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.

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.

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.

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

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.

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.

[Depression in Patients with Age-Related Macular Degeneration].

PubMed

Narváez, Yamile Reveiz; Gómez-Restrepo, Carlos

2012-09-01

Age-related macular degeneration is a cause for disability in the elderly since it greatly affects their quality of life and increases depression likelihood. This article discusses the negative effect depression has on patients with age-related macular degeneration and summarizes the interventions available for decreasing their depression index. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

ANTERIOR CHAMBER FLARE DURING BEVACIZUMAB TREATMENT IN EYES WITH EXUDATIVE AGE-RELATED MACULAR DEGENERATION.

PubMed

Hautamäki, Asta; Luoma, Arto; Immonen, Ilkka

2016-11-01

To study the anterior chamber flare during bevacizumab treatment of exudative age-related macular degeneration. During a 2-year prospective follow-up, 50 patients recently diagnosed with exudative age-related macular degeneration were treated at once-a-month visits if subretinal or intraretinal fluid or a new hemorrhage was present in the lesion area. Flare was measured weekly during the first month and then monthly in both eyes. Higher flare was associated with older age (P = 0.007, Linear Mixed Model), higher number of smoking pack-years (P = 0.019), macular cysts (P = 0.041), and pseudophakia (P = 0.003). The levels gradually increased during the follow-up (P < 0.0001) but less in the eyes with classic CNV (P = 0.011). Flare decreased during treatment-free periods lasting for at least two consecutive visits (P = 0.005). A peak in flare was observed 1 week after the first injection (P = 0.034, Wilcoxon signed rank test). In the fellow eyes, higher flare values in the beginning of the follow-up were associated with later conversion into exudative age-related macular degeneration (P = 0.015, Mann-Whitney U test). Anterior chamber flare correlated poorly with the CNV activity. Higher levels may, however, precede or exist early in the process that leads to the development of exudative age-related macular degeneration.

Associations between Rs4244285 and Rs762551 gene polymorphisms and age-related macular degeneration.

PubMed

Stasiukonyte, Neringa; Liutkeviciene, Rasa; Vilkeviciute, Alvita; Banevicius, Mantas; Kriauciuniene, Loresa

2017-01-01

Age-related macular degeneration is the leading cause of blindness in elderly individuals in developed countries. The etiology and pathophysiology of age-related macular degeneration have not been elucidated yet. Knowing that the main pathological change of age-related macular degeneration is formation of drusen containing about 40% of lipids, there have been attempts to find associations between age-related macular degeneration and genes controlling lipid metabolism. To determine the frequency of CYP2C19 (G681A) Rs4244285 and CYP1A2 (-163C>A) Rs762551 genotypes in patients with age-related macular degeneration. The study enrolled 150 patients with early age-related macular degeneration and 296 age- and gender-matched healthy controls. The genotyping of Rs4244285 and Rs762551 was carried out by using the real-time polymerase chain reaction method. The CYP1A2 (-163C>A) Rs762551 C/C genotype was more frequently detected in patients with age-related macular degeneration than in the control group (32.7% vs. 21.6%, p = 0.011) and was associated with an increased risk of developing early age-related macular degeneration (OR = 1.759, 95% CI: 1.133-2.729; p = 0.012). The CYP1A2 (-163C>A) Rs762551 C/A genotype was more frequently documented in the control group compared with patients with age-related macular degeneration (46.3% vs. 30.7%, p = 0.002) and was associated with a decreased risk of having age-related macular degeneration (OR = 0.580. 95% CI: 0.362-0.929, p = 0.023) in the co-dominant model. The study showed that the CYP1A2 (-163C>A) Rs762551 C/C genotype was associated with an increased risk of age-related macular degeneration.

Age-Related Macular Degeneration.

PubMed

Mehta, Sonia

2015-09-01

Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly. AMD is diagnosed based on characteristic retinal findings in individuals older than 50. Early detection and treatment are critical in increasing the likelihood of retaining good and functional vision. Copyright © 2015 Elsevier Inc. All rights reserved.

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%.

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.

Value-based medicine and interventions for macular degeneration.

PubMed

Brown, Melissa M; Brown, Gary C; Brown, Heidi

2007-05-01

The aim of this article is to review the patient value conferred by interventions for neovascular macular degeneration. Value-based medicine is the practice of medicine based upon the patient value (improvement in quality of life and length of life) conferred by an intervention. For ophthalmologic interventions, in which length-of-life is generally unaffected, the value gain is equivalent to the improvement in quality of life. Photodynamic therapy delivers a value gain (improvement in quality of life) of 8.1% for the average person with classic subfoveal choroidal neovascularization, while laser photocoagulation for the same entity confers a 4.4% improvement in quality of life. Preliminary data suggest the value gain for the treatment of occult/minimally classic choroidal neovascularization with ranibizumab is greater than 15%. The average value gain for statins for the treatment of hyperlipidemia is 3.9%, while that for the use of biphosphonates for the treatment of osteoporosis is 1.1% and that for drugs to treat benign prostatic hyperplasia is 1-2%. Interventions, especially ranibizumab therapy, for neovascular macular degeneration appear to deliver an extraordinary degree of value compared with many other interventions across healthcare.

