Association of Human Plasma Metabolomics with Delayed Dark Adaptation in Age-Related Macular Degeneration

The purpose of this study was to analyze the association between plasma metabolite levels and dark adaptation (DA) in age-related macular degeneration (AMD). This was a cross-sectional study including patients with AMD (early, intermediate, and late) and control subjects older than 50 years without any vitreoretinal disease. Fasting blood samples were collected and used for metabolomic profiling with ultra-performance liquid chromatography–mass spectrometry (LC-MS). Patients were also tested with the AdaptDx (MacuLogix, Middletown, PA, USA) DA extended protocol (20 min). Two measures of dark adaptation were calculated and used: rod-intercept time (RIT) and area under the dark adaptation curve (AUDAC). Associations between dark adaption and metabolite levels were tested using multilevel mixed-effects linear modelling, adjusting for age, gender, body mass index (BMI), smoking, race, AMD stage, and Age-Related Eye Disease Study (AREDS) formulation supplementation. We included a total of 71 subjects: 53 with AMD (13 early AMD, 31 intermediate AMD, and 9 late AMD) and 18 controls. Our results revealed that fatty acid-related lipids and amino acids related to glutamate and leucine, isoleucine and valine metabolism were associated with RIT (p < 0.01). Similar results were found when AUDAC was used as the outcome. Fatty acid-related lipids and amino acids are associated with DA, thus suggesting that oxidative stress and mitochondrial dysfunction likely play a role in AMD and visual impairment in this condition.

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Patient Use of Dietary Supplements, Home Monitoring, or Genetic Testing for Nonneovascular Age-Related Macular Degeneration

Journal of VitreoRetinal Diseases ◽

10.1177/2474126421989228 ◽

2021 ◽

pp. 247412642198922

Author(s):

Brittany C. Tsou ◽

T.Y. Alvin Liu ◽

Jun Kong ◽

Susan B. Bressler ◽

J. Fernando Arevalo ◽

...

Keyword(s):

Genetic Testing ◽

Macular Degeneration ◽

Dietary Supplements ◽

Home Monitoring ◽

Cross Sectional Study ◽

Age Related Macular Degeneration ◽

Cross Sectional ◽

Supplement Use ◽

Age Related ◽

Disease Study

Purpose: This work evaluated the use and type of dietary supplements and home monitoring for nonneovascular age-related macular degeneration (AMD), as well as the prevalence of genetic testing among patients with AMD. Methods: A cross-sectional study was conducted of 129 participants older than 50 years who completed self-administered questionnaires regarding usage and type of dietary supplements and home monitoring, as well as the participants’ use of genetic testing for AMD. Results: Of 91 participants with AMD, 83 (91.2%) took vitamins, including 55 (60.4%) who used an Age-Related Eye Disease Study (AREDS) or AREDS2 formulation. Of 38 without AMD, 31 (81.6%) took vitamins (difference from participants with AMD = 9.6% [95% CI, 0%-23.2%]), including 2 on an AREDS formulation. Among 82 participants with AMD who were AREDS candidates (intermediate or advanced AMD in 1 or both eyes), 51 (62.2%; 95% CI, 51.7%-72.7%) took an AREDS or AREDS2 formulation, and 31 (37.8%) did not (5 were unsure). Additionally, 50 (61.0%; 95% CI, 50.4%-71.6%) AREDS candidates did some type of home monitoring. Only 1 (1.2%; 95% CI, 0%-3.6%) underwent genetic testing for AMD. Among 9 with AMD who were not AREDS candidates, 4 (44.4%) used an AREDS formulation, 4 (44.4%) did not, and 1 (11.1%) was unsure; only 1 (11.1%) of these 9 performed home monitoring. Conclusions: Despite similar results from past surveys and AREDS2 data supporting supplement use in 2013 and home monitoring in 2014, these findings suggest about one-third of AREDS candidates do not do so, providing further support for improving education regarding appropriate supplement and home monitoring usage. Genetic testing for AMD also appears infrequent.

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Cross-sectional study of the association between age-related macular degeneration and arthritis in the National Health and Nutrition Examination Survey 2005–2008

BMJ Open ◽

10.1136/bmjopen-2019-035805 ◽

2020 ◽

Vol 10 (12) ◽

pp. e035805

Author(s):

Zhuoting Zhu ◽

Huan Liao ◽

Sen Liu ◽

Jian Zhang ◽

Yifan Chen ◽

...

