The genetics of age-related macular degeneration (AMD)--Novel targets for designing treatment options?

PubMed

Grassmann, Felix; Fauser, Sascha; Weber, Bernhard H F

2015-09-01

Age-related macular degeneration (AMD) is a progressive disease of the central retina and the main cause of legal blindness in industrialized countries. Risk to develop the disease is conferred by both individual as well as genetic factors with the latter being increasingly deciphered over the last decade. Therapeutically, striking advances have been made for the treatment of the neovascular form of late stage AMD while for the late stage atrophic form of the disease, which accounts for almost half of the visually impaired, there is currently no effective therapy on the market. This review highlights our current knowledge on the genetic architecture of early and late stage AMD and explores its potential for the discovery of novel, target-guided treatment options. We reflect on current clinical and experimental therapies for all forms of AMD and specifically note a persisting lack of efficacy for treatment in atrophic AMD. We further explore the current insight in AMD-associated genes and pathways and critically question whether this knowledge is suited to design novel treatment options. Specifically, we point out that known genetic factors associated with AMD govern the risk to develop disease and thus may not play a role in its severity or progression. Treatments based on such knowledge appear appropriate rather for prevention than treatment of manifest disease. As a consequence, future research in AMD needs to be greatly focused on approaches relevant to the patients and their medical needs. Copyright © 2015 Elsevier B.V. All rights reserved.

Nutritional modulation of age-related macular degeneration

USDA-ARS?s Scientific Manuscript database

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly worldwide. It affects 30-50 million individuals and clinical hallmarks of AMD are observed in at least one third of persons over the age of 75 in industrialized countries (Gehrs et al., 2006). Costs associated wi...

Awareness, Knowledge, and Concern about Age-Related Macular Degeneration

ERIC Educational Resources Information Center

Cimarolli, Verena R.; Laban-Baker, Allie; Hamilton, Wanda S.; Stuen, Cynthia

2012-01-01

Age-related macular degeneration (AMD)--a common eye disease causing vision loss--can be detected early through regular eye-health examinations, and measures can be taken to prevent visual decline. Getting eye examinations requires certain levels of awareness, knowledge, and concern related to AMD. However, little is known about AMD-related…

Complement pathway biomarkers and age-related macular degeneration

PubMed Central

Gemenetzi, M; Lotery, A J

2016-01-01

In the age-related macular degeneration (AMD) ‘inflammation model', local inflammation plus complement activation contributes to the pathogenesis and progression of the disease. Multiple genetic associations have now been established correlating the risk of development or progression of AMD. Stratifying patients by their AMD genetic profile may facilitate future AMD therapeutic trials resulting in meaningful clinical trial end points with smaller sample sizes and study duration. PMID:26493033

Role of the vitreous in age-related macular degeneration.

PubMed

Ondeş, F; Yilmaz, G; Acar, M A; Unlü, N; Kocaoğlan, H; Arsan, A K

2000-01-01

To investigate the relationship between posterior vitreous detachment (PVD) and age-related macular degeneration (AMD). The condition of the vitreous was examined by slit-lamp funduscopy and ultrasonography in 93 eyes of 50 patients with AMD (exudative or dry) and 100 eyes of 50 controls. There was complete PVD in 31 of the 93 eyes (33.3%) of 50 patients with AMD and the posterior vitreous was attached in 62 of these eyes (66.6%). In the control group, in 50 eyes (50%) of 50 subjects there was posterior vitreous detachment. The prevalence of PVD in eyes with macular degeneration was significantly lower (P < .05). There was no statistically significant difference between the exudative and the nonexudative groups in respect to PVD. PVD may have a protective role against the development of AMD. Chronic vitreomacular traction and/or continuous exposure to free radicals and cytokines may possibly be one of the causes of AMD in eyes with attached vitreous.

Identification of Age-Related Macular Degeneration Using OCT Images

NASA Astrophysics Data System (ADS)

Arabi, Punal M., Dr; Krishna, Nanditha; Ashwini, V.; Prathibha, H. M.

2018-02-01

Age-related Macular Degeneration is the most leading retinal disease in the recent years. Macular degeneration occurs when the central portion of the retina, called macula deteriorates. As the deterioration occurs with the age, it is commonly referred as Age-related Macular Degeneration. This disease can be visualized by several imaging modalities such as Fundus imaging technique, Optical Coherence Tomography (OCT) technique and many other. Optical Coherence Tomography is the widely used technique for screening the Age-related Macular Degeneration disease, because it has an ability to detect the very minute changes in the retina. The Healthy and AMD affected OCT images are classified by extracting the Retinal Pigmented Epithelium (RPE) layer of the images using the image processing technique. The extracted layer is sampled, the no. of white pixels in each of the sample is counted and the mean value of the no. of pixels is calculated. The average mean value is calculated for both the Healthy and the AMD affected images and a threshold value is fixed and a decision rule is framed to classify the images of interest. The proposed method showed an accuracy of 75%.

Orientation Discrimination with Macular Changes Associated with Early AMD

PubMed Central

Bedell, Harold E.; Tong, Jianliang; Woo, Stanley Y.; House, Jon R.; Nguyen, Tammy

2010-01-01

Purpose Age-related macular degeneration (AMD) is a condition that progressively reduces central vision in elderly individuals, resulting in a reduced capacity to perform many daily activities and a diminished quality of life. Recent studies identified clinical treatments that can slow or reverse the progression of exudative (wet) AMD and ongoing research is evaluating earlier interventions. Because early diagnosis is critical for an optimal outcome, the goal of this study is to assess psychophysical orientation discrimination for randomly positioned short line segments as a potential indicator of subtle macular changes in eyes with early AMD. Methods Orientation discrimination was measured in a sample of 74 eyes of patients aged 47 to 82 years old, none of which had intermediate or advanced AMD. Amsler-grid testing was performed as well. A masked examiner graded each eye as level 0, 1, 2, or 3 on a streamlined version of the Age-Related Eye Disease Study (AREDS) scale for AMD, based on the presence and extent of macular drusen or retinal pigment epithelium (RPE) changes. Visual acuity in the 74 eyes ranged from 20/15 to 20/40+1, with no significant differences among the grading levels. Humphrey 10–2 and Nidek MP-1 micro-perimetry were used to assess retinal sensitivity at test locations 1° from the locus of fixation. Results Average orientation-discrimination thresholds increased systematically from 7.4° to 11.3° according to the level of macular changes. In contrast, only 3 of 74 eyes exhibited abnormalities on the Amsler grid and central-field perimetric defects occurred with approximately equal probability at all grading levels. Conclusions In contrast to Amsler grid and central-visual-field testing, psychophysical orientation discrimination has the capability to distinguish between eyes with and without subtle age-related macular changes. PMID:19319009

Development of Age-Related Macular Degeneration (AMD) in the Fellow Eye of Patients with AMD Treated by Treat-and-Extend Intravitreal Therapy with Aflibercept.

PubMed

Mimura, Kensuke; Matsumoto, Hidetaka; Morimoto, Masahiro; Akiyama, Hideo

2018-01-01

To evaluate the development of neovascular age-related macular degeneration (nAMD) in the fellow eye in patients with unilateral nAMD treated by a treat-and-extend (TAE) regimen with intravitreal aflibercept injections. We retrospectively studied 104 patients with treatment-naïve unilateral nAMD. We assessed best-corrected visual acuity (BCVA) and exudative changes in the treated eyes and development of nAMD in the fellow eye for 2 years. The subjects included 46 patients with typical AMD (tAMD), 44 with polypoidal choroidal vasculopathy (PCV), and 14 with retinal angiomatous proliferation (RAP). BCVA was significantly improved after the loading phase in all subtypes. Forty-six patients (44.2%) had no recurrence within 2 years after the loading phase, including 12 (26.1%) with tAMD, 23 (52.2%) with PCV, and 11 (78.6%) with RAP (p < 0.01). Eleven patients (10.6%) developed nAMD in the fellow eye within 2 years, including 4 (8.7%) with tAMD, 0 (0%) with PCV, and 7 (50.0%) with RAP (p < 0.001). Patients with RAP had significantly more frequent development of nAMD in the fellow eye compared to other subtypes, while they showed significantly less recurrence during the TAE regimen with intravitreal aflibercept injections. Development of nAMD in the fellow eye should be monitored in RAP when the injection interval is extended. © 2017 S. Karger AG, Basel.

Generation of Transplantable Retinal Pigmented Epithelial (RPE) Cells for Treatment of Age-Related Macular Degeneration (AMD).

PubMed

Surendran, Harshini; Rathod, Reena J; Pal, Rajarshi

2018-06-13

Age-related macular degeneration (AMD) is the foremost cause of blindness in people over the age of 60 worldwide. Clinically, this disease starts with distortion in central vision eventually leading to legal blindness. Vision loss has a significant impact on quality of life and incurs a substantial cost to the economy. Furthermore, AMD is a complex and progressive neurodegenerative disorder that triggers visual impairment due to the loss of retinal pigmented epithelium (RPE) and the light-sensitive photoreceptors that they support, protect and provide nutrition. Currently, there is no curative treatment for the most common form of this disease, i.e., dry AMD. A novel approach to treat AMD involves the transplantation of RPE cells derived from human induced pluripotent stem cells (iPSCs) in the outer retina. These iPSC-derived RPE cells not only show characteristics similar to native RPE but also could replace as well as regenerate damaged pathologic RPE and produce supportive growth factors and cytokines. Several clinical trials are being conducted taking advantage of a variety of cell- and tissue engineering-based approaches. Here, we present a simple, cost effective, and scalable cell-culture model for generation of purified RPE thus providing the foundation for developing an allogeneic cell therapy for AMD.

Introduction to the issue regarding research regarding age related macular degeneration

USDA-ARS?s Scientific Manuscript database

Blindness is the second greatest fear among the elderly. Age-related macular degeneration (AMD) is the leading cause of vision loss among the elderly in most industrialized nations. AMD first compromises central high acuity vision. Subsequently, all vision may be lost. AMD is a progressive retinal d...

The macular degeneration and aging study: Design and research protocol of a randomized trial for a psychosocial intervention with macular degeneration patients.

PubMed

Sörensen, Silvia; White, Katherine; Mak, Wingyun; Zanibbi, Katherine; Tang, Wan; O'Hearn, Amanda; Hegel, Mark T

2015-05-01

Age-related Macular Degeneration (AMD) is the leading cause of irreversible and predictable blindness among older adults with serious physical and mental health consequences. Visual impairment is associated with negative future outlook and depression and has serious consequences for older adults' quality of life and, by way of depression, on long-term survival. Psychosocial interventions have the potential to alleviate and prevent depression symptoms among older AMD patients. We describe the protocol of the Macular Degeneration and Aging Study, a randomized clinical trial of a psychosocial Preventive Problem-Solving Intervention. The intervention is aimed at enhancing well-being and future planning among older adults with macular degeneration by increasing preparation for future care. Adequate randomization and therapeutic fidelity were achieved. Current retention rates were acceptable, given the vulnerability of the population. Acceptability (adherence and satisfaction) was high. Given the high public health significance and impact on quality of life among older adults with vision loss, this protocol contributes a valid test of a promising intervention for maintaining mental and physical health in this population. Copyright © 2015 Elsevier Inc. All rights reserved.

[Macular choroidal blood flow in concurrent age-related macular degeneration and primary open-angle glaucoma].

PubMed

Panova, I E; Ermak, E M; Shaimova, T A; Shaimova, V A

2016-01-01

Ocular circulation disorders are an important factor in the development of primary open-angle glaucoma (POAG) and age-related macular degeneration (AMD). To date, however, there have been no studies on choroidal blood flow peculiarities in case of concurrent AMD and POAG. to determine distinctive features of choroidal blood flow characteristic of concurrent AMD and POAG and to assess their role in disease pathogenesis. Macular choroidal blood flow, including blood supply, was assessed in 54 patients (102 eyes) by means of Doppler ultrasound. Three groups were formed: group 1 - 38 eyes with both AMD and POAG; group 2 - 41 eyes with AMD and no signs of optic nerve pathology; and group 3 - 23 eyes with POAG and no signs of AMD. Groups 1 and 2 were subdivided into two subgroups each: А - atrophic AMD and B - macular drusen. The mean patient age was 78.7±8.4 years. The following parameters of choroidal blood flow were of interest: peak systolic velocity (Vps), end diastolic velocity (Ved), time-averaged maximum velocity (Vtamax), and resistance index (RI). Groups 1, 3, and 2A had an evident choroidal hypoperfusion in the macular area (decreased Vtamax) with uncompensated perfusion deficit, despite autoregulation efforts (decreased Vps, Ved, decreased or normal RI). Group 2B demonstrated a significantly higher rate of choroidal hyperperfusion (increased Vps, Ved, Vtamax, and RI). Concurrent AMD and POAG are notable for choroidal hypoperfusion in the macular area that leads to inadequate trophism of the neurosensory retina and can aggravate the course of AMD contributing to progression of its atrophic form.

Transpalpebral electrotherapy for dry age-related macular degeneration (AMD): an exploratory trial.

PubMed

Anastassiou, Gerasimos; Schneegans, Anna-Lena; Selbach, Michael; Kremmer, Stephan

2013-01-01

To evaluate the effect of transpalpebral electrotherapy on patients with dry age-related macular degeneration (AMD). 22 patients were randomized in two groups to either receive therapy (n = 12) or placebo (n = 10). There was no statistically significant difference for age and initial visual acuity (VA) between the two groups (p = 0.6; ANOVA). Treatment was performed on 5 consecutive days. On each day two sessions were applied. Every session included 8 spots (40 sec/spot) around the eye globe. The current applied (changing frequency 5-80 Hz) varied individually between 150 and 220 μA. Patients were examined before treatment, at the end of the 5-day treatment period, after 4 weeks and at 6 months. Examinations included a standardized VA testing, using ETDRS letters, contrast sensitivity, macular sensitivity and fixation stability using microperimetry and measurements with SD-OCT. At the end of week 1, mean VA improved markedly (p = 0.001; T test), with 7 out of 12 patients showing an improvement of more than 5 letters. After 4 weeks, there was an improvement of more than 10 letters in 3 patients (mean + 5.7 letters; p = 0.001; T test) whereas at 6 months a loss of 1.6 letters was observed. Only 4 (33%) of our patients did not show any improvement at all. Contrast sensitivity displayed a similar pattern. Within one week after treatment, there was a rapid improvement (+4.4 optotypes; p = 0.006; T test). After 6 months, contrast sensitivity declined again (+1.5 optotypes; p = 0.2; T test). Compared to the placebo group changes on VA failed statistical significance (p = 0.1 at 4 week; T test) whereas changes on contrast sensitivity were statistically significant (p = 0.01 at week 4; T test). No adverse events were seen or reported during the study period. To the best of our knowledge, this is the first report of a transpalpebral electrostimulation in patients with dry AMD that demonstrates a temporary increase in visual function in some of these patients; results that

Role of long-chain and very-long-chain polyunsaturated fatty acids in macular degenerations and dystrophies

PubMed Central

Liu, Aihua; Lin, Yanhua; Terry, Ryan; Nelson, Kelly; Bernstein, Paul S

2014-01-01

Macular degeneration is a progressive, bilateral eye disorder that damages the macula of the human eye. The most common form of macular degeneration is age-related macular degeneration (AMD), which is the leading cause of irreversible blindness in people older than 50 years in developed countries. Autosomal dominant Stargardt disease-3 (STGD3) is an inherited macular dystrophy that has clinical features similar to dry AMD, but occurs at a much earlier age. It is caused by a mutation in the elongation of very-long-chain fatty acids-like 4 (ELOVL4) gene, which is responsible for encoding the elongase enzyme that converts shorter chain fatty acids into C28–C38 very long-chain polyunsaturated fatty acids (VLCPUFAs, total number of carbons ≥24). Diets rich in long-chain polyunsaturated fatty acids (LCPUFAs) have inverse associations with the progression of AMD and STGD3, and a deficiency in retinal LCPUFAs and VLCPUFAs has been detected in AMD retinas and STGD3 animal models. This article systematically summarizes the roles of LCPUFAs and VLCPUFAs in AMD and STGD3, and discusses future research directions. PMID:25324899

Prevention and treatment of age-related macular degeneration: an update for pharmacists.

PubMed

Marshall, Leisa L; Roach, J Michael

2013-11-01

Review the current recommendations for the prevention and treatment of age-related macular degeneration (AMD). Articles indexed in PubMed (National Library of Medicine), the Cochrane Reviews and Trials, Dynamed, and Iowa Drug Information Service (IDIS) in the last 10 years using the key words macular degeneration, agerelated macular degeneration (AMD), AMD and treatment, AMD and prevention. Sixty-nine published papers were reviewed, and criteria supporting the primary objective were used to identify useful resources. The literature included practice guidelines, original research articles, review articles, product prescribing information, and supplement product information for the prevention and treatment of AMD. AMD is a leading cause of visual impairment in older adults. At present there is no cure for advanced AMD, but intravitreal vascular endothelial growth factor inhibitors minimize and even reverse vision loss in patients with AMD of the neovascular type. In the Age-Related Eye Disease Study (AREDS), participants with intermediate AMD who received a supplement combination of vitamins C and E, beta-carotene, and zinc had a greater delay in progression to advanced AMD than those participants who received a portion of these supplements. In the second AREDS, AREDS2, the addition of lutein + zeaxanthin, docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA), or lutein + zeaxanthin and DHA + EPA to the complete AREDS formulation did not further reduce the risk of progression to advanced AMD. Subgroup analyses indicated that additional research with lutein + zeaxanthin supplementation is warranted as it was beneficial in participants with low dietary intake of lutein + zeaxanthin. A formulation without beta-carotene may be best for most patients, especially smokers or former smokers. Health care professionals will want to consider patient-specific information before recommending ocular health supplements.

Genetic factors of age-related macular degeneration

PubMed Central

Tuo, Jingsheng; Bojanowski, Christine M.; Chan, Chi-Chao

2007-01-01

Age-related macular degeneration (AMD) is a leading cause of blindness in the United States and developed countries. Although the etiology and pathogenesis of AMD remain unknown, a complex interaction of genetic and environmental factors is thought to exist. The incidence and progression of all of the features of AMD are known to increase significantly with age. The tendency for familial aggregation and the findings of gene variation association studies implicate a significant genetic component in the development of AMD. This review summarizes in detail the AMD-related genes identified by studies on genetically engineered and spontaneously gene-mutated (naturally mutated) animals, AMD chromosomal loci identified by linkage studies, AMD-related genes identified through studies of monogenic degenerative retinal diseases, and AMD-related gene variation identified by association studies. PMID:15094132

Classification of wet aged related macular degeneration using optical coherence tomographic images

NASA Astrophysics Data System (ADS)

Haq, Anam; Mir, Fouwad Jamil; Yasin, Ubaid Ullah; Khan, Shoab A.

2013-12-01

Wet Age related macular degeneration (AMD) is a type of age related macular degeneration. In order to detect Wet AMD we look for Pigment Epithelium detachment (PED) and fluid filled region caused by choroidal neovascularization (CNV). This form of AMD can cause vision loss if not treated in time. In this article we have proposed an automated system for detection of Wet AMD in Optical coherence tomographic (OCT) images. The proposed system extracts PED and CNV from OCT images using segmentation and morphological operations and then detailed feature set are extracted. These features are then passed on to the classifier for classification. Finally performance measures like accuracy, sensitivity and specificity are calculated and the classifier delivering the maximum performance is selected as a comparison measure. Our system gives higher performance using SVM as compared to other methods.

Macular xanthophylls, lipoprotein-related genes, and age-related macular degeneration1234

PubMed Central

Koo, Euna; Neuringer, Martha; SanGiovanni, John Paul

2014-01-01

Plant-based macular xanthophylls (MXs; lutein and zeaxanthin) and the lutein metabolite meso-zeaxanthin are the major constituents of macular pigment, a compound concentrated in retinal areas that are responsible for fine-feature visual sensation. There is an unmet need to examine the genetics of factors influencing regulatory mechanisms and metabolic fates of these 3 MXs because they are linked to processes implicated in the pathogenesis of age-related macular degeneration (AMD). In this work we provide an overview of evidence supporting a molecular basis for AMD-MX associations as they may relate to DNA sequence variation in AMD- and lipoprotein-related genes. We recognize a number of emerging research opportunities, barriers, knowledge gaps, and tools offering promise for meaningful investigation and inference in the field. Overviews on AMD- and high-density lipoprotein (HDL)–related genes encoding receptors, transporters, and enzymes affecting or affected by MXs are followed with information on localization of products from these genes to retinal cell types manifesting AMD-related pathophysiology. Evidence on the relation of each gene or gene product with retinal MX response to nutrient intake is discussed. This information is followed by a review of results from mechanistic studies testing gene-disease relations. We then present findings on relations of AMD with DNA sequence variants in MX-associated genes. Our conclusion is that AMD-associated DNA variants that influence the actions and metabolic fates of HDL system constituents should be examined further for concomitant influence on MX absorption, retinal tissue responses to MX intake, and the capacity to modify MX-associated factors and processes implicated in AMD pathogenesis. PMID:24829491

Estrogen signalling in the pathogenesis of age-related macular degeneration.

PubMed

Kaarniranta, Kai; Machalińska, Anna; Veréb, Zoltán; Salminen, Antero; Petrovski, Goran; Kauppinen, Anu

2015-02-01

Age-related macular degeneration (AMD) is a multifactorial eye disease that is associated with aging, family history, smoking, obesity, cataract surgery, arteriosclerosis, hypertension, hypercholesterolemia and unhealthy diet. Gender has commonly been classified as a weak or inconsistent risk factor for AMD. This disease is characterized by degeneration of retinal pigment epithelial (RPE) cells, Bruch's membrane, and choriocapillaris, which secondarily lead to damage and death of photoreceptor cells and central visual loss. Pathogenesis of AMD involves constant oxidative stress, chronic inflammation, and increased accumulation of lipofuscin and drusen. Estrogen has both anti-oxidative and anti-inflammatory capacity and it regulates signaling pathways that are involved in the pathogenesis of AMD. In this review, we discuss potential cellular signaling targets of estrogen in retinal cells and AMD pathology.

Diabetic macular edema, retinopathy and age-related macular degeneration as inflammatory conditions

PubMed Central

2016-01-01

Diabetic macular edema (DME) and diabetic retinopathy (DR) are complications affecting about 25% of all patients with long-standing type 1 and type 2 diabetes mellitus and are a major cause of significant decrease in vision and quality of life. Age-related macular degeneration (AMD) is not uncommon, and diabetes mellitus affects the incidence and progression of AMD through altering hemodynamics, increasing oxidative stress, accumulating advanced glycation end products, etc. Recent studies suggest that DME, DR and AMD are inflammatory conditions characterized by a breakdown of the blood-retinal barrier, inflammatory processes and an increase in vascular permeability. Key factors that seem to have a dominant role in DME, DR and AMD are angiotensin II, prostaglandins and the vascular endothelial growth factor and a deficiency of anti-inflammatory bioactive lipids. The imbalance between pro- and anti-inflammatory eicosanoids and enhanced production of pro-angiogenic factors may initiate the onset and progression of DME, DR and AMD. This implies that bioactive lipids that possess anti-inflammatory actions and suppress the production of angiogenic factors could be employed in the prevention and management of DME, DR and AMD. PMID:27695506

Five-year progression of unilateral age-related macular degeneration to bilateral involvement: the Three Continent AMD Consortium report

PubMed Central

Joachim, Nichole; Colijn, Johanna Maria; Kifley, Annette; Lee, Kristine E; Buitendijk, Gabriëlle H S; Klein, Barbara E K; Myers, Chelsea E; Meuer, Stacy M; Tan, Ava G; Holliday, Elizabeth G; Attia, John; Liew, Gerald; Iyengar, Sudha K; de Jong, Paulus T V M; Hofman, Albert; Vingerling, Johannes R; Mitchell, Paul; Klaver, Caroline C W; Klein, Ronald; Wang, Jie Jin

2018-01-01

Purpose To assess the 5-year progression from unilateral to bilateral age-related macular degeneration (AMD) and associated risk factors. Design Pooled data analyses of three prospective population-based cohorts, the Blue Mountains Eye Study, Beaver Dam Eye Study and Rotterdam Study. Methods Retinal photography and interview with comprehensive questionnaires were conducted at each visit of three studies. AMD was assessed following the modified Wisconsin AMD grading protocol. Progression to bilateral any (early and late) or late AMD was assessed among participants with unilateral involvement only. Factors associated with the progression were assessed using logistic regression models while simultaneously adjusting for other significant risk factors. Results In any 5-year duration, 19–28% of unilateral any AMD cases became bilateral and 27–68% of unilateral late AMD became bilateral. Factors associated with the progression to bilateral involvement of any AMD were age (per year increase, adjusted OR 1.07), carrying risk alleles of the complement factor H and age-related maculopathy susceptibility 2 genes (compared with none, OR 1.76 for 1 risk allele and OR 3.34 for 2+ risk alleles), smoking (compared with non-smokers, OR 1.64 for past and OR 1.67 for current smokers), and the presence of large drusen area or retinal pigmentary abnormalities in the first eye. Conclusion One in four to one in five unilateral any AMD cases, and up to one in two unilateral late AMD cases, progressed to bilateral in 5 years. Known AMD risk factors, including smoking, are significantly associated with the progression to bilateral involvement. PMID:28108569

Circulating vitamin D concentration and age-related macular degeneration: Systematic review and meta-analysis.

PubMed

Annweiler, Cedric; Drouet, Morgane; Duval, Guillaume T; Paré, Pierre-Yves; Leruez, Stephanie; Dinomais, Mickael; Milea, Dan

2016-06-01

Vitamin D may be involved in ocular function in older adults, but there is no current consensus on a possible association between circulating concentrations of 25-hydroxyvitamin D (25OHD) and the occurrence of age-related macular degeneration (AMD). Our objective was to systematically review and quantitatively assess the association of circulating 25OHD concentration with AMD. A Medline search was conducted in November 2015, with no date limit, using the MeSH terms "Vitamin D" OR "Vitamin D deficiency" OR "Ergocalciferols" OR 'Cholecalciferol' combined with "Age-related macular degeneration" OR "Macular degeneration" OR "Retinal degeneration" OR "Macula lutea" OR "Retina". Fixed and random-effects meta-analyses were performed to compute (i) standard mean difference in 25OHD concentration between AMD and non-AMD patients; (ii) AMD risk according to circulating 25OHD concentration. Of the 243 retrieved studies, 11 observational studies-10 cross-sectional studies and 1 cohort study-met the selection criteria. The number of participants ranged from 65 to 17,045 (52-100% women), and the number with AMD ranged from 31 to 1440. Circulating 25OHD concentration was 15% lower in AMD compared with non-AMD on average. AMD was inversely associated with the highest 25OHD quintile compared with the lowest (summary odds ratio (OR)=0.83 [95%CI:0.71-0.97]), notably late AMD (summary OR=0.47 [95%CI:0.28-0.79]). Circulating 25OHD<50nmol/L was also associated with late-stage AMD (summary OR=2.18 [95%CI:1.34-3.56]), an association that did not persist when all categories of AMD were considered (summary OR=1.26 [95%CI:0.90-1.76]). In conclusion, this meta-analysis provides evidence that high 25OHD concentrations may be protective against AMD, and that 25OHD concentrations below 50nmol/L are associated with late AMD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Diminishing risk for age related macular degeneration with nutrition: A current view

USDA-ARS?s Scientific Manuscript database

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. Clinical hallmarks of AMD are observed in one third of the elderly in industrialized countries. Preventative interventions through dietary modification are attractive strategies because they are more affordable...

Age-Related Macular Degeneration: Advances in Management and Diagnosis

PubMed Central

Yonekawa, Yoshihiro; Miller, Joan W.; Kim, Ivana K.

2015-01-01

Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment in older populations in industrialized nations. AMD is a late-onset deterioration of photoreceptors and retinal pigment epithelium in the central retina caused by various environmental and genetic factors. Great strides in our understanding of AMD pathogenesis have been made in the past several decades, which have translated into revolutionary therapeutic agents in recent years. In this review, we describe the clinical and pathologic features of AMD and present an overview of current diagnosis and treatment strategies. PMID:26239130

Lighting Needs and Lighting Comfort During Reading with Age-Related Macular Degeneration

ERIC Educational Resources Information Center

Fosse, Per; Valberg, Arne

2004-01-01

This study investigated the effects of changes in luminance on the oral reading speeds of 13 participants with age-related macular degeneration (AMD) and a control group of six age-matched persons with typical vision. For the AMD participants, self-reports of light preferences were also recorded. In the AMD group, reading rates depended on light…

Prevention of age-related macular degeneration

PubMed Central

Koo, Simon Chi Yan; Chan, Clement Wai Nang

2010-01-01

Age-related macular degeneration (AMD) is one of the leading causes of blindness in the developed world. Although effective treatment modalities such as anti-VEGF treatment have been developed for neovascular AMD, there is still no effective treatment for geographical atrophy, and therefore the most cost-effective management of AMD is to start with prevention. This review looks at current evidence on preventive measures targeted at AMD. Modalities reviewed include (1) nutritional supplements such as the Age-Related Eye Disease Study (AREDS) formula, lutein and zeaxanthin, omega-3 fatty acid, and berry extracts, (2) lifestyle modifications, including smoking and body-mass-index, and (3) filtering sunlight, i.e. sunglasses and blue-blocking intraocular lenses. In summary, the only proven effective preventive measures are stopping smoking and the AREDS formula. PMID:20862519

Prevention of age-related macular degeneration.

PubMed

Wong, Ian Yat Hin; Koo, Simon Chi Yan; Chan, Clement Wai Nang

2011-02-01

Age-related macular degeneration (AMD) is one of the leading causes of blindness in the developed world. Although effective treatment modalities such as anti-VEGF treatment have been developed for neovascular AMD, there is still no effective treatment for geographical atrophy, and therefore the most cost-effective management of AMD is to start with prevention. This review looks at current evidence on preventive measures targeted at AMD. Modalities reviewed include (1) nutritional supplements such as the Age-Related Eye Disease Study (AREDS) formula, lutein and zeaxanthin, omega-3 fatty acid, and berry extracts, (2) lifestyle modifications, including smoking and body-mass-index, and (3) filtering sunlight, i.e. sunglasses and blue-blocking intraocular lenses. In summary, the only proven effective preventive measures are stopping smoking and the AREDS formula.

Lifestyle modification, nutritional and vitamins supplements for age-related macular degeneration.

PubMed

Sin, Helena P Y; Liu, David T L; Lam, Dennis S C

2013-02-01

To provide a systematic review of the published studies pertaining to the lifestyle modification, dietary, nutritional and vitamins supplements for preventing occurrence or halting deterioration of age-related macular degeneration (AMD). The literature searches from 1990 to December 2010 with following keywords, 'age related macular degeneration', 'nutrition', 'antioxidant', 'diet' and 'vitamins supplements' using search engines Pubmed, Google Scholar, Medline and the Cochrane Library. Meta-analyses, population-based cohort studies and case-controlled trials were reviewed, whereas small cases series, case reports, commentaries, abstracts in proceedings or personal observations were excluded. Smoking and obesity are identified risk factors for AMD. High dietary intakes of omega-3 fatty acids, and macular xanthophylls lutein and zeaxanthin have been associated with a lower risk of prevalence and incidence in AMD. Vitamin B and extracts from wolfberry, Gingko biloba and berry anthocyanins were also subjects of intense research interests, but there has been no concluding scientific evidence yet. The Age-Related Eye Disease study (AREDS) is the only large-scale randomized controlled clinical trial to show beneficial effect of AREDS formulation of vitamins C, E, beta-carotene and zinc with copper in reducing the risk progression to advanced AMD in patients with intermediate AMD or with advanced AMD in one eye. Quit smoking is an important advice to patients to prevent or slow the progress of AMD. There is no recommendation for routine nutritional or vitamins supplementation for primary prevention. However, patients with documented intermediate risk of AMD or advanced AMD in one eye are recommended to take AREDS-type vitamin supplements. © 2012 The Authors. Acta Ophthalmologica © 2012 Acta Ophthalmologica Scandinavica Foundation.

Clinical Characteristics and Current Treatment of Age-Related Macular Degeneration

PubMed Central

Yonekawa, Yoshihiro; Kim, Ivana K.

2015-01-01

Age-related macular degeneration (AMD) is a multifactorial degeneration of photoreceptors and retinal pigment epithelium. The societal impact is significant, with more than 2 million individuals in the United States alone affected by advanced stages of AMD. Recent progress in our understanding of this complex disease and parallel developments in therapeutics and imaging have translated into new management paradigms in recent years. However, there are many unanswered questions, and diagnostic and prognostic precision and treatment outcomes can still be improved. In this article, we discuss the clinical features of AMD, provide correlations with modern imaging and histopathology, and present an overview of treatment strategies. PMID:25280900

Association of HTRA1 rs11200638 with age-related macular degeneration (AMD) in Brazilian patients.

PubMed

Lana, Tamires Prates; da Silva Costa, Sueli Matilde; Ananina, Galina; Hirata, Fábio Endo; Rim, Priscila Hae Hyun; Medina, Flávio MacCord; de Vasconcellos, José Paulo Cabral; de Melo, Mônica Barbosa

2018-01-01

Age-related macular degeneration is a multifactorial disease that can lead to vision impairment in older individuals. Although the etiology of age-related macular degeneration remains unknown, risk factors include age, ethnicity, smoking, hypertension, obesity, and genetic factors. Two main loci have been identified through genome-wide association studies, on chromosomes 1 and 10. Among the variants located at the 10q26 region, rs11200638, located at the HTRA1 gene promoter, has been associated with age-related macular degeneration in several populations and is considered the main polymorphism. We conducted a replication case-control study to analyze the frequency and participation of rs11200638 in the etiology of age-related macular degeneration in a sample of patients and controls from the State of São Paulo, Brazil, through polymerase chain reaction and enzymatic digestion. The frequency of the A allele was 57.60% in patients with age-related macular degeneration and 36.45% in controls (p value < 1e-07), representing a 2.369-fold higher risk factor for the disease. Both the AA and AG genotypes were observed more frequently in the age-related macular degeneration group compared to the control group (p = 1.21 e-07 and 0.0357, respectively). No statistically significant results were observed after stratification in dry versus wet types or advanced versus non-advanced forms. To our knowledge, this is the first time the association between rs11200638 and overall age-related macular degeneration has been reported in South America.

Clinical classification of age-related macular degeneration.

PubMed

Ferris, Frederick L; Wilkinson, C P; Bird, Alan; Chakravarthy, Usha; Chew, Emily; Csaky, Karl; Sadda, SriniVas R

2013-04-01

To develop a clinical classification system for age-related macular degeneration (AMD). Evidence-based investigation, using a modified Delphi process. Twenty-six AMD experts, 1 neuro-ophthalmologist, 2 committee chairmen, and 1 methodologist. Each committee member completed an online assessment of statements summarizing current AMD classification criteria, indicating agreement or disagreement with each statement on a 9-step scale. The group met, reviewed the survey results, discussed the important components of a clinical classification system, and defined new data analyses needed to refine a classification system. After the meeting, additional data analyses from large studies were provided to the committee to provide risk estimates related to the presence of various AMD lesions. Delphi review of the 9-item set of statements resulting from the meeting. Consensus was achieved in generating a basic clinical classification system based on fundus lesions assessed within 2 disc diameters of the fovea in persons older than 55 years. The committee agreed that a single term, age-related macular degeneration, should be used for the disease. Persons with no visible drusen or pigmentary abnormalities should be considered to have no signs of AMD. Persons with small drusen (<63 μm), also termed drupelets, should be considered to have normal aging changes with no clinically relevant increased risk of late AMD developing. Persons with medium drusen (≥ 63-<125 μm), but without pigmentary abnormalities thought to be related to AMD, should be considered to have early AMD. Persons with large drusen or with pigmentary abnormalities associated with at least medium drusen should be considered to have intermediate AMD. Persons with lesions associated with neovascular AMD or geographic atrophy should be considered to have late AMD. Five-year risks of progressing to late AMD are estimated to increase approximately 100 fold, ranging from a 0.5% 5-year risk for normal aging changes to a

Age-related macular degeneration: current treatments

PubMed Central

Hubschman, Jean Pierre; Reddy, Shantan; Schwartz, Steven D

2009-01-01

Purpose: Although important progress has been made in understanding age-related macular degeneration (AMD), management of the disease continues to be a challenge. AMD research has led to a widening of available treatment options and improved prognostic perspectives. This essay reviews these treatment options. Design: Interpretative essay. Methods: Literature review and interpretation. Results: Current treatments to preserve vision in patients with non-exudative AMD include antioxidant vitamins and mineral supplementations. Exudative AMD is currently most often treated monthly with anti-VEGF intravitreal injections. However, investigators are beginning to experiment with combination therapy and surgical approaches in an attempt to limit the number of treatment and reduce the financial burden on the health care system. Conclusion: By better understanding the basis and pathogenesis of AMD, newer therapies will continue to be developed that target specific pathways in patients with AMD, with the hoped for outcome of better management of the disease and improved visual acuity. PMID:19668560

Bmp6 Regulates Retinal Iron Homeostasis and Has Altered Expression in Age-Related Macular Degeneration

PubMed Central

Hadziahmetovic, Majda; Song, Ying; Wolkow, Natalie; Iacovelli, Jared; Kautz, Leon; Roth, Marie-Paule; Dunaief, Joshua L.

2011-01-01

Iron-induced oxidative stress causes hereditary macular degeneration in patients with aceruloplasminemia. Similarly, retinal iron accumulation in age-related macular degeneration (AMD) may exacerbate the disease. The cause of retinal iron accumulation in AMD is poorly understood. Given that bone morphogenetic protein 6 (Bmp6) is a major regulator of systemic iron, we examined the role of Bmp6 in retinal iron regulation and in AMD pathogenesis. Bmp6 was detected in the retinal pigment epithelium (RPE), a major site of pathology in AMD. In cultured RPE cells, Bmp6 was down-regulated by oxidative stress and up-regulated by iron. Intraocular Bmp6 protein injection in mice up-regulated retinal hepcidin, an iron regulatory hormone, and altered retinal labile iron levels. Bmp6−/− mice had age-dependent retinal iron accumulation and degeneration. Postmortem RPE from patients with early AMD exhibited decreased Bmp6 levels. Because oxidative stress is associated with AMD pathogenesis and down-regulates Bmp6 in cultured RPE cells, the diminished Bmp6 levels observed in RPE cells in early AMD may contribute to iron build-up in AMD. This may in turn propagate a vicious cycle of oxidative stress and iron accumulation, exacerbating AMD and other diseases with hereditary or acquired iron excess. PMID:21703414

Prevention of Age-Related Macular Degeneration.

PubMed

Singh, Niharika; Srinivasan, Sangeetha; Muralidharan, Vinata; Roy, Rupak; V, Jayprakash; Raman, Rajiv

2017-01-01

Age-related macular degeneration (AMD) compromises quality of life. However, the available therapeutic options are limited. This has led to the identification of modifiable risk factors to prevent the development or alter the natural course and prognosis of AMD. The identification and modification of risk factors has the potential for greater public health impact on reducing morbidity from AMD. Likewise, identifying the imaging clues and genetic clues could serve as a guide to recognizing the propensity for progression to severe and end stages of the disease. Several attempts, both successful and unsuccessful, have been made for interventions that could delay the progression of AMD. Of these, pharmacological interventions have shown promising results. The Age-Related Eye Disease Study 1 and 2 have shown the beneficial role of antioxidants in a selected group of patients. Copyright 2017 Asia-Pacific Academy of Ophthalmology.

Decreased Thickness and Integrity of the Macular Elastic Layer of Bruch’s Membrane Correspond to the Distribution of Lesions Associated with Age-Related Macular Degeneration

PubMed Central

Chong, N.H. Victor; Keonin, Jason; Luthert, Phil J.; Frennesson, Christina I.; Weingeist, David M.; Wolf, Rachel L.; Mullins, Robert F.; Hageman, Gregory S.

2005-01-01

Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly. In its severest form, choroidal neovessels breach the macular Bruch’s membrane, an extracellular matrix compartment comprised of elastin and collagen laminae, and grow into the retina. We sought to determine whether structural properties of the elastic lamina (EL) correspond to the region of the macula that is predilected toward degeneration in AMD. Morphometric assessment of the macular and extramacular regions of 121 human donor eyes, with and without AMD, revealed a statistically significant difference in both the integrity (P < 0.0001) and thickness (P < 0.0001) of the EL between the macular and extramacular regions in donors of all ages. The EL was three to six times thinner and two to five times less abundant in the macula than in the periphery. The integrity of the macular EL was significantly lower in donors with early-stage AMD (P = 0.028), active choroidal neovascularization (P = 0.020), and disciform scars (P = 0.003), as compared to unaffected, age-matched controls. EL thickness was significantly lower only in individuals with disciform scars (P = 0.008). The largest gaps in macular EL integrity were significantly larger in all categories of AMD (each P < 0.0001), as compared to controls. EL integrity, thickness, and gap length in donors with geographic atrophy did not differ from those of controls. These structural properties of the macular EL correspond spatially to the distribution of macular lesions associated with AMD and may help to explain why the macula is more susceptible to degenerative events that occur in this disease. PMID:15632016

Five-year follow-up of low-level laser therapy (LLLT) in patients with age-related macular degeneration (AMD)

NASA Astrophysics Data System (ADS)

Koev, K.; Avramov, L.; Borissova, E.

2018-03-01

The objective of this study was to examine long-term effects of low-level laser therapy (LLLT) in patients with age-related macular degeneration (AMD). The research was implemented for a period of five years. For LLLT, a He-Ne Laser with continuous emission at 633 nm (0.1 mW/cm2) was used in patients with AMD of all stages (dry to wet exudative forms were included). In total, 33 patients (16 men and 17 women – 66 eyes) with AMD of various stages and a mean age of 68.7 ± 4.2 years were included in the study. Progressive, exudative AMD was diagnosed in 8 eyes. 58 eyes had drusen or were depigmented. Laser radiation was applied transpupillary to the macula for six times for three minutes once in two days; 22 patients with AMD (44 eyes) were randomly selected to receive mock treatment (control group 10 men and 12 women with a mean age of 69.3 ± 4.8 years). The visual acuity was followed for a five-year period. The perimetry and Amsler test were used to screen central scotomas. The fluorescein angiography of AMD and the control groups was examined. The visual acuity remained unchanged in all patients in the control group. There was a statistically significant increase in the visual acuity (p<0.001, end of study versus baseline) for AMD patients for the period of five years after the treatment. The edema and hemorrhage in the patients with progressive, exudative AMD significantly decreased. No side effects were observed during the therapy. The prevalence of metamorphopsia, scotoma in AMD group was reduced. In conclusion, this study shows that LLLT may be a novel long-lasting therapeutic option for both forms of AMD. It is a highly-effective treatment that results in a long-term improvement of the visual acuity.

The association of aspirin use with age-related macular degeneration.

PubMed

Liew, Gerald; Mitchell, Paul; Wong, Tien Yin; Rochtchina, Elena; Wang, Jie Jin

2013-02-25

To determine whether regular aspirin use is associated with a higher risk for developing age-related macular degeneration (AMD) by using analyzed data from a 15-year prospective cohort. A prospective analysis was conducted of data from an Australian population-based cohort with 4 examinations during a 15-year period (1992-1994 to 2007-2009). Participants completed a detailed questionnaire at baseline assessing aspirin use, cardiovascular disease status, and AMD risk factors. Age-related macular degeneration was graded side-by-side from retinal photographs taken at each study visit to assess the incidence of neovascular (wet) AMD and geographic atrophy (dry AMD) according to the international AMD classification. Of 2389 baseline participants with follow-up data available, 257 individuals (10.8%) were regular aspirin users and 63 of the 2389 developed neovascular AMD. Persons who were regular aspirin users were more likely to have incident neovascular AMD: the 15-year cumulative incidence was 9.3% in users and 3.7% in nonusers. After adjustment for age, sex, smoking, history of cardiovascular disease, systolic blood pressure, and body mass index, persons who were regular aspirin users had a higher risk of developing neovascular AMD (odds ratio [OR], 2.46; 95% CI, 1.25-4.83). The association showed a dose-response effect (multivariate-adjusted P = .01 for trend). Aspirin use was not associated with the incidence of geographic atrophy (multivariate-adjusted OR, 0.99; 95% CI, 0.59-1.65). Regular aspirin use is associated with increased risk of incident neovascular AMD, independent of a history of cardiovascular disease and smoking.

Involvement of a gut-retina axis in protection against dietary glycemia induced age-related macular degeneration

USDA-ARS?s Scientific Manuscript database

Age-related macular degeneration (AMD) is the major cause of blindness in developed nations. AMD is characterized by retinal pigmented epithelial cell (RPE) dysfunction and loss of photoreceptor cells. Epidemiologic studies indicate important contributions of dietary patterns on risk for AMD, but th...

Humanin G (HNG) protects age-related macular degeneration (AMD) transmitochondrial ARPE-19 cybrids from mitochondrial and cellular damage.

PubMed

Nashine, Sonali; Cohen, Pinchas; Chwa, Marilyn; Lu, Stephanie; Nesburn, Anthony B; Kuppermann, Baruch D; Kenney, M Cristina

2017-07-20

Age-related macular degeneration (AMD) ranks third among the leading causes of visual impairment with a blindness prevalence rate of 8.7%. Despite several treatment regimens, such as anti-angiogenic drugs, laser therapy, and vitamin supplementation, being available for wet AMD, to date there are no FDA-approved therapies for dry AMD. Substantial evidence implicates mitochondrial damage and retinal pigment epithelium (RPE) cell death in the pathogenesis of AMD. However, the effects of AMD mitochondria and Humanin G (HNG), a more potent variant of the mitochondrial-derived peptide (MDP) Humanin, on retinal cell survival have not been elucidated. In this study, we characterized mitochondrial and cellular damage in transmitochondrial cybrid cell lines that contain identical nuclei but possess mitochondria from either AMD or age-matched normal (Older-normal (NL)) subjects. AMD cybrids showed (1) reduced levels of cell viability, lower mtDNA copy numbers, and downregulation of mitochondrial replication/transcription genes and antioxidant enzyme genes; and (2) elevated levels of genes related to apoptosis, autophagy and ER-stress along with increased mtDNA fragmentation and higher susceptibility to amyloid-β-induced toxicity compared to NL cybrids. In AMD cybrids, HNG protected the AMD mitochondria, reduced pro-apoptosis gene and protein levels, upregulated gp130 (a component of the HN receptor complex), and increased the protection against amyloid-β-induced damage. In summary, in cybrids, damaged AMD mitochondria mediate cell death that can be reversed by HNG treatment. Our results also provide evidence of Humanin playing a pivotal role in protecting cells with AMD mitochondria. In the future, it may be possible that AMD patient's blood samples containing damaged mitochondria may be useful as biomarkers for this condition. In conclusion, HNG may be a potential therapeutic target for treatment of dry AMD, a debilitating eye disease that currently has no available

Vitamin D and Age-Related Macular Degeneration.

PubMed

Layana, Alfredo Garcia; Minnella, Angelo Maria; Garhöfer, Gerhard; Aslam, Tariq; Holz, Frank G; Leys, Anita; Silva, Rufino; Delcourt, Cécile; Souied, Eric; Seddon, Johanna M

2017-10-13

In recent years, the relationship between vitamin D and health has received growing attention from the scientific and medical communities. Vitamin D deficiencies have been repeatedly associated with various acute and chronic diseases, including age-related macular degeneration (AMD). Its active metabolite, 1α,25-dihydoxy vitamin D, acts as a modulator of cell proliferation, differentiation and apoptosis, and cumulative data from experimental and observational studies suggest that relatively a lower vitamin D status could be a potential risk factor for the development of early and/or late AMD. Herein, we made a narrative review of the mechanisms linking a potential role of vitamin D with the current concepts of AMD pathophysiology.

A Revised Hemodynamic Theory of Age-Related Macular Degeneration

PubMed Central

Gelfand, Bradley D.; Ambati, Jayakrishna

2016-01-01

Age-related macular degeneration (AMD) afflicts one out of every 40 individuals worldwide, causing irreversible central blindness in millions. The transformation of various tissue layers within the macula in the retina has led to competing conceptual models of the molecular pathways, cell types, and tissues responsible for the onset and progression of AMD. A model that has persisted for over 6 decades is the hemodynamic, or vascular theory of AMD progression, which states that vascular dysfunction of the choroid underlies AMD pathogenesis. Here, we re-evaluate this hypothesis in light of recent advances on molecular, anatomic, and hemodynamic changes underlying choroidal dysfunction in AMD. We propose an updated, detailed model of hemodynamic dysfunction as a mechanism of AMD development and progression. PMID:27423265

OCT Angiography Helps Distinguish Between Proliferative Macular Telangiectasia Type 2 and Neovascular Age-Related Macular Degeneration.

PubMed

Zheng, Fang; Motulsky, Elie H; de Oliveira Dias, João Rafael; de López, Edith Pérez; Gregori, Giovanni; Rosenfeld, Philip J

2018-05-01

To demonstrate the advantage of optical coherence tomography angiography (OCTA) for the diagnosis and management of proliferative macular telangiectasia type 2 (MacTel2) masquerading as neovascular age-related macular degeneration (AMD). This is an observational cases series. Three patients referred with the diagnosis of neovascular AMD were identified in this retrospective study. In addition to color fundus, fluorescein angiography, and spectral-domain OCT (SD-OCT) imaging, SD-OCTA (AngioPlex; Carl Zeiss Meditec, Dublin, CA) was performed. SD-OCTA revealed bilateral parafoveal retinal microvascular changes in three patients and unambiguously confirmed the diagnosis of MacTel2. OCTA is an important tool for the correct diagnosis of MacTel2 in older patients with the concomitant or masquerading diagnosis of AMD. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:303-312.]. Copyright 2018, SLACK Incorporated.

Prevalence of age-related macular degeneration in rural southern China: the Yangxi Eye Study.

PubMed

Jin, Guangming; Ding, Xiaohu; Xiao, Wei; Xu, Xiao; Wang, Lanhua; Han, Xiaotong; Xiao, Ou; Liu, Ran; Wang, Wei; Yan, William; An, Lei; Zhao, Jialiang; He, Mingguang

2018-05-01

To describe the prevalence of age-related macular degeneration (AMD) among older adults in rural southern mainland China. Eligible persons aged 50 years or over were identified by geographically defined cluster sampling from Yangxi County, Guangdong Province, China. Participants underwent a standardised interview and comprehensive eye examinations from August to November in 2014. Digital retinal photographs were graded for AMD lesions using the Clinical Classification of Age-Related Macular Degeneration developed by the Beckman Initiative for Macular Research Classification Committee. Age-standardised prevalence of AMD and AMD lesions was calculated using the 2010 world population data and compared with those of other populations. Of 5825 subjects who participated (90.7% response rate), 4881 (83.8%) had fundus photographs gradable for AMD. Early, intermediate and late AMD were present in 2003 (41.0%), 879 (18.0%) and 42 (0.86%) participants. The age-standardised prevalence of early, intermediate and late AMD was 40.4% (95% CI 39.6% to 41.2%), 17.6% (95% CI 17.0% to 18.2%) and 0.79% (95% CI 0.65% to 0.95%), respectively. Total AMD was more prevalent in men than in women (62.8% vs 57.1%). AMD is an important public health concern for rural southern China, and the prevalence of AMD was higher in men than in women. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Knowledge and Use of Low Vision Services Among Persons with Age-Related Macular Degeneration

ERIC Educational Resources Information Center

Casten, Robin J.; Maloney, Eileen K.; Rovner, Barry W.

2005-01-01

Visual impairment (blindness or low vision) is a leading cause of disability among older adults and is most often due to age-related macular degeneration (AMD). It is predicted that 2.95 million people will have AMD by 2020 (Eye Diseases Prevalence Research Group, 2004). Unfortunately, there is no cure for AMD, nor can lost vision be restored.…

Declines in arrestin and rhodopsin in the macula with progression of age-related macular degeneration.

PubMed

Ethen, Cheryl M; Feng, Xiao; Olsen, Timothy W; Ferrington, Deborah A

2005-03-01

Biochemical analysis of age-related macular degeneration (AMD) at distinct stages of the disease will help further understanding of the molecular events associated with disease progression. This study was conducted to determine the ability of a new grading system for eye bank eyes, the Minnesota Grading System (MGS), to discern distinct stages of AMD so that retinal region-specific changes in rod photoreceptor protein expression from donors could be determined. Donor eyes were assigned to a specific level of AMD by using the MGS. Expression of the rod photoreceptor proteins rhodopsin and arrestin was evaluated by Western immunoblot analysis in the macular and peripheral regions of the neurosensory retina from donors at different stages of AMD. A significant linear decline in both arrestin and rhodopsin content correlated with progressive MGS levels in the macula. In contrast, the peripheral region showed no significant correlation between MGS level and the content of either protein. The statistically significant relationship between decreasing macular rod photoreceptor proteins and progressive MGS levels of AMD demonstrates the utility of the clinically based MGS to correspond with specific protein changes found at known, progressive stages of degeneration. Future biochemical analysis of clinically characterized donor eyes will further understanding of the pathobiochemistry of AMD.

Macular degeneration (image)

MedlinePlus

Macular degeneration is a disease of the retina that affects the macula in the back of the eye. ... see fine details. There are two types of macular degeneration, dry and wet. Dry macular degeneration is more ...

HEALTH CONDITIONS LINKED TO AGE-RELATED MACULAR DEGENERATION ASSOCIATED WITH DARK ADAPTATION.

PubMed

Laíns, Inês; Miller, John B; Mukai, Ryo; Mach, Steven; Vavvas, Demetrios; Kim, Ivana K; Miller, Joan W; Husain, Deeba

2018-06-01

To determine the association between dark adaption (DA) and different health conditions linked with age-related macular degeneration (AMD). Cross-sectional study, including patients with AMD and a control group. Age-related macular degeneration was graded according to the Age-Related Eye Disease Study (AREDS) classification. We obtained data on medical history, medications, and lifestyle. Dark adaption was assessed with the extended protocol (20 minutes) of AdaptDx (MacuLogix). For analyses, the right eye or the eye with more advanced AMD was selected. Multivariate linear and logistic regressions were performed, accounting for age and AMD stage. Seventy-eight subjects (75.6% AMD; 24.4% controls) were included. Multivariate assessments revealed that body mass index (BMI; β = 0.30, P = 0.045), taking AREDS vitamins (β = 5.51, P < 0.001), and family history of AMD (β = 2.68, P = 0.039) were significantly associated with worse rod intercept times. Abnormal DA (rod intercept time ≥ 6.5 minutes) was significantly associated with family history of AMD (β = 1.84, P = 0.006), taking AREDS supplements (β = 1.67, P = 0.021) and alcohol intake (β = 0.07, P = 0.017). Besides age and AMD stage, a higher body mass index, higher alcohol intake, and a family history of AMD seem to impair DA. In this cohort, the use of AREDS vitamins was also statistically linked with impaired DA, most likely because of an increased severity of disease in subjects taking them.

Iris colour, ethnic origin and progression of age-related macular degeneration.

PubMed

Nicolas, Caroline M; Robman, Luba D; Tikellis, Gabriella; Dimitrov, Peter N; Dowrick, Adam; Guymer, Robyn H; McCarty, Catherine A

2003-12-01

To investigate the relationship between iris colour, ethnic origin and the progression of age-related macular degeneration (AMD). Participants were recruited from the population-based Melbourne Visual Impairment Project or the prospective, randomized, double-masked Vitamin E, Cataract and Age-Related Macular Degeneration study. From these two cohorts, 171 participants aged between 52 and 93 years who were identified as having early AMD features at their baseline examination (1992-1995) were followed for an average of 6.8 years (until 2001) to determine the progression rate of early AMD. The participants' iris colour was categorized as light, intermediate or dark. Ethnic origin was categorized as Anglo-Saxon or non-Anglo-Saxon, according to the participants' grandparents' country of birth. In total, 53 (31%) of the 171 participants showed signs of AMD progression. Participants with light iris colour had twofold the risk of AMD progression of those with dark or intermediate iris colours, although the age-adjusted and multivariate-adjusted associations were not significant (both P = 0.13). Age-adjusted and multivariate comparisons of Anglo-Saxon ethnic origin to non-Anglo-Saxon ethnic origin showed a noticeable but non-significant association with progression of AMD (P= 0.22 and P= 0.14, respectively). Individuals with light iris colour or of Anglo-Saxon ethnic origin had a strong tendency to greater progression of AMD. A larger sample is required to confirm these clinically important, but statistically non-significant, associations.

Nutritional supplements in age-related macular degeneration.

PubMed

Schmidl, Doreen; Garhöfer, Gerhard; Schmetterer, Leopold

2015-03-01

Age-related macular degeneration (AMD) is the most frequent cause of blindness in the Western World. While with new therapies that are directed towards vascular endothelial growth factor (VEGF), a potentially efficient treatment option for the wet form of the disease has been introduced, a therapeutic regimen for dry AMD is still lacking. There is evidence from several studies that oral intake of supplements is beneficial in preventing progression of the disease. Several formulations of micronutrients are currently available. The present review focuses on the role of supplements in the treatment and prevention of AMD and sums up the current knowledge about the most frequently used micronutrients. In addition, regulatory issues are discussed, and future directions for the role of supplementation in AMD are highlighted. © 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Apolipoprotein E polymorphisms in Japanese patients with polypoidal choroidal vasculopathy and exudative age-related macular degeneration.

PubMed

Gotoh, Norimoto; Kuroiwa, Sachiko; Kikuchi, Takanobu; Arai, Jun; Arai, Satoko; Yoshida, Noriko; Yoshimura, Nagahisa

2004-10-01

To study the genotypes, allelic frequencies, and polymorphisms of apolipoprotein E (Apo E) in unrelated Japanese patients with polypoidal choroidal vasculopathy (PCV) or exudative age-related macular degeneration (AMD) and control subjects without macular degeneration. Cross-sectional study. Blood samples from 225 subjects older than 50 years were used. The 225 subjects included 58 patients with PCV, 85 with AMD, and 82 without macular degeneration. Coding exons of the Apo E gene were amplified by polymerase chain reaction, and the DNA sequences were determined by direct sequencing with an automated sequencer. Apo E epsilon3/epsilon3 was the most frequent genotype with a prevalence of 79.3% in PCV patients, 76.5% in AMD patients, and 67.1% in the control subjects. However, the differences in the percentages were not statistically significant among the three groups. The most frequently found allele in the three groups was epsilon3. Patients with PCV and AMD were less likely to have epsilon2 and epsilon4 than the control subjects, but the differences were not statistically significant. Five minor Apo E single nucleotide polymorphisms, including epsilon5 and epsilon7, were found. Japanese patients with PCV and AMD were less likely to have epsilon2 and epsilon4 polymorphisms, but the differences from the normals were not statistically significant for the Apo E genotypes and allelic frequencies.

Dry Age-Related Macular Degeneration Pharmacology

PubMed Central

Wright, Charles B.

