Search

Ginsenosides, constituting 2–3% of Panax ginseng Meyer, are noteworthy for their anticancer and antioxidant effects. Despite demonstrating promise in various diseases, their specific impact on age-related macular degeneration (AMD) remains unclear. This research investigates whether ginsenosides can inhibit the progression of dry AMD and explores the mechanisms by which they influence apoptosis, providing insight into their regulatory role in programmed cell death. Human retinal pigment epithelial (ARPE-19) cells were pre-treated with ginsenosides, followed by induction of oxidative stress using hydrogen peroxide. Pre-treatment with 20(S)-ginsenoside Rg3 significantly increased cell viability and reduced apoptotic markers, including Annexin V, Bax, Bim S, cleaved caspase 3, cleaved caspase 9, and cleaved PARP. Furthermore, 20(S)-ginsenoside Rg3 effectively diminished the activation of the ERK and NF-κB signaling pathways. 20(S)-ginsenoside Rg3 could be a good prevention for AMD by modulating apoptosis, offering valuable therapeutic insights for AMD. [ABSTRACT FROM AUTHOR]

The article in the journal "Molecular Neurodegeneration" discusses the development of a novel AAV vector, AAV206, for gene therapy of RPE-related retinal degenerative diseases via intravitreal delivery. The study highlights the high specificity and efficiency of AAV206 in transducing RPE cells, with lower retinal toxicity and immunogenicity compared to conventional AAV2 vectors. Additionally, the research demonstrates that AAV206-sFLT shows superior efficacy in inhibiting CNV formation in a laser-induced CNV mouse model compared to AAV2-sFLT. The findings suggest that AAV206 holds promise as a valuable tool for treating RPE-related retinal degenerative diseases. [Extracted from the article]

Age‐related macular degeneration (AMD) diagnosis using fundus images is one of the critical missions of the eye‐care screening program in many countries. Various proposed deep learning models have been studied for this research interest, which aim to achieve the mission and outperform human‐based approaches. However, research efforts are still required for the improvement of model classification accuracy, sensitivity, and specificity values. In this study, we proposed the model named as ViT‐AMD, which is based on the latest Vision Transformer (ViT) structure, to diagnosis a fundus image as normal, dry AMD, or wet AMD types. Unlike convolution neural network models, ViT consists of the attention map layers, which show more effective performance for image classification task. Our training process is based on the 5‐fold cross‐validation and transfer learning techniques using Chula‐AMD dataset at the Department of Ophthalmology, the King Chulalongkorn Memorial Hospital, Bangkok. Furthermore, we also test the performance of trained model using an independent image datasets. The results showed that for the 3‐classes AMD classification (normal vs. dry AMD vs. wet AMD) on the Chula‐AMD dataset, the averaged accuracy, precision, sensitivity, and specificity of our trained model are about 93.40%, 92.15%, 91.27%, and 96.57%, respectively. For result testing on independent datasets, the averaged accuracy, precision, sensitivity, and specificity of trained model are about 74, 20%, 75.35%, 74.13%, and 87.07%, respectively. Compared with the results from the baseline CNN‐based model (DenseNet201), the trained ViT‐AMD model has outperformed significantly. In conclusion, the ViT‐AMD model have proved their usefulness to assist the ophthalmologist to diagnosis the AMD disease. [ABSTRACT FROM AUTHOR]

This study investigates the efficacy of predicting age-related macular degeneration (AMD) activity through deep neural networks (DNN) using a cross-instrument training dataset composed of Optical coherence tomography-angiography (OCTA) images from two different manufacturers. A retrospective cross-sectional study analyzed 2D vascular en-face OCTA images from Heidelberg Spectralis (1478 samples: 1102 training, 276 validation, 100 testing) and Optovue Solix (1003 samples: 754 training, 189 validation, 60 testing). OCTA scans were labeled based on clinical diagnoses and adjacent B-scan OCT fluid information, categorizing activity into normal, dry AMD, active wet AMD, and wet AMD in remission. Experiments explored cross-instrument disease classification using separate and combined datasets for training the DNN. Testing involved 100 Heidelberg and 60 Optovue samples. Training on Heidelberg data alone yielded 73% accuracy on Heidelberg images and 60% on Optovue images. Training on Optovue data alone resulted in 34% accuracy on Heidelberg and 85% on Optovue images. Combined training data from both instruments achieved 78% accuracy on Heidelberg and 76% on Optovue test sets. Results indicate that cross-instrument classifier training demonstrates high classification prediction accuracy, making cross-instrument training viable for future clinical applications. This implies that vascular morphology in OCTA can predict disease progression. [ABSTRACT FROM AUTHOR]

Background: Metabolic disruptions were observed in patients with optic neurodegenerative diseases (OND). However, evidence for the causal association between metabolites and OND is limited. Methods: Two-sample Mendelian randomization (MR). Summary data for 128 blood metabolites was selected from three genome-wide association study (GWASs) involving 147,827 participants of European descent. GWASs Data for glaucoma (20906 cases and 391275 controls) and age-related macular degeneration (AMD, 9721 cases and 381339 controls) came from FinnGen consortium. A bi-directional MR was conducted to assess causality, and a Mediation MR was further applied to explore the indirect effect, a phenome-wide MR analysis was then performed to identify possible side-effects of the therapies. Results: All the results underwent correction for multiple testing and rigorous sensitivity analyses. We identified N-acetyl glycine, serine, uridine were linked to an elevated risk of glaucoma. 1-arachidonic-glycerol-phosphate-ethanolamine, 4-acetamido butanoate, o-methylascorbate, saturated fatty acids, monounsaturated fatty acids, VLDL cholesterol, serum total cholesterol, X-11,529 were linked to reduced risk of glaucoma. There were 4 metabolites linked to a reduced risk of AMD, including tryptophan betaine, 4-androsten-3beta-17beta-diol disulfate, apolipoprotein B, VLDL cholesterol. We discovered IOP, AS, T2D as glaucoma risk factors, while BMI, AS, GCIPL as AMD factors. And 6 metabolites showed associations with risk factors in the same direction as their associations with glaucoma/AMD. Phenome-wide MR indicated that selected metabolites had protective/adverse effects on other diseases. Conclusions: By integrating genomics and metabolomics, this study supports new insights into the intricate mechanisms, and helps prevent and screen glaucoma and AMD. [ABSTRACT FROM AUTHOR]

