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Low luminance visual acuity as a clinical measure and clinical trial outcome measure: a scoping review.
Wood, LJ, Jolly, JK, Buckley, TM, Josan, AS, MacLaren, RE
Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists). 2021;(2):213-223
Abstract
PURPOSE The measurement of standard visual acuity (VA) is the most well-known part of any ophthalmic examination to indicate visual function. Despite this, it is insensitive in detecting early disease changes. Therefore, other visual function tests have been developed including low luminance VA (LLVA) and low luminance deficit (LLD). This scoping literature review aims to summarise the current published applications of LLVA and LLD assessments to evaluate their utility as clinical markers and research outcome measures in a variety of ophthalmic conditions. RECENT FINDINGS Sixty-five peer-reviewed publications were included. LLVA was pioneered for use in geographic atrophy, a subtype of age-related macular degeneration, which remains the mainstay of its clinical application. However, other studies have reported additional useful applications in inherited retinal diseases including rare maculopathies and rod-cone dystrophies. Although there are some variations in testing methodology, use of the standard Early Treatment Diabetic Retinopathy Study (ETDRS) chart with a 2.0 log unit neutral density filter is the most popular approach. The optimal testing luminance is still to be defined. SUMMARY Overall, LLVA is an earlier clinical marker of change in central retinal function than standard VA. It has been shown to be a risk factor for disease progression and a better indicator of a patient's level of everyday visual function. It is inexpensive and simple to implement using readily available standard ophthalmic equipment.
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Impact of the Natural Compound Urolithin A on Health, Disease, and Aging.
D'Amico, D, Andreux, PA, Valdés, P, Singh, A, Rinsch, C, Auwerx, J
Trends in molecular medicine. 2021;(7):687-699
Abstract
Urolithin A (UA) is a natural compound produced by gut bacteria from ingested ellagitannins (ETs) and ellagic acid (EA), complex polyphenols abundant in foods such as pomegranate, berries, and nuts. UA was discovered 40 years ago, but only recently has its impact on aging and disease been explored. UA enhances cellular health by increasing mitophagy and mitochondrial function and reducing detrimental inflammation. Several preclinical studies show how UA protects against aging and age-related conditions affecting muscle, brain, joints, and other organs. In humans, benefits of UA supplementation in the muscle are supported by recent clinical trials in elderly people. Here, we review the state of the art of UA's biology and its translational potential as a nutritional intervention in humans.
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Potential Therapeutic Benefit of NAD+ Supplementation for Glaucoma and Age-Related Macular Degeneration.
Cimaglia, G, Votruba, M, Morgan, JE, André, H, Williams, PA
Nutrients. 2020;(9)
Abstract
Glaucoma and age-related macular degeneration are leading causes of irreversible blindness worldwide with significant health and societal burdens. To date, no clinical cures are available and treatments target only the manageable symptoms and risk factors (but do not remediate the underlying pathology of the disease). Both diseases are neurodegenerative in their pathology of the retina and as such many of the events that trigger cell dysfunction, degeneration, and eventual loss are due to mitochondrial dysfunction, inflammation, and oxidative stress. Here, we critically review how a decreased bioavailability of nicotinamide adenine dinucleotide (NAD; a crucial metabolite in healthy and disease states) may underpin many of these aberrant mechanisms. We propose how exogenous sources of NAD may become a therapeutic standard for the treatment of these conditions.
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Beyond AREDS Formulations, What Is Next for Intermediate Age-Related Macular Degeneration (iAMD) Treatment? Potential Benefits of Antioxidant and Anti-inflammatory Apocarotenoids as Neuroprotectors.
Camelo, S, Latil, M, Veillet, S, Dilda, PJ, Lafont, R
Oxidative medicine and cellular longevity. 2020;:4984927
Abstract
Age-related macular degeneration (AMD) is the commonest cause of severe visual loss and blindness in developed countries among individuals aged 60 and older. AMD slowly progresses from early AMD to intermediate AMD (iAMD) and ultimately late-stage AMD. Late AMD encompasses either neovascular AMD (nAMD) or geographic atrophy (GA). nAMD is defined by choroidal neovascularization (CNV) and hemorrhage in the subretinal space at the level of the macula. This induces a rapid visual impairment caused by the death of photoreceptor cells. Intravitreal injection of anti-vascular endothelial growth factor (VEGF) antibodies is the standard treatment of nAMD but adds to the burden of patient care. GA is characterized by slowly expanding photoreceptor, and retinal pigment epithelium (RPE) degeneration patches progressively leading to blindness. There is currently no therapy to cure GA. Late AMD continues to be an unmet medical need representing a major health problem with millions of patients worldwide. Oxidative stress and inflammation are recognized as some of the main risk factors to developing late AMD. The antioxidant formulation AREDS (Age-Related Eye Disease Studies), contains β-carotene, which has been replaced by lutein and zeaxanthin in AREDS2, are given to patients with iAMD but have a limited effect on the incidence of nAMD and GA. Thus, to avoid or slowdown the development of late stages of AMD (nAMD or GA), new therapies targeting iAMD are needed such as crocetin obtained through hydrolysis of crocin, an important component of saffron (Crocus sativus L.), and norbixin derived from bixin extracted from Bixa orellana seeds. We have shown that these apocarotenoids preserved more effectively RPE cells against apoptosis following blue light exposure in the presence of A2E than lutein and zeaxanthin. In this review, we will discuss the potential use of apocarotenoids to slowdown the progression of iAMD, to reduce the incidence of both forms of late AMD.
