Age-related Macular Degeneration Cases Research Articles

Complement Inhibitors for Geographic Atrophy in Age-Related Macular Degeneration-A Systematic Review.

Age-related macular degeneration (AMD) is one of the main causes of blindness and visual impairment worldwide. Intravitreal complement inhibitors are an emergent approach in the treatment of AMD, which have had encouraging results. This systematic review analyzes the outcomes and safety of complement inhibitor therapies for GA in AMD cases. A comprehensive search on the PubMed and Web of Science databases returned 18 studies involving various complement inhibitor agents, with a total of 4272 patients and a mean follow-up of 68.2 ± 20.4 weeks. Most treated patients were white (96.8%) and female (55.8%), with a mean age of 78.3 ± 7.8 years and a mean GA area of 8.0 ± 3.9 mm2. There were no differences in visual function change between treated and control participants. The mean GA area change was 2.4 ± 0.7 mm2 in treated participants vs. 2.7 ± 0.8 mm2 in control groups (p < 0.001). The ocular and systemic side effects were similar to those of intravitreal anti-VEGF. A less-understood effect was that of the onset of choroidal neovascularization (CNV) in 1.1-13% of patients; this effect was found to be more frequent in patients with neovascular AMD in the fellow eye or nonexudative CNV in the study eye at baseline. Complement inhibitors may represent a useful therapy for GA in AMD, but a personalized approach to patient selection is necessary to optimize the outcomes.

Clinical utility of swept-source optical coherence tomography angiography for the diagnosis of exudative maculopathy.

To assess the feasibility of swept-source optical coherence tomography angiography (SS-OCTA) to differentiate macular diseases, including nonpolypoidal macular neovascularization (MNV), polypoidal choroidal vasculopathy (PCV), type 3 MNV, and chronic central serous chorioretinopathy (CSC) without indocyanine green angiography (ICGA). Retrospective observational study. This study examined 63 eyes of 63 patients with treatment-naive neovascular age-related macular degeneration(AMD), including 23 eyes with nonpolypoidal MNV, 17 eyes with PCV, and 1 eye with type 3 MNV and 22 eyes with chronic CSC. Two independent retina specialists, blinded to the clinical diagnosis, assessed each case of neovascular AMD and chronic CSC using only B-scan and en face images of SS-OCTA without referring to other examination outcomes. By SS-OCTA alone, 19 eyes were diagnosed with nonpolypoidal MNV, 17 eyes with PCV, 2 eyes with type 3 MNV, and 22 eyes with chronic CSC, indicating high sensitivity (82.6%, 94.1%, 100%, and 100%, respectively) and specificity (100%, 97.8%, 98.4%, and 100%, respectively); however, three eyes could not be diagnosed because of obscure images. The agreement of diagnosis with SS-OCTA alone was high between the two specialists (κ = 0.82). SS-OCTA showed high sensitivity and specificity in the differentiation of nonpolypoidal MNV, PCV, type 3 MNV, and chronic CSC. The differential criteria based on SS-OCTA could be a substitute for the ICGA-based diagnoses.

Psoriasis as a Predictor of Neovascular Age-Related Macular Degeneration in Type 2 Diabetes Mellitus: A Nationwide Cohort Study

PurposeThe objective of this study is to evaluate the relationship of psoriasis and neovascular Age-related Macular Degeneration (AMD) in diabetic mellitus (DM) population. DesignNationwide, population-based, retrospective cohort study. MethodsRecords of patients who had been diagnosed with type 2 diabetes mellitus over 40 years of age from January 2009 to December 2012 were analyzed. The incidence of neovascular AMD was observed from the index year to December 2018 in all subjects. We compared the incidence rate of neovascular AMD among the psoriasis group and control group. Covariates include age, sex, BMI, income level, smoking status, drinking status, regular exercise habits, hypertension, dyslipidemia, end-stage renal disease, diabetic retinopathy, glucose level, the prescription of more than three oral hypoglycemic agents, and a history of diabetes mellitus exceeding five years. ResultsOf 2,245,358 type 2 DM patients, 20,853 patients were classified in the psoriasis group, and the other 2,224,505 individuals in the control group. A total of 105 neovascular AMD cases occurred in the psoriasis group and 7,459 cases in the control group. According to multivariable Cox proportional hazard models, individuals with psoriasis had a significantly higher risk for neovascular AMD compared to controls (HR=1.329, 95% confidence interval: 1.096-1.612) after adjustments for covariates. ConclusionThis study demonstrated that psoriasis was an independent risk factor for developing neovascular AMD in DM patients. Therefore, physicians should be alert to the development of neovascular AMD in DM patients who also have psoriasis.

