Age-related Macular Degeneration Severity Research Articles

Developing an image-based grading scale for peripheral drusen to investigate associations of peripheral drusen type with age-related macular degeneration

Age-related macular degeneration (AMD) is a leading cause of blindness. It is associated with peripheral drusen which has not been categorized. We investigated peripheral drusen to validate an image grading system and to understand possible associations between peripheral drusen and AMD. We collated clinical data, ultra-widefield (UWF) pseudocolor fundus images and Spectral-Domain Optical Coherence Tomography (SD-OCT) scans from consecutive retinal patients. SD-OCT scans were used to determine AMD stage. A masked retinal specialist recorded the types of peripheral drusen observed in UWF images. Eyes whose UWF images did not pass quality screening and those without AMD and peripheral drusen were excluded from the study. Statistical tests were utilized to determine the validity of our grading system and associations of peripheral drusen with AMD. A total of 481 eyes (283 subjects) were included in the study (mean age 73.1 ± 1.2years, 64.3% female). Interobserver and test–retest statistical analyses to evaluate the UWF image grading system resulted in Cohen’s Kappa 0.649 (p < 0.001) and 0.922 (p < 0.001) respectively. A total of 284 (59.0%), 28 (5.8%), 15 (3.1%), 22 (4.6%), 4 (0.8%), 39 (8.1%), and 32 (6.7%) eyes had hard, soft, reticular, cuticular, atrophic, mixed drusen, and mixed drusen and atrophy respectively in at least one peripheral retinal quadrant. Hard peripheral drusen was significantly associated with the presence of AMD (p = 0.010). Peripheral drusen types were variably seen in retinal patients with and without AMD. We validated a peripheral drusen grading system and provided an image library to assist in the identification of peripheral drusen. Our study found an association between peripheral hard drusen and an AMD diagnosis but did not find a link between peripheral drusen and severity of AMD.

Correlation between corneal endothelial layer features and age-related macular degeneration severity.

This study aimed to investigate the relationship between corneal endothelial layer features and the severity of age-related macular degeneration (AMD). The study included 119 patients, with 47 females and 72 males. Patients were categorized into four groups based on the AREDS grading system: no AMD (group 1), mild AMD (group 2), moderate AMD (group 3), and advanced AMD (group 4). Only the right eye of patients with both eyes suitable for the study was included. Corneal endothelial cell density (CD), coefficient of variation (CoV), hexagonal cell ratio (HEX), and central corneal thickness (CCT) were measured using specular microscopy (Konan Medical Inc., Nishinomiya, Japan). Group 1 had 40 patients, group 2 had 27 patients, and groups 3 and 4 had 26 patients each. Significant differences were observed between the mean endothelial CD, CoV, and HEX values among the groups, while no significant difference was found in CCT values (p = 0.049, p = 0.002, p = 0.004, and p = 0.883, respectively). A mild negative correlation was observed between AMD severity and CD and HEX values, while a mild positive correlation was found between AMD severity and CoV. Increasing severity of AMD may negatively impact corneal endothelial layer values.

Choriocapillaris Impairment, Visual Function, and Distance to Fovea in Aging and Age-Related Macular Degeneration: ALSTAR2 Baseline.