2017-01-01

Age-related macular degeneration (AMD), the most common form of irreversible blindness in the industrially developed world, can present years before a patient begins to lose vision. For most of these patients, AMD never progresses past its early stages to the advanced forms that are principally responsible for the vast majority of vision loss. Advanced AMD can manifest as either an advanced avascular form known as geographic atrophy (GA) marked by regional retinal pigment epithelium (RPE) cell death or as an advanced form known as neovascular AMD marked by the intrusion of fragile new blood vessels into the normally avascular retina. Physicians have several therapeutic interventions available to combat neovascular AMD, but GA has no approved effective therapies as of yet. In this chapter, we will discuss the current strategies for limiting dry AMD in patients. We will also discuss previous attempts at pharmacological intervention that were tested in a clinical setting and consider reasons why these putative therapeutics did not perform successfully in large-scale trials. Despite the number of unsuccessful past trials, new pharmacological interventions may succeed. These future therapies may aid millions of AMD patients worldwide. PMID:27900609

ASSOCIATION BETWEEN VISUAL FUNCTION AND SUBRETINAL DRUSENOID DEPOSITS IN NORMAL AND EARLY AGE-RELATED MACULAR DEGENERATION EYES.

PubMed

Neely, David; Zarubina, Anna V; Clark, Mark E; Huisingh, Carrie E; Jackson, Gregory R; Zhang, Yuhua; McGwin, Gerald; Curcio, Christine A; Owsley, Cynthia

2017-07-01

To examine the association between subretinal drusenoid deposits (SDDs) identified by multimodal retinal imaging and visual function in older eyes with normal macular health or in the earliest phases of age-related macular degeneration (AMD). Age-related macular degeneration status for each eye was defined according to the Age-Related Eye Disease Study (AREDS) 9-step classification system (normal = Step 1, early AMD = Steps 2-4) based on color fundus photographs. Visual functions measured were best-corrected photopic visual acuity, contrast and light sensitivity, mesopic visual acuity, low-luminance deficit, and rod-mediated dark adaptation. Subretinal drusenoid deposits were identified through multimodal imaging (color fundus photographs, infrared reflectance and fundus autofluorescence images, and spectral domain optical coherence tomography). The sample included 1,202 eyes (958 eyes with normal health and 244 eyes with early AMD). In normal eyes, SDDs were not associated with any visual function evaluated. In eyes with early AMD, dark adaptation was markedly delayed in eyes with SDDs versus no SDD (a 4-minute delay on average), P = 0.0213. However, this association diminished after age adjustment, P = 0.2645. Other visual functions in early AMD eyes were not associated with SDDs. In a study specifically focused on eyes in normal macular health and in the earliest phases of AMD, early AMD eyes with SDDs have slower dark adaptation, largely attributable to the older ages of eyes with SDD; they did not exhibit deficits in other visual functions. Subretinal drusenoid deposits in older eyes in normal macular health are not associated with any visual functions evaluated.

Statin use and the incidence of advanced age-related macular degeneration in the Complications of Age-related Macular Degeneration Prevention Trial.

PubMed

Maguire, Maureen G; Ying, Gui-shuang; McCannel, Colin A; Liu, Chengcheng; Dai, Yang

2009-12-01

To evaluate the impact of statin use on the incidence of advanced age-related macular degeneration (AMD) and its components, choroidal neovascularization (CNV) and geographic atrophy (GA), among patients with bilateral large drusen. Cohort study within a multicenter, randomized, clinical trial. Patients enrolled in the Complications of Age-related Macular Degeneration Prevention Trial (CAPT). Eligibility criteria for the clinical trial required that participants have >or=10 large (>125 microm) drusen and visual acuity >or=20/40 in each eye. Patients scheduled for their final CAPT visit after May 2005 were interviewed on their history of use of cholesterol-lowering medications, including statins. Trained readers identified CNV and end point GA (>1 Macular Photocoagulation Study disc area of GA) based on review of fluorescein angiograms and fundus photographs taken at annual follow-up visits and when patients reported symptoms. The risk ratio for participants developing CNV or developing GA associated with statin use was estimated with time-dependent Cox proportional hazards models. Development of advanced AMD, CNV, and end point GA. Among 764 patients eligible for the interview, 744 (97.4%) patients completed the interview on medication use. Statin use was reported by 296 (39.8%) of those interviewed, with the majority, 187 (63.2%) of the 296, beginning use after enrollment in CAPT. Among 744 patients, advanced AMD developed in 332 (22.5%) eyes of 242 (32.5%) patients, CNV in 222 (15%) eyes of 176 (23.7%) patients, and GA in 114 (7.7%) eyes of 80 (10.8%) patients. With adjustment for other risk factors, the estimated risk ratio for eyes (95% confidence interval) associated with statin use was 1.15 (0.87-1.52) for advanced AMD, 1.35 (0.99-1.83) for CNV, and 0.80 (0.46-1.39) for GA. The CAPT data are not consistent with a strong protective effect (risk ratio, AMD among patients with bilateral large drusen.

A Qualitative Analysis of Reading Rehabilitation of Persons with Age-Related Macular Degeneration

ERIC Educational Resources Information Center

Feely, Mary; Vetere, Arlene; Myers, Lynn B.

2007-01-01

One of the most prevalent visual impairments of people aged 60 and older is age-related macular degeneration (AMD), which ranks third globally as a cause of visual impairment (World Health Organization, 2006). The purpose of this study was to conduct a tentative subjective assessment of eccentric viewing by persons with AMD. The authors recruited…

Animal models of age related macular degeneration

PubMed Central

Pennesi, Mark E.; Neuringer, Martha; Courtney, Robert J.

2013-01-01

Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the histological features of AMD and provided much insight into the underlying pathological mechanisms of this disease. In spite of the large number of models developed, no one model yet recapitulates all of the features of human AMD. However, these models have helped reveal the roles of chronic oxidative damage, inflammation and immune dysregulation, and lipid metabolism in the development of AMD. Models for induced choroidal neovascularization have served as the backbone for testing new therapies. This article will review the diversity of animal models that exist for AMD as well as their strengths and limitations. PMID:22705444

Age-related macular degeneration.

PubMed

Cheung, Lily K; Eaton, Angie

2013-08-01

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, and the prevalence of the disease increases exponentially with every decade after age 50 years. It is a multifactorial disease involving a complex interplay of genetic, environmental, metabolic, and functional factors. Besides smoking, hypertension, obesity, and certain dietary habits, a growing body of evidence indicates that inflammation and the immune system may play a key role in the development of the disease. AMD may progress from the early form to the intermediate form and then to the advanced form, where two subtypes exist: the nonneovascular (dry) type and the neovascular (wet) type. The results from the Age-Related Eye Disease Study have shown that for the nonneovascular type of AMD, supplementation with high-dose antioxidants (vitamin C, vitamin E, and β-carotene) and zinc is recommended for those with the intermediate form of AMD in one or both eyes or with advanced AMD or vision loss due to AMD in one eye. As for the neovascular type of the advanced AMD, the current standard of therapy is intravitreal injections of vascular endothelial growth factor inhibitors. In addition, lifestyle and dietary modifications including improved physical activity, reduced daily sodium intake, and reduced intake of solid fats, added sugars, cholesterol, and refined grain foods are recommended. To date, no study has demonstrated that AMD can be cured or effectively prevented. Clearly, more research is needed to fully understand the pathophysiology as well as to develop prevention and treatment strategies for this devastating disease. © 2013 Pharmacotherapy Publications, Inc.

Triple therapy for age-related macular degeneration.

PubMed

Augustin, Albert

2009-06-01

Choroidal neovascularization is a hallmark sign of wet age-related macular degeneration (AMD) but it is not an isolated feature. Several processes are likely to contribute to the fibrotic scarring and vision loss that accompanies progressive disease. In a case series, a triple therapy approach to wet AMD was based on the goals of halting choroidal neovascularization, controlling the inflammatory response, and modifying proliferative factors. To address each of these goals, respectively, patients received photodynamic therapy, bevacizumab, and the steroid dexamethasone. The encouraging rate of response, including significant improvements in visual acuity, is consistent with the combined activities of these agents and provides the basis for more definitive studies.

Patient-reported utilities in bilateral visual impairment from amblyopia and age-related macular degeneration.

PubMed

van de Graaf, Elizabeth S; Despriet, Dominiek D G; Klaver, Caroline C W; Simonsz, Huibert J

2016-05-17

Utility of visual impairment caused by amblyopia is important for the cost-effectiveness of screening for amblyopia (lazy eye, prevalence 3-3.5 %). We previously measured decrease of utility in 35-year-old persons with unilateral persistent amblyopia. The current observational case-control study aimed to measure loss of utility in patients with amblyopia with recent decrease of vision in their better eye. As these patients are rare, the sample was supplemented by patients with bilateral age-related macular degeneration with similar decrease of vision. From our out-patient department, two groups of patients with recent deterioration to bilateral visual acuity less than Snellen 0.5 (bilateral visual impairment, BVI) were recruited, with either persistent amblyopia and age-related macular degeneration (AMB + AMD), or with bilateral age-related macular degeneration (BAMD). To measure utility, the time trade-off method and the standard gamble method were applied through interviews. Correlations were sought between utility values and visual acuity, age and Visual Function Questionnaire-25 scores. Seventeen AMB + AMD patients (mean age 72.9 years), and 63 BAMD patients (mean age 79.6 years) were included in the study. Among AMB + AMD, 80 % were willing to trade lifetime in exchange for cure. The overall mean time trade-off utility was 0.925. Among BAMD, 75 % were willing to trade, utility was 0.917. Among AMB + AMD, 38 % accepted risk of death in exchange for cure, overall mean standard gamble utility was 0.999. Among BAMD, 49 % accepted risk of death, utility was 0.998. Utility was not related to visual acuity but it was to age (p = 0.02). Elderly patients with BVI, caused by persistent amblyopia and age-related macular degeneration (AMD) or by bilateral AMD, had an approximately 8 % loss of TTO utility. Notably, the 8 % loss in elderly with BVI differs little from the 3.7 % loss we found previously in 35-year-old persons with unilateral

Macular degeneration

MedlinePlus Videos and Cool Tools

... center of the field of vision. Macular degeneration results from a partial breakdown of the insulating layer ... of blood vessels behind the retina. Macular degeneration results in the loss of central vision only.

Risk assessment model for development of advanced age-related macular degeneration.

PubMed

Klein, Michael L; Francis, Peter J; Ferris, Frederick L; Hamon, Sara C; Clemons, Traci E

2011-12-01

To design a risk assessment model for development of advanced age-related macular degeneration (AMD) incorporating phenotypic, demographic, environmental, and genetic risk factors. We evaluated longitudinal data from 2846 participants in the Age-Related Eye Disease Study. At baseline, these individuals had all levels of AMD, ranging from none to unilateral advanced AMD (neovascular or geographic atrophy). Follow-up averaged 9.3 years. We performed a Cox proportional hazards analysis with demographic, environmental, phenotypic, and genetic covariates and constructed a risk assessment model for development of advanced AMD. Performance of the model was evaluated using the C statistic and the Brier score and externally validated in participants in the Complications of Age-Related Macular Degeneration Prevention Trial. The final model included the following independent variables: age, smoking history, family history of AMD (first-degree member), phenotype based on a modified Age-Related Eye Disease Study simple scale score, and genetic variants CFH Y402H and ARMS2 A69S. The model did well on performance measures, with very good discrimination (C statistic = 0.872) and excellent calibration and overall performance (Brier score at 5 years = 0.08). Successful external validation was performed, and a risk assessment tool was designed for use with or without the genetic component. We constructed a risk assessment model for development of advanced AMD. The model performed well on measures of discrimination, calibration, and overall performance and was successfully externally validated. This risk assessment tool is available for online use.

Aging Is Not a Disease: Distinguishing Age-Related Macular Degeneration from Aging

PubMed Central

Ardeljan, Daniel; Chan, Chi-Chao

2013-01-01

Age-related macular degeneration (AMD) is a disease of the outer retina, characterized most significantly by atrophy of photoreceptors and retinal pigment epithelium accompanied with or without choroidal neovascularization. Development of AMD has been recognized as contingent on environmental and genetic risk factors, the strongest being advanced age. In this review, we highlight pathogenic changes that destabilize ocular homeostasis and promote AMD development. With normal aging, photoreceptors are steadily lost, Bruch's membrane thickens, the choroid thins, and hard drusen may form in the periphery. In AMD, many of these changes are exacerbated in addition to the development of disease-specific factors such as soft macular drusen. Para-inflammation, which can be thought of as an intermediate between basal and robust levels of inflammation, develops within the retina in an attempt to maintain ocular homeostasis, reflected by increased expression of the anti-inflammatory cytokine IL-10 coupled with shifts in macrophage plasticity from the pro-inflammatory M1 to the anti-inflammatory M2 polarization. In AMD, imbalances in the M1 and M2 populations together with activation of retinal microglia are observed and potentially contribute to tissue degeneration. Nonetheless, the retina persists in a state of chronic inflammation and increased expression of certain cytokines and inflammasomes is observed. Since not everyone develops AMD, the vital question to ask is how the body establishes a balance between normal age-related changes and the pathological phenotypes in AMD. PMID:23933169

IMPROVING THE AGE-RELATED MACULAR DEGENERATION CONSTRUCT: A New Classification System.

PubMed

Spaide, Richard F

2018-05-01

Previous models of disease in age-related macular degeneration (AMD) were incomplete in that they did not encompass subretinal drusenoid deposits (pseudodrusen), subtypes of neovascularization, and polypoidal choroidal vasculopathy. In addition, Type 3 neovascularization starts in the retina and may not necessarily involve the choroid. As such, the term choroidal neovascularization is not appropriate for these eyes. The new aspects in the AMD construct are to include specific lipoprotein extracellular accumulations, namely drusen and subretinal drusenoid deposits, as early AMD. The deposition of specific types of deposit seems to be highly correlated with choroidal thickness and topographical location in the macula. Late AMD includes macular neovascularization or atrophy. The particular type of extracellular deposit is predictive of the future course of the patient. For example, eyes with subretinal drusenoid deposits have a propensity to develop outer retinal atrophy, complete outer retinal and retinal pigment epithelial atrophy, or Type 3 neovascularization as specific forms of late AMD. Given Type 3 neovascularization may never involve the choroid, the term macular neovascularization is suggested for the entire spectrum of neovascular disease in AMD. In contrast to older classification systems, the proposed system encompasses the relevant presentations of disease and more precisely predicts the future course of the patient. In doing so, the concept was developed that there may be genetic risk alleles, which are not necessarily the same alleles that influence disease expression.

Do nutritional supplements have a role in age macular degeneration prevention?

PubMed

Pinazo-Durán, Maria D; Gómez-Ulla, Francisco; Arias, Luis; Araiz, Javier; Casaroli-Marano, Ricardo; Gallego-Pinazo, Roberto; García-Medina, Jose J; López-Gálvez, Maria Isabel; Manzanas, Lucía; Salas, Anna; Zapata, Miguel; Diaz-Llopis, Manuel; García-Layana, Alfredo

2014-01-01

Purpose. To review the proposed pathogenic mechanisms of age macular degeneration (AMD), as well as the role of antioxidants (AOX) and omega-3 fatty acids ( ω -3) supplements in AMD prevention. Materials and Methods. Current knowledge on the cellular/molecular mechanisms of AMD and the epidemiologic/experimental studies on the effects of AOX and ω -3 were addressed all together with the scientific evidence and the personal opinion of professionals involved in the Retina Group of the OFTARED (Spain). Results. High dietary intakes of ω -3 and macular pigments lutein/zeaxanthin are associated with lower risk of prevalence and incidence in AMD. The Age-Related Eye Disease study (AREDS) showed a beneficial effect of high doses of vitamins C, E, beta-carotene, and zinc/copper in reducing the rate of progression to advanced AMD in patients with intermediate AMD or with one-sided late AMD. The AREDS-2 study has shown that lutein and zeaxanthin may substitute beta-carotene because of its potential relationship with increased lung cancer incidence. Conclusion. Research has proved that elder people with poor diets, especially with low AOX and ω -3 micronutrients intake and subsequently having low plasmatic levels, are more prone to developing AMD. Micronutrient supplementation enhances antioxidant defense and healthy eyes and might prevent/retard/modify AMD.

Automated Age-related Macular Degeneration screening system using fundus images.

PubMed

Kunumpol, P; Umpaipant, W; Kanchanaranya, N; Charoenpong, T; Vongkittirux, S; Kupakanjana, T; Tantibundhit, C

2017-07-01

This work proposed an automated screening system for Age-related Macular Degeneration (AMD), and distinguishing between wet or dry types of AMD using fundus images to assist ophthalmologists in eye disease screening and management. The algorithm employs contrast-limited adaptive histogram equalization (CLAHE) in image enhancement. Subsequently, discrete wavelet transform (DWT) and locality sensitivity discrimination analysis (LSDA) were used to extract features for a neural network model to classify the results. The results showed that the proposed algorithm was able to distinguish between normal eyes, dry AMD, or wet AMD with 98.63% sensitivity, 99.15% specificity, and 98.94% accuracy, suggesting promising potential as a medical support system for faster eye disease screening at lower costs.

[Anti-VEGF therapy resistance in neovascular age-related macular degeneration].

PubMed

Budzinskaya, M V; Plyukhova, A A; Sorokin, P A

With account to the increase in the elderly population in most of the developed countries, the WHO defines age-related macular degeneration (AMD) as one of the main causes of blindness in the world. A large percentage of disability is accounted for by exudative, or neovascular, form of AMD. Today, a total of 5 anti-VEGF drugs exist that are recommended for treatment of exudative AMD: pegaptanib, ranibizumab, bevacizumab, aflibercept, and conbercept. Despite significant progress in the treatment of neovascular AMD yielded by the introduction into clinical practice of anti-VEGF drugs, some patients report a lack (down to complete lack) of response with standard treatment patterns and even a decrease in treatment efficacy after repeated intravitreal injections.

Advances in Age-related Macular Degeneration Understanding and Therapy

PubMed Central

Miller, Joan W; Bagheri, Saghar; Vavvas, Demetrios G

2017-01-01

While the development of anti-vascular endothelial growth factor (anti-VEGF) as a therapy for neovascular age-related macular degeneration (AMD) was a great success, the pathologic processes underlying dry AMD that eventually leads to photoreceptor dysfunction, death, and vision loss remain elusive to date, with a lack of effective therapies and increasing prevalence of the disease. There is an overwhelming need to improve the classification system of AMD, to increase our understanding of cell death mechanisms involved in both neovascular and non-neovascular AMD, and to develop better biomarkers and clinical endpoints to eventually be able to identify better therapeutic targets—especially early in the disease process. There is no doubt that it is a matter of time before progress will be made and better therapies will be developed for non-neovascular AMD. PMID:29142592

Retinal vascular caliber, iris color, and age-related macular degeneration in the Irish Nun Eye Study.

PubMed

McGowan, Amy; Silvestri, Giuliana; Moore, Evelyn; Silvestri, Vittorio; Patterson, Christopher C; Maxwell, Alexander P; McKay, Gareth J

2014-12-18

To evaluate the relationship between retinal vascular caliber (RVC), iris color, and age-related macular degeneration (AMD) in elderly Irish nuns. Data from 1233 participants in the cross-sectional observational Irish Nun Eye Study were assessed from digital photographs with a standardized protocol using computer-assisted software. Macular images were graded according to the modified Wisconsin Age-related Maculopathy Grading System. Regression models were used to assess associations, adjusting for age, mean arterial blood pressure, body mass index, refraction, and fellow RVC. In total, 1122 (91%) participants had gradable retinal images of sufficient quality for vessel assessment (mean age: 76.3 years [range, 56-100 years]). In an unadjusted analysis, we found some support for a previous finding that individuals with blue iris color had narrower retinal venules compared to those with brown iris color (P < 0.05), but this was no longer significant after adjustment. Age-related macular degeneration status was categorized as no AMD, any AMD, and late AMD only. Individuals with any AMD (early or late AMD) had significantly narrower arterioles and venules compared to those with no AMD in an unadjusted analysis, but this was no longer significant after adjustment. A nonsignificant reduced risk of any AMD or late AMD only was observed in association with brown compared to blue iris color, in both unadjusted and adjusted analyses. Retinal vascular caliber was not significantly associated with iris color or early/late AMD after adjustment for confounders. A lower but nonsignificant AMD risk was observed in those with brown compared to blue iris color. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

Parainflammation, chronic inflammation and age-related macular degeneration

PubMed Central

Chen, Mei; Xu, Heping

2016-01-01

Inflammation is an adaptive response of the immune system to noxious insults to maintain homeostasis and restore functionality. The retina is considered an immune privileged tissue due to its unique anatomical and physiological properties. During aging, the retina suffers from a low-grade chronic oxidative insult, which sustains for decades and increases in level with advancing age. As a result, the retinal innate immune system, particularly microglia and the complement system, undergo low levels of activation (para-inflammation). In many cases, this para-inflammatory response can maintain homeostasis in the healthy aging eye. However, in patients with age-related macular degeneration (AMD), this para-inflammatory response becomes dysregulated and contributes to macular damage. Factors contributing to the dysregulation of age-related retinal para-inflammation include genetic predisposition, environmental risk factors and old age. Dysregulated para-inflammation (chronic inflammation) in AMD damages the blood retina barrier (BRB), resulting in the breach of retinal immune privilege leading to the development of retinal lesions. This review discusses the basic principles of retinal innate immune responses to endogenous chronic insults in normal aging and in AMD, and explores the difference between beneficial para-inflammation and the detrimental chronic inflammation in the context of AMD. PMID:26292978

Resource utilization and costs of age-related macular degeneration.

PubMed

Halpern, Michael T; Schmier, Jordana K; Covert, David; Venkataraman, Krithika

2006-01-01

Data were analyzed from the 1999-2001 Medicare Beneficiary Encrypted Files for patients with age-related macular degeneration (AMD), an ophthalmic condition characterized by central vision loss. Classifying AMD subtype by International Classification of Diseases, Ninth Revision, Clinical Modifications (ICD-9-CM) (Centers for Disease Control and Prevention, 2003) code, resource utilization rates increased with disease progression. Individuals with more severe disease (wet only or wet and dry AMD) had greater costs than did those with less severe disease (drusen only or dry only). Costs among patients with wet disease increased yearly at rates exceeding inflation, possibly due in part to increased rates of treatment with photodynamic therapy among these individuals and the aging of the population.

Resource Utilization and Costs of Age-Related Macular Degeneration

PubMed Central

Halpern, Michael T.; Schmier, Jordana K.; Covert, David; Venkataraman, Krithika

2006-01-01

Data were analyzed from the 1999-2001 Medicare Beneficiary Encrypted Files for patients with age-related macular degeneration (AMD), an ophthalmic condition characterized by central vision loss. Classifying AMD subtype by International Classification of Diseases, Ninth Revision, Clinical Modifications (ICD-9-CM) (Centers for Disease Control and Prevention, 2003) code, resource utilization rates increased with disease progression. Individuals with more severe disease (wet only or wet and dry AMD) had greater costs than did those with less severe disease (drusen only or dry only). Costs among patients with wet disease increased yearly at rates exceeding inflation, possibly due in part to increased rates of treatment with photodynamic therapy among these individuals and the aging of the population. PMID:17290647

[Influence of the lutein-rich products consumption on its supply in diet of individuals with age-related macular degeneration (AMD)].

PubMed

Włodarek, Dariusz; Głabska, Dominika

2011-01-01

The aim of the study was analysis of the influence of the lutein-rich products consumption on its supply in diet of individuals with age-related macular degeneration The object of conducted analysis were 127 nutrition questionnaires from 64 individuals with AMD (44 female, 20 male) and 63 without AMD--control group (49 female, 14 male). The age of participants was 50-88. The nutrition questionnaire concerned: AMD and its course, consumption of lutein-rich products and lutein supplementation. Lutein supply was assessed on the base of most often consumed products and lutein content in typical servings as well as on the base of applied supplementation. Patients with AMD, in comparison with control group, were significantly more often choosing green bean, parsley, dill (Anethum graveolens) and young beetroot leaves, as well as were consuming more diversified lutein-rich products. Lutein supply from diet was significanly increased in case of spinach consumption (very high in lutein) and broccoli consumption (high in lutein and chosen relatively often). Other products did not cause increase of lutein supply from diet, even if they evoked increase of lutein content in the typical serving or of quantity of servings. Patients with AMD, in comparison with healthy individuals, more often consume lutein-rich products, but lutein supply from diet in both groups do not differ. Significant increase of lutein supply may be achieved only by consumption of products characterized by the highest content of it. Patients with AMD, in comparison with healthy individuals, more often apply lutein supplementation, that influences lutein daily supply.

Fully automated detection of diabetic macular edema and dry age-related macular degeneration from optical coherence tomography images

PubMed Central

Srinivasan, Pratul P.; Kim, Leo A.; Mettu, Priyatham S.; Cousins, Scott W.; Comer, Grant M.; Izatt, Joseph A.; Farsiu, Sina

2014-01-01

We present a novel fully automated algorithm for the detection of retinal diseases via optical coherence tomography (OCT) imaging. Our algorithm utilizes multiscale histograms of oriented gradient descriptors as feature vectors of a support vector machine based classifier. The spectral domain OCT data sets used for cross-validation consisted of volumetric scans acquired from 45 subjects: 15 normal subjects, 15 patients with dry age-related macular degeneration (AMD), and 15 patients with diabetic macular edema (DME). Our classifier correctly identified 100% of cases with AMD, 100% cases with DME, and 86.67% cases of normal subjects. This algorithm is a potentially impactful tool for the remote diagnosis of ophthalmic diseases. PMID:25360373

Updates on the Epidemiology of Age-Related Macular Degeneration.

PubMed

Jonas, Jost B; Cheung, Chui Ming Gemmy; Panda-Jonas, Songhomitra

2017-01-01

This meta-analysis reports on current estimates of the prevalence of age-related macular degeneration (AMD) based on a review of recent meta-analyses and literature research. Within an age of 45-85 years, global prevalences of any AMD, early AMD, and late AMD were 8.7% [95% credible interval (CrI), 4.3‒17.4], 8.0% (95% CrI, 4.0‒15.5), and 0.4% (95% CrI, 0.2-0.8). Early AMD was more common in individuals of European ancestry (11.2%) than in Asians (6.8%), whereas prevalence of late AMD did not differ significantly. AMD of any type was less common in individuals of African ancestry. The number of individuals with AMD was estimated to be 196 million (95% CrI, 140‒261) in 2020 and 288 million (95% CrI, 205‒399) in 2040. The worldwide number of persons blind (presenting visual acuity < 3/60) or with moderate to severe vision impairment (MSVI; presenting visual acuity < 6/18 to 3/60 inclusive) due to macular disease in 2010 was 2.1 million [95% uncertainty interval (UI), 1.9‒2.7] individuals out of 32.4 million individuals blind and 6.0 million (95% UI, 5.2‒8.1) persons out of 191 million people with MSVI. Age-standardized prevalence of macular diseases as cause of blindness in adults aged 50+ years worldwide decreased from 0.2% (95% UI, 0.2‒0.2) in 1990 to 0.1% (95% UI, 0.1‒0.2) in 2010; as cause for MSVI, it remained mostly unchanged (1990: 0.4%; 95% UI, 0.3‒0.5; 2010: 0.4%; 95% UI, 0.4‒0.6), with no significant sex difference. In 2015, AMD was the fourth most common cause of blindness globally (in approximately 5.8% of blind individuals) and third most common cause for MSVI (3.9%). These data show the globally increasing importance of AMD. Copyright 2017 Asia-Pacific Academy of Ophthalmology.

Benefits, Potential Harms, and Optimal Use of Nutritional Supplementation for Preventing Progression of Age-Related Macular Degeneration.

PubMed

Rojas-Fernandez, Carlos H; Tyber, Kevin

2017-03-01

To briefly review age-related macular degeneration (AMD), the main findings from the Age Related Eye Disease Study (AREDS) report number 8 on the use of nutritional supplements for AMD, and to focus on data suggesting that supplement use should be guided using genetic testing of AMD risk genes. A literature search (January 2001 through October 26, 2016) was conducted using MEDLINE and the following MeSH terms: Antioxidants/therapeutic use, Genotype, Macular Degeneration/drug therapy, Macular degeneration/genetics, Dietary Supplements, Proteins/genetics, and Zinc Compounds/therapeutic use. Bibliographies of publications identified were also reviewed. English-language studies assessing AREDS supplement response in patients with AMD in relation to complement factor H gene ( CFH) and age-related maculopathy susceptibility 2 gene ( ARMS2) risk alleles were evaluated. Three of the 4 studies demonstrated a treatment interaction between ARMS2 and CFH genotypes and a differential response to supplements. The fourth study documented an interaction for the CFH genotype only. Reported response interactions included attenuated response, no response, and good response, whereas a subset showed increased progression of AMD. Conversely, one study reported no interactions between CFH and ARMS2 risk alleles and response to supplements. The weight of the evidence supports using genetic testing to guide selection of ocular vitamin use. This approach will avoid using supplements that could speed the progression of AMD in vulnerable patients, avoid using supplements that will have little to no effect in others, and result in appropriately using supplements in those that are likely to derive meaningful benefits.

Focal macular electroretinograms after intravitreal injections of bevacizumab for age-related macular degeneration.

PubMed

Iwata, Eiji; Ueno, Shinji; Ishikawa, Kohei; Ito, Yasuki; Uetani, Ruka; Piao, Chang-Hua; Kondo, Mineo; Terasaki, Hiroko

2012-06-28

To evaluate the changes in the best-corrected visual acuity (BCVA), macular thickness, and focal macular electroretinograms (FMERGs) after three intravitreal injections of bevacizumab for a choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD). The medical records of 18 eyes of 18 patients who had received three consecutive monthly intravitreal injections of bevacizumab were retrospectively studied. The BCVA, macular thickness determined by optical coherence tomography (OCT), and FMERGs were measured before the first injection, and 10 days after each of the intravitreal bevacizumab injections. The number of eyes with improvement in BCVA after the first injection was one (6%), after the second injection was four (22%), and after the third injection was five (28%). The number of eyes with reduction in macular thickness was 4 (33%), 8 (44%), and 10 (56%) after each of the three injections. The number of eyes with increase in b-wave amplitude of the FMERGs was 7 (38%), 6 (33%), and 10 (56%) after each of the three each injections. The mean macular thickness was significantly thinner after the first injection, and the mean BCVA was significantly improved after the second injection. The mean amplitude and implicit time of the b-wave of the FMERGs were significantly improved only after the third injection (P<0.05). All parameters improved but the best was after the third injection, indicating that three monthly intravitreous injections with bevacizumab may be an effective treatment regimen for AMD.

Cfh genotype interacts with dietary glycemic index to modulate age-related macular degeneration-like features in mice

USDA-ARS?s Scientific Manuscript database

Age-related macular degeneration (AMD) is a leading cause of visual impairment worldwide. Genetics and diet contribute to the relative risk for developing AMD, but their interactions are poorly understood. Genetic variations in Complement Factor H (CFH), and dietary glycemic index (GI) are major ris...

Tear film proteome in age-related macular degeneration.

PubMed

Winiarczyk, Mateusz; Kaarniranta, Kai; Winiarczyk, Stanisław; Adaszek, Łukasz; Winiarczyk, Dagmara; Mackiewicz, Jerzy

2018-06-01

Age-related macular degeneration (AMD) is the main reason for blindness in elderly people in the developed countries. Current screening protocols have limitations in detecting the early signs of retinal degeneration. Therefore, it would be desirable to find novel biomarkers for early detection of AMD. Development of novel biomarkers would help in the prevention, diagnostics, and treatment of AMD. Proteomic analysis of tear film has shown promise in this research area. If an optimal set of biomarkers could be obtained from accessible body fluids, it would represent a reliable way to monitor disease progression and response to novel therapies. Tear films were collected on Schirmer strips from a total of 22 patients (8 with wet AMD, 6 with dry AMD, and 8 control individuals). 2D electrophoresis was used to separate tear film proteins prior to their identification with matrix-assisted laser desorption/ionization time of flight spectrometer (MALDI-TOF/TOF) and matching with functional databases. A total of 342 proteins were identified. Most of them were previously described in various proteomic studies concerning AMD. Shootin-1, histatin-3, fidgetin-like protein 1, SRC kinase signaling inhibitor, Graves disease carrier protein, actin cytoplasmic 1, prolactin-inducible protein 1, and protein S100-A7A were upregulated in the tear film samples isolated from AMD patients and were not previously linked with this disease in any proteomic analysis. The upregulated proteins supplement our current knowledge of AMD pathogenesis, providing evidence that certain specific proteins are expressed into the tear film in AMD. As far we are aware, this is the first study to have undertaken a comprehensive in-depth analysis of the human tear film proteome in AMD patients.

Dietary compound score and risk of age-related macular degeneration in the Age-Related Eye Disease Study

USDA-ARS?s Scientific Manuscript database

Purpose: Because foods provide many nutrients, which may interact with each other to modify risk for multifactorial diseases such as age-related macular degeneration (AMD), we sought to develop a composite scoring system to summarize the combined effect of multiple dietary nutrients on AMD risk. Th...

Cellular models and therapies for age-related macular degeneration

PubMed Central

Forest, David L.; Johnson, Lincoln V.; Clegg, Dennis O.

2015-01-01

ABSTRACT Age-related macular degeneration (AMD) is a complex neurodegenerative visual disorder that causes profound physical and psychosocial effects. Visual impairment in AMD is caused by the loss of retinal pigmented epithelium (RPE) cells and the light-sensitive photoreceptor cells that they support. There is currently no effective treatment for the most common form of this disease (dry AMD). A new approach to treating AMD involves the transplantation of RPE cells derived from either human embryonic or induced pluripotent stem cells. Multiple clinical trials are being initiated using a variety of cell therapies. Although many animal models are available for AMD research, most do not recapitulate all aspects of the disease, hampering progress. However, the use of cultured RPE cells in AMD research is well established and, indeed, some of the more recently described RPE-based models show promise for investigating the molecular mechanisms of AMD and for screening drug candidates. Here, we discuss innovative cell-culture models of AMD and emerging stem-cell-based therapies for the treatment of this vision-robbing disease. PMID:26035859

Automated detection of age-related macular degeneration in OCT images using multiple instance learning

NASA Astrophysics Data System (ADS)

Sun, Weiwei; Liu, Xiaoming; Yang, Zhou

2017-07-01

Age-related Macular Degeneration (AMD) is a kind of macular disease which mostly occurs in old people，and it may cause decreased vision or even lead to permanent blindness. Drusen is an important clinical indicator for AMD which can help doctor diagnose disease and decide the strategy of treatment. Optical Coherence Tomography (OCT) is widely used in the diagnosis of ophthalmic diseases, include AMD. In this paper, we propose a classification method based on Multiple Instance Learning (MIL) to detect AMD. Drusen can exist in a few slices of OCT images, and MIL is utilized in our method. We divided the method into two phases: training phase and testing phase. We train the initial features and clustered to create a codebook, and employ the trained classifier in the test set. Experiment results show that our method achieved high accuracy and effectiveness.

Macular Degeneration: An Overview.

ERIC Educational Resources Information Center

Chalifoux, L. M.

1991-01-01

This article presents information on macular degeneration for professionals helping persons with this disease adjust to their visual loss. It covers types of macular degeneration, the etiology of the disease, and its treatment. Also considered are psychosocial problems and other difficulties that persons with age-related macular degeneration face.…

Nutrition and age-related macular degeneration: research evidence in practice.

PubMed

Downie, Laura Elizabeth; Keller, Peter Richard

2014-08-01

Age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment in developed countries. In the absence of effective treatments to slow AMD progression, it is predicted that the prevalence of AMD will double over the next 20 years. One area of significant interest is the potential role that nutrition may play in preventing and/or delaying the progression of AMD. Specifically, is there any benefit in oral antioxidant and/or mineral supplementation? This review critically evaluates the currently available evidence relating to nutrition and AMD, with particular reference to the key findings of two large National Eye Institute-sponsored clinical studies, namely, the Age-Related Eye Disease Study (AREDS) and AREDS2. Topical controversies relating to nutrition and AMD are considered and analyzed in the context of the published literature to guide practitioners through assessing the merit, or otherwise, of common claims. This article provides a foundation for clinicians to provide informed advice to AMD patients based on available research evidence.

Memory Loss, Dementia, and Stroke: Implications for Rehabilitation of Older Adults with Age-Related Macular Degeneration

ERIC Educational Resources Information Center

Warren, Mary

2008-01-01

Older adults with age-related macular degeneration (AMD) are not immune to the other diseases of aging. Although AMD is the leading cause of low vision in older Americans, stroke is the leading cause of disability, and dementias affect another 2.5 million older Americans. Each condition alone can significantly impair a person's ability to…

The relationship of major American dietary patterns to age-related macular degeneration

USDA-ARS?s Scientific Manuscript database

We hypothesized that major American dietary patterns are associated with age-related macular degeneration (AMD) risk. This was a cross-sectional study with 8,103 eyes from 4,088 eligible participants in the baseline Age-Related Eye Disease Study (AREDS) were classified into control (n=2,739), early ...

Dry Macular Degeneration

MedlinePlus

... developing macular degeneration. Include fish in your diet. Omega-3 fatty acids, which are found in fish, may ... macular degeneration. Nuts, such as walnuts, also contain omega-3 fatty acids. By Mayo Clinic Staff . Mayo Clinic ...

Macular Atrophy in Neovascular Age-Related Macular Degeneration with Monthly versus Treat-and-Extend Ranibizumab: Findings from the TREX-AMD Trial.

PubMed

Abdelfattah, Nizar S; Al-Sheikh, Mayss; Pitetta, Sean; Mousa, Ahmed; Sadda, SriniVas R; Wykoff, Charles C

2017-02-01

To compare the enlargement rate of macular atrophy (ERMA) in eyes treated with ranibizumab monthly or using a treat-and-extend (TREX) regimen for neovascular age-related macular degeneration (AMD) or fellow control eyes, as well as analyze risk factors for macular atrophy (MA) development and progression. Eighteen-month, multicenter, randomized, controlled clinical trial. Sixty patients with treatment-naïve neovascular AMD in 1 eye randomized 1:2 to monthly or TREX ranibizumab. Patients' study and fellow eyes were followed for 18 months using spectral-domain optical coherence tomography (SD OCT) and fundus autofluorescence (FAF) imaging. The MA was quantified on FAF images using Heidelberg Region Finder software (Heidelberg Engineering, Heidelberg, Germany), with suspected areas of atrophy confirmed by SD OCT and infrared reflectance imaging. For eyes without baseline MA yet developed MA by 18 months, intervening visits were assessed to determine the first visit at which MA appeared to define progression rates. Foveal choroidal thickness (FCT), subretinal hyperreflective material (SHRM), and pigment epithelial detachment (PED), were assessed at baseline to determine whether they influenced MA progression. Mean ERMA at 18 months. Relationship between visual acuity and MA, and the baseline risk factors for ERMA were also assessed. The final analysis cohort included 88 eyes in 3 groups: monthly (n = 19), TREX (n = 30), and control fellow eyes (n = 39). Mean ERMA over 18 months was 0.39±0.67 (monthly), 1.1±1.9 (TREX), and 0.49±1 mm 2 (control, P = 0.12). Mean ERMA per group among the 40.9% (n = 36) of baseline patients with MA was 0.9±1, 1.9±2.2, and 1±1.3 mm 2 , respectively (P = 0.31). The incidence rate of MA in the 3 groups was 40%, 0%, and 8.3%, respectively. Mann-Whitney U test revealed a statistically significant association between baseline FCT (127±46 vs. 155±55 μm, P = 0.01) and SHRM thickness (106±131 vs. 50±85 μm, P = 0.02) on MA. In

HUMAN HtrA1 IN THE ARCHIVED EYES WITH AGE-RELATED MACULAR DEGENERATION

PubMed Central

Chan, Chi-Chao; Shen, Defen; Zhou, Min; Ross, Robert J.; Ding, Xiaoyan; Zhang, Kang; Green, W. Richard; Tuo, Jingsheng

2007-01-01

Purpose HtrA1 belongs to the high temperature requirement factor A family of serine proteases, which are involved in protein quality control and cell fate. A single-nucleotide polymorphism (SNP), rs11200638, in the promoter of HtrA1 at chromosome 10q26 is reported as a likely causal variant for age-related macular degeneration (AMD). The SNP is located in the regulatory region and increases production of HtrA1 protein. This study investigates HtrA1 expression and SNP genotypes in archived ocular slides with AMD. Methods Macular, nonretinal, and peripheral retinal cells were microdissected from archived slides from 57 eyes with AMD and 16 age-matched, non-AMD controls. HtrA1 rs11200638 SNP genotyping was performed using polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis. HtrA1 transcripts were measured using real-time reverse transcriptase–PCR. HtrA1 protein expression was evaluated using avidin-biotin complex immunohistochemistry. Results HtrA1 (G/A) SNP was successfully genotyped in 52 AMD cases and 13 non-AMD subjects. The frequencies of the risk allele (A) were 55 of 104 (52.9%) and 8 of 26 (30.8%) in AMD and control groups, respectively. HtrA1 mRNA was detected in normal peripheral and macular retinas, higher in the periphery than maculae. HtrA1 mRNA was much higher in the macula and a lot lower in the periphery of the AMD eyes as compared to control eyes. HtrA1 protein was expressed in normal retinal vascular endothelia and retinal pigment epithelia. Intense immunoreaction against HtrA1 was found in AMD lesions, slightly more in wet than dry AMD lesions. Conclusion This study successfully analyzes HtrA1 SNP and transcript expression in microdissected cells from archived paraffin fixed slides. Up-regulation of HtrA1 is detected in the macular lesions of AMD eyes. The data further suggest that rs11200638 in HtrA1 promoter is associated with AMD development. PMID:18427598

Mediated-reality magnification for macular degeneration rehabilitation

NASA Astrophysics Data System (ADS)

Martin-Gonzalez, Anabel; Kotliar, Konstantin; Rios-Martinez, Jorge; Lanzl, Ines; Navab, Nassir

2014-10-01

Age-related macular degeneration (AMD) is a gradually progressive eye condition, which is one of the leading causes of blindness and low vision in the Western world. Prevailing optical visual aids compensate part of the lost visual function, but omitting helpful complementary information. This paper proposes an efficient magnification technique, which can be implemented on a head-mounted display, for improving vision of patients with AMD, by preserving global information of the scene. Performance of the magnification approach is evaluated by simulating central vision loss in normally sighted subjects. Visual perception was measured as a function of text reading speed and map route following speed. Statistical analysis of experimental results suggests that our magnification method improves reading speed 1.2 times and spatial orientation to find routes on a map 1.5 times compared to a conventional magnification approach, being capable to enhance peripheral vision of AMD subjects along with their life quality.

Maculoplasty for age-related macular degeneration: reengineering Bruch's membrane and the human macula.

PubMed

Del Priore, Lucian V; Tezel, Tongalp H; Kaplan, Henry J

2006-11-01

Age-related macular degeneration (AMD) is the leading cause of blindness in the western world. Over the last decade, there have been significant advances in the management of exudative AMD with the introduction of anti-VEGF drugs; however, many patients with exudative AMD continue to lose vision and there are no effective treatments for advanced exudative AMD or geographic atrophy. Initial attempts at macular reconstruction using cellular transplantation have not been effective in reversing vision loss. Herein we discuss the current status of surgical attempts to reconstruct damaged subretinal anatomy in advanced AMD. We reinforce the concept of maculoplasty for advanced AMD, which is defined as reconstruction of macular anatomy in patients with advanced vision loss. Successful maculoplasty is a three-step process that includes replacing or repairing damaged cells (using transplantation, translocation or stimulation of autologous cell proliferation); immune suppression (if allografts are used to replace damaged cells); and reconstruction or replacement of Bruch's membrane (to restore the integrity of the substrate for proper cell attachment). In the current article we will review the rationale for maculoplasty in advanced AMD, and discuss the results of initial clinical attempts at macular reconstruction. We will then discuss the role of Bruch's membrane damage in limiting transplant survival and visual recovery, and discuss the effects of age-related changes within human Bruch's membrane on the initial attachment and subsequent proliferation of transplanted cells. We will discuss attempts to repair Bruch's membrane by coating with extracellular matrix ligands, anatomic reconstitution of the inner collagen layer, and the effects of Bruch's membrane reconstruction of ultrastuctural anatomy and subsequent cell behavior. Lastly, we will emphasize the importance of continued efforts required for successful maculoplasty.

[The age-related macular degeneration as a vascular disease/part of systemic vasculopathy: contributions to its pathogenesis].

PubMed

Fischer, Tamás

2015-03-01

The wall of blood vessels including those in choroids may be harmed by several repeated and/or prolonged mechanical, physical, chemical, microbiological, immunologic, and genetic impacts (risk factors), which may trigger a protracted response, the so-called host defense response. As a consequence, pathological changes resulting in vascular injury (e. g. atherosclerosis, age-related macular degeneration) may be evolved. Risk factors can also act directly on the endothelium through an increased production of reactive oxygen species promoting an endothelial activation, which leads to endothelial dysfunction, the onset of vascular disease. Thus, endothelial dysfunction is a link between the harmful stimulus and vascular injury; any kind of harmful stimuli may trigger the defensive chain that results in inflammation that may lead to vascular injury. It has been shown that even early age-related macular degeneration is associated with the presence of diffuse arterial disease and patients with early age-related macular degeneration demonstrate signs of systemic and retinal vascular alterations. Chronic inflammation, a feature of AMD, is tightly linked to diseases associated with ED: AMD is accompanied by a general inflammatory response, in the form of complement system activation, similar to that observed in degenerative vascular diseases such as atherosclerosis. All these facts indicate that age-related macular degeneration may be a vascular disease (or part of a systemic vasculopathy). This recognition could have therapeutic implications because restoration of endothelial dysfunction may prevent the development or improve vascular disease resulting in prevention or improvement of age-related macular degeneration as well.

RECURRENCE OF CHOROIDAL NEOVASCULARIZATION LESION ACTIVITY AFTER AFLIBERCEPT TREATMENT FOR AGE-RELATED MACULAR DEGENERATION.

PubMed

Wakazono, Tomotaka; Yamashiro, Kenji; Oishi, Akio; Ooto, Sotaro; Tamura, Hiroshi; Akagi-Kurashige, Yumiko; Hata, Masayuki; Takahashi, Ayako; Tsujikawa, Akitaka; Yoshimura, Nagahisa

2017-11-01

To examine the recurrence rate of choroidal neovascularization (CNV) lesion activity in age-related macular degeneration (AMD) and associated factors after 1-year aflibercept treatment. Age-related macular degeneration eyes with 1-year aflibercept fixed-regimen treatment and a follow-up period of at least 18 months from the initial aflibercept injection for treatment-naive exudative AMD were retrospectively evaluated. The recurrence rate was examined. Age, gender, visual acuity, AMD subtype, greatest linear dimension, and retinal and choroidal thicknesses at the 12th month examination were compared between eyes with and without recurrence. Presence of remnant polyps and pigment epithelial detachment (PED) morphology were also compared in polypoidal choroidal vasculopathy (PCV) eyes. Of the 98 eyes studied, 69 displayed a dry macula at the 12th month examination; 43.7% exhibited recurrence during the subsequent 12-month period in Kaplan-Meier analysis. Although no factors associated with recurrence were detected in AMD, remnant polyps and pigment epithelial detachment morphology at the 12th month examination were significantly associated with recurrence in polypoidal choroidal vasculopathy (P = 0.018 and 0.048, respectively). Continuous, proactive treatment would be considered overtreatment for more than half of the AMD eyes that achieved a dry macula. Angiography and optical coherence tomography analyses may be useful for predicting recurrence in polypoidal choroidal vasculopathy eyes.

Suspected macular degeneration in a captive Western lowland gorilla (Gorilla gorilla gorilla).

PubMed

Steinmetz, Andrea; Bernhard, Andreas; Sahr, Sabine; Oechtering, Gerhard

2012-09-01

The case of a 31-year-old captive female Western lowland gorilla (Gorilla gorilla gorilla) with decreased near vision but good distance vision is presented. Examination of the fundus revealed drusen-like bodies in the macula presumably because of an age-related macular degeneration (AMD). © 2012 American College of Veterinary Ophthalmologists.

Reticular pseudodrusen in age-related macular degeneration.

PubMed

Hogg, Ruth Esther

2014-08-01

Historically, drusen, which are recognized as the hallmark of age-related macular degeneration (AMD), have been described in terms of size, margins, and texture, and several studies have emphasized the importance of large soft drusen particularly when combined with focal pigmentary irregularities in determining the risk of progression to neovascular AMD. However, recent developments in imaging over the past decade have revealed a further distinct phenotype strongly associated with the development of late AMD, namely, reticular pseudodrusen (RPD) or reticular drusen. Reticular pseudodrusen appear as yellowish interlacing networks in the fundus and, although visible on color photography, are better visualized using infrared imaging or spectral domain optical coherence tomography. Studies correlating spectral domain optical coherence tomography and confocal scanning laser ophthalmoscopy have shown that RPD are subretinal deposits located internal to the retinal pigment epithelium in contrast to traditional drusen, which are located external to the retinal pigment epithelium. As multiple longitudinal studies have revealed RPD are strong predictors for progression to both neovascular AMD and geographic atrophy, the interest in understanding the role that RPD play in the pathogenesis of AMD has grown. This review focuses on the current literature concerning RPD and considers what is currently known regarding their epidemiology, risk factors, appearance in both retinal imaging and histology, impact on visual function, relationship to other AMD lesions, and association with the development of late AMD.

miRNAs as potential therapeutic targets for age-related macular degeneration.

PubMed

Wang, Shusheng; Koster, Kyle M; He, Yuguang; Zhou, Qinbo

2012-03-01

Since their recent discovery, miRNAs have been shown to play critical roles in a variety of pathophysiological processes. Such processes include pathological angiogenesis, the oxidative stress response, immune response and inflammation, all of which have been shown to have important and interdependent roles in the pathogenesis and progression of age-related macular degeneration (AMD). Here we present a brief review of the pathological processes involved in AMD and review miRNAs and other noncoding RNAs involved in regulating these processes. Specifically, we discuss several candidate miRNAs that show promise as AMD therapeutic targets due to their direct involvement in choroidal neovascularization or retinal pigment epithelium atrophy. We discuss potential miRNA-based therapeutics and delivery methods for AMD and provide future directions for the field of miRNA research with respect to AMD. We believe the future of miRNAs in AMD therapy is promising.

Removal of choroidal neovascular membrane in a case of macular hole after anti-VEGF therapy for age-related macular degeneration.

PubMed

Hirata, Akira; Hayashi, Ken; Murata, Kazuhisa; Nakamura, Kei-Ichiro

2018-03-01

The formation of macular hole after receiving anti-vascular endothelial growth factor (anti-VEGF) therapy is rare. We report a case of macular hole that occurred after intravitreal injection of an anti-VEGF agent for age-related macular degeneration (AMD) in a patient, who underwent vitrectomy combined with choroidal neovascularization (CNV) removal. A 64-year-old female with AMD affecting her right eye received an intravitreal injection of an anti-VEGF agent. After treatment, we identified a full thickness macular hole (MH) that was associated with the rapid resolution of the macular edema and contraction of the CNV. After performing vitrectomy combined with CNV removal, the MH closed and her visual acuity improved. Examination of the removed CNV revealed a network of microvessels devoid of pericytes. and Importance: The present findings suggest that rapid resolution of macular edema and contraction of the CNV and/or mild increase in the vitreous traction after anti-VEGF therapy could potentially cause MH. CNV removal via the MH may be an acceptable procedure, if the MH remains open, the CNV is of the classic type, and it spares a central portion of the fovea.

Comparison of macular choroidal thickness among patients older than age 65 with early atrophic age-related macular degeneration and normals.

PubMed

Sigler, Eric J; Randolph, John C

2013-09-19

To compare macular choroidal thickness between patients older than 65 years with early atrophic age-related macular degeneration (AMD) and normals. This was a consecutive, cross-sectional observational study. Enhanced depth imaging spectral-domain optical coherence tomography using horizontal raster scanning at 12 locations throughout the macula was performed in one eye of consecutive patients presenting with large soft drusen alone, drusen with additional features of early AMD, or a normal fundus. Choroidal thickness was measured at 7 points for each raster scan in the central 3 mm of the macula (total 84 points per eye). In addition, a single subfoveolar measurement was obtained for each eye. One hundred fifty eyes of 150 patients were included. There was no significant difference between mean refractive error for each diagnosis category via one-way ANOVA (P = 0.451). Mean macular choroidal thickness (CT) was 235 ± 49 μm (range, 125-334 μm; median 222 μm) for normals, 161 ± 39 μm (range, 89-260 μm; median = 158 μm) for the drusen group, and 115 ± 40 μm (range, 22-256 μm; median = 112 μm) for patients with AMD. Mean macular CT was significantly different via one-way ANOVA among all diagnosis categories (P < 0.001). The presence of features of early AMD without geographic atrophy and/or soft drusen alone is associated with decreased mean macular CT in vivo compared to that in patients with no chorioretinal pathology. Using enhanced depth imaging, measurement of a single subfoveolar choroidal thickness is highly correlated to mean central macular CT.

Gut microbiota modify risk for dietary glycemia-induced age-related macular degeneration.

PubMed

Rowan, Sheldon; Taylor, Allen

2018-03-21

Age-related macular degeneration (AMD) is a leading cause of blindness world-wide. Although the etiology of AMD is multifactorial, diet and nutrition have strong epidemiologic associations with disease onset and progression. Recent studies indicate a role for gut microbiota in development of AMD in mouse models and in some forms of human AMD. We previously found that consuming lower glycemia diets is associated with protection against AMD in humans and switching from higher to lower glycemia diets arrests AMD phenotypes in mice. Gut microbiota populations and circulating microbial cometabolites were altered in response to dietary carbohydrates, indicating a gut-retina axis. Here we explore additional gut microbiota-AMD interactions that point toward pathogenic roles for some gut microbiota families, including Ruminococcaceae and Lachnospiraceae, and individual members of Turicibacteraceae, Clostridiaceae, and Mogibacteriaceae. We also speculate on potential mechanisms by which gut microbiota influence AMD, with the objective of devising new AMD diagnoses and treatments.

Reproducibility of Macular Thickness Measurements in Eyes Affected by Dry Age-Related Macular Degeneration From Two Different SD-OCT Instruments.

PubMed

Tepelus, Tudor C; Hariri, Amir H; Balasubramanian, Siva; Sadda, SriniVas R

2018-06-01

To compare macular thickness measurement algorithms of two different spectral-domain optical coherence tomography (SD-OCT) devices in eyes affected by dry age-related macular degeneration (AMD). Patients with dry AMD and healthy volunteers from the retina clinic of the Doheny Eye Center - UCLA were imaged using two different SD-OCT devices: the RS-3000 Advance (Nidek, Padova, Italy) and the Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA). All patients had been previously diagnosed with drusen or geographic atrophy due to AMD. The commercial instrument software was used to generate the macular retinal thickness measurements, and measurements were compared between devices. Eighty-five diseased eyes from 49 patients and 16 healthy control eyes from eight normal volunteers were included in this study. The macular thickness measurements generated by the two instruments in eyes with AMD differed significantly in mean retinal thickness in the foveal center subfield (257.34 μm ± 51.72 μm using the Nidek OCT vs. 238.20 μm ± 51.89 μm using the Cirrus OCT; P < .001). The mean difference in macular thickness between the two devices was 19.14 μm ± 5.84 μm for diseased eyes and 17.06 μm ± 5.28 μm in normal control eyes, and this was not statistically different between the two groups (P > .05). The macular thickness measurements in diseased eyes, as evaluated by the two different instruments, however, showed excellent correlation (r = 0.99; P < .001), with an intraclass correlation coefficient of 0.99 (95% confidence interval, 0.98-0.99). Post hoc evaluation of cases with larger differences also showed differences in foveal center selection and variabilities in boundary selection with specific pathology. Macular thickness measurements provided by the Nidek and Cirrus OCT instruments in eyes with dry AMD are highly correlated but show a consistent difference, which may allow the use of a standard correction factor to be applied to better interrelate measurements between

A 5-year multicenter prospective cohort study on the long-term visual prognosis and predictive factors for visual outcome in Japanese patients with age-related macular degeneration: the AMD2000 study.

PubMed

Akagi-Kurashige, Yumiko; Tsujikawa, Akitaka; Yuzawa, Mitsuko; Ishibashi, Tatsuro; Nakanishi, Hideo; Nakatani, Eiji; Teramukai, Satoshi; Fukushima, Masanori; Yoshimura, Nagahisa

2018-03-01

In this study (AMD2000), we aimed to determine the visual prognosis of Japanese patients with age-related macular degeneration (AMD). This was a multicenter prospective observational cohort study. In total, 460 patients with AMD were recruited from April 2006 to March 2009 from 18 clinical trial sites in Japan. They were followed up for 5 years, as they continued to receive medical treatment. Of the 409 study eyes followed up for at least 1 year, 243 eyes (59.4%) were treated with photodynamic therapy (PDT) using verteporfin, and 58 eyes (14.2%) were treated with intravitreal injections of antivascular endothelial growth factor agents as the initial treatment. The mean best-corrected visual acuities (BCVA) for typical AMD (tAMD; 0.688 ± 0.498) and polypoidal choroidal vasculopathy (PCV; 0.451 ± 0.395) were significantly less at 2 years (tAMD, 0.779 ± 0.632, P < 0.05; PCV, 0.534 ± 0.618, P < 0.05) and at 5 years (AMD, 0.873 ± 0.718, P < 0.05; PCV, 0.635 ± 0.668, P < 0.05) than at baseline. In eyes with tAMD, absence of blocked fluorescence was associated with 5-year maintenance of the baseline BCVA. Regarding PCV, the presence of polypoidal lesions and cystoid macular edema as well as the lesion size was associated with 5-year maintenance of the baseline BCVA. In some patients, the diagnosis changed: of the 192 eyes initially diagnosed with typical AMD, 19 were newly diagnosed with PCV during follow-up. Maintaining the baseline BCVA over the long term is difficult in Japanese eyes with wet AMD.

Real-world use of ranibizumab for neovascular age-related macular degeneration in Taiwan.

PubMed

Chang, Yi-Sheng; Lee, Wan-Ju; Lim, Chen-Chee; Wang, Shih-Hao; Hsu, Sheng-Min; Chen, Yi-Chian; Cheng, Chia-Yi; Teng, Yu-Ti; Huang, Yi-Hsun; Lai, Chun-Chieh; Tseng, Sung-Huei

2018-05-10

This study investigated the "real-world" use of ranibizumab for neovascular age-related macular degeneration (nAMD) in Taiwan and assessed the visual outcome. We reviewed the medical records at National Cheng Kung University Hospital, Taiwan, during 2012-2014 for 264 consecutive eyes of 229 patients with nAMD, who applied for ranibizumab covered by national health insurance. A total of 194 eyes (73.5%) in 179 patients (65.5% men; mean ± standard deviation age 69.4 ± 10.7 years) were pre-approved for treatment. Applications for treatment increased year by year, but approval rates decreased during this time. The major causes of rejection for funding were diseases mimicking nAMD, including macular pucker/epiretinal membrane, macular scarring, dry-type AMD, and possible polypoidal choroidal vasculopathy. After completion of three injections in 147 eyes, visual acuity significantly improved, gaining ≥1 line in 51.8% of eyes and stabilising in 38.3% of 141 eyes in which visual acuity was measured. The 114 eyes approved with only one application had a better visual outcome than the 27 eyes approved after the second or third applications. In conclusion, ranibizumab is effective for nAMD; however, approval after the second or third application for national health insurance cover is a less favourable predictor of visual outcome.

