Age-related Macular Degeneration In Order Research Articles

Retinal neurodegeneration in age-related macular degeneration.

Age-related macular degeneration (AMD) is a complex and multifactorial disease characterized by the damage of the unit comprised of the photoreceptors, retinal pigment epithelium (RPE), Bruch's membrane, and choriocapillaris. Although the outer retina appears to be mainly affected in this disorder, several evidences exhibit that also the inner retina may be impaired. In this review we will provide a description of the prominent histologic and imaging findings suggesting an inner retinal loss in these eyes. In details, structural optical coherence tomography (OCT) technology proved either the inner and outer retina is impacted by AMD and that these two impairments are associated. Therefore, the purpose of this review is to provide a description of the role of neurodegeneration in AMD in order to better understand the relationship between neuronal loss and the outer retinal damage in this disease.

Age-related macular degeneration and diabetic eye lesion. Socio-economic aspects

Diabetic retinopathy (DR) and age-related macular degeneration (AMD) comprise a significant socio-medical problem for Russia. The article presents an analysis aimed at identifying the prerequisites for further research on the socio-economic consequences of retinal pathology. Studying the epidemiological aspects of DR and AMD, as well as the conditions for receiving medical aid helped define the main approaches to assessing the economic burden of retinal diseases in Russia. It also revealed the problems associated with completeness of registration and accounting of patients, the disparity between the volume of medical aid required and funding, and between the required and provided assistance for patients with these pathologies in clinical practice. Analysis of the disease cost will allow not only to determine the socio-economic consequences of retinal diseases, but also to find further directions for improving the quality of medical care for patients with DR and AMD in order to reduce its economic cost for the state and society. Evidently, there is a need for comprehensive assessment of the total burden of retinal diseases in Russia that would serve as a basis for subsequent assessment of the economic effectiveness of prevention and treatment measures.

Optical coherence tomography angiography in age-related macular degeneration: The game changer.

Optical coherence tomography angiography is one of the biggest advances in ophthalmic imaging. It enables a depth-resolved assessment of the retinal and choroidal blood flow, far exceeding the levels of detail commonly obtained with dye angiographies. One of the first applications of optical coherence tomography angiography was in detecting the presence of choroidal neovascularization in age-related macular degeneration and establishing its position in relation to the retinal pigmented epithelium and Bruch's membrane, and thereby classifying the CNV as type 1, type 2, type 3, or mixed lesions. Optical coherence tomography angiograms, due to the longer wavelength used by optical coherence tomography, showed a more distinct choroidal neovascularization vascular pattern than fluorescein angiography, since there is less suffering from light scattering or is less obscured by overlying subretinal hemorrhages or exudation. Qualitative and quantitative assessments of optical coherence tomography angiography findings in exudative and nonexudative age-related macular degeneration have been largely investigated within the past 3 years both in clinical and experimental settings. This review constitutes an up-to-date of all the potential applications of optical coherence tomography angiography in age-related macular degeneration in order to better understand how to translate its theoretical usefulness into the current clinical practice.

Pharmacological therapy of age-related macular degeneration based on etiopathogenesis

It is of great therapeutic significance that disordered function of the vascular endothelium which supply the affected ocular structures plays a major role in the pathogenesis and development of age-related macular degeneration. Chronic inflammation is closely linked to diseases associated with endothelial dysfunction, and age-related macular degeneration is accompanied by a general inflammatory response. According to current concept, age-related macular degeneration is a local manifestation of systemic vascular disease. This recognition could have therapeutic implications because restoration of endothelial dysfunction can restabilize the condition of chronic vascular disease including age-related macular degeneration as well. Restoration of endothelial dysfunction by pharmaacological or non pharmacological interventions may prevent the development or improve endothelial dysfunction, which result in prevention or improvement of age related macular degeneration as well. Medicines including inhibitors of the renin-angiotensin system (converting enzyme inhibitors, angiotensin-receptor blockers and renin inhibitors), statins, acetylsalicylic acid, trimetazidin, third generation beta-blockers, peroxisome proliferator-activated receptor gamma agonists, folate, vitamin D, melatonin, advanced glycation end-product crosslink breaker alagebrium, endothelin-receptor antagonist bosentan, coenzyme Q10; "causal" antioxidant vitamins, N-acetyl-cysteine, resveratrol, L-arginine, serotonin receptor agonists, tumor necrosis factor-alpha blockers, specific inhibitor of the complement alternative pathway, curcumin and doxycyclin all have beneficial effects on endothelial dysfunction. Restoration of endothelial dysfunction can restabilize chronic vascular disease including age-related macular degeneration as well. Considering that the human vascular system is consubstantial, medicines listed above should be given to patients (1) who have no macular degeneration but have risk factors for the disease and are older than 50 years; (2) who have been diagnosed with unilateral age-related macular degeneration in order to prevent damage of the contralateral eye; (3) who have bilateral age-related macular degeneration in order to avert deterioration and in the hope of a potential improvement. However, randomised prospective clinical trials are still needed to elucidate the potential role of these drug treatments in the prevention and treatment of age-related macular degeneration.