In aging and early-intermediate age-related macular degeneration (AMD), rod-mediated dark adaptation (RMDA) slows more at 5° superior than at 12°. Using optical coherence tomography angiography (OCTA), we asked whether choriocapillaris flow deficits are related to distance from the fovea. Persons ≥60years stratified for AMD via the Age-Related Eye Disease Study's nine-step system underwent RMDA testing. Two adjacent 4.4° × 4.4° choriocapillaris OCTA slabs were centered on the fovea and 12° superior. Flow signal deficits (FD%) in concentric arcs (outer radii in mm, 0.5, 1.5, 2.2, 4.0, and 5.0 superior) were correlated with rod intercept time (RIT) and best-corrected visual acuity (BCVA). In 366 eyes (170 normal, 111 early AMD, 85 intermediate AMD), FD% was significantly worse with greater AMD severity in all regions (overall P < 0.05) and poorest under the fovea (P < 0.0001). In pairwise comparisons, FD% worsened with greater AMD severity (P < 0.05) at distances <2.2mm. At greater distances, eyes with intermediate, but not early AMD differed from normal eyes. Foveal FD% was more strongly associated with longer RIT at 5° (r = 0.52) than RIT at 12° (r = 0.39) and BCVA (r = 0.21; all P < 0.0001). Choroidal thickness was weakly associated with longer RIT at 5° and 12° (r = 0.10-0.20, P < 0.05) and not associated with AMD severity. Reduced transport across the choriocapillaris-Bruch's membrane-retinal pigment epithelium complex, which contributes to drusen formation under the macula lutea (and fovea), may also reduce retinoid resupply to rods encircling the high-risk area. FD% has potential as a functionally validated imaging biomarker for AMD emergence.

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.

CLINICAL-OPHTHALMOLOGICAL INDICATORS WHICH DETERMINE THE SEVERITY OF AGE-MACULAR DEGENERATION

Background. The search for biomarkers and simple mathematical systems for predicting the severity of age-related macular degeneration (AMD) is necessary and relevant.&#x0D; Aim: to determine prognostic clinical and ophthalmological indicators that determine the severity of AMD.&#x0D; Material and methods. The study included observational data of 302 eyes (152 patients), in which the stage of AMD was determined according to the recommendations of the AREDS study. The age of the patients was 71.18 years, 59.9% were women, 40.1% were men. Visual acuity, maximum corrected visual acuity (MCVA), the number of drusen of various calibers, the presence of changes in the retinal pigment epithelium, subretinal neovascular membrane (SNM) and geographic atrophy were determined.&#x0D; Results. By age, patients with a mild course of AMD were younger than those with a severe course by 6.9 years (p&lt;0.001). Smokers accounted for 31.5% of patients, the course of AMD in such patients was more often severe – 37.2% versus 21.9% in non-smokers (p=0.006). Visual acuity and MCVA were significantly worse in patients with severe AMD (p&lt;0.001). There was no significant difference in the number of small and medium-sized drusen (p&gt;0.5). Large drusen, pigmentary changes and SNM were found almost only in patients with severe AMD. Moreover, pigmentary changes were present in almost all patients with severe AMD (92.6%), and SNM and geographic atrophy – in 23.9% and 21.8%, respectively. According to the data of the discriminant analysis, almost all indicators had a clear relationship with the course of AMD, but the F coefficient was the largest for pigmentary changes, MCVA, the number of large drusen and age. These indicators were included in the system of discriminant equations for determining the AMD severity.&#x0D; Conclusion. With the help of discriminant analysis, the indicators determining the severity of the course of AMD were found.

Quality of Life After Cataract Surgery in Patients with Age-Related Macular Degeneration: A Literature Review

Abstract&#x0D; Introduction &amp; Objectives : Age-related macular degeneration (AMD) is a common ocular disease that affects millions of people worldwide. Cataract surgery is one of the most performed surgical procedures in the world and is effective to improve visual function and quality of life (QoL) in individuals with cataracts. Both cataract and AMD are conditions that occur in late age. However, the presence of AMD may complicate the postoperative outcomes and QoL of these patients. This review aims to examine the impact of cataract surgery on the QoL of patients with AMD.&#x0D; Methods : A search of the literature was conducted using electronic databases. Studies were included if they evaluated QoL outcomes in patients with AMD who underwent cataract surgery.&#x0D; Results : The results of the review suggest that cataract surgery can improve visual acuity and QoL in patients with AMD. However, the degree of improvement is influenced by the severity of AMD. Patients with mild to moderate AMD tended to have greater improvements in QoL and visual acuity compared to those with advanced AMD. Incidentally, it is still cost effective to perform cataract surgery in patients with advanced AMD.&#x0D; Conclusion : Overall, patients with AMD who underwent cataract surgery experienced improvements in their QoL. Nevertheless, individual characteristics including severity of AMD must be considered to optimize the procedure outcomes. Further research, particularly with longer follow up times, is needed to determine the long-term effects of cataract surgery on QoL in patients with AMD.

