Macular Degeneration Research Articles

Loss of paired immunoglobin-like type 2 receptor B gene associated with age-related macular degeneration impairs photoreceptor function in mouse retina.

Genome-wide association studies have uncovered mostly non-coding variants at over 60 genetic loci linked to susceptibility for age-related macular degeneration (AMD). To ascertain the causal gene at the PILRB/PILRA locus, we used a CRISPR strategy to produce germline deletions in the mouse paired immunoglobin-like type 2 receptor (Pilr) genes that encode highly related activating (PILRB) and inhibitory (PILRA) receptors. We show that a combined loss of Pilrb1 and Pilrb2, but not Pilra, leads to an early but relatively stationary defect as the electroretinography (ERG) amplitudes of Pilrb1/2-/- mice exhibit a marked reduction as early as postnatal day 15 and do not show additional significant decrease at 3 and 12-months. No alterations are evident in Müller glia, microglia, bipolar, amacrine and horizontal cells based on immunohistochemistry using cell-type specific markers. PILRB immunostaining is specifically detected at the proximal part of photoreceptor outer segment. Reduced expression of select calcium-regulated phototransduction and synapse-associated proteins, including GCAP1 and 2, PDE6b, AIPL1, PSD95, and CTBP1 indicates dysregulation of calcium homeostasis as a possible mechanism of retinal phenotype in Pilrb1/2-/- mice. Our studies suggest a novel function of PILRB in retinal photoreceptors and an association of PILRB, but not PILRA, with AMD pathogenesis.

Abstract 4128491: Dietary N-3 Very-Long-Chain Polyunsaturated Fatty Acids Improve Retinal Function And Reduce Aortic Atherosclerosis In ApoE-Deficient Mice

Introduction: N-3 very-long-chain polyunsaturated fatty acids (VLCPUFA; C≥24), which are found primarily in retina and a few other select tissues, are known to play critical roles in specific biological systems. Although n-3 PUFA, such as eicosapentanoic acid (EPA, C20:5 n-3) and docosahexaenoic acid (DHA, C22:6 n-3), may confer cardiovascular benefits, they did not improve age-related macular degeneration (AMD), a leading cause of blindness worldwide, in clinical trials. The activity of ELOVL fatty acid elongase 2 (ELOVL2), an enzyme that converts EPA into tetracosapentaenoic acid (TPA, C24:5 n-3), is known to decrease in the retina with age due to promoter methylation. Hypothesis: We hypothesized that dietary VLCPUFA may delay or prevent AMD, by bypassing the ELOVL2-mediated lipid elongation step. We also hypothesize that VLCPUFA may benefit cardiometabolic health like shorter-chain n-3 PUFA through similar mechanisms. Aims: We aimed to investigate the effect of dietary VLCPUFA on retinal function and cardiometabolic risk factors in mice. Methods: We have produced a new fish oil that contains ~40% (w/w) of C24-C28-rich VLCPUFA. We fed 9-month-old ApoE -/- mice with normal or VLCPUFA fortified diet (1% or 3% (w/w)) for 8 weeks, and age-matched C57BL/6J mice were used as control. We conducted electroretinography (ERG) and cognitive ability tests at the end of feeding period. In in vitro studies, we performed PPAR reporter assay and investigated the anti-inflammatory effects of TPA in lipopolysaccharide-stimulated RAW264.7 cells. Results: Supplementation of VLCPUFA showed a significant and dose-dependent improvement in ERG response. Like EPA and DHA, we also observed favorable cardiometabolic changes and decreased atherosclerotic plaque area due to dietary VLCPUFA. Intriguingly, VLCPUFA supplemented aging mice exhibit better cognitive performance compared with control. Transcriptome analysis revealed that VLCPUFA-enriched fish oil favorably regulated genes involved in nuclear receptor signaling pathways, lipid metabolism and inflammation. Furthermore, purified TPA potently activates PPARs, and suppressed inflammation in macrophage cells. Conclusions: Overall, our studies revealed for the first time several potential health benefits for our new VLCPUFA-enriched fish oil in several age-related diseases and support its future development as a new dietary supplement.