Pharmacogenetics and nutritional supplementation in age-related macular degeneration.

The Age-Related Eye Disease Study (AREDS) recommended treatment with antioxidants plus zinc in patients with intermediate or advanced age-related macular degeneration in order to reduce progression risks. Recent pharmacogenetic studies have reported differences in treatment outcomes with respect to variants in genes for CFH and ARMS2, although the treatment recommendations based on these differences are controversial. Different retrospective analyses of subsets of patients from the same AREDS trial have drawn different conclusions. The practicing clinician, who is not an expert on genetics, clinical trial design, or statistical analysis, may be uncertain how to interpret these results. Based on the balance of the available literature, we suggest not changing established practice recommendations until additional evidence from clinical trials becomes available.

Modeling the risk of age-related macular degeneration and its predictive comparisons in a population in South India

Background: Objective of current study was to develop and cross-validate the prediction models for Age-related Macular Degeneration (AMD) by using Logistic Regression (LR) and Artificial Neural Networks (ANN). Methods: A population based cross-sectional epidemiologic study. The data (n=3723) were analyzed on participants aged ≥40 years in Andhra Pradesh, South India. Sub-population data from this sample was drawn by using random under sampling and random over sampling techniques to derive a risk score from the LR model. The models were compared for their predictive abilities by an Area under the Receiver Operating Characteristic Curve (AUROC). Results: The LR risk score was built with a score ranging from 0 to 60 for a sub-population dataset (n=213). A cut-off score of ≥30 had a sensitivity of 79% and a specificity of 69%. The predictive performance of ANN and LR was statistically equivalent (76% vs. 78%; P = 0.624). Both the models were stable and consistently obtained the same predictive accuracies in a 30-fold split-sample cross validation. Conclusions: The sensitivity analysis of the ANN model indicated the relative importance of prioritizing modifiable risk factors for AMD in order to base preventive interventions to reduce the impact of the modifiable factors on AMD.

Analysis of complement factor H Y402H, LOC387715, HTRA1 polymorphisms and ApoE alleles with susceptibility to age‐related macular degeneration in Hungarian patients

Recent studies strongly support the role of genetic factors in the aetiology of age-related macular degeneration (AMD). We investigated the frequency of Tyr402His polymorphism of the complement factor H (CFH) gene, Ser69Ala polymorphism at LOC387715, rs11200638 polymorphism of the HTRA1 gene and different apolipoprotein E (ApoE) alleles in Hungarian patients with AMD in order to determine the disease risk conferred by these factors. In a case-control study, we performed clinical and molecular genetic examination of 105 AMD patients (48 patients in the early and 57 in the late subgroup) and 95 unrelated healthy controls. Detailed patient histories were recorded with the use of a questionnaire focusing on known risk factors for AMD. In the early AMD subgroup, homozygous CFH, LOC387715 or HTRA1 polymorphisms conferred a 4.9-fold (95% confidence interval [CI] 1.7-14.2), 7.4-fold (95% CI 2.1-26.2) or 10.1-fold (95% CI 2.5-40.8) risk of disease, respectively. In the late AMD subgroup, carriers of two CFH, LOC387715 or HTRA1 risk alleles were at 10.7-fold (95% CI 3.7-31.0), 11.3-fold (95% CI 3.2-40.4) or 13.5-fold (95% CI 3.3-55.4) greater disease risk, respectively. Two CFH and one LOC387715 risk alleles in combination conferred a 15.0-fold (95% CI 3.2-71.0) increase in risk, whereas two LOC387715 risk alleles combined with one CFH risk allele was associated with a 14.0-fold (95% CI 2.1-95.1) increased risk for late AMD. ApoE alleles neither increased disease risk nor proved to be protective. The CFH, LOC387715 and HTRA1 polymorphisms are strongly associated with the development of AMD in the Hungarian population. The association is particularly pronounced when homozygous risk alleles are present and in the late stages of the disease.