QUALITY OF LIFE AFTER CATARACT SURGERY IN PATIENTS WITH AGE-RELATED MACULAR DEGENERATION: A LITERATURE REVIEW

Objective: Age-related macular degeneration (AMD) is a common ocular disease that affects millions of people worldwide. Cataract surgery is one of the most performed surgical procedures in the world and is effective to improve visual function and quality of life (QOL) in individuals with cataracts. Both cataract and AMD are conditions that occur in late age. However, the presence of AMD may complicate the postoperative outcomes and quality of life (QOL) of these patients. This review aims to examine the impact of cataract surgery on the QOL of patients with AMD. Methods: A search of the literature was conducted using electronic databases. Studies were included if they evaluated QOL outcomes in patients with AMD who underwent cataract surgery. Result: The results of the review suggest that cataract surgery can improve visual acuity and QOL in patients with AMD. However, the degree of improvement is influenced by the severity of AMD. Patients with mild to moderate AMD tended to have greater improvements in QOL and visual acuity compared to those with advanced AMD. Incidentally, it is still cost effective to perform cataract surgery in patients with advanced AMD. Conclusion: Overall, cataract surgery is found to be able to improve QOL and visual acuity in patients with AMD. Nevertheless, individual characteristics including severity of AMD must be considered to optimize the outcomes. Further research, particularly with longer follow up times, is needed to determine the long-term effects of cataract surgery on QOL in patients with AMD.

Predictive Performance of an Updated Polygenic Risk Score for Age-Related Macular Degeneration

ObjectiveA recent genome-wide association study of age-related macular degeneration (AMD) has identified new AMD-associated risk variants. These variants can now be incorporated into an updated polygenic risk score (PRS). This study aimed to assess the performance of an updated polygenic risk score (PRS2023) in an independent cohort of older individuals with retinal imaging data, and compare performance with an older PRS (PRS2016). DesignCross-sectional study. ParticipantsA total of 4,175 participants of European ancestry aged ≥70 years with genotype and retinal imaging data from the ASPirin in Reducing Events in the Elderly trial. MethodsWe used logistic regression models and area under the curve (AUC) to assess the performance of the PRS2023 compared with PRS2016. AMD status and severity were graded using colour fundus photography. Main Outcome MeasuresAssociation of PRS2023 and PRS2016 with AMD risk at baseline. ResultsAt enrolment among 4,175 participants, 2,605 (62.4%) had no AMD, 853 (20.4%), 671 (16.1%) and 46 (1.1%) had early, intermediate and late-stage AMD, respectively. More than 27% of the participants with a high PRS2023 (top quartile) had intermediate or late-stage AMD, compared with <15% for those in the middle two quartiles and <13% for those in the lowest quartile. Both PRS2023 and PRS2016 were significantly associated with AMD after adjustment for age, sex, smoking status and lipid levels, with increasing odds ratios (OR) for worsening AMD grades. The PRS2023 outperformed PRS2016 (DeLong test comparing AUC, P=0.03 for all AMD, P=0.03 for late AMD). PRS2023 was associated with late-stage AMD with an adjusted OR of 5.05 [3.41-7.47] per standard deviation. Assuming a population prevalence of 10% for late-stage AMD, the PRS2023 explained 42.2% of disease liability. The AUC of a model containing conventional/non-genetic risk factors and the PRS2023 was 91% [87%-95%] for predicting late-stage AMD, which improved 12% over the model without the PRS (AUC=79%, P<0.001 for difference). ConclusionsA new PRS (PRS2023) for AMD outperforms a previous PRS, and predicts increasing risk for late-stage AMD (with stronger association for more severe imaging-confirmed AMD grades). Our findings have clinical implications for the improved prediction and risk stratification of AMD.

