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.
Objective To observe the baseline characteristics and visual outcomes after two years follow-up of exudative age-related macular degeneration (AMD) patients treated with ranibizumb. Methods Forty-four eyes of 44 patients with exudative AMD were enrolled into this retrospective study, 19 were men and 25 were women. The mean age was 78 years (range 64 – 92 years). All patients were underwent best corrected visual acuity (BCVA, Early Treatment of Diabetic Retinopathy Study), fundus color photography, fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA) and optical coherence tomography (OCT). The mean BCVA was (50.36±14.43) letters, the mean central foveal thickness (CFT) was (291.95±82.19) μm, and the fluorescence leakage area of choroidal neovascularization (CNV) was (7.61±5.84) mm2. All patients received three initial intravitreous injection of ranibizumb (IVR) and were retreated with monthly IVR when needed. The mean follow up time was 25.6 months (range 24 – 29 months). On 1, 2, 3, 6, 12, 18 and 24 months after treatment, BCVA and OCT were repeated. On 3, 6, 12, 18 and 24 months after treatment, FFA and ICGA were repeated. The change of BCVA, CFT and fluorescence leakage area of CNV were observed. The association of baseline characteristics and two year visual outcomes were analyzed. Results On 1, 2, 3, 6, 12, 18 and 24 months after treatment, the BCVA were improved significantly (t= −1.89, −3.51, −4.61, −4.04, −5.77, −4.69;P＜0.05), the CFT were decreased significantly (t=1.51, 2.30, 3.40, 3.28, 3.54, 3.88, 3.73;P＜0.05). On 3, 6, 12, 18 and 24 months after treatment, the fluorescence leakage area of CNV were reduced significantly (t=2.12, 2.90, 3.51, 4.12, 4.06;P＜0.05). The lower baseline BCVA, the more improved after treatment. The BCVA improvement degree has a negative relationship with baseline BCVA and fluorescence leakage area of CNV (r=0.505, −0.550;P＜0.05), but no correlation with baseline CFT (r=0.210,P＞0.05). Conclusion Two year visual outcomes of exudative AMD patients treated with ranibizumb is negative correlated with baseline BCVA and fluorescence leakage area of CNV, but not correlated with baseline CFT.
Polypoidal choroidal vasculopathy (PCV) is originally defined as a separate disease, but with the development of imaging techniques, it has now been included in the spectrum of neovascularization. In the Asian population, the prevalence of PCV is high, and with the deepening of clinical studies, the pathological characteristics, pathogenesis and clinical manifestations of PCV have been more deeply understood. Through dynamic observation and histopathological study of PCV lesions during operation, it can be confirmed that the lesions are mainly located between the retinal pigment epithelium and the Bruch membrane, rather than originating from the choroidal circulation, which is of great significance for understanding the origin and natural course of PCV. It is worth noting that although a theoretical bridge has been established between age-related macular degeneration (AMD)/PCV, there is a lack of intuitive clinical data on the ultrastructural and molecular manifestations of the cells/stroma in the local lesions of the eye, especially the progression of AMD/PCV from early/middle stage to exudative stage. It is precisely because of this that highly attractive research topics and exploration space are proposed for 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.
Human amnion (hAM), as a biomaterial, has made significant progress in the field of ophthalmology, particularly in the treatment of retinal diseases. hAM possesses biological properties such as promoting tissue repair, inhibiting inflammation and neovascularization, and reducing fibrosis, which have led to its promising clinical outcomes in treating macular holes, retinal detachment, proliferative vitreoretinopathy, optic disc depression-related macular detachment, and age-related macular degeneration. The application of hAM can improve surgical success rates and promote vision recovery, with no significant rejection reactions observed due to its low immunogenicity. Nevertheless, the use of hAM still faces challenges in optimizing preparation and storage techniques, enhancing therapeutic efficacy, and reducing the risk of infectious disease transmission. Future research should focus on addressing these issues to further promote the application of hAM in retinal disease treatment and enhance its effectiveness.
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.
ObjectiveTo observe the clinical features of bacillary layer detachment (BALAD) in neovascular age-related macular degeneration (nAMD) and its response to anti-vascular endothelial growth factor (VEGF) therapy. MethodsA retrospective clinical study. From July 2019 to July 2024, 188 patients (188 eyes) with nAMD who were continuously admitted to Tianjin University Aier Eye Hospital and received anti-VEGF drug treatment were included in the study. All eyes underwent best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) examinations. Treatment consisted of intravitreal anti-VEGF injections monthly for 3 months, followed by a pro re nata regimen. Based on the presence of BALAD on baseline OCT, eyes were divided into a BALAD group and a control group. BCVA was measured using a standard logarithmic visual acuity chart and converted to the logarithm of the minimum angle of resolution; central retinal thickness (CRT) was measured by OCT. Patients were followed for ≥12 months. Differences in CRT, BCVA, macular neovascularization (MNV) subtypes, and treatment outcomes at 12 months were compared between the two groups. The Scheirer-Ray-Hare test was used for non-normally distributed repeated measures data to compare interactions between time and group for BCVA and CRT; Spearman's rank correlation was used for correlation analysis of continuous variables between groups. ResultsThe number of eyes in the BALAD group and the control group was 33 (17.55%, 33/188) and 155 (82.45%, 155/188) respectively. Among the 33 eyes in the BALAD group, 21 eyes (63.64%, 21/33) had type 1 MNV, among which 18 eyes had polypoid choroidal vascular disease (PCV). There was no statistically significant difference in the gender composition ratio and MNV classification between the two groups of patients (χ2=2.09, 1.87, P＞0.05). There were statistically significant differences in age (t=-2.63), the proportion of PCV (χ2=13.73), and CRT (Z=-3.03) (P＜0.05). Twelve months after treatment, the cystic cavities of 84.85% (28/33) of the affected eyes in the BALAD group subsided. The BCVA of both groups of affected eyes improved over time (H=17.93, P＜0.05), but the overall BCVA of the BALAD group was still worse than that of the control group (H=17.80, P＜0.05). There was a significant difference in the improvement degree of CRT between the two groups (H=43.87, P＜0.05), and only in the control group was a significant positive correlation between BCVA and CRT (r=0.24, P＜0.05). ConclusionsIn nAMD, BALAD is associated with type 1 MNV, particularly the PCV subtype, and may serve as a biomarker for predicting anti-VEGF response. Although the BALAD structure is sensitive to anti-VEGF therapy and readily resolves, the limited functional improvement suggests it may be an imaging indicator of poor 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.
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.