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Optical Coherence Tomography (Angiography) Biomarkers in the Assessment and Monitoring of Diabetic Macular Edema.
Suciu, CI, Suciu, VI, Nicoara, SD
Journal of diabetes research. 2020;:6655021
Abstract
Retinopathy is one of the most severe diabetes-related complications, and macular edema is the major cause of central vision loss in patients with diabetes mellitus. Significant progress has been made in recent years in optical coherence tomography and angiography technology. At the same time, various parameters have been attributed the role of biomarkers creating the frame for new monitoring and treatment strategies and offering new insights into the pathogenesis of diabetic retinopathy and diabetic macular edema. In this review, we gathered the results of studies that investigated various specific OCT (angiography) parameters in diabetic macular edema, such as central subfoveal thickness (CST), cube average thickness (CAT), cube volume (CV), choroidal thickness (CT), retinal nerve fiber layer (RNFL), retinal thickness at the fovea (RTF), subfoveal choroidal thickness (SFCT), central macular thickness (CMT), choroidal vascularity index (CVI), total macular volume (TMV), central choroid thickness (CCT), photoreceptor outer segment (PROS), perfused capillary density (PCD), foveal avascular zone (FAZ), subfoveal neuroretinal detachment (SND), hyperreflective foci (HF), disorganization of the inner retinal layers (DRIL), ellipsoid zone (EZ), inner segment/outer segment (IS/OS) junctions, vascular density (VD), deep capillary plexus (DCP), and superficial capillary plexus (SCP), in order to provide a synthesis of biomarkers that are currently used for the early diagnosis, assessment, monitoring, and outlining of prognosis.
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Risk factors for progression of age-related macular degeneration.
Heesterbeek, TJ, Lorés-Motta, L, Hoyng, CB, Lechanteur, YTE, den Hollander, AI
Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists). 2020;(2):140-170
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Abstract
PURPOSE Age-related macular degeneration (AMD) is a degenerative disease of the macula, often leading to progressive vision loss. The rate of disease progression can vary among individuals and has been associated with multiple risk factors. In this review, we provide an overview of the current literature investigating phenotypic, demographic, environmental, genetic, and molecular risk factors, and propose the most consistently identified risk factors for disease progression in AMD based on these studies. Finally, we describe the potential use of these risk factors for personalised healthcare. RECENT FINDINGS While phenotypic risk factors such as drusen and pigment abnormalities become more important to predict disease progression during the course of the disease, demographic, environmental, genetic and molecular risk factors are more valuable at earlier disease stages. Demographic and environmental risk factors such as age and smoking are consistently reported to be related to disease progression, while other factors such as sex, body mass index (BMI) and education are less often associated. Of all known AMD variants, variants that are most consistently reported with disease progression are rs10922109 and rs570618 in CFH, rs116503776 in C2/CFB/SKIV2L, rs3750846 in ARMS2/HTRA1 and rs2230199 in C3. However, it seems likely that other AMD variants also contribute to disease progression but to a lesser extent. Rare variants have probably a large effect on disease progression in highly affected families. Furthermore, current prediction models do not include molecular risk factors, while these factors can be measured accurately in the blood. Possible promising molecular risk factors are High-Density Lipoprotein Cholesterol (HDL-C), Docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), zeaxanthin and lutein. SUMMARY Phenotypic, demographic, environmental, genetic and molecular risk factors can be combined in prediction models to predict disease progression, but the selection of the proper risk factors for personalised risk prediction will differ among individuals and is dependent on their current disease stage. Future prediction models should include a wider set of genetic variants to determine the genetic risk more accurately, and rare variants should be taken into account in highly affected families. In addition, adding molecular factors in prediction models may lead to preventive strategies and personalised advice.
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Mechanisms enhancing the protective functions of macular xanthophylls in the retina during oxidative stress.
Widomska, J, Subczynski, WK
Experimental eye research. 2019;:238-246
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Macular xanthophylls (MXs) are distinguished from other dietary carotenoids by their high membrane solubility and preferential transmembrane orientation. Additionally, these properties enhance the chemical and physical stability of MXs in the eye retina, and maximize their protective activities. The effectiveness of MXs' protection is also enhanced by their selective accumulation in the most vulnerable domains of retinal membranes. The retina is protected by MXs mainly through blue-light filtration, quenching of the excited triplet states of potent photosensitizers, and physical quenching of singlet oxygen. To perform these physical, photo-related actions, the structure of MXs should remain intact. However, the conjugated double-bond structure of MXs makes them highly chemically reactive and susceptible to oxidation. Chemical quenching of singlet oxygen and scavenging of free radicals destroy their intact structure and consume MXs. Consequently, their physical actions, which are critical to the protection of retina, are diminished. Thus, it is timely and important to identify mechanisms whereby the chemical destruction (bleaching) of MXs in retinal membranes can be reduced. It was shown that nitroxide free radicals (spin labels) located in membranes protect MXs against destruction, and their effect is especially pronounced during the light-induced formation of singlet oxygen. That should extend and enhance their positive action in the retina through physical processes. In this review, we will discuss possible applications of this new strategy during ophthalmological procedures, which can cause acute bleaching of MXs and damage the retina through oxidative processes.