Metabolic activity of visceral adipose tissue is associated with age-related macular degeneration: a pilot 18F-FDG PET/CT study.

Obesity is known to increase the risk and severity of age-related macular degeneration (AMD). Increased inflamed metabolic activity of visceral adipose tissue (VAT) is considered as a crucial underlying mechanism for the harmful effects of obesity. In this study, we aimed to investigate the inflamed metabolic activity of VAT with 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and their association with AMD. A total of 57 elderly participants (aged ≥ 50 years) who underwent 18F-FDG PET/CT for health screening and subsequent fundoscopic exam for complaint of recently impaired vision were enrolled. The metabolic activity of VAT was measured from the maximum standardized uptake value (SUVmax) of VAT. The early AMD participant was defined as the participant with either eye satisfying AMD and without any sign of advanced AMD (neovascular AMD or geographic atrophy). The late AMD participant was defined as the participant with either eye satisfying advanced AMD. VAT SUVmax was highest in participants with late AMD, intermediate in early AMD, and lowest in non-AMD participants. The levels of systemic inflammation surrogate markers were also highest in late AMD group. Furthermore, VAT SUVmax was positively correlated with systemic inflammation surrogate markers and independently associated with the late AMD. The metabolic activity of VAT evaluated by 18F-FDG PET/CT was associated with the severity of AMD and synchronized with the level of systemic inflammation. Thus, VAT SUVmax could be potentially employed as a surrogate marker of obesity-driven VAT inflammation associated with AMD.

Deep-learning-based automated measurement of outer retinal layer thickness for use in the assessment of age-related macular degeneration, applicable to both swept-source and spectral-domain OCT imaging.

Effective biomarkers are required for assessing the progression of age-related macular degeneration (AMD), a prevalent and progressive eye disease. This paper presents a deep learning-based automated algorithm, applicable to both swept-source OCT (SS-OCT) and spectral-domain OCT (SD-OCT) scans, for measuring outer retinal layer (ORL) thickness as a surrogate biomarker for outer retinal degeneration, e.g., photoreceptor disruption, to assess AMD progression. The algorithm was developed based on a modified TransUNet model with clinically annotated retinal features manifested in the progression of AMD. The algorithm demonstrates a high accuracy with an intersection of union (IoU) of 0.9698 in the testing dataset for segmenting ORL using both SS-OCT and SD-OCT datasets. The robustness and applicability of the algorithm are indicated by strong correlation (r = 0.9551, P < 0.0001 in the central-fovea 3 mm-circle, and r = 0.9442, P < 0.0001 in the 5 mm-circle) and agreement (the mean bias = 0.5440 um in the 3-mm circle, and 1.392 um in the 5-mm circle) of the ORL thickness measurements between SS-OCT and SD-OCT scans. Comparative analysis reveals significant differences (P < 0.0001) in ORL thickness among 80 normal eyes, 30 intermediate AMD eyes with reticular pseudodrusen, 49 intermediate AMD eyes with drusen, and 40 late AMD eyes with geographic atrophy, highlighting its potential as an independent biomarker for predicting AMD progression. The findings provide valuable insights into the ORL alterations associated with different stages of AMD and emphasize the potential of ORL thickness as a sensitive indicator of AMD severity and progression.