Factors Affecting Compliance and Visual Outcomes in Patients Receiving Intravitreal Bevacizumab Injections.

Background Vascular endothelial growth factor (VEGF) is a powerful mitogen for endothelial cells that promotes migration, proliferation, and tube formation necessary for the angiogenic development of new blood vessels. When VEGF increases significantly, it causes pathological angiogenesis and increased vascular permeability in eye conditions such as diabetic retinopathy (DR), age-related macular degeneration (AMD), and retinal vein occlusion (RVO). These disorders have become important global sources of morbidity and have a substantial financial impact not only on the medical community but also on the patients. Therefore, this study aims to determine the success rates of intravitreal bevacizumab therapy and the visual outcomes which may be increased by determining the factors affecting patient compliance and raising awareness about DR, neovascular AMD, and RVOamong patients and studying the factors responsible for non-compliance to treatment. Methodology This experimental pre-post study was conducted in the ophthalmology department at a tertiary care hospital and research center in western Maharashtra from September 2022 to June 2024. A total of 150 eyes of 150 patients who were diagnosed cases of DR, neovascular AMD, and non-ischemic RVOwere included in the study.Written informed consent was obtained from each patient. Data were entered in Microsoft Excel (Microsoft Corp., Redmond, WA, USA) and statistical analysis was done using SPSS 27.0 software (IBM Corp., Armonk, NY, USA). The chi-square test was employed to check the association between categorical variables. Pearson's correlation test was used, and p-values <0.05 were considered significant. Results The compliance rate in our study was 79.3% (113 individuals). In our study, 58% (87 individuals) were male while 42% (63 individuals) were females. Most patients were from urban areas 74.7% (112 individuals). Among the study participants, DR patients constituted 48.6% (73 individuals), while neovascular AMD and RVO were seen in 32% (48 individuals) and 19.4% (29 individuals), with 62% (93 individuals) being diabetic and 64.7% (97 individuals) being hypertensive. In our study, 92% (138 individuals) were willing to take treatment, with 88.7% (133 individuals) worried about their visual outcomes and 66% (99 individuals) afraid of getting injected. Appointments posed a financial burden to 30.7% (46 individuals) of patients, with 55.3% (83 individuals) having transportation issues. Overall, 18.7% (28 individuals) of patients had missed appointments between 14 and 90 days while 30.7% (46 individuals) had missed their appointments by 90 and 365 days. Younger patients with a shorter duration of diabetes had higher compliance rates. Post-injection, there was an overall significant improvement in vision as well as a reduction in the central subfield macular thickness, volume cube, and thickness average cube. Conclusions In the present study, four-fifths of the patients were compliant with treatment, and visual improvement was significant. In addition, there was a significant reduction in the macular thickness after the treatment. One of the factors for non-compliance included in our study was the need for follow-up. Younger patients and those with a shorter duration of diabetes had significantly higher compliance. We recommend further studies should be conducted to compare the effectiveness with the control group in randomized control trials.

Association of ARMS2, HTRA1 and CFH genes polymorphisms in patients with age-related macular degeneration in the Malaysian population