The Association of Lipoprotein Parameters and C-Reactive Protein in Patients with Age-Related Macular Degeneration

Background: Age-related macular degeneration (AMD) is the most common cause of visual impairment in individuals over 50 years of age, with the prevalence of 0.05% before the age of 50 rising to 30% after 74 years of age. An elevated concentration of plasma lipoproteins is considered to be one of the risk factors of AMD development. The aim of our study was to analyze the concentration of serum lipoproteins – total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), non-LDL cholesterol and triglycerides – as well as apolipoproteins – apoA1, apoB and Lp(a) – along with C-reactive protein (CRP) in patients with AMD in order to explore the possible association of lipid and inflammatory parameters with the pathogenesis of AMD. Material and Methods: In the cross-sectional study in the University clinical setting, 79 patients with AMD, aged 71.47 ± 7.02 years, and 84 aged-matched control subjects were included. The patients underwent complete ophthalmological examination including visual acuity assessment, color fundus photography and fluorescein angiography. Results: Statistical processing data revealed significantly higher total (p = 0.0002), LDL (p = 0.023), non-HDL cholesterol (p = 0.0014) and CRP (p = 0.049) values in AMD patients compared to control subjects. Conclusions: Based on the obtained results, it may be concluded that lipid status disorder and inflammation could play an important role in the development of AMD in elderly people.

064 Bis OCT spectral domain versus OCT Stratus dans l’évaluation de la morphologie de la macula dans la DMLA humide

A new generation of OCT technology was recently introduced and is currently in clinical use. These devices, called Spectral- or Fourier-domain OCT use a spectrometer able to sample more than 20,000 A-scans and, therefore, collect far more data than is possible using the Time-domain system. The Spectral -domain OCT technique offers better axial resolution (5 micron). The aim of this study is to compare the agreement between Spectral-domain OCT and Stratus-domain OCT to evaluate macular morphology in wet age-related macular degeneration in order to decide the treatment timing. We considered seventy-seven randomly chosen consecutive eyes of 77 patients with wet age-related macular degeneration. Inclusion criteria were patients with primary or recurring subfoveal CNV secondary to AMD, including those with predominantly classic, minimally classic or occult lesions with no classic component. All patients underwent OCT examination using Zeiss Stratus OCT 3 and Opko/OTI SLO/OCT Spectral-domain System. During every examination we evaluated the presence of pigment epithelium detachment, sensory retina serous detachment, cystoids macular edema, epiretinal membrane, inner limiting membrane thickening and exudates. Levels of agreement between the two evaluations were quantified by Kappa measures of agreement. Agreement in the evaluation of macular morphology between Spectral-domain OCT and Stratus-domain OCT is strongly dependent on the parameter measured. Substantial agreement was found in the evaluation of sensory retina serous detachment; moderate agreement was found in the evaluation of epiretinal membrane; slight agreement was found in the evaluation of cystoids macular edema, pigment epithelium detachment, inner limiting membrane thickening and exudates. The new Spectral OCTs allow a better evaluation of macular morphologhy of wet age-related macular degeneration.

Use of intravitreal injection of triamcinolone acetonide in the treatment of age-related macular degeneration

Age-related macular degeneration (AMD) is now considered an important and leading cause of blindness among elderly patients in developed and developing countries. AMD has two forms, dry and wet; both can lead to visual loss. However, occurrence of subfoveal choroidal neovascular (CNV) membrane in the wet form results in severe visual impairment. Treatment options for choroidal neovascularization are available in order to maintain and in some cases improve vision. Photodynamic therapy (PDT) has been used to treat both classic and occult membranes. It has known to cause choroidal hypoperfusion and production of vascular endothelial growth factor. Intravitreal steroid can possibly reduce the damage caused due to these undesirable effects. In the recent past, intravitreal injection of triamcinolone acetonide (IVTA) has been used extensively as an adjunct to PDT in AMD in order to reduce the number of PDT sessions and evaluate possible beneficial effects on vision. This article reviews the pharmacological attributes of triamcinolone, available evidence of its use as monotherapy or combination therapy to treat AMD, ocular side-effects thereof and ongoing clinical trials on IVTA.

Visual acuity and structural findings in old age-related macular degeneration

Although exudative age-related macular degeneration (AMD) leads to a substantial visual loss in most patients there is still significant variation in the end- stage visual acuity level. We analysed lesions in eyes with long-standing AMD in order to find contributing factors for this variation. Sixty-one out of 121 patients examined for exudative AMD and still alive 4.8-9.2 (mean 6.8) years after the acute phase were re-examined. The lesion size, area of subretinal fibrosis, geographic atrophy, presence of a persistent exudative process, and shortest distance to normal looking retina were measured from digital fundus photographs taken at the re-examination and correlated with visual acuity. Lesion size, the presence of a continuing exudative process, or subretinal fibrosis were independent predictors for poor vision. Better vision in the other eye was connected with poor vision in the affected study eye. In addition to lesion size, the presence of a continuing exudative process and subretinal fibrosis also have deleterious effects on long-term visual acuity after exudative AMD.