Vision protection therapy for prevention of neovascular age-related macular degeneration

To access the effect of vision protection therapy on neovascular conversion in age-related macular degeneration (AMD). Patient unidentified data aggregated by Vestrum Health, LLC (VH) from over 320 US retina specialists was analyzed to compare the conversion rate from dry to neovascular (wet) AMD in a practice employing VPT (VPT group) compared to those employing standard care alone (SCA group) between January 2017 through July 2023. 500,00 eyes were filtered then matched for neovascular conversion risk factors by propensity scoring and compared in a 10/1 ratio of 7370 SCA and 737 VPT treated eyes. SCA eyes had significantly fewer clinical encounters and shorter follow up than the VPT group. Despite this, the risk of neovascular conversion by PS was significantly lower in the VPT group compared to SCA (HR 5.73, p < 0.0001). Analysis matching the encounter frequency of both groups as a post-randomization variable produced a similar HR (HR 5.98, p < 0.0001). Because 9% of eyes in the VPT group were not treated with VPT due to bilateral early (low-risk) AMD, analysis comparing the SCA group to VPT-treated eyes was done that also showed significantly lower conversion rates in the VPT-treated eyes, with or without encounter frequency matching (HR 5.84, 5.65, p < 0.0001). Visual acuity was consistently better in VPT eyes compared to SCA eyes throughout the study time window. The advantage of VPT over SCA increased with increased SCA encounter frequency and higher conversion risk factors, including age and ICD10 coded dry AMD severity. Neovascular (wet) AMD is the main cause of irreversible visual loss worldwide. Consistent with two prior studies, the current study finds Vision Protection Therapy markedly more effective at both recognizing and preventing neovascular AMD than the current standard of care, benefiting the highest risk dry AMD eyes the most.

Choriocapillaris Impairment Is Associated With Delayed Rod-Mediated Dark Adaptation in Age-Related Macular Degeneration.

Progress toward treatment and prevention of age-related macular degeneration (AMD) requires imaging end points that relate to vision. We investigated choriocapillaris flow signal deficits (FD%) and visual function in eyes of individuals aged ≥60 years, with and without AMD. One eye of each participant in the baseline visit of the Alabama Study on Early Age-Related Macular Degeneration 2 (ALSTAR2; NCT04112667) was studied. AMD presence and severity was determined using the Age-Related Eye Disease Study (AREDS) grading system. FD% was quantified using macular spectral domain optical coherence tomography angiography (OCTA) scans. Vision tests included rod-mediated dark adaptation (RMDA), best-corrected visual acuity, and contrast sensitivity (photopic and mesopic), and microperimetric light sensitivity (scotopic, mesopic, and photopic). Presence of subretinal drusenoid deposits (SDD) was determined using multimodal imaging. In 410 study eyes of 410 participants (mean [SD] age = 71.7 years [5.9]), FD% was higher in early AMD (mean [SD] = 54.0% [5.5], N = 122) and intermediate AMD (59.8% [7.4], N = 92), compared to normal (52.1% [5.3], N = 196) eyes. Among visual functions evaluated, RMDA showed the strongest association with FD% (r = 0.35, P < 0.0001), followed by contrast sensitivity (r = -0.22, P < 0.0001). Eyes with SDD had worse FD% (58.3% [7.4], N = 87), compared to eyes without SDD (53.4% [6.0], N = 323, P = < 0.0001). Choriocapillaris FD% were associated with AMD severity and with impaired vision, especially RMDA. Reduced metabolic transport and exchange across the choriocapillaris-Bruch's membrane retinal pigment epithelium (RPE) complex, a causal factor for high-risk soft drusen formation, also may impair photoreceptor sustenance from the circulation. This includes retinoid resupply, essential to dynamic rod function.

Genetic Risk Score Analysis Supports a Joint View of TwoClassification Systems for Age-Related Macular Degeneration.