Keyword(s):

Macular Degeneration ◽

National Health ◽

Logistic Models ◽

Cross Sectional Study ◽

Age Related Macular Degeneration ◽

Nutrition Examination Survey ◽

Sectional Study ◽

Cross Sectional ◽

Health And Nutrition ◽

Age Related

ObjectiveTo explore the association between age-related macular degeneration (AMD) and arthritis in a representative sample of the US population.DesignPopulation-based, cross-sectional study.SettingThe National Health and Nutrition Examination Survey (NHANES) 2005–2008.ParticipantsA total of 4813 participants aged 40 years and older with available information on AMD and arthritis in the 2005–2008 NHANES.MethodsThe status and types of arthritis were obtained from questionnaires. Non-mydriatic fundus photographs were collected. The types of AMD were assessed using the modified Wisconsin Age-Related Maculopathy Grading Classification Scheme. The association between arthritis and AMD was evaluated using logistic regression models.ResultsAfter adjusting for covariates, participants with any or early AMD had significantly lower odds of having any type of arthritis (any AMD: OR=0.56, 95% CI: 0.36–0.86; early AMD: OR=0.55, 95% CI: 0.34–0.88) or osteoarthritis (OA) (any AMD: OR=0.43, 95% CI: 0.26–0.71; early AMD: OR=0.44, 95% CI: 0.25–0.76) compared with those without AMD. When considering AMD as the outcome, significant negative associations were also found between any arthritis or OA and any (any arthritis: OR=0.64, 95% CI: 0.43–0.94; OA: OR=0.52, 95% CI: 0.33–0.82) or early AMD (any arthritis: OR=0.61, 95% CI: 0.40–0.93; OA: OR=0.51, 95% CI: 0.31–0.86) in the multivariable logistic models. There was no significant association between different types of arthritis and late AMD.ConclusionsPeople with arthritis, especially those with OA, were less likely to have AMD compared with those without arthritis and vice versa. Further studies are needed to confirm this potential protective effect of arthritis and/or arthritis treatment on AMD and to explore the underlying mechanisms.

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Prevalence and characteristics of macular atrophy in eyes with neovascular age-related macular degeneration. A study from a long-term observational dataset: the Fight Retinal Blindness! project

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2019-315055 ◽

2019 ◽

Vol 104 (8) ◽

pp. 1064-1069

Author(s):

Vincent Daien ◽

Vuong Nguyen ◽

Rohan W Essex ◽

Robin Guymer ◽

Jennifer J Arnold ◽

...

Keyword(s):

Risk Factors ◽

Macular Degeneration ◽

Cross Sectional Study ◽

Age Related Macular Degeneration ◽

Vegf Inhibitors ◽

Cross Sectional ◽

Macular Atrophy ◽

Anti Vegf ◽

Age Related ◽

History Of

BackgroundTo assess the prevalence and characteristics associated with macular atrophy (MA) in eyes with neovascular age-related macular degeneration (nAMD) treated with vascular endothelial growth factor (VEGF) inhibitors.MethodsThis was a retrospective, cross-sectional study of nAMD eyes that commenced anti-VEGF between January 2006 and August 2016. MA (absent/extrafoveal/subfoveal) was graded by treating practitioners based on multimodal imaging from April 2016. The prevalence of MA over time and risk factors of MA were assessed.ResultsThe prevalence of MA in a cohort of 1689 eyes was 9.9% (22/222) in eyes within 1 year of starting treatment, 41.5% (71/171) after 5 years and 48.4% (30/62) after 9 years of treatment. Risk factors for subfoveal MA included the proportion of visits at which the lesion was graded as inactive ((adjusted OR (AOR) 3.72 for the highest vs lowest the quartile of frequency of inactive gradings (95% CI 2.33 to 6.07)), age (AOR 1.05 per year (95% CI 1.02 to 1.07)), baseline visual acuity (AOR 3.9 for ≤35 letters vs ≥70 letters (95% CI 2.4 to 6.4)) and the number of injections received (AOR 1.20 every 10 injections (95% CI 1.08 to 1.33)). Similar associations were observed with extrafoveal MA.ConclusionsThe risk of MA appeared to drop in eyes that had not developed it within 5 years. Low choroidal neovascularisation activity was by far the strongest predictor. We could not determine whether the increased prevalence of MA with time was due to anti-VEGF treatment or the natural history of the condition.