BackgroundDespite extensive research efforts, understanding the precise causes and molecular underpinnings of age-related macular degeneration (AMD) remains elusive. Exploring different populations becomes crucial to establish conclusive insights into the role of genetic factors in AMD.MethodologyThis study aimed to investigate the association between the well-documented major risk alleles in the HTRA1, ARMS2 and CFH genes with AMD in the Malaysian multi-ethnic population. A total of 205 subjects were enrolled in this study, 103 were diagnosed with AMD while 102 represented the control subjects. Genomic DNA was extracted from peripheral blood mononuclear cells and gene amplification was performed by polymerase chain reaction. Subsequently, genotyping for the HTRA1, ARMS2 and CFH genes was performed using direct DNA sequencing analysis.ResultsSignificant associations (p < 0.05) were detected with AMD for both SNP rs11200638: G > A in the promoter of HTRA1 and rs10490924: G > T in ARMS2 but not for variant Y402H in CFH gene (p > 0.05) in our study population. The A allele frequency of rs11200638 in the HTRA1 promoter was 51.9% in cases versus 39.2% in controls (p = 0.010). The frequency of AA genotype was 28.2% for AMD cases, compared to 17.6% in controls (OR 2.58, 95% CI 1.19–5.58; p = 0.043). The frequency of the TT genotype of rs10490924 in ARMS2 was 25.2% in cases versus 8.8% in controls (OR 2.23, 95% CI 0.83–5.99; p = 0.002).ConclusionThe study reveals an association between specific genetic variants in the HTRA1 and ARMS2 genes and the occurrence of AMD in the Malaysian population. However, contrary to expectations, the study did not identify a substantial correlation between AMD and the Y402H variant of the CFH gene in this specific population.

Therapeutic targets for age-related macular degeneration: proteome-wide Mendelian randomization and colocalization analyses.

Currently, effective therapeutic drugs for age-related macular degeneration (AMD) are urgently needed, and it is crucial to explore new treatment targets. The proteome is indispensable for exploring disease targets, so we conducted a Mendelian randomization (MR) of the proteome to identify new targets for AMD and its related subtypes. The plasma protein level data used in this study were obtained from two large-scale studies of protein quantitative trait loci (pQTL), comprising 35,559 and 54,219 samples, respectively. The expression quantitative trait loci (eQTL) data were sourced from eQTLGen and GTEx Version 8. The discovery set for AMD data and subtypes was derived from the FinnGen study, consisting of 9,721 AMD cases and 381,339 controls, 5,239 wet AMD cases and 273,920 controls, and 6,651 dry AMD cases and 272,504 controls. The replication set for AMD data was obtained from the study by Winkler TW et al., comprising 14,034 cases and 91,234 controls. Summary Mendelian randomization (SMR) analysis was employed to assess the association between QTL data and AMD and its subtypes, while colocalization analysis was performed to determine whether they share causal variants. Additionally, chemical exploration and molecular docking were utilized to validate potential drugs targeting the identified proteins. SMR and colocalization analysis jointly identified risk-associated proteins for AMD and its subtypes, including 5 proteins (WARS1, BRD2, IL20RB, TGFB1, TNFRSF10A) associated with AMD, 2 proteins (WARS1, IL20RB) associated with Dry-AMD, and 9 proteins (COL10A1, WARS1, VTN, SDF2, LBP, CD226, TGFB1, TNFRSF10A, CSF2) associated with Wet-AMD. The results revealed potential therapeutic chemicals, and molecular docking indicated a good binding between the chemicals and protein structures. Proteome-wide MR have identified risk-associated proteins for AMD and its subtypes, suggesting that these proteins may serve as potential therapeutic targets worthy of further clinical investigation.

The role of blood related inflammatory factors on age-related macular degeneration (AMD)

BackgroundAge-related macular degeneration (AMD) is a significant retinal disease that leads to irreversible low vision, particularly in developing countries. The variation in AMD prevalence among different racial groups and highlighted role of inflammation on disease pathology from previous studies which yielded in inconsistent findings, It seems to be of great importance to do more investigation in this field.MethodsThis case control study involved 204 participants, divided into four groups of equal size (51 individuals per group). Three groups represented AMD cases of varying severity according to Beckman classification (3 groups) and one healthy control group. Sampling was conducted exhaustively until the desired sample size was reached. The control group comprised healthy individuals without any infectious or inflammatory systemic, ophthalmic disease. Blood samples were collected to measure inflammatory factors, including lymphocytes, monocytes, neutrophils, neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein (CRP). Collected data were analyzed by statistical methods in SPSS version 21.ResultsOf the participants, 51% were women, and their ages ranged from 47 to 89 years (62.2 ± 8). According to multiple logistic regression analysis, age exhibited a statistically significant positive association with AMD severity (P = 0.038, odds ratio [OR] = 1.034). ANOVA results indicated a significant association between neutrophil count and AMD severity (P < 0.001). As the disease severity increased, the number of neutrophils decreased. The mean ± SD neutrophil counts for early, intermediate and advanced AMD were 3849 ± 800, 3702 ± 734, and 3342 ± 823, respectively. No statistically significant associations were found between lymphocyte count, monocyte count, neutrophil-to-lymphocyte ratio, CRP, and AMD.ConclusionThere was a significant relationship between the number of neutrophils in peripheral blood and the severity of AMD in study participants which needs more evaluation for the potential utility of this factor in the prognosis of AMD. There was not any significant relationship among the other factors and AMD.