The purpose of this study was to evaluate the utility of combining the Clinical Classification (CC) and the Three Continent age-related macular degeneration (AMD) Consortium Severity Scale (3CACSS) for classification of AMD. In two independent cross-sectional datasets of our population-based AugUR study (Altersbezogene Untersuchungen zur Gesundheit der Universität Regensburg), we graded AMD via color fundus images applying two established classification systems (CC and 3CACSS). We calculated the genetic risk score (GRS) across 50 previously identified variants for late AMD, its association via logistic regression, and area under the curve (AUC) for each AMD stage. We analyzed 2188 persons aged 70 to 95 years. When comparing the two classification systems, we found a distinct pattern: CC "age-related changes" and CC "early AMD" distinguished individuals with 3CACSS "no AMD"; 3CACSS "mild/moderate/severe early AMD" stages, and distinguished CC "intermediate AMD". This suggested a 7-step scale combining the 2 systems: (i) "no AMD", (ii) "age-related changes", (iii) "very early AMD", (i.e. CC "early"), (iv) "mild early AMD", (v) "moderate early AMD", (vi) "severe early AMD", and (vii) "late AMD". GRS association and diagnostic accuracy increased stepwise by increased AMD severity in the 7-step scale and by increased restriction of controls (e.g. for CC "no AMD without age-related changes": AUC = 55.1%, 95% confidence interval [CI] = 51.6, 58.6, AUC = 62.3%, 95% CI=59.1, 65.6, AUC = 63.8%, 95% CI=59.3, 68.3, AUC=78.1%, 95% CI=73.6, 82.5, AUC = 82.2%, 95% CI = 78.4, 86.0, and AUC = 79.2%, 95% CI = 75.4, 83.0). A stepwise increase was also observed by increased drusen size and area. The utility of a 7-step scale is supported by our clinical and GRS data. This harmonization and full data integration provides an immediate simplification over using either CC or 3CACSS and helps to sharpen the control group.

The risk of fracture in age-related macular degeneration according to the presence of visual disability: a nationwide cohort study.

To evaluate the association between age-related macular degeneration (AMD) with or without visual disability (VD) and the risk of fracture using the National Health Insurance data in South Korea. In total, 3,894,702 individuals who had taken part in health-screening programs between January 1, 2009, and December 31, 2009, were included in the cohort and followed until December 31, 2019. The participants with VD, which could be related to the severity of AMD, were defined as those with a loss of vision or visual field defect as certified by the Korean government's Ministry of Health and Welfare. The hazard ratio was calculated for groups (control and AMD with/without VD) using the multivariable-adjusted cox regression analysis. In total, 466,890 participants (11.99%) were diagnosed with fractures during the study period. An increased risk of fracture was observed in individuals with AMD compared with the control (adjusted hazard ratio (aHR), 1.09, 95% confidence interval (CI), 1.06-1.11). Furthermore, among the AMD individuals, an increased risk of fracture was prominent in individuals with VD (aHR 1.17, 95% CI 1.08-1.27) than those without VD (aHR 1.08, 95% CI 1.06-1.11) compared with the reference group (control). AMD was associated with an increased risk of fracture even without VD. Prevention for fracture should be considered in AMD patients, especially when accompanied by VD.

Analysis of Retinol Binding Protein 4 and ABCA4 Gene Variation in Non-Neovascular Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) may be associated with ABCA4 variants and is characterized by the accumulation of visual cycle-byproduct lipofuscin. Reducing retinol-binding protein 4 (RBP4), a retinol transporter protein, may reduce lipofuscin production. This study aims to assess the associations between plasma RBP4, the ABCA4 variation, and AMD severity. Sixty-seven participants were grouped into healthy/mild AMD (n = 32) and severe AMD (n = 35) groups. The latter group was older than the former group and had higher levels of RBP4 (36.8 ± 8.3 vs. 30.4 ± 7.0 μg/mL, p = 0.0012). The ten participants with six ABCA4 linked-variants had higher RBP4 than those without (37.8 ± 7.7 vs. 32.4 ± 7.9 μg/mL; p = 0.026), and eight of them had severe AMD. Univariate analyses showed that severe AMD was related to older age (OR, 1.26; 95% CI, 1.13-1.40; p < 0.0001) and to higher RBP4 levels (OR, 1.12; 95% CI, 1.04-1.20; p = 0.003), whereas the linked ABCA4 variants had no associations. After adjustment, however, only age remained significantly associated with severe AMD. This pilot study shows a trend of higher plasma RBP4 levels in severe AMD or the ABCA4-linked variants, and further age-matched studies are warranted.