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Causes of low vision and use of optical aids in the elderly

Revista do Hospital das Clínicas ◽

10.1590/s0041-87812004000400001 ◽

2004 ◽

Vol 59 (4) ◽

pp. 157-160 ◽

Cited By ~ 5

Author(s):

Keila Monteiro de Carvalho ◽

Gelse Beatriz Martins Monteiro ◽

Cassiano Rodrigues Isaac ◽

Lineu Oto Shiroma ◽

Marcela Scabello Amaral

Keyword(s):

Macular Degeneration ◽

Elderly Population ◽

Low Vision ◽

The Elderly ◽

Cross Sectional Study ◽

Age Related Macular Degeneration ◽

Rehabilitation Service ◽

Visual Rehabilitation ◽

Cross Sectional ◽

Age Related

PURPOSE: To determine the causes of low vision in an elderly population attended by a university visual rehabilitation service and to check for the use of prescribed optical aids. METHOD: A cross-sectional study was carried out on patients aged 60 years or over attending for the first time a university low vision service in 2001. Ophthalmic reevaluation and interview were performed by means of a structured questionnaire in 2002. RESULTS: The sample comprised 50 subjects aged between 60 and 90 years. Severe low vision (<FONT FACE=Symbol><</FONT>20/200) was present in 68.0% of patients. The main cause of low vision was age-related macular degeneration (44.0%). Regarding literacy, 16.0% were illiterate and 72.0% had completed fundamental schooling. Thirty-one patients (62.0%) had been prescribed optical aids; 54.8% of these patients stated that they use them. A majority (70.6%) held a favorable opinion of these aids. CONCLUSIONS: The main cause of low vision was age-related macular degeneration. Approximately half of those receiving prescriptions reported actually using the aids in their daily activities. Making best use of residual vision in the elderly population with visual impairment is a priority, given the social context, if the independence necessary for enhanced quality of life is to be achieved.

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A Pattern of Age-related Macular Degeneration

Journal of Nepal Medical Association ◽

10.31729/jnma.184 ◽

2009 ◽

Vol 48 (175) ◽

Cited By ~ 1

Author(s):

Suprada Pokhrel ◽

O K Malla ◽

C L Pradhananga ◽

S N Joshi

Keyword(s):

Macular Degeneration ◽

College Teaching ◽

Female Gender ◽

Cross Sectional Study ◽

Age Related Macular Degeneration ◽

Cross Sectional ◽

Medical College ◽

Age Related ◽

Increased Risk ◽

Number Of Individuals

Introduction: Age related macular degeneration is a disorder of the macula most often clinicallyapparent affecting central vision and is one of the leading causes of blindness in the populationabove 50 years. The aim of this study is to determine clinical profi le of AMD in Nepalese presentingto a Teaching Hospital in Kathmandu.Methods: It was a hospital-based cross-sectional study. The subjects included in the study were thosepresenting to the Ophthalmology department of Kathmandu Medical College Teaching Hospitalfrom July 2007- Dec 2007.The total number of individuals included in the study were 402 and totalnumber of eyes were 804.Results: AMD was observed in 5.2% out of 402 subjects of 40 years and above age group withprevalence increasing with age. The prevalence of AMD was 0.7% within 40-50 years of age-groupindividuals increasing to 2.6% in 51-60 years, 6.5% in 61-70 years and to 19.3% among subjectsabove 71 years. This study revealed that the prevalence of AMD in females was higher with femalepreponderance in ratio of 2.5:1. 52.5 % AMD subjects in our study had visual impairment with 6/24-6/60 vision and 15% had vision <3/60-PL. Our study revealed statistically signifi cant increased riskfor AMD with aging (p=0.00). Increased risk was observed in female gender and diabetics though theOdds ratio (OR) was statistically insignifi cant (p=>0.01).Conclusions: Prevalence of AMD in Nepalese presenting to Kathmandu Medical College TeachingHospital was 5% with female preponderance in ratio of 2.5:1. Aging showed statistically signifi cantincreased risk for AMD development in this study.Key Words: Age-related macular degeneration, blindness, Nepalese, prevalence

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Percentage of Foveal versus Total Macular Geographic Atrophy as a Predictor of Visual Acuity in Age-related Macular Degeneration

10.1101/544254 ◽

2019 ◽

Author(s):

Saghar Bagheri ◽

Ines Lains ◽

Rebecca Silverman ◽

Ivana Kim ◽

Dean Eliott ◽

...