Rutin-Activated Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) Attenuates Corneal and Heart Damage in Mice

Background: Corneal degeneration is a form of progressive cell death caused by multiple factors, such as diabetic retinopathy. It is the most well-known neural degenerative disease caused by macular degeneration in the aged and those with retinitis pigmentosa. Myocardial infarction is becoming a more common burden, causing cardiomyocyte degeneration, ischemia, and heart tissue death. This study examined the preventive effects of rutin on isoproterenol (ISO)-induced oxidative damage (that is, inflammation) on rabbit corneal epithelial cells and mouse heart injuries. Methods: These investigations involved a cytotoxicity test, biochemical analysis, qRT-PCR, Western blotting, and mouse cardiac histopathology. Results: The results showed that rutin enhanced ADH7 and ALDH1A1, retinoic acid signaling components in SIRC1 rabbit corneal cell lines. The production of NO by ocular epithelial cells was significantly reduced. It reduced cTnT and cTnI, CK-MB, and LDH contents in mouse cardiac tissue. The nuclear expressions of Nrf2, Sirt, and HO-1 were all increased by rutin. Docking studies revealed a good interaction between rutin and the Keap protein, enhancing Nrf2 nuclear activity. Conclusions: This showed that rutin can potentially enhance ADH7 and ALDH1A1 corneal signaling components, preventing corneal degeneration and mitigating ISO-induced myocardial infarction (MI) via Keap/Nrf2 expressions.

Risk of Age-Related Macular Degeneration in Patients with Exfoliation Syndrome: The Utah Project on Exfoliation Syndrome (UPEXS)

Objective: To investigate any relationships between exfoliation syndrome or exfoliation glaucoma and age-related macular degeneration utilizing the Utah population database. Design: This was a retrospective, case–control cohort study. Subjects, Participants, and/or Controls: We identified 3405 patients diagnosed with exfoliation syndrome (XFS) or exfoliation glaucoma (XFG) during a dilated eye exam within the UHealth system from 1996 to 2021, whose dry or wet age-related macular degeneration (AMD) status was assessed. A population-based control pool of 257,714 UHealth patients with no XFS/XFG diagnosis and a dilated eye exam history from 1996 to 2021 was compiled, with its patients randomly selected and individually matched 3:1 to cases based on sex and age at index diagnosis of their respective case. Methods: A covariate analysis was performed of characteristics and risk factors associated with XFS/XFG, which included race/ethnicity, residence location, partner/marital status, and family history of XFS/XFG, obesity, tobacco use, alcohol use, osteoporosis/vitamin D deficiency, primary/essential hypertension, ocular hypertension, and cataract surgery. Main Outcome Measure: We studied the trends of non-exudative (dry) or exudative (wet) AMD in a large Utah population study of XFS/XFG patients and controls. Results: Of 3396 XFS/XFG patients, as well as 10,179 individually matched 3:1 control patients, 64% were female and the average age of XFS onset was 74.3 yrs. In a univariate model, we observed a very modest increased risk of wet AMD in XFS/XFG patients (odds ratio, OR = 1.14, 95% confidence interval (CI) 0.99–1.32), which did not achieve statistical significance (p = 0.07). After adjusting for the main effects of potential confounders, there was no greater presentation of AMD in XFS/XFG patients when compared with controls (dry AMD: OR = 0.94, 95% CI 0.85–1.05, p = 031; wet AMD: OR = 0.98, 95% CI 0.83–1.14, p = 0.76). In XFS/XFG patients compared to controls, the risk of having cataract surgery was elevated (OR = 2.39, 95% CI 2.18–2.62). However, after accounting for an interaction with AMD, XFS/XFG patients who underwent cataract surgery did not exhibit an increased risk of either dry or wet AMD (dry AMD: OR = 0.91, 95% CI 0.80–1.03; wet AMD: OR = 0.89, 95% CI 0.75–1.07). The risk of AMD in XFS/XFG patients vs. controls showed no association with osteoporosis/vitamin D deficiency for dry (OR 0.78 95% CI 0.66–0.92 p = 0.004) or wet AMD (OR = 0.72 95% CI 0.56–0.92 p = 0.01), while we found a borderline positive association with both dry and wet AMD if they had osteoporosis/vitamin D deficiency. Conclusion: Using the Utah Population Database, we found that a cataract surgery history significantly impacts the association between AMD and XFS, and that vitamin D deficiency/osteoporosis is a significant confounder of the association. However, no direct association between XFS and AMD was found in this study.