Risk Factors and Biomarkers of Age-Related Macular Degeneration

PubMed Central

Lambert, Nathan G.; Singh, Malkit K.; ElShelmani, Hanan; Mansergh, Fiona C.; Wride, Michael A.; Padilla, Maximilian; Keegan, David; Hogg, Ruth E.; Ambati, Balamurali K.

2016-01-01

A biomarker can be a substance or structure measured in body parts, fluids or products that can affect or predict disease incidence. As age-related macular degeneration (AMD) is the leading cause of blindness in the developed world, much research and effort has been invested in the identification of different biomarkers to predict disease incidence, identify at risk individuals, elucidate causative pathophysiological etiologies, guide screening, monitoring and treatment parameters, and predict disease outcomes. To date, a host of genetic, environmental, proteomic, and cellular targets have been identified as both risk factors and potential biomarkers for AMD. Despite this, their use has been confined to research settings and has not yet crossed into the clinical arena. A greater understanding of these factors and their use as potential biomarkers for AMD can guide future research and clinical practice. This article will discuss known risk factors and novel, potential biomarkers of AMD in addition to their application in both academic and clinical settings. PMID:27156982

Genetics of Age-Related Macular Degeneration: Current Concepts, Future Directions

PubMed Central

DeAngelis, Margaret M.; Silveira, Alexandra C.; Carr, Elizabeth A.; Kim, Ivana K.

2014-01-01

Age-related macular degeneration (AMD) is a progressive degenerative disease which leads to blindness, affecting the quality of life of millions of Americans. More than 1.75 million individuals in the United States are affected by the advanced form of AMD. The etiological pathway of AMD is not yet fully understood, but there is a clear genetic influence on disease risk. To date, the 1q32 (CFH) and 10q26 (PLEKHA1/ARMS2/HTRA1) loci are the most strongly associated with disease; however, the variation in these genomic regions alone is unable to predict disease development with high accuracy. Therefore, current genetic studies are aimed at identifying new genes associated with AMD and their modifiers, with the goal of discovering diagnostic or prognostic biomarkers. Moreover, these studies provide the foundation for further investigation into the pathophysiology of AMD by utilizing a systems-biology-based approach to elucidate underlying mechanistic pathways. PMID:21609220

Rare genetic variants in Tunisian Jewish patients suffering from age-related macular degeneration.

PubMed

Pras, Eran; Kristal, Dana; Shoshany, Nadav; Volodarsky, Dina; Vulih, Inna; Celniker, Gershon; Isakov, Ofer; Shomron, Noam; Pras, Elon

2015-07-01

To explore the molecular basis of familial, early onset, age-related macular degeneration (AMD) with diverse phenotypes, using whole exome sequencing (WES). We performed WES on four patients (two sibs from two families) manifesting early-onset AMD and searched for disease-causing genetic variants in previously identified macular degeneration related genes. Validation studies of the variants included bioinformatics tools, segregation analysis of mutations within the families and mutation screening in an AMD cohort of patients. The index patients were in their 50s when diagnosed and displayed a wide variety of clinical AMD presentations: from limited drusen in the posterior pole to multiple basal-laminar drusen extending peripherally. Severe visual impairment due to extensive geographic atrophy and/or choroidal-neovascularisation was common by the age of 75 years. Approximately, 400 000 genomic variants for each DNA sample were included in the downstream bioinformatics analysis, which ended in the discovery of two novel variants; in one family a single bp deletion was identified in the Hemicentin (HMCN1) gene (c.4162delC), whereas in the other, a missense variant (p.V412M) in the Complement Factor-I (CFI) gene was found. Screening for these variants in a cohort of patients with AMD identified another family with the CFI variant. This report uses WES to uncover rare genetic variants in AMD. A null-variant in HMCN1 has been identified in one AMD family, and a missense variant in CFI was discovered in two other families. These variants confirm the genetic complexity and significance of rare genetic variants in the pathogenesis of AMD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Long-term effectiveness of ranibizumab for age-related macular degeneration and diabetic macular edema

PubMed Central

Fong, Angie HC; Lai, Timothy YY

2013-01-01

Neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME) are major causes of visual impairment in the elderly population worldwide. With the aging population, the prevalence of neovascular AMD and DME has increased substantially over the recent years. Vascular endothelial growth factor (VEGF) has been implicated as playing an important role in the pathogenesis of both neovascular AMD and DME. Since its introduction in 2006, ranibizumab, a recombinant, humanized, monoclonal antibody fragment against all isoforms of VEGF-A, has revolutionized the treatment of neovascular AMD and DME. The efficacy and safety of ranibizumab in neovascular AMD has been demonstrated in the ANCHOR and MARINA trials. Further studies including the PIER, PrONTO, and SUSTAIN trials have also evaluated the optimal dosing regimen of ranibizumab in neovascular AMD. The CATT and IVAN trials compared the safety and efficacy of ranibizumab with off-label use of bevacizumab. Studies such as SUSTAIN and HORIZON have shown that ranibizumab has a good safety profile and is well tolerated for over 4 years with very few serious ocular and systemic adverse events. For DME, Phase II RESOLVE study and Phase III RISE and RIDE studies have demonstrated superiority of ranibizumab treatment in improving vision over placebo controls. Phase II READ and Phase III RESOLVE and REVEAL studies have shown that ranibizumab is more effective both as monotherapy and in combination with laser compared with laser monotherapy. The 3-year results from the DRCRnet protocol I study found that ranibizumab with deferred laser resulted in better long-term visual outcome compared with ranibizumab with prompt laser. This review summarizes various important clinical trials on the long-term efficacy and safety of ranibizumab in the treatment of neovascular AMD and DME. The pharmacological properties of ranibizumab, its cost effectiveness, and impact on quality of life will also be discussed. PMID:23766636

Hot Topics in Pharmacogenetics of Age-Related Macular Degeneration.

PubMed

Schwartz, Stephen G; Brantley, Milam A; Kovach, Jaclyn L; Grzybowski, Andrzej

2017-01-01

Age-related macular degeneration (AMD) is a leading cause of irreversible visual loss and is primarily treated with nutritional supplementation as well as with anti-vascular endothelial growth factor (VEGF) agents for certain patients with neovascular disease. AMD is a complex disease with both genetic and environmental risk factors. In addition, treatment outcomes from nutritional supplementation and anti-VEGF agents vary considerably. Therefore, it is reasonable to suspect that there may be pharmacogenetic influences on these treatments. Many series have reported individual associations with variants in complement factor H (CFH), age-related maculopathy susceptibility 2 (ARMS2), and other loci. However, at this time there are no validated associations. With respect to AMD, pharmacogenetics remains an intriguing area of research but is not helpful for routine clinical management. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Imaging Polarimetry in Age-Related Macular Degeneration

PubMed Central

Miura, Masahiro; Yamanari, Masahiro; Iwasaki, Takuya; Elsner, Ann E.; Makita, Shuichi; Yatagai, Toyohiko; Yasuno, Yoshiaki

2010-01-01

PURPOSE To evaluate the birefringence properties of eyes with age-related macular degeneration (AMD). To compare the information from two techniques—scanning laser polarimetry (GDx) and polarization-sensitive spectral-domain optical coherence tomography (OCT)—and investigate how they complement each other. METHODS The authors prospectively examined the eyes of two healthy subjects and 13 patients with exudative AMD. Using scanning laser polarimetry, they computed phase-retardation maps, average reflectance images, and depolarized light images. To obtain polarimetry information with improved axial resolution, they developed a fiber-based, polarization-sensitive, spectral-domain OCT system and measured the phase retardation associated with birefringence in the same eyes. RESULTS Both GDx and polarization-sensitive spectral-domain optical coherence tomography detected abnormal birefringence at the locus of exudative lesions. Polarization-sensitive, spectral-domain OCT showed that in the old lesions with fibrosis, phase-retardation values were significantly larger than in the new lesions (P = 0.020). Increased scattered light and altered polarization scramble were associated with portions of the lesions. CONCLUSIONS GDx and polarization-sensitive spectral-domain OCT are complementary in probing birefringence properties in exudative AMD. Polarimetry findings in exudative AMD emphasized different features and were related to the progression of the disease, potentially providing a noninvasive tool for microstructure in exudative AMD. PMID:18515594

Autophagy regulating kinases as potential therapeutic targets for age-related macular degeneration.

PubMed

Kaarniranta, Kai; Kauppinen, Anu; Blasiak, Janusz; Salminen, Antero

2012-11-01

Age-related macular degeneration (AMD) is the leading cause of central vision loss in the elderly in the developed countries. The number of AMD patients will double during the next decades due to increasing number of aged people. Chronic oxidative stress, inflammation and accumulation of protein-rich deposits both in the retinal pigment epithelium lysosomes and under the retinal pigment epithelium herald the onset of AMD. The disease can be divided into dry and wet AMD forms. The dry form of the disease is more prevalent accounting for up to 90% of all cases. Continued intraocular injections are the current treatment strategy to prevent progression of wet AMD. It is a major challenge to develop new drugs that could prevent or at least ease the symptoms of the increasing population of AMD patients. Since AMD pathology is clearly associated with accumulated protein deposits, the autophagy clearance system might represent a potential future therapeutic target for AMD as is thoroughly discussed here.

Concordance of Macular Pigment Measurement Using Customized Heterochromatic Flicker Photometry and Fundus Autofluorescence in Age-Related Macular Degeneration.

PubMed

Akuffo, Kwadwo Owusu; Beatty, Stephen; Stack, Jim; Peto, Tunde; Leung, Irene; Corcoran, Laura; Power, Rebecca; Nolan, John M

2015-12-01

We compared macular pigment (MP) measurements using customized heterochromatic flicker photometry (Macular Metrics Densitometer) and dual-wavelength fundus autofluorescence (Heidelberg Spectralis HRA + OCT MultiColor) in subjects with early age-related macular degeneration (AMD). Macular pigment was measured in 117 subjects with early AMD (age, 44-88 years) using the Densitometer and Spectralis, as part of the Central Retinal Enrichment Supplementation Trial (CREST; ISRCTN13894787). Baseline and 6-month study visits data were used for the analyses. Agreement was investigated at four different retinal eccentricities, graphically and using indices of agreement, including Pearson correlation coefficient (precision), accuracy coefficient, and concordance correlation coefficient (ccc). Agreement was poor between the Densitometer and Spectralis at all eccentricities, at baseline (e.g., at 0.25° eccentricity, accuracy = 0.63, precision = 0.35, ccc = 0.22) and at 6 months (e.g., at 0.25° eccentricity, accuracy = 0.52, precision = 0.43, ccc = 0.22). Agreement between the two devices was significantly greater for males at 0.5° and 1.0° of eccentricity. At all eccentricities, agreement was unaffected by cataract grade. In subjects with early AMD, MP measurements obtained using the Densitometer and Spectralis are not statistically comparable and should not be used interchangeably in either the clinical or research setting. Despite this lack of agreement, statistically significant increases in MP, following 6 months of supplementation with macular carotenoids, were detected with each device, confirming that these devices are capable of measuring change in MP within subjects over time. (http://www.controlled-trials.com number, ISRCTN13894787.).

Comparison of macular pigment optical density in patients with dry and wet age-related macular degeneration.

PubMed

Ozyurt, Ayhan; Kocak, Nilufer; Akan, Pınar; Calan, Ozlem Gursoy; Ozturk, Taylan; Kaya, Mahmut; Karahan, Eyup; Kaynak, Suleyman

2017-06-01

The aim of the study was to evaluate the macular pigment optical density (MPOD) levels in patients with wet age-related macular degeneration (AMD), dry AMD, and also in healthy controls. This study was conducted at Department of Ophthalmology, and the study design was a prospective study. Forty-eight patients with wet AMD, 51 patients with dry AMD, and 50 controls were included in the study. All patients were naive to both previous lutein or zeaxanthin administration and any previous intravitreal injections. Fundus reflectance (VISUCAM 500, reflectance of a single 460 nm wavelength) was used to measure the MPOD levels. Three groups were compared regarding age, gender, serum lutein, and zeaxanthin concentrations as well as MPOD levels. Serum lutein and zeaxanthin levels were significantly higher in control group when compared with wet AMD (Group 1) and dry AMD (Group 2) (P = 0.001 and P< 0.001, respectively). Mean MPOD was found to be similar in all of the three study subgroups (P = 0.630). However, maximum MPOD was significantly higher in control group when compared with Group 1 and 2 (P = 0.003). There was no correlation between serum lutein or zeaxanthin concentrations and mean MPOD levels (P = 0.815, r = 0.014 and P = 0.461, r = 0.043, respectively), but there was a weak correlation between serum zeaxanthin concentration and maximum MPOD level (P = 0.042, r = 0.124). Maximum MPOD level was found to be correlated with the level of AMD (Group 1, 2, and 3; r = 0.184, P = 0.041). Maximum MPOD level was found to be lower in patients with AMD when compared with control cases. Mean MPOD and maximum MPOD levels were similar in wet and dry AMD Groups. These results can be applied clinically keeping in mind that MPOD measurements with one wavelength reflectometry may not be completely reliable.

Mechanism of Inflammation in Age-Related Macular Degeneration

PubMed Central

Parmeggiani, Francesco; Romano, Mario R.; Costagliola, Ciro; Semeraro, Francesco; Incorvaia, Carlo; D'Angelo, Sergio; Perri, Paolo; De Palma, Paolo; De Nadai, Katia; Sebastiani, Adolfo

2012-01-01

Age-related macular degeneration (AMD) is a multifactorial disease that represents the most common cause of irreversible visual impairment among people over the age of 50 in Europe, the United States, and Australia, accounting for up to 50% of all cases of central blindness. Risk factors of AMD are heterogeneous, mainly including increasing age and different genetic predispositions, together with several environmental/epigenetic factors, that is, cigarette smoking, dietary habits, and phototoxic exposure. In the aging retina, free radicals and oxidized lipoproteins are considered to be major causes of tissue stress resulting in local triggers for parainflammation, a chronic status which contributes to initiation and/or progression of many human neurodegenerative diseases such as AMD. Experimental and clinical evidences strongly indicate the pathogenetic role of immunologic processes in AMD occurrence, consisting of production of inflammatory related molecules, recruitment of macrophages, complement activation, microglial activation and accumulation within those structures that compose an essential area of the retina known as macula lutea. This paper reviews some attractive aspects of the literature about the mechanisms of inflammation in AMD, especially focusing on those findings or arguments more directly translatable to improve the clinical management of patients with AMD and to prevent the severe vision loss caused by this disease. PMID:23209345

Prevalence of Undiagnosed Age-Related Macular Degeneration in Primary Eye Care.

PubMed

Neely, David C; Bray, Kevin J; Huisingh, Carrie E; Clark, Mark E; McGwin, Gerald; Owsley, Cynthia

2017-06-01

Age-related macular degeneration (AMD) is the leading cause of irreversible vision impairment in older adults in the United States, yet little is known about whether AMD is appropriately diagnosed in primary eye care. To examine the prevalence of eyes with AMD in patients seen in primary eye care clinics who purportedly have normal macular health per their medical record and the association of AMD with patient and physician characteristics. In this cross-sectional study of primary eye care practices in Birmingham, Alabama, 644 persons 60 years or older with normal macular health per medical record based on their most recent dilated comprehensive eye examination by a primary eye care ophthalmologist or optometrist were enrolled from May 1, 2009, through December 31, 2011. Data analysis was performed from May 1, 2016, through December 20, 2016. Presence of AMD as defined by the Clinical Age-Related Maculopathy Staging system based on color fundus photography and a masked grader. Types of AMD-associated lesions were noted. Patient health and physician characteristics were collected. The sample consisted of 1288 eyes from 644 participants (231 [35.9%] male and 413 [64.1%] female; mean [SD] age, 69.4 [6.1] years; 611 white [94.9%]) seen by 31 primary eye care ophthalmologists or optometrists. A total of 968 eyes (75.2%) had no AMD, in agreement with their medical record; 320 (24.8%) had AMD despite no diagnosis of AMD in the medical record. Among eyes with undiagnosed AMD, 32 (10.0%) had hyperpigmentation, 43 (13.4%) had hypopigmentation, 249 (77.8%) had small drusen, 250 (78.1%) had intermediate drusen, and 96 (30.0%) had large drusen. Undiagnosed AMD was associated with older patient age (odds ratio [OR], 1.06; 95% CI, 1.04-1.09; P < .001), male sex (age-adjusted OR, 1.39; 95% CI, 1.02-1.91; P = .04), and less than a high school education (age-adjusted OR, 2.40; 95% CI, 1.03-5.62; P = .04). Prevalence of undiagnosed AMD was not different for

Lipids, lipid genes, and incident age-related macular degeneration: the three continent age-related macular degeneration consortium.

PubMed

Klein, Ronald; Myers, Chelsea E; Buitendijk, Gabriëlle H S; Rochtchina, Elena; Gao, Xiaoyi; de Jong, Paulus T V M; Sivakumaran, Theru A; Burlutsky, George; McKean-Cowdin, Roberta; Hofman, Albert; Iyengar, Sudha K; Lee, Kristine E; Stricker, Bruno H; Vingerling, Johannes R; Mitchell, Paul; Klein, Barbara E K; Klaver, Caroline C W; Wang, Jie Jin

2014-09-01

To describe associations of serum lipid levels and lipid pathway genes to the incidence of age-related macular degeneration (AMD). Meta-analysis. setting: Three population-based cohorts. population: A total of 6950 participants from the Beaver Dam Eye Study (BDES), Blue Mountains Eye Study (BMES), and Rotterdam Study (RS). observation procedures: Participants were followed over 20 years and examined at 5-year intervals. Hazard ratios associated with lipid levels per standard deviation above the mean or associated with each additional risk allele for each lipid pathway gene were calculated using random-effects inverse-weighted meta-analysis models, adjusting for known AMD risk factors. main outcome measures: Incidence of AMD. The average 5-year incidences of early AMD were 8.1%, 15.1%, and 13.0% in the BDES, BMES, and RS, respectively. Substantial heterogeneity in the effect of cholesterol and lipid pathway genes on the incidence and progression of AMD was evident when the data from the 3 studies were combined in meta-analysis. After correction for multiple comparisons, we did not find a statistically significant association between any of the cholesterol measures, statin use, or serum lipid genes and any of the AMD outcomes in the meta-analysis. In a meta-analysis, there were no associations of cholesterol measures, history of statin use, or lipid pathway genes to the incidence and progression of AMD. These findings add to inconsistencies in earlier reports from our studies and others showing weak associations, no associations, or inverse associations of high-density lipoprotein cholesterol and total cholesterol with AMD. Copyright © 2014 Elsevier Inc. All rights reserved.

Hypomethylation of IL17RC Promoter Associates with Age-related Macular Degeneration

PubMed Central

Wei, Lai; Liu, Baoying; Tuo, Jingsheng; Shen, Defen; Chen, Ping; Li, Zhiyu; Liu, Xunxian; Ni, Jia; Dagur, Pradeep; Sen, H. Nida; Jawad, Shayma; Ling, Diamond; Park, Stanley; Chakrabarty, Sagarika; Meyerle, Catherine; Agron, Elvira; Ferris, Frederick L.; Chew, Emily Y.; McCoy, J. Philip; Blum, Emily; Francis, Peter J.; Klein, Michael L.; Guymer, Robyn H.; Baird, Paul N.; Chan, Chi-Chao; Nussenblatt, Robert B.

2012-01-01

SUMMARY Age related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly population worldwide. While recent studies have demonstrated strong genetic associations of single nucleotide polymorphisms within a number of genes and AMD, other modes of regulation are also likely to play a role in its etiology. We identified a significantly decreased level of methylation on the IL17RC promoter in AMD patients. Further, we showed that hypomethylation of the IL17RC promoter in AMD patients led to an elevated expression of its protein and mRNA in peripheral blood as well as in the affected retina and choroid, suggesting that the DNA methylation pattern and expression of IL17RC may potentially serve as a biomarker for the diagnosis of AMD and likely plays a role in disease pathogenesis. PMID:23177625

Automatic age-related macular degeneration detection and staging

NASA Astrophysics Data System (ADS)

van Grinsven, Mark J. J. P.; Lechanteur, Yara T. E.; van de Ven, Johannes P. H.; van Ginneken, Bram; Theelen, Thomas; Sánchez, Clara I.

2013-03-01

Age-related macular degeneration (AMD) is a degenerative disorder of the central part of the retina, which mainly affects older people and leads to permanent loss of vision in advanced stages of the disease. AMD grading of non-advanced AMD patients allows risk assessment for the development of advanced AMD and enables timely treatment of patients, to prevent vision loss. AMD grading is currently performed manually on color fundus images, which is time consuming and expensive. In this paper, we propose a supervised classification method to distinguish patients at high risk to develop advanced AMD from low risk patients and provide an exact AMD stage determination. The method is based on the analysis of the number and size of drusen on color fundus images, as drusen are the early characteristics of AMD. An automatic drusen detection algorithm is used to detect all drusen. A weighted histogram of the detected drusen is constructed to summarize the drusen extension and size and fed into a random forest classifier in order to separate low risk from high risk patients and to allow exact AMD stage determination. Experiments showed that the proposed method achieved similar performance as human observers in distinguishing low risk from high risk AMD patients, obtaining areas under the Receiver Operating Characteristic curve of 0.929 and 0.934. A weighted kappa agreement of 0.641 and 0.622 versus two observers were obtained for AMD stage evaluation. Our method allows for quick and reliable AMD staging at low costs.

Interactome Mapping Guided by Tissue-Specific Phosphorylation in Age-Related Macular Degeneration

PubMed Central

Sripathi, Srinivas R.; He, Weilue; Prigge, Cameron L.; Sylvester, O’Donnell; Um, Ji-Yeon; Powell, Folami L.; Neksumi, Musa; Bernstein, Paul S.; Choo, Dong-Won; Bartoli, Manuela; Gutsaeva, Diana R.; Jahng, Wan Jin

2017-01-01

The current study aims to determine the molecular mechanisms of age-related macular degeneration (AMD) using the phosphorylation network. Specifically, we examined novel biomarkers for oxidative stress by protein interaction mapping using in vitro and in vivo models that mimic the complex and progressive characteristics of AMD. We hypothesized that the early apoptotic reactions could be initiated by protein phosphorylation in region-dependent (peripheral retina vs. macular) and tissue-dependent (retinal pigment epithelium vs. retina) manner under chronic oxidative stress. The analysis of protein interactome and oxidative biomarkers showed the presence of tissue- and region-specific post-translational mechanisms that contribute to AMD progression and suggested new therapeutic targets that include ubiquitin, erythropoietin, vitronectin, MMP2, crystalline, nitric oxide, and prohibitin. Phosphorylation of specific target proteins in RPE cells is a central regulatory mechanism as a survival tool under chronic oxidative imbalance. The current interactome map demonstrates a positive correlation between oxidative stress-mediated phosphorylation and AMD progression and provides a basis for understanding oxidative stress-induced cytoskeletal changes and the mechanism of aggregate formation induced by protein phosphorylation. This information could provide an effective therapeutic approach to treat age-related neurodegeneration. PMID:28580316

Interactome Mapping Guided by Tissue-Specific Phosphorylation in Age-Related Macular Degeneration.

PubMed

Sripathi, Srinivas R; He, Weilue; Prigge, Cameron L; Sylvester, O'Donnell; Um, Ji-Yeon; Powell, Folami L; Neksumi, Musa; Bernstein, Paul S; Choo, Dong-Won; Bartoli, Manuela; Gutsaeva, Diana R; Jahng, Wan Jin

2017-02-01

The current study aims to determine the molecular mechanisms of age-related macular degeneration (AMD) using the phosphorylation network. Specifically, we examined novel biomarkers for oxidative stress by protein interaction mapping using in vitro and in vivo models that mimic the complex and progressive characteristics of AMD. We hypothesized that the early apoptotic reactions could be initiated by protein phosphorylation in region-dependent (peripheral retina vs. macular) and tissue-dependent (retinal pigment epithelium vs. retina) manner under chronic oxidative stress. The analysis of protein interactome and oxidative biomarkers showed the presence of tissue- and region-specific post-translational mechanisms that contribute to AMD progression and suggested new therapeutic targets that include ubiquitin, erythropoietin, vitronectin, MMP2, crystalline, nitric oxide, and prohibitin. Phosphorylation of specific target proteins in RPE cells is a central regulatory mechanism as a survival tool under chronic oxidative imbalance. The current interactome map demonstrates a positive correlation between oxidative stress-mediated phosphorylation and AMD progression and provides a basis for understanding oxidative stress-induced cytoskeletal changes and the mechanism of aggregate formation induced by protein phosphorylation. This information could provide an effective therapeutic approach to treat age-related neurodegeneration.

Visual function 5 years or more after macular translocation surgery for myopic choroidal neovascularisation and age-related macular degeneration.

PubMed

Takeuchi, K; Kachi, S; Iwata, E; Ishikawa, K; Terasaki, H

2012-01-01

To evaluate the changes in the best-corrected visual acuity (BCVA) after 1 year and after ≥ 5 years after macular translocation for age-related macular degeneration (AMD) or myopic choroidal neovascularisation (mCNV). The medical records of 61 consecutive patients who underwent macular translocation with 360° retinotomy for AMD (35 eyes) or mCNV (26 eyes) were reviewed. Overall, 40 patients, 17 mCNV and 23 AMD, were followed for at least 5 years. BCVA and area of the Goldmann visual field (VF) measured before, 12 months after surgery, and at the final visit. In the 23 AMD eyes followed for ≥ 5 years, the mean preoperative BCVA was 1.149 ± 0.105 logMAR units, which significantly improved to 0.69 ± 0.06 logMAR units at 1 year (P<0.001). This BCVA was maintained at 0.633 ± 0.083 logMAR units on their final examination. In the 17 eyes with mCNV followed for ≥ 5 years, the mean preoperative BCVA was 1.083 ± 0.119 logMAR units, which was significantly improved to 0.689 ± 0.121 logMAR units at 1 year (P = 0.001). This BCVA was maintained at 0.678 ± 0.142 logMAR units on their final examination. The area of the VF was significantly decreased at 12 months and did not change significantly thereafter. Our results show that macular translocation surgery significantly improves the BCVA and significantly decreases the VF area of eyes with mCNV or AMD after first 1 year. The BCVA and VF area do not change significantly from the values at 1 year for at least 5 years.

Diminishing Risk for Age-Related Macular Degeneration with Nutrition: A Current View

PubMed Central

Schleicher, Molly; Weikel, Karen; Garber, Caren; Taylor, Allen

2013-01-01

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. Clinical hallmarks of AMD are observed in one third of the elderly in industrialized countries. Preventative interventions through dietary modification are attractive strategies, because they are more affordable than clinical therapies, do not require specialists for administration and many studies suggest a benefit of micro- and macro-nutrients with respect to AMD with few, if any, adverse effects. The goal of this review is to provide information from recent literature on the value of various nutrients, particularly omega-3 fatty acids, lower glycemic index diets and, perhaps, some carotenoids, with regard to diminishing risk for onset or progression of AMD. Results from the upcoming Age-Related Eye Disease Study (AREDS) II intervention trial should be particularly informative. PMID:23820727

DETECTION OF TREATMENT-NAIVE CHOROIDAL NEOVASCULARIZATION IN AGE-RELATED MACULAR DEGENERATION BY SWEPT SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PubMed

Ahmed, Daniel; Stattin, Martin; Graf, Alexandra; Forster, Julia; Glittenberg, Carl; Krebs, Ilse; Ansari-Shahrezaei, Siamak

2017-09-04

To compare the detection rate of choroidal neovascularization (CNV) in treatment-naive neovascular age-related macular degeneration by swept source optical coherence tomography angiography (SS-OCTA, Topcon's DRI Triton) working at 1,050 nm wavelength versus fluorescence angiography. Cross-sectional analysis of 156 eyes (107 neovascular age-related macular degeneration and 49 dry AMD) in 98 patients, previously diagnosed by multimodal imaging using fluorescein (FA) and indocyanine green angiography (Heidelberg's Spectralis) in a tertiary retina center, evaluated by SS-OCTA 4.5 mm × 4.5 mm and 6 mm × 6 mm macular cubes. Main outcome measures were sensitivity and specificity of SS-OCTA in AMD. Potential factors influencing CNV detection rate were analyzed. Swept source optical coherence tomography angiography detected CNV in 81 of 107 eyes, resulting in a sensitivity of 75.7%. In 49 eyes with dry AMD, no CNV could be identified (specificity 100%). A statistical significance was calculated for nondetection of treatment-naive CNV by SS-OCTA in pigment epithelial detachment over 400 μm (P = 0.0238). Topcon's SS-OCTA was not able to detect all CNV lesions. Large pigment epithelial detachments were associated with signal loss. Fluorescence angiography still remains the gold standard, but the tested SS-OCTA device can be considered as a feasible additional diagnostic tool in AMD.

Recent developments in age-related macular degeneration: a review.

PubMed

Al-Zamil, Waseem M; Yassin, Sanaa A

2017-01-01

Visual impairment in elderly people is a considerable health problem that significantly affects quality of life of millions worldwide. The magnitude of this issue is becoming more evident with an aging population and an increasing number of older individuals. The objective of this article was to review the clinical and pathological aspects of age-related macular degeneration (AMD), diagnostic tools, and therapeutic modalities presently available or underway for both atrophic and wet forms of the disease. An online review of the PubMed database was performed, searching for the key words. The search was limited to articles published since 1980 to date. Several risk factors have been linked to AMD, such as age (>60 years), lifestyle (smoking and diet), and family history. Although the pathogenesis of AMD remains unclear, genetic factors have been implicated in the condition. Treatment for atrophic AMD is mainly close observation, coupled with nutritional supplements such as zinc and antioxidants, whereas treatment of wet AMD is based on targeting choroidal neovascular membranes. Identification of modifiable risk factors would improve the possibilities of preventing the progression of AMD. The role of anti-vascular endothelial growth factor (anti-VEGF) agents has transformed the therapeutic approach of the potentially blinding disease "wet AMD" into a more favorable outcome.

Statins for age-related macular degeneration

PubMed Central

Gehlbach, Peter; Li, Tianjing; Hatef, Elham

2013-01-01

Background Age-related macular degeneration (AMD) is a progressive late onset disorder of the macula affecting central vision. Age-related macular degeneration is the leading cause of blindness in people over 65 years in industrialized countries (Congdon 2003). Recent epidemiologic, genetic and pathological evidence has shown AMD shares a number of risk factors with atherosclerosis, leading to the hypothesis that statins may exert protective effects in AMD. Objectives To examine the effectiveness of statins compared with other treatments, no treatment, or placebo in delaying the onset and/or progression of AMD. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 9), MEDLINE (January 1950 to September 2011), EMBASE (January 1980 to September 2011), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to September 2011), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 16 September 2011. Selection criteria We included randomized controlled trials (RCTs) that compared statins with other treatments, no treatment, or placebo in participants who were either susceptible to or diagnosed as having early stages of AMD. Data collection and analysis Two authors independently evaluated the search results against the selection criteria. Two Italian speaking colleagues extracted data. One author entered data. We did not perform a meta-analysis because only one completed RCT was identified. Main results Two studies met the selection criteria. One trial reported insufficient details to assess the risk of bias; the other trial is ongoing. Of the completed trial, the

Retinal pigment epithelium, age-related macular degeneration and neurotrophic keratouveitis.

PubMed

Bianchi, Enrica; Scarinci, Fabio; Ripandelli, Guido; Feher, Janos; Pacella, Elena; Magliulo, Giuseppe; Gabrieli, Corrado Balacco; Plateroti, Rocco; Plateroti, Pasquale; Mignini, Fiorenzo; Artico, Marco

2013-01-01

Age-related macular degeneration (AMD) is the leading cause of impaired vision and blindness in the aging population. The aims of our studies were to identify qualitative and quantitative alterations in mitochondria in human retinal pigment epithelium (RPE) from AMD patients and controls and to test the protective effects of pigment epithelium-derived factor (PEDF), a known neurotrophic and antiangiogenic substance, against neurotrophic keratouveitis. Histopathological alterations were studied by means of morphometry, light and electron microscopy. Unexpectedly, morphometric data showed that the RPE alterations noted in AMD may also develop in normal aging, 10-15 years later than appearing in AMD patients. Reduced tear secretion, corneal ulceration and leukocytic infiltration were found in capsaicin (CAP)-treated rats, but this effect was significantly attenuated by PEDF. These findings suggest that PEDF accelerated the recovery of tear secretion and also prevented neurotrophic keratouveitis and vitreoretinal inflammation. PEDF may have a clinical application in inflammatory and neovascular diseases of the eye.

Do statins have a role in the prevention of age-related macular degeneration?

PubMed

Tsao, Sean W; Fong, Donald S

2013-04-01

Age-related macular degeneration (AMD) is a leading cause of blindness worldwide for which preventative therapies are few. Evidence suggesting shared common risk factors and mirrored pathophysiology between cardiovascular disease and AMD led to the hypothesis that hydroxymethylglutaryl-CoA reductase inhibitors (statins) could be helpful in preventing AMD. For over a decade, observational studies have repeatedly investigated this hypothesis with conflicting conclusions. Although many reports conclude that statin use has no effect on the risk of AMD, no randomized controlled trial has yet been completed. Furthermore, relatively few studies factor characteristics of statin use into their analysis. A few studies have observed an incompletely explained protective effect against drusen, a funduscopic finding associated with AMD. Although there is insufficient evidence for a preventive effect of statins on dry AMD, there does seem to be stronger evidence against any effect on the development of exudative AMD. Overall, we find that there is insufficient evidence to conclude whether statin use is helpful in preventing AMD.

Physics of Lipofuscin Formation and Growth in Age Related Macular Degeneration

NASA Astrophysics Data System (ADS)

Family, Fereydoon; Mazzitello, K. I.; Arizmendi, C. M.; Grossniklaus, Hans E.

2010-02-01

Age-related macular degeneration (AMD) is the leading cause of blindness beyond the age of 50 years. The most common pathogenic mechanism that leads to AMD is choroidal neovascularization (CNV). CNV is produced by accumulation of residual material caused by aging of retinal pigment epithelium cells (RPE). With time, incompletely degraded membrane material builds up in the RPE in the form of lipofuscin. Lipofuscin is made of free-radical-damaged protein and fat, which forms not only in AMD, but also Alzheimer disease, and Parkinson disease. We will present the results of a study of the kinetics of lipofuscin growth in RPE cells using Kinetic Monte Carlo simulations and scaling theory on a cluster aggregation model. The model captures the essential physics of lipofuscin growth in the cells. A remarkable feature is that small particles may be removed from the cells while the larger ones become fixed and grow by aggregation. We compare our results to the number of lipofuscin granules in eyes with early age-related degeneration. )

The Societal Impact of Age-Related Macular Degeneration: Use of Social Support Resources Differs by the Severity of the Impairment

ERIC Educational Resources Information Center

Brennan, Mark; Horowitz, Amy; Reinhardt, Joann P.; Stuen, Cynthia; Rubio, Roman; Oestreicher, Nina

2011-01-01

Age-related macular degeneration (AMD) is the leading cause of legal blindness among persons aged 50 years and older and is most prevalent among individuals of European descent aged 65 and older (Friedman et al., 2004; Rosenthal & Thompson, 2003). By affecting central vision, AMD interferes with such tasks as reading, driving, and activities…

The Psychosocial Impact of Closed-Circuit Televisions on Persons with Age-Related Macular Degeneration

ERIC Educational Resources Information Center

Huber, Jessica G.; Jutai, Jeffrey W.; Strong, J. Graham; Plotkin, Ann D.

2008-01-01

Closed-circuit televisions (CCTVs) are used by many elderly people who have age-related macular degeneration (AMD). The functional vision of 68 participants, which was measured immediately after they adopted CCTVs, suggested successful outcomes, but the psychosocial impact of the use of CCTVs did not peak until a month later. The findings help…

Nutritional Modulation of Age-Related Macular Degeneration

PubMed Central

Weikel, Karen A; Taylor, Allen

2012-01-01

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly worldwide. It affects 30–50 million individuals and clinical hallmarks of AMD are observed in at least one third of persons over the age of 75 in industrialized countries (Gehrs et al., 2006). Costs associated with AMD are in excess of $340 billion US (American-Health-Assistance-Foundation, 2012). The majority of AMD patients in the United States are not eligible for clinical treatments (Biarnes et al., 2011; Klein et al., 2011). Preventive interventions through dietary modulation are attractive strategies because many studies suggest a benefit of micro and macronutrients with respect to AMD, as well as other age-related debilities, and with few, if any, adverse effects (Chiu, 2011). Preservation of vision would enhance quality of life for millions of elderly people, and alleviate the personal and public health financial burden of AMD (Frick et al., 2007; Wood et al., 2011). Observational studies indicate that maintaining adequate levels of omega-3 fatty acids (i.e. with 2 servings/wk of fish) or a low glycemic index diet may be particularly beneficial for early AMD and that higher levels of carotenoids may be protective, most probably, against neovascular AMD. Intervention trials are needed to better understand the full effect of these nutrients and/or combinations of nutrients on retinal health. Analyses that describe effects of a nutrient on onset and/or progress of AMD are valuable because they indicate the value of a nutrient to arrest AMD at the early stages. This comprehensive summary provides essential information about the value of nutrients with regard to diminishing risk for onset or progress of AMD and can serve as a guide until data from ongoing intervention trials are available. PMID:22503690

A systematic review on zinc for the prevention and treatment of age-related macular degeneration

USDA-ARS?s Scientific Manuscript database

Zinc is a potential candidate for the prevention and treatment of age-related macular degeneration (AMD) due to its high concentration in the retina and role as a cofactor for antioxidant enzymes. The objective of this work was to conduct a systematic review of studies that investigated dietary inta...

The role of omega-3 and micronutrients in age-related macular degeneration.

PubMed

Querques, Giuseppe; Souied, Eric H

2014-01-01

Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in the United States, Europe, and other developed countries. Although the pathogenesis of AMD remains unclear, current evidence suggests a multifactorial aetiology. Nutrition may play an important role in the development and progression of AMD. There have been several epidemiological studies suggesting that omega-3 fatty acids could have a protective role in AMD, but a beneficial effect remains to be demonstrated in randomized controlled trials. There also exists a substantial body of evidence suggesting that protection against AMD may be provided by specific micronutrients (vitamins and minerals and antioxidants). The identification of risk factors for the development and progression of AMD is of particular importance for understanding the origins of the disorder and for establishing strategies for its prevention. We examine the relationship between dietary omega-3 intake and the incidence and progression of AMD, as well as the role of omega-3 supplementation in the prevention of the disorder, and also explore the role of other micronutrients in AMD. Copyright © 2014 Elsevier Inc. All rights reserved.

Current knowledge and trends in age-related macular degeneration: genetics, epidemiology, and prevention.

PubMed

Velez-Montoya, Raul; Oliver, Scott C N; Olson, Jeffrey L; Fine, Stuart L; Quiroz-Mercado, Hugo; Mandava, Naresh

2014-03-01

To address the most dynamic and current issues concerning human genetics, risk factors, pharmacoeconomics, and prevention regarding age-related macular degeneration. An online review of the database Pubmed and Ovid was performed, searching for the key words: age-related macular degeneration, AMD, pharmacoeconomics, risk factors, VEGF, prevention, genetics and their compound phrases. The search was limited to articles published since 1985 to date. All returned articles were carefully screened and their references were manually reviewed for additional relevant data. The webpage www.clinicaltrials.gov was also accessed in search of relevant research trials. A total of 366 articles were reviewed, including 64 additional articles extracted from the references and 25 webpages and online databases from different institutions. At the end, only 244 references were included in this review. Age-related macular degeneration is a complex multifactorial disease that has an uneven manifestation around the world but with one common denominator, it is increasing and spreading. The economic burden that this disease poses in developed nations will increase in the coming years. Effective preventive therapies need to be developed in the near future.

Pegaptanib sodium as maintenance therapy in neovascular age-related macular degeneration: the LEVEL study.

PubMed

Friberg, Thomas R; Tolentino, Michael; Weber, Pamela; Patel, Sunil; Campbell, Scott; Goldbaum, Mauro

2010-12-01

To assess the efficacy of pegaptanib as maintenance therapy in neovascular age-related macular degeneration (NV-AMD) patients after induction therapy. A phase IV, prospective, open-label, uncontrolled exploratory study including subjects with subfoveal NV-AMD who had had one to three induction treatments 30-120 days before entry and showed investigator-determined clinical/anatomical NV-AMD improvement. Lesions in the study eye were: any subtype, 12 or fewer disc areas; postinduction centre point thickness (CPT) 275 μm or less or thinning of 100 μm or more (optical coherence tomography); visual acuity (VA) 20/20-20/400. Intravitreal pegaptanib 0.3 mg was administered as maintenance every 6 weeks for 48 weeks with follow-up to week 54. Booster treatment additional unscheduled treatment for wet age-related macular degeneration, was allowed in the study eye at the investigators' discretion for clinical deterioration. Of 568 enrolled subjects, 86% completed 1 year of pegaptanib. Mean VA improvement during induction (49.6 to 65.5 letters) was well preserved (54-week mean 61.8 letters). Mean CPT was relatively stable during maintenance (20 μm increase during the study). Fifty per cent did not receive unscheduled booster treatment to week 54; 46% did have one such booster (mean 147 days after maintenance initiation). An induction-maintenance strategy, using non-selective then selective vascular endothelial growth factor (VEGF) inhibitors, could be considered for NV-AMD. This approach may have particular relevance for patients with systemic comorbidities who require long-term anti-VEGF therapy for NV-AMD.

Age related macular degeneration and visual disability.

PubMed

Christoforidis, John B; Tecce, Nicola; Dell'Omo, Roberto; Mastropasqua, Rodolfo; Verolino, Marco; Costagliola, Ciro

2011-02-01

Age-related macular degeneration (AMD) is the leading cause of central blindness or low vision among the elderly in industrialized countries. AMD is caused by a combination of genetic and environmental factors. Among modifiable environmental risk factors, cigarette smoking has been associated with both the dry and wet forms of AMD and may increase the likelihood of worsening pre-existing AMD. Despite advances, the treatment of AMD has limitations and affected patients are often referred for low vision rehabilitation to help them cope with their remaining eyesight. The characteristic visual impairment for both forms of AMD is loss of central vision (central scotoma). This loss results in severe difficulties with reading that may be only partly compensated by magnifying glasses or screen-projection devices. The loss of central vision associated with the disease has a profound impact on patient quality of life. With progressive central visual loss, patients lose their ability to perform the more complex activities of daily living. Common vision aids include low vision filters, magnifiers, telescopes and electronic aids. Low vision rehabilitation (LVR) is a new subspecialty emerging from the traditional fields of ophthalmology, optometry, occupational therapy, and sociology, with an ever-increasing impact on the usual concepts of research, education, and services for visually impaired patients. Relatively few ophthalmologists practise LVR and fewer still routinely use prismatic image relocation (IR) in AMD patients. IR is a method of stabilizing oculomotor functions with the purpose of promoting better function of preferred retinal loci (PRLs). The aim of vision rehabilitation therapy consists in the achievement of techniques designed to improve PRL usage. The use of PRLs to compensate for diseased foveae has offered hope to these patients in regaining some function. However, in a recently published meta-analysis, prism spectacles were found to be unlikely to be of

Spectral thresholds in macular degeneration.

PubMed Central

Alvarez, S L; King-Smith, P E; Bhargava, S K

1983-01-01

Spectral sensitivities were measured in 18 normal eyes, 9 eyes in patients with senile macular degeneration, 4 patients with Stargardt's juvenile macular degeneration (JMD), and 2 patients without conclusive signs--that is, genetic or morphological abnormalities--to indicate the cause of loss of central vision. Spectral sensitivity, testing for which included measurements on white, yellow, purple, and blue backgrounds, is here used as an aid in differential diagnosis for cases of macular degeneration. PMID:6871142

Age-Related Macular Degeneration: Genetics and Biology Coming Together

PubMed Central

Fritsche, Lars G.; Fariss, Robert N.; Stambolian, Dwight; Abecasis, Gonçalo R.; Curcio, Christine A.

2014-01-01

Genetic and genomic studies have enhanced our understanding of complex neurodegenerative diseases that exert a devastating impact on individuals and society. One such disease, age-related macular degeneration (AMD), is a major cause of progressive and debilitating visual impairment. Since the pioneering discovery in 2005 of complement factor H (CFH) as a major AMD susceptibility gene, extensive investigations have confirmed 19 additional genetic risk loci, and more are anticipated. In addition to common variants identified by now-conventional genome-wide association studies, targeted genomic sequencing and exome-chip analyses are uncovering rare variant alleles of high impact. Here, we provide a critical review of the ongoing genetic studies and of common and rare risk variants at a total of 20 susceptibility loci, which together explain 40–60% of the disease heritability but provide limited power for diagnostic testing of disease risk. Identification of these susceptibility loci has begun to untangle the complex biological pathways underlying AMD pathophysiology, pointing to new testable paradigms for treatment. PMID:24773320

ASSOCIATION BETWEEN THE VITREOMACULAR INTERFACE AND OPTICAL COHERENCE TOMOGRAPHY CHARACTERISTICS IN WET AGE-RELATED MACULAR DEGENERATION.

PubMed

Ashraf, Mohammed; Souka, Ahmed; Adelman, Ron A

2017-09-01

To study the effect of the vitreomacular interface on various wet age-related macular degeneration (AMD) characteristics including the size and type of choroidal neovascularization (CNV), choroidal thickness, and activity of the CNV. This was a retrospective observational cross-sectional study. The study included 43 patients (51 eyes) with treatment-naive age-related macular degeneration. Twenty-six patients with wet AMD in one eye and dry AMD in the other eye were included in a paired-eye analysis. Patients underwent optical coherence tomography examination using Heidelberg Spectralis (spectral domain optical coherence tomography) at presentation to determine the type of CNV and the vitreomacular status. In addition, various parameters were measured including the choroidal thickness and horizontal width and vertical height measurements of the CNV. There was no correlation between the height, width, activity or type of the CNV, and the presence or absence of vitreomacular adhesion. The mean choroidal thickness (using enhanced depth imaging) in cases with vitreomacular adhesion was 272.57 μm compared with 197.32 μm in cases with no vitreomacular adhesion, a statistically significant difference (P = 0.003). In the paired-eye study (21 patients), there was no significant difference between the eyes with wet AMD and dry AMD with regard to vitreomacular status or the choroidal thickness. In a subgroup analysis, patients with Type 1 CNV had a significantly higher percentage of vitreomacular adhesion compared with the other eye with dry AMD (P = 0.034). In conclusion, the vitreomacular interface does seem to be associated with an increased choroidal thickness in cases of wet AMD. Furthermore, the association between the vitreomacular interface and wet AMD is more significant for Type 1 CNV.

Cellular and molecular mechanisms of age-related macular degeneration: from impaired autophagy to neovascularization.

PubMed

Klettner, Alexa; Kauppinen, Anu; Blasiak, Janusz; Roider, Johan; Salminen, Antero; Kaarniranta, Kai

2013-07-01

Age-related macular degeneration (AMD) is a complex, degenerative and progressive disease involving multiple genetic and environmental factors. It can result in severe visual loss e.g. AMD is the leading cause of blindness in the elderly in the western countries. Although age, genetics, diet, smoking, and many cardiovascular factors are known to be linked with this disease there is increasing evidence that long-term oxidative stress, impaired autophagy clearance and inflammasome mediated inflammation are involved in the pathogenesis. Under certain conditions these may trigger detrimental processes e.g. release of vascular endothelial growth factor (VEGF), causing choroidal neovascularization e.g. in wet AMD. This review ties together these crucial pathological threads in AMD. Copyright © 2013 Elsevier Ltd. All rights reserved.

Can HMG Co-A reductase inhibitors (“statins”) slow the progression of age-related macular degeneration? The Age-Related Maculopathy Statin Study (ARMSS)

PubMed Central

Guymer, Robyn H; Dimitrov, Peter N; Varsamidis, Mary; Lim, Lyndell L; Baird, Paul N; Vingrys, Algis J; Robman, Luba

2008-01-01

Age-related macular degeneration (AMD) is responsible for the majority of visual impairment in the Western world. The role of cholesterol-lowering medications, HMG Co-A reductase inhibitors or statins, in reducing the risk of AMD or of delaying its progression has not been fully investigated. A 3-year prospective randomized controlled trial of 40 mg simvastatin per day compared to placebo in subjects at high risk of AMD progression is described. This paper outlines the primary aims of the Age-Related Maculopathy Statin Study (ARMSS), and the methodology involved. Standardized clinical grading of macular photographs and comparison of serial macular digital photographs, using the International grading scheme, form the basis for assessment of primary study outcomes. In addition, macular function is assessed at each visit with detailed psychophysical measurements of rod and cone function. Information collected in this study will assist in the assessment of the potential value of HMG Co-A reductase inhibitors (statins) in reducing the risk of AMD progression. PMID:18982929

Radiation therapy: age-related macular degeneration.

PubMed

Mendez, Carlos A Medina; Ehlers, Justis P

2013-01-01

Age-related macular degeneration (AMD) is the leading cause of severe irreversible vision loss in patients over the age of 50 years in the developed world. Neovascular AMD (NVAMD) is responsible for 90% of the cases with severe visual loss. In the last decade, the treatment paradigm for NVAMD has been transformed by the advent of anti-vascular endothelial growth factor therapy. Despite the excellent results of anti-vascular endothelial growth factor therapy, frequent injections remain a necessity for most patients. The burden of these frequent visits as well as the cumulative risks of indefinite intravitreal injections demand continued pursuit of more enduring therapy that provides similar functional results. Radiotherapy has been studied for two decades as a potential therapy for NVAMD. Because of its antiangiogenic properties, radiation therapy remains a promising potential adjunctive resource for the treatment of choroidal neovascularization secondary to NVAMD. This review considers the past, present and future of radiation as a treatment or combination treatment of NVAMD. Copyright © 2013 S. Karger AG, Basel.

Effects of Age-Related Macular Degeneration on Postural Sway

PubMed Central

Chatard, Hortense; Tepenier, Laure; Jankowski, Olivier; Aussems, Antoine; Allieta, Alain; Beydoun, Talal; Salah, Sawsen; Bucci, Maria P.

2017-01-01

Purpose: To compare the impact of unilateral vs. bilateral age-related macular degeneration (AMD) on postural sway, and the influence of different visual conditions. The hypothesis of our study was that the impact of AMD will be different between unilateral and bilateral AMD subjects compared to age-matched healthy elderly. Methods: Postural stability was measured with a platform (TechnoConcept®) in 10 elderly unilateral AMD subjects (mean age: 71.1 ± 4.6 years), 10 elderly bilateral AMD subjects (mean age: 70.8 ± 6.1 years), and 10 healthy age-matched control subjects (mean age: 69.8 ± 6.3 years). Four visual conditions were tested: both eyes viewing condition (BEV), dominant eye viewing (DEV), non-dominant eye viewing (NDEV), and eyes closed (EC). We analyzed the surface area, the length, the mean speed, the anteroposterior (AP), and mediolateral (ML) displacement of the center of pressure (CoP). Results: Bilateral AMD subjects had a surface area (p < 0.05) and AP displacement of the CoP (p < 0.01) higher than healthy elderly. Unilateral AMD subjects had more AP displacement of the CoP (p < 0.05) than healthy elderly. Conclusions: We suggest that ADM subjects could have poor postural adaptive mechanisms leading to increase their postural instability. Further studies will aim to improve knowledge on such issue and to develop reeducation techniques in these patients. PMID:28408876

Fundus Autofluorescence in Age-related Macular Degeneration

PubMed Central

Ly, Angelica; Nivison-Smith, Lisa; Assaad, Nagi; Kalloniatis, Michael

2017-01-01

ABSTRACT Fundus autofluorescence (FAF) provides detailed insight into the health of the retinal pigment epithelium (RPE). This is highly valuable in age-related macular degeneration (AMD) as RPE damage is a hallmark of the disease. The purpose of this paper is to critically appraise current clinical descriptions regarding the appearance of AMD using FAF and to integrate these findings into a chair-side reference. A wide variety of FAF patterns have been described in AMD, which is consistent with the clinical heterogeneity of the disease. In particular, FAF imaging in early to intermediate AMD has the capacity to reveal RPE alterations in areas that appear normal on funduscopy, which aids in the stratification of cases and may have visually significant prognostic implications. It can assist in differential diagnoses and also represents a reliable, sensitive method for distinguishing reticular pseudodrusen. FAF is especially valuable in the detection, evaluation, and monitoring of geographic atrophy and has been used as an endpoint in clinical trials. In neovascular AMD, FAF reveals distinct patterns of classic choroidal neovascularization noninvasively and may be especially useful for determining which eyes are likely to benefit from therapeutic intervention. FAF represents a rapid, effective, noninvasive imaging method that has been underutilized, and incorporation into the routine assessment of AMD cases should be considered. However, the practicing clinician should also be aware of the limitations of the modality, such as in the detection of foveal involvement and in the distinction of phenotypes (hypo-autofluorescent drusen from small areas of geographic atrophy). PMID:27668639

TU-F-CAMPUS-T-02: Monte Carlo Evaluation of Kilovoltage Radiosurgery with AuNPs for Age Related Macular Degeneration (AMD)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brivio, D; Zygmanski, P; Sajo, E

2015-06-15

Purpose: To evaluate the benefit of gold nanoparticles (AuNP) in radiosurgery of Age related Macular Degeneration (AMD) using Monte Carlo (MC) simulation. AMD disease causes vision loss due to a leaky vasculature of the endothelial cells. Radiosurgical therapy aims to destroy this vasculature while minimizing the delivered dose to healthy tissues of the eye. AuNP known to enhance local dose have been targeted to the macular choroidal endothelial cells to increase the therapeutic efficacy. Methods: Dose enhancement ratio (DER) in macula endothelial cells due to a thin layer of AuNP has been calculated by a MC radiation transport simulation. AuNPmore » layer (10–100nm) has been placed on the bottom of the macula at 2.4cm depth in a water parallelepiped 3×3×6cm3. This layer has been modeled considering various concentrations of AuNP ranging from 5.5–200mg per gram of endothelial cell (volume 10×10×2um3). The x-ray source is 100kVp 4mm diameter beam tilted 0°-30° with respect to the lens. Results: DER in endothelial cell for AuNP concentration of 31mg/g (shown experimentally feasible) and 10–100nm sizes is about 1.8. Tilting 4mm-beam does not reduce the enhancement but allows to avoid the surrounding tissues. Dose distribution in the AuNP vicinity has a significant increase within 30um, peaked at AuNP interface. DER inside and outside of the irradiation 4mm-field are the same while the actual delivered dose is more than one order of magnitude lower outside the field. Compared to 100kVp, usage of filtered spectra with enhanced flux in the region 20keV-40keV shows further increase of DER by about 20%. Dose to the neighboring organs such as retina/optic nerve are reduced accordingly. Conclusion: The results of this MC simulation provide further confirmation of the potential to enhance DER with AuNP from previous analytical calculations. This study provides impetus to improve treatment effectiveness of AMD disease with radiotherapy.« less

Optical coherence tomography angiography reproducibility of lesion size measurements in neovascular age-related macular degeneration (AMD).

PubMed

Amoroso, Francesca; Miere, Alexandra; Semoun, Oudy; Jung, Camille; Capuano, Vittorio; Souied, Eric H

2018-06-01

To evaluate the reproducibility and interuser agreement of measurements of choroidal neovascularisation in optical coherence tomography angiography (OCTA). Prospective non-interventional study. Consecutive patients, presenting with neovascular age-related macular degeneration (AMD), underwent two sequential OCTA examinations (AngioVue, Optovue, Fremont, California, USA), performed by the same trained examiner. Neovascular lesion area was then measured on both examinations in the choriocapillaris automatic segmentation by two masked readers, using the semiautomated measuring software embedded in the instrument. Two measuring features were used: the first corresponding to the total manually contoured lesion area with the flow draw tool (select area) and the second to the total area of solely vessels with high flow within the lesion (vessel area). These measurements were then compared in order to assess both the reproducibility of OCTA examination and the interuser agreement with the embedded software. Forty-eight eyes of 46 patients (77.4 mean age,+/-8.2 SD, range from 62 to 95 years old, eight men, 38 women) were included in our study. Mean choroidal neovascularisation area was of 0.72+/-0.7 mm 2 for the first measurement and 0.75+/-0.76 mm 2 for the second measurement; difference between the first and the second measurement was 0.03 mm 2 . Intrauser agreement was of 0.98 (CI 0.98 to 0.99) for both 'vessel area' and 'select area' features. Interuser agreement was of 0.98 (CI 0.97 to 0.99) for 'select area' and 'vessel area' features. Our data suggest that OCTA provide reproducible imaging for evaluation of the neovascular size in the setting of AMD. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

ATAC-Seq analysis reveals a widespread decrease of chromatin accessibility in age-related macular degeneration.

PubMed

Wang, Jie; Zibetti, Cristina; Shang, Peng; Sripathi, Srinivasa R; Zhang, Pingwu; Cano, Marisol; Hoang, Thanh; Xia, Shuli; Ji, Hongkai; Merbs, Shannath L; Zack, Donald J; Handa, James T; Sinha, Debasish; Blackshaw, Seth; Qian, Jiang

2018-04-10

Age-related macular degeneration (AMD) is a significant cause of vision loss in the elderly. The extent to which epigenetic changes regulate AMD progression is unclear. Here we globally profile chromatin accessibility using ATAC-Seq in the retina and retinal pigmented epithelium (RPE) from AMD and control patients. Global decreases in chromatin accessibility occur in the RPE with early AMD, and in the retina of advanced disease, suggesting that dysfunction in the RPE drives disease onset. Footprints of photoreceptor and RPE-specific transcription factors are enriched in differentially accessible regions (DARs). Genes associated with DARs show altered expression in AMD. Cigarette smoke treatment of RPE cells recapitulates chromatin accessibility changes seen in AMD, providing an epigenetic link between a known risk factor for AMD and AMD pathology. Finally, overexpression of HDAC11 is partially responsible for the observed reduction in chromatin accessibility, suggesting that HDAC11 may be a potential new therapeutic target for AMD.

Complement Factor D in Age-Related Macular Degeneration

PubMed Central

Stanton, Chloe M.; Yates, John R.W.; den Hollander, Anneke I.; Seddon, Johanna M.; Swaroop, Anand; Stambolian, Dwight; Fauser, Sascha; Hoyng, Carel; Yu, Yi; Atsuhiro, Kanda; Branham, Kari; Othman, Mohammad; Chen, Wei; Kortvely, Elod; Chalmers, Kevin; Hayward, Caroline; Moore, Anthony T.; Dhillon, Baljean; Ueffing, Marius

2011-01-01

Purpose. To examine the role of complement factor D (CFD) in age-related macular degeneration (AMD) by analysis of genetic association, copy number variation, and plasma CFD concentrations. Methods. Single nucleotide polymorphisms (SNPs) in the CFD gene were genotyped and the results analyzed by binary logistic regression. CFD gene copy number was analyzed by gene copy number assay. Plasma CFD was measured by an enzyme-linked immunosorbent assay. Results. Genetic association was found between CFD gene SNP rs3826945 and AMD (odds ratio 1.44; P = 0.028) in a small discovery case-control series (462 cases and 325 controls) and replicated in a combined cohorts meta-analysis of 4765 cases and 2693 controls, with an odds ratio of 1.11 (P = 0.032), with the association almost confined to females. Copy number variation in the CFD gene was identified in 13 out of 640 samples examined but there was no difference in frequency between AMD cases (1.3%) and controls (2.7%). Plasma CFD concentration was measured in 751 AMD cases and 474 controls and found to be elevated in AMD cases (P = 0.00025). The odds ratio for those in the highest versus lowest quartile for plasma CFD was 1.81. The difference in plasma CFD was again almost confined to females. Conclusions. CFD regulates activation of the alternative complement pathway, which is implicated in AMD pathogenesis. The authors found evidence for genetic association between a CFD gene SNP and AMD and a significant increase in plasma CFD concentration in AMD cases compared with controls, consistent with a role for CFD in AMD pathogenesis. PMID:22003108

Individual Test Point Fluctuations of Macular Sensitivity in Healthy Eyes and Eyes With Age-Related Macular Degeneration Measured With Microperimetry.