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Asian age-related macular degeneration: from basic science research perspective.
Yanagi, Y, Foo, VHX, Yoshida, A
Eye (London, England). 2019;(1):34-49
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In Asian populations, polypoidal choroidal vasculopathy (PCV), a distinct phenotype of neovascular age-related macular degeneration (AMD), is more prevalent than Caucasians. Recently, there has been significant focus on how PCV differs from typical AMD. Although typical AMD and PCV share a variety of mechanisms by which abnormal angiogenic process occurs at the retinochoroidal interface, PCV has different clinical characteristics such as aneurysm-like dilation at the terminal of choroidal neovascular membranes, less frequent drusen and inner choroidal degeneration due to the thickened choroid. Recent studies support an important role for inflammation, angiogenesis molecules and lipid metabolism in the pathogenesis of neovascular AMD. Furthermore, although less attention has been paid to the role of the choroid in AMD, accumulating evidence suggests that the choriocapillaris and choroid also play a pivotal role in drusenogenesis, typical AMD and PCV. This review discusses the basic pathogenic mechanisms of AMD and explores the difference between typical AMD and PCV.
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Antecedents of Soft Drusen, the Specific Deposits of Age-Related Macular Degeneration, in the Biology of Human Macula.
Curcio, CA
Investigative ophthalmology & visual science. 2018;(4):AMD182-AMD194
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AMD pathobiology was irreversibly changed by the recent discovery of extracellular cholesterol-containing deposits in the subretinal space, between the photoreceptors and retinal pigment epithelium (RPE), called subretinal drusenoid deposits (SDDs). SDDs strikingly mirror the topography of rod photoreceptors in human macula, raising the question of whether an equivalent process results in a deposition related to foveal cones. Herein we propose that AMD's pathognomonic lesion-soft drusen and basal linear deposit (BLinD, same material, diffusely distributed)-is the leading candidate. Epidemiologic, clinical, and histologic data suggest that these deposits are most abundant in the central macula, under the fovea. Strong evidence presented in a companion article supports the idea that the dominant ultrastructural component is large apolipoprotein B,E-containing lipoproteins, constitutively secreted by RPE. Lipoprotein fatty acids are dominated by linoleate (implicating diet) rather than docosahexaenoate (implicating photoreceptors); we seek within the retina cellular relationships and dietary drivers to explain soft druse topography. The delivery of xanthophyll pigments to highly evolved and numerous Müller cells in the human fovea, through RPE, is one strong candidate, because Müller cells are the main reservoir of these pigments, which replenish from diet. We propose that the evolution of neuroglial relations and xanthophyll delivery that underlie exquisite human foveal vision came with a price, that is, soft drusen and sequela, long after our reproductive years.
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Retinal complications of gout: a case report and review of the literature.
Jiang, Y, Brenner, JE, Foster, WJ
BMC ophthalmology. 2018;(1):11
Abstract
BACKGROUND There have been few reported findings of posterior segment complications of gout. While exudative lesions, an increased risk of macular degeneration, and vascular occlusions have been previously reported, to our knowledge, refractile macular lesions have not been reported in a patient with chronic uncontrolled gout. CASE PRESENTATION Highly refractile, crystal-like lesions were found in the macula of a 62 year old male patient with chronically uncontrolled gout. The lesions appeared at the termination of retinal arterioles and were located at the level of the retinal pigment epithelium. The lesions did not stain with fluorescein and were associated with larger areas geographic atrophy. Review of the patient's blood tests revealed well-controlled vasculopathic risk factors. Fundus appearance and best-corrected visual acuity remained stable over 12 months of follow-up during which the uric acid levels were well controlled. CONCLUSION Retinopathy may be associated with chronically uncontrolled gout and patients with visual complaints should undergo a dilated examination in addition to the typical anterior segment slit-lamp exam.
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On the relationship between visual acuity and central retinal (macular) thickness after interventions for macular oedema in diabetics: a review.