Background: Previous Mendelian randomization (MR) studies showed an association between hypothyroidism and cataract and between high-normal free thyroxine (FT4) and late age-related macular degeneration (AMD), but not between FT4, thyroid stimulating hormone (TSH), or hyperthyroidism and diabetic retinopathy or cataract. These studies included a limited number of genetic variants for thyroid function and did not investigate autoimmune thyroid disease (AITD) or glaucoma, include bidirectional and multivariable MR (MVMR), and examine sex differences or potential mediation effects of diabetes. We aimed to address this knowledge gap. Methods: We examined the causality and directionality of the associations of AITD, and FT4 and TSH within the reference range with common age-related eye diseases (diabetic retinopathy, cataract, early and late AMD, and primary open-angle glaucoma). We conducted a bidirectional two-sample MR study utilizing publicly available genome-wide association study (GWAS) summary statistics from international consortia (ThyroidOmics, International AMD Genetics Consortium, deCODE, UK Biobank, FinnGen, and DIAGRAM). Bidirectional MR tested directionality, whereas MVMR estimated independent causal effects. Furthermore, we investigated type 1 diabetes (T1D) and type 2 diabetes (T2D) as potential mediators. Results: Genetic predisposition to AITD was associated with increased risk of diabetic retinopathy (p = 3 × 10−4), cataract (p = 3 × 10−3), and T1D (p = 1 × 10−3), but less likely T2D (p = 0.01). MVMR showed attenuated estimates for diabetic retinopathy and cataract when adjusting for T1D, but not T2D. We found pairwise bidirectional associations between AITD, T1D, and diabetic retinopathy. Genetic predisposition to both T1D and T2D increased the risk of diabetic retinopathy and cataract (p < 4 × 10−4). Moreover, genetically predicted higher FT4 within the reference range was associated with an increased risk of late AMD (p = 0.01), particularly in women (p = 7 × 10−3). However, we neither found any association between FT4 and early AMD nor between TSH and early and late AMD. No other associations were observed. Conclusions: Genetic predisposition to AITD is associated with risk of diabetic retinopathy and cataract, mostly mediated through increased T1D risk. Reciprocal associations between AITD, diabetic retinopathy, and T1D imply a shared autoimmune origin. The role of FT4 in AMD and potential sex discrepancies needs further investigation. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD), the leading cause of irreversible blindness in the elderly, is primarily characterized by the degeneration of the retinal pigment epithelium (RPE). However, effective therapeutic options for dry AMD are currently lacking, necessitating further exploration into preventive and pharmaceutical interventions. This study aimed to investigate the protective effects of gastrodin on RPE cells exposed to oxidative stress. We constructed an in vitro oxidative stress model of 4-hydroxynonenal (4-HNE) and performed RNA-seq, and demonstrated the protective effect of gastrodin through mouse experiments. Our findings reveal that gastrodin can inhibit 4-HNE-induced oxidative stress, effectively improving the mitochondrial and lysosomal dysfunction of RPE cells. We further elucidated that gastrodin promotes autophagy and phagocytosis through activating the PPARα-TFEB/CD36 signaling pathway. Interestingly, these outcomes were corroborated in a mouse model, in which gastrodin maintained retinal integrity and reduced RPE disorganization and degeneration under oxidative stress. The accumulation of LC3B and SQSTM1 in mouse RPE-choroid was also reduced. Moreover, activating PPARα and downstream pathways to restore autophagy and phagocytosis, thereby countering RPE injury from oxidative stress. In conclusion, this study demonstrated that gastrodin maintains the normal function of RPE cells by reducing oxidative stress, enhancing their phagocytic function, and restoring the level of autophagic flow. These findings suggest that gastrodin is a novel formulation with potential applications in the development of AMD disease. [Display omitted] • Gastrodin alleviates oxidative stress and phagocytic dysfunction in RPE cells. • Gastrodin protects the quantity and function of mitochondria and lysosomes. • Gastrodin lessens LC3B-II, SQSTM1 buildup, restoring autophagy flux. • Gastrodin promotes autophagy, phagocytosis via PPARα - TFEB signaling. • In vivo, gastrodin protects the RPE cell layer effectively. [ABSTRACT FROM AUTHOR]

To identify genetic influences on subfoveal choroidal thickness of older adults using a genome-wide association study (GWAS). We recruited 300 participants from the population-based Korean Longitudinal Study on Health and Aging (KLoSHA) and Korean Longitudinal Study on Cognitive Aging and Dementia (KLOSCAD) cohort studies and 500 participants from the Bundang age-related macular degeneration (AMD) cohort study dataset. We conducted a GWAS on older adult populations in the KLoSHA and KLOSCAD cohorts. Single nucleotide polymorphisms (SNPs) associated with choroidal thickness were identified with P values < 1.0 × 10−4 in both the right and left eyes, followed by validation using the Bundang AMD cohort dataset. This association was further confirmed by a functional in vitro study using human umbilical vein endothelial cells (HUVECs). The ages of the cohort participants in the discovery and validation datasets were 73.5 ± 3.3 and 71.3 ± 7.9 years, respectively. In the discovery dataset, three SNPs (rs1916762, rs7587019, and rs13320098) were significantly associated with choroidal thickness in both eyes. This association was confirmed for rs1916762 (genotypes GG, GA, and AA) and rs7587019 (genotypes GG, GA, and AA), but not for rs13320098. The mean choroidal thickness decreased by 56.7 μm (AA, 73.8%) and 31.1 μm (GA, 85.6%) compared with that of the GG genotype of rs1916762, and by 55.4 μm (AA, 74.2%) and 28.2 μm (GA, 86.7%) compared with that of the GG genotype of rs7587019. The SNPs rs1916762 and rs7587019 were located close to the FAM124B gene near its cis-regulatory region. Moreover, FAM124B was highly expressed in vascular endothelial cells. In vitro HUVEC experiments showed that the inhibition of FAM124B was associated with decreased vascular endothelial proliferation, suggesting a potential mechanism of choroidal thinning. FAM124B was identified as a susceptibility gene affecting subfoveal choroidal thickness in older adults. This gene may be involved in mechanisms underlying retinal diseases associated with altered choroidal thickness, such as age-related macular degeneration. [ABSTRACT FROM AUTHOR]

Background/Objectives: This study investigates whether there is an increased propensity to systemic conditions in patients with both age-related macular degeneration (AMD) and glaucoma in order to provide greater insight into patients' overall health and response to physiologic stress. Methods: A large retrospective dataset review was conducted between April 2004 and June 2018, distinguishing four groups based on international classification of diseases (ICD) codes: glaucoma only, AMD only, glaucoma and AMD, and cataracts only (as an age-matched control). The systemic disease prevalence of each group was calculated, and a Friedman analysis was used to compare the prevalence between the groups. Results: This study identified 5243 patients with glaucoma only, 6726 with AMD only, 402 with combined disease, and 25,450 with cataracts only. Age and racial distributions varied between groups in a predictable manner. Two conditions, heart failure (HF) and dementia, had a statistically higher prevalence in patients with both glaucoma and AMD compared to those with glaucoma alone (HF p = 0.036, dementia p = 0.024) and cataracts alone (HF p = 0.003, dementia p = 0.036). There was no significant difference observed in terms of ethnicity and gender among the different disease groups (p > 0.05). Conclusions: Both AMD and glaucoma individually portend a higher rate of comorbidities than age-matched controls. Patients with concomitant AMD and glaucoma demonstrate a uniquely higher prevalence of heart failure and dementia than those with either disease alone. The underlying association and pathologic mechanisms warrant further investigation to improve the overall health management and prognostication for these individuals. [ABSTRACT FROM AUTHOR]

Glyburide, a sulfonylurea drug used to treat type 2 diabetes, boasts neuroprotective effects by targeting the sulfonylurea receptor 1 (SUR1) and associated ion channels in various cell types, including those in the central nervous system and the retina. Previously, we demonstrated that glyburide therapy improved retinal function and structure in a rat model of diabetic retinopathy. In the present study, we explore the application of glyburide in non-neovascular ("dry") age-related macular degeneration (AMD), another progressive disease characterized by oxidative stress-induced damage and neuroinflammation that trigger cell death in the retina. We show that glyburide administration to a human cone cell line confers protection against oxidative stress, inflammasome activation, and apoptosis. To corroborate our in vitro results, we also conducted a case-control study, controlling for AMD risk factors and other diabetes medications. It showed that glyburide use in patients reduces the odds of new-onset dry AMD. A positive dose-response relationship is observed from this analysis, in which higher cumulative doses of glyburide further reduce the odds of new-onset dry AMD. In the quest for novel therapies for AMD, glyburide emerges as a promising repurposable drug given its known safety profile. The results from this study provide insights into the multifaceted actions of glyburide and its potential as a neuroprotective agent for retinal diseases; however, further preclinical and clinical studies are needed to validate its therapeutic potential in the context of degenerative retinal disorders such as AMD. [ABSTRACT FROM AUTHOR]

Abstract This study investigates the efficacy of predicting age-related macular degeneration (AMD) activity through deep neural networks (DNN) using a cross-instrument training dataset composed of Optical coherence tomography-angiography (OCTA) images from two different manufacturers. A retrospective cross-sectional study analyzed 2D vascular en-face OCTA images from Heidelberg Spectralis (1478 samples: 1102 training, 276 validation, 100 testing) and Optovue Solix (1003 samples: 754 training, 189 validation, 60 testing). OCTA scans were labeled based on clinical diagnoses and adjacent B-scan OCT fluid information, categorizing activity into normal, dry AMD, active wet AMD, and wet AMD in remission. Experiments explored cross-instrument disease classification using separate and combined datasets for training the DNN. Testing involved 100 Heidelberg and 60 Optovue samples. Training on Heidelberg data alone yielded 73% accuracy on Heidelberg images and 60% on Optovue images. Training on Optovue data alone resulted in 34% accuracy on Heidelberg and 85% on Optovue images. Combined training data from both instruments achieved 78% accuracy on Heidelberg and 76% on Optovue test sets. Results indicate that cross-instrument classifier training demonstrates high classification prediction accuracy, making cross-instrument training viable for future clinical applications. This implies that vascular morphology in OCTA can predict disease progression.