PubMed

Barboni, Mirella Telles Salgueiro; Szepessy, Zsuzsanna; Ventura, Dora Fix; Németh, János

2018-04-01

To establish fluctuation limits, it was considered that not only overall macular sensitivity but also fluctuations of individual test points in the macula might have clinical value. Three repeated measurements of microperimetry were performed using the Standard Expert test of Macular Integrity Assessment (MAIA) in healthy subjects ( N = 12, age = 23.8 ± 1.5 years old) and in patients with age-related macular degeneration (AMD) ( N = 11, age = 68.5 ± 7.4 years old). A total of 37 macular points arranged in four concentric rings and in four quadrants were analyzed individually and in groups. The data show low fluctuation of macular sensitivity of individual test points in healthy subjects (average = 1.38 ± 0.28 dB) and AMD patients (average = 2.12 ± 0.60 dB). Lower sensitivity points are more related to higher fluctuation than to the distance from the central point. Fixation stability showed no effect on the sensitivity fluctuation. The 95th percentile of the standard deviations of healthy subjects was, on average, 2.7 dB, ranging from 1.2 to 4 dB, depending on the point tested. Point analysis and regional analysis might be considered prior to evaluating macular sensitivity fluctuation in order to distinguish between normal variation and a clinical change. S tatistical methods were used to compare repeated microperimetry measurements and to establish fluctuation limits of the macular sensitivity. This analysis could add information regarding the integrity of different macular areas and provide new insights into fixation points prior to the biofeedback fixation training.

Early and intermediate age-related macular degeneration: update and clinical review.

PubMed

García-Layana, Alfredo; Cabrera-López, Francisco; García-Arumí, José; Arias-Barquet, Lluís; Ruiz-Moreno, José M

2017-01-01

Age-related macular degeneration (AMD) is the leading cause of irreversible central vision loss in developed countries. With the aging of population, AMD will become globally an increasingly important and prevalent disease worldwide. It is a complex disease whose etiology is associated with both genetic and environmental risk factors. An extensive decline in the quality of life and progressive need of daily living assistance resulting from AMD among those most severely affected highlights the essential role of preventive strategies, particularly advising patients to quit smoking. In addition, maintaining a healthy diet, controlling other risk factors (such as hypertension, obesity, and atherosclerosis), and the use of nutritional supplements (antioxidants) are recommendable. Genetic testing may be especially important in patients with a family history of AMD. Recently, unifying criteria for the clinical classification of AMD, defining no apparent aging changes; normal aging changes; and early, intermediate, and late AMD stages, are of value in predicting AMD risk of progression and in establishing recommendations for the diagnosis, therapeutic approach, and follow-up of patients. The present review is focused on early and intermediate AMD and presents a description of the clinical characteristics and ophthalmological findings for these stages, together with algorithms for the diagnosis and management of patients, which are easily applicable in daily clinical practice.

Early and intermediate age-related macular degeneration: update and clinical review

PubMed Central

García-Layana, Alfredo; Cabrera-López, Francisco; García-Arumí, José; Arias-Barquet, Lluís; Ruiz-Moreno, José M

2017-01-01

Age-related macular degeneration (AMD) is the leading cause of irreversible central vision loss in developed countries. With the aging of population, AMD will become globally an increasingly important and prevalent disease worldwide. It is a complex disease whose etiology is associated with both genetic and environmental risk factors. An extensive decline in the quality of life and progressive need of daily living assistance resulting from AMD among those most severely affected highlights the essential role of preventive strategies, particularly advising patients to quit smoking. In addition, maintaining a healthy diet, controlling other risk factors (such as hypertension, obesity, and atherosclerosis), and the use of nutritional supplements (antioxidants) are recommendable. Genetic testing may be especially important in patients with a family history of AMD. Recently, unifying criteria for the clinical classification of AMD, defining no apparent aging changes; normal aging changes; and early, intermediate, and late AMD stages, are of value in predicting AMD risk of progression and in establishing recommendations for the diagnosis, therapeutic approach, and follow-up of patients. The present review is focused on early and intermediate AMD and presents a description of the clinical characteristics and ophthalmological findings for these stages, together with algorithms for the diagnosis and management of patients, which are easily applicable in daily clinical practice. PMID:29042759

Current knowledge and trends in age-related macular degeneration: today's and future treatments.

PubMed

Velez-Montoya, Raul; Oliver, Scott C N; Olson, Jeffrey L; Fine, Stuart L; Mandava, Naresh; Quiroz-Mercado, Hugo

2013-09-01

To address the most dynamic and current issues concerning today's treatment options and promising research efforts regarding treatment for age-related macular degeneration. This review is aimed to serve as a practical reference for more in-depth reviews on the subject. An online review of the database PubMed and Ovid were performed, searching for the key words age-related macular degeneration, AMD, VEGF, treatment, PDT, steroids, bevacizumab, ranibizumab, VEGF-trap, radiation, combined therapy, as well as their compound phrases. The search was limited to articles published since 1985. All returned articles were carefully screened, and their references were manually reviewed for additional relevant data. The web page www.clinicaltrials.gov was also accessed in search of relevant research trials. A total of 363 articles were reviewed, including 64 additional articles extracted from the references. At the end, only 160 references were included in this review. Treatment for age-related macular degeneration is a very dynamic research field. While current treatments are mainly aimed at blocking vascular endothelial growth factor, future treatments seek to prevent vision loss because of scarring. Promising efforts have been made to address the dry form of the disease, which has lacked effective treatment.

Recent developments in age-related macular degeneration: a review

PubMed Central

Al-Zamil, Waseem M; Yassin, Sanaa A

2017-01-01

Background Visual impairment in elderly people is a considerable health problem that significantly affects quality of life of millions worldwide. The magnitude of this issue is becoming more evident with an aging population and an increasing number of older individuals. Objective The objective of this article was to review the clinical and pathological aspects of age-related macular degeneration (AMD), diagnostic tools, and therapeutic modalities presently available or underway for both atrophic and wet forms of the disease. Methods An online review of the PubMed database was performed, searching for the key words. The search was limited to articles published since 1980 to date. Results Several risk factors have been linked to AMD, such as age (>60 years), lifestyle (smoking and diet), and family history. Although the pathogenesis of AMD remains unclear, genetic factors have been implicated in the condition. Treatment for atrophic AMD is mainly close observation, coupled with nutritional supplements such as zinc and antioxidants, whereas treatment of wet AMD is based on targeting choroidal neovascular membranes. Conclusion Identification of modifiable risk factors would improve the possibilities of preventing the progression of AMD. The role of anti-vascular endothelial growth factor (anti-VEGF) agents has transformed the therapeutic approach of the potentially blinding disease “wet AMD” into a more favorable outcome. PMID:28860733

Role of diet and food intake in age-related macular degeneration: a systematic review.

PubMed

Chapman, Naoko A; Jacobs, Robert J; Braakhuis, Andrea J

2018-06-21

A systematic literature review was conducted to evaluate the role of diet and food intake in age-related macular degeneration (AMD). Eighteen high-quality studies were identified. Adherence to a Mediterranean diet had decreased risk of AMD progression. An Oriental diet pattern had decreased association with AMD prevalence, whereas a Western diet pattern had increased association with AMD prevalence. High consumption of vegetables rich in carotenoids, and fatty fish containing omega-3 fatty acids was beneficial for those at risk of AMD. Vegetable oils and animal fats containing omega-6 fatty acids, and red/processed meat should be consumed minimally to reduce the risk of AMD progression. High glycaemic index diets and alcohol consumption of greater than two drinks a day had increased association with AMD. As the quality of diet and food intake had a vital role in AMD, the provision of appropriate nutritional advice to those at risk of AMD is recommended. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Corneal thickness of eyes with unilateral age-related macular degeneration.

PubMed

Arikan, Sedat; Ersan, Ismail; Kara, Selcuk; Gencer, Baran; Korkmaz, Safak; Vural, Azer Sara

2015-01-01

To compare the central corneal thicknesses (CCT), peripheral corneal thicknesses, and corneal volumes (CV) of the 2 eyes of patients with unilateral age-related macular degeneration (AMD). Twenty patients who were diagnosed with unilateral AMD were included in this prospective study for the purpose of making comparison between the diseased and healthy eyes. Optical coherence tomography and fundus fluorescein angiography imaging were applied to all patients in order to confirm and reveal the presence of unilateral AMD. Then, the measurements of CCT, peripheral corneal thickness measured 4 mm distant from the center of the cornea (4 mm CT), and CV of each eye of these patients were obtained through the rotating Scheimpflug corneal topographer. Wilcoxon signed-rank test did not demonstrate a statistically significant difference between the 2 eyes of patients with unilateral AMD when we compared the CCT and CV of diseased and healthy eyes (p>0.05). However, 4 mm CT of the diseased eyes of these patients were statistically significantly thicker than the healthy eyes (p<0.05). The significant difference in terms of 4 mm CT between the diseased and healthy eyes of patients with unilateral AMD may demonstrate the possible effect of peripheral corneal thickness on the development of AMD.

Review of nutrient actions on age-related macular degeneration.

PubMed

Zampatti, Stefania; Ricci, Federico; Cusumano, Andrea; Marsella, Luigi Tonino; Novelli, Giuseppe; Giardina, Emiliano

2014-02-01

The actions of nutrients and related compounds on age-related macular degeneration (AMD) are explained in this review. The findings from 80 studies published since 2003 on the association between diet and supplements in AMD were reviewed. Antioxidants and other nutrients with an effect on AMD susceptibility include carotenoids (lutein and zeaxanthin, β-carotene), vitamins (vitamin A, E, C, D, B), mineral supplements (zinc, copper, selenium), dietary fatty acids [monounsaturated fatty acids, polyunsaturated fatty acids (PUFA both omega-3 PUFA and omega-6 PUFA), saturated fatty acids and cholesterol], and dietary carbohydrates. The literature revealed that many of these antioxidants and nutrients exert a protective role by functioning synergistically. Specifically, the use of dietary supplements with targeted actions can provide minimal benefits on the onset or progression of AMD; however, this does not appear to be particularly beneficial in healthy people. Furthermore, some supplements or nutrients have demonstrated discordant effects on AMD in some studies. Since intake of dietary supplements, as well as exposure to damaging environmental factors, is largely dependent on population habits (including dietary practices) and geographical localization, an overall healthy diet appears to be the best strategy in reducing the risk of developing AMD. As of now, the precise mechanism of action of certain nutrients in AMD prevention remains unclear. Thus, future studies are required to examine the effects that nutrients have on AMD and to determine which factors are most strongly correlated with reducing the risk of AMD or preventing its progression. Copyright © 2014 Elsevier Inc. All rights reserved.

Nutrition, Genes, and Age-Related Macular Degeneration: What Have We Learned from the Trials?

PubMed

Chew, Emily Y

2017-01-01

The Age-Related Eye Disease Study (AREDS) and AREDS2 provided evidence for treating persons with age-related macular degeneration (AMD) with antioxidant vitamins and minerals to reduce the risk of development of late AMD. The AREDS2 data suggest that the beta-carotene in the original AREDS supplements be replaced by lutein and zeaxanthin, providing a safer drug for those who are smokers or former smokers. Even though consuming fish reduced the risk of AMD in observational studies, the AREDS2 results showed that omega-3 long-chain polyunsaturated fatty acids (docosahexaenoic acid/eicosapentaenoic acid) had no beneficial effect on AMD. Despite the major progress in the discovery of gene variants associated with AMD, the use of genetic testing to predict disease has not been clinically useful. The use of genetic testing prior to AMD therapies such as administering AREDS supplements is not recommended by the American Academy of Ophthalmology and other organizations. © 2017 S. Karger AG, Basel.

Relationship between macular pigment and visual function in subjects with early age-related macular degeneration.

PubMed

Akuffo, Kwadwo Owusu; Nolan, John M; Peto, Tunde; Stack, Jim; Leung, Irene; Corcoran, Laura; Beatty, Stephen

2017-02-01

To investigate the relationship between macular pigment (MP) and visual function in subjects with early age-related macular degeneration (AMD). 121 subjects with early AMD enrolled as part of the Central Retinal Enrichment Supplementation Trial (CREST; ISRCTN13894787) were assessed using a range of psychophysical measures of visual function, including best corrected visual acuity (BCVA), letter contrast sensitivity (CS), mesopic and photopic CS, mesopic and photopic glare disability (GD), photostress recovery time (PRT), reading performance and subjective visual function, using the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25). MP was measured using customised heterochromatic flicker photometry. Letter CS, mesopic and photopic CS, photopic GD and mean reading speed were each significantly (p<0.05) associated with MP across a range of retinal eccentricities, and these statistically significant relationships persisted after controlling for age, sex and cataract grade. BCVA, NEI VFQ-25 score, PRT and mesopic GD were unrelated to MP after controlling for age, sex and cataract grade (p>0.05, for all). MP relates positively to many measures of visual function in unsupplemented subjects with early AMD. The CREST trial will investigate whether enrichment of MP influences visual function among those afflicted with this condition. ISRCTN13894787. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Association of age-related macular degeneration and reticular macular disease with cardiovascular disease.

PubMed

Rastogi, Neelesh; Smith, R Theodore

2016-01-01

Age-related macular degeneration is the leading cause of adult blindness in the developed world. Thus, major endeavors to understand the risk factors and pathogenesis of this disease have been undertaken. Reticular macular disease is a proposed subtype of age-related macular degeneration correlating histologically with subretinal drusenoid deposits located between the retinal pigment epithelium and the inner segment ellipsoid zone. Reticular lesions are more prevalent in females and in older age groups and are associated with a higher mortality rate. Risk factors for developing age-related macular degeneration include hypertension, smoking, and angina. Several genes related to increased risk for age-related macular degeneration and reticular macular disease are also associated with cardiovascular disease. Better understanding of the clinical and genetic risk factors for age-related macular degeneration and reticular macular disease has led to the hypothesis that these eye diseases are systemic. A systemic origin may help to explain why reticular disease is diagnosed more frequently in females as males suffer cardiovascular mortality at an earlier age, before the age of diagnosis of reticular macular disease and age-related macular degeneration. Copyright © 2015 Elsevier Inc. All rights reserved.

Genetic studies of Age-related macular degeneration: lessons, challenges and opportunities for disease management

PubMed Central

Ratna Priya, Rinki; Chew, Emily Y.; Swaroop, Anand

2012-01-01

Age-related macular degeneration (AMD) is a common cause of visual impairment in individuals over 55 years of age worldwide. The varying clinical phenotypes of AMD result from contributions of genetic, epigenetic and non-genetic (environmental) factors. Genetic studies of AMD have come of age as a direct result of tremendous gains from human genome project, genomewide association studies and identification of numerous susceptibility loci. These findings have implicated immune response, high-density lipoprotein cholesterol metabolism, extracellular matrix, and angiogenesis signaling pathways in disease pathophysiology. Here, we address how the wealth of genetic findings in AMD is expected to impact the practice of medicine, providing opportunities for improved risk assessment, molecular diagnosis, preventive and therapeutic intervention. We propose that the potential of using genetic variants for monitoring treatment response (pharmacogenetics) may usher a new era of personalized medicine in the clinical management of AMD. PMID:23009893

Further mapping of 10q26 supports strong association of HTRA1 polymorphisms with age-related macular degeneration.

PubMed

Gibbs, Daniel; Yang, Zhenglin; Constantine, Ryan; Ma, Xiang; Camp, Nicola J; Yang, Xian; Chen, Hayou; Jorgenson, Adam; Hau, Vincent; Dewan, Andrew; Zeng, Jiexi; Harmon, Jennifer; Buehler, Jeanette; Brand, John M; Hoh, Josephine; Cameron, D Joshua; Dixit, Manjusha; Tong, Zongzhong; Zhang, Kang

2008-02-01

Age-related macular degeneration (AMD) is a complex disorder with genetic and environmental influences. The genetic influences affecting AMD are not well understood and few genes have been consistently implicated and replicated for this disease. A polymorphism (rs11200638) in a transcription factor binding site of the HTRA1 gene has been described, in previous reports, as being most significantly associated with AMD. In this paper, we investigate haplotype association and individual polymorphic association by genotyping additional variants in the AMD risk-associated region of chromosome 10q26. We demonstrate that rs11200638 in the promoter region and rs2293870 in exon 1 of HTRA1, are among the most significantly associated variants for advanced forms of AMD.

C-Reactive Protein as a Therapeutic Target in Age-Related Macular Degeneration.

PubMed

Molins, Blanca; Romero-Vázquez, Sara; Fuentes-Prior, Pablo; Adan, Alfredo; Dick, Andrew D

2018-01-01

Age-related macular degeneration (AMD), a retinal degenerative disease, is the leading cause of central vision loss among the elderly population in developed countries and an increasing global burden. The major risk is aging, compounded by other environmental factors and association with genetic variants for risk of progression. Although the etiology of AMD is not yet clearly understood, several pathogenic pathways have been proposed, including dysfunction of the retinal pigment epithelium, inflammation, and oxidative stress. The identification of AMD susceptibility genes encoding complement factors and the presence of complement and other inflammatory mediators in drusen, the hallmark deposits of AMD, support the concept that local inflammation and immune-mediated processes play a key role in AMD pathogenesis that may be accelerated through systemic immune activation. In this regard, increased levels of circulating C-reactive protein (CRP) have been associated with higher risk of AMD. Besides being a risk marker for AMD, CRP may also play a role in the progression of the disease as it has been identified in drusen, and we have recently found that its monomeric form (mCRP) induces blood retinal barrier disruption in vitro . In this review, we will address recent evidence that links CRP and AMD pathogenesis, which may open new therapeutic opportunities to prevent the progression of AMD.

Lack of association of CFD polymorphisms with advanced age-related macular degeneration.

PubMed

Zeng, Jiexi; Chen, Yuhong; Tong, Zongzhong; Zhou, Xinrong; Zhao, Chao; Wang, Kevin; Hughes, Guy; Kasuga, Daniel; Bedell, Matthew; Lee, Clara; Ferreyra, Henry; Kozak, Igor; Haw, Weldon; Guan, Jean; Shaw, Robert; Stevenson, William; Weishaar, Paul D; Nelson, Mark H; Tang, Luosheng; Zhang, Kang

2010-11-03

Age-related macular degeneration (AMD) is the most common cause of irreversible central vision loss worldwide. Research has linked AMD susceptibility with dysregulation of the complement cascade. Typically, complement factor H (CFH), complement factor B (CFB), complement component 2 (C2), and complement component 3 (C3) are associated with AMD. In this paper, we investigated the association between complement factor D (CFD), another factor of the complement system, and advanced AMD in a Caucasian population. Six single nucleotide polymorphisms (SNPs), rs1683564, rs35186399, rs1683563, rs3826945, rs34337649, and rs1651896, across the region covering CFD, were chosen for this study. One hundred and seventy-eight patients with advanced AMD and 161 age-matched normal controls were genotyped. Potential positive signals were further tested in another independent 445 advanced AMD patients and 190 controls. χ2 tests were performed to compare the allele frequencies between case and control groups. None of the six SNPs of CFD was found to be significantly associated with advanced AMD in our study. Our findings suggest that CFD may not play a major role in the genetic susceptibility to AMD because no association was found between the six SNPs analyzed in the CFD region and advanced AMD.

Associations between genetic polymorphisms of insulin-like growth factor axis genes and risk for age-related macular degeneration

USDA-ARS?s Scientific Manuscript database

Purpose: Our objective was to investigate if insulin-like growth factor (IGF) axis genes affect the risk for age-related macular degeneration (AMD). Methods: 864 Caucasian non-diabetic participants from the Age-Related Eye Disease Study (AREDS) Genetic Repository were used in this case control st...

Past physical activity and age-related macular degeneration: the Melbourne Collaborative Cohort Study.

PubMed

McGuinness, Myra B; Karahalios, Amalia; Simpson, Julie A; Guymer, Robyn H; Robman, Luba D; Hodge, Allison M; Cerin, Ester; Giles, Graham G; Finger, Robert P

2016-10-01

To assess the association between past physical activity and early, intermediate and late age-related macular degeneration (AMD) in a community-based cohort study in Melbourne, Australia. Diet and lifestyle information was recorded at baseline (1990-1994) and total recreational activity was derived from walking, vigorous and non-vigorous exercise. At follow-up (2003-2007), digital macular photographs were graded for early, intermediate and late AMD. Data were analysed using multinomial logistic regression controlling for age, sex, smoking, region of descent, diet and alcohol. Effect modification by sex was investigated. Out of 20 816 participants, early, intermediate and late AMD were detected at follow-up in 4244 (21%), 2661 (13%) and 122 (0.6%) participants, respectively. No association was detected between past total recreational physical activity and early, intermediate or late AMD. Frequent (≥3 times/week) and less frequent (1-2 times/week) vigorous exercise were associated with lower odds of intermediate and late AMD in univariable models. After controlling for confounders, there was evidence of effect modification by sex and frequent vigorous exercise was associated with a 22% decrease in the odds of intermediate AMD (95% CI 4% to 36%) in women, but no association was found for men. Past frequent vigorous exercise may be inversely related to the presence of intermediate AMD in women. Further studies are needed to confirm whether physical activity and exercise have a protective effect for AMD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

PGC-1α repression and high fat diet induce age-related macular degeneration-like phenotypes in mice.

PubMed

Zhang, Meng; Chu, Yi; Mowery, Joseph; Konkel, Brandon; Galli, Susana; Theos, Alexander C; Golestaneh, Nady

2018-06-20

Age-related macular degeneration (AMD) is the major cause of blindness in the elderly in developed countries and its prevalence is increasing with the aging population. AMD initially affects the retinal pigment epithelium (RPE) and gradually leads to secondary photoreceptor degeneration. Recent studies have associated mitochondrial damage with AMD, and we have observed mitochondrial and autophagic dysfunction and repressed peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1α in native RPE from AMD donor eyes and their respective induced pluripotent stem cell-derived RPE (AMD RPE-iPSC-RPE). To further investigate the effect of PGC-1α repression we have established a mouse model by feeding PGC-1α + /- mice with high fat diet (HFD) and investigated the RPE and retinal health. Here we show that when mice expressing lower levels of Pgc-1α are exposed to HFD, they present AMD-like abnormalities in RPE and retinal morphology and function. These abnormalities include basal laminar deposits, thickening of Bruch's membrane (BM) with drusen marker-containing deposits, RPE and photoreceptor degeneration, decreased mitochondrial activity, increased ROS levels, decreased autophagy dynamics/ flux, and increased inflammatory response in the RPE/retina. Our study show that the PGC-1α is important in outer retina biology and that PGC-1α + /- mouse fed with HFD is a promising model to study AMD and opens doors for novel treatment strategies in AMD. © 2018. Published by The Company of Biologists Ltd.

Familial aggregation of age-related macular degeneration in the Utah population.

PubMed

Luo, Ling; Harmon, Jennifer; Yang, Xian; Chen, Haoyu; Patel, Shrena; Mineau, Geraldine; Yang, Zhenglin; Constantine, Ryan; Buehler, Jeanette; Kaminoh, Yuuki; Ma, Xiang; Wong, Tien Y; Zhang, Maonian; Zhang, Kang

2008-02-01

We examined familial aggregation and risk of age-related macular degeneration in the Utah population using a population-based case-control study. Over one million unique patient records were searched within the University of Utah Health Sciences Center and the Utah Population Database (UPDB), identifying 4764 patients with AMD. Specialized kinship analysis software was used to test for familial aggregation of disease, estimate the magnitude of familial risks, and identify families at high risk for disease. The population-attributable risk (PAR) for AMD was calculated to be 0.34. Recurrence risks in relatives indicate increased relative risks in siblings (2.95), first cousins (1.29), second cousins (1.13), and parents (5.66) of affected cases. There were 16 extended large families with AMD identified for potential use in genetic studies. Each family had five or more living affected members. The familial aggregation of AMD shown in this study exemplifies the merit of the UPDB and supports recent research demonstrating significant genetic contribution to disease development and progression.

The role of the carotenoids, lutein and zeaxanthin, in protecting against age-related macular degeneration: a review based on controversial evidence.

PubMed

Mozaffarieh, Maneli; Sacu, Stefan; Wedrich, Andreas

2003-12-11

A review of the role of the carotenoids, lutein and zeaxanthin, and their function in altering the pathogenesis of age-related macular degeneration (AMD). Medline and Embase search. Recent evidence introduces the possibility that lutein and zeaxanthin, carotenoids found in a variety of fruits and vegetables may protect against the common eye disease of macular degeneration. This potential and the lack to slow the progression of macular degeneration, has fueled high public interest in the health benefits of these carotenoids and prompted their inclusion in various supplements. The body of evidence supporting a role in this disease ranges from basic studies in experimental animals to various other clinical and epidemiological studies. Whilst some epidemiological studies suggest a beneficial role for carotenoids in the prevention of AMD, others are found to be unrelated to it. Results of some clinical studies indicate that the risk for AMD is reduced when levels of the carotenoids are elevated in the serum or diet, but this correlation is not observed in other studies. Published data concerning the toxicity of the carotenoids or the optimum dosage of these supplements is lacking. An intake of dietary supplied nutrients rich in the carotenoids, lutein and zeaxanthin, appears to be beneficial in protecting retinal tissues, but this is not proven. Until scientifically sound knowledge is available we recommend for patients judged to be at risk for AMD to: alter their diet to more dark green leafy vegetables, wear UV protective lenses and a hat when outdoors. Future investigations on the role of nutrition, light exposure, genetics, and combinations of photodynamic therapy with intravitreal steroid (triamcinolone-acetonide) injections hold potential for future treatment possibilities.

Smoking, Dietary Betaine, Methionine, and Vitamin D in Monozygotic Twins with Discordant Macular Degeneration: Epigenetic Implications

PubMed Central

Seddon, Johanna M.; Reynolds, Robyn; Shah, Heeral R.; Rosner, Bernard

2012-01-01

Objective We evaluated monozygotic twin pairs with discordant age-related macular degeneration (AMD) phenotypes to assess differences in behavioral and nutritional factors. Design Case series. Participants Caucasian male twin pairs from the United States Twin Study of Macular Degeneration. Methods Twin pairs were genotyped to confirm monozygosity. Ocular characteristics were evaluated based on fundus photographs using the Wisconsin Grading System and a 5-grade Clinical Age-Related Maculopathy Staging System. We selected twin pairs discordant in each of the following phenotypic categories: Stage of AMD (n = 28), drusen area (n = 60), drusen size (n = 40), and increased pigment area (n = 56). The Wilcoxon signed-rank test and linear regression were used to assess associations between behavioral and nutritional characteristics and each phenotype within discordant twin pairs. Main Outcome Measures Differences in smoking and dietary factors within twin pairs discordant for stage of AMD, drusen area, drusen size, and pigment area. Results Representative fundus photographs depict the discordant phenotypes. Pack-years of smoking were higher for the twin with the more advanced stage of AMD (P = 0.05). Higher dietary intake of vitamin D was present in the twins with less severe AMD (P = 0.01) and smaller drusen size (P = 0.05) compared with co-twins, adjusted for smoking and age. Dietary intakes of betaine and methionine were significantly higher in the twin with lower stage of AMD (P = 0.009) and smaller drusen area (P = 0.03), respectively. Conclusions The twin with the more advanced stage of AMD, larger drusen area, drusen size, and pigment area tended to be the heavier smoker. The twin with the earlier stage of AMD, smaller drusen size and area, and less pigment tended to have higher dietary vitamin D, betaine, or methionine intake. Results suggest that behavioral and nutritional factors associated with epigenetic mechanisms are involved in the etiology of AMD, in

Present and future treatment possibilities in macular degeneration

NASA Astrophysics Data System (ADS)

Fisher, E.; Wegner, A.; Pfeiler, T.; Mertz, M.

2005-11-01

Purpose: To discuss present and future treatment possibilities in different types of choroidal neovascularisation. Methods: Presented are angiographic- and OCT-findings in patients with macular degeneration of different origin. Choroidal neovascularisations, which are not likely to respond positively to established procedures like thermal laser coagulation or photodynamic therapy will be discussed. Results and conclusions: Present study-guidelines and new methods of pharmacological intervention are analysed in different patterns of macular degeneration. Conventional laser coagulation in the treatment of classic, extrafoveal CNV and photodynamic therapy of predominantly classic subfoveal CNV still represent a gold standard. There are new recommendations, loosening the tight criteria of the TAP and VIP-guidelines, which cover, for instance, wider visual acuity ranges and the treatment of juxtafoveally located choroidal neovascularisations. Positive findings in literature confirm the role of PDT in pathologic myopia and other non-AMD CNV. Studies about surgical procedures, like macula- or RPE-translocation after surgical removal or thermal laser destruction of the CNV are in progress and are expected to show promising results. Phase II/III studies will soon point out the effect of anti-VEGF agents. The application of intravitreal (triamcinolone) or peribulbar (anecortave acetat) steroids could be useful. The combination with surgical or laser techniques could bring further benefit to the patient.

[Coping with wet age-related macular degeneration--a study from Switzerland].

PubMed

Hüsler, S; Schmid, H

2013-12-01

Age-related macular degeneration (AMD) affects the quality of life of about 40,000 patients in Switzerland. The treatment of wet AMD with intravitreal injected anti-vascular endothelial growth factor (VEGF) can be a heavy burden for many patients. The aim of this study was to understand the quality of life of the patients and to seek ways to improve the treatment compliance. Half-structured telephone interviews with 28 patients between 56 and 94 years of age were transcribed and analysed. In 21 patients, both eyes were concerned with AMD. The quality of life of patients with AMD is reduced. Many activities of daily living are hindered. Dependence on others increases. Communication of the diagnosis is perceived as a shock. Most interviewees wish for more information about their specific situation. Auxiliary means and counselling possibilities are hardly known. Wet AMD impacts on the quality of life of the patient. Treatment should therefore not be limited to the medical treatment of the ill eye. Triage to rehabilitation and counselling services should be included as important duties of the medical practitioners. Georg Thieme Verlag KG Stuttgart · New York.

Cost-Effectiveness Models in Age-Related Macular Degeneration: Issues and Challenges.

PubMed

Schmier, Jordana K; Hulme-Lowe, Carolyn K

2016-03-01

Age-related macular degeneration (AMD) is a common ophthalmic condition that can have few symptoms in its early stage but can progress to major visual impairment. While there are no treatments for early-stage AMD, there are multiple modalities of treatment for advanced disease. Given the increasing prevalence of the disease, there are dozens of analyses of cost effectiveness of AMD treatments, but methods and approaches vary broadly. The goal of this review was to identify, characterize, and critique published models in AMD and provide guidance for their interpretation. After a literature review was performed to identify studies, and exclusion criteria applied to limit the review to studies comparing treatments for AMD, we compared methods across the 36 studies meeting the review criteria. To some extent, variation was related to targeting different audiences or acknowledging the most appropriate population for a given treatment. However, the review identified potential areas of uncertainty and difficulty in interpretation, particularly regarding duration of observation periods and the importance of visual acuity as an endpoint or a proxy for patient-reported utilities. We urge thoughtful consideration of these study characteristics when comparing results.

Rehabilitation Approaches in Macular Degeneration Patients

PubMed Central

Maniglia, Marcello; Cottereau, Benoit R.; Soler, Vincent; Trotter, Yves

2016-01-01

Age related macular degeneration (AMD) is a visual disease that affects elderly population. It entails a progressive loss of central vision whose consequences are dramatic for the patient’s quality of life. Current rehabilitation programs are restricted to technical aids based on visual devices. They only temporarily improve specific visual functions such as reading skills. Considering the rapid increase of the aging population worldwide, it is crucial to intensify clinical research on AMD in order to develop simple and efficient methods that improve the patient’s visual performances in many different contexts. One very promising approach to face this challenge is based on perceptual learning (PL). Through intensive practice, PL can induce neural plasticity in sensory cortices and result in long-lasting enhancements for various perceptual tasks in both normal and visually impaired populations. A growing number of studies showed how appropriate PL protocols improve visual functions in visual disorders, namely amblyopia, presbyopia or myopia. In order to successfully apply these approaches to more severe conditions such as AMD, numerous challenges have to be overcome. Indeed, the overall elderly age of patients and the reduced cortical surface that is devoted to peripheral vision potentially limit neural plasticity in this population. In addition, ocular fixation becomes much less stable because patients have to rely on peripheral fixation spots outside the scotoma whose size keeps on evolving. The aim of this review article is to discuss the recent literature on this topic and to offer a unified approach for developing new rehabilitation programs of AMD using PL. We argue that with an appropriate experimental and training protocol that is adapted to each patient needs, PL can offer fascinating opportunities for the development of simple, non-expensive rehabilitation approaches a large spectrum of visual functions in AMD patients. PMID:28082876

Cellular regeneration strategies for macular degeneration: past, present and future.

PubMed

Chichagova, Valeria; Hallam, Dean; Collin, Joseph; Zerti, Darin; Dorgau, Birthe; Felemban, Majed; Lako, Majlinda; Steel, David H

2018-05-01

Despite considerable effort and significant therapeutic advances, age-related macular degeneration (AMD) remains the commonest cause of blindness in the developed world. Progressive late-stage AMD with outer retinal degeneration currently has no proven treatment. There has been significant interest in the possibility that cellular treatments may slow or reverse visual loss in AMD. A number of modes of action have been suggested, including cell replacement and rescue, as well as immune modulation to delay the neurodegenerative process. Their appeal in this enigmatic disease relate to their generic, non-pathway-specific effects. The outer retina in particular has been at the forefront of developments in cellular regenerative therapies being surgically accessible, easily observable, as well as having a relatively simple architecture. Both the retinal pigment epithelium (RPE) and photoreceptors have been considered for replacement therapies as both sheets and cell suspensions. Studies using autologous RPE, and to a lesser extent, foetal retina, have shown proof of principle. A wide variety of cell sources have been proposed with pluripotent stem cell-derived cells currently holding the centre stage. Recent early-phase trials using these cells for RPE replacement have met safety endpoints and hinted at possible efficacy. Animal studies have confirmed the promise that photoreceptor replacement, even in a completely degenerated outer retina may restore some vision. Many challenges, however, remain, not least of which include avoiding immune rejection, ensuring long-term cellular survival and maximising effect. This review provides an overview of progress made, ongoing studies and challenges ahead.

Age-related macular degeneration: genome-wide association studies to translation.

PubMed

Black, James R M; Clark, Simon J

2016-04-01

In recent years, genome-wide association studies (GWAS), which are able to analyze the contribution to disease of genetic variations that are common within a population, have attracted considerable investment. Despite identifying genetic variants for many conditions, they have been criticized for yielding data with minimal clinical utility. However, in this regard, age-related macular degeneration (AMD), the most common form of blindness in the Western world, is a striking exception. Through GWAS, common genetic variants at a number of loci have been discovered. Two loci in particular, including genes of the complement cascade on chromosome 1 and the ARMS2/HTRA1 genes on chromosome 10, have been shown to convey significantly increased susceptibility to developing AMD. Today, although it is possible to screen individuals for a genetic predisposition to the disease, effective interventional strategies for those at risk of developing AMD are scarce. Ongoing research in this area is nonetheless promising. After providing brief overviews of AMD and common disease genetics, we outline the main recent advances in the understanding of AMD, particularly those made through GWAS. Finally, the true merit of these findings and their current and potential translational value is examined.Genet Med 18 4, 283-289.

Description of the Age-Related Eye Disease Study 9-step severity scale applied to participants in the Complications of Age-related Macular Degeneration Prevention Trial.

PubMed

Ying, Gui-shuang; Maguire, Maureen G; Alexander, Judith; Martin, Revell W; Antoszyk, Andrew N

2009-09-01

To describe characteristics of the Age-Related Eye Disease Study (AREDS) 9-step severity scale applied to participants in the Complications of Age-related Macular Degeneration Prevention Trial (CAPT). Eligibility criteria for CAPT required 10 or more large (>or=125 microm) drusen in each eye. Readers graded baseline photographs from all participants and all follow-up photographs from 402 untreated eyes. Drusen and pigment characteristics were used to assign the AREDS scale score. Choroidal neovascularization was identified from fluorescein angiograms. Geographic atrophy involving the macular center was identified from color photographs. Among 1001 untreated eyes, 90% were at steps 5 to 7 at baseline. The 5-year incidence of advanced age-related macular degeneration (AMD) increased with each step from 8% (step 4) to 40% (steps 8 and 9 combined). These rates were similar to those reported in AREDS. Among 261 eyes with all 5 annual photograph gradings available and without progression to advanced AMD, 55% of eyes had scores that indicated improvement at least once. Before progression to advanced AMD, only 32% of 141 eyes either went through step 8 or 9 or had an increase of 2 or more steps from baseline. The AREDS 9-step severity scale was predictive of development of advanced AMD. The AREDS scale has deficiencies as a surrogate outcome for progression to advanced AMD.

Healthy Lifestyles Related to Subsequent Prevalence of Age-Related Macular Degeneration

PubMed Central

Mares, JA; Voland, R.; Sondel, SA; Millen, A.E.; LaRowe, T; Moeller, SM; Klein, M.L.; Blodi, B.A; Chappell, R.; Tinker, L.; Ritenbaugh, C; Gehrs, K; Sarto, G; Johnson, E.J; Snodderly, M; Wallace, RB

2010-01-01

Purpose The relationships between lifestyle behaviors of diet, smoking and physical activity and the subsequent prevalence of age-related macular degeneration (AMD) were investigated. Methods The population included 1,313 participants (55 to 74 years) in the Carotenoids in Age-Related Eye Disease Study (CAREDS), an ancillary study of the Women's Health Initiative Observational Study (WHIOS). Scores on a modified 2005 Healthy Eating Index (mHEI) were assigned using responses to a food frequency questionnaire administered at WHIOS baseline (1994-1998). Physical activity and lifetime smoking history were queried. An average of six years later, stereoscopic fundus photographs were taken to assess presence and severity of AMD; present in 202 women, 94% of whom had early AMD, the primary outcome. Results In multivariate models, women whose diets scored in the highest compared with the lowest quintile on the mHEI had a 46% lower odds for early AMD. Women in the highest vs. lowest quintile for physical activity (MET- Hrs/Wk) had 54% lower odds for early AMD. Although smoking, alone was not independently associated with AMD, having a combination of three healthy lifestyles (healthy diet, physical activity and not smoking) was associated with a 71% lower odds for AMD compared with having high risk scores (P=0.0004). Conclusions Modifying lifestyles might reduce risk for early AMD as much as 3-fold, lowering the risk for advanced AMD in a person's lifetime and the social and economic costs of AMD to society. PMID:21149749

Optical Coherence Tomography Updates on Clinical and Technical Developments. Age-Related Macular Degeneration: Drusen and Geographic Atrophy

NASA Astrophysics Data System (ADS)

Fleckenstein, Monika; Schmitz-Valckenberg, Steffen; Holz, Frank G.

Age-related macular degeneration (AMD) is a complex disease with both genetic and environmental factors influencing its development. With the advent of high-resolution OCT imaging, the characterization of drusen in AMD has become possible. The in vivo morphologic characteristics imaged with SD-OCT may represent distinct subclasses of drusen variants, may relate closely to ultrastructural drusen elements identified in donor eyes, and may be useful imaging biomarkers for disease severity or risk of progression [Khanifar et al. Ophthalmology 115(11):1883-1890, 2008].

Optical Coherence Tomography and the Development of Antiangiogenic Therapies in Neovascular Age-Related Macular Degeneration

PubMed Central

Rosenfeld, Philip J.

2016-01-01

Purpose To explain the pivotal role optical coherence tomography (OCT) imaging had in the development of antiangiogenic therapies for the treatment of neovascular age-related macular degeneration (nvAMD). Methods A historical literature review was combined with personal perspectives from the introduction of OCT imaging and the early clinical use of vascular endothelial growth factor (VEGF) inhibitors. Results At the time that OCT emerged, the gold standard for imaging of nvAMD was fluorescein angiography (FA), a time-consuming, dye-based, invasive technique that provided en face images of the retina and was used to characterize leakage, perfusion status, and the types of macular neovascularization (MNV). In comparison, OCT imaging was a fast, safe, noninvasive technique that complemented FA imaging by providing cross-sectional images of the macula. OCT was able to visualize and quantify the macular fluid that was associated with the presence of excess VEGF, which was identified by intraretinal fluid, subretinal fluid, and fluid under the retinal pigment epithelium (RPE). Clinicians quickly appreciated the benefits of OCT imaging for following macular fluid after anti-VEGF therapy. By observing the qualitative and quantitative changes in macular fluid depicted by OCT imaging, clinicians were empowered to compare anti-VEGF drugs and move from fixed-dosing regimens to patient-specific dosing strategies requiring fewer injections. Conclusions Optical coherence tomography imaging was adopted as a VEGF-meter, a method to detect excess VEGF, and evolved to become the gold standard imaging strategy for diagnosing nvAMD, assessing treatment responses to anti-VEGF drugs, deciding when to re-treat, and evaluating disease progression. PMID:27409464

RISK FACTORS AND CLINICAL SIGNIFICANCE OF PRECHOROIDAL CLEFT IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PubMed

Kim, Jong Min; Kang, Se Woong; Son, Dae Yong; Bae, Kunho

2017-11-01

To investigate the risk factors associated with prechoroidal cleft occurrence after treatment for neovascular age-related macular degeneration (nAMD) and to elucidate its clinical significance. Two hundred thirty-four subjects who were treated for neovascular age-related macular degeneration were assessed to identify prechoroidal cleft on optical coherence tomography. Clinical variables were compared between patients manifesting a cleft (cleft group) and patients who did not (control group). Prechoroidal cleft was detected in 29 of 234 patients (8.1%). Although the baseline visual acuity was not different between the 2 groups, logMAR visual acuity at final visit was 0.89 ± 0.74 (with approximate Snellen equivalent of 20/160) in the cleft group and 0.65 ± 0.69 (with approximate Snellen equivalent of 20/100) in controls (P < 0.05). Within cleft group, the early-onset (<6 months) subgroup had even worse visual outcomes than the late-onset subgroup (P < 0.05). Multiple logistic regression analyses revealed that the incidence of prechoroidal cleft was positively correlated with having received intravitreal gas injection to displace a submacular hemorrhage and a diagnosis of retinal angiomatous proliferation and typical neovascular age-related macular degeneration (P < 0.05). Diagnosis of retinal angiomatous proliferation and typical neovascular age-related macular degeneration, and a submacular hemorrhage treated by pneumatic displacement were the independent risk factors for development of prechoroidal cleft. Eyes with a cleft, especially clefts that develop early, generally had worse prognoses than eyes without clefts.

Macular morphology and visual acuity in the comparison of age-related macular degeneration treatments trials.

PubMed

Jaffe, Glenn J; Martin, Daniel F; Toth, Cynthia A; Daniel, Ebenezer; Maguire, Maureen G; Ying, Gui-Shuang; Grunwald, Juan E; Huang, Jiayan

2013-09-01

To describe the effects of treatment for 1 year with ranibizumab or bevacizumab on macular morphology and the association of macular morphology with visual acuity (VA) in eyes with neovascular age-related macular degeneration (AMD). Prospective cohort study within a randomized clinical trial. Participants in the Comparison of Age-related Macular Degeneration Treatments Trials. Participants were assigned randomly to treatment with ranibizumab or bevacizumab on a monthly or as-needed schedule. Optical coherence tomography (OCT), fluorescein angiography (FA), color fundus photography (FP), and VA testing were performed periodically throughout 52 weeks. Masked readers graded images. General linear models were applied to evaluate effects of time and treatment on outcomes. Fluid type and location and thickness by OCT, size, and lesion composition on FP, FA, and VA. Intraretinal fluid (IRF), subretinal fluid (SRF), subretinal pigment epithelium fluid, and retinal, subretinal, and subretinal tissue complex thickness decreased in all treatment groups. A higher proportion of eyes treated monthly with ranibizumab had fluid resolution at 4 weeks, and the difference persisted through 52 weeks. At 52 weeks, there was little association between the presence of fluid of any type (without regard to fluid location) and the mean VA. However, at all time points, eyes with residual IRF, especially foveal IRF, had worse mean VA (9 letters) than those without IRF. Eyes with abnormally thin (<120 μm) or thick (>212 μm) retinas had worse VA than those with normal thickness (120-212 μm). At week 52, eyes with larger neovascular lesions or with foveal scar had worse VA than eyes without these features. Anti-vascular endothelial growth factor (VEGF) therapy reduced lesion activity and improved VA in all treatment groups. At all time points, eyes with residual IRF had worse VA than those without. Eyes with abnormally thin or thick retinas, residual large lesions, and scar also had worse VA

Systems-level analysis of age-related macular degeneration reveals global biomarkers and phenotype-specific functional networks

PubMed Central

2012-01-01

Background Age-related macular degeneration (AMD) is a leading cause of blindness that affects the central region of the retinal pigmented epithelium (RPE), choroid, and neural retina. Initially characterized by an accumulation of sub-RPE deposits, AMD leads to progressive retinal degeneration, and in advanced cases, irreversible vision loss. Although genetic analysis, animal models, and cell culture systems have yielded important insights into AMD, the molecular pathways underlying AMD's onset and progression remain poorly delineated. We sought to better understand the molecular underpinnings of this devastating disease by performing the first comparative transcriptome analysis of AMD and normal human donor eyes. Methods RPE-choroid and retina tissue samples were obtained from a common cohort of 31 normal, 26 AMD, and 11 potential pre-AMD human donor eyes. Transcriptome profiles were generated for macular and extramacular regions, and statistical and bioinformatic methods were employed to identify disease-associated gene signatures and functionally enriched protein association networks. Selected genes of high significance were validated using an independent donor cohort. Results We identified over 50 annotated genes enriched in cell-mediated immune responses that are globally over-expressed in RPE-choroid AMD phenotypes. Using a machine learning model and a second donor cohort, we show that the top 20 global genes are predictive of AMD clinical diagnosis. We also discovered functionally enriched gene sets in the RPE-choroid that delineate the advanced AMD phenotypes, neovascular AMD and geographic atrophy. Moreover, we identified a graded increase of transcript levels in the retina related to wound response, complement cascade, and neurogenesis that strongly correlates with decreased levels of phototransduction transcripts and increased AMD severity. Based on our findings, we assembled protein-protein interactomes that highlight functional networks likely to be

Stem cell therapies for age-related macular degeneration: the past, present, and future.

PubMed

Dang, Yalong; Zhang, Chun; Zhu, Yu

2015-01-01

In the developed world, age-related macular degeneration (AMD) is one of the major causes of irreversible blindness in the elderly. Although management of neovascular AMD (wet AMD) has dramatically progressed, there is still no effective treatment for nonneovascular AMD (dry AMD), which is characterized by retinal pigment epithelial (RPE) cell death (or dysfunction) and microenvironmental disruption in the retina. Therefore, RPE replacement and microenvironmental regulation represent viable treatments for dry AMD. Recent advances in cell biology have demonstrated that RPE cells can be easily generated from several cell types (pluripotent stem cells, multipotent stem cells, or even somatic cells) by spontaneous differentiation, coculturing, defined factors or cell reprogramming, respectively. Additionally, in vivo studies also showed that the restoration of visual function could be obtained by transplanting functional RPE cells into the subretinal space of recipient. More importantly, clinical trials approved by the US government have shown promising prospects in RPE transplantation. However, key issues such as implantation techniques, immune rejection, and xeno-free techniques are still needed to be further investigated. This review will summarize recent advances in cell transplantation for dry AMD. The obstacles and prospects in this field will also be discussed.

Visual Function Metrics in Early and Intermediate Dry Age-related Macular Degeneration for Use as Clinical Trial Endpoints.

PubMed

Cocce, Kimberly J; Stinnett, Sandra S; Luhmann, Ulrich F O; Vajzovic, Lejla; Horne, Anupama; Schuman, Stefanie G; Toth, Cynthia A; Cousins, Scott W; Lad, Eleonora M

2018-05-01

To evaluate and quantify visual function metrics to be used as endpoints of age-related macular degeneration (AMD) stages and visual acuity (VA) loss in patients with early and intermediate AMD. Cross-sectional analysis of baseline data from a prospective study. One hundred and one patients were enrolled at Duke Eye Center: 80 patients with early AMD (Age-Related Eye Disease Study [AREDS] stage 2 [n = 33] and intermediate stage 3 [n = 47]) and 21 age-matched, normal controls. A dilated retinal examination, macular pigment optical density measurements, and several functional assessments (best-corrected visual acuity, macular integrity assessment mesopic microperimety, dark adaptometry, low-luminance visual acuity [LLVA] [standard using a log 2.0 neutral density filter and computerized method], and cone contrast test [CCT]) were performed. Low-luminance deficit (LLD) was defined as the difference in numbers of letters read at standard vs low luminance. Group comparisons were performed to evaluate differences between the control and the early and intermediate AMD groups using 2-sided significance tests. Functional measures that significantly distinguished between normal and intermediate AMD were standard and computerized (0.5 cd/m 2 ) LLVA, percent reduced threshold and average threshold on microperimetry, CCTs, and rod intercept on dark adaptation (P < .05). The intermediate group demonstrated deficits in microperimetry reduced threshhold, computerized LLD2, and dark adaptation (P < .05) relative to early AMD. Our study suggests that LLVA, microperimetry, CCT, and dark adaptation may serve as functional measures differentiating early-to-intermediate stages of dry AMD. Copyright © 2018 Elsevier Inc. All rights reserved.

Absolute and estimated values of macular pigment optical density in young and aged Asian participants with or without age-related macular degeneration.

PubMed

Ozawa, Yoko; Shigeno, Yuta; Nagai, Norihiro; Suzuki, Misa; Kurihara, Toshihide; Minami, Sakiko; Hirano, Eri; Shinoda, Hajime; Kobayashi, Saori; Tsubota, Kazuo

2017-08-29

Lutein and zeaxanthin are suggested micronutrient supplements to prevent the progression of age-related macular degeneration (AMD), a leading cause of blindness worldwide. To monitor the levels of lutein/zeaxanthin in the macula, macular pigment optical density (MPOD) is measured. A commercially available device (MPSII®, Elektron Technology, Switzerland), using technology based on heterochromatic flicker photometry, can measure both absolute and estimated values of MPOD. However, whether the estimated value is applicable to Asian individuals and/or AMD patients remains to be determined. The absolute and estimated values of MPOD were measured using the MPSII® device in 77 participants with a best-corrected visual acuity (BCVA) > 0.099 (logMAR score). The studied eyes included 17 young (20-29 years) healthy, 26 aged (>50 years) healthy, 18 aged and AMD-fellow, and 16 aged AMD eyes. The mean BCVA among the groups were not significantly different. Both absolute and estimated values were measurable in all eyes of young healthy group. However, absolute values were measurable in only 57.7%, 66.7%, and 43.8%, of the aged healthy, AMD-fellow, and AMD groups, respectively, and 56.7% of the eyes included in the 3 aged groups. In contrast, the estimated value was measurable in 84.6%, 88.9% and 93.8% of the groups, respectively, and 88.3% of eyes in the pooled aged group. The estimated value was correlated with absolute value in individuals from all groups by Spearman's correlation coefficient analyses (young healthy: R 2  = 0.885, P = 0.0001; aged healthy: R 2  = 0.765, P = 0.001; AMD-fellow: R 2  = 0.851, P = 0.0001; and AMD: R 2  = 0.860, P = 0.013). Using the estimated value, significantly lower MPOD values were found in aged AMD-related eyes, which included both AMD-fellow and AMD eyes, compared with aged healthy eyes by Student's t-test (P = 0.02). Absolute, in contrast to estimated, value was measurable in a limited number of aged participants

Pesticide Use and Age-Related Macular Degeneration in the Agricultural Health Study

PubMed Central

Montgomery, Martha P.; Postel, Eric; Umbach, David M.; Richards, Marie; Watson, Mary; Blair, Aaron; Chen, Honglei; Sandler, Dale P.; Schmidt, Silke

2017-01-01

Background: Age-related macular degeneration (AMD) is a leading cause of blindness in developed countries. Few studies have investigated its relationship to environmental neurotoxicants. In previous cross-sectional studies, we found an association between pesticide use and self-reported retinal degeneration. Objective: We evaluated the association of pesticide use with physician-confirmed incident AMD. Methods: The Agricultural Health Study (AHS) is a prospective cohort of pesticide applicators and their spouses enrolled from 1993–1997 in Iowa and North Carolina. Cohort members reported lifetime use of 50 specific pesticides at enrollment. Self-reports of incident AMD during follow-up through 2007 were confirmed by reports from participants’ physicians and by independent evaluation of retinal photographs provided by the physicians. Confirmed cases (n=161) were compared with AHS cohort members without AMD (n=39,108). We estimated odds ratios (ORs) and 95% confidence intervals (CIs) by logistic regression with adjustment for age, gender, and smoking. Results: AMD was associated with ever use of organochlorine [OR=2.7 (95% CI: 1.8, 4.0)] and organophosphate [OR=2.0 (95% CI: 1.3, 3.0)] insecticides and phenoxyacetate herbicides [OR=1.9 (95% CI: 1.2, 2.8)]. Specific pesticides consistently associated with AMD included chlordane, dichlorodiphenyltrichloroethane (DDT), malathion, and captan; others with notable but slightly less consistent associations were heptachlor, diazinon, phorate, 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), and 2,4-dichlorophenoxyacetic acid (2,4-D). Results were similar for men and women. Some specific pesticides were associated with both early- and late-stage AMD, but others were associated with only one stage. Conclusions: Exposures to specific pesticides may be modifiable risk factors for AMD. https://doi.org/10.1289/EHP793 PMID:28886597

Pharmacologic Treatment of Wet Type Age-related Macular Degeneration; Current and Evolving Therapies.

PubMed

Shams Najafabadi, Hoda; Daftarian, Narsis; Ahmadieh, Hamid; Soheili, Zahra-Soheila

2017-08-01

Age-related macular degeneration as the major cause of blindness in the elderly population has remained at the epicenter of clinical research in ophthalmology. This retinal disorder is characterized by the photoreceptor and retinal pigment epithelial cells loss, occurring within the macula. The disease represents a spectrum of clinical manifestations. It is a multifactorial disease resulting from a combination of genetic predispositions and environmental risk factors. AMD is classified into two different types, dry and wet. Wet AMD is in close relation with angiogenesis and inflammatory processes.A variety of anti-angiogenesis and anti-inflammatory drugs have been proposed for the treatment of the disease. The purpose of this paper is to briefly review the pharmacological therapies of the wet form of AMD and focus on new drugs that are currently in different stages of research and development.

Oxidative stress in dry age-related macular degeneration and exfoliation syndrome.

PubMed

Chiras, Dimitrios; Kitsos, George; Petersen, Michael B; Skalidakis, Iosif; Kroupis, Christos

2015-02-01

Oxidative stress refers to cellular or molecular damage caused by reactive oxygen species, which especially occurs in age-related conditions as a result of an imbalance between the production of reactive oxygen species and the antioxidant defense response. Dry age-related macular degeneration (AMD) and exfoliation syndrome (XFS) are two common and complex age-related conditions that can cause irreversible vision loss. Two subtypes of AMD, which is the leading cause of blindness in the Western world, exist: the most prevalent dry type and the most severe wet type. Early dry AMD is characterized by formation of drusen, which are sub-retinal deposits, in the macular area and may progress to geographic atrophy with more dramatic manifestation. XFS is a systemic disorder of the extracellular matrix characterized by the accumulation of elastic fibrils that leads, in most cases, to glaucoma development with progressive and irreversible vision loss. Due to the aging population, the prevalence of these already-widespread conditions is increasing and is resulting in significant economic and psychological costs for individuals and for society. The exact composition of the abnormal drusen and XFS material as well as the mechanisms responsible for their production and accumulation still remain elusive, and consequently treatment for both diseases is lacking. However, recent epidemiologic, genetic and molecular studies support a major role for oxidative stress in both dry AMD and XFS development. Understanding the early molecular events in their pathogenesis and the exact role of oxidative stress may provide novel opportunities for therapeutic intervention for the prevention of progression to advanced disease.

A risk score for the prediction of advanced age-related macular degeneration: Development and validation in 2 prospective cohorts

USDA-ARS?s Scientific Manuscript database

We aimed to develop an eye specific model which used readily available information to predict risk for advanced age-related macular degeneration (AMD). We used the Age-Related Eye Disease Study (AREDS) as our training dataset, which consisted of the 4,507 participants (contributing 1,185 affected v...

Dry age-related macular degeneration: mechanisms, therapeutic targets, and imaging.

PubMed

Bowes Rickman, Catherine; Farsiu, Sina; Toth, Cynthia A; Klingeborn, Mikael

2013-12-13

Age-related macular degeneration is the leading cause of irreversible visual dysfunction in individuals over 65 in Western Society. Patients with AMD are classified as having early stage disease (early AMD), in which visual function is affected, or late AMD (generally characterized as either "wet" neovascular AMD, "dry" atrophic AMD or both), in which central vision is severely compromised or lost. Until recently, there have been no therapies available to treat the disorder(s). Now, the most common wet form of late-stage AMD, choroidal neovascularization, generally responds to treatment with anti-vascular endothelial growth factor therapies. Nevertheless, there are no current therapies to restore lost vision in eyes with advanced atrophic AMD. Oral supplementation with the Age-Related Eye Disease Study (AREDS) or AREDS2 formulation (antioxidant vitamins C and E, lutein, zeaxanthin, and zinc) has been shown to reduce the risk of progression to advanced AMD, although the impact was in neovascular rather than atrophic AMD. Recent findings, however, have demonstrated several features of early AMD that are likely to be druggable targets for treatment. Studies have established that much of the genetic risk for AMD is associated with complement genes. Consequently, several complement-based therapeutic treatment approaches are being pursued. Potential treatment strategies against AMD deposit formation and protein and/or lipid deposition will be discussed, including anti-amyloid therapies. In addition, the role of autophagy in AMD and prevention of oxidative stress through modulation of the antioxidant system will be explored. Finally, the success of these new therapies in clinical trials and beyond relies on early detection, disease typing, and predicting disease progression, areas that are currently being rapidly transformed by improving imaging modalities and functional assays.