Family History of Age-Related Macular Degeneration and Genetics Predict Progression to Advanced Age-Related Macular Degeneration Adjusting for Macular Status, Demographic, and Lifestyle Factors

To determine if a family history of age-related macular degeneration (AMD) and genetic variants identify eyes at higher risk for progression to advanced AMD (AAMD), after controlling for baseline demographics, behavioral factors, and macular status. Prospective, longitudinal cohort study. Eyes were classified using the Age-Related Eye Disease Study severity scale. Non-genetic and genetic predictors for progression to AAMD, geographic atrophy, and neovascular disease were evaluated. Cox proportional hazards models using the eye as the unit of analysis were used to calculate hazard ratios (HRs), accounting for correlated data. Discrimination between progressing and non-progressing eyes was assessed using C-statistics and net reclassification improvement (NRI). Among 4910 eyes, 863 progressed to AAMD over 12 years. Baseline AMD severity scale and status of the fellow eye were important predictors; genes provided additional discrimination. A family history of AMD also independently predicted progression after accounting for genetic and other covariates: 1 family member versus none (HR 1.21 [95% confidence interval {CI} 1.02-1.43]; P=0.03); ≥2 family members versus none (HR 1.55 [95% CI 1.26-1.90]; P < 0.001). A composite risk score calculated using β estimates of both non-genetic and significant genetic factors predicted progression to AAMD (HR 5.57; 90th vs 10th percentile; area under the receiver operating characteristic curve [AUC] = 0.92), providing superior fit compared with other models, including one with only ocular variables (NRI=0.34; P < 0.001; AUC = 0.87, ΔAUC 0.05 ± 0.005; P < 0.001). Genetic variants and family history provided additional discrimination for predicting progression to AAMD, after accounting for baseline macular status and other covariates.

Increased risk of Parkinson's disease among patients with age-related macular degeneration and visual disability: A nationwide cohort study.

The association between Parkinson's disease (PD) and age-related macular degeneration (AMD) has been shown in previous reports. However, the association between the severity of AMD and PD development is unknown. We aimed to evaluate the association of AMD with/without visual disability (VD) with the risk of PD occurrence using the National Health Insurance data in South Korea. A total of 4,205,520 individuals, older than or equal to 50 years and without a previous diagnosis of PD, participated in the Korean National Health Screening Program in 2009. AMD was verified using diagnostic codes, and participants with VD were defined as those with loss of vision or visual field defect as certified by the Korean government. The participants were followed up until 31 December, 2019, and incident cases of PD were identified using registered diagnostic codes. The hazard ratio was calculated for groups (control and AMD with/without visual disability) using multivariable adjusted Cox regression analysis. In total, 37,507 participants (0.89%) were diagnosed with PD. Among individuals with AMD, the risk of PD development was higher in individuals with VD (aHR 1.35, 95% CI 1.09-1.67) than those without (aHR 1.22, 95% CI 1.15-1.30) compared with controls. Additionally, an increased risk of PD was observed in individuals with AMD compared with controls, regardless of the presence of VD (aHR 1.23, 95% CI 1.16-1.31). VD in AMD was associated with the development of PD. This suggests that neurodegeneration in PD and AMD may have common pathways.

Biologically Guided Optimization of Test Target Location for Rod-mediated Dark Adaptation in Age-related Macular Degeneration: Alabama Study on Early Age-related Macular Degeneration 2 Baseline.