Abstract Background Metabolic disruptions were observed in patients with optic neurodegenerative diseases (OND). However, evidence for the causal association between metabolites and OND is limited. Methods Two-sample Mendelian randomization (MR). Summary data for 128 blood metabolites was selected from three genome-wide association study (GWASs) involving 147,827 participants of European descent. GWASs Data for glaucoma (20906 cases and 391275 controls) and age-related macular degeneration (AMD, 9721 cases and 381339 controls) came from FinnGen consortium. A bi-directional MR was conducted to assess causality, and a Mediation MR was further applied to explore the indirect effect, a phenome-wide MR analysis was then performed to identify possible side-effects of the therapies. Results All the results underwent correction for multiple testing and rigorous sensitivity analyses. We identified N-acetyl glycine, serine, uridine were linked to an elevated risk of glaucoma. 1-arachidonic-glycerol-phosphate-ethanolamine, 4-acetamido butanoate, o-methylascorbate, saturated fatty acids, monounsaturated fatty acids, VLDL cholesterol, serum total cholesterol, X-11,529 were linked to reduced risk of glaucoma. There were 4 metabolites linked to a reduced risk of AMD, including tryptophan betaine, 4-androsten-3beta-17beta-diol disulfate, apolipoprotein B, VLDL cholesterol. We discovered IOP, AS, T2D as glaucoma risk factors, while BMI, AS, GCIPL as AMD factors. And 6 metabolites showed associations with risk factors in the same direction as their associations with glaucoma/AMD. Phenome-wide MR indicated that selected metabolites had protective/adverse effects on other diseases. Conclusions By integrating genomics and metabolomics, this study supports new insights into the intricate mechanisms, and helps prevent and screen glaucoma and AMD.

Abstract To identify genetic influences on subfoveal choroidal thickness of older adults using a genome-wide association study (GWAS). We recruited 300 participants from the population-based Korean Longitudinal Study on Health and Aging (KLoSHA) and Korean Longitudinal Study on Cognitive Aging and Dementia (KLOSCAD) cohort studies and 500 participants from the Bundang age-related macular degeneration (AMD) cohort study dataset. We conducted a GWAS on older adult populations in the KLoSHA and KLOSCAD cohorts. Single nucleotide polymorphisms (SNPs) associated with choroidal thickness were identified with P values

Age‐related macular degeneration (AMD), a leading cause of blindness, is characterized by mitochondrial dysfunction of retinal pigment epithelium (RPE) cells. EUK‐134 is a mimetic of SOD2 and catalase, widely used for its antioxidant properties in models of light‐induced damage or oxidative stress. However, its effects on the retina are not yet clear. Here, we investigated the capability of EUK‐134 in averting AMD using sodium iodate (NaIO3)‐induced Balb/c mouse and ARPE‐19 cells (adult RPE cell line). In vivo, EUK‐134 effectively antagonized NaIO3‐induced retinal deformation and prevented outer and inner nuclear layer thinning. In addition, it was found that the EUK‐134‐treated group significantly down‐regulated the expression of cleaved caspase‐3 compared with the group treated with NaIO3 alone. Our results found that EUK‐134 notably improved cell viability by preventing mitochondrial ROS accumulation‐induced membrane potential depolarization‐mediated apoptosis in NaIO3‐inducted ARPE‐19 cells. Furthermore, we found that EUK‐134 could inhibit p‐ERK, p‐p38, p‐JNK, p‐p53, Bax, cleaved caspase‐9, cleaved caspase‐3, and cleaved PARP by increasing Bcl‐2 protein expression. Additionally, we employed MAPK pathway inhibitors by SB203580 (a p38 inhibitor), U0126 (an ERK inhibitor), and SP600125 (a JNK inhibitor) to corroborate the aforementioned observation. The results support that EUK‐134 may effectively prevent mitochondrial oxidative stress‐mediated retinal apoptosis in NaIO3‐induced retinopathy. [ABSTRACT FROM AUTHOR]

Abstract Age-related macular degeneration (AMD) and diabetic macular edema (DME) are significant causes of blindness worldwide. The prevalence of these diseases is steadily increasing due to population aging. Therefore, early diagnosis and prevention are crucial for effective treatment. Classification of Macular Degeneration OCT Images is a widely used method for assessing retinal lesions. However, there are two main challenges in OCT image classification: incomplete image feature extraction and lack of prominence in important positional features. To address these challenges, we proposed a deep learning neural network model called MSA-Net, which incorporates our proposed multi-scale architecture and spatial attention mechanism. Our multi-scale architecture is based on depthwise separable convolution, which ensures comprehensive feature extraction from multiple scales while minimizing the growth of model parameters. The spatial attention mechanism is aim to highlight the important positional features in the images, which emphasizes the representation of macular region features in OCT images. We test MSA-NET on the NEH dataset and the UCSD dataset, performing three-class (CNV, DURSEN, and NORMAL) and four-class (CNV, DURSEN, DME, and NORMAL) classification tasks. On the NEH dataset, the accuracy, sensitivity, and specificity are 98.1%, 97.9%, and 98.0%, respectively. After fine-tuning on the UCSD dataset, the accuracy, sensitivity, and specificity are 96.7%, 96.7%, and 98.9%, respectively. Experimental results demonstrate the excellent classification performance and generalization ability of our model compared to previous models and recent well-known OCT classification models, establishing it as a highly competitive intelligence classification approach in the field of macular degeneration.

Abstract Cell adhesion to the extracellular matrix and its natural outcome of cell spreading, along with the maintenance of barrier activity, are essential behaviors of epithelial cells, including retinal pigment epithelium (RPE). Disruptions in these characteristics can result in severe vision-threatening diseases such as diabetic macular edema and age-related macular degeneration. However, the precise mechanisms underlying how RPE cells regulate their barrier integrity and cell spreading are not fully understood. This study aims to elucidate the relative importance of upper glycolytic components in governing these cellular behaviors of RPE cells. Electric Cell-Substrate Impedance Sensing (ECIS) technology was utilized to assess in real-time the effects of targeting various upper glycolytic enzymes on RPE barrier function and cell spreading by measuring cell resistance and capacitance, respectively. Specific inhibitors used included WZB117 for Glut1 inhibition, Lonidamine for Hexokinase inhibition, PFK158 for PFKFB3/PFK axis inhibition, and TDZD-8 for Aldolase inhibition. Additionally, the viability of RPE cells was evaluated using a lactate dehydrogenase (LDH) cytotoxicity assay. The most significant decrease in electrical resistance and increase in capacitance of RPE cells were observed due to dose-dependent inhibition of Glut1 using WZB117, as well as Aldolase inhibition with TDZD-8. LDH level analysis at 24–72 h post-treatment with WZB117 (1 and 10 μM) or TDZD-8 (1 μM) showed no significant difference compared to the control, indicating that the disruption of RPE functionality was not attributed to cell death. Lastly, inhibition of other upper glycolytic components, including PFKFB3/PFK with PFK158 or Hexokinase with Lonidamine, did not significantly affect RPE cell behavior. This study provides insights into the varied roles of upper glycolytic components in regulating the functionality of RPE cells. Specifically, it highlights the critical roles of Glut1 and Aldolase in preserving barrier integrity and promoting RPE cell adhesion and spreading. Such understanding will guide the development of safe interventions to treat RPE cell dysfunction in various retinal disorders.