Age-Related Macular Degeneration and Extramacular Drusen: Genetic Associations in the Coimbra Eye Study.

To explore the association between the genetics of age-related macular degeneration (AMD) and extramacular drusen (EMD) in patients with and without AMD. We included 1753 eyes (912 subjects) with phenotypic characterization regarding AMD and EMD. Genetic sequencing and the genetic risk score (GRS) for AMD were performed according to the EYE-RISK consortium methodology. To test for differences in the GRS from EMD cases, AMD cases, and controls, a clustered Wilcoxon rank-sum test was used. The association of AMD, EMD, and the GRS was evaluated using logistic regression models adjusted for age and sex. Individual associations of common risk variants for AMD with EMD were explored. EMD were found in 755 eyes: 252 (14.4%) with AMD and 503 (28.7%) without. In total, 122 eyes (7.0%) had only AMD, and 876 (50.0%) were controls. EMD were strongly associated with AMD (odds ratio [OR], 3.333; 95% confidence interval [CI], 2.356-4.623; P < 0.001). The GRS was associated with an increased risk of AMD (OR, 1.416; 95% CI, 1.218-1.646; P < 0.001) but not with EMD. Individually, the common risk variants ARMS2 rs10490924 (P = 0.042), C3 rs2230199 (P = 0.042), and CETP rs5817082 (P = 0.042) were associated with EMD, after adjustment for AMD, sex, and age. We found a strong association between EMD and AMD, suggesting a common pathogenesis. The GRS for AMD was not associated with EMD, but a partially overlapping genetic basis was suggested when assessing individual risk variants. We propose that EMD per se do not represent an increase in the global genetic risk for AMD.

Drusen in AMD from the Perspective of Cholesterol Metabolism and Hypoxic Response.

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.

Association of age at diagnosis of diabetes with subsequent risk of age-related ocular diseases and vision acuity

BACKGROUND The importance of age on the development of ocular conditions has been reported by numerous studies. Diabetes may have different associations with different stages of ocular conditions, and the duration of diabetes may affect the development of diabetic eye disease. While there is a dose-response relationship between the age at diagnosis of diabetes and the risk of cardiovascular disease and mortality, whether the age at diagnosis of diabetes is associated with incident ocular conditions remains to be explored. It is unclear which types of diabetes are more predictive of ocular conditions. AIM To examine associations between the age of diabetes diagnosis and the incidence of cataract, glaucoma, age-related macular degeneration (AMD), and vision acuity. METHODS Our analysis was using the UK Biobank. The cohort included 8709 diabetic participants and 17418 controls for ocular condition analysis, and 6689 diabetic participants and 13378 controls for vision analysis. Ocular diseases were identified using inpatient records until January 2021. Vision acuity was assessed using a chart. RESULTS During a median follow-up of 11.0 years, 3874, 665, and 616 new cases of cataract, glaucoma, and AMD, respectively, were identified. A stronger association between diabetes and incident ocular conditions was observed where diabetes was diagnosed at a younger age. Individuals with type 2 diabetes (T2D) diagnosed at &lt; 45 years [HR (95%CI): 2.71 (1.49-4.93)], 45-49 years [2.57 (1.17-5.65)], 50-54 years [1.85 (1.13-3.04)], or 50-59 years of age [1.53 (1.00-2.34)] had a higher risk of AMD independent of glycated haemoglobin. T2D diagnosed &lt; 45 years [HR (95%CI): 2.18 (1.71-2.79)], 45-49 years [1.54 (1.19-2.01)], 50-54 years [1.60 (1.31-1.96)], or 55-59 years of age [1.21 (1.02-1.43)] was associated with an increased cataract risk. T2D diagnosed &lt; 45 years of age only was associated with an increased risk of glaucoma [HR (95%CI): 1.76 (1.00-3.12)]. HRs (95%CIs) for AMD, cataract, and glaucoma associated with type 1 diabetes (T1D) were 4.12 (1.99-8.53), 2.95 (2.17-4.02), and 2.40 (1.09-5.31), respectively. In multivariable-adjusted analysis, individuals with T2D diagnosed &lt; 45 years of age [β 95%CI: 0.025 (0.009,0.040)] had a larger increase in LogMAR. The β (95%CI) for LogMAR associated with T1D was 0.044 (0.014, 0.073). CONCLUSION The younger age at the diagnosis of diabetes is associated with a larger relative risk of incident ocular diseases and greater vision loss.