We evaluate the impact of test target location in assessing rod-mediated dark adaptation (RMDA) along the transition from normal aging to intermediate age-related macular degeneration (AMD). We consider whether RMDA slows because the test locations are near mechanisms leading to or resulting from high-risk extracellular deposits. Soft drusen cluster under the fovea and extend to the inner ring of the ETDRS grid where rods are sparse. Subretinal drusenoid deposits (SDDs) appear first in the outer superior subfield of the ETDRS grid where rod photoreceptors are maximal and spread toward the fovea without covering it. Cross-sectional. Adults ≥ 60 years with normal older maculas, early AMD, or intermediate AMD as defined by the Age-Related Eye Disease Study (AREDS) 9-step and Beckman grading systems. In 1 eye per participant, RMDA was assessed at 5° and at 12° in the superior retina. Subretinal drusenoid deposit presence was identified with multi-modal imaging. Rod intercept time (RIT) as a measure of RMDA rate at 5° and 12°. In 438 eyes of 438 persons, RIT was significantly longer (i.e., RMDA is slower) at 5° than at 12° for each AMD severity group. Differences among groups were bigger at 5° than at 12°. At 5°, SDD presence was associated with longer RIT as compared to SDD absence at early and intermediate AMD but not in normal eyes. At 12°, SDD presence was associated with longer RIT in intermediate AMD only, and not in normal or early AMD eyes. Findings were similar in eyes stratified by AREDS 9-step and Beckman systems. We probed RMDA in relation to current models of deposit-driven AMD progression organized around photoreceptor topography. In eyes with SDD, slowed RMDA occurs at 5° where these deposits typically do not appear until later in AMD. Even in eyes lacking detectable SDD, RMDA at 5° is slower than at 12°. The effect at 5° may be attributed to mechanisms associated with the accumulation of soft drusen and precursors under the macula lutea throughout adulthood. These data will facilitate the design of efficient clinical trials for interventions that aim to delay AMD progression.

Does the Presence of the Cilioretinal Artery Affect the Incidence, Clinical Picture and Progression of Age-Related Macular Degeneration?

The aims of this study were to analyze the relationship between the presence of the cilioretinal artery (CRA) and the incidence, severity and progression of age-related macular degeneration (AMD) and to estimate the influence of the CRA on choroidal and retinal parameters. A total of 287 patients with AMD and 110 healthy controls were enrolled in the study. CRA occurrence was determined using color fundus images. AMD progression was assessed after 3 years. There was no difference in the incidence of CRA between the AMD and control groups (23.34% vs. 24.55%; p = 0.8). Lower-stage AMD was more frequently observed in eyes with the CRA than in eyes without the artery (p = 0.016). The CRA did not influence disease progression (p = 0.79). The CRA did not influence retinal and choroidal thickness and volume parameters or the retinal vessel caliber and functionality in either the AMD or control groups. There was no relationship between CRA presence and CFH Y402H and ARMS2 A69S risk variants. The results did not show a protective effect of the CRA on the incidence and progression of AMD. The CRA may affect the severity of AMD; however, the mechanism of this phenomenon is unclear.

Retinal Aging Transcriptome and Cellular Landscape in Association With the Progression of Age-Related Macular Degeneration.

Age is the main risk factor for age-related macular degeneration (AMD), a leading cause of blindness in the elderly, with limited therapeutic options. Here, we analyze the transcriptomic characteristics and cellular landscape of the aging retinas from controls and patients with AMD. We identify the aging genes in the neural retina, which are associated with innate immune response and inflammation. Deconvolution analysis reveals that the estimated proportions of M2 macrophages are significantly increased with both age and AMD severity. Moreover, we find that proportions of Müller glia are significantly increased only with age but not with AMD severity. Several genes associated with both age and AMD severity, particularly C1s and MR1, are strong positively correlated with the proportions of Müller glia. Our studies expand the genetic and cellular landscape of AMD and provide avenues for further studies on the relationship between age and AMD.