Abstract Age-related macular degeneration (AMD) is one of the leading causes of blindness. AMD is currently incurable; the best solution is to prevent its occurrence. To develop drugs for AMD, it is crucial to have a model system that mimics the symptoms and mechanisms in patients. It is most important to develop safer and more effective anti-AMD drug. In this study, the dose of A2E and the intensity of blue light were evaluated to establish an appropriate atrophic in vitro model of AMD and anti-AMD effect and therapeutic mechanism of Codonopsis lanceolata. The experimental groups included a control group an AMD group treated with A2E and blue light, a lutein group treated with 25 μM lutein after AMD induction, and three groups treated with different doses of C. lanceolata (10, 20, and 50 μg/mL) after AMD induction. Intrinsic apoptotic pathway (Bcl-2 family), anti-oxidative system (Keap1/Nrf2/HO-1 antioxidant response element), and anti-carbonyl effect (4-hydroxynonenal [4-HNE]) were evaluated using immunofluorescence, MTT, TUNEL, FACS, and western blotting analyses. A2E accumulation in the cytoplasm of ARPE-19 cells depending on the dose of A2E. Cell viability of ARPE-19 cells according to the dose of A2E and/or blue light intensity. The population of apoptotic or necrotic cells increased based on the A2E dose and blue light intensity. Codonopsis lanceolata dose-dependently prevented cell death which was induced by A2E and blue light. The antiapoptotic effect of that was caused by activating Keap1/Nrf2/HO-1 pathway, suppressing 4-HNE, and modulating Bcl-2 family proteins like increase of antiapoptotic proteins such as Bcl-2 and Bcl-XL and decrease of proapoptotic protein such as Bim. Based on these findings, 30 μM A2E and 20 mW/cm2 blue light on adult retinal pigment epithelium-19 cells was an appropriate condition for AMD model and C. lanceolata shows promise as an anti-AMD agent.

The ocular condition known as age-related macular degeneration (AMD) affects the retina and impairs vision in the elderly. For both controlling and detecting retinal illnesses like AMD, optical coherence tomography (OCT) is an important investigative tool. The accurate segmentation of retinal layers is critical, as accurately segmenting the layers helps ophthalmologists for early diagnosis of AMD. An accurate and effective detection technique is created using the proposed Water Cycle Corona Virus Optimization-based Deep Residual Network (WCCVO-based DRN) to address these problems and identify AMD at the early stages. In the first step, the active contour model is used to segment the layers, and features such as reflectivity, thickness, curvature, statistical features, and the devised Local Directional Gradient Pattern Histogram (LDGPH) are retrieved. The LDGPH is designed based on the concept of Local Directional pattern (LDP) and Local Gradient pattern (LGP). At last, for the AMD detection DRN classifier is used, which is trained by the devised WCCVO. The accuracy, sensitivity, and specificity metrics for the WCCVO-based DRN achieved satisfactory performance with values of 0.916, 0.923, and 0.919. [ABSTRACT FROM AUTHOR]

Background: Pre-clinical studies related to the use of rapamycin (Sirolimus®), a mammalian target of rapamycin (mTOR) inhibitors, for age-related macular degeneration (AMD) have shown improved therapeutic outcomes. However, knowledge of its dose–effect relationship in humans with AMD has been limited and requires further investigation. Objective: The aim of this study is to assess the safety and efficacy of Sirolimus® for treatment of AMD in humans and determine the dose range for its application in the eye. Methods: A systematic literature review was conducted following the PRISMA guidelines. The MEDLINE, Embase, CINAHL, Scopus and Cochrane Central Registry of Controlled Trials databases were searched for original clinical studies examining the effects of Sirolimus® on outcomes linked to AMD in humans. This review has been registered in the PROSPERO database. Results: Only four studies were found to satisfy the inclusion and exclusion criteria and were analyzed in this systematic review in a narrative way. The dose range of rapamycin in the limited number of studies appears to be toxic to the retina. Conclusion: Future studies should focus on establishing the optimal low-dose range of Sirolimus® that effectively induces autophagy without causing retinal toxicity, as current data indicate a potential therapeutic window that remains underexplored. Specifically, longitudinal, controlled studies with larger, heterogeneous patient populations are necessary to determine the precise dosing that balances efficacy and safety in treating AMD. [ABSTRACT FROM AUTHOR]

Cell adhesion to the extracellular matrix and its natural outcome of cell spreading, along with the maintenance of barrier activity, are essential behaviors of epithelial cells, including retinal pigment epithelium (RPE). Disruptions in these characteristics can result in severe vision-threatening diseases such as diabetic macular edema and age-related macular degeneration. However, the precise mechanisms underlying how RPE cells regulate their barrier integrity and cell spreading are not fully understood. This study aims to elucidate the relative importance of upper glycolytic components in governing these cellular behaviors of RPE cells. Electric Cell-Substrate Impedance Sensing (ECIS) technology was utilized to assess in real-time the effects of targeting various upper glycolytic enzymes on RPE barrier function and cell spreading by measuring cell resistance and capacitance, respectively. Specific inhibitors used included WZB117 for Glut1 inhibition, Lonidamine for Hexokinase inhibition, PFK158 for PFKFB3/PFK axis inhibition, and TDZD-8 for Aldolase inhibition. Additionally, the viability of RPE cells was evaluated using a lactate dehydrogenase (LDH) cytotoxicity assay. The most significant decrease in electrical resistance and increase in capacitance of RPE cells were observed due to dose-dependent inhibition of Glut1 using WZB117, as well as Aldolase inhibition with TDZD-8. LDH level analysis at 24–72 h post-treatment with WZB117 (1 and 10 μM) or TDZD-8 (1 μM) showed no significant difference compared to the control, indicating that the disruption of RPE functionality was not attributed to cell death. Lastly, inhibition of other upper glycolytic components, including PFKFB3/PFK with PFK158 or Hexokinase with Lonidamine, did not significantly affect RPE cell behavior. This study provides insights into the varied roles of upper glycolytic components in regulating the functionality of RPE cells. Specifically, it highlights the critical roles of Glut1 and Aldolase in preserving barrier integrity and promoting RPE cell adhesion and spreading. Such understanding will guide the development of safe interventions to treat RPE cell dysfunction in various retinal disorders. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) and diabetic retinopathy (DR) are common retinal diseases responsible for most blindness in working-age and elderly populations. Oxidative stress and mitochondrial dysfunction play roles in these pathogenesis, and new therapies counteracting these contributors could be of great interest. Some molecules, like coenzyme Q10 (CoQ10), are considered beneficial to maintain mitochondrial homeostasis and contribute to the prevention of cellular apoptosis. We investigated the impact of adding CoQ10 (Q) to a nutritional antioxidant complex (Nutrof Total®; N) on the mitochondrial status and apoptosis in an in vitro hydrogen peroxide (H2O2)-induced oxidative stress model in human retinal pigment epithelium (RPE) cells. H2O2 significantly increased 8-OHdG levels (p < 0.05), caspase-3 (p < 0.0001) and TUNEL intensity (p < 0.01), and RANTES (p < 0.05), caspase-1 (p < 0.05), superoxide (p < 0.05), and DRP-1 (p < 0.05) levels, and also decreased IL1β, SOD2, and CAT gene expression (p < 0.05) vs. control. Remarkably, Q showed a significant recovery in IL1β gene expression, TUNEL, TNFα, caspase-1, and JC-1 (p < 0.05) vs. H2O2, and NQ showed a synergist effect in caspase-3 (p < 0.01), TUNEL (p < 0.0001), mtDNA, and DRP-1 (p < 0.05). Our results showed that CoQ10 supplementation is effective in restoring/preventing apoptosis and mitochondrial stress-related damage, suggesting that it could be a valid strategy in degenerative processes such as AMD or DR. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD), a prevalent and progressive degenerative disease of the macula, is the leading cause of blindness in elderly individuals in developed countries. The advanced stages include neovascular AMD (nAMD), characterized by choroidal neovascularization (CNV), leading to subretinal fibrosis and permanent vision loss. Despite the efficacy of anti-vascular endothelial growth factor (VEGF) therapy in stabilizing or improving vision in nAMD, the development of subretinal fibrosis following CNV remains a significant concern. In this review, we explore multifaceted aspects of subretinal fibrosis in nAMD, focusing on its clinical manifestations, risk factors, and underlying pathophysiology. We also outline the potential sources of myofibroblast precursors and inflammatory mechanisms underlying their recruitment and transdifferentiation. Special attention is given to the potential role of mast cells in CNV and subretinal fibrosis, with a focus on putative mast cell mediators, tryptase and granzyme B. We summarize our findings on the role of GzmB in CNV and speculate how GzmB may be involved in the pathological transition from CNV to subretinal fibrosis in nAMD. Finally, we discuss the advantages and drawbacks of animal models of subretinal fibrosis and pinpoint potential therapeutic targets for subretinal fibrosis. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is one of the leading causes of blindness. AMD is currently incurable; the best solution is to prevent its occurrence. To develop drugs for AMD, it is crucial to have a model system that mimics the symptoms and mechanisms in patients. It is most important to develop safer and more effective anti-AMD drug. In this study, the dose of A2E and the intensity of blue light were evaluated to establish an appropriate atrophic in vitro model of AMD and anti-AMD effect and therapeutic mechanism of Codonopsis lanceolata. The experimental groups included a control group an AMD group treated with A2E and blue light, a lutein group treated with 25 μM lutein after AMD induction, and three groups treated with different doses of C. lanceolata (10, 20, and 50 μg/mL) after AMD induction. Intrinsic apoptotic pathway (Bcl-2 family), anti-oxidative system (Keap1/Nrf2/HO-1 antioxidant response element), and anti-carbonyl effect (4-hydroxynonenal [4-HNE]) were evaluated using immunofluorescence, MTT, TUNEL, FACS, and western blotting analyses. A2E accumulation in the cytoplasm of ARPE-19 cells depending on the dose of A2E. Cell viability of ARPE-19 cells according to the dose of A2E and/or blue light intensity. The population of apoptotic or necrotic cells increased based on the A2E dose and blue light intensity. Codonopsis lanceolata dose-dependently prevented cell death which was induced by A2E and blue light. The antiapoptotic effect of that was caused by activating Keap1/Nrf2/HO-1 pathway, suppressing 4-HNE, and modulating Bcl-2 family proteins like increase of antiapoptotic proteins such as Bcl-2 and Bcl-XL and decrease of proapoptotic protein such as Bim. Based on these findings, 30 μM A2E and 20 mW/cm2 blue light on adult retinal pigment epithelium-19 cells was an appropriate condition for AMD model and C. lanceolata shows promise as an anti-AMD agent. [ABSTRACT FROM AUTHOR]