Pro re nata anti-VEGF treatment in pachychoroid neovasculopathy compared with age-related macular degeneration based on optical coherence tomography.

To compare anti-vascular endothelial growth factor (anti-VEGF) treatment in pachychoroid neovasculopathy (PNV) and age related macular degeneration (AMD). Cases having pro re nata (PRN) anti-VEGF treatment for choroidal neovascularization were reviewed and grouped as PNV and AMD. Groups were compared according to central foveal thickness (CFT), best corrected visual acuity (BCVA), and total injection over 12months. The correlation of beginning choroidal thickness, CFT, and BCVA with final BCVA was analyzed. Forty-seven PNV and 65 AMD cases were reviewed. Both the PNV group (p = 0.0001) and the AMD group (p = 0.003) had a significant improvement in BCVA and a significant decrease in CFT (p = 0.0001). However, BCVA was better at the 3-, 6-, and 12-month follow-up in PNV (p = 0.003, 0.002, 0.02). No significant CFT difference was observed between groups. The total number of injections was 5.7 ± 1.7 for PNV and 5.2 ± 1.5 for AMD (p = 0.09). Beginning BCVA was positively correlated with final BCVA in both groups. The PRN treatment regimen was effective for PNV and AMD in terms of visual and anatomical outcomes. Visual response was better in PNV with PRN treatment with the same number of injections.

Epidemiology of Diagnosed Age-related Macular Degeneration in Germany: An Evaluation of the Prevalence Using AOK PLUS Claims Data.

Epidemiologic data on age-related macular degeneration (AMD) are mainly based on cohort studies, including both diagnosed and undiagnosed cases. Using health claims data allows estimating epidemiological data of diagnosed subjects with AMD within the health care system using diagnosis codes from a regional claims database (AOK PLUS) to estimate the prevalence and incidence of non-exudative and exudative AMD in Germany. Patients with AMD were identified among AOK PLUS insured patients based on at least two outpatient, ophthalmologic or one inpatient H35.3 diagnoses for the years 2012 to 2021. Patients without continuous observation in a calendar year were excluded. Prevalence was assessed, and 1-year cumulative incidence was determined by the number of newly diagnosed patients divided by the number of individuals at risk. For 2020 and 2021, the AMD stage was assessed by diagnostic subcodes for non-exudative and exudative AMD, respectively. For 2012 to 2019, patient numbers were estimated based on the average proportions of non-exudative AMD and exudative AMD, respectively, in 2020 and 2021. Incidence and prevalence numbers were then extrapolated to Germany. Between 2012 to 2021, the prevalence of diagnosed AMD cases remained relatively stable among approximately 3.27 million AOK PLUS insured persons, ranging from 0.96% (minimum in 2021) to 1.31% (maximum in 2014) for non-exudative AMD, about twice as high as for exudative AMD (min-max: 0.53-0.72%). The age- and sex-adjusted projections amounted to 644,153 diagnosed non-exudative and 367,086 diagnosed German patients with exudative AMDs in 2021. The 1-year cumulative incidence for non-exudative and exudative AMD, respectively, ranged from 122,427-142,932 to 46,092-86,785 newly diagnosed cases. The number of diagnosed cases with AMD in Germany has increased slightly over the past decade. For the first time, patient counts with non-exudative and exudative AMD were approximated for Germany based on a representative, large-scale database study.