Efficacy and safety of intravitreal conbercept and triamcinolone acetonide for wet age-related macular degeneration in China: a meta-analysis.

Several studies have investigated the efficacy and safety of Conbercept versus Triamcinolone acetonide for the treatment of wet age-related macular degeneration (wAMD), but the results are controversial. Therefore, this meta-analysis aims to evaluate the efficacy and safety of Conbercept versus Triamcinolone acetonide for the treatment of wAMD. A total of seven databases were searched for literature on the treatment of wAMD with Conbercept, with the search period from database inception to May 2024. Patients in the experimental group received Conbercept treatment, while patients in the control group received Triamcinolone acetonide treatment. The observed indicators included central macular thickness, incidence of adverse reactions, clinical efficacy, and best-corrected visual acuity. Relative risk (RR) and mean difference (MD) were used as effect measures. A total of 12 studies with 864 patients were included in the meta-analysis. The results showed that the experimental group had a significantly better central macular thickness (MD = - 42.68, 95% CI = - 55.04 ~ - 30.32, P < 0.001), clinical response rate (RR = 1.25, 95% CI = 1.12 ~ 1.39, P < 0.001), and best-corrected visual acuity (MD = 0.16, 95% CI = 0.12 ~ 0.20, P < 0.001) compared to the control group. In terms of adverse events, the overall incidence of adverse events was lower in the experimental group (RR = 0.26, 95% CI = 0.14 ~ 0.51, P < 0.001) compared to the control group. Specifically, the incidence of intraocular pressure elevation (RR = 0.33, 95% CI = 0.12 ~ 0.94, P = 0.04) and intraocular inflammation (RR = 0.17, 95% CI = 0.03 ~ 0.97, P = 0.05) was lower in the experimental group compared to the control group, but there was no significant difference in the incidence of subconjunctival hemorrhage (RR = 0.7, 95% CI = 0.14 ~ 3.5, P = 0.66) and corneal edema (RR = 0.2, 95% CI = 0.04 ~ 1.12, P = 0.07). Conbercept demonstrated superior efficacy in treating wAMD compared to triamcinolone acetonide, with a lower incidence of adverse reactions. However, the current meta-analysis included a limited number of studies, with only two studies evaluating best-corrected visual acuity (BCVA). Further high-quality randomized controlled trials (RCTs) are warranted to validate these findings.

Association between dietary consumption of multiple vitamins and age-related macular degeneration: a cross-sectional observational study in the National Health and Nutrition Examination Survey 2005–2008

PurposeAge-related macular degeneration (AMD) is one of the common causes of blindness in the elderly worldwide. Its prevention and monitoring indicators remain a key area of research. This study aims to examine the association between vitamin intake and AMD prevalence.MethodsData from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2008 were used for cross-sectional analysis. Logistic regression models, subgroup analyses and multicollinearity regression were employed to assess the association between vitamin intake and AMD.ResultsA total of 1,627 participants were included, with 54.5% (weighted) males and 45.5% (weighted) females. Significant differences were observed in the intake of vitamins B (B1, B2, B6, and B12), E, and folic acid between the AMD and Non-AMD groups. The Non-AMD group had higher average intakes (weighted) of vitamin B1 (1.71 ± 1.10 vs. 1.37 ± 0.64), B2 (2.42 ± 1.22 vs. 1.86 ± 0.70), B6 (2.05 ± 1.25 vs. 1.71 ± 0.85), B12 (5.73 ± 6.18 vs. 4.54 ± 3.27), E (7.93 ± 5.47 vs. 6.39 ± 2.86), and folic acid (181.87 ± 178.04 vs. 140.72 ± 124.60). Logistic regression and subgroup analyses further supported these findings.ConclusionThis study found that higher vitamin intakes B and E were associated with a lower prevalence of AMD in the U.S. population. Eating a healthy diet rich in vitamins B and E, particularly B2 (eggs, green vegetables, meat, mushrooms, and almonds) may help to reduce vision loss due to AMD. However, since this is a cross-sectional study, causal associations between vitamin intake and AMD cannot be established. Further randomized clinical trials are needed to confirm these findings.