Keyword(s):

Visual Acuity ◽

Macular Degeneration ◽

Fundus Autofluorescence ◽

Cross Sectional Study ◽

Geographic Atrophy ◽

Age Related Macular Degeneration ◽

Cross Sectional ◽

Age Related ◽

The Impact ◽

Foveal Sparing

AbstractObjectivesTo investigate the relationship between visual acuity (VA), total area of geographic atrophy (GA) and percentage of foveal GA.MethodsMulticenter, retrospective cross-sectional study of patients with GA due to age-related macular degeneration. Demographics, VA, fundus autofluorescence (FAF) and optical coherence tomography (OCT) images were collected. Using FAF images aided by OCT, foveal sparing status, GA pattern, total GA size, and percentage of GA covering the foveal area - area within a 1.5 mm diameter circle centered on the fovea centralis - were assessed. Univariable and multiple linear regression analyses were performed.Results54 eyes (mean age 78.7 ±7.7 (SD), 60.0% female) were studied. Mean VA was 0.8 ± 0.6 logMAR, mean total GA 8.8 ± 6.7 mm2 and mean percentage of foveal GA was 71.5 ± 30.9%. Of all assessed eyes, 48.2% (n = 26) presented with multifocal GA, and 18.5% (n = 10) had foveal sparing. Multiple regression analysis revealed that, controlling for age and GA pattern, the percentage of foveal GA presented a statistically significant association with VA (ß = 0.41, P = 0.004). No significant associations were observed with mean total GA size, while controlling for the same variables (ß = 0.010, P = 0.440).ConclusionPercentage of foveal GA was significantly associated with VA impairment, while the same was not verified for total GA area. These findings suggest that percentage of foveal GA may represent a more useful tool for assessing the impact of GA on VA. Further validation is needed in larger cohorts.

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Cross-sectional study of the association between cataract surgery and age-related macular degeneration in the era of phacoemulsification in the national health and nutrition examination survey 2005–2008

BMJ Open ◽

10.1136/bmjopen-2019-032745 ◽

2020 ◽

Vol 10 (9) ◽

pp. e032745

Author(s):

Zhuoting Zhu ◽

Wei Wang ◽

Huan Liao ◽

Stuart Keel ◽

Jian Zhang ◽

...

Keyword(s):

Cataract Surgery ◽

Macular Degeneration ◽

National Health ◽

Cross Sectional Study ◽

Age Related Macular Degeneration ◽

Nutrition Examination Survey ◽

Sectional Study ◽

Cross Sectional ◽

Health And Nutrition ◽

Age Related

ObjectiveTo determine the association between cataract surgery and age-related macular degeneration (AMD) in a representative US sample.DesignPopulation-based, cross-sectional study.SettingThe US National Health and Nutrition Examination Survey 2005–2008.ParticipantsA total of 5401 participants aged ≥40 years had information in cataract surgery status and gradable retinal photographs for right eyes.MethodsCataract surgery status was obtained from questionnaire. Non-mydriatic fundus photographs were collected and AMD status was assessed. The associations between AMD and cataract surgery were evaluated in right eyes using logistic regression models.ResultsOf 338 right eyes with any AMD, 107 right eyes (28.9%) had cataract surgery. After adjusting for multiple variables, there were significant associations between cataract surgery and any AMD (OR 1.36; 95% CI 1.03 to 1.81) or late AMD (OR 2.48; 95% CI 1.01 to 6.09). No significant association was found between cataract surgery and early AMD after adjusting for multiple covariates (OR 1.20; 95% CI 0.91 to 1.59).ConclusionOur results suggest that cataract surgery is associated with the presence of AMD, particularly for late AMD. Longitudinal studies investigating the risk and progression of AMD after cataract surgery are needed in the era of phacoemulsification.