Sight is arguably the most precious of our senses. With the aging world population, it is vitally important to learn about the four major conditions that affect people as they age, namely, Macular Degeneration or Age-Related Macular Degeneration (AMD); Cataracts; Diabetic Retinopathy; and Glaucoma. This column will offer information on web-based sites that not only provide accurate and reliable information on these conditions to patients and their care-givers, but also identify help available to protect vision, treat vision conditions, and ways and encouragement that allow individuals to continue to live fulfilling lives. [ABSTRACT FROM AUTHOR]

The rapid advancement of computational infrastructure has led to unprecedented growth in machine learning, deep learning, and computer vision, fundamentally transforming the analysis of retinal images. By utilizing a wide array of visual cues extracted from retinal fundus images, sophisticated artificial intelligence models have been developed to diagnose various retinal disorders. This paper concentrates on the detection of Age-Related Macular Degeneration (AMD), a significant retinal condition, by offering an exhaustive examination of recent machine learning and deep learning methodologies. Additionally, it discusses potential obstacles and constraints associated with implementing this technology in the field of ophthalmology. Through a systematic review, this research aims to assess the efficacy of machine learning and deep learning techniques in discerning AMD from different modalities as they have shown promise in the field of AMD and retinal disorders diagnosis. Organized around prevalent datasets and imaging techniques, the paper initially outlines assessment criteria, image preprocessing methodologies, and learning frameworks before conducting a thorough investigation of diverse approaches for AMD detection. Drawing insights from the analysis of more than 30 selected studies, the conclusion underscores current research trajectories, major challenges, and future prospects in AMD diagnosis, providing a valuable resource for both scholars and practitioners in the domain. [ABSTRACT FROM AUTHOR]

Wet Age-related macular degeneration (AMD) is the leading cause of vision loss in industrialized nations, often resulting in blindness. Biologics, therapeutic agents derived from biological sources, have been effective in AMD, albeit at a high cost. Due to the high cost of AMD treatment, it is critical to determine the binding affinity of biologics to ensure their efficacy and make quantitative comparisons between different drugs. This study evaluates the in vitro VEGF binding affinity of two drugs used for treating wet AMD, monoclonal antibody-based bevacizumab and fusion protein-based aflibercept, performing quantitative binding measurements on an Interferometric Reflectance Imaging Sensor (IRIS) system. Both biologics can inhibit Vascular Endothelial Growth Factor (VEGF). For comparison, the therapeutic molecules were immobilized on to the same support in a microarray format, and their real-time binding interactions with recombinant human VEGF (rhVEGF) were measured using an IRIS. The results indicated that aflibercept exhibited a higher binding affinity to VEGF than bevacizumab, consistent with previous studies using ELISA and SPR. The IRIS system's innovative and cost-effective features, such as silicon-based semiconductor chips for enhanced signal detection and multiplexed analysis capability, offer new prospects in sensor technologies. These attributes make IRISs a promising tool for future applications in the development of therapeutic agents, specifically biologics. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is a leading cause of blindness among the elderly worldwide. Anti-vascular endothelial growth factor (anti-VEGF) injections remain the first-line therapy for AMD. However, their high cost and the need for frequent administration pose challenges to long-term adherence, highlighting the need for accessible and cost-effective preventive strategies. Emerging evidence suggests that traditional antidiabetic drugs, such as metformin, sulfonylureas, and thiazolidinediones, may offer neuroprotective benefits, opening new avenues for AMD prevention. Among these, metformin has emerged as the most promising candidate, demonstrating significant potential in reducing AMD risk, even at low cumulative doses, primarily through AMP-activated protein kinase (AMPK) activation. Sulfonylureas, although effective in stimulating insulin secretion, carry risks such as hypoglycemia, hyperinsulinemia, and a possible association with increased cancer risk. Similarly, thiazolidinediones, while improving insulin sensitivity, are associated with adverse effects, including cardiovascular risks and macular edema, limiting their broader application in AMD prevention. This paper explores the preventive potential and underlying mechanisms of these antidiabetic drugs in AMD and discusses the role of artificial intelligence in optimizing individualized prevention strategies. By advancing precision medicine, these approaches may improve public health outcomes and reduce the burden of aging-related vision loss.

Abstract Background Age-related macular degeneration (AMD) affects quality of life and independence, and its incidence and prevalence are increasing due to ageing of the population. Access to effective timely treatment can improve vision and reduce incidence of blindness. This study aimed to explore the perspectives of ophthalmologists in the Israeli public healthcare system regarding timely treatment of AMD patients. Methods Qualitative semi-structured interviews were conducted in 2020-2021 with 22 senior ophthalmologists, from 10 general hospitals and from two HMOs, representing different geographic regions. All interviewees specialize in retinal diseases and work with AMD patients. Interviews discussed patient pathways involved in the diagnosis and treatment of AMD, access to care, and obstacles to timely care. Thematic analysis was conducted. Results Based on the interviews, we describe the usual referral and treatment pathways. Themes included regional disparities, long wait times in some areas, a lack of retina specialists, differences in referral pathways, inappropriate use of emergency department to obtain timely treatment, and second-line treatment not fully covered by insurance, most affecting the weakest segments of the population. Conclusions Loss of vision incurs high health and societal costs. In the context of insufficient medical manpower in Israel, the healthcare system will need to assess future resources to cope with accumulating burden of AMD cases over time in an ageing population. Precise referral information, and simultaneous referral to imaging and retinal clinics, may minimize delays in treatment. Awareness of AMD symptoms and the importance of early intervention could be highlighted by campaigns, particularly among high-risk groups. Highlights • Interviews with hospital-based and community ophthalmologists showed regional disparities in AMD treatment, with long wait times and a lack of retina specialists in some areas. • Differences in referral pathways, inappropriate use of emergency department to obtain timely treatment, and second line treatment not fully covered by insurance were highlighted. • The healthcare system will need to assess future resources to cope with accumulating burden of AMD cases over time in an ageing population • Precise referral information, and simultaneous referral to imaging and retinal clinics, may minimize delays in treatment. • Awareness of AMD symptoms and the importance of early intervention should be emphasized in high-risk groups.