Bong, A, Doughty, MJ, Button, NF, Mansfield, DC
Clinical & experimental optometry. 2016;(6):491-497
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PURPOSE The aim was to compare efficacy of treatments for diabetic macular oedema (DMO) from changes in visual acuity (VA) and central macular thickness (CMT). METHODS Peer-reviewed articles from 2004 to 2014 reporting intravitreal injections of bevacizumab (IVB), ranibizumab (IVR) or triamcinolone acetonide (IVTA) or laser photocoagulation therapy (LPT) provided data on pre-treatment (baseline) and final outcome measures. Net changes and relative changes (percentage) were assessed by linear regression analyses. RESULTS From 88 data sets the overall net change of VA was -0.10 ± 0.12 logMAR (mean ± standard deviation), being -0.13 ± 0.11 logMAR for IVB, 0 ± 0.08 logMAR for IVR and -0.12 ± 0.08 logMAR for IVTA as compared to 0.01 ± 0.14 logMAR for LPT. For CMT, the overall net change was -103 ± 71 microns, being -108 ± 64 microns for IVB, -182 ± 73 microns for IVR, and -102 ± 57 microns for IVTA and was -49 ± 60 microns for LPT. Overall, modest correlations were found between the absolute central retinal (macular) thickness change and the VA change, and the relative changes in these measures (p < 0.001, r = 0.522 or 0.457). The predicted visual outcome from a 100 microns reduction in CMT was -0.083 logMAR units, an effect not substantially influenced by the CMT measurement method. CONCLUSIONS Pharmacological treatment of DMO can be expected to result in a predictable decrease in CMT with an accompanying increase in VA, with the overall outcome being better than laser treatment.
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[Macular pigments].
Canovas, R, Cypel, M, Farah, ME, Belfort, R
Arquivos brasileiros de oftalmologia. 2009;(6):839-44
Abstract
Lutein and Zeaxanthin are yellow pigments located at the macula. Because of your location macular pigments decrease and filter the amount of blue light that reach photoreceptors, protect the outer retina from oxidative stress and may improve the vision quality. This is a review regarding incorporation mechanism, function and knowledge update.
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Resonance Raman detection of carotenoid antioxidants in living human tissue.
Ermakov, IV, Sharifzadeh, M, Ermakova, M, Gellermann, W
Journal of biomedical optics. 2005;(6):064028
Abstract
Increasing evidence points to the beneficial effects of carotenoid antioxidants in the human body. Several studies, for example, support the protective role of lutein and zeaxanthin in the prevention of age-related eye diseases. If present in high concentrations in the macular region of the retina, lutein and zeaxanthin provide pigmentation in this most light sensitive retinal spot, and as a result of light filtering and/or antioxidant action, delay the onset of macular degeneration with increasing age. Other carotenoids, such as lycopene and beta-carotene, play an important role as well in the protection of skin from UV and short-wavelength visible radiation. Lutein and lycopene may also have protective function for cardiovascular health, and lycopene may play a role in the prevention of prostate cancer. Motivated by the growing importance of carotenoids in health and disease, and recognizing the lack of any accepted noninvasive technology for the detection of carotenoids in living human tissue, we explore resonance Raman spectroscopy as a novel approach for noninvasive, laser optical carotenoid detection. We review the main results achieved recently with the Raman detection approach. Initially we applied the method to the detection of macular carotenoid pigments, and more recently to the detection of carotenoids in human skin and mucosal tissues. Using skin carotenoid Raman instruments, we measure the carotenoid response from the stratum corneum layer of the palm of the hand for a population of 1375 subjects and develop a portable skin Raman scanner for field studies. These experiments reveal that carotenoids are a good indicator of antioxidant status. They show that people with high oxidative stress, like smokers, and subjects with high sunlight exposure, in general, have reduced skin carotenoid levels, independent of their dietary carotenoid consumption. We find the Raman technique to be precise, specific, sensitive, and well suitable for clinical as well as field studies. The noninvasive laser technique may become a useful method for the correlation between tissue carotenoid levels and risk for malignancies or other degenerative diseases associated with oxidative stress.
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Noninvasive detection of macular pigments in the human eye.
Gellermann, W, Bernstein, PS
Journal of biomedical optics. 2004;(1):75-85
Abstract
There is currently strong interest in developing noninvasive technologies for the detection of macular carotenoid pigments in the human eye. These pigments, consisting of lutein and zeaxanthin, are taken up from the diet and are thought to play an important role in the prevention of age-related macular degeneration, the leading cause of blindness in the elderly in the Western world. It may be possible to prevent or delay the onset of this debilitating disease with suitable dietary intervention strategies. We review the most commonly used detection techniques based on heterochromatic flicker photometry, fundus reflectometry, and autofluorescense techniques and put them in perspective with recently developed more molecule-specific Raman detection methods.