Dry Age-Related Macular Degeneration: Mechanisms, Therapeutic Targets, and Imaging

PubMed Central

Bowes Rickman, Catherine; Farsiu, Sina; Toth, Cynthia A.; Klingeborn, Mikael

2013-01-01

Age-related macular degeneration is the leading cause of irreversible visual dysfunction in individuals over 65 in Western Society. Patients with AMD are classified as having early stage disease (early AMD), in which visual function is affected, or late AMD (generally characterized as either “wet” neovascular AMD, “dry” atrophic AMD or both), in which central vision is severely compromised or lost. Until recently, there have been no therapies available to treat the disorder(s). Now, the most common wet form of late-stage AMD, choroidal neovascularization, generally responds to treatment with anti–vascular endothelial growth factor therapies. Nevertheless, there are no current therapies to restore lost vision in eyes with advanced atrophic AMD. Oral supplementation with the Age-Related Eye Disease Study (AREDS) or AREDS2 formulation (antioxidant vitamins C and E, lutein, zeaxanthin, and zinc) has been shown to reduce the risk of progression to advanced AMD, although the impact was in neovascular rather than atrophic AMD. Recent findings, however, have demonstrated several features of early AMD that are likely to be druggable targets for treatment. Studies have established that much of the genetic risk for AMD is associated with complement genes. Consequently, several complement-based therapeutic treatment approaches are being pursued. Potential treatment strategies against AMD deposit formation and protein and/or lipid deposition will be discussed, including anti-amyloid therapies. In addition, the role of autophagy in AMD and prevention of oxidative stress through modulation of the antioxidant system will be explored. Finally, the success of these new therapies in clinical trials and beyond relies on early detection, disease typing, and predicting disease progression, areas that are currently being rapidly transformed by improving imaging modalities and functional assays. PMID:24335072

Does eating particular diets alter risk of age-related macular degeneration in users of the Age-Related Eye Disease Study supplements?

USDA-ARS?s Scientific Manuscript database

Background: Recent information suggests that the Age-Related Eye Disease Study (AREDS) supplement, enhanced intake of omega-3 fatty acids, and diminishing dietary glycemic index (dGI) are protective against advanced age-related macular degeneration (AMD). Methods: Dietary information was collected a...

Risk Factors for Four-Year Incidence and Progression of Age-Related Macular Degeneration: The Los Angeles Latino Eye Study

PubMed Central

CHOUDHURY, FARZANA; VARMA, ROHIT; MCKEAN-COWDIN, ROBERTA; KLEIN, RONALD; AZEN, STANLEY P.

2011-01-01

PURPOSE To identify risk factors for 4-year incidence and progression of age-related macular degeneration (AMD) in adult Latinos. DESIGN Population-based prospective cohort study. METHODS Participants, aged 40 or older, from The Los Angeles Latino Eye Study (LALES) underwent standardized comprehensive ophthalmologic examinations at baseline and at 4 years of follow-up. Age-related macular degeneration was detected by grading 30-degree stereoscopic fundus photographs using the modified Wisconsin Age-Related Maculopathy Grading System. Multivariate stepwise logistic regression was used to examine the independent association of incidence and progression of AMD and baseline sociodemographic, behavioral, clinical, and ocular characteristics. RESULTS Multivariate analyses revealed that older age (OR per decade of age: 1.52; 95% CI: 1.29, 1.85) and higher pulse pressure (OR per 10 mm Hg: 2.54; 95% CI: 1.36, 4.76) were independently associated with the incidence of any AMD. The same factors were associated with early AMD, soft indistinct drusen, and retinal pigmentary abnormalities. Additionally, presence of clinically diagnosed diabetes mellitus was independently associated with increased retinal pigment (OR: 1.66; 95% CI: 1.01, 2.85), and male gender was associated with retinal pigment epithelial depigmentation (OR 2.50; 95% CI: 1.48, 4.23). Older age (OR per decade of age: 2.20; 95% CI: 1.82, 2.67) and current smoking (OR: 2.85; 95% CI: 1.66, 4.90) were independently associated with progression of AMD. CONCLUSIONS Several modifiable risk factors were associated with 4-year incidence and progression of AMD in Latinos. The results suggest that interventions aimed at reducing pulse pressure and promoting smoking cessation may reduce incidence and progression of AMD, respectively. PMID:21679916

Oral docosahexaenoic acid in the prevention of exudative age-related macular degeneration: the Nutritional AMD Treatment 2 study.

PubMed

Souied, Eric H; Delcourt, Cécile; Querques, Giuseppe; Bassols, Ana; Merle, Bénédicte; Zourdani, Alain; Smith, Theodore; Benlian, Pascale

2013-08-01

To evaluate the efficacy of docosahexaenoic acid (DHA)-enriched oral supplementation in preventing exudative age-related macular degeneration (AMD). The Nutritional AMD Treatment 2 study was a randomized, placebo-controlled, double-blind, parallel, comparative study. Two hundred sixty-three patients 55 years of age or older and younger than 85 years with early lesions of age-related maculopathy and visual acuity better than 0.4 logarithm of minimum angle of resolution units in the study eye and neovascular AMD in the fellow eye. Patients were assigned randomly to receive either 840 mg/day DHA and 270 mg/day eicosapentaenoic acid (EPA) from fish oil capsules or the placebo (olive oil capsules) for 3 years. The primary outcome measure was time to occurrence of choroidal neovascularization (CNV) in the study eye. Secondary outcome measures in the study eye were: incidence of CNV developing in patients, changes in visual acuity, occurrence and progression of drusen, and changes in EPA plus DHA level in red blood cell membrane (RBCM). Time to occurrence and incidence of CNV in the study eye were not significantly different between the DHA group (19.5±10.9 months and 28.4%, respectively) and the placebo group (18.7±10.6 months and 25.6%, respectively). In the DHA group, EPA plus DHA levels increased significantly in RBCM (+70%; P<0.001), suggesting that DHA easily penetrated cells, but this occurred unexpectedly also in the placebo group (+9%; P = 0.007). In the DHA-allocated group, patients steadily achieving the highest tertile of EPA plus DHA levels in RBCM had significantly lower risk (-68%; P = 0.047; hazard ratio, 0.32; 95% confidence interval, 0.10-0.99) of CNV developing over 3 years. No marked changes from baseline in best-corrected visual acuity, drusen progression, or geographic atrophy in the study eye were observed throughout the study in either group. In patients with unilateral exudative AMD, 3 years of oral DHA-enriched supplementation had the same

Imaging of Melanin Disruption in Age-Related Macular Degeneration Using Multispectral Imaging.

PubMed

Dugel, Pravin U; Zimmer, Cheryl N

2016-02-01

To investigate whether multispectral imaging (MSI) is able to obtain a noninvasive view of melanin disruption associated with age-related macular degeneration (AMD), which could support early diagnosis and potential treatment strategies. A single retinal center, retrospective, observational, image analysis study of MSI images of 43 patients was done to determine the extent of melanin pigment exhibited in association with AMD, based on the Age-Related Eye Disease Study classification and grading scale. Corresponding fundus photos were also graded for 12 of the eyes. Fifty-one of 61 eyes (84%) of 43 patients with AMD were determined to have melanin disruption in their MSI images in at least the central and/or one of four inner ETDRS areas. There was a relationship between severity of disease and the degree of melanin disruption. The sensitivity of fundus photography for melanin pigment as compared to MSI was only 62.5%, with three false-negatives. A direct, noninvasive, unobstructed view of melanin disruption associated with AMD can be observed using MSI. Copyright 2016, SLACK Incorporated.

Population-based incidence of exudative age-related macular degeneration and ranibizumab treatment load.

PubMed

Geirsdottir, Asbjorg; Jonsson, Oskar; Thorisdottir, Sigridur; Helgadottir, Gudleif; Jonasson, Fridbert; Stefansson, Einar; Sigurdsson, Haraldur

2012-03-01

The use of intravitreal vascular endothelial growth factor antibodies for exudative age-related macular degeneration (AMD) has stressed ophthalmology services and drug budgets throughout the world. The authors study the population-based incidence of exudative AMD in Iceland and the use of intravitreal ranibizumab in a defined population. This is a prospective study of 439 consecutive patients aged 60 years and older with exudative AMD starting intravitreal ranibizumab for exudative AMD in Iceland from March 2007 to December 2009. All patients initially received three consecutive ranibizumab injections, with regular follow-up visits and re-treatment as needed. In total, 517 eyes from 439 patients received treatment for exudative AMD (mean age 79 years). The annual incidence of exudative AMD in the population 60 years and older is 0.29%. The incidence increased with advancing age, double for patients 85 years and older compared with those 75-79 years. Approximately 2400 ranibizumab injections per 100,000 persons aged 60 years and older were given each year for exudative AMD. These data allow an estimation of the incidence of exudative AMD in a Caucasian population and the treatment load with ranibizumab, which may help plan anti-vascular endothelial growth factor treatment programmes and estimate costs.

Statins for age-related macular degeneration.

PubMed

Gehlbach, Peter; Li, Tianjing; Hatef, Elham

2015-02-11

Age-related macular degeneration (AMD) is a progressive late onset disorder of the macula affecting central vision. Age-related macular degeneration is the leading cause of blindness in people over 65 years in industrialized countries. Recent epidemiologic, genetic, and pathological evidence has shown AMD shares a number of risk factors with atherosclerosis, leading to the hypothesis that statins may exert protective effects in AMD. The objective of this review was to examine the effectiveness of statins compared with other treatments, no treatment, or placebo in delaying the onset and progression of AMD. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 6), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2014), EMBASE (January 1980 to June 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to June 2014), PubMed (January 1946 to June 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 5 June 2014. We included randomized controlled trials (RCTs) that compared statins with other treatments, no treatment, or placebo in participants who were either susceptible to or diagnosed as having early stages of AMD. We used standard methodological procedures expected by The Cochrane Collaboration. Two authors independently evaluated the search results against the selection criteria, abstracted data, and assessed risk of bias. We did not perform meta-analysis due to heterogeneity in the interventions and outcomes among the included studies. Two RCTs with 144 total participants met the selection criteria

Efficacy of vitrectomy and epiretinal membrane peeling in eyes with dry age-related macular degeneration.

PubMed

Mason, John O; Patel, Shyam A

2015-01-01

To study the efficacy of epiretinal membrane (ERM) peeling in eyes with dry age-related macular degeneration (AMD). We retrospectively analyzed patient charts on 17 eyes (16 patients) that underwent ERM peeling with a concurrent diagnosis of dry AMD. Eyes with concurrent dry AMD and with a good preoperative best-corrected visual acuity (BCVA) (better than or equal to 20/50) had a statistically significant mean BCVA improvement at 6 months after ERM peeling. There was a statistical increase in mean BCVA from 20/95 to 20/56 in dry AMD eyes, and no eyes showed worsening in BCVA at 6 months or at most recent follow-up. Five/seventeen (29.4%) eyes had cataract formation or progression. There were no other complications, reoperations, or reoccurrences. ERM peeling in eyes with dry AMD may show significant improvement, especially in eyes with good preoperative BCVA. The procedure is relatively safe with low complications and reoccurrences.

Circulating anti-retinal antibodies as immune markers in age-related macular degeneration

PubMed Central

Patel, Nishal; Ohbayashi, Masahara; Nugent, Alex K; Ramchand, Kanchan; Toda, Masako; Chau, Kai-Yin; Bunce, Catey; Webster, Andrew; Bird, Alan C; Ono, Santa Jeremy; Chong, Victor

2005-01-01

Age-related macular maculopathy (ARM) and age-related macular degeneration (AMD) are the leading causes of blindness in the Western world. Despite the magnitude of this clinical problem, very little is known about the pathogenesis of the disease. In this study, we analysed the sera (using indirect immunohistochemistry and Western blot analysis) from a very large cohort of such patients and normal age-matched controls to detect circulating anti-retinal antibodies. Patients with bilateral drusen (n = 64) and with chorioretinal neovascularization (CNV) (n = 51) were recruited in addition to age-matched control subjects (n = 39). The sera were analysed for anti-retinal immunoglobulins on retinal sections. The data were then correlated with the clinical features graded according to the International Classification and Grading System of ARM and AMD. The sera of patients with drusen (93·75%) and CNV (82·27%) were found to have a significantly (P = 0·02) higher titre of autoantibodies to the retina in comparison with controls (8·69%), indicating significant evidence of involvement of the immune process in early stages of AMD. Subsequent statistical analysis of the drusen group showed significant progressive staining (P = 0·0009) in the nuclei layers from early to late stages of ARM. Western blotting confirmed the presence of anti-retinal immunoglobulins to retinal antigens. As anti-retinal immunoglobulins are present in patients with bilateral drusen and exudative AMD, these antibodies could play a significant role in the pathogenesis of AMD. Whilst we do not have evidence that these antibodies precede disease onset, the possibility that their presence might contribute to disease progression needs to be investigated. Finally, the eventual identification of the target antigens detected by these antibodies may permit the future development of new diagnostic methods for ARM and AMD. PMID:15946260

Evaluation of new and established age-related macular degeneration susceptibility genes in the Women's Health Initiative Sight Exam (WHI-SE) Study

USDA-ARS?s Scientific Manuscript database

To assess whether established and newly reported genetic variants, independent of known lifestyle factors, are associated with the risk of age-related macular degeneration (AMD) among women participating in the Women's Health Initiative Sight Exam (WHI-SE) Genetic Ancillary Study. This is a multice...

Nutritional and Lifestyle Interventions for Age-Related Macular Degeneration: A Review

PubMed Central

Carneiro, Ângela

2017-01-01

Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world. In this narrative review, we will summarize the nutritional interventions evaluated in numerous observational studies and a few randomized clinical trials. The AREDS and AREDS2 studies demonstrated that supplements including vitamins C and E, beta-carotene, and zinc may reduce the progression to advanced AMD, in some patients, by 25% in five years. This is one of the few nutritional supplements known to have beneficial effects in any eye disease. Lutein/zeaxanthin supplementation may have beneficial effects in some individuals whereas omega-3 fatty acids supplementation needs to be further investigated and supported by more evidence. Genetic factors may explain the different patterns of response and explain differences found among individuals. More importantly, a combination of lifestyle behaviors such as the avoidance of smoking, physical activity, and the adoption of a healthy dietary pattern like the Mediterranean diet was associated with a lower prevalence of AMD. The adoption of these lifestyles may reduce the prevalence of the early stages of AMD and decrease the number of individuals who develop advanced AMD and consequently the onerous and climbing costs associated with the treatment of this disease. PMID:28154734

Antioxidant vitamin and mineral supplements for preventing age-related macular degeneration.

PubMed

Evans, Jennifer R; Lawrenson, John G

2012-06-13

There is inconclusive evidence from observational studies to suggest that people who eat a diet rich in antioxidant vitamins (carotenoids, vitamins C and E) or minerals (selenium and zinc) may be less likely to develop age-related macular degeneration (AMD). To examine the evidence as to whether or not taking antioxidant vitamin or mineral supplements prevents the development of AMD. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 12), MEDLINE (January 1950 to January 2012), EMBASE (January 1980 to January 2012), Open Grey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 26 January 2012. We included all randomised controlled trials (RCTs) comparing an antioxidant vitamin and/or mineral supplement (alone or in combination) to control. Both review authors independently assessed risk of bias in the included studies and extracted data. One author entered data into RevMan 5 and the other author checked the data entry. We pooled data using a fixed-effect model. We included four RCTs in this review; 62,520 people were included in the analyses. The trials were conducted in Australia, Finland and the USA and investigated vitamin E and beta-carotene supplements. Overall the quality of the evidence was high. People who took these supplements were not at decreased (or increased) risk of developing AMD. The pooled risk ratio for any antioxidant supplement in the prevention of any AMD was 0.98 (95% confidence interval 0.89 to 1.08) and for advanced AMD was 1.05 (95% CI 0.80 to 1.39). Similar results were seen when the analyses were

Can genetic risk information for age-related macular degeneration influence motivation to stop smoking? A pilot study

PubMed Central

Rennie, C A; Stinge, A; King, E A; Sothirachagan, S; Osmond, C; Lotery, A J

2012-01-01

Aims Smoking can increase the risk of macular degeneration and this is more than additive if a person also has a genetic risk. The purpose of this study was to examine whether knowledge of genetic risk for age-related macular degeneration (AMD) could influence motivation to quit smoking. Methods A questionnaire-based study of hypothetical case scenarios given to 49 smokers without AMD. Participants were randomly allocated to a generic risk, high genetic risk, or low genetic risk of developing AMD scenario. Results Forty-seven percent knew of the link between smoking and eye disease. In all, 76%, 67%, and 46% for the high risk, generic, and low risk groups, respectively, would rethink quitting (Pfor trend=0.082). In all, 67%, 40%, and 38.5%, respectively, would be likely, very likely, or would definitely quit in the following month (Pfor trend=0.023). Few participants (<16% of any group) were very likely to or would definitely attend a quit smoking session with no difference across groups. In all, 75.5% of participants would consider taking a genetic test for AMD. Conclusion In this pilot study, a trend was seen for the group given high genetic risk information to be more likely to quit than the generic or low genetic risk groups. Participants were willing to take a genetic test but further work is needed to address the cost benefits of routine genetic testing for risk of AMD. More generic risk information should be given to the public, and health warnings on cigarette packets that ‘smoking causes blindness' is a good way to achieve this. PMID:22037055

Interleukin-17 retinotoxicity is prevented by gene transfer of a soluble interleukin-17 receptor acting as a cytokine blocker: implications for age-related macular degeneration.

PubMed

Ardeljan, Daniel; Wang, Yujuan; Park, Stanley; Shen, Defen; Chu, Xi Kathy; Yu, Cheng-Rong; Abu-Asab, Mones; Tuo, Jingsheng; Eberhart, Charles G; Olsen, Timothy W; Mullins, Robert F; White, Gary; Wadsworth, Sam; Scaria, Abraham; Chan, Chi-Chao

2014-01-01

Age-related macular degeneration (AMD) is a common yet complex retinal degeneration that causes irreversible central blindness in the elderly. Pathology is widely believed to follow loss of retinal pigment epithelium (RPE) and photoreceptor degeneration. Here we report aberrant expression of interleukin-17A (IL17A) and the receptor IL17RC in the macula of AMD patients. In vitro, IL17A induces RPE cell death characterized by the accumulation of cytoplasmic lipids and autophagosomes with subsequent activation of pro-apoptotic Caspase-3 and Caspase-9. This pathology is reduced by siRNA knockdown of IL17RC. IL17-dependent retinal degeneration in a mouse model of focal retinal degeneration can be prevented by gene therapy with adeno-associated virus vector encoding soluble IL17 receptor. This intervention rescues RPE and photoreceptors in a MAPK-dependent process. The IL17 pathway plays a key role in RPE and photoreceptor degeneration and could hold therapeutic potential in AMD.

HYPERSPECTRAL AUTOFLUORESCENCE IMAGING OF DRUSEN AND RETINAL PIGMENT EPITHELIUM IN DONOR EYES WITH AGE-RELATED MACULAR DEGENERATION.

PubMed

Tong, Yuehong; Ben Ami, Tal; Hong, Sungmin; Heintzmann, Rainer; Gerig, Guido; Ablonczy, Zsolt; Curcio, Christine A; Ach, Thomas; Smith, R Theodore

2016-12-01

To elucidate the molecular pathogenesis of age-related macular degeneration (AMD) and interpretation of fundus autofluorescence imaging, the authors identified spectral autofluorescence characteristics of drusen and retinal pigment epithelium (RPE) in donor eyes with AMD. Macular RPE/Bruch membrane flat mounts were prepared from 5 donor eyes with AMD. In 12 locations (1-3 per eye), hyperspectral autofluorescence images in 10-nm-wavelength steps were acquired at 2 excitation wavelengths (λex 436, 480 nm). A nonnegative tensor factorization algorithm was used to recover 5 abundant emission spectra and their corresponding spatial localizations. At λex 436 nm, the authors consistently localized a novel spectrum (SDr) with a peak emission near 510 nm in drusen and sub-RPE deposits. Abundant emission spectra seen previously (S0 in Bruch membrane and S1, S2, and S3 in RPE lipofuscin/melanolipofuscin, respectively) also appeared in AMD eyes, with the same shapes and peak wavelengths as in normal tissue. Lipofuscin/melanolipofuscin spectra localizations in AMD eyes varied widely in their overlap with drusen, ranging from none to complete. An emission spectrum peaking at ∼510 nm (λex 436 nm) appears to be sensitive and specific for drusen and sub-RPE deposits. One or more abundant spectra from RPE organelles exhibit characteristic relationships with drusen.

Physical activity and the 15-year incidence of age-related macular degeneration.

PubMed

Gopinath, Bamini; Liew, Gerald; Burlutsky, George; Mitchell, Paul

2014-11-11

There is uncertainty in the published literature as to whether physical activity should be advocated for age-related macular degeneration (AMD) prevention. We aimed to assess prospectively the association between physical activity and the 15-year incidence of AMD in older adults. We assessed AMD from retinal photographs. Participants provided details of walking exercise and the performance of moderate or vigorous activities, which were used to calculate metabolic equivalents (METs). After adjusting for age, adults aged ≥ 75 years in the highest tertile (the most physically active) compared to those in the lowest tertile (least physically active) were 79% less likely to have incident late AMD over the 15 years (odds ratio [OR], 0.21; 95% confidence intervals [CI], 0.05-0.95). However, after further adjusting for sex, body mass index, smoking, fish consumption, and white cell count, this association was no longer statistically significant (OR, 0.26; 95% CI, 0.06-1.28). Significant associations were not found in those aged <75 or with the 15-year cumulative incidence of early AMD. Physical activity did not influence the risk of AMD over 15 years in older adults, independent of diet, smoking, white cell count, and body mass index. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Figure ground discrimination in age-related macular degeneration.

PubMed

Tran, Thi Ha Chau; Guyader, Nathalie; Guerin, Anne; Despretz, Pascal; Boucart, Muriel

2011-03-01

To investigate impairment in discriminating a figure from its background and to study its relation to visual acuity and lesion size in patients with neovascular age-related macular degeneration (AMD). Seventeen patients with neovascular AMD and visual acuity <20/50 were included. Seventeen age-matched healthy subjects participated as controls. Complete ophthalmologic examination was performed on all participants. The stimuli were photographs of scenes containing animals (targets) or other objects (distractors), displayed on a computer monitor screen. Performance was compared in four background conditions: the target in the natural scene; the target isolated on a white background; the target separated by a white space from a structured scene; the target separated by a white space from a nonstructured, shapeless background. Target discriminability (d') was recorded. Performance was lower for patients than for controls. For the patients, it was easier to detect the target when it was separated from its background (under isolated, structured, and nonstructured conditions) than it was when located in a scene. Performance was improved in patients with increasing exposure time but remained lower in controls. Correlations were found between visual acuity, lesion size, and sensitivity for patients. Figure/ground segregation is impaired in patients with AMD. A white space surrounding an object is sufficient to improve the object's detection and to facilitate figure/ground segregation. These results may have practical applications to the rehabilitation of the environment in patients with AMD.

[Surgery for age-related macular degeneration. Still an option in the age of pharmacotherapy?].

PubMed

Joussen, A M; Kirchhof, B

2014-09-01

This review assesses the relevance of surgical approaches for age-related macular degeneration (AMD) with respect to the pathophysiology of AMD and the current pharmacological possibilities. We discuss the different surgical approaches such as subretinal membrane excision, cell transplantation (IPE and RPE) and transplantation of retina and choroid (PATCH), as well as translocation surgery. Peeling of epiretinal membranes in patients with drusen as well as vitrectomy before epiretinal brachytherapy (VIDEON system) are the final topics. While overall pharmacotherapy has displaced surgical approaches, surgery is worthy of consideration in selected cases. For these patients surgical options need to be maintained in the armamentarium of retinal surgeons. Georg Thieme Verlag KG Stuttgart · New York.

Macular Degeneration

MedlinePlus

... happens when the light-sensitive cells in the macula slowly break down. Your gradually lose your central vision. A common early symptom is that straight lines appear crooked. Regular comprehensive eye exams can detect macular degeneration before the disease causes vision loss. Treatment can ...

HISTORY OF SUNLIGHT EXPOSURE IS A RISK FACTOR FOR AGE-RELATED MACULAR DEGENERATION.

PubMed

Schick, Tina; Ersoy, Lebriz; Lechanteur, Yara T E; Saksens, Nicole T M; Hoyng, Carel B; den Hollander, Anneke I; Kirchhof, Bernd; Fauser, Sascha

2016-04-01

To evaluate effects of current and past sunlight exposure and iris color on early and late age-related macular degeneration (AMD). Of 3,701 individuals from the EUGENDA database, 752 (20.3%) showed early AMD, 1,179 (31.9%) late AMD, and 1,770 (47.8%) were controls. Information about current and past sunlight exposure, former occupation type, subdivided in indoor working and outdoor working, and iris color were obtained by standardized interviewer-assisted questionnaires. Associations between environmental factors adjusted for age, gender, and smoking and early and late AMD were performed by multivariate regression analysis. Current sunlight exposure showed no association with early AMD or late AMD, but past sunlight exposure (≥8 hours outside daily) was significantly associated with early AMD (odds ratio: 5.54, 95% confidence interval 1.25-24.58, P = 0.02) and late AMD (odds ratio: 2.77, 95% confidence interval 1.25-6.16, P = 0.01). Outside working was found to be associated with late AMD (odds ratio: 2.57, 95% confidence interval 1.89-3.48, P = 1.58 × 10). No association was observed between iris color and early or late AMD. Sunlight exposure during working life is an important risk factor for AMD, whereas sunlight exposure after retirement seems to have less influence on the disease development. Therefore, preventive measures, for example, wearing sunglasses to minimize sunlight exposure, should start early to prevent development of AMD later in life.

Can innate and autoimmune reactivity forecast early and advance stages of age-related macular degeneration?

PubMed

Adamus, Grazyna

2017-03-01

Age-related macular degeneration (AMD) is a major cause of central vision loss in persons over 55years of age in developed countries. AMD is a complex disease in which genetic, environmental and inflammatory factors influence its onset and progression. Elevation in serum anti-retinal autoantibodies, plasma and local activation of complement proteins of the alternative pathway, and increase in secretion of proinflammatory cytokines have been seen over the course of disease. Genetic studies of AMD patients confirmed that genetic variants affecting the alternative complement pathway have a major influence on AMD risk. Because the heterogeneity of this disease, there is no sufficient strategy to identify the disease onset and progression sole based eye examination, thus identification of reliable serological biomarkers for diagnosis, prognosis and response to treatment by sampling patient's blood is necessary. This review provides an outline of the current knowledge on possible serological (autoantibodies, complement factors, cytokines, chemokines) and related genetic biomarkers relevant to the pathology of AMD, and discusses their application for prediction of disease activity and prognosis in AMD. Copyright © 2017 Elsevier B.V. All rights reserved.

Automatic Screening and Grading of Age-Related Macular Degeneration from Texture Analysis of Fundus Images

PubMed Central

Phan, Thanh Vân; Seoud, Lama; Chakor, Hadi; Cheriet, Farida

2016-01-01

Age-related macular degeneration (AMD) is a disease which causes visual deficiency and irreversible blindness to the elderly. In this paper, an automatic classification method for AMD is proposed to perform robust and reproducible assessments in a telemedicine context. First, a study was carried out to highlight the most relevant features for AMD characterization based on texture, color, and visual context in fundus images. A support vector machine and a random forest were used to classify images according to the different AMD stages following the AREDS protocol and to evaluate the features' relevance. Experiments were conducted on a database of 279 fundus images coming from a telemedicine platform. The results demonstrate that local binary patterns in multiresolution are the most relevant for AMD classification, regardless of the classifier used. Depending on the classification task, our method achieves promising performances with areas under the ROC curve between 0.739 and 0.874 for screening and between 0.469 and 0.685 for grading. Moreover, the proposed automatic AMD classification system is robust with respect to image quality. PMID:27190636

Genetic studies of age-related macular degeneration: lessons, challenges, and opportunities for disease management.

PubMed

Priya, Rinki Ratna; Chew, Emily Y; Swaroop, Anand

2012-12-01

Age-related macular degeneration (AMD) is a common cause of visual impairment in individuals >55 years of age worldwide. The varying clinical phenotypes of AMD result from contributions of genetic, epigenetic, and nongenetic (environmental) factors. Genetic studies of AMD have come of age as a direct result of tremendous gains from the human genome project, genome-wide association studies, and identification of numerous susceptibility loci. These findings have implicated immune response, high-density lipoprotein cholesterol metabolism, extracellular matrix, and angiogenesis signaling pathways in disease pathophysiology. Herein, we address how the wealth of genetic findings in AMD is expected to impact the practice of medicine, providing opportunities for improved risk assessment, molecular diagnosis, preventive, and therapeutic intervention. We propose that the potential of using genetic variants for monitoring treatment response (pharmacogenetics) may usher in a new era of personalized medicine in the clinical management of AMD. Proprietary or commercial disclosures may be found after the references. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Resistance to anti-VEGF therapy in neovascular age-related macular degeneration: a comprehensive review

PubMed Central

Yang, Shiqi; Zhao, Jingke; Sun, Xiaodong

2016-01-01

As a progressive chronic disease, age-related macular degeneration (AMD) is the leading cause of irreversible vision impairment worldwide. Experimental and clinical evidence has demonstrated that vascular endothelial growth factor (VEGF) plays a vital role in the formation of choroidal neovascularization. Intravitreal injections of anti-VEGF agents have been recommended as a first-line treatment for neovascular AMD. However, persistent fluid or recurrent exudation still occurs despite standardized anti-VEGF therapy. Patients suffering from refractory or recurrent neovascular AMD may develop mechanisms of resistance to anti-VEGF therapy, which results in a diminished therapeutic effect. Until now, there has been no consensus on the definitions of refractory neovascular AMD and recurrent neovascular AMD. This article aims at clarifying these concepts to evaluate the efficacy of switching drugs, which contributes to making clinical decision more scientifically. Furthermore, insight into the causes of resistance to anti-VEGF therapy would be helpful for developing possible therapeutic approaches, such as combination therapy and multi-target treatment that can overcome this resistance. PMID:27330279

Prospective study of plasma homocysteine level and risk of age-related macular degeneration in women.

PubMed

Christen, William G; Cook, Nancy R; Ridker, Paul M; Buring, Julie E

2015-04-01

Prospective data to examine the association of homocysteine with age-related macular degeneration (AMD) are limited. We examined the prospective relation of plasma homocysteine level and AMD in a large cohort of apparently healthy women. We evaluated the relationship between baseline levels of plasma homocysteine and incident AMD among 27,479 female health professionals aged 40 years or older. Main outcome measures were total AMD, defined as self-report documented by medical record evidence of an initial diagnosis after randomization, and visually significant AMD, defined as confirmed incident AMD with visual acuity 20/30 or worse attributable to this condition. During an average 10 years of follow-up, a total of 452 cases of AMD, including 182 cases of visually significant AMD, were documented. Women in the highest versus lowest quartile of plasma homocysteine had modestly, but statistically non-significant, increased risks of total AMD (hazard ratio, HR, 1.24, 95% confidence interval, CI, 0.95-1.63; p for trend 0.07) and visually significant AMD (HR 1.41, 95% CI 0.92-2.17; p for trend 0.052) in age- and treatment-adjusted analyses. These prospective data from a large cohort of apparently healthy women do not support a strong role for homocysteine in AMD occurrence.

The association between statin use and risk of age-related macular degeneration

PubMed Central

Ma, Le; Wang, Yafeng; Du, Junhui; Wang, Mingxu; Zhang, Rui; Fu, Yihao

2015-01-01

The aim of the present study was to evaluate the association between statin use and the risk of age-related macular degeneration (AMD). A systematic search of the PubMed, EMBASE and ISI web of science databases was used to identify eligible published literatures without language restrictions up to April 2015. Summary relative ratios (RRs) and 95% CIs were estimated using a fixed-effect or random-effects model. A total of 14 studies met the inclusion criteria and were included in this meta-analysis. No significant association was observed between statin use and the risk of any AMD (RR, 0.95; 95% CI, 0.74–1.15); and stratified analysis showed that statins had a significantly different effects on early and late stages of AMD. For early AMD, statin use significantly reduced the risk approximately 17% (RR, 0.83; 95% CI, 0.66–0.99). At the late stage, we observed a significant protective association of statin use with exudative AMD (RR, 0.90; 95% CI, 0.80–0.99), in contrast with the absent association between statins and geographic atrophy (RR, 1.16; 95% CI, 0.77–1.56). These results demonstrated that statin use was protective for early and exudative AMD. Additional large prospective cohort studies and RCTs are required to determine the potential effect of statins on AMD prevention. PMID:26658620

Lipids, oxidized lipids, oxidation-specific epitopes, and Age-related Macular Degeneration.

PubMed

Handa, James T; Cano, Marisol; Wang, Lei; Datta, Sayantan; Liu, Tongyun

2017-04-01

Age-related Macular Degeneration (AMD) is the leading cause of blindness among the elderly in western societies. While antioxidant micronutrient treatment is available for intermediate non-neovascular disease, and effective anti-vascular endothelial growth factor treatment is available for neovascular disease, treatment for early AMD is lacking due to an incomplete understanding of the early molecular events. The role of lipids, which accumulate in the macula, and their oxidation, has emerged as an important factor in disease development. These oxidized lipids can either directly contribute to tissue injury or react with amine on proteins to form oxidation-specific epitopes, which can induce an innate immune response. If inadequately neutralized, the inflammatory response from these epitopes can incite tissue injury during disease development. This review explores how the accumulation of lipids, their oxidation, and the ensuing inflammatory response might contribute to the pathogenesis of AMD. This article is part of a Special Issue entitled: Lipid modification and lipid peroxidation products in innate immunity and inflammation edited by Christoph J. Binder . Copyright © 2016 Elsevier B.V. All rights reserved.

Plasma Protein Pentosidine and Carboxymethyllysine, Biomarkers for Age-related Macular Degeneration*

PubMed Central

Ni, Jiaqian; Yuan, Xianglin; Gu, Jiayin; Yue, Xiuzhen; Gu, Xiaorong; Nagaraj, Ram H.; Crabb, John W.

2009-01-01

Age-related macular degeneration (AMD) causes severe vision loss in the elderly; early identification of AMD risk could help slow or prevent disease progression. Toward the discovery of AMD biomarkers, we quantified plasma protein Nε-carboxymethyllysine (CML) and pentosidine from 58 AMD and 32 control donors. CML and pentosidine are advanced glycation end products that are abundant in Bruch membrane, the extracellular matrix separating the retinal pigment epithelium from the blood-bearing choriocapillaris. We measured CML and pentosidine by LC-MS/MS and LC-fluorometry, respectively, and found higher mean levels of CML (∼54%) and pentosidine (∼64%) in AMD (p < 0.0001) relative to normal controls. Plasma protein fructosyl-lysine, a marker of early glycation, was found by amino acid analysis to be in equal amounts in control and non-diabetic AMD donors, supporting an association between AMD and increased levels of CML and pentosidine independent of other diseases like diabetes. Carboxyethylpyrrole (CEP), an oxidative modification from docosahexaenoate-containing lipids and also abundant in AMD Bruch membrane, was elevated ∼86% in the AMD cohort, but autoantibody titers to CEP, CML, and pentosidine were not significantly increased. Compellingly higher mean levels of CML and pentosidine were present in AMD plasma protein over a broad age range. Receiver operating curves indicate that CML, CEP adducts, and pentosidine alone discriminated between AMD and control subjects with 78, 79, and 88% accuracy, respectively, whereas CML in combination with pentosidine provided ∼89% accuracy, and CEP plus pentosidine provided ∼92% accuracy. Pentosidine levels appeared slightly altered in AMD patients with hypertension and cardiovascular disease, indicating further studies are warranted. Overall this study supports the potential utility of plasma protein CML and pentosidine as biomarkers for assessing AMD risk and susceptibility, particularly in combination with CEP

The Modification of Fluorescein Angiography and Its Applications in Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy.

PubMed

Peng, Qing; Chen, Yutong; Hua, Rui

2018-06-07

To establish a novel retinal angiography method, red-free angiography (RFA), to investigate retinal changes in age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). Following the venous phase of fundus fluorescein angiography (FFA), the detection mode was switched to red-free reflectance to acquire RFA images using the same parameters. RFA showed subretinal fluid, polyps, and outer retinal tubulation, with a higher definition than the FFA and red-free reflectance results. The absorption coefficients in RFA provided more detailed images for AMD and PCV diagnosis. RFA is therefore a promising approach to supplement FFA. © 2018 S. Karger AG, Basel.

Immunotherapy for choroidal neovascularization in a laser-induced mouse model simulating exudative (wet) macular degeneration

NASA Astrophysics Data System (ADS)

Bora, Puran S.; Hu, Zhiwei; Tezel, Tongalp H.; Sohn, Jeong-Hyeon; Kang, Shin Goo; Cruz, Jose M. C.; Bora, Nalini S.; Garen, Alan; Kaplan, Henry J.

2003-03-01

Age-related macular degeneration (AMD) is the leading cause of blindness after age 55 in the industrialized world. Severe loss of central vision frequently occurs with the exudative (wet) form of AMD, as a result of the formation of a pathological choroidal neovasculature (CNV) that damages the macular region of the retina. We tested the effect of an immunotherapy procedure, which had been shown to destroy the pathological neovasculature in solid tumors, on the formation of laser-induced CNV in a mouse model simulating exudative AMD in humans. The procedure involves administering an Icon molecule that binds with high affinity and specificity to tissue factor (TF), resulting in the activation of a potent cytolytic immune response against cells expressing TF. The Icon binds selectively to TF on the vascular endothelium of a CNV in the mouse and pig models and also on the CNV of patients with exudative AMD. Here we show that the Icon dramatically reduces the frequency of CNV formation in the mouse model. After laser treatment to induce CNV formation, the mice were injected either with an adenoviral vector encoding the Icon, resulting in synthesis of the Icon by vector-infected mouse cells, or with the Icon protein. The route of injection was i.v. or intraocular. The efficacy of the Icon in preventing formation of laser-induced CNV depends on binding selectively to the CNV. Because the Icon binds selectively to the CNV in exudative AMD as well as to laser-induced CNV, the Icon might also be efficacious for treating patients with exudative AMD.

Retinal Spectral Domain Optical Coherence Tomography in Early Atrophic Age-Related Macular Degeneration (AMD) and a New Metric for Objective Evaluation of the Efficacy of Ocular Nutrition

PubMed Central

Richer, Stuart; Cho, Jane; Stiles, William; Levin, Marc; Wrobel, James S.; Sinai, Michael; Thomas, Carla

2012-01-01

Purpose: A challenge in ocular preventive medicine is identification of patients with early pathological retinal damage that might benefit from nutritional intervention. The purpose of this study is to evaluate retinal thinning (RT) in early atrophic age-related macular degeneration (AMD) against visual function data from the Zeaxanthin and Visual Function (ZVF) randomized double masked placebo controlled clinical trial (FDA IND #78973). Methods: Retrospective, observational case series of medical center veterans with minimal visible AMD retinopathy (AREDS Report #18 simplified grading 1.4/4.0 bilateral retinopathy). Foveal and extra-foveal four quadrant SDOCT RT measurements were evaluated in n = 54 clinical and ZVF AMD patients. RT by age was determined and compared to the OptoVue SD OCT normative database. RT by quadrant in a subset of n = 29 ZVF patients was correlated with contrast sensitivity and parafoveal blue cone increment thresholds. Results: Foveal RT in AMD patients and non-AMD patients was preserved with age. Extrafoveal regions, however, showed significant slope differences between AMD patients and non-AMD patients, with the superior and nasal quadrants most vulnerable to retinal thinning (sup quad: −5.5 μm/decade thinning vs. Non-AMD: −1.1 μm/decade, P < 0.02; nasal quad: −5.0 μm/decade thinning vs. Non-AMD: −1.0 μm/decade, P < 0.04). Two measures of extrafoveal visual deterioration were correlated: A significant inverse correlation between % RT and contrast sensitivity (r = −0.33, P = 0.01, 2 Tailed Paired T) and an elevated extrafoveal increment blue cone threshold (r = +0.34, P = 0.01, 2 Tailed T). Additional SD OCT RT data for the non-AMD oldest age group (ages 82–91) is needed to fully substantiate the model. Conclusion: A simple new SD OCT clinical metric called “% extra-foveal RT” correlates well with functional visual loss in early AMD patients having minimal visible retinopathy. This metric can be used to follow the

[Quality of life in patients with age-related macular degeneration - medical and social problem].

PubMed

Muzyka-Woźniak, Maria; Misiuk-Hojło, Marta; Wesolowska, Alicja

2011-01-01

Age-related macular degeneration (AMD) is a leading cause of blindness over the age of 50 in western countries. People with AMD are suffering from serious vision-related disability and their social life is compromised. The aim of our study was to assess quality of life (QoL) in patients with exudative AMD. The study group was 100 patients treated for AMD, the control group were 30 age and sex matched subjects without ophthalmic disorders. Patients were treated with anti-VEGF therapy, by means of National Eye Institute Visual Function Questionnaire (NEI VFQ-25). As well as visual function, the NEI-VFQ investigates social functioning, mental health and dependency. There was statistically significant difference in QoL overall score between study group and control group. Patients with AMD obtained 51.1 (+/- 20.5 ) overall score, control group reached 83.7 (+/- 11.7) overall score, p = 0.001. Detailed analysis of study group revealed low acceptance of the disease and strong dependency. QoL in patients with AMD assessed with NEI VFQ-25, is significantly impaired. Low quality of life and difficulties in performing daily activities point at the need of formal psychological and social care.

Roles for the ubiquitin-proteasome pathway in protein quality control and signaling in the retina: implications in the pathogenesis of age-related macular degeneration

USDA-ARS?s Scientific Manuscript database

The accumulation of damaged or postsynthetically modified proteins and dysregulation of inflammatory responses and angiogenesis in the retina/RPE are thought be etiologically related to formation of drusen and choroidal neovascularization (CNV), hallmarks of age-related macular degeneration (AMD). T...

Hyperhomocysteinemia and Age-related Macular Degeneration: Role of Inflammatory Mediators and Pyroptosis; A Proposal.

PubMed

Singh, Mahavir; Tyagi, Suresh C

2017-08-01

Age-related macular degeneration (AMD) and pyroptosis cause irreversible vascular changes in the eyes leading to central vision loss in patients. It is the most common eye disease affecting millions of people aged 50years or older, and is slowly becoming a major health problem worldwide. The disease mainly affects macula lutea, an oval-shaped pigmented area surrounding fovea near the center of retina, a region responsible for visual acuity. It is fairly a complex disease as genetics of patients, environmental triggers as well as risk factors such as age, family history of CVDs, diabetes, gender, obesity, race, hyperopia, iris color, smoking, diabetes, exposure to sun light and pyroptosis have all been clubbed together as probable causes of macular degeneration. Among genes that are known to play a role include variant polymorphisms in the complement cascade components such as CFH, C2, C3, and CFB as potential genetic risk factors. So far, AMD disease hypothesized theories have not resulted into the anticipated impact towards the development of effective or preventive therapies in order to help alleviate patients' suffering because, as of today, it is still unclear what actually initiates or leads to this dreaded eye condition. Based upon our extensive work on the metabolism of homocysteine (Hcy) in various disease conditions we, therefore, are proposing a novel hypothesis for AMD pathogenesis as we strongly believe that Hcy and events such as pyroptosis make a greater contribution to the overall etiology of AMD disease in a target population of susceptible hosts by inciting and accelerating the inherent inflammatory changes in the retina of these patients (Fig. 2). In this context, we further state that Hcy and pyroptosis should be considered as legitimate and valuable markers of retinal dysfunction as they not only aid and abet in the development but also in the progression of AMD in older people as discussed in this paper. This discussion should open up new

Macular Atrophy in the HARBOR Study for Neovascular Age-Related Macular Degeneration.

PubMed

Sadda, SriniVas R; Tuomi, Lisa L; Ding, Beiying; Fung, Anne E; Hopkins, J Jill

2018-06-01

To evaluate macular atrophy (MA) presence in the 24-month HARBOR study (NCT00891735) for neovascular age-related macular degeneration (AMD). Post hoc analysis of a phase 3 multicenter, prospective, randomized, double-masked, active treatment-controlled clinical trial. Evaluable subjects (N = 1095) with subfoveal choroidal neovascularization (CNV) secondary to neovascular AMD treated with ranibizumab 0.5 mg or 2.0 mg monthly or pro re nata (PRN). Fluorescein angiograms (FAs) and color fundus photographs at baseline and months 3, 12, and 24 were retrospectively graded by masked graders for MA: well-defined areas of depigmentation with increased choroidal vessel visibility, diameter ≥250 μm, corresponding to flat areas of well-demarcated staining on FA, excluding atrophy associated with retinal pigment epithelium tears. Atrophy immediately within, adjacent, and nonadjacent to CNV lesions was included. Macular atrophy incidence, best-corrected visual acuity (BCVA). At baseline, MA was detected in 11.2% (123/1095) of study eyes. At month 24, 29.4% (229/778) of eyes without baseline atrophy had detectable MA. Eyes with and without baseline MA had significant mean BCVA gains from baseline at month 24 (letters [95% confidence interval]: +6.7 [4.1-9.3]; +9.1 [8.0-10.2], respectively). Among eyes with and without MA at month 24, mean month 24 BCVA was 62.0 [60.3-63.7] and 64.7 [63.2-66.3] letters, respectively. Baseline risk factors for month 24 MA presence included intraretinal cysts (hazard ratio [HR], 2.45 [1.76-3.42]) and fellow eye atrophy (HR, 2.02 [1.42-2.87]); subretinal fluid was associated with a lower MA risk (HR, 0.50 [0.33-0.74]). Ranibizumab dose was not associated with MA development. Monthly versus PRN treatment trended toward an association with MA (HR, 1.29 [0.99-1.68]), but was not statistically significant. New MA was detected in 29% of study eyes after 24 months of treatment. Clinically significant BCVA gains were achieved with MA present over 24

[Retrospective investigation of anti-VEGF treatment reality and effectiveness in patients with neovascular age-related macular degeneration (AMD) in Germany: treatment reality of ranibizumab for neovascular AMD in Germany].

PubMed

Ziemssen, F; Eter, N; Fauser, S; Bopp, S; Radermacher, M; Hasanbasic, Z; Holz, F G

2015-03-01

Neovascular (wet) age-related macular degeneration (wAMD) is a progressive and degenerative retinal disease. This study reports the real-life use in Germany of the standard anti-vascular endothelial growth factor (VEGF) therapy for wAMD as an intravitreal operative drug application. Within the framework of an international retrospective study the medical records of patients with wAMD who were first treated with ranibizumab between 1 January and 31 August 2009 were evaluated. Data were collected until the end of treatment and/or monitoring or until 31 August 2011. The primary objective was to evaluate changes in visual acuity after the start of anti-VEGF therapy. Secondary outcomes included determining real-life anti-VEGF treatment regimens and disease-monitoring practices. Out of 2227 patients who received ≥ 1 anti-VEGF injection with a baseline visual acuity assessment and ≥ 1 post-baseline visual acuity assessment for the treated eye, 420 were included in the German cohort. Visual acuity improved until about day 90 but these gains in visual acuity were not maintained. The mean changes in visual acuity scores from baseline to years 1 and 2 were 1.1 ± 15.7 and - 0.8 ± 17.2 letters, respectively. Patients received a mean of 4.3 ± 1.9 and 1.3 ± 2.2 injections in years 1 and 2, respectively. The majority of visits ( 98.6 %) were conducted irregularly and outside the time frame recommended at the time of the study, with an average of 47.7 ± 36.7 days between visits. More frequent visits and injections were associated with greater improvements in visual acuity. Treatment intensity was not sufficient to maintain the initial improvement in visual acuity by ranibizumab treatment. Real-life results for visual acuity and injection frequency in the German cohort were worse at that time than in other countries. Regular follow-up visits as well as timely retreatment in the presence of signs of disease activity are required to achieve optimal

Mediterranean Diet Score and Its Association with Age-Related Macular Degeneration: The European Eye Study.

PubMed

Hogg, Ruth E; Woodside, Jayne V; McGrath, Alanna; Young, Ian S; Vioque, Jesus L; Chakravarthy, Usha; de Jong, Paulus T; Rahu, Mati; Seland, Johan; Soubrane, Gisele; Tomazzoli, Laura; Topouzis, Fotis; Fletcher, Astrid E

2017-01-01

To examine associations between adherence to a Mediterranean diet and prevalence of age-related macular degeneration (AMD) in countries ranging from Southern to Northern Europe. Cross-sectional, population-based epidemiologic study. Of 5060 randomly sampled people aged 65 years or older from 7 study centers across Europe (Norway, Estonia, United Kingdom, France, Italy, Greece, and Spain), full dietary data were available in 4753. The mean age of participants was 73.2 years (standard deviation, 5.6), and 55% were women. Participants underwent an eye examination and digital retinal color photography. The images were graded at a single center. Dietary intake during the previous 12 months was assessed by using a semiquantitative food-frequency questionnaire (FFQ). A previously published Mediterranean Diet Score (MDS) was used to classify participants according to their responses on the FFQ. Multivariable logistic regression was used to investigate the association of the MDS score and AMD, taking account of potential confounders and the multicenter study design. Images were graded according to the International Classification System for age-related maculopathy and stratified using the Rotterdam staging system into 5 exclusive stages (AMD 0-4) and a separate category of large drusen (≥125 μm). Age-related macular degeneration 4 included neovascular AMD (nvAMD) and geographic atrophy (GA). Increasing MDS was associated with reduced odds of nvAMD in unadjusted and confounder-adjusted analysis. Compared with the lowest MDS adherence (≤4 score), those in the highest category MDS adherence (>6 score) showed lower odds of nvAMD (odds ratio, 0.53; 0.27-1.04; P trend = 0.01). The association with MDS did not differ by Y204H risk allele (P = 0.89). For all early AMD (grade 1-3), there was no relationship with MDS (P trend = 0.9). There was a weak trend (P = 0.1) between MDS and large drusen; those in the highest category of MDS had 20% reduced odds compared with those in

Effects of Age-Related Macular Degeneration on Driving Performance

PubMed Central

Wood, Joanne M.; Black, Alex A.; Mallon, Kerry; Kwan, Anthony S.; Owsley, Cynthia

2018-01-01

Purpose To explore differences in driving performance of older adults with age-related macular degeneration (AMD) and age-matched controls, and to identify the visual determinants of driving performance in this population. Methods Participants included 33 older drivers with AMD (mean age [M] = 76.6 ± 6.1 years; better eye Age-Related Eye Disease Study grades: early [61%] and intermediate [39%]) and 50 age-matched controls (M = 74.6 ± 5.0 years). Visual tests included visual acuity, contrast sensitivity, visual fields, and motion sensitivity. On-road driving performance was assessed in a dual-brake vehicle by an occupational therapist (masked to drivers' visual status). Outcome measures included driving safety ratings (scale of 1–10, where higher values represented safer driving), types of driving behavior errors, locations at which errors were made, and number of critical errors (CE) requiring an instructor intervention. Results Drivers with AMD were rated as less safe than controls (4.8 vs. 6.2; P = 0.012); safety ratings were associated with AMD severity (early: 5.5 versus intermediate: 3.7), even after adjusting for age. Drivers with AMD had higher CE rates than controls (1.42 vs. 0.36, respectively; rate ratio 3.05, 95% confidence interval 1.47–6.36, P = 0.003) and exhibited more observation, lane keeping, and gap selection errors and made more errors at traffic light–controlled intersections (P < 0.05). Only motion sensitivity was significantly associated with driving safety in the AMD drivers (P = 0.005). Conclusions Drivers with early and intermediate AMD can exhibit impairments in their driving performance, particularly during complex driving situations; motion sensitivity was most strongly associated with driving performance. These findings have important implications for assessing the driving ability of older drivers with visual impairment. PMID:29340641

[Potential of melatonin for prevention of age-related macular degeneration: experimental study].

PubMed

Stefanova, N A; Zhdankina, A A; Fursova, A Zh; Kolosova, N G

2013-01-01

Decline with age of the content of melatonin is considered as one of the leading mechanisms of aging and development of associated diseases, including age-related macular degeneration (AMD)--the disease, which becomes the most common cause of blindness and acuity of vision deterioration in elderly. The prospects of the use of melatonin in the prevention of AMD is being actively discussed, but as a rule on the basis of the results of the experiments on cells in retinal pigment epithelium (RPE). We showed previously that the senescence-accelerated OXYS rat is an adequate animal model of AMD, already used for identifying the relevant therapeutic targets. Here we have investigated the effect of Melatonin (Melaksen, 0,004 mg per kg--a dose equivalent to the recommended one for people) on the development of retinopathy similar to AMD in OXYS rats. Ophthalmoscopic examinations show that Melatonin supplementation decreased the incidence and severity of retinopathy and improved some (but not all) histological abnormalities associated with retinopathy. Thus, melatonin prevented the structural and functional changes in RPE cells, reduced the severity of microcirculatory disorders. Importantly, Melatonin prevented destruction of neurosensory cells, associative and gangliolar neurons in the retina. Taken together, our data suggest the therapeutic potential of Melatonin for treatment and prevention of AMD.

Peripheral blood mononuclear cells from neovascular age-related macular degeneration patients produce higher levels of chemokines CCL2 (MCP-1) and CXCL8 (IL-8).

PubMed

Lechner, Judith; Chen, Mei; Hogg, Ruth E; Toth, Levente; Silvestri, Giuliana; Chakravarthy, Usha; Xu, Heping

2017-02-23

Infiltrating immune cells including monocytes/macrophages have been implicated in the pathogenesis of neovascular age-related macular degeneration (nAMD). The aim of this study was to investigate the cytokine and chemokine expression and secretion profile of peripheral blood mononuclear cells (PBMCs) from nAMD patients and the relationship between the cytokine/chemokine expression profile and clinical phenotype of nAMD, including macular fibrosis, macular atrophy or the responsiveness to anti-VEGF therapy. One hundred sixty-one nAMD patients and 43 controls were enrolled in this study. nAMD patients were divided into subgroups based on the presence/absence of (1) macular atrophy, (2) macular fibrosis and (3) responsiveness to anti-VEGF therapy; 25-30 ml of peripheral blood were obtained from all participants and 5 ml were used for serum collection, and the remaining were used for PBMC isolation using density gradient centrifugation. Intracellular cytokine expressions by PBMCs following phorbol 12-myristate 13-acetate (PMA) and ionomycin stimulation were examined using flow cytometry. Cytokine productions in lipopolysaccharides (LPS)-or 1% oxygen -treated PBMC were measured using cytometric bead array (CBA) assay. In addition, cytokine and chemokine levels in the serum were also measured by CBA assay. PBMCs from nAMD patients secreted higher levels of IL-8, CCL2 and VEGF, especially following LPS and 1% oxygen stimulation, than those from controls. 60~80% of IL-8 producing cells were CD11b + CD3 - monocytes. The percentage of CD11b + CD3 - IL-8 + was significantly increased in nAMD patients compared to controls. PBMCs from nAMD patients without macular fibrosis produced the highest levels of IL-8 and CCL2, whilst PBMCs from nAMD patients with macular atrophy produced highest levels of VEGF. In addition, PBMCs from patients who partially responded to anti-VEGF produced higher levels of IL-8 compared to the cells from complete responders. Interestingly, serum level

Targeted Vision Function Goals and Use of Vision Resources in Ophthalmology Patients with Age-Related Macular Degeneration and Comorbid Depressive Symptoms

ERIC Educational Resources Information Center

Casten, Robin; Rovner, Barry W.; Fontenot, Joseph L.

2016-01-01

Introduction: This study characterizes self-reported functional vision goals and the use of low vision resources (for example, services and devices) in ophthalmology clinic patients with age-related macular degeneration (AMD) and comorbid depressive symptoms. Methods: From July 2009 to February 2013, we assessed 188 consecutive patients (age 65+;…

Evaluation of real-world mobility in age-related macular degeneration.

PubMed

Sengupta, Sabyasachi; Nguyen, Angeline M; van Landingham, Suzanne W; Solomon, Sharon D; Do, Diana V; Ferrucci, Luigi; Friedman, David S; Ramulu, Pradeep Y

2015-01-30

Previous research has suggested an association between poor vision and decreased mobility, including restricted levels of physical activity and travel away from home. We sought to determine the impact of age-related macular degeneration (AMD) on these measures of mobility. Fifty-seven AMD patients with bilateral, or severe unilateral, visual impairment were compared to 59 controls with normal vision. All study subjects were between the ages of 60 and 80. Subjects wore accelerometers and cellular network-based tracking devices over 7 days of normal activity. Number of steps taken, time spent in moderate-to-vigorous physical activity (MVPA), number of excursions from home, and time spent away from home were the primary outcome measures. In multivariate negative binomial regression models adjusted for age, gender, race, comorbidities, and education, AMD participants took fewer steps than controls (18% fewer steps per day, p = 0.01) and spent significantly less time in MVPA (35% fewer minutes, p < 0.001). In multivariate logistic regression models adjusting for age, sex, race, cognition, comorbidities, and grip strength, AMD subjects showed an increased likelihood of not leaving their home on a given day (odds ratio = 1.36, p = 0.04), but did not show a significant difference in the magnitude of time spent away from home (9% fewer minutes, p = 0.11). AMD patients with poorer vision engage in significantly less physical activity and take fewer excursions away from the home. Further studies identifying the factors mediating the relationship between vision loss and mobility are needed to better understand how to improve mobility among AMD patients.

Correlation of neutrophil/lymphocyte and platelet/lymphocyte ratio with visual acuity and macular thickness in age-related macular degeneration

PubMed Central

Sengul, Elvan Alper; Artunay, Ozgur; Kockar, Alev; Afacan, Ceyda; Rasier, Rifat; Gun, Palmet; Yalcin, Nazli Gul; Yuzbasioglu, Erdal

2017-01-01

AIM To investigate the place of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in the diagnosis of and prognosis for neovascular age-related macular degeneration (AMD). METHODS One hundred AMD patients and 100 healthy controls were included in the study. Blood samples were obtained from the venous blood, which is used for routine analysis, and these samples were subjected to complete blood count. NLR was defined as the neutrophil count divided by the number of lymphocytes, and PLR was defined as the platelet count divided by the number of lymphocytes. RESULTS No statistically significant difference was observed between the two groups under consideration in terms of demographic features (P>0.05). The average NLR in the patient group was found to be significantly higher than that in the healthy control group (P<0.05). The average PLR was significantly higher in the patient group as compared to the control group (P<0.05). As best corrected visual acuity (BCVA) increased, both NLR and PLR decreased (significant negative correlations at 49.8% and 63.0%, respectively), whereas as central macular thickness (CMT) increased, both NLR and PLR increased (significant positive correlations at 59.3% and 70.0%, respectively). CONCLUSION NLR and PLR levels are higher among neovascular AMD patients as compared to healthy control group. NLR and PLR levels were found to be inversely proportional to BCVA and directly proportional to CMT. PMID:28546933

Automated age-related macular degeneration classification in OCT using unsupervised feature learning

NASA Astrophysics Data System (ADS)

Venhuizen, Freerk G.; van Ginneken, Bram; Bloemen, Bart; van Grinsven, Mark J. J. P.; Philipsen, Rick; Hoyng, Carel; Theelen, Thomas; Sánchez, Clara I.