Interpretable multimodal classification for age-related macular degeneration diagnosis.

Explainable Artificial Intelligence (XAI) is an emerging machine learning field that has been successful in medical image analysis. Interpretable approaches are able to "unbox" the black-box decisions made by AI systems, aiding medical doctors to justify their diagnostics better. In this paper, we analyze the performance of three different XAI strategies for medical image analysis in ophthalmology. We consider a multimodal deep learning model that combines optical coherence tomography (OCT) and infrared reflectance (IR) imaging for the diagnosis of age-related macular degeneration (AMD). The classification model is able to achieve an accuracy of 0.94, performing better than other unimodal alternatives. We analyze the XAI methods in terms of their ability to identify retinal damage and ease of interpretation, concluding that grad-CAM and guided grad-CAM can be combined to have both a coarse visual justification and a fine-grained analysis of the retinal layers. We provide important insights and recommendations for practitioners on how to design automated and explainable screening tests based on the combination of two image sources.

Research progress on the pathogenesis of PM2.5 in ophthalmic diseases

PM2.5 is a fine particulate matter with an aerodynamic equivalent diameter of less than or equal to 2.5 μm, and it is the primary pollutant that causes haze. In recent years, numerous research results have shown that PM2.5 is associated with various ophthalmic diseases and its pathogenic mechanism is complex. It can disrupt the homeostasis of the tear film and the function of the meibomian glands, leading to dry eye; increase the risk of allergic and other types of conjunctivitis; may cause blepharitis; affect the homeostasis of the corneal epithelium and promote the development of keratopathy; the correlation with cataract is controversial; it is related to the risk of glaucoma; it is associated with age-related macular degeneration; it may also indirectly promote diabetic retinopathy. Prevention and control measures include controlling the level of PM2.5, strengthening publicity and screening, reducing going out and wearing goggles, etc. PM2.5 is closely related to ophthalmic diseases, but its specific pathogenic mechanism still requires more research to explore.

The impact of vitreomacular traction on vitreous vascular endothelial growth factor and placental growth factor levels in neovascular age-related macular degeneration patients.

To investigate the effect of vitreomacular traction (VMT) on vitreous vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) levels in patients with active neovascular age-related macular degeneration (nAMD). A prospective, interventional, case-control study. The study included a total of 70 patients from whom vitreous samples were obtained. The patients were categorized into four group: 10 patients with active nAMD accompanying VMT, 17 patients with VMT, 24 patients with active nAMD and 19 healthy patients without any diagnosis other than cataract. VEGF and PlGF levels were measured. The mean vitreous VEGF level was 34.7 ± 4.98 pg/ml in the nAMD and VMT group, 32.36 ± 4.55 pg/ml in the VMT group, 34.02 ± 3.79 pg/ml in the nAMD group, and 32.33 ± 2.4 pg/ml in the healthy control group. The mean vitreous PlGF level was 58.92 ± 20.83 pg/ml in the nAMD and VMT group, 46.29 ± 3.45 pg/ml in the VMT group, 54.64 ± 16.88 pg/ml in the nAMD group, and 53.66 ± 19.35 pg/ml in the healthy control group. No significant differences were observed in terms of vitreous VEGF and PlGF concentrations among the groups (p > 0.05 and p > 0.05, respectively). Aqueous humour VEGF and PlGF levels were significantly higher than vitreous levels in nAMD patients (p = 0.005 and p = 0.005, respectively). The present study found no increases in vitreous VEGF and PlGF levels in both VMT + nAMD and VMT cases. Furthermore, patients with nAMD had significantly higher levels of PlGF and VEGF in aqueous humour compared to vitreous levels.

Real-World Long-Term Outcomes of Intravitreal Faricimab in Previously Treated Chronic Neovascular Age-Related Macular Degeneration.