MACULAR CHOROIDAL VOLUME CHANGES AFTER INTRAVITREAL BEVACIZUMAB FOR EXUDATIVE AGE-RELATED MACULAR DEGENERATION.

PubMed

Palkovits, Stefan; Seidel, Gerald; Pertl, Laura; Malle, Eva M; Hausberger, Silke; Makk, Johanna; Singer, Christoph; Osterholt, Julia; Herzog, Sereina A; Haas, Anton; Weger, Martin

2017-12-01

To evaluate the effect of intravitreal bevacizumab on the macular choroidal volume and the subfoveal choroidal thickness in treatment naïve eyes with exudative age-related macular degeneration. The macular choroidal volume and the subfoveal choroidal thickness were measured using enhanced depth imaging optical coherence tomography. After a screening examination, each patient received 3 monthly intravitreal injections of 1.25 mg bevacizumab. One month after the third injection was a final assessment. Forty-seven patients with a mean age of 80 ± 6.4 years were included. The macular choroidal volume decreased significantly from median 4.1 mm (interquartile range 3.4-5.9) to median 3.9 mm (interquartile range 3.1-5.6) between the baseline and final examination (difference -0.46 mm, 95% confidence interval: -0.57 to 0.35, P < 0.001). Similarly, subfoveal choroidal thickness had decreased from 157.0 μm (interquartile range 116.0-244.5) at baseline to 139.0 μm (interquartile range 102.5-212.0) at the final examination (P < 0.001). Both parameters macular choroidal volume at baseline and subfoveal choroidal thickness at baseline were not associated with the response to treatment. The macular choroidal volume and the subfoveal choroidal thickness decreased significantly after 3 monthly bevacizumab injections for exudative age-related macular degeneration.

[Vitreomacular adhesion in HD-OCT images in the age-related macular degeneration].

PubMed

Latalska, Małgorzata; Swiech-Zubilewicz, Anna; Mackiewicz, Jerzy

2013-01-01

The aim of this study was to evaluate an incidence of the vitreomacular adhesion in patients with age-related macular degeneration. We examined 472 eyes in 241 patients (136 W/ 105 M) in age of 54-92 years (mean 62.6 years +/- 8.5) with dry or wet age-related macular degeneration using Cirrus HD-OCT (Zeiss) macular cube 512x128 program or 5-line pro-gram. Vitreomacular adhesion was observed in 139 eyes with dry age-related macular degeneration (29.4%, p=0.000*), in 101 eyes with drusen (21.4%, p=0.000*), in 38 eyes with retinal pigment epithelium alterations (8%, p=0.202), in 278 eyes with wet age-related macular degeneration (58.9%, p=0.001*), in 21 eyes with pigment epithelial detachment (4.4%, p=0.303), in 161 eyes with choroidal neovascularzation (34. 1%, p=0.031*/ and in 96 eyes with scar (20.4%, p=0.040*). Probably, vitreomacular adhesion alone is not able to induce age-related macular degeneration, but it may be associated with choroidal neovascularization development, it can contribute to exudate formation and choroidal neovascularization, it may induces or sustains a chronic low-grade inflammation in the macula region.

Lipofuscin accumulation, abnormal electrophysiology, and photoreceptor degeneration in mutant ELOVL4 transgenic mice: a model for macular degeneration.

PubMed

Karan, G; Lillo, C; Yang, Z; Cameron, D J; Locke, K G; Zhao, Y; Thirumalaichary, S; Li, C; Birch, D G; Vollmer-Snarr, H R; Williams, D S; Zhang, K

2005-03-15

Macular degeneration is a heterogeneous group of disorders characterized by photoreceptor degeneration and atrophy of the retinal pigment epithelium (RPE) in the central retina. An autosomal dominant form of Stargardt macular degeneration (STGD) is caused by mutations in ELOVL4, which is predicted to encode an enzyme involved in the elongation of long-chain fatty acids. We generated transgenic mice expressing a mutant form of human ELOVL4 that causes STGD. In these mice, we show that accumulation by the RPE of undigested phagosomes and lipofuscin, including the fluorophore, 2-[2,6-dimethyl-8-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1E,3E,5E,7E-octatetraenyl]-1-(2-hyydroxyethyl)-4-[4-methyl-6-(2,6,6,-trimethyl-1-cyclohexen-1-yl)-1E,3E,5E-hexatrienyl]-pyridinium (A2E) is followed by RPE atrophy. Subsequently, photoreceptor degeneration occurs in the central retina in a pattern closely resembling that of human STGD and age-related macular degeneration. The ELOVL4 transgenic mice thus provide a good model for both STGD and dry age-related macular degeneration, and represent a valuable tool for studies on therapeutic intervention in these forms of blindness.