2015-03-01

Age-related Macular Degeneration (AMD) is a common eye disorder with high prevalence in elderly people. The disease mainly affects the central part of the retina, and could ultimately lead to permanent vision loss. Optical Coherence Tomography (OCT) is becoming the standard imaging modality in diagnosis of AMD and the assessment of its progression. However, the evaluation of the obtained volumetric scan is time consuming, expensive and the signs of early AMD are easy to miss. In this paper we propose a classification method to automatically distinguish AMD patients from healthy subjects with high accuracy. The method is based on an unsupervised feature learning approach, and processes the complete image without the need for an accurate pre-segmentation of the retina. The method can be divided in two steps: an unsupervised clustering stage that extracts a set of small descriptive image patches from the training data, and a supervised training stage that uses these patches to create a patch occurrence histogram for every image on which a random forest classifier is trained. Experiments using 384 volume scans show that the proposed method is capable of identifying AMD patients with high accuracy, obtaining an area under the Receiver Operating Curve of 0:984. Our method allows for a quick and reliable assessment of the presence of AMD pathology in OCT volume scans without the need for accurate layer segmentation algorithms.

Interventions for Age-Related Macular Degeneration: Are Practice Guidelines Based on Systematic Reviews?

PubMed

Lindsley, Kristina; Li, Tianjing; Ssemanda, Elizabeth; Virgili, Gianni; Dickersin, Kay

2016-04-01

Are existing systematic reviews of interventions for age-related macular degeneration incorporated into clinical practice guidelines? High-quality systematic reviews should be used to underpin evidence-based clinical practice guidelines and clinical care. We examined the reliability of systematic reviews of interventions for age-related macular degeneration (AMD) and described the main findings of reliable reviews in relation to clinical practice guidelines. Eligible publications were systematic reviews of the effectiveness of treatment interventions for AMD. We searched a database of systematic reviews in eyes and vision without language or date restrictions; the database was up to date as of May 6, 2014. Two authors independently screened records for eligibility and abstracted and assessed the characteristics and methods of each review. We classified reviews as reliable when they reported eligibility criteria, comprehensive searches, methodologic quality of included studies, appropriate statistical methods for meta-analysis, and conclusions based on results. We mapped treatment recommendations from the American Academy of Ophthalmology (AAO) Preferred Practice Patterns (PPPs) for AMD to systematic reviews and citations of reliable systematic reviews to support each treatment recommendation. Of 1570 systematic reviews in our database, 47 met inclusion criteria; most targeted neovascular AMD and investigated anti-vascular endothelial growth factor (VEGF) interventions, dietary supplements, or photodynamic therapy. We classified 33 (70%) reviews as reliable. The quality of reporting varied, with criteria for reliable reporting met more often by Cochrane reviews and reviews whose authors disclosed conflicts of interest. Anti-VEGF agents and photodynamic therapy were the only interventions identified as effective by reliable reviews. Of 35 treatment recommendations extracted from the PPPs, 15 could have been supported with reliable systematic reviews; however, only 1

Bilateral polypoidal choroidal vasculopathy coexisting with exudative and atrophic age-related macular degeneration.

PubMed

Aronés-Santivañez, J R; Dyrda, A; Alarcón Valero, I

2016-12-01

To present the case of simultaneous presentation of polypoidal choroidal vasculopathy (PCV) and aged-related macular degeneration (AMD). An 83-year-old woman presented with decreased vision in the left eye (LE). In the examination there was an orange peripapillary lesion surrounded by lipid exudates and another subfoveal greyish lesion in the LE. Disciform scarring was observed in the right eye. Fluorescein angiography showed a classic neovascular membrane in in the LE fovea. Indocyanine angiography (ICGA) showed a polyp-like peri-papillary aneurysmal dilation in both eyes. The patient was treated with photodynamic therapy and anti-VEFG injections with stabilisation of the lesions. PCV and AMD can co-exist in unusual cases. When PCV is suspected, ICGA is mandatory for diagnosis. Copyright © 2016. Publicado por Elsevier España, S.L.U.

Dissecting microRNA dysregulation in age-related macular degeneration: new targets for eye gene therapy.

PubMed

Askou, Anne Louise; Alsing, Sidsel; Holmgaard, Andreas; Bek, Toke; Corydon, Thomas J

2018-02-01

MicroRNAs (miRNAs) are key regulators of gene expression in humans. Overexpression or depletion of individual miRNAs is associated with human disease. Current knowledge suggests that the retina is influenced by miRNAs and that dysregulation of miRNAs as well as alterations in components of the miRNA biogenesis machinery are involved in retinal diseases, including age-related macular degeneration (AMD). Furthermore, recent studies have indicated that the vitreous has a specific panel of circulating miRNAs and that this panel varies according to the specific pathological stress experienced by the retinal cells. MicroRNA (miRNA) profiling indicates subtype-specific miRNA profiles for late-stage AMD highlighting the importance of proper miRNA regulation in AMD. This review will describe the function of important miRNAs involved in inflammation, oxidative stress and pathological neovascularization, the key molecular mechanisms leading to AMD, and focus on dysregulated miRNAs as potential therapeutic targets in AMD. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Combined treatment modalities for age related macular degeneration.

PubMed

Das, R A; Romano, A; Chiosi, F; Menzione, M; Rinaldi, M

2011-02-01

Age-related macular degeneration (AMD) is a condition that accounts for 75% of cases of legal blindness in individuals over the age of 50. The objective of this review has been to evaluate the clinical effectiveness of available combined treatments modalities in the treatment of neovascular AMD. Central and Medline were searched for original research studies (Phase I, II, III), abstracts, and review articles concerning combination therapies for the control of neovascular AMD. We included randomized controlled trials (RCTs). The results of therapeutic trials focused on the actual options in the management of neovascular AMD are discussed. Intravitreal treatment with substances targeting all isotypes of vascular endothelial growth factor (VEGF) results in a significant increase in visual acuity in patients with neovascular AMD. The combination with occlusive therapies like verteporfin photodynamic therapy (V-PDT) potentially offers a reduction of re-treatment frequency rate and long-term maintenance of the benefit reached. Despite the promise from combining anti-VEGF therapies with V-PDT, other combinations to improve outcomes with V-PDT deserve attention. Corticosteroids demonstrated an antiangiogenic effect and targeted the extravascular components of CNV, such as inflammatory cells and fibrocytes. Nevertheless, the study on the clinical application of corticosteroids will require a better understanding of the potential complications. Further developments interacting with various steps in the angiogenic cascade are under clinical or preclinical evaluation and may soon become available. In AMD the goal of a combination regimen is to address the therapy toward neovascular, inflammatory, and proliferative components of the disease. Combined treatments strategies are an obvious step providing disease control when it is not achieved with a single therapeutic approach. One risk of using a single therapy to control AMD is a rebound induced by compensatory stimulation of

Phacoemulsification surgery in eyes with neovascular age-related macular degeneration.

PubMed

Grixti, Andre; Papavasileiou, Evangelia; Cortis, Dominic; Kumar, Balakrishna Vineeth; Prasad, Som

2014-01-01

Purpose. To evaluate the visual outcomes and effect of phacoemulsification surgery on the progression of neovascular age-related macular degeneration (AMD). Methods. Retrospective, noncomparative, and interventional case series. Thirty eyes from 29 subjects with neovascular AMD treated with intravitreal antivascular endothelial growth factor (VEGF) injections who underwent phacoemulsification and had a postsurgery follow-up of 6 months were included. LogMAR best corrected visual acuity (BCVA) was assessed preoperatively; 1 month, 3 months, and 6 months postoperatively; and finally at the last visit. The frequency of anti-VEGF therapy, calculated as the number of intravitreal injections per month, and central macular thickness (CMT) before and after cataract surgery were determined. Results. Median (range) logMAR BCVA was 0.69 (0.16 to 1.32) preoperatively; 0.55 (-0.04 to 1.32) at 1 month, 0.52 (-0.1 to 1.32) at 3 months, and 0.50 (0.0 to 1.32) at 6 months postoperatively; and 0.6 (0.0 to 1.4) at final visit (P = 0.0011). There was no difference in the frequency of anti-VEGF injections between the immediate 6 months before and after phacoemulsification, which was equal to 0.1667 injections per month (P = 0.6377). Median CMT measured 203  μ m preoperatively, which temporarily increased to 238  μ m at 1 month after surgery (P = 0.0093) and then spontaneously returned to baseline, measuring 212.5  μ m at 3 months postoperatively (P = 0.3811). Conclusion. Phacoemulsification surgery significantly improved vision in patients with neovascular AMD, with no increased need for anti-VEGF injections to keep the macula dry postoperatively.

Phacoemulsification Surgery in Eyes with Neovascular Age-Related Macular Degeneration

PubMed Central

Papavasileiou, Evangelia; Kumar, Balakrishna Vineeth; Prasad, Som

2014-01-01

Purpose. To evaluate the visual outcomes and effect of phacoemulsification surgery on the progression of neovascular age-related macular degeneration (AMD). Methods. Retrospective, noncomparative, and interventional case series. Thirty eyes from 29 subjects with neovascular AMD treated with intravitreal antivascular endothelial growth factor (VEGF) injections who underwent phacoemulsification and had a postsurgery follow-up of 6 months were included. LogMAR best corrected visual acuity (BCVA) was assessed preoperatively; 1 month, 3 months, and 6 months postoperatively; and finally at the last visit. The frequency of anti-VEGF therapy, calculated as the number of intravitreal injections per month, and central macular thickness (CMT) before and after cataract surgery were determined. Results. Median (range) logMAR BCVA was 0.69 (0.16 to 1.32) preoperatively; 0.55 (−0.04 to 1.32) at 1 month, 0.52 (−0.1 to 1.32) at 3 months, and 0.50 (0.0 to 1.32) at 6 months postoperatively; and 0.6 (0.0 to 1.4) at final visit (P = 0.0011). There was no difference in the frequency of anti-VEGF injections between the immediate 6 months before and after phacoemulsification, which was equal to 0.1667 injections per month (P = 0.6377). Median CMT measured 203 μm preoperatively, which temporarily increased to 238 μm at 1 month after surgery (P = 0.0093) and then spontaneously returned to baseline, measuring 212.5 μm at 3 months postoperatively (P = 0.3811). Conclusion. Phacoemulsification surgery significantly improved vision in patients with neovascular AMD, with no increased need for anti-VEGF injections to keep the macula dry postoperatively. PMID:24719771

Identification of pathogenic genes and upstream regulators in age-related macular degeneration.

PubMed

Zhao, Bin; Wang, Mengya; Xu, Jing; Li, Min; Yu, Yuhui

2017-06-26

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in older individuals. Our study aims to identify the key genes and upstream regulators in AMD. To screen pathogenic genes of AMD, an integrated analysis was performed by using the microarray datasets in AMD derived from the Gene Expression Omnibus (GEO) database. The functional annotation and potential pathways of differentially expressed genes (DEGs) were further discovered by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. We constructed the AMD-specific transcriptional regulatory network to find the crucial transcriptional factors (TFs) which target the DEGs in AMD. Quantitative real time polymerase chain reaction (qRT-PCR) was performed to verify the DEGs and TFs obtained by integrated analysis. From two GEO datasets obtained, we identified 1280 DEGs (730 up-regulated and 550 down-regulated genes) between AMD and normal control (NC). After KEGG analysis, steroid biosynthesis is a significantly enriched pathway for DEGs. The expression of 8 genes (TNC, GRP, TRAF6, ADAMTS5, GPX3, FAP, DHCR7 and FDFT1) was detected. Except for TNC and GPX3, the other 6 genes in qRT-PCR played the same pattern with that in our integrated analysis. The dysregulation of these eight genes may involve with the process of AMD. Two crucial transcription factors (c-rel and myogenin) were concluded to play a role in AMD. Especially, myogenin was associated with AMD by regulating TNC, GRP and FAP. Our finding can contribute to developing new potential biomarkers, revealing the underlying pathogenesis, and further raising new therapeutic targets for AMD.

Are Lung Disease and Function Related to Age-related Macular Degeneration?

PubMed Central

Moorthy, Sonia; Cheung, Ning; Klein, Ronald; Shahar, E; Wong, Tien Y

2010-01-01

Purpose To describe the relationship of lung disease and function with early age-related macular degeneration (AMD) in a population-based study. Design A population-based, cross-sectional study of 12,596 middle-aged participants from the Atherosclerosis Risk in Communities Study. Methods Lung function was assessed by spirometry. Physician diagnosis of asthma and lung disease was ascertained from a standardized questionnaire. AMD signs were graded from fundus photographs according to the Wisconsin grading protocol. Results Of our study population, 587 (4.7%) had early AMD, 638 (5.1%) had asthma and 581 (4.6%) had lung disease. After adjusting for age, gender, smoking and hypertension, each litre increase in predicted forced expiratory volume in one second (FEV1) (odds ratio [OR]: 1.27; 95% confidence interval [CI]: 0.89, 1.80), forced vital capacity (FVC) (OR 1.18; 95% CI: 0.93, 1.51) and peak expiratory flow rate (OR 1.12; 95% CI: 0.95, 1.33) were not significantly associated with early AMD. FEV1/FVC ratio (second quartile OR 1.61; 95%CI 0.88–2.93, third quartile OR 1.65; CI 0.90–3.03, fourth quartile OR 1.28; 95%CI 0.68–2.40) was not significantly associated with early AMD. Similarly, asthma (OR 1.06; 95% CI: 0.86, 1.27) and other lung diseases (OR 1.08; 95% CI: 0.90, 1.29) were not associated with early AMD. Conclusion Our data do not support a cross-sectional association between lung disease and risk of early AMD. PMID:21168814

Plasma metabolomic study in Chinese patients with wet age-related macular degeneration.

PubMed

Luo, Dan; Deng, Tingting; Yuan, Wei; Deng, Hui; Jin, Ming

2017-09-06

Age-related macular degeneration (AMD) is a leading disease associated with blindness. It has a high incidence and complex pathogenesis. We aimed to study the metabolomic characteristics in Chinese patients with wet AMD by analyzing the morning plasma of 20 healthy controls and 20 wet AMD patients for metabolic differences. We used ultra-high-pressure liquid chromatography and quadrupole-time-of-flight mass spectrometry for this analysis. The relationship of these differences with AMD pathophysiology was also assessed. Remaining data were normalized using Pareto scaling, and then valid data were handled using multivariate data analysis with MetaboAnalysis software, including unsupervised principal component analysis and supervised partial least squares-discriminate analysis. The purpose of the present work was to identify significant metabolites for the analyses. Hierarchical clustering was conducted to identify metabolites that differed between the two groups. Significant metabolites were then identified using the established database, and features were mapped on the Kyoto Encyclopedia of Genes and Genomes. A total of 5443 ion peaks were detected, all of them attributable to the same 10 metabolites. These included some amino acids, isomaltose, hydrocortisone, and biliverdin. The heights of these peaks differed significantly between the two groups. The biosynthesis of amino acids pathways also differed profoundly between patients with wet AMD and controls. These findings suggested that metabolic profiles and and pathways differed between wet AMD and controls and may provide promising new targets for AMD-directed therapeutics and diagnostics.

Combining macula clinical signs and patient characteristics for age-related macular degeneration diagnosis: a machine learning approach.

PubMed

Fraccaro, Paolo; Nicolo, Massimo; Bonetto, Monica; Giacomini, Mauro; Weller, Peter; Traverso, Carlo Enrico; Prosperi, Mattia; OSullivan, Dympna

2015-01-27

To investigate machine learning methods, ranging from simpler interpretable techniques to complex (non-linear) "black-box" approaches, for automated diagnosis of Age-related Macular Degeneration (AMD). Data from healthy subjects and patients diagnosed with AMD or other retinal diseases were collected during routine visits via an Electronic Health Record (EHR) system. Patients' attributes included demographics and, for each eye, presence/absence of major AMD-related clinical signs (soft drusen, retinal pigment epitelium, defects/pigment mottling, depigmentation area, subretinal haemorrhage, subretinal fluid, macula thickness, macular scar, subretinal fibrosis). Interpretable techniques known as white box methods including logistic regression and decision trees as well as less interpreitable techniques known as black box methods, such as support vector machines (SVM), random forests and AdaBoost, were used to develop models (trained and validated on unseen data) to diagnose AMD. The gold standard was confirmed diagnosis of AMD by physicians. Sensitivity, specificity and area under the receiver operating characteristic (AUC) were used to assess performance. Study population included 487 patients (912 eyes). In terms of AUC, random forests, logistic regression and adaboost showed a mean performance of (0.92), followed by SVM and decision trees (0.90). All machine learning models identified soft drusen and age as the most discriminating variables in clinicians' decision pathways to diagnose AMD. Both black-box and white box methods performed well in identifying diagnoses of AMD and their decision pathways. Machine learning models developed through the proposed approach, relying on clinical signs identified by retinal specialists, could be embedded into EHR to provide physicians with real time (interpretable) support.

Autophagy regulates death of retinal pigment epithelium cells in age-related macular degeneration.

PubMed

Kaarniranta, Kai; Tokarz, Paulina; Koskela, Ali; Paterno, Jussi; Blasiak, Janusz

2017-04-01

Age-related macular degeneration (AMD) is an eye disease underlined by the degradation of retinal pigment epithelium (RPE) cells, photoreceptors, and choriocapillares, but the exact mechanism of cell death in AMD is not completely clear. This mechanism is important for prevention of and therapeutic intervention in AMD, which is a hardly curable disease. Present reports suggest that both apoptosis and pyroptosis (cell death dependent on caspase-1) as well as necroptosis (regulated necrosis dependent on the proteins RIPK3 and MLKL, caspase-independent) can be involved in the AMD-related death of RPE cells. Autophagy, a cellular clearing system, plays an important role in AMD pathogenesis, and this role is closely associated with the activation of the NLRP3 inflammasome, a central event for advanced AMD. Autophagy can play a role in apoptosis, pyroptosis, and necroptosis, but its contribution to AMD-specific cell death is not completely clear. Autophagy can be involved in the regulation of proteins important for cellular antioxidative defense, including Nrf2, which can interact with p62/SQSTM, a protein essential for autophagy. As oxidative stress is implicated in AMD pathogenesis, autophagy can contribute to this disease by deregulation of cellular defense against the stress. However, these and other interactions do not explain the mechanisms of RPE cell death in AMD. In this review, we present basic mechanisms of autophagy and its involvement in AMD pathogenesis and try to show a regulatory role of autophagy in RPE cell death. This can result in considering the genes and proteins of autophagy as molecular targets in AMD prevention and therapy.

Synthesis and structural characterization of carboxyethylpyrrole-modified proteins: mediators of age-related macular degeneration.

PubMed

Lu, Liang; Gu, Xiaorong; Hong, Li; Laird, James; Jaffe, Keeve; Choi, Jaewoo; Crabb, John; Salomon, Robert G

2009-11-01

Protein modifications in which the epsilon-amino group of lysyl residues is incorporated into a 2-(omega-carboxyethyl)pyrrole (CEP) are mediators of age-related macular degeneration (AMD). They promote both angiogenesis into the retina ('wet AMD') and geographic retinal atrophy ('dry AMD'). Blood levels of CEPs are biomarkers for clinical prognosis of the disease. To enable mechanistic studies of their role in promoting AMD, for example, through the activation of B- and T-cells, interaction with receptors, or binding with complement proteins, we developed an efficient synthesis of CEP derivatives, that is especially effective for proteins. The structures of tryptic peptides derived from CEP-modified proteins were also determined. A key finding is that 4,7-dioxoheptanoic acid 9-fluorenylmethyl ester reacts with primary amines to provide 9-fluorenylmethyl esters of CEP-modified proteins that can be deprotected in situ with 1,8-diazabicyclo[5.4.0]undec-7-ene without causing protein denaturation. The introduction of multiple CEP-modifications with a wide variety of CEP:protein ratios is readily achieved using this strategy.

Wet Macular Degeneration

MedlinePlus

... has a hereditary component. Researchers have identified several genes related to developing the condition. Smoking. Smoking cigarettes or being regularly exposed to smoke significantly increases your risk of macular degeneration. Obesity. Research indicates that being obese increases the chance ...

Genetic association study of Age-Related Macular Degeneration in the Spanish population

PubMed Central

Brión, María; Sanchez-Salorio, Manuel; Cortón, Marta; de la Fuente, Maria; Pazos, Belen; Othman, Mohammad; Swaroop, Anand; Abecasis, Goncalo; Sobrino, Beatriz; Carracedo, Angel

2017-01-01

Purpose To investigate new genetic risk factors and replicate reported associations with advanced age related macular degeneration (AMD) in a prospective case - control study developed with a Spanish cohort. Methods Three hundred and fifty-three unrelated patients with advanced AMD (225 with atrophic AMD, 57 with neovascular AMD, and 71 with mixed AMD) and 282 age-matched controls were included. Functional and tagging SNPs in 55 candidate genes were genotyped using the SNPlex™ genotyping system. Single SNP and haplotype association analysis were performed to determine possible genetic associations; interaction effects between SNPs were also investigated. Results In agreement with previous reports, ARMS2 and CFH genes were strongly associated with AMD in the studied Spanish population. Moreover, both loci influenced risk independently giving support to different pathways implicated in AMD pathogenesis. No evidence for association of advanced AMD with other previous reported susceptibility genes, such as CST3, CX3CR1, FBLN5, HMCN1, PON1, SOD2, TLR4, VEGF and VLDLR, was detected. However, two additional genes appear to be candidate markers for the development of advanced AMD. A variant located at the 3´UTR of the FGF2 gene (rs6820411) was highly associated with atrophic AMD, and the functional SNP rs3112831 at ABCA4 showed a marginal association with the disease. Conclusion We performed a large gene association study in advanced AMD in a Spanish population. Our findings show that CFH and ARMS2 genes seem to be the principal risk loci contributing independently to AMD in our cohort. We report new significant associations that could also influence the development of advanced AMD. These findings should be confirmed in further studies with larger cohorts. PMID:21106043

Optical Coherence Tomography Reflective Drusen Substructures Predict Progression to Geographic Atrophy in Age-related Macular Degeneration.

PubMed

Veerappan, Malini; El-Hage-Sleiman, Abdul-Karim M; Tai, Vincent; Chiu, Stephanie J; Winter, Katrina P; Stinnett, Sandra S; Hwang, Thomas S; Hubbard, G Baker; Michelson, Michelle; Gunther, Randall; Wong, Wai T; Chew, Emily Y; Toth, Cynthia A

2016-12-01

Structural and compositional heterogeneity within drusen comprising lipids, carbohydrates, and proteins have been previously described. We sought to detect and define phenotypic patterns of drusen heterogeneity in the form of optical coherence tomography-reflective drusen substructures (ODS) and examine their associations with age-related macular degeneration (AMD)-related features and AMD progression. Retrospective analysis in a prospective study. Patients with intermediate AMD (n = 349) enrolled in the multicenter Age-Related Eye Disease Study 2 (AREDS2) ancillary spectral-domain optical coherence tomography (SD OCT) study. Baseline SD OCT scans of 1 eye per patient were analyzed for the presence of ODS. Cross-sectional and longitudinal associations of ODS presence with AMD-related features visible on SD OCT and color photographs, including drusen volume, geographic atrophy (GA), and preatrophic features, were evaluated for the entire macular region. Similar associations were also made locally within a 0.5-mm-diameter region around individual ODS and corresponding control region without ODS in the same eye. Preatrophy SD OCT changes and GA, central GA, and choroidal neovascularization (CNV) from color photographs. Four phenotypic subtypes of ODS were defined: low reflective cores, high reflective cores, conical debris, and split drusen. Among the 349 participants, there were 307 eligible eyes and 74 (24%) had at least 1 ODS. The ODS at baseline were associated with (1) greater macular drusen volume at baseline (P < 0.001), (2) development of preatrophic changes at year 2 (P = 0.001-0.01), and (3) development of macular GA (P = 0.005) and preatrophic changes at year 3 (P = 0.002-0.008), but not development of CNV. The ODS at baseline in a local region were associated with (1) presence of preatrophy changes at baseline (P = 0.02-0.03) and (2) development of preatrophy changes at years 2 and 3 within the region (P = 0.008-0.05). Optical coherence tomography

Consecutive case series of 244 age-related macular degeneration patients undergoing implantation with an extended macular vision IOL.

PubMed

Qureshi, Muhammad A; Robbie, Scott J; Hengerer, Fritz H; Auffarth, Gerd U; Conrad-Hengerer, Ina; Artal, Pablo

2018-03-01

To determine safety and visual outcomes in eyes with age-related macular degeneration (AMD) implanted with a novel intraocular lens (IOL) that delivers an optimized retinal image to all macular areas within 10 degrees of retinal eccentricity. This was a consecutive case series of 244 eyes with dry/stable wet AMD and logMAR visual acuity ≥0.3 implanted with iolAMD Eyemax mono TM (London Eye Hospital Pharma), a single-piece, injectable, hydrophobic acrylic IOL sited in the capsular bag. Primary outcome was safety. Secondary outcomes were changes in corrected distance visual acuity (CDVA) and corrected near visual acuity (CNVA) (logMAR). Mean age at surgery was 80 years. Mean duration of follow-up was 3 months (range 1-16 months). No eyes had worsening of CDVA. Frequency of perioperative complications was equivalent to standard IOL implantation. Postoperative refractive outcomes were within ±1 D of the target refraction in 88% of cases. Mean preoperative CDVA improved from 1.06 to 0.71 postoperatively (mean of differences -0.35; 95% confidence interval [CI] -0.3886 to -0.3223; p<0.0001), equating to an approximate Early Treatment Diabetic Retinopathy Study gain of 18 letters. Mean preoperative CNVA (N-point; logMAR conversion) improved from 1.36 to 0.88 postoperatively (mean of differences -0.48; 95% CI -0.53 to -0.44; p<0.0001). This novel IOL appears safe in the short to medium term. Improvements in postoperative CDVA and CNVA exceed those observed with standard implants.

Statins for age-related macular degeneration

PubMed Central

Gehlbach, Peter; Li, Tianjing; Hatef, Elham

2016-01-01

Background Age-related macular degeneration (AMD) is a progressive late onset disorder of the macula affecting central vision. Age-related macular degeneration is the leading cause of blindness in people over 65 years in industrialized countries. Recent epidemiologic, genetic, and pathological evidence has shown AMD shares a number of risk factors with atherosclerosis, leading to the hypothesis that statins may exert protective effects in AMD. Objectives The objective of this review was to examine the effectiveness of statins compared with other treatments, no treatment, or placebo in delaying the onset and progression of AMD. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 6), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2014), EMBASE (January 1980 to June 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to June 2014), PubMed (January 1946 to June 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 5 June 2014. Selection criteria We included randomized controlled trials (RCTs) that compared statins with other treatments, no treatment, or placebo in participants who were either susceptible to or diagnosed as having early stages of AMD. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. Two authors independently evaluated the search results against the selection criteria, abstracted data, and assessed risk of bias. We did not perform meta-analysis due to heterogeneity in the interventions and outcomes among the

Measurement of macular pigment optical density in a healthy chinese population sample

USDA-ARS?s Scientific Manuscript database

Macular pigment may protect against age-related macular degeneration (AMD) by its capability to absorb blue light and scavenge free radicals. Current information on human macular pigment density has been largely from studies on Caucasians populations. The purpose of this study was to assess macular ...

Exploring the cross talk between ER stress and inflammation in age-related macular degeneration.

PubMed

Kheitan, Samira; Minuchehr, Zarrin; Soheili, Zahra-Soheila

2017-01-01

Increasing evidence demonstrates that inflammation and endoplasmic reticulum (ER) stress is implicated in the development and progression of age-related macular degeneration (AMD), a multifactorial neurodegenerative disease. However the cross talk between these cellular mechanisms has not been clearly and fully understood. The present study investigates a possible intersection between ER stress and inflammation in AMD. In this study, we recruited two collections of involved protein markers to retrieve their interaction information from IMEx-curated databases, which are the most well- known protein-protein interaction collections, allowing us to design an intersection network for AMD that is unprecedented. In order to find expression activated subnetworks, we utilized AMD expression profiles in our network. In addition, we studied topological characteristics of the most expressed active subnetworks to identify the hubs. With regard to topological quantifications and expressional activity, we reported a list of the most pivotal hubs which are potentially applicable as probable therapeutic targets. Furthermore, we introduced MAPK signaling pathway as a significantly involved pathway in the association between ER stress and inflammation, leading to promising new directions in discovering AMD formation mechanisms and possible treatments.

Exploring the cross talk between ER stress and inflammation in age-related macular degeneration

PubMed Central

Kheitan, Samira; Soheili, Zahra-Soheila

2017-01-01

Increasing evidence demonstrates that inflammation and endoplasmic reticulum (ER) stress is implicated in the development and progression of age-related macular degeneration (AMD), a multifactorial neurodegenerative disease. However the cross talk between these cellular mechanisms has not been clearly and fully understood. The present study investigates a possible intersection between ER stress and inflammation in AMD. In this study, we recruited two collections of involved protein markers to retrieve their interaction information from IMEx-curated databases, which are the most well- known protein-protein interaction collections, allowing us to design an intersection network for AMD that is unprecedented. In order to find expression activated subnetworks, we utilized AMD expression profiles in our network. In addition, we studied topological characteristics of the most expressed active subnetworks to identify the hubs. With regard to topological quantifications and expressional activity, we reported a list of the most pivotal hubs which are potentially applicable as probable therapeutic targets. Furthermore, we introduced MAPK signaling pathway as a significantly involved pathway in the association between ER stress and inflammation, leading to promising new directions in discovering AMD formation mechanisms and possible treatments. PMID:28742151

Is There a Relationship Between Use of Anti-Vascular Endothelial Growth Factor Agents and Atrophic Changes in Age-Related Macular Degeneration Patients?

PubMed

Kaynak, Süleyman; Kaya, Mahmut; Kaya, Derya

2018-04-01

Choroidal neovascularization due to age-related macular degeneration (AMD) is currently treated successfully with anti-vascular endothelial growth factor (VEGF) intravitreal agents. Emerging evidence suggests that anti-VEGF treatment may potentially increase development of geographic atrophy. However, there is not yet direct proof of a causal relationship between geographic atrophy and use of anti-VEGF agents in neovaskuler AMD. The aim of this review is to discuss the evidence concerning the association between anti-VEGF therapy and progression of geographic atrophy.

Prevalence of subretinal drusenoid deposits in older persons with and without age-related macular degeneration, by multimodal imaging

PubMed Central

Zarubina, Anna V.; Neely, David C.; Clark, Mark E.; Huisingh, Carrie E.; Samuels, Brian C.; Zhang, Yuhua; McGwin, Gerald; Owsley, Cynthia; Curcio, Christine A.

2015-01-01

Purpose To assess the prevalence of subretinal drusenoid deposits (SDD) in older adults with healthy maculas and early and intermediate age-related macular degeneration (AMD) using multimodal imaging. Design Cross-sectional study. Participants A total of 651 subjects aged ≥60 years enrolled in the Alabama Study of Early Age-Related Macular Degeneration from primary care ophthalmology clinics. Methods Subjects were imaged using spectral domain optical coherence tomography (SD-OCT) of the macula and optic nerve head (ONH), infrared reflectance, fundus autofluorescence, and color fundus photographs (CFP). Eyes were assessed for AMD presence and severity using the AREDS 9-step scale. Criteria for SDD presence were identification on ≥1 en-face modality plus SD-OCT or on ≥2 en-face modalities if absent on SD-OCT. SDD were considered present at the person-level if present in 1 or both eyes. Main outcomes measures Prevalence of SDD in participants with and without AMD. Results Overall prevalence of SDD was 32% (197/611), with 62% (122/197) affected in both eyes. Persons with SDD were older than those without SDD (70.6 vs. 68.7 years, p =0.0002). Prevalence of SDD was 23% in subjects without AMD and 52% in subjects with AMD (p<0.0001). Among those with early and intermediate AMD, SDD prevalence was 49% and 79%, respectively. After age adjustment, those with SDD were 3.4x more likely to have AMD than those without SDD (95% CI 2.3–4.9). By using CFP only for SDD detection per the AREDS protocol, prevalence of SDD was 2% (12/610). Of persons with SDD detected by SD-OCT and confirmed by at least one en-face modality 47% (89/190) were detected exclusively on the ONH SD-OCT volume. Conclusion SDD are present in approximately one quarter of older adults with healthy maculae and in more than half of persons with early to intermediate AMD, even by stringent criteria. The prevalence of SDD is strongly associated with AMD presence and severity and increases with age, and its

A Discussion of Commercially Available Intra-ocular Telescopic Implants for Patients with Age-Related Macular Degeneration.

PubMed

Dunbar, Hannah M P; Dhawahir-Scala, Felipe E

2018-06-01

Age-related macular degeneration (AMD) is the leading cause of visual impairment in the western world, causing significant reduction in quality of life. Despite treatment advances, the burden of visual impairment caused by AMD continues to rise. In addition to traditional low vision rehabilitation and support, optical and electronic aids, and strategies to enhance the use of peripheral vision, implantable telescopic devices have been indicated as a surgical means of enhancing vision. Here we examine the literature on commercially available telescopic devices discussing their design, mode of action, surgical procedure and published outcomes on visual acuity, quality of life, surgical complication rates and cost effectiveness data where available.Funding Article processing charges were funded by VisionCare Inc.

Predictive models of long-term anatomic outcome in age-related macular degeneration treated with as-needed Ranibizumab.

PubMed

Gonzalez-Buendia, Lucia; Delgado-Tirado, Santiago; Sanabria, M Rosa; Fernandez, Itziar; Coco, Rosa M

2017-08-18

To analyze predictors and develop predictive models of anatomic outcome in neovascular age-related macular degeneration (AMD) treated with as-needed ranibizumab after 4 years of follow-up. A multicenter consecutive case series non-interventional study was performed. Clinical, funduscopic and OCT characteristics of 194 treatment-naïve patients with AMD treated with as-needed ranibizumab for at least 2 years and up to 4 years were analyzed at baseline, 3 months and each year until the end of the follow-up. Baseline demographic and angiographic characteristics were also evaluated. R Statistical Software was used for statistical analysis. Main outcome measure was final anatomic status. Factors associated with less probability of preserved macula were diagnosis in 2009, older age, worse vision, presence of atrophy/fibrosis, pigment epithelium detachment, and geographic atrophy/fibrotic scar/neovascular AMD in the fellow eye. Factors associated with higher probability of GA were presence of atrophy and greater number of injections, whereas male sex, worse vision, lesser change in central macular thickness and presence of fibrosis were associated with less probability of GA as final macular status. Predictive model of preserved macula vs. GA/fibrotic scar showed sensibility of 77.78% and specificity of 69.09%. Predictive model of GA vs. fibrotic scar showed sensibility of 68.89% and specificity of 72.22%. We identified predictors of final macular status, and developed two predictive models. Predictive models that we propose are based on easily harvested variables, and, if validated, could be a useful tool for individual patient management and clinical research studies.

Apolipoprotein E promotes subretinal mononuclear phagocyte survival and chronic inflammation in age-related macular degeneration.

PubMed

Levy, Olivier; Calippe, Bertrand; Lavalette, Sophie; Hu, Shulong J; Raoul, William; Dominguez, Elisa; Housset, Michael; Paques, Michel; Sahel, José-Alain; Bemelmans, Alexis-Pierre; Combadiere, Christophe; Guillonneau, Xavier; Sennlaub, Florian

2015-02-01

Physiologically, the retinal pigment epithelium (RPE) expresses immunosuppressive signals such as FAS ligand (FASL), which prevents the accumulation of leukocytes in the subretinal space. Age-related macular degeneration (AMD) is associated with a breakdown of the subretinal immunosuppressive environment and chronic accumulation of mononuclear phagocytes (MPs). We show that subretinal MPs in AMD patients accumulate on the RPE and express high levels of APOE. MPs of Cx3cr1(-/-) mice that develop MP accumulation on the RPE, photoreceptor degeneration, and increased choroidal neovascularization similarly express high levels of APOE. ApoE deletion in Cx3cr1(-/-) mice prevents pathogenic age- and stress-induced subretinal MP accumulation. We demonstrate that increased APOE levels induce IL-6 in MPs via the activation of the TLR2-CD14-dependent innate immunity receptor cluster. IL-6 in turn represses RPE FasL expression and prolongs subretinal MP survival. This mechanism may account, in part, for the MP accumulation observed in Cx3cr1(-/-) mice. Our results underline the inflammatory role of APOE in sterile inflammation in the immunosuppressive subretinal space. They provide rationale for the implication of IL-6 in AMD and open avenues toward therapies inhibiting pathogenic chronic inflammation in late AMD. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.

Genetic and Functional Dissection of HTRA1 and LOC387715 in Age-Related Macular Degeneration

PubMed Central

Zeng, Jiexi; Lu, Fang; Sun, Xufang; Zhao, Chao; Wang, Kevin; Davey, Lisa; Chen, Haoyu; London, Nyall; Muramatsu, Daisuke; Salasar, Francesca; Carmona, Ruben; Kasuga, Daniel; Wang, Xiaolei; Bedell, Matthew; Dixie, Manjuxia; Zhao, Peiquan; Yang, Ruifu; Gibbs, Daniel; Liu, Xiaoqi; Li, Yan; Li, Cai; Li, Yuanfeng; Campochiaro, Betsy; Constantine, Ryan; Zack, Donald J.; Campochiaro, Peter; Fu, Yinbin; Li, Dean Y.; Katsanis, Nicholas; Zhang, Kang

2010-01-01

A common haplotype on 10q26 influences the risk of age-related macular degeneration (AMD) and encompasses two genes, LOC387715 and HTRA1. Recent data have suggested that loss of LOC387715, mediated by an insertion/deletion (in/del) that destabilizes its message, is causally related with the disorder. Here we show that loss of LOC387715 is insufficient to explain AMD susceptibility, since a nonsense mutation (R38X) in this gene that leads to loss of its message resides in a protective haplotype. At the same time, the common disease haplotype tagged by the in/del and rs11200638 has an effect on the transcriptional upregulation of the adjacent gene, HTRA1. These data implicate increased HTRA1 expression in the pathogenesis of AMD and highlight the importance of exploring multiple functional consequences of alleles in haplotypes that confer susceptibility to complex traits. PMID:20140183

The new methods of treatment for age-related macular degeneration using the ultra-short pulsed laser

NASA Astrophysics Data System (ADS)

Iwamoto, Yumiko; Awazu, Kunio; Suzuki, Sachiko; Ohshima, Tetsuro; Sawa, Miki; Sakaguchi, Hirokazu; Tano, Yasuo; Ohji, Masahito

2007-02-01

The non-invasive methods of treatments have been studying for the improvement of quality of life (QOL) of patients undergoing treatment. A photodynamic therapy (PDT) is one of the non-invasive treatments. PDT is the methods of treatment using combination of a laser and a photosensitizer. PDT has few risks for patients. Furthermore, PDT enables function preservation of a disease part. PDT has been used for early cancer till now, but in late years it is applied for age-related macular degeneration (AMD). AMD is one of the causes of vision loss in older people. However, PDT for AMD does not produce the best improvement in visual acuity. The skin photosensivity by an absorption characteristic of a photosensitizer is avoided. We examined new PDT using combination of an ultra-short pulsed laser and indocyanine green (ICG).

Two-Year Outcomes of a Treat-and-Extend Regimen Using Intravitreal Aflibercept Injections for Typical Age-Related Macular Degeneration.

PubMed

Ito, Arisa; Matsumoto, Hidetaka; Morimoto, Masahiro; Mimura, Kensuke; Akiyama, Hideo

2017-01-01

The aim of this study was to evaluate the efficacy of a treat-and-extend (TAE) regimen using intravitreal injection of aflibercept (IVA) for typical age-related macular degeneration (tAMD). We retrospectively studied 61 treatment-naïve eyes with tAMD. Best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), number of injections, and complications during 2 years were evaluated. BCVA significantly improved by on average 0.13 logMAR units, and CMT and CCT significantly decreased after 2 years. The number of injections was on average 13.6. In the second year, eyes with classic choroidal neovascularization (CNV) needed significantly fewer treatments than eyes with occult CNV. Fourteen eyes, which developed subfoveal fibrosis, showed significantly poorer BCVA after 2 years. Subfoveal fibrosis was significantly common in classic CNV. A TAE regimen using IVA for tAMD might be effective for improving BCVA and exudative changes. The exudation may be suppressed with fewer treatments in classic CNV compared to occult CNV. © 2017 S. Karger AG, Basel.

Prevalence of age-related macular degeneration in a large European cohort: results from the population-based Gutenberg Health Study.

PubMed

Korb, Christina A; Kottler, Ulrike B; Wolfram, Christian; Hoehn, René; Schulz, Andreas; Zwiener, Isabella; Wild, Philipp S; Pfeiffer, Norbert; Mirshahi, Alireza

2014-09-01

The aim of this study was to describe the sex- and age-specific prevalence of age-related macular degeneration (AMD) and its correlation with urban or rural residence in a large and relatively young European cohort. We evaluated fundus photographs from participants in the Gutenberg Health Study (GHS), a population-based, prospective, observational, single-centre study in the Rhineland-Palatine region in midwestern Germany. The participants were 35-74 years of age at enrolment. The fundus images were classified as described in the Rotterdam Study and were graded independently by two experienced ophthalmologists (CK and UBK) based on the presence of hard and soft drusen, retinal pigmentary abnormalities, and signs of atrophic or neovascular age-related macular generation (AMD). Photographs from 4,340 participants were available for grading. Small, hard drusen (<63 μm, stages 0b and 0c) were present in 37.4% of participants (95% confidence interval [CI], stage 0b, 31.6% [30.3-33.7]; stage 0c, 5.8% [5.1-6.5]). Early AMD (soft drusen, pigmentary abnormalities, stages 1-3) was present in 3.8% of individuals in the youngest age group (35-44 years) (95% CI, stage 1a, 0.4% [0.3-0.5%]; stage 1b, 3.2% [2.9-3.5%]; stage 2a, 0.1% [0.1-0.2%]; stage 2b, 0% [0-0.0%]; stage 3, 0.1% [0.1-0.2%]), whereas late AMD (stages 4a and 4b) did not appear in the youngest age group. In all age groups, signs of early AMD were detected in 11.9% of individuals (stage 1a, 2.1% [1.7-2.6]; stage 1b, 8.0% [7.2-8.8]; stage 2a, 1.0% [0.7-1.3]; stage 2b, 0.5% [0.3-0.7]; stage 3, 0.3% [0.2-0.6]). Late AMD (geographic atrophy or neovascular AMD) was found in 0.2% of individuals (stage 4a, 0.1 % [0.0-0.2]; stage 4b, 0.1% [0.0-0.2]). AMD increased significantly with age (odds ratio [OR], 1.09; 95% CI, 1.08-1.10). Sex, iris colour, and residence (rural vs. urban) were not associated with different rates of AMD. In this study, the prevalence of AMD increased dramatically with age; however, although AMD is

Ethnic Differences in the Association Between Age-Related Macular Degeneration and Vision-Specific Functioning

PubMed Central

Fenwick, Eva K.; Man, Ryan E. K.; Cheung, Chui Ming Gemmy; Sabanayagam, Charumathi; Cheng, Ching-Yu; Neelam, Kumari; Chua, Jacqueline; Gan, Alfred T. L.; Mitchell, Paul; Wong, Tien Y.

2017-01-01

Importance Understanding the link between ethnicity and health is critical to making appropriate public policy decisions. Few population-level data are available about this connection, however, including the influence of ethnicity on the association between age-related macular degeneration (AMD) and vision-specific functioning (VSF). Objective To identify the influence of ethnicity on VSF among Chinese, Malay, and Indian patients with AMD. Design, Setting, and Participants This cross-sectional, population-based study relied on patients and their data from 3 population-based studies in 3 ethnic groups: Chinese, Malay and Indian. Of 10 033 Chinese, Malay, and Indian adults who participated in the study, 9962 (99.3%) who had gradable fundus images and Visual Function Index (VF-11) data available were included in the analyses for the present study. Uniocular presenting distance visual acuity was measured using the logMAR chart. Separate multiple linear regression models examined the association between AMD and VSF in the 3 ethnic groups, adjusting for age, sex, presenting visual acuity in the better-seeing eye, educational level, income, smoking status, hypertension, diabetes, cardiovascular disease, total cholesterol level, and other eye conditions. Data were collected between January 20, 2004, and December 19, 2011; data analysis was conducted between November 12, 2015, and December 28, 2016. Exposures Age-related macular degeneration according to fundus photographs graded using a modified Wisconsin Age-Related Maculopathy Grading System. Main Outcomes and Measures Rasch analysis was used to convert VF-11 questionnaire scores to estimated interval measures of VSF. Results Of the 9962 participants, the mean (SD) age was 58.8 (10.4) years; 4909 (49.3%) were male; 590 (5.9%) had early AMD (241 Chinese, 161 Malays, and 188 Indians) and 60 (0.6%) had late AMD (25 Chinese, 21 Malays, and 14 Indians). In the adjusted models, compared with no AMD, early AMD was

Update on Clinical Trials in Dry Age-related Macular Degeneration

PubMed Central

Taskintuna, Ibrahim; Elsayed, M. E. A. Abdalla; Schatz, Patrik

2016-01-01

This review article summarizes the most recent clinical trials for dry age-related macular degeneration (AMD), the most common cause of vision loss in the elderly in developed countries. A literature search through websites https://www.pubmed.org and https://www.clinicaltrials.gov/, both accessed no later than November 04, 2015, was performed. We identified three Phase III clinical trials that were completed over the recent 5 years Age-Related Eye Disease Study 2 (AREDS2), implantable miniature telescope and tandospirone, and several other trials targeting a variety of mechanisms including, oxidative stress, complement inhibition, visual cycle inhibition, retinal and choroidal blood flow, stem cells, gene therapy, and visual rehabilitation. To date, none of the biologically oriented therapies have resulted in improved vision. Vision improvement was reported with an implantable mini telescope. Stem cells therapy holds a potential for vision improvement. The AREDS2 formulas did not add any further reduced risk of progression to advanced AMD, compared to the original AREDS formula. Several recently discovered pathogenetic mechanisms in dry AMD have enabled development of new treatment strategies, and several of these have been tested in recent clinical trials and are currently being tested in ongoing trials. The rapid development and understanding of pathogenesis holds promise for the future. PMID:26957835

[Pharmacological therapy of age-related macular degeneration based on etiopathogenesis].

PubMed

Fischer, Tamás

2015-11-15

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

Divergence in the lived experience of people with macular degeneration.

PubMed

McCloud, Christine; Khadka, Jyoti; Gilhotra, Jagjit Singh; Pesudovs, Konrad

2014-08-01

The aim of this study was to understand people's experience with age-related macular degeneration (AMD) in light of new treatment successes. An interpretive qualitative methodology was used to facilitate understanding of the experience of people with AMD. Rich in-depth data were collected using focus groups and individual interviews. Thematic analysis of the data occurred through the processes of line-by-line coding, aggregation, and theme development using the NVivo 10 software. A total of 4 focus groups and 16 individual interviews were conducted with 34 people (median age = 81 years; range = 56 to 102 years; 19 females) with AMD. Four major themes arose from the narratives of the participants: cautious optimism, enduring, adaptation, and profound loss. Cautious optimism resonated for participants who had received successful treatment and stabilization of AMD. Enduring emerged as participants with exudative AMD described an ongoing need for invasive and frequent treatments (anti-vascular endothelial growth factor injections) that maintained their vision. Adaptation was evident in the narratives of all participants and was directly related to the physical and psychological limitations that were a consequence of visual disability. Profound loss encompassed both physical and emotional aspects of deteriorating vision and was most evident in patients for whom treatment had failed or had not been considered appropriate for their disease. The findings of this study shed new light on the influence of underlying pathology, disease trajectory, and success of new treatments on quality of life of people living with AMD. Optimism toward maintaining vision in the presence of exudative AMD was described by participants, moderated by ongoing caution and a need for endurance of frequent and often problematic intravitreal treatments. These findings add a deeper understanding of this complex and life-changing experience.

Nature and nurture- genes and environment- predict onset and progression of macular degeneration.

PubMed

Sobrin, Lucia; Seddon, Johanna M

2014-05-01

Age-related macular degeneration (AMD) is a common cause of irreversible visual loss and the disease burden is rising world-wide as the population ages. Both environmental and genetic factors contribute to the development of this disease. Among environmental factors, smoking, obesity and dietary factors including antioxidants and dietary fat intake influence onset and progression of AMD. There are also several lines of evidence that link cardiovascular, immune and inflammatory biomarkers to AMD. The genetic etiology of AMD has been and continues to be an intense and fruitful area of investigation. Genome-wide association studies have revealed numerous common variants associated with AMD and sequencing is increasing our knowledge of how rare genetic variants strongly impact disease. Evidence for interactions between environmental, therapeutic and genetic factors is emerging and elucidating the mechanisms of this interplay remains a major challenge in the field. Genotype-phenotype associations are evolving. The knowledge of non-genetic, modifiable risk factors along with information about heritability and genetic risk variants for this disease acquired over the past 25 years have greatly improved patient management and our ability to predict which patients will develop or progress to advanced forms of AMD. Personalized medicine and individualized prevention and treatment strategies may become a reality in the near future. Copyright © 2014. Published by Elsevier Ltd.

Current Treatment Limitations in Age-Related Macular Degeneration and Future Approaches Based on Cell Therapy and Tissue Engineering

PubMed Central

Fernández-Robredo, P.; Sancho, A.; Johnen, S.; Recalde, S.; Gama, N.; Thumann, G.; Groll, J.; García-Layana, A.

2014-01-01

Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world. With an ageing population, it is anticipated that the number of AMD cases will increase dramatically, making a solution to this debilitating disease an urgent requirement for the socioeconomic future of the European Union and worldwide. The present paper reviews the limitations of the current therapies as well as the socioeconomic impact of the AMD. There is currently no cure available for AMD, and even palliative treatments are rare. Treatment options show several side effects, are of high cost, and only treat the consequence, not the cause of the pathology. For that reason, many options involving cell therapy mainly based on retinal and iris pigment epithelium cells as well as stem cells are being tested. Moreover, tissue engineering strategies to design and manufacture scaffolds to mimic Bruch's membrane are very diverse and under investigation. Both alternative therapies are aimed to prevent and/or cure AMD and are reviewed herein. PMID:24672707

Alteration of travel patterns with vision loss from glaucoma and macular degeneration.

PubMed

Curriero, Frank C; Pinchoff, Jessie; van Landingham, Suzanne W; Ferrucci, Luigi; Friedman, David S; Ramulu, Pradeep Y

2013-11-01

The distance patients can travel outside the home influences how much of the world they can sample and to what extent they can live independently. Recent technological advances have allowed travel outside the home to be directly measured in patients' real-world routines. To determine whether decreased visual acuity (VA) from age-related macular degeneration (AMD) and visual field (VF) loss from glaucoma are associated with restricted travel patterns in older adults. Cross-sectional study. Patients were recruited from an eye clinic, while travel patterns were recorded during their real-world routines using a cellular tracking device. Sixty-one control subjects with normal vision, 84 subjects with glaucoma with bilateral VF loss, and 65 subjects with AMD with bilateral or severe unilateral loss of VA had their location tracked every 15 minutes between 7 am and 11 pm for 7 days using a tracking device. Average daily excursion size (defined as maximum distance away from home) and average daily excursion span (defined as maximum span of travel) were defined for each individual. The effects of vision loss on travel patterns were evaluated after controlling for individual and geographic factors. In multivariable models comparing subjects with AMD and control subjects, average excursion size and span decreased by approximately one-quarter mile for each line of better-eye VA loss (P ≤ .03 for both). Similar but not statistically significant associations were observed between average daily excursion size and span for severity of better-eye VF loss in subjects with glaucoma and control subjects. Being married or living with someone and younger age were associated with more distant travel, while less-distant travel was noted for older individuals, African Americans, and those living in more densely populated regions. Age-related macular degeneration-related loss of VA, but not glaucoma-related loss of VF, is associated with restriction of travel to more nearby locations

Health State Utility Values for Age-Related Macular Degeneration: Review and Advice.

PubMed

Butt, Thomas; Tufail, Adnan; Rubin, Gary

2017-02-01

Health state utility values are a major source of uncertainty in economic evaluations of interventions for age-related macular degeneration (AMD). This review identifies and critiques published utility values and methods for eliciting de novo utility values in AMD. We describe how utility values have been used in healthcare decision making and provide guidance on the choice of utility values for future economic evaluations for AMD. Literature was searched using PubMed, and health technology assessments (HTA) were searched using HTA agency websites to identify articles reporting utility values or approaches to derive utility values in AMD and articles applying utilities for use in healthcare decision making relating to treatments for AMD. A total of 70 studies qualified for data extraction, 22 of which were classified as containing utility values and/or elicitation methods, and 48 were classified as using utility values in decision making. A large number of studies have elicited utility values for AMD, although those applied to decision making have focused on a few of these. There is an appreciation of the challenges in the measurement and valuation of health states, with recent studies addressing challenges such as the insensitivity of generic health-related quality of life (HRQoL) questionnaires and utility in the worse-seeing eye. We would encourage careful consideration when choosing utility values in decision making and an explicit critique of their applicability to the decision problem.

The burden of age-related macular degeneration: a value-based analysis.

PubMed

Brown, Melissa M; Brown, Gary C; Sharma, Sanjay; Stein, Joshua D; Roth, Zachary; Campanella, Joseph; Beauchamp, George R

2006-06-01

The quality-of-life loss and the financial consequences associated with age-related macular degeneration are assessed. The quality-of-life loss associated with macular degeneration is markedly underestimated by the general public, nonophthalmic physicians, and ophthalmologists who treat patients with this condition. Mild age-related macular degeneration causes a 17% decrement in the quality of life of the average patient, similar to that encountered with moderate cardiac angina or symptomatic human immunodeficiency virus syndrome. Moderate age-related macular degeneration causes a 40% decrease in the average patient's quality of life, similar to that associated with severe cardiac angina or renal dialysis. Very severe age-related macular degeneration causes a large 63% decrease in the average patient's quality of life, similar to that encountered with end-stage prostatic cancer or a catastrophic stroke that leaves a person bedridden, incontinent and requiring constant nursing care. The return on investment is high for both treatment with current age-related macular degeneration therapies and the research costs invested in the development of age-related macular degeneration treatment modalities. Age-related macular degeneration is a major public health problem that has a devastating effect upon patients and marked adverse financial consequences for the economy.

Oxysterol Signatures Distinguish Age-Related Macular Degeneration from Physiologic Aging.

PubMed

Lin, Jonathan B; Sene, Abdoulaye; Santeford, Andrea; Fujiwara, Hideji; Sidhu, Rohini; Ligon, Marianne M; Shankar, Vikram A; Ban, Norimitsu; Mysorekar, Indira U; Ory, Daniel S; Apte, Rajendra S

2018-06-11

Macrophage aging is pathogenic in numerous diseases, including age-related macular degeneration (AMD), a leading cause of blindness in older adults. Although prior studies have explored the functional consequences of macrophage aging, less is known about its cellular basis or what defines the transition from physiologic aging to disease. Here, we show that despite their frequent self-renewal, macrophages from old mice exhibited numerous signs of aging, such as impaired oxidative respiration. Transcriptomic profiling of aged murine macrophages revealed dysregulation of diverse cellular pathways, especially in cholesterol homeostasis, that manifested in altered oxysterol signatures. Although the levels of numerous oxysterols in human peripheral blood mononuclear cells and plasma exhibited age-associated changes, plasma 24-hydroxycholesterol levels were specifically associated with AMD. These novel findings demonstrate that oxysterol levels can discriminate disease from physiologic aging. Furthermore, modulation of cholesterol homeostasis may be a novel strategy for treating age-associated diseases in which macrophage aging is pathogenic. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Age-related macular degeneration: the importance of family history as a risk factor.

PubMed

Shahid, Humma; Khan, Jane C; Cipriani, Valentina; Sepp, Tiina; Matharu, Baljinder K; Bunce, Catey; Harding, Simon P; Clayton, David G; Moore, Anthony T; Yates, John R W

2012-03-01

Family history is considered a risk factor for age-related macular degeneration (AMD). With the advent of effective therapy for the disease, the importance of family history merits further investigation. This study quantifies the risk associated with family history, first, by a case-control study of reported family history and, second, by examining the siblings of AMD cases. The authors recruited cases with advanced AMD, spouses and siblings. All subjects were carefully phenotyped. Clinical findings in the siblings were compared with spouses. Information about family history was collected. The ORs for reported family history of AMD were calculated. Analyses were adjusted for age, smoking and genotype. 495 AMD cases, 259 spouses and 171 siblings were recruited. The OR for AMD was 27.8 (CI 3.8 to 203.0; p=0.001) with a reported family history of an affected parent and 12.0 (CI 3.7 to 38.6; p<0.0001) with a history of an affected sibling. ORs adjusted for age and smoking were higher. Examination of siblings confirmed their increased risk with 23% affected by AMD and an OR of 10.8 (4.5 to 25.8; p<0.0001). Adjusting for age increased the OR to 16.1 (6.2 to 41.8). The risk of AMD is greatly increased by having an affected first-degree relative. Those at risk need to be made aware of this and AMD patients should advise siblings and children to seek prompt ophthalmological advice if they develop visual symptoms of distortion or reduced vision.

Optical coherence tomography angiography in the management of age-related macular degeneration.

PubMed

Schneider, Eric W; Fowler, Samuel C

2018-05-01

Optical coherence tomography angiography (OCT-A) provides rapid, flow-based imaging of the retinal and choroidal vasculature in a noninvasive manner. This review contrasts this novel technique with conventional angiography and discusses its current uses and limitations in the management of age-related macular degeneration (AMD). Initial work with OCT-A has focused on its ability to identify choriocapillaris flow alterations in dry AMD and to sensitively detect choroidal neovascular membranes (CNVs) in neovascular AMD. Reduced choriocapillaris flow beyond the borders of geographic atrophy seen on OCT-A suggests a primary vascular cause in geographic atrophy. Longitudinal OCT-A analysis of CNV morphology has demonstrated the transition from an immature to mature CNV phenotype following treatment. Current clinical applications of OCT-A include identification of asymptomatic CNV and monitoring for CNV development in the setting of an acquired vitelliform lesion. OCT-A remains a promising diagnostic tool but one still very much in evolution. Larger studies will be needed to more accurately describe its sensitivity and specificity for CNV detection and to better characterize longitudinal CNV morphologic changes. Anticipated hardware and software updates including swept-source light sources, automated montaging, and manual adjustment of interscan timing should enhance the capabilities of OCT-A in the management of AMD.

Influence of new societal factors on neovascular age-related macular degeneration outcomes.

PubMed

Giocanti-Aurégan, Audrey; Chbat, Elige; Darugar, Adil; Morel, Christophe; Morin, Bruno; Conrath, John; Devin, François

2018-02-01

To assess the impact of unstudied societal factors for neovascular age-related macular degeneration (nAMD) on functional outcomes after anti-VEGFs. Charts of 94 nAMD patients treated in the Monticelli-Paradis Centre, Marseille, France, were reviewed. Phone interviews were conducted to assess societal factors, including transportation, living status, daily reading and social security scheme (SSS). Primary outcome was the impact of family support and disease burden on functional improvement in nAMD. Between baseline and month 24 (M24), 42.4% of the variability in best-corrected visual acuity (BCVA) was explained by the cumulative effect of the following societal factors: intermittent out-patient follow-up, marital status, daily reading, transportation type, commuting time. No isolated societal factor significantly correlated with ETDRS BCVA severity at M24. A trend to correlation was observed between the EDTRS score at M24 and the SSS (P = 0.076), economic burden (P = 0.075), time between diagnosis and treatment initiation (P = 0.070). A significant correlation was found for the disease burdensome on the patient (P = 0.034) and low vision rehabilitation (P = 0.014). Societal factors could influence functional outcomes in nAMD patients treated with anti-VEGFs. They could contribute to the healing process or sustain disease progression.