To study the real-world outcomes of intravitreal faricimab (IVF) in longstanding neovascular age-related macular degeneration (nAMD) over a one-year study period. Retrospective single-center cohort study of patients with previously treated nAMD receiving IVF with at least 12 months of follow up. Main outcome measures include injection intervals, visual acuity (VA), and optical coherence tomography features. 263 eyes from 217 patients received 6.4±2.3 IVF injections over one year. Injection interval increased after switching to IVF (5.9±1.8 vs 7.6±2.4 weeks) (p<0.01). There was no improvement in VA after switching to IVF at any time period (p>0.15). Average CST decreased after the first IVF injection and was sustained for one year (313.7±96.0 vs. 288.2±80.6 μm) (p<0.01). There was a statistically significant resolution of subretinal fluid but not IRF at all time points (40.8-50.4%) (p<0.01). Persistent fluid after the first IVF injection was resolved in 34.4% (n=45) by one year. IVF was discontinued in 31 eyes (11.8%), four (1.6%) that experienced intraocular inflammation. Longstanding nAMD eyes switched to IVF experienced a significant extension in injection interval, stable visual acuity, improvement in CST, and resolution of fluid on OCT in many patients over one year.

The perspective of ceRNA regulation of circadian rhythm on choroidal neovascularization

Abnormal growth of blood vessels (choroidal neovascularization) can lead to age-related macular degeneration (AMD) and eventually cause vision loss due to detachment of the retinal pigmented epithelium. This indicates that choroidal neovascularization is important for the treatment of AMD. The circadian clock in the mammalian retina is responsible for controlling various functions of the retina, enabling it to adjust to changes in light and darkness. Recent studies have revealed a potential connection between the circadian clock and eye diseases, although a cause-and-effect relationship has not been definitively established. C57BL/6J male mice (aged 6 weeks) were randomly divided into two groups (Control group: 9:00–21:00 light period (300 lx); Jet lag group: 8-hour phase advance once every 4 days). A laser-induced CNV model was created after 2 weeks of feeding in a controlled or jet-lagged environment. Then, full transcriptome sequencing was performed. The pathways regulated by differentially expressed mRNAs were identified by GO analysis and GSEA. Further protein networks were constructed with the STRING database and Cytoscape software. WGCNA was used to further explore the co-expression modules of these differential genes and the correlation between these differential genes and phenotypes. ceRNA networks were constructed with miRanda and TargetScan. The pathways associated with the overlapping differentially expressed mRNAs in the ceRNA network were identified, and the hub genes were validated by qPCR. A total of 661 important DEGs, 31 differentially expressed miRNAs, 106 differentially expressed lncRNAs and 87 differentially expressed circRNAs were identified. GO and GSEA showed that the upregulated DEGs were mainly involved in reproductive structure development and reproductive system development. The STRING database and Cytoscape were used to determine the protein interaction relationships of these DEGs. WGCNA divided the expression of these genes into several modules and screened the hub genes of each module separately. Furthermore, a ceRNA network was constructed. GO analysis and GSEA showed that these target DEmRNAs mainly function in wound healing, cell spreading, epiboly involved in wound healing, epiboly, and morphogenesis of an epithelial sheet. Finally, ten key genes were identified, and their expression patterns were confirmed by real-time qPCR. In this study, we investigated the regulatory mechanism of ceRNAs in choroidal neovascularization according to different light-dark cycles in the eyeball.

Impairment of Neurovascular Function in Intermediate Age-Related Macular Degeneration.

To investigate neurovascular function in eyes with age-related macular degeneration (AMD). Subjects with bilateral large drusen (intermediate AMD) and healthy controls ≥50years old were recruited. The vasculature within the central 6 × 6-mm retinal area was captured using optical coherence tomography angiography (OCTA) and segmented to return superficial plexus, deep plexus, choriocapillaris, and choroid. OCTA scans were acquired without flicker light stimulation (conventional OCTA) and during flicker light stimulation to increase retinal activity and metabolic demand (functional OCTA). Vascular area density (VAD) and the vascular reactivity index (VRI; change in VAD induced by flicker stimulation) were determined and compared between control and AMD eyes. Thirty-five subjects (19 AMD cases and 16 healthy controls) participated in the study. In healthy eyes, flicker stimulation induced an increase in VAD (positive VRI, vasodilation) in the superficial plexus (P < 0.001) and deep plexus (P < 0.001). There was a trend for increased VAD in the choriocapillaris (P = 0.077), but there was no change in the choroid (P = 0.654). In AMD eyes, there was no change in VAD in response to flicker stimulation in any of the vascular layers examined (P ≥ 0.294). Linear mixed models confirmed that AMD was associated with a reduced VRI in the superficial plexus (P < 0.001) and deep plexus (P < 0.001). Eyes with large drusen show a reduction in retinal vascular reactivity compared to healthy eyes, which suggests that there is impairment of retinal neurovascular function in intermediate AMD. Functional OCTA could be used to study neurovascular function in retinal diseases.