Purpose: To apply methods for quantifying uncertainty of deep learning segmentation of geographic atrophy (GA). Design: Retrospective analysis of OCT images and model comparison. Participants: One hundred twenty-six eyes from 87 participants with GA in the SWAGGER cohort of the Nonexudative Age-Related Macular Degeneration Imaged with Swept-Source OCT (SS-OCT) study. Methods: The manual segmentations of GA lesions were conducted on structural subretinal pigment epithelium en face images from the SS-OCT images. Models were developed for 2 approximate Bayesian deep learning techniques, Monte Carlo dropout and ensemble, to assess the uncertainty of GA semantic segmentation and compared to a traditional deep learning model. Main Outcome Measures: Model performance (Dice score) was compared. Uncertainty was calculated using the formula for Shannon Entropy. Results: The output of both Bayesian technique models showed a greater number of pixels with high entropy than the standard model. Dice scores for the Monte Carlo dropout method (0.90, 95% confidence interval 0.87–0.93) and the ensemble method (0.88, 95% confidence interval 0.85–0.91) were significantly higher (P

Purpose: Spectral-domain OCT angiography (SD-OCTA) scans were tested in an algorithm developed for use with swept-source OCT angiography (SS-OCTA) scans to determine if SD-OCTA scans yielded similar results for the detection and measurement of persistent choroidal hypertransmission defects (hyperTDs). Design: Retrospective study. Participants: Forty pairs of scans from 32 patients with late-stage nonexudative age-related macular degeneration (AMD). Methods: Patients underwent both SD-OCTA and SS-OCTA imaging at the same visit using the 6 × 6 mm OCTA scan patterns. Using a semiautomatic algorithm that helped with outlining the hyperTDs, 2 graders independently validated persistent hyperTDs, which are defined as having a greatest linear dimension ≥250 μm on the en face images generated using a slab extending from 64 to 400 μm beneath Bruch’s membrane. The number of lesions and square root (sqrt) total area of the hyperTDs were obtained from the algorithm using each imaging method. Main Outcome Measures: The mean sqrt area measurements and the number of hyperTDs were compared. Results: The number of lesions and sqrt total area of the hyperTDs were highly concordant between the 2 instruments (rc = 0.969 and rc = 0.999, respectively). The mean number of hyperTDs was 4.3 ± 3.1 for SD-OCTA scans and 4.5 ± 3.3 for SS-OCTA scans (P = 0.06). The mean sqrt total area measurements were 1.16 ± 0.64 mm for the SD-OCTA scans and 1.17 ± 0.65 mm for the SS-OCTA scans (P < 0.001). Because of the small standard error of the differences, the mean difference between the scans was statistically significant but not clinically significant. Conclusions: Spectral-domain OCTA scans provide similar results to SS-OCTA scans when used to obtain the number and area measurements of persistent hyperTDs through a semiautomated algorithm previously developed for SS-OCTA. This facilitates the detection of atrophy with a more widely available scan pattern and the longitudinal study of early to late-stage AMD. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Background: Age-related macular degeneration (AMD) affects quality of life and independence, and its incidence and prevalence are increasing due to ageing of the population. Access to effective timely treatment can improve vision and reduce incidence of blindness. This study aimed to explore the perspectives of ophthalmologists in the Israeli public healthcare system regarding timely treatment of AMD patients. Methods: Qualitative semi-structured interviews were conducted in 2020-2021 with 22 senior ophthalmologists, from 10 general hospitals and from two HMOs, representing different geographic regions. All interviewees specialize in retinal diseases and work with AMD patients. Interviews discussed patient pathways involved in the diagnosis and treatment of AMD, access to care, and obstacles to timely care. Thematic analysis was conducted. Results: Based on the interviews, we describe the usual referral and treatment pathways. Themes included regional disparities, long wait times in some areas, a lack of retina specialists, differences in referral pathways, inappropriate use of emergency department to obtain timely treatment, and second-line treatment not fully covered by insurance, most affecting the weakest segments of the population. Conclusions: Loss of vision incurs high health and societal costs. In the context of insufficient medical manpower in Israel, the healthcare system will need to assess future resources to cope with accumulating burden of AMD cases over time in an ageing population. Precise referral information, and simultaneous referral to imaging and retinal clinics, may minimize delays in treatment. Awareness of AMD symptoms and the importance of early intervention could be highlighted by campaigns, particularly among high-risk groups. Highlights: • Interviews with hospital-based and community ophthalmologists showed regional disparities in AMD treatment, with long wait times and a lack of retina specialists in some areas. • Differences in referral pathways, inappropriate use of emergency department to obtain timely treatment, and second line treatment not fully covered by insurance were highlighted. • The healthcare system will need to assess future resources to cope with accumulating burden of AMD cases over time in an ageing population • Precise referral information, and simultaneous referral to imaging and retinal clinics, may minimize delays in treatment. • Awareness of AMD symptoms and the importance of early intervention should be emphasized in high-risk groups. [ABSTRACT FROM AUTHOR]

Introduction: Age-related macular degeneration (AMD) is a prevalent, chronic and progressive retinal degenerative disease characterized by an inflammatory response mediated by activated microglia accumulating in the retina. In this study, we demonstrate the therapeutically effects and the underlying mechanisms of microglial repopulation in the laser-induced choroidal neovascularization (CNV) model of exudative AMD. Methods: The CSF1R inhibitor PLX3397 was used to establish a treatment paradigm for microglial repopulation in the retina. Neovascular leakage and neovascular area were examined by fundus fluorescein angiography (FFA) and immunostaining of whole-mount RPE-choroid-sclera complexes in CNV mice receiving PLX3397. Altered cellular senescence was measured by beta-galactosidase (SA-β-gal) activity and p16INK4a expression. The effect and mechanisms of repopulated microglia on leukocyte infiltration and the inflammatory response in CNV lesions were analyzed. Results: We showed that ten days of the CSF1R inhibitor PLX3397 treatment followed by 11 days of drug withdrawal was sufficient to stimulate rapid repopulation of the retina with new microglia. Microglial repopulation attenuated pathological choroid neovascularization and dampened cellular senescence in CNV lesions. Repopulating microglia exhibited lower levels of activation markers, enhanced phagocytic function and produced fewer cytokines involved in the immune response, thereby ameliorating leukocyte infiltration and attenuating the inflammatory response in CNV lesions. Discussion: The microglial repopulation described herein are therefore a promi s ing strategy for rest r icting inflammation and choroidal neovascularization, which are important players in the pathophysiology of AMD. [ABSTRACT FROM AUTHOR]

Drusen are one of the most characteristic pathologies of precursor lesion of age-related macular degeneration (AMD). Drusen comprise a yellowish white substance that accumulates typically under the retinal pigment epithelium (RPE), and their constituents are lipids, complement, amyloid, crystallin, and others. In the past, many researchers have focused on drusen and tried to elucidate the pathophysiology of AMD because they believed that disease progression from early AMD to advanced AMD might be based on drusen or drusen might cause AMD. In fact, it is well established that drusen are the hallmark of precursor lesion of AMD and a major risk factor for AMD progression mainly based on their size and number. However, the existence of advanced AMD without drusen has long been recognized. For example, polypoidal choroidal vasculopathy (PCV), which comprises the majority of AMD cases in Asians, often lacks drusen. Thus, there is the possibility that drusen might be no more than a biomarker of AMD and not a cause of AMD. Now is the time to reconsider the relationship between AMD and drusen. In this review, we focus on early AMD pathogenesis based on basic research from the perspective of cholesterol metabolism and hypoxic response in the retina, and we discuss the role of drusen. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is characterized by the degenerative senescence in the retinal pigment epithelium (RPE) and photoreceptors, which is accompanied by the accumulation of iron ions in the aging retina. However, current models of acute oxidative stress are still insufficient to simulate the gradual progression of AMD. To address this, we established chronic injury models by exposing the aRPE-19 cells, 661W cells, and mouse retina to iron ion overload over time. Investigations at the levels of cell biology and molecular biology were performed. It was demonstrated that long-term treatment of excessive iron ions induced senescence-like morphological changes, decreased cell proliferation, and impaired mitochondrial function, contributing to apoptosis. Activation of the mitogen-activated protein kinase (MAPK) pathway and the downstream molecules were confirmed both in the aRPE-19 and 661W cells. Furthermore, iron ion overload resulted in dry AMD-like lesions and decreased visual function in the mouse retina. These findings suggest that chronic exposure to overloading iron ions plays a significant role in the pathogenesis of retinopathy and provide a potential model for future studies on AMD. NEW & NOTEWORTHY: To explore the possibility of constructing reliable research carriers on age-related macular degeneration (AMD), iron ion overload was applied to establish models in vitro and in vivo. Subsequent investigations into cellular physiology and molecular biology confirmed the presence of senescence in these models. Through this study, we hope to provide a better option of feasible methods for future researches into AMD. [ABSTRACT FROM AUTHOR]