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Dietary Patterns, Carbohydrates, and Age-Related Eye Diseases.
Francisco, SG, Smith, KM, Aragonès, G, Whitcomb, EA, Weinberg, J, Wang, X, Bejarano, E, Taylor, A, Rowan, S
Nutrients. 2020;(9)
Abstract
Over a third of older adults in the U.S. experience significant vision loss, which decreases independence and is a biomarker of decreased health span. As the global aging population is expanding, it is imperative to uncover strategies to increase health span and reduce the economic burden of this age-related disease. While there are some treatments available for age-related vision loss, such as surgical removal of cataracts, many causes of vision loss, such as dry age-related macular degeneration (AMD), remain poorly understood and no treatments are currently available. Therefore, it is necessary to better understand the factors that contribute to disease progression for age-related vision loss and to uncover methods for disease prevention. One such factor is the effect of diet on ocular diseases. There are many reviews regarding micronutrients and their effect on eye health. Here, we discuss the impact of dietary patterns on the incidence and progression of age-related eye diseases, namely AMD, cataracts, diabetic retinopathy, and glaucoma. Then, we focus on the specific role of dietary carbohydrates, first by outlining the physiological effects of carbohydrates on the body and then how these changes translate into eye and age-related ocular diseases. Finally, we discuss future directions of nutrition research as it relates to aging and vision loss, with a discussion of caloric restriction, intermittent fasting, drug interventions, and emerging randomized clinical trials. This is a rich field with the capacity to improve life quality for millions of people so they may live with clear vision for longer and avoid the high cost of vision-saving surgeries.
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Genetic Association of Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy.
Chen, LJ
Asia-Pacific journal of ophthalmology (Philadelphia, Pa.). 2020;(2):104-109
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Abstract
Age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) are leading causes of irreversible blindness among the elderly population in developed countries. Although being considered as different subtypes of a same disease, neovascular AMD and PCV have differences in clinical, epidemiological, therapeutic, and genetic profiles. Both AMD and PCV are complex diseases involving multiple genetic and environmental risk factors. Different genetic strategies have been adopted to discover associated genes and variants for neovascular AMD and PCV, including genome-wide association study (GWAS), next-generation sequencing (NGS) based sequence analysis, and candidate gene analyses. So far, a number of susceptible genes have been identified for AMD and/or PCV, such as CFH, ARMS2-HTRA1, C2-CFB-SKIV2L, C3, CETP, and FGD6. Although many of these genes are shared by AMD and PCV, some showed difference between them, such as ARMS2-HTRA1 and FGD6. Also, some of the genes showed ethnic diversities, such as the CFH p.Tyr402His variant. Further larger-scale genomic studies should be warranted to identify more susceptibility genes for AMD and, in particular, PCV among different populations, and differentiate the genetic architectures between neovascular AMD and PCV.
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NOD-like Receptors in the Eye: Uncovering Its Role in Diabetic Retinopathy.
Lim, RR, Wieser, ME, Ganga, RR, Barathi, VA, Lakshminarayanan, R, Mohan, RR, Hainsworth, DP, Chaurasia, SS
International journal of molecular sciences. 2020;(3)
Abstract
Diabetic retinopathy (DR) is an ocular complication of diabetes mellitus (DM). International Diabetic Federations (IDF) estimates up to 629 million people with DM by the year 2045 worldwide. Nearly 50% of DM patients will show evidence of diabetic-related eye problems. Therapeutic interventions for DR are limited and mostly involve surgical intervention at the late-stages of the disease. The lack of early-stage diagnostic tools and therapies, especially in DR, demands a better understanding of the biological processes involved in the etiology of disease progression. The recent surge in literature associated with NOD-like receptors (NLRs) has gained massive attraction due to their involvement in mediating the innate immune response and perpetuating inflammatory pathways, a central phenomenon found in the pathogenesis of ocular diseases including DR. The NLR family of receptors are expressed in different eye tissues during pathological conditions suggesting their potential roles in dry eye, ocular infection, retinal ischemia, cataract, glaucoma, age-related macular degeneration (AMD), diabetic macular edema (DME) and DR. Our group is interested in studying the critical early components involved in the immune cell infiltration and inflammatory pathways involved in the progression of DR. Recently, we reported that NLRP3 inflammasome might play a pivotal role in the pathogenesis of DR. This comprehensive review summarizes the findings of NLRs expression in the ocular tissues with special emphasis on its presence in the retinal microglia and DR pathogenesis.