Cross-instrument optical coherence tomography-angiography (OCTA)-based prediction of age-related macular degeneration (AMD) disease activity using artificial intelligence

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.

Aflibercept 8 mg/0.07 mL (Eylea HD)

Reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class. The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada’s federal, provincial, and territorial governments, with the exception of Quebec. This review assesses aflibercept (Eylea HD) 8 mg (0.07 mL), solution for intravitreal injection. Indication: For the treatment of neovascular (wet) age-related macular degeneration (nAMD).

A pilot study : retinal sensitivity change in neovascular age-related macular degeneration patients with better baseline visual acuity

This study evaluated changes in retinal sensitivity (RS) during aflibercept treatment in neovascular age-related macular degeneration (nAMD) patients with good vision. Treatment-naive nAMD patients with visual acuity better than 20/40 were treated with an aflibercept loading regiment, and RS was measured using the MAIA microperimetry device. The study examined RS differences based on visit, region, adjacent local pathology, outer retinal changes and optical coherence tomography angiography (OCTA) data were investigated. Twelve patients completed the protocol. Mean RS improved from 17.9 (3.9) µm at baseline to 20.4 (4.7) µm at final visit, while best-corrected visual acuity (BCVA) did not change. (P = 0.041) RS at baseline is worst in the presence of intraretinal fluid (IRF) and improved after treatment for all retinal pathologies except IRF. RS improvement occurred even with initial outer retinal damage. A Linear mixed model showed subretinal hyperreflective material, baseline IRF height, outer retinal integrity, fibrovascular pigment epithelial detachment height, and local choroidal vascular index as factors associated with RS. In conclusion, RS improved with aflibercept treatment in nAMD eyes with good initial visual acuity, despite no change in BCVA, except when IRF was present.

Machine learning model for age-related macular degeneration based on heavy metals: The National Health and Nutrition Examination Survey 2005 to 2008

Age-related macular degeneration (AMD) is the leading cause of blindness in older people in developed countries. It has been suggested that heavy metal exposure may be associated with the development of AMD, but most studies have focused on the effects of a single metal with traditional methods. In this study, we analyzed the relationship between 13 urinary heavy metal concentrations and AMD using NHANES data between 2005 and 2008. We constructed and compared 11 machine learning models to identify the best model for predicting AMD risk. We further interpreted the models by Permutation Feature Importance (PFI), Partial Dependence Plot (PDP) analysis, and SHapley Additive exPlanations (SHAP) analysis. 216 AMD patients out of 2380 participants. The random forest (RF) model performed optimally in predicting the risk of AMD, with an AUC value of 0.970. PFI analyses revealed that age and urinary cadmium (Cd) were the main factors influencing the risk of AMD. SHAP analyses further confirmed the significance of Cd concentration in predicting the risk of AMD, and we revealed a significant interaction with significant interaction of race. Our study firstly explored the relationship between heavy metal exposure levels and AMD based on machine learning techniques, found that urinary Cd concentration had the greatest impact on AMD, and revealed the superior predictive performance of machine learning methods. Furthermore, our study provided a new perspective for early screening and intervention of AMD.

Levodopa is associated with reduced development of new-onset geographic atrophy in patients with age-related macular degeneration.