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.

Impact of age-related macular degeneration in patients with glaucoma: understanding the patients' perspective.

PubMed

Skalicky, Simon E; Fenwick, Eva; Martin, Keith R; Crowston, Jonathan; Goldberg, Ivan; McCluskey, Peter

2016-07-01

The aim of the study is to measure the impact of age-related macular degeneration on vision-related activity limitation and preference-based status for glaucoma patients. This was a cross-sectional study. Two-hundred glaucoma patients of whom 73 had age-related macular degeneration were included in the research. Sociodemographic information, visual field parameters and visual acuity were collected. Age-related macular degeneration was scored using the Age-Related Eye Disease Study system. The Rasch-analysed Glaucoma Activity Limitation-9 and the Visual Function Questionnaire Utility Index measured vision-related activity limitation and preference-based status, respectively. Regression models determined factors predictive of vision-related activity limitation and preference-based status. Differential item functioning compared Glaucoma Activity Limitation-9 item difficulty for those with and without age-related macular degeneration. Mean age was 73.7 (±10.1) years. Lower better eye mean deviation (β: 1.42, 95% confidence interval: 1.24-1.63, P < 0.001) and age-related macular degeneration (β: 1.26 95% confidence interval: 1.10-1.44, P = 0.001) were independently associated with worse vision-related activity limitation. Worse eye visual acuity (β: 0.978, 95% confidence interval: 0.961-0.996, P = 0.018), high risk age-related macular degeneration (β: 0.981, 95% confidence interval: 0.965-0.998, P = 0.028) and severe glaucoma (β: 0.982, 95% confidence interval: 0.966-0.998, P = 0.032) were independently associated with worse preference-based status. Glaucoma patients with age-related macular degeneration found using stairs, walking on uneven ground and judging distances of foot to step/curb significantly more difficult than those without age-related macular degeneration. Vision-related activity limitation and preference-based status are negatively impacted by severe glaucoma and age-related macular degeneration. Patients with both conditions

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.

Ernest Borgnine Lays it on the Line Hollywood Hero Focuses on Macular Degeneration

MedlinePlus

... it on the Line Hollywood Hero Focuses on Macular Degeneration Past Issues / Summer 2008 Table of Contents For ... going strong at 91, and speaking out on macular degeneration for the National Eye Institute. Photo courtesy of ...

A Layered Approach to Raising Public Awareness of Macular Degeneration in Australia

PubMed Central

Heraghty, Julie; Cummins, Robert

2012-01-01

Between 2007 and 2011, the Australian Macular Degeneration Foundation conducted a multifaceted campaign to increase public awareness of macular degeneration. Regular national polls conducted by an independent social research company have shown that awareness of macular degeneration increased from 47% to 80% in Australians aged 16 years or older and from 58% to 92% in those aged 50 years or older. The percentage of people aged 50 years or older who reported having had their macula checked in the 2 years prior to the survey increased from 33% to 70% from 2007 to 2011. Other measures, including analysis of Medicare data, have confirmed the success of the campaign. PMID:22813341

[Age-related macular degeneration as a local manifestation of atherosclerosis - a novel insight into pathogenesis].

PubMed

Machalińska, Anna

2013-01-01

Age-related macular degeneration is the leading cause of irreversible visual impairment and disability among the elderly in developed countries. There is compelling evidence that atherosclerosis and age-related macular degeneration share a similar pathogenic process. The association between atherosclerosis and age-related macular degeneration has been inferred from histological, biochemical and epidemiological studies. Many published data indicate that drusen are similar in molecular composition to plaques in atherosclerosis. Furthermore, a great body of evidence has emerged over the past decade that implicates the chronic inflammatory processes in the pathogenesis and progression of both disorders. We speculate that vascular atherosclerosis and age-related macular degeneration may represent different manifestations of the same disease induced by a pathologic tissue response to the damage caused by oxidative stress and local ischemia. In this review, we characterise in detail a strong association between age-related macular degeneration and atherosclerosis development, and we postulate the hypothesis that age-related macular degeneration is a local manifestation of a systemic disease. This provides a new approach for understanding the aspects of pathogenesis and might improve the prevention and treatment of both diseases which both result from ageing of the human body.

Driving and Age-Related Macular Degeneration

ERIC Educational Resources Information Center

Owsley, Cynthia; McGwin, Gerald, Jr.

2008-01-01

This article reviews the research literature on driving and age-related macular degeneration, which is motivated by the link between driving and the quality of life of older adults and their increased collision rate. It addresses the risk of crashes, driving performance, driving difficulty, self-regulation, and interventions to enhance, safety,…

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.