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[Safety management of the treatment with antimalarial drugs in rheumatology. Interdisciplinary recommendations based on a systematic literature search].
Fiehn, C, Ness, T, Weseloh, C, Specker, C, Hadjiski, D, Detert, J, Krüger, K, ,
Zeitschrift fur Rheumatologie. 2020;(2):186-194
Abstract
BACKGROUND Antimalarial medication (AM) plays an important role in the treatment of rheumatic diseases. OBJECTIVE Updated evidence-based recommendations on the safety management of rheumatological treatment with AM are presented. METHODS A systematic literature search in the databases Medline (PubMed) and Cochrane identified 1160 studies on the safety of treatment with AM in rheumatology. In addition, a manual search was carried out and 67 publications considered to be particularly relevant by the authors were analyzed in more detail. These publications served as a basis for consensus-based recommendations. RESULTS Treatment with AM in rheumatology should be carried out with hydroxychloroquine (HCQ) with a dosage not exceeding 5 mg/kg body weight/day. Patients should undergo a basic ophthalmological examination within the first 6 months of AM treatment. Pre-existing maculopathy, renal insufficiency (glomerular filtration rate, GFR <60 ml/min), tamoxifen comedication, a daily dose of >5 mg/kg HCQ or treatment with chloroquine (CQ) show an increased risk for AM-induced retinopathy. These patients should undergo an annual ophthalmological check from the beginning of the treatment, whereas patients with no risk factors are recommended to start this only after 5 years of taking the medication. The ophthalmological examination should comprise at least both an appropriate subjective and an objective method and these are usually an automated visual field test and optical coherence tomography (OCT). A visual field test revealing a parafoveal sensitivity loss and an OCT showing a parafoveal circumscribed loss of the photoreceptor layer or focal interruptions of the structural line of the outer segment are signs of a possible AM retinopathy. Determination of creatine kinase (CK) and lactate dehydrogenase (LDH) in blood is appropriate to screen for cardiomyopathy and myopathy and should be checked before starting the treatment and then ca. every 3 months. The use of cardiac biomarkers, such as brain natriuretic peptide (BNP) or troponin in serum, electrocardiograph (ECG) or cardiac imaging should be considered depending on the situation. An intake of HCQ is safe during pregnancy and breastfeeding according to the current state of knowledge and is protective for mother and child in patients with systemic lupus erythematosus. CONCLUSION The updated recommendations on AM treatment in rheumatology in particular include a more rigorous measuring of doses, risk stratification in monitoring and defined ophthalmological examination methods to detect a possible retinopathy.
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The value of nutritional supplements in treating Age-Related Macular Degeneration: a review of the literature.
Mukhtar, S, Ambati, BK
International ophthalmology. 2019;(12):2975-2983
Abstract
PURPOSE To describe and evaluate the value of nutritional supplements in the management of age-related macular degeneration (AMD) through a review of the current literature. METHODS An extensive literature search was performed, and key research articles exploring AREDS and AREDS-2 formulations, genetics, omega fatty acids, calcium and folic acid in high-risk women were reviewed. PubMed and Web of Science databases were used for generating articles to review. RESULTS The AREDS and AREDS-2 trials, while difficult to validate, show support for antioxidant supplementation in reducing AMD progression in Caucasian populations. While genetic guided personalized medicine has been studied mainly with complement factor H and age-related maculopathy susceptibility 2 risk alleles, the data have not been reproducible. Women at a higher risk of cardiovascular disease may benefit from antioxidant therapies in preventing AMD. Omega 3 fatty acid supplementation has been widely supported through observational studies; however, randomized controlled trials have not shown benefit in disease progression. Calcium exposure has been linked to increased mechanisms in cell death and may be detrimental to older individuals with AMD. CONCLUSION The data regarding nutritional supplements in preventing AMD progression are inconclusive, and therefore recommendations should be based on risk factors and demographic data.
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An evidence-based approach to the routine use of optical coherence tomography.
Ly, A, Phu, J, Katalinic, P, Kalloniatis, M
Clinical & experimental optometry. 2019;(3):242-259
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Abstract
Optical coherence tomography is an imaging technology that has revolutionised the detection, assessment and management of ocular disease. It is now a mainstream technology in clinical practice and is performed by non-specialised personnel in some settings. This article provides a clinical perspective on the implications of that movement and describes best practice using multimodal imaging and an evidence-based approach. Practical, illustrative guides on the interpretation of optical coherence tomography are provided for three major diseases of the ocular fundus, in which optical coherence tomography is often crucial to management: age-related macular degeneration, diabetic retinopathy and glaucoma. Topics discussed include: cross-sectional and longitudinal signs in ocular disease, so-called 'red-green' disease whereby clinicians rely on machine/statistical comparisons for diagnosis in managing treatment-naïve patients, and the utility of optical coherence tomography angiography and machine learning.