Geographic atrophy (GA) is a significant cause of vision loss in patients with age-related macular degeneration (AMD). Current treatments are limited to anti-complement drugs, which have limited efficacy to delay progression with significant risk of complications. Levodopa (L-DOPA) is a byproduct of melanin synthesis that is associated with reduced development of neovascular AMD. In this study, we determined if L-DOPA was associated with a reduced likelihood of new-onset GA. We performed a retrospective analysis in the Vestrum Health Retina Database. We included eyes with non-neovascular AMD without GA and 1-5years of follow-up. Eyes were divided into two groups. Exposed to L-DOPA before or on the date of non-neovascular AMD without GA diagnosis, and eyes not exposed to L-DOPA. We extracted age, sex, AREDS2 status, dry AMD stage, smoking history, and conversion rate to GA at years 1 through 5. Propensity score matching was used to match L-DOPA and control groups. Cox proportional hazard regression, adjusting for age, sex, AMD severity, AREDS2 use, smoking status, and L-DOPA use was employed to calculate hazard ratios for new-onset GA detection. We identified 112,089 control and 844 L-DOPA exposed eyes with non-neovascular AMD without GA. After propensity score matching, 2532 control and 844 L-DOPA exposed eyes remained that were well-matched for age, sex, AMD severity, AREDS2 use, and smoking status. We found that L-DOPA exposure was associated with a significantly reduced likelihood (HR = 0.68, 95% CI: 0.48-0.95, P = 0.025) of new-onset GA detection. L-DOPA use was associated with reduced detection of new-onset GA.

Exploring the relationship between cathepsin and age-related macular degeneration using Mendelian randomization

PurposeAge-related macular degeneration (AMD) is the leading cause of low vision and even blindness in the elderly population worldwide. However, no studies have been conducted to analyze the causal relationship between the cathepsin family and AMD. The present study aimed to explore and analyze this potential association using Mendelian randomization (MR).MethodsIn this study, AMD was classified into two types: exudative AMD and atrophic AMD. Inverse-variance weighting (IVW) was used as the main analysis method. The association between nine cathepsins and the two classifications of AMD were analyzed using multivariable Mendelian randomization (MVMR). Sensitivity analysis included Cochran’s Q-test and the MR-Egger intercept test.ResultsTwo-sample MR analysis showed that higher levels of cathepsin L2 were associated with a delay in the development of atrophic AMD (IVW: p = 0.017; OR = 0.885; 95% CI = 0.799–0.979). Reverse MR analysis indicated that cathepsin E levels were increased in individuals with atrophic (IVW: p = 0.023; OR = 1.058; 95% CI = 1.007–1.111) and exudative AMD (IVW: p = 0.018; OR = 1.061; 95% CI 1 = 1.010–1.115). MVMR analysis indicated a causal relationship between cathepsin G (IVW: p = 0.025; OR = 1.124; 95% CI = 1.014–1.245), cathepsin O (IVW: p = 0.043, OR = 1.158, 95% CI = 1.004–1.336), and exudative AMD after coordinating for other types of cathepsin.ConclusionThis study demonstrated a potential link between the cathepsin family and the onset of AMD. Elevated serum concentrations of cathepsin L2 may serve as a protective factor for atrophic AMD, while increased levels of serum cathepsin G and O concentrations may promote the development of exudative AMD. Besides, the development of AMD may be associated with elevated serum concentrations of cathepsin E.

Current advances in multimodal imaging in geographic atrophy secondary to age-related macular degeneration: A review

Abstract: As we move toward an era in which there will be treatment options for geographic atrophy (GA) secondary to age-related macular degeneration, the need to accurately understand and interpret multimodal imaging (MMI) for the condition is paramount. This review discusses the evolution of MMI in GA and how it has led to a greater understanding of different phenotypes and risk factors for progression. These advancements have allowed novel imaging biomarkers to be used as end points in large interventional studies exploring new therapies for GA treatment. Due to differences in drug approval timing, ophthalmologists in some jurisdictions are already treating patients with complement inhibiting intravitreal therapies and using MMI to guide management. Cementing knowledge of how GA appears on MMI and evolves over time will be vital for best practice as these interventions become more widely available.

A Method for Retina Segmentation by Means of U-Net Network

Retinal image segmentation plays a critical role in diagnosing and monitoring ophthalmic diseases such as diabetic retinopathy and age-related macular degeneration. We propose a deep learning-based approach utilizing the U-Net network for the accurate and efficient segmentation of retinal images. U-Net, a convolutional neural network widely used for its performance in medical image segmentation, is employed to segment key retinal structures, including the optic disc and blood vessels. We evaluate the proposed model on a publicly available retinal image dataset, demonstrating interesting performance in automatic retina segmentation, thus showing the effectiveness of the proposed method. Our proposal provides a promising method for automated retinal image analysis, aiding in early disease detection and personalized treatment planning.