Management of Wet Age-Related Macular Degeneration: A Case Report

Introduction: Age-related macular degeneration (AMD) is a progressive neurodegenerative disease of the photoreceptors and retinal pigment epithelium (RPE). It is a leading cause of blindness and visual impairment in the elderly population, despite recent advances in treatment. We reported a case of wet AMD and its management.&#x0D; Case Presentation: A 69 years old woman complained of blurred vision, especially in the left eye, which she had experienced since 3 years ago, progressively worsen since the last 3 months. Fundoscopy and OCT examination was done. Fundoscopy found no foveal reflex with a drusen and perifoveal haemorrhage found on left eye. She was diagnosed with wet age-related macular degeneration type II of left eye. She had done intravitreal anti-VEGF injection with local anaesthesia.&#x0D; Conclusion: AMD management relies heavily on observation, lifestyle changes, frequent follow-up evaluations, early recognition of visual impairment and detection of CNV. Meanwhile, the current modality for wet AMD therapy is intravitreal anti-VEGF injection to preserve patient’s visual acuity and improve quality of life.

Identification of systemic biomarkers and potential drug targets for age-related macular degeneration.

Since age-related macular degeneration (AMD) is tightly associated with aging and cellular senescence, objective of this study was to investigate the association between plasma levels of senescence-related proteins (SRPs) and risk of AMD. The whole study was based on two-sample Mendelian randomization (MR) analysis. For MR analysis, the primary approach for MR analysis was the inverse-variance weighted (IVW) method and the heterogeneity and pleiotropy of results were tested. The instrumental single-nucleotide polymorphisms (SNPs) associated with 110 SRPs were filtered and selected from a large genome-wide association study (GWAS) for plasma proteome involving 35,559 participants. The GWAS data of AMD was obtained from FinnGen consortium (6,157 AMD cases and 288,237 controls) and further validated by using data from UK Biobank consortium (3,553 AMD cases and 147,089 controls). The MR results at both discovery and validation stages supported the causality (IVW-P < 0.00045) between plasma levels of 4 SRPs (C3b, CTNNB1, CCL1, and CCL3L1) and the risk of AMD and supported potential causality (IVW-P < 0.05) between other 10 SRPs and risk of AMD. No heterogeneity or pleiotropy in these results was detected. Our findings supported that high plasma levels of C3b, CTNNB1, CCL1, and CCL3L1 were associated with increased risk of AMD, thereby highlighting the role of systemic inflammation in AMD pathogenesis and providing the rationale for developing new preventative and therapeutic strategies.

Lifestyle factors associated with age-related macular degeneration: Case-control study.

Age-related macular degeneration (AMD) is one of the major causes of vision loss in individuals aged ≥ 65 years in developed countries. This study aimed to determine the associations between modifiable risk factors and AMD. This is the first study describing the relationship between lifestyle factors and AMD in the Czech Republic. In this cross-sectional case-control study, 93 AMD cases and 58 controls without AMD and cataract were included. All participants were examined by Optical coherence tomography at the Clinic of Eye Treatment at the University Hospital Brno. Data were collected using a pre-tested self-report questionnaire in a face-to-face interview. We found significant associations between those who were living in the city (OR 95% CI: 2.19 (1.0-4.6); p = 0,039), with a positive family history of AMD (OR 95% CI: 12.75 (1.6-98.6); p = 0,015), exposure to cigarette smoke (OR 95% CI: 2.72 (1.4-5.4); p = 0,004), and daily exposure to passive smoking (OR 95% CI: 2.29 (1.0-5.1); p = 0,045) and AMD. In men, we found significant associations between daily sunlight exposure (OR 95% CI: 2.98 (1.0-8.5); p = 0,041), short or long sleep duration (OR 95% CI: 3.98 (1.2-13.2); p = 0,024) and AMD. Men daily exposed to sunlight were at a 2.98 times higher risk of AMD than men with less than daily sunlight exposure. Men with short or long sleep duration (< 6 and > 8 h) were at a 3.98 times higher risk of AMD than men with recommended sleep duration of 6-8 h. An increased risk of AMD was observed for living in the city, family history of AMD, exposure to cigarette smoke, and daily exposure to passive smoking. Increased risk of AMD was observed for daily sunlight exposure and short or long sleep duration; however, only in men.

Associations of Socioeconomic Status Inequity with Incident Age-related Macular Degeneration in Middle-Aged and Elderly Population.

