controlled trials and longer follow-up time are needed to explore its pathogenesis, pathological characteristics and treatment prognosis.
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.
Subtype classification of age-related macular degeneration (AMD) based on optical coherence tomography (OCT) images serves as an effective auxiliary tool for clinicians in diagnosing disease progression and formulating treatment plans. To improve the classification accuracy of AMD subtypes, this study proposes a keypoint-based, attention-enhanced residual network (KPA-ResNet). The proposed architecture adopts a 50-layer residual network (ResNet-50) as the backbone, preceded by a keypoint localization module based on heatmap regression to outline critical lesion regions. A two-dimensional relative self-attention mechanism is incorporated into convolutional layers to enhance the representation of key lesion areas. Furthermore, the network depth is appropriately increased and an improved residual module, ConvNeXt, is introduced to enable comprehensive extraction of high-dimensional features and enrich the detail of lesion boundary contours, ultimately achieving higher classification accuracy of AMD subtypes. Experimental results demonstrate that KPA-ResNet achieves significant improvements in overall classification accuracy compared with conventional convolutional neural networks. Specifically, for the wet AMD subtypes, the classification accuracies for inactive choroidal neovascularization (CNV) and active CNV reach 92.8% and 95.2%, respectively, representing substantial improvement over ResNet-50. These findings validate the superior performance of KPA-ResNet in AMD subtype classification tasks. This work provides a high-accuracy, generalizable network architecture for OCT-based AMD subtype classification and offers new insights into integrating attention mechanisms with convolutional neural networks in ophthalmic image analysis.
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 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.
With the tremendous progress in fundus imaging and histopathology over the past decade, the understanding of age-related macular degeneration (AMD) has taken a qualitative leap. AMD is defined as a progressive neurodegenerative disease of photoreceptors and retinal pigment epithelium (RPE) characterized by extracellular deposits under RPE and the retina, including drusen, basal laminar and linear deposits, and subretinal drusenoid deposits, that can evolve to atrophy of the retina, RPE and choroid and neovascularization in the choroid and/or retina. It is the leading cause of blindness and visual impairment in older populations, despite recent advances in treatments. AMD is a multifactorial disease with genetic and environmental factors including advanced age, smoking, high-fat diet, and cardiovascular disorder to enhance the disease susceptibility. The physiopathologic mechanism includes inflammatory processes (complement pathway dysregulation, inflammasome activation), intrinsic (e.g., photo-oxidation) and extrinsic oxidative insult to the retina, age-related metabolic impairment (mitochondrial, autophagic and endoplasmic reticulum stress). Autophagy dysfunction and local inflammation in aged RPE specially result in the extracellular deposits, cell death and AMD. Further investigation of the pathogenesis of AMD will provide with new therapeutic targets and strategy for prevention and treatment of the disease in the early stages.
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.
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 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.