Macular pigment density variation after supplementation of lutein and zeaxanthin using the Visucam® 200 pigment module: Impact of age-related macular degeneration and lens status.

PubMed

Azar, G; Quaranta-El Maftouhi, M; Masella, J-J; Mauget-Faÿsse, M

2017-04-01

To assess the evolution of macular pigment optical density (MPOD) following supplementation with various macular formulations obtained with the Visucam ® 200, and to study the factors affecting MPOD measurements. In this prospective, randomized, double-masked multicenter study, patients were divided into 2 groups: group A (patients without retinal pathology who underwent cataract surgery 1 month previously) and group B (patients with neovascular age-related macular degeneration [AMD] in one eye). In each group, half of the patients were randomly assigned to receive a food supplementation either with or without carotenoids (5mg of Lutein and 1mg of Zeaxanthin). Outcome measures included MPOD responses obtained with the Visucam ® 200 for one year. In total, 126 subjects (52 men, 74 women) with a mean age of 75.3±7.61 years were enrolled. Mean MPOD values at the time of inclusion were statistically lower in group A (0.088 density unit [DU]) compared to group B (0.163 DU, P<0.05). No statistically significant increase in MPOD was noted in either group, even after discontinuation of the supplementation. By multiple regression analysis, age, female gender, lens status and the presence of AMD seemed to significantly affect MPOD measurements. No significant improvement in MPOD seems to be detected with the Visucam ® 200 after carotenoid supplementation. The MPOD measurement seems to be highly affected by cataract extraction and the presence of AMD. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

[The effect of yellow filter intraocular lens on the macula after cataract phacoemulsification in patients with age macular degeneration].

PubMed

Shpak, A A; Maliugin, B É; Fadeeva, T V

2012-01-01

Macula changes diagnosed with optical coherence tomography (OCT) within a year after cataract phacoemulsification (PE) with intraocular lens implantation with and without yellow filter are presented. 32 patients (36 eyes) with early stages of age macular degeneration (AMD) were included into the experimental group and 35 patients (36 eyes) served as controls. IOLs with yellow filter were implanted in 21 eyes, and in 15 cases IOLs without filter were used in each group. According to OCT data thickening of fovea and increasing of macula volume developed within 6 months after cataract PE. Implantation of yellow filter IOLs reduced the intensity of these changes after surgery in patients with AMD. The progression of early AMD into advanced stages within a year after PE was not observed.

Effect of ambient light and age-related macular degeneration on precision walking.

PubMed

Alexander, M Scott; Lajoie, Kim; Neima, David R; Strath, Robert A; Robinovitch, Stephen N; Marigold, Daniel S

2014-08-01

To determine how age-related macular degeneration (AMD) and changes in ambient light affect the control of foot placement while walking. Ten older adults with AMD and 11 normal-sighted controls performed a precision walking task under normal (∼600 lx), dim (∼0.7 lx), and after a sudden reduction (∼600 to 0.7 lx) of light. The precision walking task involved subjects walking and stepping to the center of a series of irregularly spaced, low-contrast targets. Habitual visual acuity and contrast sensitivity and visual field function were also assessed. There were no differences between groups when performing the walking task in normal light (p > 0.05). In reduced lighting, older adults with AMD were less accurate and more variable when stepping across the targets compared to controls (p < 0.05). A sudden reduction of light proved the most challenging for this population. In the AMD group, contrast sensitivity and visual acuity were not significantly correlated with walking performance. Visual field thresholds in the AMD group were only associated with greater foot placement error and variability in the dim light walking condition (r = -0.69 to -0.87, p < 0.05). While walking performance is similar between groups in normal light, poor ambient lighting results in decreased foot placement accuracy in older adults with AMD. Improper foot placement while walking can lead to a fall and possible injury. Thus, to improve the mobility of those with AMD, strategies to enhance the environment in reduced lighting situations are necessary.

Recent developments in the management of dry age-related macular degeneration

PubMed Central

Buschini, Elisa; Fea, Antonio M; Lavia, Carlo A; Nassisi, Marco; Pignata, Giulia; Zola, Marta; Grignolo, Federico M

2015-01-01

Dry age-related macular degeneration (AMD), also called geographic atrophy, is characterized by the atrophy of outer retinal layers and retinal pigment epithelium (RPE) cells. Dry AMD accounts for 80% of all intermediate and advanced forms of the disease. Although vision loss is mainly due to the neovascular form (75%), dry AMD remains a challenge for ophthalmologists because of the lack of effective therapies. Actual management consists of lifestyle modification, vitamin supplements, and supportive measures in the advanced stages. The Age-Related Eye Disease Study demonstrated a statistically significant protective effect of dietary supplementation of antioxidants (vitamin C, vitamin E, beta-carotene, zinc, and copper) on dry AMD progression rate. It was also stated that the consumption of omega-3 polyunsaturated fatty acids, such as docosahexaenoic acid and eicosapentaenoic acid, has protective effects. Other antioxidants, vitamins, and minerals (such as crocetin, curcumin, and vitamins B9, B12, and B6) are under evaluation, but the results are still uncertain. New strategies aim to 1) reduce or block drusen formation, 2) reduce or eliminate inflammation, 3) lower the accumulation of toxic by-products from the visual cycle, 4) reduce or eliminate retinal oxidative stress, 5) improve choroidal perfusion, 6) replace/repair or regenerate lost RPE cells and photoreceptors with stem cell therapy, and 7) develop a target gene therapy. PMID:25878491

Involvement of a gut-retina axis in protection against dietary glycemia-induced age-related macular degeneration.

PubMed

Rowan, Sheldon; Jiang, Shuhong; Korem, Tal; Szymanski, Jedrzej; Chang, Min-Lee; Szelog, Jason; Cassalman, Christa; Dasuri, Kalavathi; McGuire, Christina; Nagai, Ryoji; Du, Xue-Liang; Brownlee, Michael; Rabbani, Naila; Thornalley, Paul J; Baleja, James D; Deik, Amy A; Pierce, Kerry A; Scott, Justin M; Clish, Clary B; Smith, Donald E; Weinberger, Adina; Avnit-Sagi, Tali; Lotan-Pompan, Maya; Segal, Eran; Taylor, Allen

2017-05-30

Age-related macular degeneration (AMD) is the major cause of blindness in developed nations. AMD is characterized by retinal pigmented epithelial (RPE) cell dysfunction and loss of photoreceptor cells. Epidemiologic studies indicate important contributions of dietary patterns to the risk for AMD, but the mechanisms relating diet to disease remain unclear. Here we investigate the effect on AMD of isocaloric diets that differ only in the type of dietary carbohydrate in a wild-type aged-mouse model. The consumption of a high-glycemia (HG) diet resulted in many AMD features (AMDf), including RPE hypopigmentation and atrophy, lipofuscin accumulation, and photoreceptor degeneration, whereas consumption of the lower-glycemia (LG) diet did not. Critically, switching from the HG to the LG diet late in life arrested or reversed AMDf. LG diets limited the accumulation of advanced glycation end products, long-chain polyunsaturated lipids, and their peroxidation end-products and increased C3-carnitine in retina, plasma, or urine. Untargeted metabolomics revealed microbial cometabolites, particularly serotonin, as protective against AMDf. Gut microbiota were responsive to diet, and we identified microbiota in the Clostridiales order as being associated with AMDf and the HG diet, whereas protection from AMDf was associated with the Bacteroidales order and the LG diet. Network analysis revealed a nexus of metabolites and microbiota that appear to act within a gut-retina axis to protect against diet- and age-induced AMDf. The findings indicate a functional interaction between dietary carbohydrates, the metabolome, including microbial cometabolites, and AMDf. Our studies suggest a simple dietary intervention that may be useful in patients to arrest AMD.

Dynamics of Inflammatory Factors in Aqueous Humor during Ranibizumab or Aflibercept Treatment for Age-Related Macular Degeneration.

PubMed

Motohashi, Ryosuke; Noma, Hidetaka; Yasuda, Kanako; Kotake, Osamu; Goto, Hiroshi; Shimura, Masahiko

2017-01-01

To evaluate the dynamic changes of the aqueous humor levels of inflammatory factors between patients receiving intravitreal ranibizumab injection (IRI) and aflibercept injection (IAI) in patients with exudative age-related macular degeneration (AMD). The study was performed on 30 eyes with AMD that were scheduled to receive 3 doses of IRI (15 eyes) or IAI (15 eyes) at monthly intervals. Aqueous humor samples were collected when injection was done. The concentrations of VEGF, monocyte chemoattractant protein 1 (MCP-1), platelet-derived growth factor (PDGF)-AA, interleukin (IL)-6, and IL-8 were measured in aqueous humor samples from the 30 AMD patients and 10 cataract patients (as controls) by the suspension array method. Aqueous levels of the inflammatory factors (MCP-1, PDGF-AA, IL-6, and IL-8) were significantly correlated with each other. In both the IRI-treated eyes and the IAI-treated eyes, visual acuity and central macular thickness improved significantly, and the aqueous level of VEGF showed a significant decrease. In IAI-treated eyes, the aqueous levels of MCP-1 and PDGF-AA were significantly decreased at 2 months. These findings suggest that the inflammatory factors are involved in the pathogenesis of AMD and also the possibility that the interaction between these inflammatory factors and IRI or IAI is different. © 2017 S. Karger AG, Basel.

Complement factor H polymorphisms in Japanese population with age-related macular degeneration.

PubMed

Okamoto, Haru; Umeda, Shinsuke; Obazawa, Minoru; Minami, Masayoshi; Noda, Toru; Mizota, Atsushi; Honda, Miki; Tanaka, Minoru; Koyama, Risa; Takagi, Ikue; Sakamoto, Yoshihiro; Saito, Yoshihiro; Miyake, Yozo; Iwata, Takeshi

2006-03-06

To study the frequency of five haplotypes previously reported in the complement factor H (CFH) gene for Japanese patients with age-related macular degeneration (AMD). Genomic DNA was isolated from peripheral blood samples taken from 96 Japanese AMD patients and 89 age-matched controls. All patients were diagnosed as having exudative (wet-type) AMD. The amplified polymerase chain reaction (PCR) products of CFH exons 2, 9, and 13, and intron 6 were analyzed by temperature gradient capillary electrophoresis (TGCE) and by direct sequencing. The haplotypes were identified, and their frequencies were calculated and compared with reported results. Five haplotypes were identified in the Japanese population including four already reported in the American population. The frequencies of these haplotypes were significantly different between Japanese and American in both control and case groups. The haplotype containing Y402H, which was previously reported to be associated with AMD, was only 4% in the control and case population, with a p value of 0.802. However, two other haplotypes were found as risk factors, which gave an increased likelihood of AMD of 1.9 and 2.5 fold (95% CI 1.12-3.69 and 1.42-6.38). One protective haplotype that decreased the likelihood of AMD by 1.6 fold (95% CI 0.26-0.67) was identified. The frequencies for five haplotypes previously identified were analyzed in a Japanese population with AMD. Four previously found haplotypes were identified and one additional haplotype was found. The frequencies of each haplotype were significantly different from that in found Americans affected with AMD. Two of the haplotypes were identified as risk factors and one was considered protective.

Ocular Risk Factors for Age-related Macular Degeneration: The Los Angeles Latino Eye Study (LALES)

PubMed Central

Fraser-Bell, Samantha; Choudhury, Farzana; Klein, Ronald; Azen, Stanley; Varma, Rohit

2010-01-01

Purpose To assess the association of ocular factors and age-related macular degeneration (AMD) in Latinos. Design Population-based, cross-sectional study of 6357 self-identified Latinos aged 40 years and older. Methods Ophthalmic examination included subjective refraction, measurement of axial length, evaluation of iris color, Lens Opacities Classification System II (LOCS II) grading of cataracts, and stereoscopic macular photographs for AMD lesions. Generalized estimating equation analysis incorporated data from both eyes to estimate odds ratios adjusted for covariates. Results After controlling for confounders (age, gender and smoking), prior cataract surgery was associated with advanced AMD (OR: 2.8, 95% CI 1.0, 7.8), increased retinal pigment (OR: 1.6, 95% CI 1.0, 1.5) and retinal pigment epithelial depigmentation (OR: 2.2, 95% CI 1.1, 4.4). The presence of any lens opacity was associated with soft drusen (OR: 1.2; 95% CI 1.0, 1.5). Longer axial length (per mm) was associated with a decreased odds of soft drusen, increased retinal pigment, and geographic atrophy (GA) (ORs: 0.8 [95% CI 0.7, 0.9], 0.8 [95% CI 0.7, 0.9], 0.7 [95% CI 0.5, 0.9], respectively. Myopia was inversely associated with soft drusen (OR: 0.8; 95% CI 0.7, 1.0). Lighter colored irises were associated with GA (OR: 5.0; 95% CI 1.0, 25.3). Conclusions Cross-sectional associations of ocular factors such as cataract, cataract surgery, and refractive errors with early AMD lesions found in Latinos were consistent with those in whites. Additionally, prior cataract surgery was associated with advanced AMD. PMID:20138605

Intravitreal aflibercept versus intravitreal ranibizumab in patients with age-related macular degeneration: a comparative effectiveness study.

PubMed

Smit, Cornelis; Wiertz-Arts, Karin; van de Garde, Ewoudt Mw

2018-06-01

A hospital-wide, unselected switch of ranibizumab to aflibercept in treatment of age-related macular degeneration (AMD) allowed us to compare the clinical effectiveness of these agents. In a single-center before-after, observational study design new AMD-patients started with aflibercept treatment in 2013-2014 were compared with a control group of AMD-patients on ranibizumab before the switch. The mean difference in visual acuity (in logMAR units) after 1 year was comparable (+0.012 [aflibercept, n = 37] vs +0.17 [ranibizumab, n = 30], p = 0.154). However, the aflibercept-group did receive more intravitreal injections (5.8 vs 4.7 injections, p = 0.004) and were treated longer (265.7 vs 197.7 days; p = 0.011). With no difference in clinical effectiveness, longer treatment intervals for aflibercept should be investigated.

[Current concepts in pathogenesis of age-related macular degeneration].

PubMed

Kubicka-Trząska, Agnieszka; Karska-Basta, Izabella; Romanowska-Dixon, Bożena

2014-01-01

Age-related macular degeneration is the leading cause of central blindness in elderly population of the western world. The pathogenesis of this disease, likely multifactorial, is not well known, although a number of theories have been put forward, including oxidative stress, genetic interactions, hemodynamic imbalance, immune and inflammatory processes. The understanding of age-related macular degeneration pathogenesis will give rise to new approaches in prevention and treatment of the early and late stages of both atrophic and neovascular age-related macular degeneration.

Juvenile Macular Degenerations

PubMed Central

Altschwager, Pablo; Ambrosio, Lucia; Swanson, Emily A.; Moskowitz, Anne; Fulton, Anne B.

2017-01-01

In this paper we review three common juvenile macular degenerations: Stargardt disease, X-linked retinoschisis, and Best vitelliform macular dystrophy. These are inherited disorders that typically present during childhood, when vision is still developing. They are sufficiently common that they should be included in the differential diagnosis of visual loss in pediatric patients. Diagnosis is secured by a combination of clinical findings, optical coherence tomography (OCT) imaging, and genetic testing. Early diagnosis promotes optimal management. While there is currently no definitive cure for these conditions, therapeutic modalities under investigation include pharmacologic treatment, gene therapy, and stem cell transplantation. PMID:28941524

Interventions for Age-Related Macular Degeneration: Are Practice Guidelines Based on Systematic Reviews?

PubMed Central

Lindsley, Kristina; Li, Tianjing; Ssemanda, Elizabeth; Virgili, Gianni; Dickersin, Kay

2016-01-01

Topic Are existing systematic reviews of interventions for age-related macular degeneration incorporated into clinical practice guidelines? Clinical relevance High-quality systematic reviews should be used to underpin evidence-based clinical practice guidelines and clinical care. We have examined the reliability of systematic reviews of interventions for age-related macular degeneration (AMD) and described the main findings of reliable reviews in relation to clinical practice guidelines. Methods Eligible publications are systematic reviews of the effectiveness of treatment interventions for AMD. We searched a database of systematic reviews in eyes and vision and employed no language or date restrictions; the database is up-to-date as of May 6, 2014. Two authors independently screened records for eligibility and abstracted and assessed the characteristics and methods of each review. We classified reviews as “reliable” when they reported eligibility criteria, comprehensive searches, appraisal of methodological quality of included studies, appropriate statistical methods for meta-analysis, and conclusions based on results. We mapped treatment recommendations from the American Academy of Ophthalmology Preferred Practice Patterns (AAO PPP) for AMD to the identified systematic reviews and assessed whether any reliable systematic review was cited or could have been cited to support each treatment recommendation. Results Of 1,570 systematic reviews in our database, 47 met our inclusion criteria. Most of the systematic reviews targeted neovascular AMD and investigated anti-vascular endothelial growth factor (anti-VEGF) interventions, dietary supplements or photodynamic therapy. We classified over two-thirds (33/47) of the reports as reliable. The quality of reporting varied, with criteria for reliable reporting met more often for Cochrane reviews and for reviews whose authors disclosed conflicts of interest. Although most systematic reviews were reliable, anti

Management of neovascular age-related macular degeneration: current state-of-the-art care for optimizing visual outcomes and therapies in development

PubMed Central

Agarwal, Aniruddha; Rhoades, William R; Hanout, Mostafa; Soliman, Mohamed Kamel; Sarwar, Salman; Sadiq, Mohammad Ali; Sepah, Yasir Jamal; Do, Diana V; Nguyen, Quan Dong

2015-01-01

Contemporary management of neovascular age-related macular degeneration (AMD) has evolved significantly over the last few years. The goal of treatment is shifting from merely salvaging vision to maintaining a high quality of life. There have been significant breakthroughs in the identification of viable drug targets and gene therapies. Imaging tools with near-histological precision have enhanced our knowledge about pathophysiological mechanisms that play a role in vision loss due to AMD. Visual, social, and vocational rehabilitation are all important treatment goals. In this review, evidence from landmark clinical trials is summarized to elucidate the optimum modern-day management of neovascular AMD. Therapeutic strategies currently under development, such as gene therapy and personalized medicine, are also described. PMID:26089632

KUS121, an ATP regulator, mitigates chorioretinal pathologies in animal models of age-related macular degeneration.

PubMed

Muraoka, Yuki; Iida, Yuto; Ikeda, Hanako O; Iwai, Sachiko; Hata, Masayuki; Iwata, Takeshi; Nakayama, Mao; Shimozawa, Nobuhiro; Katakai, Yuko; Kakizuka, Akira; Yoshimura, Nagahisa; Tsujikawa, Akitaka

2018-05-01

Age-related macular degeneration (AMD) is a leading cause of blindness among elderly people. The appearance of drusen is a clinical manifestation and a harbinger of both exudative and atrophic AMD. Recently, antibody-based medicines have been used to treat the exudative type. However, they do not restore good vision in patients. Moreover, no effective treatment is available for atrophic AMD. We have created small chemicals (Kyoto University Substances; KUSs) that act as ATP regulators inside cells. In the present study, we examined the in vivo efficacy of KUS121 in C-C chemokine receptor type 2-deficient mice, a mouse model of AMD. Systemic administration of KUS121 prevented or reduced drusen-like lesions and endoplasmic reticulum stress, and then substantially mitigated chorioretinal pathologies with significant preservation of visual function. Additionally, we confirmed that long-term oral administration of KUS121 caused no systemic complications in drusen-affected monkeys. ATP regulation by KUSs may represent a novel strategy in the treatment of drusen and prevention of disease progression in AMD.

Ranibizumab (Lucentis) in neovascular age-related macular degeneration: evidence from clinical trials.

PubMed

Mitchell, P; Korobelnik, J-F; Lanzetta, P; Holz, F G; Prünte, C; Schmidt-Erfurth, U; Tano, Y; Wolf, S

2010-01-01

Neovascular age-related macular degeneration (AMD) has a poor prognosis if left untreated, frequently resulting in legal blindness. Ranibizumab is approved for treating neovascular AMD. However, further guidance is needed to assist ophthalmologists in clinical practice to optimise treatment outcomes. An international retina expert panel assessed evidence available from prospective, multicentre studies evaluating different ranibizumab treatment schedules (ANCHOR, MARINA, PIER, SAILOR, SUSTAIN and EXCITE) and a literature search to generate evidence-based and consensus recommendations for treatment indication and assessment, retreatment and monitoring. Ranibizumab is indicated for choroidal neovascular lesions with active disease, the clinical parameters of which are outlined. Treatment initiation with three consecutive monthly injections, followed by continued monthly injections, has provided the best visual-acuity outcomes in pivotal clinical trials. If continued monthly injections are not feasible after initiation, a flexible strategy appears viable, with monthly monitoring of lesion activity recommended. Initiation regimens of fewer than three injections have not been assessed. Continuous careful monitoring with flexible retreatment may help avoid vision loss recurring. Standardised biomarkers need to be determined. Evidence-based guidelines will help to optimise treatment outcomes with ranibizumab in neovascular AMD.

Detection of Early Loss of Color Vision in Age-Related Macular Degeneration - With Emphasis on Drusen and Reticular Pseudodrusen.

PubMed

Vemala, Roopa; Sivaprasad, Sobha; Barbur, John L

2017-05-01

To evaluate chromatic sensitivity in patients with age-related macular degeneration (AMD) characterized by drusen and reticular pseudodrusen. To investigate whether the severity of color vision loss can distinguish between various stages of AMD and hence be used as an index of progression toward advanced AMD. Chromatic sensitivity was measured by using the Color Assessment and Diagnosis (CAD) test in asymptomatic individuals with early and intermediate AMD and compared to normative data. All study participants had logMAR visual acuity of 0.3 or better. The CAD thresholds measured in eyes with and without reticular pseudodrusen were also compared and related to central macular thickness (CMT). Student's t-test P values < 0.05 were considered significant. All early- and intermediate-AMD eyes (n = 90) had chromatic sensitivity loss in either RG (red/green) or YB (yellow/blue), or both (P < 0.0001) as compared to age-matched normal subjects. The eyes exhibited a range of CAD thresholds affecting both color mechanisms, but YB color thresholds were in general higher than RG thresholds (P < 0.001). Intermediate-AMD patients exhibited large intersubject variability. In general, eyes with reticular pseudodrusen and eyes with CMT < 200 μm had significantly higher CAD thresholds. The anatomic integrity of cone photoreceptors remains relatively unaffected in early and intermediate stages of AMD. The processing of cone signals in the retina can, however, be heavily disrupted with subsequent loss of both YB and RG chromatic sensitivity. The greatest losses were observed in eyes with reticular pseudodrusen.

Efficacy of treat-and-extend regimen with aflibercept for pachychoroid neovasculopathy and Type 1 neovascular age-related macular degeneration.

PubMed

Matsumoto, Hidetaka; Hiroe, Takashi; Morimoto, Masahiro; Mimura, Kensuke; Ito, Arisa; Akiyama, Hideo

2018-03-01

To evaluate the efficacy of intravitreal aflibercept therapy using a treat-and-extend regimen on treatment-naïve pachychoroid neovasculopathy (PNV) and Type 1 neovascular age-related macular degeneration (AMD). We retrospectively studied 42 eyes with PNV and 60 eyes with Type 1 neovascular AMD. We assessed best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), and total number of injections over 2 years. The BCVA and CMT improvements during the 2-year treatment period did not differ significantly between PNV and AMD; however, CCT decreased significantly in PNV than in AMD (P<0.05). Management of PNV required significantly fewer injections than AMD during the 2-year period (P<0.05). There were no significant differences in BCVA, CMT and CCT changes between PNV with and without polypoidal lesions (28 vs. 14 eyes) during the 2 year period. Significantly fewer injections were needed for PNV with polypoidal lesions than for PNV without (P<0.01). There were no significant differences in BCVA, CMT and CCT changes, or in the number of injections during the 2-year treatment period, between AMD with and without polypoidal lesions (30 vs. 30 eyes). Treat-and-extend regimen of intravitreal aflibercept injection may be equally effective in terms of improvement of BCVA and exudative changes both in eyes with PNV and those with Type 1 neovascular AMD requiring fewer injections for the former. Among eyes with PNV, those with polypoidal lesions needed fewer injections than those without polypoidal lesions.

HTRA1 variant confers similar risks to geographic atrophy and neovascular age-related macular degeneration.

PubMed

Cameron, D Joshua; Yang, Zhenglin; Gibbs, Daniel; Chen, Haoyu; Kaminoh, Yuuki; Jorgensen, Adam; Zeng, Jiexi; Luo, Ling; Brinton, Eric; Brinton, Gregory; Brand, John M; Bernstein, Paul S; Zabriskie, Norman A; Tang, Shibo; Constantine, Ryan; Tong, Zongzhong; Zhang, Kang

2007-05-02

Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment in the developed world. The two forms of advanced AMD, geographic atrophy (GA) and choroidal neovascularization (wet AMD), represent two types of degenerative processes in the macula that lead to loss of central vision. Soft confluent drusen, characterized by deposits in macula without visual loss are considered a precursor of advanced AMD. A single nucleotide polymorphism, rs11200638, in the promoter of HTRA1 has been shown to increases the risk for wet AMD. However, its impact on soft confluent drusen and GA or the relationship between them is unclear. To better understand the role the HTRA1 polymorphism plays in AMD subtypes, we genotyped an expanded Utah population with 658 patients having advanced AMD or soft confluent drusen and 294 normal controls and found that the rs11200638 was significantly associated with GA. This association remains significant conditional on LOC387715 rs10490924. In addition, rs11200638 was significantly associated with soft confluent drusen, which are strongly immunolabeled with HTRA1 antibody in an AMD eye with GA similar to wet AMD. Two-locus analyses were performed for CFH Y402H variant at 1q31 and the HTRA1 polymorphism. Together CFH and HTRA1 risk variants increase the odds of having AMD by more than 40 times. These findings expand the role of HTRA1 in AMD. Understanding the underlying molecular mechanism will provide an important insight in pathogenesis of AMD.

Sporadic visual acuity loss in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT).

PubMed

Kim, Benjamin J; Ying, Gui-Shuang; Huang, Jiayan; Levy, Nicole E; Maguire, Maureen G

2014-07-01

To evaluate transient, large visual acuity (VA) decreases, termed sporadic vision loss, during anti-vascular endothelial growth factor treatment for neovascular age-related macular degeneration (AMD). Cohort within a randomized clinical trial. setting: Comparison of Age-Related Macular Degeneration Treatments Trials (CATT). study population: Total of 1185 CATT patients. main outcome measures: Incidence of sporadic vision loss and odds ratio (OR) for association with patient and ocular factors. Sporadic vision loss was a decline of ≥15 letters from the previous visit, followed by a return at the next visit to no more than 5 letters worse than the visit before the VA loss. There were 143 sporadic vision loss events in 122 of 1185 patients (10.3%). Mean VA at 2 years for those with and without sporadic vision loss was 58.5 (∼20/63) and 68.4 (∼20/40) letters, respectively (P < .001). Among patients treated pro re nata, no injection was given for 27.6% (27/98) of sporadic vision loss events. Multivariate analysis demonstrated that baseline predictors for sporadic vision loss included worse baseline VA (OR 2.92, 95% confidence interval [CI]:1.65-5.17 for ≤20/200 compared with ≥20/40), scar (OR 2.21, 95% CI:1.22-4.01), intraretinal foveal fluid on optical coherence tomography (OR 1.80, 95% CI:1.11-2.91), and medical history of anxiety (OR 1.90, 95% CI:1.12-3.24) and syncope (OR 2.75, 95% CI:1.45-5.22). Refraction decreased the likelihood of sporadic vision loss (OR 0.62, 95%CI: 0.42-0.91). Approximately 10% of CATT patients had sporadic vision loss. Baseline predictors included AMD-related factors and factors independent of AMD. These data are relevant for clinicians in practice and those involved in clinical trials. Copyright © 2014 Elsevier Inc. All rights reserved.

Optical Coherence Tomography Reflective Drusen Substructures Predict Progression to Geographic Atrophy in Non-neovascular Age-related Macular Degeneration

PubMed Central

Veerappan, Malini; El-Hage Sleiman, Abdul-Karim M.; Tai, Vincent; Chiu, Stephanie J.; Winter, Katrina P.; Stinnett, Sandra S.; Hwang, Thomas S.; Hubbard, G. Baker; Michelson, Michelle; Gunther, Randall; Wong, Wai T.; Chew, Emily Y.; Toth, Cynthia A.

2016-01-01

Purpose Structural and compositional heterogeneity within drusen, composed of lipid, carbohydrates, and proteins, have been previously described. We sought to detect and define phenotypic patterns of drusen heterogeneity in the form of optical coherence tomography–reflective drusen substructures (ODS) and examine their associations with age-related macular degeneration (AMD)-related features and AMD progression. Design Retrospective analysis in a prospective study. Participants Patients with intermediate AMD (n = 349) enrolled in the multicenter Age-Related Eye Disease Study 2 (AREDS2) ancillary spectral domain optical coherence tomography (SD OCT) study. Methods Baseline SD OCT scans of 1 eye per patient were analyzed for presence of ODS. Cross-sectional and longitudinal associations of ODS presence with AMD-related features visible on SD OCT and color photographs, including drusen volume, geographic atrophy (GA), and preatrophic features, were evaluated for the entire macular region. Similar associations were also made locally within a 0.5-mm diameter region around individual ODS and corresponding control region without ODS in the same eye. Main Outcome Measures Preatrophy SD OCT changes and GA, central GA, and choroidal neovascularization (CNV) from color photographs. Results Four phenotypic subtypes of ODS were defined: low reflective cores, high reflective cores, conical debris, and split drusen. Of the 349 participants, there were 307 eligible eyes and 74 (24%) had at least 1 ODS. The ODS at baseline were associated with (1) greater macular drusen volume at baseline (P < 0.001), (2) development of preatrophic changes at year 2 (P = 0.001–0.01), and (3) development of macular GA (P = 0.005) and preatrophic changes at year 3 (P = 0.002–0.008), but not development of CNV. The ODS at baseline in a local region were associated with (1) presence of preatrophy changes at baseline (P = 0.02-0.03) and (2) development of preatrophy changes at years 2 and 3 within

The use of microperimetry in assessing visual function in age-related macular degeneration.

PubMed

Cassels, Nicola K; Wild, John M; Margrain, Tom H; Chong, Victor; Acton, Jennifer H

Microperimetry is a novel technique for assessing visual function that appears particularly suitable for age-related macular degeneration (AMD). Compared with standard automated perimetry, microperimetry offers several unique features. It simultaneously images the fundus, incorporates an eye-tracking system to correct the stimulus location for fixation loss, and identifies any preferred retinal loci. We identified 52 articles that met the inclusion criteria for a systematic review of microperimetry in the assessment of visual function in AMD. We discuss microperimetry and AMD in relation to disease severity, structural imaging outcomes, other measures of visual function, and evaluation of the efficacy of surgical and/or medical therapies in clinical trials. The evidence for the use of microperimetry in the functional assessment of AMD is encouraging. Disruptions of the ellipsoid zone band and retinal pigment epithelium are clearly associated with reduced differential light sensitivity despite the maintenance of good visual acuity. Reduced differential light sensitivity is also associated with outer segment thinning and retinal pigment epithelium thickening in early AMD and with both a thickening and a thinning of the whole retina in choroidal neovascularization. Microperimetry, however, lacks the robust diffuse and focal loss age-corrected probability analyses associated with standard automated perimetry, and the technique is currently limited by this omission. Copyright © 2017 Elsevier Inc. All rights reserved.

Automated Grading of Age-Related Macular Degeneration From Color Fundus Images Using Deep Convolutional Neural Networks.

PubMed

Burlina, Philippe M; Joshi, Neil; Pekala, Michael; Pacheco, Katia D; Freund, David E; Bressler, Neil M

2017-11-01

Age-related macular degeneration (AMD) affects millions of people throughout the world. The intermediate stage may go undetected, as it typically is asymptomatic. However, the preferred practice patterns for AMD recommend identifying individuals with this stage of the disease to educate how to monitor for the early detection of the choroidal neovascular stage before substantial vision loss has occurred and to consider dietary supplements that might reduce the risk of the disease progressing from the intermediate to the advanced stage. Identification, though, can be time-intensive and requires expertly trained individuals. To develop methods for automatically detecting AMD from fundus images using a novel application of deep learning methods to the automated assessment of these images and to leverage artificial intelligence advances. Deep convolutional neural networks that are explicitly trained for performing automated AMD grading were compared with an alternate deep learning method that used transfer learning and universal features and with a trained clinical grader. Age-related macular degeneration automated detection was applied to a 2-class classification problem in which the task was to distinguish the disease-free/early stages from the referable intermediate/advanced stages. Using several experiments that entailed different data partitioning, the performance of the machine algorithms and human graders in evaluating over 130 000 images that were deidentified with respect to age, sex, and race/ethnicity from 4613 patients against a gold standard included in the National Institutes of Health Age-related Eye Disease Study data set was evaluated. Accuracy, receiver operating characteristics and area under the curve, and kappa score. The deep convolutional neural network method yielded accuracy (SD) that ranged between 88.4% (0.5%) and 91.6% (0.1%), the area under the receiver operating characteristic curve was between 0.94 and 0.96, and kappa coefficient (SD

Forecasting age-related macular degeneration through the year 2050: the potential impact of new treatments.

PubMed

Rein, David B; Wittenborn, John S; Zhang, Xinzhi; Honeycutt, Amanda A; Lesesne, Sarah B; Saaddine, Jinan

2009-04-01

To forecast age-related macular degeneration (AMD) and its consequences in the United States through the year 2050 with different treatment scenarios. We simulated cases of early AMD, choroidal neovascularization (CNV), geographic atrophy (GA), and AMD-attributable visual impairment and blindness with 5 universal treatment scenarios: (1) no treatment; (2) focal laser and photodynamic therapy (PDT) for CNV; (3) vitamin prophylaxis at early-AMD incidence with focal laser/PDT for CNV; (4) no vitamin prophylaxis followed by focal laser treatment for extra and juxtafoveal CNV and anti-vascular endothelial growth factor treatment; and (5) vitamin prophylaxis at early-AMD incidence followed by CNV treatment, as in scenario 4. Cases of early AMD increased from 9.1 million in 2010 to 17.8 million in 2050 across all scenarios. In non-vitamin-receiving scenarios, cases of CNV and GA increased from 1.7 million in 2010 to 3.8 million in 2050 (25% lower in vitamin-receiving scenarios). Cases of visual impairment and blindness increased from 620 000 in 2010 to 1.6 million in 2050 when given no treatment and were 2.4%, 22.0%, 16.9%, and 34.5% lower in scenarios 2, 3, 4, and 5, respectively. Prevalence of AMD will increase substantially by 2050, but the use of new therapies can mitigate its effects.

AMD-like retinopathy associated with intravenous iron

PubMed Central

Song, Delu; Kanu, Levi N.; Li, Yafeng; Kelly, Kristen L.; Bhuyan, Rupak K.; Aleman, Tomas; Morgan, Jessica I. W.; Dunaief, Joshua L.

2016-01-01

Iron accumulation in the retina is associated with the development of age-related macular degeneration (AMD). IV iron is a common method to treat iron deficiency anemia in adults, and its retinal manifestations have not hitherto been identified. To assess whether IV iron formulations can be retina-toxic, we generated a mouse model for iron-induced retinal damage. Male C57BL/6J mice were randomized into groups receiving IV iron-sucrose (+Fe) or 30% sucrose (−Fe). Iron levels in neurosensory retina (NSR), retinal pigment epithelium (RPE), and choroid were assessed using immunofluorescence, quantitative PCR, and the Perls’ iron stain. Iron levels were most increased in the RPE and choroid while levels in the NSR did not differ significantly in +Fe mice compared to controls. Eyes from +Fe mice shared histological features with AMD, including Bruch’s membrane (BrM) thickening with complement C3 deposition, as well as RPE hypertrophy and vacuolization. This focal degeneration correlated with areas with high choroidal iron levels. Ultrastructural analysis provided further detail of the RPE/photoreceptor outer segment vacuolization and Bruch’s membrane thickening. Findings were correlated with a clinical case of a 43-year-old patient who developed numerous retinal drusen, the hallmark of AMD, within 11 months of IV iron therapy. Our results suggest that IV iron therapy may have the potential to induce or exacerbate a form of retinal degeneration. This retinal degeneration shares features with AMD, indicating the need for further study of AMD risk in patients receiving IV iron treatment. PMID:27565570

Assessment of visual distortions in age-related macular degeneration: emergence of new approaches

PubMed Central

Vazquez, Noelia Pitrelli; Knox, Paul C.

2016-01-01

Aims With the arrival of effective treatments for neovascular age-related macular degeneration (nvAMD) there is a need to find improved tests that would allow early detection. Ideally, these tests would allow monitoring of vision by patients themselves from home. The aim of this review is to discuss the available evidence for two recently developed vision tests designed for this purpose: the Preferential Hyperacuity Perimeter (PHP) test and the Radial Shape Discrimination (RSD) test. Methods Articles that investigated detection of nvAMD were reviewed. The methodology of the clinical evidence, where available, was judged for bias and applicability of the results to the general population using the QUADAS-2 quality assessment tool. Results The PHP test has proved to be good at detecting nvAMD but many studies assessed in this review were biased in the selection of patients, restricting the results to only those patients who can use the test and produce reliable results. On the other hand the RSD test is a simple test, well accepted by elderly patients with AMD. However, clinical studies to determine its value in the detection of early signs of nvAMD are still required. Conclusions To date, more studies have investigated the utility of the PHP test compared with the RSD test for detection of nvAMD. Both tests show promise but further evidence is needed to determine the real generalisability of the PHP test and the sensitivity of the RSD test. PMID:27738450

The reduction of serum soluble Flt-1 in patients with neovascular age-related macular degeneration.

PubMed

Uehara, Hironori; Mamalis, Christina; McFadden, Molly; Taggart, Michael; Stagg, Brian; Passi, Samuel; Earle, Phillip; Chakravarthy, Usha; Hogg, Ruth E; Ambati, Balamurali K

2015-01-01

To evaluate serum soluble Flt-1 (sFlt-1) in age-related macular degeneration (AMD) patients. Case-control study. Study involved 56 non-AMD participants, 53 early AMD patients, and 97 neovascular AMD patients from Belfast in Northern Ireland. Serum samples were collected from each patient. Serum sFlt-1 was measured by human sVEGFR1/sFlt-1 ELISA kit. The results were analyzed by Excel and SPSS. Serum sFlt-1 concentration of non-AMD, early AMD, and neovascular AMD were 90.8 ± 2.9 pg/mL (± standard error of the mean), 88.2 ± 2.6 pg/mL, and 79.9 ± 2.2 pg/mL. sFlt-1 from neovascular AMD patients was significantly decreased compared to non-AMD and early AMD patients (ANOVA, P < .01). For each 10-point increase in sFlt-1, the odds for having neovascular AMD compared with non-AMD and neovascular AMD decrease by 27.8%, odds ratio (OR) = 0.722 (95% confidence interval [CI]: 0.588-0.888, P = .002) and 27.0%, OR = 0.730 (95% CI: 0.594-0.898, P = .003), respectively. In patients over 73 years of age, serum sFlt-1 <80 pg/mL was associated with a >6-fold higher risk of neovascular AMD. Reduced serum sFlt-1 differentiates those patients with neovascular AMD from both early AMD and non-AMD participants. In those aged over 73, serum sFlt <80 pg/mL seems to indicate a particularly high risk of neovascular AMD. Our results indicate serum sFlt-1 could be a biomarker for development of neovascular AMD. Copyright © 2015 Elsevier Inc. All rights reserved.

Macrophages Inhibit Neovascularization in a Murine Model of Age-Related Macular Degeneration

PubMed Central

Apte, Rajendra S; Richter, Jennifer; Herndon, John; Ferguson, Thomas A

2006-01-01

Background Age-related macular degeneration (AMD) is the leading cause of blindness in people over 50 y of age in at least three continents. Choroidal neovascularization (CNV) is the process by which abnormal blood vessels develop underneath the retina. CNV develops in 10% of patients with AMD but accounts for up to 90% of the blindness from AMD. Although the precise etiology of CNV in AMD remains unknown, the macrophage component of the inflammatory response, which has been shown to promote tumor growth and support atherosclerotic plaque formation, is thought to stimulate aberrant angiogenesis in blinding eye diseases. The current theory is that macrophage infiltration promotes the development of neovascularization in CNV. Methods and Findings We examined the role of macrophages in a mouse model of CNV. IL-10 −/− mice, which have increased inflammation in response to diverse stimuli, have significantly reduced CNV with increased macrophage infiltrates compared to wild type. Prevention of macrophage entry into the eye promoted neovascularization while direct injection of macrophages significantly inhibited CNV. Inhibition by macrophages was mediated by the TNF family death molecule Fas ligand (CD95-ligand). Conclusions Immune vascular interactions can be highly complex. Normal macrophage function is critical in controlling pathologic neovascularization in the eye. IL-10 regulates macrophage activity in the eye and is an attractive therapeutic target in order to suppress or inhibit CNV in AMD that can otherwise lead to blindness. PMID:16903779

Automated detection of exudative age-related macular degeneration in spectral domain optical coherence tomography using deep learning.

PubMed

Treder, Maximilian; Lauermann, Jost Lennart; Eter, Nicole

2018-02-01

Our purpose was to use deep learning for the automated detection of age-related macular degeneration (AMD) in spectral domain optical coherence tomography (SD-OCT). A total of 1112 cross-section SD-OCT images of patients with exudative AMD and a healthy control group were used for this study. In the first step, an open-source multi-layer deep convolutional neural network (DCNN), which was pretrained with 1.2 million images from ImageNet, was trained and validated with 1012 cross-section SD-OCT scans (AMD: 701; healthy: 311). During this procedure training accuracy, validation accuracy and cross-entropy were computed. The open-source deep learning framework TensorFlow™ (Google Inc., Mountain View, CA, USA) was used to accelerate the deep learning process. In the last step, a created DCNN classifier, using the information of the above mentioned deep learning process, was tested in detecting 100 untrained cross-section SD-OCT images (AMD: 50; healthy: 50). Therefore, an AMD testing score was computed: 0.98 or higher was presumed for AMD. After an iteration of 500 training steps, the training accuracy and validation accuracies were 100%, and the cross-entropy was 0.005. The average AMD scores were 0.997 ± 0.003 in the AMD testing group and 0.9203 ± 0.085 in the healthy comparison group. The difference between the two groups was highly significant (p < 0.001). With a deep learning-based approach using TensorFlow™, it is possible to detect AMD in SD-OCT with high sensitivity and specificity. With more image data, an expansion of this classifier for other macular diseases or further details in AMD is possible, suggesting an application for this model as a support in clinical decisions. Another possible future application would involve the individual prediction of the progress and success of therapy for different diseases by automatically detecting hidden image information.

Observation of curative effect of intravitreal injection of conbercept in wet age-related macular degeneration: Optical coherence tomography analysis after injection.

PubMed

Yang, Wen; Tan, Ying; Li, Chaowei; Liu, Yi; Lu, Guohua

2018-04-01

To observe the clinical efficacy of intravitreal injection of conbercept in the treatment of wet age-related macular degeneration (wAMD), optical coherence tomography (OCT) and the best corrected visual acuity (BCVA) was observed to measure the changes of anatomical changes of central macular thickness (CMT) and the area and volume of retinal pigment epithelium (RPE) uplift. Fifteen patients (15 eyes) with wet AMD were enrolled in this study. All patients underwent intravitreal injection of conbercept of 0.05 mL once. After 1 week, 1 month, and 3 months, OCT and BCVA were used to examine and to compare with the preoperative and postoperative central macular thickness and RPE uplift area. BCVA (median) increased respectively from 0.12 ± 0.13 to 0.21 ± 0.15 at 1 week, to 0.90 ± 0.25 at 1 month, to 0.38 ± 0.17 at 3 months (p < .001). The thickness of central macular decreased from 500 ± 25 μm to 256 ± 19 μm, 221 ± 29 μm, and 215 ± 14 μm, respectively. The normal physiological structure and stratification of the macular area were clear gradually. Conbercept treatment of wet AMD can significantly improve visual acuity, after 1 month up to the plateau, 3 months of continuous drug injection can make the vision maintained at a high stage, and macular retinal normal structural morphology recovery is good, the treatment has no obvious adverse reactions, and with good security. © 2018 Wiley Periodicals, Inc.

Inferring diagnosis and trajectory of wet age-related macular degeneration from OCT imagery of retina

NASA Astrophysics Data System (ADS)

Irvine, John M.; Ghadar, Nastaran; Duncan, Steve; Floyd, David; O'Dowd, David; Lin, Kristie; Chang, Tom

2017-03-01

Quantitative biomarkers for assessing the presence, severity, and progression of age-related macular degeneration (AMD) would benefit research, diagnosis, and treatment. This paper explores development of quantitative biomarkers derived from OCT imagery of the retina. OCT images for approximately 75 patients with Wet AMD, Dry AMD, and no AMD (healthy eyes) were analyzed to identify image features indicative of the patients' conditions. OCT image features provide a statistical characterization of the retina. Healthy eyes exhibit a layered structure, whereas chaotic patterns indicate the deterioration associated with AMD. Our approach uses wavelet and Frangi filtering, combined with statistical features that do not rely on image segmentation, to assess patient conditions. Classification analysis indicates clear separability of Wet AMD from other conditions, including Dry AMD and healthy retinas. The probability of correct classification of was 95.7%, as determined from cross validation. Similar classification analysis predicts the response of Wet AMD patients to treatment, as measured by the Best Corrected Visual Acuity (BCVA). A statistical model predicts BCVA from the imagery features with R2 = 0.846. Initial analysis of OCT imagery indicates that imagery-derived features can provide useful biomarkers for characterization and quantification of AMD: Accurate assessment of Wet AMD compared to other conditions; image-based prediction of outcome for Wet AMD treatment; and features derived from the OCT imagery accurately predict BCVA; unlike many methods in the literature, our techniques do not rely on segmentation of the OCT image. Next steps include larger scale testing and validation.

Effect of Soluble Inducible Costimulator Level and Its Polymorphisms on Age-Related Macular Degeneration

PubMed Central

Yu, Honghua; Zou, Xiulan; Peng, Lianghong; Wang, Yong; Zhang, Chu

2013-01-01

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly population. Evidence has shown that the human immune system may play critical roles in this disease. Inducible costimulator (ICOS) promotes T-cell activation, differentiation, and T:B-cell interactions. The aim of the study was to understand the effect of ICOS on the development of AMD from genetic polymorphism perspective and serum level perspective. Two ICOS polymorphisms, rs10183087A/C and rs10932037C/T, were tested in 223 AMD cases and 262 healthy controls. The serum level of soluble ICOS (sICOS) was compared among subjects with different genotypes, as well as between AMD patients and controls. Data showed that prevalence of rs10183087CC genotype was significantly increased in AMD than in controls (p=0.001). Function analysis revealed that subjects carrying rs10183087CC genotype had higher serum levels of sICOS than those with AA or AC genotypes (p<0.05). When we compared serum levels of sICOS between cases and controls, results showed that AMD patients had significantly increased sICOS levels than healthy donors (p<0.05). Also, wet type cases were observed to have higher sICOS levels than cases with dry type (p<0.05). These data suggested ICOS polymorphism could affect the susceptibility to AMD by elevating protein expression, and serum levels of sICOS may be closed correlated with the development and progression of this disease. PMID:24083358

The Age-Related Eye Disease 2 Study: Micronutrients in the Treatment of Macular Degeneration.

PubMed

Gorusupudi, Aruna; Nelson, Kelly; Bernstein, Paul S

2017-01-01

Age-related macular degeneration (AMD) is one of the leading causes of vision loss in the elderly. With an increasingly aged population worldwide, the need for the prevention of AMD is rising. Multiple studies investigating AMD with the use of animal models and cell culture have identified oxidative stress-related retinal damage as an important contributing factor. In general, diet is an excellent source of the antioxidants, vitamins, and minerals necessary for healthy living; moreover, the general public is often receptive to recommendations made by physicians and health care workers regarding diet and supplements as a means of empowering themselves to avoid common and worrisome ailments such as AMD, which has made epidemiologists and clinicians enthusiastic about dietary intervention studies. A wide variety of nutrients, such as minerals, vitamins, ω-3 (n-3) fatty acids, and various carotenoids, have been associated with reducing the risk of AMD. Initial results from the Age-Related Eye Disease Study (AREDS) indicated that supplementation with antioxidants (β-carotene and vitamins C and E) and zinc was associated with a reduced risk of AMD progression. The AREDS2 follow-up study, designed to improve upon the earlier formulation, tested the addition of lutein, zeaxanthin, and ω-3 fatty acids. In this review, we examine the science behind the nutritional factors included in these interventional studies and the reasons for considering their inclusion to lower the rate of AMD progression. © 2017 American Society for Nutrition.

Physical Activity and Age-related Macular Degeneration: A Systematic Literature Review and Meta-analysis.

PubMed

McGuinness, Myra B; Le, Jerome; Mitchell, Paul; Gopinath, Bamini; Cerin, Ester; Saksens, Nicole T M; Schick, Tina; Hoyng, Carel B; Guymer, Robyn H; Finger, Robert P

2017-08-01

To better understand the association, in a white population, of physical activity and age-related macular degeneration (AMD)-the main cause of irreversible severe vision loss in developed countries-given the suggestion that a healthy lifestyle may assist in delaying the onset and progression of AMD. Systematic review and meta-analysis. Medline, EMBASE, and Google Scholar were systematically searched for studies up to May 2015. Reference lists of published articles were hand searched and study authors were contacted to provide additional data. Those in the lowest category of activity in each study were compared with all other participants to assess the association between physical activity and both early and late AMD using random-effects meta-analysis. Nine studies (subject age range 30-97 years) were included in the meta-analysis. Physical activity was found to have a protective association with both early AMD (8 studies, n = 38 112, odds ratio (OR) 0.92, 95% confidence interval [CI] 0.86-0.98) and late AMD (7 studies, n = 28 854, OR 0.59, 95% CI 0.49-0.72). Physical activity is associated with lower odds of early and late AMD in white populations. These findings have important implications, reinforcing the public health message of staying active throughout life. However, further longitudinal studies are required to confirm and further characterize a protective effect of physical activity on the onset and/or progression of AMD. Copyright © 2017 Elsevier Inc. All rights reserved.

Juvenile Macular Degenerations.

PubMed

Altschwager, Pablo; Ambrosio, Lucia; Swanson, Emily A; Moskowitz, Anne; Fulton, Anne B

2017-05-01

In this article, we review the following 3 common juvenile macular degenerations: Stargardt disease, X-linked retinoschisis, and Best vitelliform macular dystrophy. These are inherited disorders that typically present during childhood, when vision is still developing. They are sufficiently common that they should be included in the differential diagnosis of visual loss in pediatric patients. Diagnosis is secured by a combination of clinical findings, optical coherence tomography imaging, and genetic testing. Early diagnosis promotes optimal management. Although there is currently no definitive cure for these conditions, therapeutic modalities under investigation include pharmacologic treatment, gene therapy, and stem cell transplantation. Copyright © 2017 Elsevier Inc. All rights reserved.

Age-related macular degeneration changes the processing of visual scenes in the brain.

PubMed

Ramanoël, Stephen; Chokron, Sylvie; Hera, Ruxandra; Kauffmann, Louise; Chiquet, Christophe; Krainik, Alexandre; Peyrin, Carole

2018-01-01

In age-related macular degeneration (AMD), the processing of fine details in a visual scene, based on a high spatial frequency processing, is impaired, while the processing of global shapes, based on a low spatial frequency processing, is relatively well preserved. The present fMRI study aimed to investigate the residual abilities and functional brain changes of spatial frequency processing in visual scenes in AMD patients. AMD patients and normally sighted elderly participants performed a categorization task using large black and white photographs of scenes (indoors vs. outdoors) filtered in low and high spatial frequencies, and nonfiltered. The study also explored the effect of luminance contrast on the processing of high spatial frequencies. The contrast across scenes was either unmodified or equalized using a root-mean-square contrast normalization in order to increase contrast in high-pass filtered scenes. Performance was lower for high-pass filtered scenes than for low-pass and nonfiltered scenes, for both AMD patients and controls. The deficit for processing high spatial frequencies was more pronounced in AMD patients than in controls and was associated with lower activity for patients than controls not only in the occipital areas dedicated to central and peripheral visual fields but also in a distant cerebral region specialized for scene perception, the parahippocampal place area. Increasing the contrast improved the processing of high spatial frequency content and spurred activation of the occipital cortex for AMD patients. These findings may lead to new perspectives for rehabilitation procedures for AMD patients.

Plasma levels of hypoxia-regulated factors in patients with age-related macular degeneration.

PubMed

Ioanna, Zygoula; Christian, Schori; Christian, Grimm; Daniel, Barthelmes

2018-02-01

Various hypoxia-related proteins are differentially expressed in the retina and secreted to the vitreous and/or aqueous humor of patients affected by dry or neovascular age-related macular degeneration (nAMD). To determine whether these conditions alter concentrations of cytokines also in the systemic circulation, we measured plasma levels of six hypoxia-related proteins. Plasma was prepared from EDTA blood that was collected from patients affected by dry AMD (n = 5), nAMD (n = 11), proliferative diabetic retinopathy (PDR; n = 9), and patients with an epiretinal membrane (ERM; n = 11). ERM samples served as negative controls, PDR samples as positive controls. Protein concentrations of vascular endothelial growth factor (VEGF), erythropoietin (EPO), angiopoietin-like 4 (ANGPTL4), placental growth factor (PlGF), tumor necrosis factor alpha (TNF-α), and pigment epithelium-derived factor (PEDF) were determined by enzyme-linked immunosorbent assay (ELISA). The concentration of PlGF was significantly increased in plasma of patients affected by nAMD. Although no statistically significant differences were found for EPO, ANGPTL4, PlGF, TNF-α, and PEDF, the mean concentration of VEGF was lowest in the nAMD group. Plasma concentrations of the six factors did not correlate with gender or age of patients. nAMD may increase plasma concentrations of PlGF, making it a candidate as a biomarker for the neovascular form of AMD. Other factors, however, were not differentially regulated, suggesting that their systemic concentrations are not generally increased in hypoxia-related retinal diseases.

Measurement of Perceived Stress in Age-Related Macular Degeneration.

PubMed

Dougherty, Bradley E; Cooley, San-San L; Davidorf, Frederick H

2017-03-01

To validate the Perceived Stress Scale (PSS) in patients with age-related macular degeneration (AMD) using Rasch analysis. Study participants with AMD were recruited from the retina service of the Department of Ophthalmology at the Ohio State University during clinical visits for treatment or observation. Visual acuity with habitual distance correction was assessed. A 10-item version of the PSS was administered in large print or by reading the items to the patient. Rasch analysis was used to investigate the measurement properties of the PSS, including fit to the model, ability to separate between people with different levels of perceived stress, category response structure performance, and unidimensionality. A total of 137 patients with a diagnosis of AMD were enrolled. The mean (±SD) age of participants was 82 ± 9 years. Fifty-four percent were female. Median Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity of the better eye was 65 letters (Snellen 20/50), with a range of approximately 20/800 to 20/15. Forty-seven percent of participants were receiving an anti-VEGF injection on the day of the study visit. The response category structure was appropriate. One item, "How often have you felt confident in your ability to handle your personal problems?" was removed due to poor fit statistics. The remaining nine items showed good fit to the model, acceptable measurement precision as assessed by the Rasch person separation statistic, and unidimensionality. There was some evidence of differential item functioning by age and visual acuity. The Perceived Stress Scale demonstrated acceptable measurement properties and may be useful for the measurement of perceived stress in patients with AMD.

NATURAL COURSE OF PATIENTS DISCONTINUING TREATMENT FOR AGE-RELATED MACULAR DEGENERATION AND FACTORS ASSOCIATED WITH VISUAL PROGNOSIS.

PubMed

Kim, Jae Hui; Chang, Young Suk; Kim, Jong Woo

2017-12-01

To evaluate the 24-month natural course of visual changes in patients discontinuing treatment despite persistent or recurrent fluid and factors predictive of visual prognosis. This retrospective, observational study included 35 patients (35 eyes) who initially received anti-vascular endothelial growth factor treatment for neovascular age-related macular degeneration (AMD), but discontinued treatment despite persistent or recurrent fluid. The best-corrected visual acuity (BCVA) at treatment discontinuation was determined and compared with the 24-month BCVA, which was then compared between polypoidal choroidal vasculopathy and other neovascular age-related macular degeneration subtypes. Baseline characteristics predictive of visual outcome and the degree of visual change were also analyzed. The mean number of anti-vascular endothelial growth factor injections before treatment discontinuation was 4.0 ± 1.6. The mean logarithm of minimal angle of resolution of BCVA at treatment discontinuation and that at 24 months were 1.02 ± 0.20 (Snellen equivalents = 20/209) and 1.60 ± 0.56 (20/796), respectively (P < 0.001). The 24-month BCVA was not different between polypoidal choroidal vasculopathy and other neovascular age-related macular degeneration subtypes (P = 0.803). The type of fluid (intraretinal fluid vs. no intraretinal fluid) was predictive of 24-month BCVA (P = 0.004) and the degree of changes in BCVA (P = 0.043). Marked deterioration in visual acuity was noted in patients discontinuing treatment, regardless of neovascular age-related macular degeneration subtypes. The presence of intraretinal fluid was associated with worse visual prognosis, suggesting that patients with intraretinal fluid should be strongly warned about their poor prognosis before they decide to discontinue treatment.

Parainflammation, chronic inflammation, and age-related macular degeneration.

PubMed

Chen, Mei; Xu, Heping

2015-11-01

Inflammation is an adaptive response of the immune system to noxious insults to maintain homeostasis and restore functionality. The retina is considered an immune-privileged tissue as a result of its unique anatomic and physiologic properties. During aging, the retina suffers from a low-grade chronic oxidative insult, which sustains for decades and increases in level with advancing age. As a result, the retinal innate-immune system, particularly microglia and the complement system, undergoes low levels of activation (parainflammation). In many cases, this parainflammatory response can maintain homeostasis in the healthy aging eye. However, in patients with age-related macular degeneration, this parainflammatory response becomes dysregulated and contributes to macular damage. Factors contributing to the dysregulation of age-related retinal parainflammation include genetic predisposition, environmental risk factors, and old age. Dysregulated parainflammation (chronic inflammation) in age-related macular degeneration damages the blood retina barrier, resulting in the breach of retinal-immune privilege, leading to the development of retinal lesions. This review discusses the basic principles of retinal innate-immune responses to endogenous chronic insults in normal aging and in age-related macular degeneration and explores the difference between beneficial parainflammation and the detrimental chronic inflammation in the context of age-related macular degeneration. © Society for Leukocyte Biology.