Background: The relationship between socioeconomic status (SES) inequity and incident age-related macular degeneration (AMD) remains unclear. We aim to investigate whether low SES increases the risk of AMD and to explore the effect of a healthy lifestyle on this association. Methods: This prospective cohort study included 316,663 UK Biobank individuals. SES inequity was identified via latent class analysis using education, household income, and occupational status. Healthy lifestyle score was calculated based on smoking, alcohol drinking, and physical activity (PA). Incident AMD was defined according to diagnosis records. Cox proportional hazards models were used to evaluate the relationship of low SES and AMD. Interrelationships of healthy lifestyle score on SES-AMD association were explored, including modification, mediation, and joint effects. Results: During the average 12.2 years of follow-up, 6,355 AMD cases were diagnosed. Participants with medium SES (hazard ratio: 1.10 [95% confidence interval (CI) 1.01 to 1.21]) and low SES (hazard ratio: 1.22 [95% CI 1.11 to 1.34]) had an increased risk of incident AMD compared to participants with high SES. PA significantly affected this association. Moreover, the association between low SES and AMD was significantly mediated (11.3%, 95% CI: 6.56 to 23.0) by smoking. Similarly, alcohol drinking suppressed (9.59%, 95% CI: 4.00 to 23.2) the association between high SES and AMD. Besides, a significant joint effect of SES and healthy lifestyle score was found. Conclusions: We provide further evidence for the relationship of socioeconomic inequity, healthy lifestyle, and incident AMD. Future public health strategies should aim to reduce socioeconomic inequity to prevent AMD.

Evaluation of inflammatory hyperreflective foci and plasma EPA as diagnostic and predictive markers for age-related macular degeneration.

To detect the plasma polyunsaturated fatty acids (PUFAs) concentrations in age-related macular degeneration (AMD) patients and healthy controls. Additionally, advanced studies were conducted to investigate the relationship between PUFAs concentrations and ophthalmological characteristics, including hyperreflective foci (HRF), visual acuity, and anti-vascular endothelial growth factor (anti-VEGF) response in patients with AMD. This prospective, single-site study recruited a total of 315 participants, consisting of 105 individuals with dry AMD (early-stage AMD group), 105 individuals with neovascular AMD (late-stage AMD group), and 105 elderly individuals without any fundus diseases (healthy controls). The levels of omega-3 and omega-6 PUFAs in plasma were detected using gas chromatography. Retinal thickness, choroidal thickness, and macular volume were quantified using optical coherence tomography angiography (OCTA) scan with a 6 × 6 mm macular area, and the amounts of HRF were analyzed with OCTA scanning data. Compared to the control group, AMD patients exhibited significantly lower plasma concentrations of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and alpha linolenic acid. HRF were observed in various retinal layers of AMD patients, particularly those with late-stage AMD. The correlation coefficient matrix and multiple linear regression models demonstrated that HRF played a crucial role in best corrected visual acuity for both early (p < 0.001) and late-stage AMD patients (p = 0.006), while EPA had an inverse effect on the logarithm of the minimum angle of resolution (logMAR) value in patients with early-stage AMD (p < 0.001). As compared to patients with good responses to anti-VEGF therapy, those with poor responses had significantly lower baseline logMAR (p < 0.001), central retina thickness (p = 0.002), macular volume (p = 0.027), HRF (p = 0.024), and plasma EPA (p < 0.001). This study used a ROC curve analysis to identify the combination of HRF and EPA as a potential biomarker for predicting the response to anti-VEGF treatment in late-stage AMD patients, with an area under the curve (AUC) value of 0.775. Reduced plasma EPA was detected in AMD cases and the lower EPA concentration was related to poorer visual acuity. Additionally, the quantity of HRF combined with concentration of plasma EPA may serve as the prognostic indicator for predicting the effect of anti-VEGF treatment in late-stage AMD patients.

Genetic Risk Assessment of Degenerative Eye Disease (GRADE): study protocol of a prospective assessment of polygenic risk scores to predict diagnosis of glaucoma and age-related macular degeneration