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Serum levels of ARMS2, COL8A1, RAD51B, and VEGF and their correlations in Age-Related Macular Degeneration

Current Neurovascular Research ◽

10.2174/1567202618666210531130711 ◽

2021 ◽

Vol 18 ◽

Author(s):

Priya Battu ◽

Kaushal Sharma ◽

Manjari Rain ◽

Ramandeep Singh ◽

Akshay Anand

Keyword(s):

Macular Degeneration ◽

Serum Levels ◽

Cross Sectional Study ◽

Statistical Correlation ◽

Age Related Macular Degeneration ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Cross Sectional ◽

Age Related ◽

Study Results

Background: Many factors including genetic and environmental are responsible for the incidence of age-related macular degeneration (AMD). However, its pathogenesis has not been clearly elucidated yet. Objective: This study aimed to estimate the Age-Related Maculopathy Susceptibility 2 (ARMS2), Collagen type VIII Alpha 1 chain (COL8A1), Rad 51 paralog(RAD51B), and Vascular Endothelial Growth Factor (VEGF) protein levels in serum of AMD and control participants and to further investigate their correlation to understand AMD pathogenesis. Methods: For this cross-sectional study, 31 healthy control and 57 AMD patients were recruited from Advanced Eye Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India. A blood sample was taken and serum was isolated from it. ELISA(enzyme-linked immunosorbent assay)was used for the estimation of proteins in the serum of patients. Results: ARMS2 and COL8A1 levels were significantly elevated in the AMD group than in the control group. The highest levels of ARMS2, COL8A1, and VEGF proteins were recorded for the wet AMD sub-group. The study results endorsed significant positive correlation between these following molecules; ARMS2 and COL8A1 (r=0.933, p<0.0001), ARMS2 and RAD51B (r=0.704, p<0.0001), ARMS2 and VEGF (r=0.925, p<0.0001), COL8A1 and RAD51B (r=0.736, p<0.0001), COL8A1 and VEGF (r=0.879, p<0.0001),and RAD51B and VEGF (r=0.691, p<0.0001). Conclusion: The ARMS2 and COL8A1 levels were significantly higher and RAD51B was significantly lower in the AMD group than controls. Also, a significant statistical correlation was detected between these molecules, indicating that their interaction may be involved in the pathogenesis of AMD.

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Investigation of time to first presentation and extrahospital factors in the treatment of neovascular age-related macular degeneration: a retrospective cross-sectional study

BMJ Open ◽

10.1136/bmjopen-2017-017771 ◽

2017 ◽

Vol 7 (12) ◽

pp. e017771 ◽

Cited By ~ 6

Author(s):

Peng Yong Sim ◽

Sonul Gajree ◽

Baljean Dhillon ◽

Shyamanga Borooah

Keyword(s):

Primary Care ◽

Macular Degeneration ◽

Symptom Onset ◽

Secondary Care ◽

Cross Sectional Study ◽

Age Related Macular Degeneration ◽

Sectional Study ◽

Cross Sectional ◽

Clinic Appointment ◽

Age Related

ObjectivesTo assess the time from symptom onset to treatment for neovascular age-related macular degeneration (nvAMD) and to measure the awareness of AMD in Southeast Scotland.DesignRetrospective cross-sectional study.SettingSecondary care, Southeast of Scotland.MethodsPatients treated with intravitreal therapy (IVT) for nvAMD in Southeast Scotland between 2013 and 2015 were identified using a treatment register. Notes were retrospectively reviewed. We measured time from: (A) symptom onset to first presentation at primary care, (B) referral to ophthalmic clinic appointment and (C) ophthalmic clinic appointment to first IVT treatment. To investigate AMD awareness, we performed a cluster random sample survey of patients visiting non-AMD ophthalmic clinics using a previously validated 12-item questionnaire.Results195 patients (mean age 78 years) were included in the study. The mean delays between the different stages—A, B and C—were 54.2 (95% CI ±13), 28.2 (95% CI ±4.0) and 31.5 (95% CI ±3.6) days, respectively. There was an additional mean delay of 7.5 (95% CI ±1.6) days when patients were indirectly referred by optometrists via general practitioners (P<0.05). 140 patients (mean age 78) participated in the awareness survey; 62.1% reported being ‘aware’ of AMD but only 37.3% described AMD symptoms correctly.ConclusionsThere was a significant delay at every step of the nvAMD care pathway. The causes for this were multifactorial and included delays in first presentation to a healthcare provider, referral from primary care and initiation of secondary care treatment. Our data are likely to underestimate prehospital delays as a large number of cases are likely to have undefined symptoms and onset. We also identified suboptimal awareness of AMD which could account for a substantial delay in presentation from symptom onset. These findings highlight the need to address AMD awareness and the need for urgent treatment to prevent avoidable vision loss resulting from nvAMD.

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