Oxidative stress, innate immunity, and age-related macular degeneration

PubMed Central

Shaw, Peter X.; Stiles, Travis; Douglas, Christopher; Ho, Daisy; Fan, Wei; Du, Hongjun; Xiao, Xu

2016-01-01

Age-related macular degeneration (AMD) is a leading cause of vision loss affecting tens of millions of elderly worldwide. Early AMD is characterized by the appearance of soft drusen, as well as pigmentary changes in the retinal pigment epithelium (RPE). These soft, confluent drusen can progress into two forms of advanced AMD: geographic atrophy (GA, or dry AMD) or choroidal neovascularization (CNV, or wet AMD). Both forms of AMD result in a similar clinical progression in terms of loss of central vision. The exact mechanism for developing early AMD, as well as triggers responsible for progressing to advanced stage of disease, is still largely unknown. However, significant evidence exists demonstrating a complex interplay of genetic and environmental factors as causes of AMD progression. Multiple genes and/or single nucleotide polymorphisms (SNPs) have been found associated with AMD, including various genes involved in the complement pathway, lipid metabolism and extracellular matrix (ECM) remodeling. Of the known genetic contributors to disease risk, the CFH Y402H and HTRA1/ARMS polymorphisms contribute to more than 50% of the genetic risk for AMD. Environmentally, oxidative stress plays a critical role in many aging diseases including cardiovascular disease, cancer, Alzheimer’s disease and AMD. Due to the exposure to sunlight and high oxygen concentration, the oxidative stress burden is higher in the eye than other tissues, which can be further complicated by additional oxidative stressors such as smoking. Increasingly, evidence is accumulating suggesting that functional abnormalities of the innate immune system incurred via high risk genotypes may be contributing to the pathogenesis of AMD by altering the inflammatory homeostasis in the eye, specifically in the handling of oxidation products. As the eye in non-pathological instances maintains a low level of inflammation despite the presence of a relative abundance of potentially inflammatory molecules, we have

Education, socio-economic status and age-related macular degeneration in Asians: the Singapore Malay Eye Study.

PubMed

Cackett, P; Tay, W T; Aung, T; Wang, J J; Shankar, A; Saw, S M; Mitchell, P; Wong, T Y

2008-10-01

Low socio-economic status is increasingly being identified as a risk marker for chronic diseases, but few studies have investigated the link between socio-economic factors and age-related macular degeneration (AMD). The present study aimed to assess the association between socio-economic status and the prevalence of AMD. A population-based cross-sectional study of 3280 (78.7% response rate) Malay adults aged 40-80 years residing in 15 south-western districts of Singapore. AMD was graded from retinal photographs at a central reading centre using the modified Wisconsin AMD scale. Early and late AMD signs were graded from retinal photographs following the Wisconsin grading system. Socio-economic status including education, housing type and income were determined from a detailed interview. Of the participants, 3265 had photographs of sufficient quality for grading of AMD. Early AMD was present in 168 (5.1%) and late AMD in 21 (0.6%). After adjusting for age, gender, smoking, hypertension, diabetes and body mass index, participants with lower educational levels were significantly more likely to have early AMD (multivariate OR 2.2, 95% CI 1.2 to 4.0). This association was stronger in persons who had never smoked (multivariate OR 3.6, 95% confidence CI 1.4 to 9.4). However, no association with housing type or income was seen. Low educational level is associated with a higher prevalence of early AMD signs in our Asian population, independent of age, cardiovascular risk factors and cigarette smoking.

An Eye on Age-Related Macular Degeneration: The Role of MicroRNAs in Disease Pathology.

PubMed

Berber, Patricia; Grassmann, Felix; Kiel, Christina; Weber, Bernhard H F

2017-02-01

Age-related macular degeneration (AMD) is the primary cause of blindness in developed countries, and is the third leading cause worldwide. Emerging evidence suggests that beside environmental and genetic factors, epigenetic mechanisms, such as microRNA (miRNA) regulation of gene expression, are relevant to AMD providing an exciting new avenue for research and therapy. MiRNAs are short, non-coding RNAs thought to be imperative for coping with cellular stress. Numerous studies have analyzed miRNA dysregulation in AMD patients, although with varying outcomes. Four studies which profiled dysregulated circulating miRNAs in AMD yielded unique sets, and there is only minimal overlap in ocular miRNA profiling of AMD. Mouse models of AMD, including oxygen-induced retinopathy and laser-induced choroidal neovascularization, showed similarities to some extent with miRNA patterns in AMD. For example, miR-146a is an extensively researched miRNA thought to modulate inflammation, and was found to be upregulated in AMD mice and cellular systems, but also in human AMD retinae and vitreous humor. Similarly, mir-17, miR-125b and miR-155 were dysregulated in multiple AMD mouse models as well as in human AMD plasma or retinae. These miRNAs are thought to regulate angiogenesis, apoptosis, phagocytosis, and inflammation. A promising avenue of research is the modulation of such miRNAs, as the phenotype of AMD mice could be ameliorated with antagomirs or miRNA-mimic treatment. However, before meaningful strides can be made to develop miRNAs as a diagnostic or therapeutic tool, reproducible miRNA profiles need to be established for the various clinical outcomes of AMD.

Vitamin D Status and Early Age-Related Macular Degeneration in Postmenopausal Women

PubMed Central

Millen, Amy E.; Voland, Rick; Sondel, Sherie A.; Parekh, Niyati; Horst, Ronald L.; Wallace, Robert B.; Hageman, Gregory S.; Chappell, Rick; Blodi, Barbara A.; Klein, Michael L.; Gehrs, Karen M.; Sarto, Gloria E.; Mares, Julie A.

2010-01-01

Objective The relationship between serum 25-hydroxyvitamin D (25(OH)D) concentrations (nmol/L) and the prevalence of early age-related macular degeneration (AMD) was investigated among participants of the Carotenoids in Age-Related Eye Disease Study. Methods Stereoscopic fundus photographs, taken from 2001–2004, assessed AMD status. Baseline (1994–1998) serum samples were available for 25(OH)D assays in 1,313 women with complete ocular and risk factor data. Odds ratios (ORs) and 95% confidence intervals (CIs) for early AMD (n=241), among 1,287 without advanced disease, were estimated with logistic regression and adjusted for age, smoking, iris pigmentation, family history of AMD, cardiovascular disease, diabetes, and hormone therapy use. Results In multivariate models, no significant relationship was observed between early AMD and 25(OH)D (OR for quintile 5 vs. 1=0.79, 95% CI=0.50–1.24; p for trend=0.47). A significant age interaction (p=0.0025) suggested selective mortality bias in women ≥75 years: serum 25(OH)D was associated with decreased odds of early AMD in women <75 years (n=968) and increased odds in women ≥75 years (n=319) (OR for quintile 5 vs. 1=0.52, 95% CI=0.29–0.91; p for trend=0.02 and 1.76, 95% CI=0.77–4.13; p for trend=0.05, respectively). Further adjustment for body mass index and recreational physical activity, predictors of 25(OH)D, attenuated the observed association in women <75 years. Additionally, among women <75 years, intake of vitamin D from foods and supplements was related to decreased odds of early AMD in multivariate models; no relationship was observed with self-reported time spent in direct sunlight. Conclusions High serum 25(OH)D concentrations may protect against early AMD in women <75 years. PMID:21482873

The Relationship of Major American Dietary Patterns to Age-related Macular Degeneration

PubMed Central

Chiu, Chung-Jung; Chang, Min-Lee; Zhang, Fang Fang; Li, Tricia; Gensler, Gary; Schleicher, Molly; Taylor, Allen

2014-01-01

PURPOSE We hypothesized that major American dietary patterns are associated with age-related macular degeneration (AMD) risk. DESIGN Cross-sectional study METHODS 8,103 eyes from 4,088 eligible participants in the baseline Age-Related Eye Disease Study (AREDS) were classified into control (n=2,739), early AMD (n=4,599), and advanced AMD (n=765) by AREDS AMD Classification System. Food consumption data were collected by a 90-item food frequency questionnaire. RESULTS Two major dietary patterns were identified by factor (principle component) analysis based on 37 food groups and named Oriental and Western patterns. The Oriental pattern was characterized by higher intake of vegetables, legumes, fruit, whole grains, tomatoes, and seafood. The Western pattern was characterized by higher intake of red meat, processed meat, high-fat dairy products, French fries, refined grains, and eggs. We ranked our participants according to how closely their diets line up with the two patterns by calculating the two factor scores for each participant. For early AMD, multivariate-adjusted odds ratio (OR) from generalized estimating equation logistic analysis comparing the highest to lowest quintile of the Oriental pattern score was ORE5O=0.74 (95% confidence interval (CI): 0.59–0.91; Ptrend=0.01), and the OR comparing the highest to lowest quintile of the Western pattern score was ORE5W=1.56 (1.18–2.06; Ptrend=0.01). For advanced AMD, the ORA5O was 0.38 (0.27–0.54; Ptrend<0.0001), and the ORA5W was 3.70 (2.31–5.92; Ptrend<0.0001). CONCLUSIONS Our data indicate that overall diet is significantly associated with the odds of AMD and that dietary management as an AMD prevention strategy warrants further study. PMID:24792100

The relationship of major American dietary patterns to age-related macular degeneration.

PubMed

Chiu, Chung-Jung; Chang, Min-Lee; Zhang, Fang Fang; Li, Tricia; Gensler, Gary; Schleicher, Molly; Taylor, Allen

2014-07-01

We hypothesized that major American dietary patterns are associated with risk for age-related macular degeneration (AMD). Cross-sectional study. We classified 8103 eyes in 4088 eligible participants in the baseline Age-Related Eye Disease Study (AREDS). They were classified into control (n = 2739), early AMD (n = 4599), and advanced AMD (n = 765) by the AREDS AMD Classification System. Food consumption data were collected by using a 90-item food frequency questionnaire. Two major dietary patterns were identified by factor (principal component) analysis based on 37 food groups and named Oriental and Western patterns. The Oriental pattern was characterized by higher intake of vegetables, legumes, fruit, whole grains, tomatoes, and seafood. The Western pattern was characterized by higher intake of red meat, processed meat, high-fat dairy products, French fries, refined grains, and eggs. We ranked our participants according to how closely their diets line up with the 2 patterns by calculating the 2 factor scores for each participant. For early AMD, multivariate-adjusted odds ratio (OR) from generalized estimating equation logistic analysis comparing the highest to lowest quintile of the Oriental pattern score was ORE5O = 0.74 (95% confidence interval (CI): 0.59-0.91; Ptrend =0.01), and the OR comparing the highest to lowest quintile of the Western pattern score was ORE5W = 1.56 (1.18-2.06; Ptrend = 0.01). For advanced AMD, the ORA5O was 0.38 (0.27-0.54; Ptrend < 0.0001), and the ORA5W was 3.70 (2.31-5.92; Ptrend < 0.0001). Our data indicate that overall diet is significantly associated with the odds of AMD and that dietary management as an AMD prevention strategy warrants further study. Copyright © 2014 Elsevier Inc. All rights reserved.

Association of neovascular age-related macular degeneration with month and season of birth in Italy

PubMed Central

Longo, Antonio; Casuccio, Alessandra; Pani, Luca; Avitabile, Teresio; Cillino, Salvatore; Uva, Maurizio G.; Bonfiglio, Vincenza; Russo, Andrea; Parisi, Guglielmo; Cennamo, Gilda; Furino, Claudio; Parravano, Mariacristina; Xoxi, Entela; Reibaldi, Michele

2017-01-01

In order to investigate the influence of season and month of birth on the risk of neovascular age-related macular degeneration (n-AMD) in Italy, we evaluated the month birth and sex of all patients, recorded in the anti-vascular endothelial growth factor (VEGF) monitoring registry of the Italian Medicines Agency, born between 1925–1944, who received intravitreal anti-VEGF injections for n-AMD between January 1, 2013 and July 29, 2015. The numbers of all births in Italy in the same years, extracted from the Italian National Institute of Statistics, were used to calculate the expected number of n-AMD cases. Overall, 45,845 patients (19,207 men, 26,638 women) received intravitreal anti-VEGF for n-AMD; in the same years, 20,140,426 people (10,334,262 male, 9,806,164 female) were born in Italy. Comparing the observed number of n-AMD cases with the expected number of n- AMD cases in each season, we found that the season-specific risk for n-AMD was 2.5% higher for those born in summer (OR=1.03, Bonferroni-corrected P=0.008) and 3% lower for those born in winter (OR=0.96, Bonferroni-corrected P=0.0004). When considering the month of birth, the risk of n-AMD was 5.9% lower for people born in January (OR=0.93, Bonferroni-corrected P=0.0012). The factors causing such differences should be determined. PMID:27997361

The role of apolipoprotein E (rs7412 and rs429358) in age-related macular degeneration.

PubMed

Liutkeviciene, Rasa; Vilkeviciute, Alvita; Smalinskiene, Alina; Tamosiunas, Abdonas; Petkeviciene, Janina; Zaliuniene, Dalia; Lesauskaite, Vaiva

2018-05-31

Age-related macular degeneration (AMD) is the most common cause of incurable visual impairment in the developed countries. The main pathological change in AMD is the formation of drusen containing 40% of lipids, dominated by esterified cholesterol (EC) and phosphatidylcholine (PC), and protein. Haplotype ε4 of apolipoprotein E (ApoE) acts as a ligand for the low-density lipoprotein receptor and is involved in the maintenance and repair of neuronal cell membranes. This study aimed to evaluate the association of AMD with ApoE gene polymorphism variants (rs7412 and rs429358). A total of 2133 subjects were enrolled in our research. The study group comprised patients with early AMD (n = 413) and exudative AMD (n = 307), and the control group enrolled randomly selected persons (n = 1413). The genotyping of ApoE (rs7412 and rs429358) was performed using the real-time polymerase chain reaction (PCR) method. Statistical analysis revealed that ApoE 4/2 genotype was less frequently observed in in older patients with exudative AMD compared to older healthy controls (0.4% vs. 4.0%, p = 0.003). Our data demonstrated that ApoE 4/2 genotype was less frequently observed in old patients (65 years and more) with exudative AMD compared to old healthy controls. It leads to hypothesis on the protective effect of ApoE 4/2 to develop AMD in the elderly.

PATTERNS OF FUNDUS AUTOFLUORESCENCE DEFECTS IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION SUBTYPES.

PubMed

Ozkok, Ahmet; Sigford, Douglas K; Tezel, Tongalp H

2016-11-01

To test define characteristic fundus autofluorescence patterns of different exudative age-related macular degeneration subtypes. Cross-sectional study. Fifty-two patients with choroidal neovascularization because of three different neovascular age-related macular degeneration subtypes were included in the study. Macular and peripheral fundus autofluorescence patterns of study subjects were compared in a masked fashion. Fundus autofluorescence patterns of all three neovascular age-related macular degeneration subtypes revealed similar patterns. However, peripapillary hypo-autofluorescence was more common among patients with polypoidal choroidal vasculopathy (88.2%) compared with patients with retinal angiomatous proliferation (12.5%) and patients without retinal angiomatous proliferation and polypoidal choroidal vasculopathy (21.1%) (P < 0.0001). Presence of peripapillary fundus autofluorescence defects in neovascular age-related macular degeneration maybe suggestive of polypoidal choroidal vasculopathy as a variant of neovascular age-related macular degeneration.

Identification of vinculin as a potential plasma marker for age-related macular degeneration.

PubMed

Kim, Hye-Jung; Woo, Se Joon; Suh, Eui Jin; Ahn, Jeeyun; Park, Ji Hyun; Hong, Hye Kyoung; Lee, Ji Eun; Ahn, Seong Joon; Hwang, Duck Jin; Kim, Ki Woong; Park, Kyu Hyung; Lee, Cheolju

2014-10-08

To identify plasma protein biomarkers for age-related macular degeneration (AMD) using a large-scale quantitative proteomic discovery procedure. Plasma proteomes from 20 exudative AMD patients and 20 healthy control patients were comparatively profiled by four-dimensional liquid chromatography-tandem mass spectrometry (LC-MS/MS). Proteins existing at statistically different levels were validated by enzyme-linked immunosorbent assay (ELISA) and Western blotting in 233 case-controlled samples. Newly discovered plasma biomarkers were further confirmed using in vivo and in vitro experiments. Out of 320 proteins identified, vinculin, protein S100A9, triosephosphate isomerase, protein S100A8, protein Z-dependent protease inhibitor, C-X-C motif chemokine 7, and tenascin X showed significantly differential expression in AMD patient plasma compared to control plasma. Among these, the area under the curve (AUC) for vinculin was 0.871 for discriminating between exudative AMD and controls (n = 201) and 0.879 for discriminating between AMD and controls (n = 233). A proteogenomic combination model using vinculin and two known risk genotypes in ARMS2 and CFH genes additionally provided excellent discrimination of AMD from controls (AUC = 0.916). The plasma level of vinculin was not associated with any confounding clinical variables, such as age, smoking, and other comorbidities. Additionally, vinculin was strongly expressed in retinal pigment epithelial cells of human eyes, and its expression was elevated when exposed to oxidative stress in vitro. Vinculin was identified as a potential plasma biomarker for AMD. The early detection of AMD using novel plasma biomarkers with genetic modeling may enable timely treatment and vision preservation in the elderly. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Diagnostic Sensitivity and Specificity of Dark Adaptometry for Detection of Age-Related Macular Degeneration

PubMed Central

Jackson, Gregory R.; Scott, Ingrid U.; Kim, Ivana K.; Quillen, David A.; Iannaccone, Alessandro; Edwards, John G.

2014-01-01

Purpose. Difficulty with night vision is a common complaint of patients with age-related macular degeneration (AMD). Consistent with this complaint, dark adaptation (DA) is substantially impaired in these patients. Because of the severity of the deficit, measurement of DA has been suggested as a means for the diagnosis of AMD. Previous methods for measurement of DA were time intensive (>30 minutes), which made them unsuitable for clinical use. This study evaluated a rapid DA test (≤6.5 minutes) for the detection of AMD. Methods. Dark adaptation was measured by using the AdaptDx dark adaptometer in two groups: subjects with normal retinal health and subjects with AMD. Subjects were assigned to their group by clinical examination and grading of fundus photographs. Subjects were classified as having DA consistent with normal retinal health (rod intercept ≤ 6.5 minutes) or having dark adaptation consistent with AMD (rod intercept > 6.5 minutes). Results. The eligible sample for analysis included 21 normal adults and 127 AMD patients. The rapid test was found to have a diagnostic sensitivity of 90.6% (P < 0.001) and specificity of 90.5% (P < 0.027). Thus, abnormal DA was detected in 115 of 127 AMD patients, and normal DA was found in 19 of 21 normal adults. Conclusions. The high diagnostic sensitivity and specificity compared favorably to long-duration research methods for the measurement of DA, and slit lamp biomicroscopy performed by a retina specialist. These results suggest that a rapid DA test is useful for the detection of AMD. PMID:24550363

Contextual cueing impairment in patients with age-related macular degeneration.

PubMed

Geringswald, Franziska; Herbik, Anne; Hoffmann, Michael B; Pollmann, Stefan

2013-09-12

Visual attention can be guided by past experience of regularities in our visual environment. In the contextual cueing paradigm, incidental learning of repeated distractor configurations speeds up search times compared to random search arrays. Concomitantly, fewer fixations and more direct scan paths indicate more efficient visual exploration in repeated search arrays. In previous work, we found that simulating a central scotoma in healthy observers eliminated this search facilitation. Here, we investigated contextual cueing in patients with age-related macular degeneration (AMD) who suffer from impaired foveal vision. AMD patients performed visual search using only their more severely impaired eye (n = 13) as well as under binocular viewing (n = 16). Normal-sighted controls developed a significant contextual cueing effect. In comparison, patients showed only a small nonsignificant advantage for repeated displays when searching with their worse eye. When searching binocularly, they profited from contextual cues, but still less than controls. Number of fixations and scan pattern ratios showed a comparable pattern as search times. Moreover, contextual cueing was significantly correlated with acuity in monocular search. Thus, foveal vision loss may lead to impaired guidance of attention by contextual memory cues.

Tachyphylaxis after intravitreal bevacizumab for exudative age-related macular degeneration.

PubMed

Forooghian, Farzin; Cukras, Catherine; Meyerle, Catherine B; Chew, Emily Y; Wong, Wai T

2009-06-01

To describe tachyphylaxis to intravitreal bevacizumab (IVB) in patients with exudative age-related macular degeneration (AMD). We retrospectively reviewed the records of 59 consecutive patients treated with IVB at the National Eye Institute over a 14-month period and identified cases demonstrating loss of treatment efficacy as revealed by spectral domain optical coherence tomography. We defined tachyphylaxis as a loss of therapeutic response to IVB 28 +/- 7 days after administration in an eye that had previously demonstrated a therapeutic response in the same time interval. Five patients (six eyes) were identified as developing tachyphylaxis after repeated treatment with IVB. High-dose IVB (2.50 mg) did not restore therapeutic response in these patients. Bilateral tachyphylaxis to IVB was seen after an episode of unilateral postinjection anterior uveitis. After the first treatment of IVB, the median time taken to develop tachyphylaxis was 100 weeks (range: 31-128 weeks), and the median number of IVB treatments to the development of tachyphylaxis was 8 treatments (range: 5-10 treatments). Tachyphylaxis can occur after long-term intravitreal use of bevacizumab in patients with AMD. The precise mechanism of tachyphylaxis is unclear, but both local and/or systemic factors may be involved.

Long-term results after limited macular translocation surgery for wet age-related macular degeneration.

PubMed

Oshima, Hisaaki; Iwase, Takeshi; Ishikawa, Kohei; Yamamoto, Kentaro; Terasaki, Hiroko

2017-01-01

To evaluate the long-term results of limited macular translocation (LMT) surgery with radial chorioscleral outfolding in patients with wet age-related macular degeneration (AMD) and subfoveal choroidal neovascularization (CNV). In addition, to identify the factors associated with the final best-corrected visual acuity (BCVA). The medical records of 20 eyes of 20 consecutive patients (65.2±9.8 years) who had undergone LMT for the treatment of wet AMD and were followed for at least 5 years, were reviewed. The surgical outcomes including the BCVA, degree of foveal displacement, and complications were recorded. The mean foveal displacement was 1332 ± 393 μm after the LMT. The CNV was removed in 16 eyes and photocoagulated in 4 eyes. The mean preoperative VA was 0.83 ± 0.33 logMAR units which significantly improved to 0.59 ± 0.37 logMAR units at 1 year after the surgery (P = 0.015). This BCVA was maintained at 0.59 ± 0.41 logMAR units on the final examination. The final BCVA was significantly correlated with that at 1 year after the surgery (r = 0.83, P<0.001). Multiple linear regression analysis showed that the final BCVA was significantly correlated with the BCVA at 1 year after the surgery (P<0.001), a recurrence of a CNV (P = 0.001), and the age (P = 0.022). LMT improves the BCVA significantly at 1 year, and the improved BCVA lasted for at least 5 years. These results indicate that the impaired function of the sensory retina at the fovea can recover on the new RPE after the displacement for at least 5 years. The ability to maintain good retinal function on the new RPE for a long period is important for future treatments of CNVs such as the transplantation of RPE cells and stem cells.

Monocyte chemoattractant protein 1, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 in exudative age-related macular degeneration.

PubMed

Jonas, Jost B; Tao, Yong; Neumaier, Michael; Findeisen, Peter

2010-10-01

To examine intraocular concentrations of monocyte chemoattractant protein 1 (MCP-1), soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1), and vascular endothelial growth factor (VEGF) in eyes with exudative age-related macular degeneration (AMD). The investigation included a study group of 28 patients (28 eyes) with exudative AMD and a control group of 25 patients (25 eyes) with cataract. The concentrations of MCP-1, sICAM-1, sVCAM-1, and VEGF in aqueous humor samples obtained during surgery were measured using a solid-phase chemiluminescence immunoassay. The study group as compared with the control group had higher aqueous concentrations of sICAM-1 (mean [SD], 844 [2073] vs 246 [206] pg/mL, respectively; P < .001), sVCAM-1 (mean [SD], 7978 [7120] vs 2999 [1426] pg/mL, respectively; P < .001), and MCP-1 (mean [SD], 587 [338] vs 435 [221] pg/mL, respectively; P = .07). The concentration of VEGF did not vary significantly between the groups (P = .76). The MCP-1 concentration was significantly associated with macular thickness (r = 0.40; P = .004). It decreased significantly with the type of subfoveal neovascular membrane (classic membrane type, occult membrane, retinal pigment epithelium detachment) (P = .009). The concentrations of sICAM-1, sVCAM-1, and VEGF were not significantly associated with membrane type and macular thickness (P ≥ .18). Concentrations of MCP-1, sICAM-1, and sVCAM-1 are significantly associated with exudative AMD, even in the presence of normal VEGF concentrations. Intraocular MCP-1 concentrations are correlated with the subfoveal neovascular membrane type and the amount of macular edema. One may infer that MCP-1, sICAM-1, and sVCAM-1 could potentially be additional target molecules in therapy for exudative AMD.

AMD and the alternative complement pathway: genetics and functional implications.

PubMed

Tan, Perciliz L; Bowes Rickman, Catherine; Katsanis, Nicholas

2016-06-21

Age-related macular degeneration (AMD) is an ocular neurodegenerative disorder and is the leading cause of legal blindness in Western societies, with a prevalence of up to 8 % over the age of 60, which continues to increase with age. AMD is characterized by the progressive breakdown of the macula (the central region of the retina), resulting in the loss of central vision including visual acuity. While its molecular etiology remains unclear, advances in genetics and genomics have illuminated the genetic architecture of the disease and have generated attractive pathomechanistic hypotheses. Here, we review the genetic architecture of AMD, considering the contribution of both common and rare alleles to susceptibility, and we explore the possible mechanistic links between photoreceptor degeneration and the alternative complement pathway, a cascade that has emerged as the most potent genetic driver of this disorder.

On the impact of different approaches to classify age-related macular degeneration: Results from the German AugUR study.

PubMed

Brandl, Caroline; Zimmermann, Martina E; Günther, Felix; Barth, Teresa; Olden, Matthias; Schelter, Sabine C; Kronenberg, Florian; Loss, Julika; Küchenhoff, Helmut; Helbig, Horst; Weber, Bernhard H F; Stark, Klaus J; Heid, Iris M

2018-06-06

While age-related macular degeneration (AMD) poses an important personal and public health burden, comparing epidemiological studies on AMD is hampered by differing approaches to classify AMD. In our AugUR study survey, recruiting residents from in/around Regensburg, Germany, aged 70+, we analyzed the AMD status derived from color fundus images applying two different classification systems. Based on 1,040 participants with gradable fundus images for at least one eye, we show that including individuals with only one gradable eye (n = 155) underestimates AMD prevalence and we provide a correction procedure. Bias-corrected and standardized to the Bavarian population, late AMD prevalence is 7.3% (95% confidence interval = [5.4; 9.4]). We find substantially different prevalence estimates for "early/intermediate AMD" depending on the classification system: 45.3% (95%-CI = [41.8; 48.7]) applying the Clinical Classification (early/intermediate AMD) or 17.1% (95%-CI = [14.6; 19.7]) applying the Three Continent AMD Consortium Severity Scale (mild/moderate/severe early AMD). We thus provide a first effort to grade AMD in a complete study with different classification systems, a first approach for bias-correction from individuals with only one gradable eye, and the first AMD prevalence estimates from a German elderly population. Our results underscore substantial differences for early/intermediate AMD prevalence estimates between classification systems and an urgent need for harmonization.

Self-reported optometric practise patterns in age-related macular degeneration.

PubMed

Ly, Angelica; Nivison-Smith, Lisa; Zangerl, Barbara; Assaad, Nagi; Kalloniatis, Michael

2017-11-01

The use of advanced imaging in clinical practice is emerging and the use of this technology by optometrists in assessing patients with age-related macular degeneration is of interest. Therefore, this study explored contemporary, self-reported patterns of practice regarding age-related macular degeneration diagnosis and management using a cross-sectional survey of optometrists in Australia and New Zealand. Practising optometrists were surveyed on four key areas, namely, demographics, clinical skills and experience, assessment and management of age-related macular degeneration. Questions pertaining to self-rated competency, knowledge and attitudes used a five-point Likert scale. Completed responses were received from 127 and 87 practising optometrists in Australia and New Zealand, respectively. Advanced imaging showed greater variation in service delivery than traditional techniques (such as slitlamp funduscopy) and trended toward optical coherence tomography, which was routinely performed in age-related macular degeneration by 49 per cent of respondents. Optical coherence tomography was also associated with higher self-rated competency, knowledge and perceived relevance to practice than other modalities. Most respondents (93 per cent) indicated that they regularly applied patient symptoms, case history, visual function results and signs from traditional testing, when queried about their management of patients with age-related macular degeneration. Over half (63 per cent) also considered advanced imaging, while 31 per cent additionally considered all of these as well as the disease stage and clinical guidelines. Contrary to the evidence base, 68 and 34 per cent rated nutritional supplements as highly relevant or relevant in early age-related macular degeneration and normal aging changes, respectively. These results highlight the emergence of multimodal and advanced imaging (especially optical coherence tomography) in the assessment of age-related macular degeneration

Prevalence of Subretinal Drusenoid Deposits in Older Persons with and without Age-Related Macular Degeneration, by Multimodal Imaging.

PubMed

Zarubina, Anna V; Neely, David C; Clark, Mark E; Huisingh, Carrie E; Samuels, Brian C; Zhang, Yuhua; McGwin, Gerald; Owsley, Cynthia; Curcio, Christine A

2016-05-01

To assess the prevalence of subretinal drusenoid deposits (SDD) in older adults with healthy maculas and early and intermediate age-related macular degeneration (AMD) using multimodal imaging. Cross-sectional study. A total of 651 subjects aged ≥60 years enrolled in the Alabama Study of Early Age-Related Macular Degeneration from primary care ophthalmology clinics. Subjects were imaged using spectral domain optical coherence tomography (SD OCT) of the macula and optic nerve head (ONH), infrared reflectance, fundus autofluorescence, and color fundus photographs (CFP). Eyes were assessed for AMD presence and severity using the Age-Related Eye Disease Study (AREDS) 9-step scale. Criteria for SDD presence were identification on ≥1 en face modality plus SD OCT or on ≥2 en face modalities if absent on SD OCT. Subretinal drusenoid deposits were considered present at the person level if present in 1 or both eyes. Prevalence of SDD in participants with and without AMD. Overall prevalence of SDD was 32% (197/611), with 62% (122/197) affected in both eyes. Persons with SDD were older than those without SDD (70.6 vs. 68.7 years, P = 0.0002). Prevalence of SDD was 23% in subjects without AMD and 52% in subjects with AMD (P < 0.0001). Among those with early and intermediate AMD, SDD prevalence was 49% and 79%, respectively. After age adjustment, those with SDD were 3.4 times more likely to have AMD than those without SDD (95% confidence interval, 2.3-4.9). By using CFP only for SDD detection per the AREDS protocol, prevalence of SDD was 2% (12/610). Of persons with SDD detected by SD OCT and confirmed by at least 1 en face modality, 47% (89/190) were detected exclusively on the ONH SD OCT volume. Subretinal drusenoid deposits are present in approximately one quarter of older adults with healthy maculae and in more than half of persons with early to intermediate AMD, even by stringent criteria. The prevalence of SDD is strongly associated with AMD presence and severity and

NUTRITIONAL SUPPLEMENTATION IN AGE-RELATED MACULAR DEGENERATION.

PubMed

Parodi, Maurizio Battaglia; Zucchiatti, Ilaria; Cicinelli, Maria Vittoria; Cascavilla, Maria Lucia; Bandello, Francesco

2016-06-01

To evaluate the rate of adherence to prescribed nutritional supplementation in patients affected by age-related macular degeneration, in an Italian tertiary referral tertiary center. Patients with age-related macular degeneration, age-related eye disease study Categories 3 and 4, were recruited and underwent an 11-item questionnaire. The study included a total of 193 patients meeting the age-related eye disease study nutritional supplementation criteria (174 patients with age-related eye disease study Category 4 and 19 with Category 3). Seventy-seven (40%) were taking oral supplementation, 70 of whom (90%) 1 tablet/day. Oral supplementation was recommended by the personal ophthalmologist in 85 patients (44%), including all those currently receiving it. Eight patients of 85 (9.4%) rejected supplementation despite it being recommended, mostly because they were already taking other medicines. Ninety-four patients (48%) claimed they had not received any information from their ophthalmologist. Our data reveal that Italian patients with age-related eye disease study Categories 3 and 4 have a low adherence to nutritional supplementation. In 65% of cases, patients were not adequately informed by their ophthalmologist of the potential benefits of oral supplementation for age-related macular degeneration; indeed, 108 patients (56%) were not even aware such nutritional treatments are available. Ophthalmologists should be aware of the importance of giving advice to persons with age-related macular degeneration regarding the benefits of oral supplements.

Association between CFH Y402H Polymorphism and Age Related Macular Degeneration in North Indian Cohort

PubMed Central

Gupta, Amod; Prabhakar, Sudesh; Singh, Ramandeep; Sharma, Suresh Kumar; Chen, Wei

2013-01-01

The purpose of the study was to determine serum complement factor H (CFH) levels in patients of age related macular degeneration (AMD) and examine its association with CFH Y402H polymorphism. 115 AMD patients and 61 normal controls were recruited in this study. The single nucleotide polymorphism was assayed by real time PCR and serum CFH levels were measured by ELISA and standardized to total serum protein. Chi-square test was applied to polymorphism analysis while Mann Whitney U-statistic for CFH-levels. Mendelian randomization approach was used for determining causal relationship. The genotype frequency differed between the AMD patients (TT- 18.3%, TC-41.3% and CC-40.4%) and controls (TT-76.3%, TC-13.6%, and CC-10.1%) (p = 0001). The frequency of alleles was also significantly different when AMD (T-39% and C-61%) was compared to controls (T-83% and C-17%) (p = 0.0001). Level of serum CFH was significantly lower in AMD patients as compared to normal controls (p = 0.001). Our data showed that the CFH Y402H polymorphism is a risk factor for AMD in the North Indian population. Mendelian randomization approach revealed that CFH Y402H polymorphism affects AMD risk through the modification of CFH serum levels. PMID:23922956

miRNA involvement in angiogenesis in age-related macular degeneration.

PubMed

Wang, Lei; Lee, Amy Yi Wei; Wigg, Jonathan P; Peshavariya, Hitesh; Liu, Ping; Zhang, Hong

2016-12-01

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. Late-stage AMD is characterized by choroidal neovascularization (CNV). miR-93 appears to play a role in regulating vascular endothelial growth factor-A (VEGF-A), a known factor involved in neovascularization. Understanding its biological significance might enable development of therapeutic interventions for diseases like AMD. We aimed to determine the role of miR-93 in AMD using a laser-induced CNV mouse model. CNV was induced by laser photocoagulation in C57BL/6 mice. The CNV mice were transfected with scrambled miR or miR-93 mimic. The treatment effect was assessed by fundus photography and fluorescein angiography and confirmed by choroidal flatmount. The expression of miR-93 and VEGF-A in ocular tissues was analysed by quantitative polymerase chain reaction (qPCR) and Western blot. The overexpression effects of miR-93 were also proved on human microvascular endothelial cells (HMECs). Significantly decreased expression of miR-93 was observed by qPCR analysis in CNV mice compared to untreated mice (p < 0.05). VEGF-A messenger RNA (mRNA) and protein expression were upregulated with CNV; these changes were ameliorated by restoration of miR-93 (p < 0.05). CNV was reduced after miR-93 transfection. Transfection of miR-93 reduced the proliferation of HMECs (p < 0.01), but no significant changes were observed in 2D capillary-like tube formation (p > 0.05) and migration (p > 0.05) compared with that in the untreated cells. miR-93 has been shown to be a negative modulator of angiogenesis in the eye. All together, these results highlight the therapeutic potential of miR-93 and suggest that it may contribute as a putative therapeutic target for AMD in humans.

Risks of newly onset hemorrhagic stroke in patients with neovascular age-related macular degeneration.

PubMed

Lee, Wan-Ju Annabelle; Cheng, Ching-Lan; Lee, Cheng-Han; Kao Yang, Yea-Huei; Lin, Swu-Jane; Hsieh, Cheng-Yang

2017-10-01

Age-related macular degeneration (AMD) is an eye disease causing blindness in the elderly. It shares many common possible pathogenic mechanisms with cardiovascular diseases. Many studies have discussed the association between AMD and stroke, but the results were inconsistent. Our aim was to determine the associations between neovascular AMD and the risk of stroke in the Taiwanese population. This is a retrospective cohort study. We used claims data from National Health Insurance Research Database. Patients aged more than 45 years without stroke, myocardial infarction, or any AMD were selected from 2001 to 2008 and followed until 2010. The index date was defined as the date of nAMD diagnosis (ICD-9 code, 362.52). The comparison group was patients without an nAMD diagnosis with age- and sex-matched to nAMD subjects at a ratio of up to 10 to 1. Kaplan-Meier survival analysis and Cox regression analysis were used. The incidence of stroke events (ICD-9 codes, 430-434) and their subtypes (hemorrhagic and ischemic) were primary outcomes. Secondary outcomes included acute myocardial infarction (AMI), composite AMI/stroke, and all-cause mortality. Patients with nAMD had a higher risk of developing stroke, with an adjusted HR of 1.30 (95% CI, 1.01-1.68). A higher risk for hemorrhagic stroke (HR, 1.70, 95% CI, 1.03-2.83) was also found. No significant differences were observed in ischemic stroke, the composite of AMI/stroke, and all-cause mortality. Patients with nAMD had a significantly higher risk of developing stroke, which was driven mainly by the increased risk of developing the hemorrhagic subtype. Copyright © 2017 John Wiley & Sons, Ltd.

Clinical risk factors for age-related macular degeneration: a systematic review and meta-analysis

PubMed Central

2010-01-01

Background Age-related macular degeneration (AMD) is the leading cause of blindness in Western countries. Numerous risk factors have been reported but the evidence and strength of association is variable. We aimed to identify those risk factors with strong levels of evidence which could be easily assessed by physicians or ophthalmologists to implement preventive interventions or address current behaviours. Methods A systematic review identified 18 prospective and cross-sectional studies and 6 case control studies involving 113,780 persons with 17,236 cases of late AMD that included an estimate of the association between late AMD and at least one of 16 pre-selected risk factors. Fixed-effects meta-analyses were conducted for each factor to combine odds ratio (OR) and/or relative risk (RR) outcomes across studies by study design. Overall raw point estimates of each risk factor and associated 95% confidence intervals (CI) were calculated. Results Increasing age, current cigarette smoking, previous cataract surgery, and a family history of AMD showed strong and consistent associations with late AMD. Risk factors with moderate and consistent associations were higher body mass index, history of cardiovascular disease, hypertension, and higher plasma fibrinogen. Risk factors with weaker and inconsistent associations were gender, ethnicity, diabetes, iris colour, history of cerebrovascular disease, and serum total and HDL cholesterol and triglyceride levels. Conclusions Smoking, previous cataract surgery and a family history of AMD are consistent risk factors for AMD. Cardiovascular risk factors are also associated with AMD. Knowledge of these risk factors that may be easily assessed by physicians and general ophthalmologists may assist in identification and appropriate referral of persons at risk of AMD. PMID:21144031

Next-generation sequencing analysis of the ARMS2 gene in Turkish exudative age-related macular degeneration patients.

PubMed

Bardak, H; Gunay, M; Ercalik, Y; Bardak, Y; Ozbas, H; Bagci, O

2017-01-23

Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. It is a complex disease with both genetic and environmental risk factors. To improve clinical management of this condition, it is important to develop risk assessment and prevention strategies for environmental influences, and establish a more effective treatment approach. The aim of the present study was to investigate age-related maculopathy susceptibility protein 2 (ARMS2) gene sequences among Turkish patients with exudative AMD. In addition to 39 advanced exudative AMD patients, 250 healthy individuals for whom exome sequencing data were available were included as a control group. Patients with a history of known environmental and systemic AMD risk factors were excluded. Genomic DNA was isolated from peripheral blood and analyzed using next-generation sequencing. All coding exons of the ARMS2 gene were assessed. Three different ARMS2 sequence variations (rs10490923, rs2736911, and rs10490924) were identified in both the patient and control group. Within the control group, two further ARMS2 gene variants (rs7088128 and rs36213074) were also detected. Logistic regression analysis revealed a relationship between the rs10490924 polymorphism and AMD in the Turkish population.

Evidence for an Association between Macular Degeneration and Thyroid Cancer in the Aged Population.

PubMed

Lin, Shih-Yi; Hsu, Wu-Huei; Lin, Cheng-Li; Lin, Cheng-Chieh; Lin, Jane-Ming; Chang, Yun-Lun; Hsu, Chung-Y; Kao, Chia-Hung

2018-05-03

Direct evidence of whether thyroid cancer patients have a higher risk of age-related macular degeneration (AMD) has yet to be investigated. Patients older than 50 years-old and newly diagnosed with thyroid cancer between 2000 and 2008 were identified from the national health insurance research database (NHIRD). We applied time-varying Cox proportional hazard models to assess the association between thyroid cancer and AMD. The multivariable models included conventional cardiovascular risk factors, myopia, vitreous floaters, hypothyroidism, hyperthyroidism, and treatment modality of thyroid cancer. The analysis process was stratified by age, gender, and comorbidity. In this study, 5253 patients were included in a thyroid cancer cohort (men 24.5%; median age 59.1 years (53.7⁻67.4 years), and 21,012 matched controls were included in a non-thyroid cancer cohort. The AMD incidence was 40.7 per 10,000 person/year in the thyroid cancer cohort. The thyroid cancer cohort had a higher risk (adjusted hazard ratio (aHR) = 1.38, 95% confidence interval, CI = 1.09⁻1.75) of AMD than the non-thyroid cohort. Thyroid cancer patients had a higher risk of AMD, especially the male patients (aHR = 1.92, 95% CI = 1.38⁻3.14) and the patients with comorbidities (aHR = 1.38, 95% CI = 1.09⁻1.74). In conclusion, thyroid cancer patients older than 50 years-old have increased risk of AMD.

Genome-wide analysis of disease progression in age-related macular degeneration.

PubMed

Yan, Qi; Ding, Ying; Liu, Yi; Sun, Tao; Fritsche, Lars G; Clemons, Traci; Ratnapriya, Rinki; Klein, Michael L; Cook, Richard J; Liu, Yu; Fan, Ruzong; Wei, Lai; Abecasis, Gonçalo R; Swaroop, Anand; Chew, Emily Y; Weeks, Daniel E; Chen, Wei

2018-03-01

Family- and population-based genetic studies have successfully identified multiple disease-susceptibility loci for Age-related macular degeneration (AMD), one of the first batch and most successful examples of genome-wide association study. However, most genetic studies to date have focused on case-control studies of late AMD (choroidal neovascularization or geographic atrophy). The genetic influences on disease progression are largely unexplored. We assembled unique resources to perform a genome-wide bivariate time-to-event analysis to test for association of time-to-late-AMD with ∼9 million variants on 2721 Caucasians from a large multi-center randomized clinical trial, the Age-Related Eye Disease Study. To our knowledge, this is the first genome-wide association study of disease progression (bivariate survival outcome) in AMD genetic studies, thus providing novel insights to AMD genetics. We used a robust Cox proportional hazards model to appropriately account for between-eye correlation when analyzing the progression time in the two eyes of each participant. We identified four previously reported susceptibility loci showing genome-wide significant association with AMD progression: ARMS2-HTRA1 (P = 8.1 × 10-43), CFH (P = 3.5 × 10-37), C2-CFB-SKIV2L (P = 8.1 × 10-10) and C3 (P = 1.2 × 10-9). Furthermore, we detected association of rs58978565 near TNR (P = 2.3 × 10-8), rs28368872 near ATF7IP2 (P = 2.9 × 10-8) and rs142450006 near MMP9 (P = 0.0006) with progression to choroidal neovascularization but not geographic atrophy. Secondary analysis limited to 34 reported risk variants revealed that LIPC and CTRB2-CTRB1 were also associated with AMD progression (P < 0.0015). Our genome-wide analysis thus expands the genetics in both development and progression of AMD and should assist in early identification of high risk individuals.

Complement inhibitors for age-related macular degeneration.

PubMed

Williams, Michael A; McKay, Gareth J; Chakravarthy, Usha

2014-01-15

Given the relatively high prevalence of age-related macular degeneration (AMD) and the increased incidence of AMD as populations age, the results of trials of novel treatments are awaited with much anticipation. The complement cascade describes a series of proteolytic reactions occurring throughout the body that generate proteins with a variety of roles including the initiation and promotion of immune reactions against foreign materials or micro-organisms. The complement cascade is normally tightly regulated, but much evidence implicates complement overactivity in AMD and so it is a logical therapeutic target in the treatment of AMD. To assess the effects and safety of complement inhibitors in the prevention or treatment of advanced AMD. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 11), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2013), EMBASE (January 1980 to November 2013), Allied and Complementary Medicine Database (AMED) (January 1985 to November 2013), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to November 2013), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), Web of Science Conference Proceedings Citation Index - Science (CPCI-S) (January 1990 to November 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 21 November 2013. We also performed handsearching of proceedings, from 2012 onwards, of meetings and conferences of specific professional organisations. We planned to include randomised controlled trials (RCTs) with

Comparison of pro re nata versus Bimonthly Injection of Intravitreal Aflibercept for Typical Neovascular Age-Related Macular Degeneration.

PubMed

Mori, Ryusaburo; Tanaka, Koji; Haruyama, Miho; Kawamura, Akiyuki; Furuya, Koichi; Yuzawa, Mitsuko

2017-01-01

The aim of this study was to clarify the 1-year outcomes of pro re nata (PRN) and bimonthly intravitreal injections of aflibercept (IVA) for typical neovascular age-related macular degeneration (tAMD) after the initial 3 monthly IVA. We conducted a prospective, interventional study. Fifty-eight treatment-naïve patients with tAMD were randomly assigned to the PRN (30 patients) or the bimonthly (28 patients) treatment group. Both groups initially received 3 monthly IVA. Visual acuity, central macular retinal thickness (CRT), and central choroidal thickness (CCT) were evaluated at 12 months. Subanalysis was performed to identify factors associated with the best-corrected visual acuity (BCVA). BCVA was significantly improved only in the bimonthly group at 12 months. CRT and CCT were significantly decreased in both groups. Subanalysis showed that the only factor associated with BCVA improvement at 12 months was the existence of pigment epithelial detachment at baseline. BCVA showed significant improvement only in the bimonthly group but not in the PRN group at 12 months. © 2017 S. Karger AG, Basel.

Prevalence of neovascular age-related macular degeneration and geographic atrophy in Denmark.

PubMed

Sedeh, Farnam Barati; Scott, Daniel Andrew Richard; Subhi, Yousif; Sørensen, Torben Lykke

2017-11-01

In Denmark, age-related macular degeneration (AMD) is the most common cause of blindness. To better understand current and future challenges, we estimated and projected the annual number of patients with neovascular AMD and geographic atrophy in Denmark from 2016 to 2060. Detailed age- and gender-stratified prevalence estimates of neovascular AMD and geographic atrophy in a Scandinavian population were identified and applied to age- and gender-stratified population numbers provided by Statistics Denmark. Prevalence estimates were calculated for each year from 2016 to 2060. Future forecasts were provided by Statistics Denmark and based on calculations by the Danish Institute for Economic Modelling and Forecasting. We estimated that there are currently ~30,000 patients with neovascular AMD and ~21,000 patients with geographic atrophy in Denmark. The majority of these patients are persons aged ≥ 85 years. For neovascular AMD, the number of patients will grow to ~33,000 in 2020, ~58,000 in 2040 and ~72,000 in 2060. For geographic atrophy, the number of patients will grow to ~23,000 in 2020, ~41,000 in 2040, and ~50,000 in 2060. We expect a steady growth in the prevalence of neovascular AMD and geographic atrophy in Denmark due to an ageing population. These numbers emphasise the importance of disease prevention, careful planning of health service activities and continuing research. none. not relevant. Articles published in the DMJ are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.

The Age-Related Eye Disease 2 Study: Micronutrients in the Treatment of Macular Degeneration123

PubMed Central

Gorusupudi, Aruna; Nelson, Kelly; Bernstein, Paul S

2017-01-01

Age-related macular degeneration (AMD) is one of the leading causes of vision loss in the elderly. With an increasingly aged population worldwide, the need for the prevention of AMD is rising. Multiple studies investigating AMD with the use of animal models and cell culture have identified oxidative stress–related retinal damage as an important contributing factor. In general, diet is an excellent source of the antioxidants, vitamins, and minerals necessary for healthy living; moreover, the general public is often receptive to recommendations made by physicians and health care workers regarding diet and supplements as a means of empowering themselves to avoid common and worrisome ailments such as AMD, which has made epidemiologists and clinicians enthusiastic about dietary intervention studies. A wide variety of nutrients, such as minerals, vitamins, ω-3 (n–3) fatty acids, and various carotenoids, have been associated with reducing the risk of AMD. Initial results from the Age-Related Eye Disease Study (AREDS) indicated that supplementation with antioxidants (β-carotene and vitamins C and E) and zinc was associated with a reduced risk of AMD progression. The AREDS2 follow-up study, designed to improve upon the earlier formulation, tested the addition of lutein, zeaxanthin, and ω-3 fatty acids. In this review, we examine the science behind the nutritional factors included in these interventional studies and the reasons for considering their inclusion to lower the rate of AMD progression. PMID:28096126

JNK inhibition reduces apoptosis and neovascularization in a murine model of age-related macular degeneration.

PubMed

Du, Hongjun; Sun, Xufang; Guma, Monica; Luo, Jing; Ouyang, Hong; Zhang, Xiaohui; Zeng, Jing; Quach, John; Nguyen, Duy H; Shaw, Peter X; Karin, Michael; Zhang, Kang

2013-02-05

Age-related macular degeneration (AMD) is the leading cause of registered blindness among the elderly and affects over 30 million people worldwide. It is well established that oxidative stress, inflammation, and apoptosis play critical roles in pathogenesis of AMD. In advanced wet AMD, although, most of the severe vision loss is due to bleeding and exudation of choroidal neovascularization (CNV), and it is well known that vascular endothelial growth factor (VEGF) plays a pivotal role in the growth of the abnormal blood vessels. VEGF suppression therapy improves visual acuity in AMD patients. However, there are unresolved issues, including safety and cost. Here we show that mice lacking c-Jun N-terminal kinase 1 (JNK1) exhibit decreased inflammation, reduced CNV, lower levels of choroidal VEGF, and impaired choroidal macrophage recruitment in a murine model of wet AMD (laser-induced CNV). Interestingly, we also detected a substantial reduction in choroidal apoptosis of JNK1-deficient mice. Intravitreal injection of a pan-caspase inhibitor reduced neovascularization in the laser-induced CNV model, suggesting that apoptosis plays a role in laser-induced pathological angiogenesis. Intravitreal injection of a specific JNK inhibitor decreased choroidal VEGF expression and reduced pathological CNV. These results suggest that JNK1 plays a key role in linking oxidative stress, inflammation, macrophage recruitment apoptosis, and VEGF production in wet AMD and pharmacological JNK inhibition offers a unique and alternative avenue for prevention and treatment of AMD.

NLRP3 Upregulation in Retinal Pigment Epithelium in Age-Related Macular Degeneration.

PubMed

Wang, Yujuan; Hanus, Jakub W; Abu-Asab, Mones S; Shen, Defen; Ogilvy, Alexander; Ou, Jingxing; Chu, Xi K; Shi, Guangpu; Li, Wei; Wang, Shusheng; Chan, Chi-Chao

2016-01-08

Inflammation and oxidative stress are involved in age-related macular degeneration (AMD) and possibly associated with an activation of neuronal apoptosis inhibitor protein/class II transcription activator of the Major Histocompatibility Complex (MHC)/heterokaryon incompatibility/telomerase-associated protein 1, leucine-rich repeat or nucleotide-binding domain, leucine-rich repeat-containing family, and pyrin domain-containing 3 (NLRP3) inflammasome. In the present study, we used a translational approach to address this hypothesis. In patients with AMD, we observed increased mRNA levels of NLRP3, pro-interleukin-1 beta (IL-1β) and pro-IL-18 in AMD lesions of the retinal pigment epithelium (RPE) and photoreceptor. In vitro, a similar increase was evoked by oxidative stress or lipopolysaccharide (LPS) stimulation in the adult retinal pigment epithelium (ARPE-19) cell line, and the increase was reduced in siRNA transfected cells to knockdown NLRP3. Ultrastructural studies of ARPE-19 cells showed a swelling of the cytoplasm, mitochondrial damage, and occurrence of autophagosome-like structures. NLRP3 positive dots were detected within autophagosome-like structures or in the extracellular space. Next, we used a mouse model of AMD, Ccl2/Cx3cr1 double knockout on rd8 background (DKO rd8) to ascertain the in vivo relevance. Ultrastructural studies of the RPE of these mice showed damaged mitochondria, autophagosome-like structures, and cytoplasmic vacuoles, which are reminiscent of the pathology seen in stressed ARPE-19 cells. The data suggest that the NLRP3 inflammasome may contribute in AMD pathogenesis.

NLRP3 Upregulation in Retinal Pigment Epithelium in Age-Related Macular Degeneration

PubMed Central

Wang, Yujuan; Hanus, Jakub W.; Abu-Asab, Mones S.; Shen, Defen; Ogilvy, Alexander; Ou, Jingxing; Chu, Xi K.; Shi, Guangpu; Li, Wei; Wang, Shusheng; Chan, Chi-Chao

2016-01-01

Inflammation and oxidative stress are involved in age-related macular degeneration (AMD) and possibly associated with an activation of neuronal apoptosis inhibitor protein/class II transcription activator of the Major Histocompatibility Complex (MHC)/heterokaryon incompatibility/telomerase-associated protein 1, leucine-rich repeat or nucleotide-binding domain, leucine-rich repeat-containing family, and pyrin domain-containing 3 (NLRP3) inflammasome. In the present study, we used a translational approach to address this hypothesis. In patients with AMD, we observed increased mRNA levels of NLRP3, pro-interleukin-1 beta (IL-1β) and pro-IL-18 in AMD lesions of the retinal pigment epithelium (RPE) and photoreceptor. In vitro, a similar increase was evoked by oxidative stress or lipopolysaccharide (LPS) stimulation in the adult retinal pigment epithelium (ARPE-19) cell line, and the increase was reduced in siRNA transfected cells to knockdown NLRP3. Ultrastructural studies of ARPE-19 cells showed a swelling of the cytoplasm, mitochondrial damage, and occurrence of autophagosome-like structures. NLRP3 positive dots were detected within autophagosome-like structures or in the extracellular space. Next, we used a mouse model of AMD, Ccl2/Cx3cr1 double knockout on rd8 background (DKO rd8) to ascertain the in vivo relevance. Ultrastructural studies of the RPE of these mice showed damaged mitochondria, autophagosome-like structures, and cytoplasmic vacuoles, which are reminiscent of the pathology seen in stressed ARPE-19 cells. The data suggest that the NLRP3 inflammasome may contribute in AMD pathogenesis. PMID:26760997

Regulation of age-related macular degeneration-like pathology by complement factor H

PubMed Central

Toomey, Christopher B.; Kelly, Una; Saban, Daniel R.; Bowes Rickman, Catherine

2015-01-01

Complement factor H (CFH) is a major susceptibility gene for age-related macular degeneration (AMD); however, its impact on AMD pathobiology is unresolved. Here, the role of CFH in the development of AMD pathology in vivo was interrogated by analyzing aged Cfh+/− and Cfh−/− mice fed a high-fat, cholesterol-enriched diet. Strikingly, decreased levels of CFH led to increased sub-retinal pigmented epithelium (sub-RPE) deposit formation, specifically basal laminar deposits, following high-fat diet. Mechanistically, our data show that deposits are due to CFH competition for lipoprotein binding sites in Bruch’s membrane. Interestingly and despite sub-RPE deposit formation occurring in both Cfh+/− and Cfh−/− mice, RPE damage accompanied by loss of vision occurred only in old Cfh+/− mice. We demonstrate that such pathology is a function of excess complement activation in Cfh+/− mice versus complement deficiency in Cfh−/− animals. Due to the CFH-dependent increase in sub-RPE deposit height, we interrogated the potential of CFH as a previously unidentified regulator of Bruch’s membrane lipoprotein binding and show, using human Bruch’s membrane explants, that CFH removes endogenous human lipoproteins in aged donors. Thus, advanced age, high-fat diet, and decreased CFH induce sub-RPE deposit formation leading to complement activation, which contributes to RPE damage and visual function impairment. This new understanding of the complicated interactions of CFH in AMD-like pathology provides an improved foundation for the development of targeted therapies for AMD. PMID:25991857

Gold nanoparticle enhancement of stereotactic radiosurgery for neovascular age-related macular degeneration

NASA Astrophysics Data System (ADS)

Ngwa, Wilfred; Makrigiorgos, G. Mike; Berbeco, Ross I.

2012-10-01

Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries for people over the age of 50. In this work, the dosimetric feasibility of using gold nanoparticles (AuNP) as radiosensitizers to enhance kilovoltage stereotactic radiosurgery for neovascular AMD is investigated. Microdosimetry calculations at the sub-cellular level were carried out to estimate the radiation dose enhancement to individual nuclei in neovascular AMD endothelial cells (nDEF) due to photon-induced photo-/Auger electrons from x-ray-irradiated AuNP. The nDEF represents the ratio of radiation doses to the endothelial cell nuclei with and without AuNP. The calculations were carried out for a range of feasible AuNP local concentrations using the clinically applicable 100 kVp x-ray beam parameters employed by a commercially available x-ray therapy system. The results revealed nDEF values of 1.30-3.26 for the investigated concentration range of 1-7 mg g-1, respectively. In comparison, for the same concentration range, nDEF values of 1.32-3.40, 1.31-3.33, 1.29-3.19, 1.28-3.12 were calculated for 80, 90, 110 and 120 kVp x-rays, respectively. Meanwhile, calculations as a function of distance from the AuNP showed that the dose enhancement, for 100 kVp, is markedly confined to the targeted neovascular AMD endothelial cells where AuNP are localized. These findings provide impetus for considering the application of AuNP to enhance therapeutic efficacy during stereotactic radiosurgery for neovascular AMD.

Novel grid combined with peripheral distortion correction for ultra-widefield image grading of age-related macular degeneration

PubMed Central

Mach, Steven; Garas, Shady; Kim, Ivana K; Vavvas, Demetrios G; Miller, Joan W; Husain, Deeba; Miller, John B

2017-01-01

Purpose Eyes with age-related macular degeneration (AMD) often harbor pathological changes in the retinal periphery and perimacular region. These extramacular changes have not been well classified, but may be phenotypically and functionally relevant. The purpose of this study was to demonstrate a novel grid to systematically study peripheral retinal abnormalities in AMD using geometric distortion-corrected ultra-widefield (UWF) imaging. Methods This is a cross-sectional observational case series. Consecutive patients with AMD without any other coexisting vitreoretinal disease and control patients over age 50 without AMD or any other vitreoretinal disease were imaged using Optos 200 Tx. Captured 200° UWF images were corrected for peripheral geometric distortion using Optos transformation software. A newly developed grid to study perimacular and peripheral abnormalities in AMD was then projected onto the images. Results Peripheral and perimacular changes such as drusen, retinal pigment epithelium changes and atrophy were found in patients with AMD. The presented grid in conjunction with geometric distortion-corrected UWF images allowed for systematic study of these peripheral changes in AMD. Conclusion We present a novel grid to study peripheral and posterior pole changes in AMD. The grid is unique in that it adds a perimacular zone, which may be important in characterizing certain phenotypes in AMD. Our UWF images were corrected for geometric peripheral distortion to accurately reflect the anatomical dimensions of the retina. This grid offers a reliable and reproducible foundation for the exploration of peripheral retinal pathology associated with AMD. PMID:29184386