This paper provides a systematic survey of artificial intelligence (AI) models that have been proposed over the past decade to screen retinal diseases, which can cause severe visual impairments or even blindness. The paper covers both the clinical and technical perspectives of using AI models in hosipitals to aid ophthalmologists in promptly identifying retinal diseases in their early stages. Moreover, this paper also evaluates various methods for identifying structural abnormalities and diagnosing retinal diseases, and it identifies future research directions based on a critical analysis of the existing literature. This comprehensive study, which reviews both the conventional and state-of-the-art methods to screen retinopathy across different modalities, is unique in its scope. Additionally, this paper serves as a helpful guide for researchers who want to work in the field of retinal image analysis in the future. [ABSTRACT FROM AUTHOR]

Long-lasting anti-vascular endothelial growth factor (anti-VEGF) agents have become an option to reduce treatment frequency, with ongoing research exploring optimal responses and safety profiles. This review delves into molecular targets, pharmacological aspects, and strategies for achieving effective and enduring disease control in neovascular age-related macular degeneration (AMD). The molecular pathways involved in macular neovascularization, including angiogenesis and arteriogenesis, are explored. VEGF, PlGF, Ang-1, and Ang-2 play crucial roles in regulating angiogenesis, influencing vessel growth, maturation, and stability. The complex interplay of these factors, along with growth factors like TGFβ and bFGF, contributes to the pathogenesis of neovascular membranes. Current anti-VEGF therapies, including bevacizumab, ranibizumab, aflibercept, brolucizumab, and faricimab, are discussed with a focus on their pharmacokinetics and clinical applications. Strategies to achieve sustained disease control in AMD involve smaller molecules, increased drug dosages, and novel formulations. This narrative review provides a comprehensive overview of the molecular targets and pharmacological aspects of neovascular AMD treatment. [ABSTRACT FROM AUTHOR]

We investigated the factors associated with the success of switching to faricimab for type 1 macular neovascularization (MNV) refractory to intravitreal aflibercept (IVA). This retrospective cohort study included patients with type 1 MNV who were switched to faricimab because they were refractory to IVA at two centers. The primary endpoint was a more than two-week extension of the treatment interval after 6 months. In addition, factors related to the success or failure of extension and visual and anatomical outcomes were assessed. The analysis included 43 eyes from 43 patients. Extended dosing intervals of >2 weeks were identified in 14 eyes (32.6%). A short dosing interval before switching, absence of polypoidal lesions, and thin central choroidal thickness before switching were identified as factors involved in successful extension. For patients with refractory type 1 MNV, switching to faricimab is a safe and potential option to extend existing dosing intervals. [ABSTRACT FROM AUTHOR]

Age-related Macular Degeneration (AMD) is a multifactorial ocular pathology that destroys the photoreceptors of the macula. Two forms are distinguished, dry and wet AMD, with different pathophysiological mechanisms. Although treatments were shown to be effective in wet AMD, they remain a heavy burden for patients and caregivers, resulting in a lack of patient compliance. For dry AMD, no real effective treatment is available in Europe. It is, therefore, essential to look for new approaches. Recently, the use of long-chain and very long-chain polyunsaturated fatty acids was identified as an interesting new therapeutic alternative. Indeed, the levels of these fatty acids, core components of photoreceptors, are significantly decreased in AMD patients. To better understand this pathology and to evaluate the efficacy of various molecules, in vitro and in vivo models reproducing the mechanisms of both types of AMD were developed. This article reviews the anatomy and the physiological aging of the retina and summarizes the clinical aspects, pathophysiological mechanisms of AMD and potential treatment strategies. In vitro and in vivo models of AMD are also presented. Finally, this manuscript focuses on the application of omega-3 fatty acids for the prevention and treatment of both types of AMD. [ABSTRACT FROM AUTHOR]

Objective: Age-related macular degeneration (AMD), particularly its exudative form, is a primary cause of vision impairment in older adults. As diabetes becomes increasingly prevalent in aging, it is crucial to explore the potential relationship between diabetic retinopathy (DR) and AMD. This study aimed to assess the risk of developing overall, non-exudative, and exudative AMD in individuals with DR compared to those without retinopathy (non-DR) based on a nationwide population study in Taiwan. Methods: A retrospective cohort study was conducted using the Taiwan National Health Insurance Database (NHIRD) (2000–2013). A total of 3413 patients were placed in the study group (DR) and 13,652 in the control group (non-DR) for analysis. Kaplan–Meier analysis and the Cox proportional hazards model were used to calculate the hazard ratios (HRs) and adjusted hazard ratios (aHRs) for the development of AMD, adjusting for confounding factors, such as age, sex, and comorbid conditions. Results: Kaplan–Meier survival analysis indicated a significantly higher cumulative incidence of AMD in the DR group compared to the non-DR group (log-rank test, p < 0.001). Adjusted analyses revealed that individuals with DR faced a greater risk of overall AMD, with an aHR of 3.50 (95% CI = 3.10–3.95). For senile (unspecified) AMD, the aHR was 3.45 (95% CI = 3.04–3.92); for non-exudative senile AMD, it was 2.92 (95% CI = 2.08–4.09); and for exudative AMD, the aHR was 3.92 (95% CI = 2.51–6.14). Conclusion: DR is a significant risk factor for both overall, senile, exudative, and non-exudative AMD, even after adjusting for demographic and comorbid conditions. DR patients tend to have a higher prevalence of vascular comorbidities; however, our findings indicate that the ocular pathologies inherent to DR might have a more significant impact on the progression to AMD. Early detection and appropriate treatment of AMD is critically important among DR patients. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD), a prevalent and progressive degenerative disease of the macula, is the leading cause of blindness in elderly individuals in developed countries. The advanced stages include neovascular AMD (nAMD), characterized by choroidal neovascularization (CNV), leading to subretinal fibrosis and permanent vision loss. Despite the efficacy of anti-vascular endothelial growth factor (VEGF) therapy in stabilizing or improving vision in nAMD, the development of subretinal fibrosis following CNV remains a significant concern. In this review, we explore multifaceted aspects of subretinal fibrosis in nAMD, focusing on its clinical manifestations, risk factors, and underlying pathophysiology. We also outline the potential sources of myofibroblast precursors and inflammatory mechanisms underlying their recruitment and transdifferentiation. Special attention is given to the potential role of mast cells in CNV and subretinal fibrosis, with a focus on putative mast cell mediators, tryptase and granzyme B. We summarize our findings on the role of GzmB in CNV and speculate how GzmB may be involved in the pathological transition from CNV to subretinal fibrosis in nAMD. Finally, we discuss the advantages and drawbacks of animal models of subretinal fibrosis and pinpoint potential therapeutic targets for subretinal fibrosis.