BackgroundGlaucoma and age-related macular degeneration (AMD) account for a substantial portion of global blindness. Both conditions are highly heritable, with recognised monogenic and polygenic inheritance patterns. Current screening guidelines lack decisive recommendations. Polygenic risk scores (PRS) allow for cost-effective broad population risk stratification for these conditions. The predictive potential of PRS could facilitate earlier diagnosis and treatment, and prevent unnecessary vision loss.MethodsThe Genetic Risk Assessment of Degenerative Eye disease (GRADE) study is a prospective study designed to generate high-quality evidence about the feasibility of PRS to stratify individuals from the general population, enabling identification of those at highest risk of developing glaucoma or AMD. The targeted recruitment is 1000 individuals aged over 50 years, from which blood or saliva samples will be used for genotyping and an individual PRS for glaucoma and AMD will be derived. Individuals with PRS values in the bottom decile (n = 100), top decile (n = 100) and middle 80% (n = 100) for both glaucoma and AMD will undergo a detailed eye examination for glaucoma and/or AMD.DiscussionThe primary objective will be to compare the prevalence of glaucoma and AMD cases between low, intermediate, and high PRS risk groups. We expect to find a higher prevalence of both diseases in the high PRS risk group, as compared to the middle and low risk groups. This prospective study will assess the clinical validity of a PRS for glaucoma and AMD in the general Australian population. Positive findings will support the implementation of PRS into clinical practice.

Clinical efficacy of conbercept injection on neovascular age-related macular degeneration under different levels of inflammation.

Age-related macular degeneration (AMD) is considered one of the most common causes of irreversible blindness among elderly patients. Neovascular AMD, which accounts for 10% of all AMD cases, can cause devastating vision loss due to choroidal neovascularization (CNV). The clinical effects and safety of intravitreal injection of conbercept in patients suffering from neovascular AMD have not been fully evaluated. The aim of the study was to evaluate the efficacy and safety of intravitreal injection of conbercept in patients with neovascular AMD with different levels of inflammation. A total of 120 consecutive patients with neovascular AMD who underwent intravitreal injection of conbercept (3 injections per month + pro re nata (3 + PRN)) were included and stratified based on the intraocular level of high-sensitivity C-reactive protein (hs-CRP). The level of inflammation was defined as low, medium or high, based on the concentration of hs-CRP prior to injection. Before and after conbercept injections, best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were compared, respectively. Moreover, cytokine markers as well as the frequency of injections and adverse events (AEs) were measured. There were significant differences in BCVA and CRT between low, medium and high tertiles. Compared to the baseline, improved BCVA was observed, and CRT declined significantly after operation. Adverse events were most observed in high tertiles. A significant decrease in vascular endothelial growth factor (VEGF), interleukin (IL)-6 and IL-8 was observed after 1 year. The effectiveness of conbercept on neovascular AMD varies depending on the level of inflammation, which could be achieved by administering different injection frequencies at different levels of inflammation. Furthermore, conbercept is associated with the reduction of inflammatory factor (IL-6 and IL-8) levels after intravitreal injection, which suggests that suppressing inflammatory response might contribute to the clinical efficacy of anti-VEGF treatment. Our results provide a novel mechanism for conbercept in patients with neovascular AMD.

Understanding and interpreting CNN's decision in optical coherence tomography-based AMD detection.

Automated assessment of age-related macular degeneration (AMD) using optical coherence tomography (OCT) has gained significant research attention in recent years. Though a list of convolutional neural network (CNN)-based methods has been proposed recently, methods that uncover the decision-making process of CNNs or critically interpret CNNs' decisions in the context are scant. This study aims to bridge this research gap. We independently trained several state-of-the-art CNN models, namely, VGG16, VGG19, Xception, ResNet50, InceptionResNetV2 for AMD detection and applied CNN visualization techniques, namely, Grad-CAM, Grad-CAM++, Score CAM, Faster Score CAM to highlight the regions of interest utilized by the CNNs in the context. Retinal layer segmentation methods were also developed to explore how the CNN regions of interest related to the layers of the retinal structure. Extensive experiments involving 2130 SD-OCT scans collected from Duke University were performed. Experimental analysis shows that Outer Nuclear Layer to Inner Segment Myeloid (ONL-ISM) influences the AMD detection decision heavily as evident from the normalized intersection (NI) scores. For AMD cases the obtained average NI scores were respectively 13.13%, 17.2%, 9.7%, 10.95%, and 11.31% for VGG16, VGG19, ResNet50, Xception, and Inception ResNet V2, whereas, for normal cases, these values were respectively 21.7%, 21.3%, 16.85%, 10.175% and 16%. Critical analysis reveals that the ONL-ISM is the most contributing layer in determining AMD, followed by Nerve Fiber Layer to Inner Plexiform Layer (NFL-IPL).