Age-related macular degeneration (AMD), characterized by macular retinal degeneration, poses a significant health concern due to the lack of effective treatments for prevalent dry AMD. The progression of AMD is closely linked to reactive oxygen species and Fas signaling, emphasizing the need for targeted interventions. In this study, we utilized a NaIO3-induced retinal degeneration mouse model to assess the efficacy of Fas-blocking peptide (FBP). Intravitreal administration of FBP successfully suppressed Fas-mediated inflammation and apoptosis, effectively arresting AMD progression in mice. We developed a 6R-conjugated FBP (6R-FBP) for eye drop administration. 6R-FBP, administered as an eye drop, reached the retinal region, attenuating degeneration by modulating the expression of inflammatory cytokines and blocking Fas-mediated apoptosis in rodent and rabbit NaIO3-induced retinal degeneration models to address practical concerns. Intravitreal FBP and 6R-FBP eye drops effectively reduced retinal degeneration and improved retinal thickness in rodent and rabbit models. This study highlights the therapeutic potential of FBP, particularly 6R-FBP as an eye drop, in inhibiting Fas-mediated cell signaling and protecting against retinal cell death and inflammation in dry AMD. Future investigations should explore the translational prospects of this approach in primates with eye structures comparable to those of humans. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss among the elderly in the developed world. Whilst AMD is a multifactorial disease, the involvement of the complement system in its pathology is well documented, with single-nucleotide polymorphisms (SNPs) in different complement genes representing an increased risk factor. With several complement inhibitors explored in clinical trials showing limited success, patients with AMD are still without a reliable treatment option. This indicates that there is still a gap of knowledge in the functional implications and manipulation of the complement system in AMD, hindering the progress towards translational treatments. Since the discovery of the CRISPR/Cas system and its development into a powerful genome engineering tool, the field of molecular biology has been revolutionised. Genetic variants in the complement system have long been associated with an increased risk of AMD, and a variety of haplotypes have been identified to be predisposing/protective, with variation in complement genes believed to be the trigger for dysregulation of the cascade leading to inflammation. AMD-haplotypes (SNPs) alter specific aspects of the activation and regulation of the complement cascade, providing valuable insights into the pathogenic mechanisms of AMD with important diagnostic and therapeutic implications. The effect of targeting these AMD-related SNPs on the regulation of the complement cascade has been poorly explored, and the CRISPR/Cas system provides an ideal tool with which to explore this avenue. Current research concentrates on the association events of specific AMD-related SNPs in complement genes without looking into the effect of targeting these SNPs and therefore influencing the complement system in AMD pathogenesis. This review will explore the current understanding of manipulating the complement system in AMD pathogenesis utilising the genomic manipulation powers of the CRISPR/Cas systems. A number of AMD-related SNPs in different complement factor genes will be explored, with a particular emphasis on factor H (CFH), factor B (CFB), and complement C3 (C3). [ABSTRACT FROM AUTHOR]

Background: Subretinal macular hemorrhage (SRMH) secondary to age-related macular degeneration (AMD) is a relatively rare condition in ophthalmology characterized by blood collection between the neurosensory retina and the retinal pigment epithelium (RPE). Without prompt treatment, visual prognosis is poor. A plethora of treatment approaches have been tried over the past years ranging from intravitreal anti-vascular endothelial growth factor (anti-VEGF) monotherapy to direct subretinal surgery, with no conclusive superiority of one over the other. Materials and Methods: We conducted a systematic review of the outcomes and treatment modalities of SRMH from inception to 14 June 2022, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA). The level of evidence was assessed for all included articles according to the quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Results: A total of 2745 articles were initially extracted, out of which 1654 articles were obtained after duplicates were removed and their abstracts screened. A total of 155 articles were included for full-text review. Finally, 81 articles remained that fulfilled the inclusion criteria. Conclusions: Even though there are solid results supporting a variety of treatments for SRMH, the best treatment modality has still not been conclusively demonstrated and further research is needed. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is a prevalent cause of vision impairment, affecting millions worldwide. This chronic condition encompasses two main forms: non-exudative (dry) AMD and exudative (wet) AMD. Dry AMD, characterized by the accumulation of drusen and alterations in the retinal pigment epithelium, can evolve into geographic atrophy (GA), culminating in irreversible vision impairment. Despite its considerable impact, therapeutic options for GA were historically constrained until recent advancements emerged. This comprehensive review underscores the pivotal role of the complement system in the pathogenesis of GA. Recent breakthroughs in AMD management have introduced innovative therapeutic modalities targeting complement factors, notably pegcetacoplan and avacincaptad pegol, both of which have garnered FDA approval. These agents have exhibited efficacy in decelerating the growth of GA lesions, offering a promising avenue for GA treatment. Additionally, we delve into past and ongoing clinical trials investigating supplementary complement inhibitors, including IONIS-FB-LRx, NGM621, ANX007, danicopan and AVD-104, highlighting their potential to shape future research endeavours and treatment paradigms. Challenges such as dosing frequency, the risk of neovascular conversion, and interindividual variability in treatment response underscore the imperative for ongoing research and the refinement of therapeutic strategies. While further investigations are warranted to delineate optimal treatment regimens and address extant challenges, the development of complement inhibitors represent a promising stride toward preserving vision and enhancing outcomes for individuals afflicted by this debilitating condition. [ABSTRACT FROM AUTHOR]

To evaluate the optical coherence tomography (OCT) features of hyperpigmented lesions in the absence of intraretinal hyperreflective foci (IHRF) on OCT in eyes with age-related macular degeneration (AMD). We retrospectively analyzed OCT images of eyes with intermediate AMD (iAMD) and macular hyperpigmentation (HP) on color fundus photograph (CFP) but without IHRF on OCT in the corresponding location. The most prominent or definite HP was selected for analysis. The infrared reflectance (IR) image registered with the CFP, and the location corresponding to the HP lesion were defined on the IR image. The location of the HP on the corresponding OCT B-scan was assessed for retinal pigment epithelium (RPE) elevation, acquired vitelliform lesion (AVL), abnormal retinal pigment epithelium + basal lamina (RPE + BL) band reflectivity, RPE + BL band thickening, as well as interdigitation zone (IZ), ellipsoid zone (EZ) and external limiting membrane (ELM) disruption. 49 eyes (39 patients) were included in this study. Forty-six (94%) of the hyperpigmented lesions showed a thickened RPE + BL band. RPE + BL band reflectivity was increased in 37 (76%) of the lesions. RPE + BL band thickening, however, was not correlated with RPE + BL band reflectivity (p-value = 0.31). Either thickening or hyperreflectivity of the RPE + BL band was present in all cases. Twenty (41%) lesions had evidence of ELM disruption, 42 (86%) demonstrated EZ disruption and 48 (98%) had IZ disruption. Five (10%) HPs demonstrated AVL. Among cases with RPE elevation (15 cases, 31%), 10 were classified as drusen, 2 as drusenoid PEDs, and 3 as fibrovascular PEDs. Thickening and/or hyperreflectivity of the RPE + BL band commonly correspond to regions of macular hyperpigmentation without IHRF in eyes with iAMD. [ABSTRACT FROM AUTHOR]

Photochemical damage to retinal pigment epithelial (RPE) cells is implicated in the pathogenesis of age-related macular degeneration. This study investigated the protective effect of mangiferin on RPE cells subjected to blue light-induced damage. Using human-derived acute RPE 19 (ARPE-19) cells as an in vitro model, we incubated ARPE-19 cells with mangiferin and subsequently subjected those cells to damage-inducing blue light irradiation. Cell viability was measured by Cell Counting Kit-8. Intracellular reactive oxygen species (ROS) level was analyzed using flow cytometry. The results indicate that mangiferin can protect ARPE-19 cell growth after blue light-induced damage. However, the preincubation of ARPE-19 cells with lutein did not demonstrate the same protective effect against photo-induced damage. Lutein increased ROS generation and reduced cell viability (72 h), but mangiferin reduced the ROS level compared with the blank control. Our results demonstrate that mangiferin had a protective effect on blue light-induced RPE cell damage. [ABSTRACT FROM AUTHOR]

The steadily growing and aging world population, in conjunction with continuously increasing prevalences of vision-threatening retinal diseases, is placing an increasing burden on the global healthcare system. The main challenges within retinology involve identifying the comparatively few patients requiring therapy within the large mass, the assurance of comprehensive screening for retinal disease and individualized therapy planning. In order to sustain high-quality ophthalmic care in the future, the incorporation of artificial intelligence (AI) technologies into our clinical practice represents a potential solution. This review sheds light onto already realized and promising future applications of AI techniques in retinal imaging. The main attention is directed at the application in diabetic retinopathy and age-related macular degeneration. The principles of use in disease screening, grading, therapeutic planning and prediction of future developments are explained based on the currently available literature. The recent accomplishments of AI in retinal imaging indicate that its implementation into our daily practice is likely to fundamentally change the ophthalmic healthcare system and bring us one step closer to the goal of individualized treatment. However, it must be emphasized that the aim is to optimally support clinicians by gradually incorporating AI approaches, rather than replacing ophthalmologists. [ABSTRACT FROM AUTHOR]