Age-related macular degeneration

PubMed Central

Querques, Giuseppe; Avellis, Fernando Onofrio; Querques, Lea; Bandello, Francesco; Souied, Eric H

2011-01-01

Clinical question: Is there any new knowledge about the pathogenesis and treatment of age-related macular degeneration (AMD)? Results: We now understand better the biochemical and pathological pathways involved in the genesis of AMD. Treatment of exudative AMD is based on intravitreal injection of new antivascular endothelial growth factor drugs for which there does not yet exist a unique recognized strategy of administration. No therapies are actually available for atrophic AMD, despite some experimental new pharmacological approaches. Implementation: strategy of administration, safety of intravitreal injection PMID:21654887

Depression in Age-Related Macular Degeneration

ERIC Educational Resources Information Center

Casten, Robin; Rovner, Barry

2008-01-01

Age-related macular degeneration (AMD) is a major cause of disability in the elderly, substantially degrades the quality of their lives, and is a risk factor for depression. Rates of depression in AMD are substantially greater than those found in the general population of older people, and are on par with those of other chronic and disabling…

Qualitative assessment of online information about age-related macular degeneration available in Portuguese.

PubMed

Agi, Jorge; Kasahara, Niro; Lottenberg, Claudio Luiz

2018-06-07

To evaluate the quality of online information on age-related macular degeneration available in Portuguese. The search term "age-related macular degeneration" was used to browse the web using four different search engines. The first 40 websites appearing on match lists provided by each search engine were recorded and those listed in at least three tab pages selected. The Sandvik Severity Index was used as to assess website quality. Quality of information available on selected websites was rated average (mean Sandvik Score 7.08±2.23). Most websites disseminating information about age-related macular degeneration were of average quality. The need to readjust web-based information to target lay public and promote increased understanding was emphasized.

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...

Costs of newly diagnosed neovascular age-related macular degeneration among medicare beneficiaries, 2004-2008.

PubMed

Qualls, Laura G; Hammill, Bradley G; Wang, Fang; Lad, Eleonora M; Schulman, Kevin A; Cousins, Scott W; Curtis, Lesley H

2013-04-01

To examine associations between newly diagnosed neovascular age-related macular degeneration and direct medical costs. This retrospective observational study matched 23,133 Medicare beneficiaries diagnosed with neovascular age-related macular degeneration between 2004 and 2008 with a control group of 92,532 beneficiaries on the basis of age, sex, and race. The index date for each case-control set corresponded to the first diagnosis for the case. Main outcome measures were total costs per patient and age-related macular degeneration-related costs per case 1 year before and after the index date. Mean cost per case in the year after diagnosis was $12,422, $4,884 higher than the year before diagnosis. Postindex costs were 41% higher for cases than controls after adjustment for preindex costs and comorbid conditions. Age-related macular degeneration-related costs represented 27% of total costs among cases in the postindex period and were 50% higher for patients diagnosed in 2008 than in 2004. This increase was attributable primarily to the introduction of intravitreous injections of vascular endothelial growth factor antagonists. Intravitreous injections averaged $203 for patients diagnosed in 2004 and $2,749 for patients diagnosed in 2008. Newly diagnosed neovascular age-related macular degeneration was associated with a substantial increase in total medical costs. Costs increased over time, reflecting growing use of anti-vascular endothelial growth factor therapies.

Mutations in ABCR (ABCA4) in patients with Stargardt macular degeneration or cone-rod degeneration.

PubMed

Briggs, C E; Rucinski, D; Rosenfeld, P J; Hirose, T; Berson, E L; Dryja, T P

2001-09-01

To determine the spectrum of ABCR mutations associated with Stargardt macular degeneration and cone-rod degeneration (CRD). One hundred eighteen unrelated patients with recessive Stargardt macular degeneration and eight with recessive CRD were screened for mutations in ABCR (ABCA4) by single-strand conformation polymorphism analysis. Variants were characterized by direct genomic sequencing. Segregation analysis was performed on the families of 20 patients in whom at least two or more likely pathogenic sequence changes were identified. The authors found 77 sequence changes likely to be pathogenic: 21 null mutations (15 novel), 55 missense changes (26 novel), and one deletion of a consensus glycosylation site (also novel). Fifty-two patients with Stargardt macular degeneration (44% of those screened) and five with CRD each had two of these sequence changes or were homozygous for one of them. Segregation analyses in the families of 19 of these patients were informative and revealed that the index cases and all available affected siblings were compound heterozygotes or homozygotes. The authors found one instance of an apparently de novo mutation, Ile824Thr, in a patient. Thirty-seven (31%) of the 118 patients with Stargardt disease and one with CRD had only one likely pathogenic sequence change. Twenty-nine patients with Stargardt disease (25%) and two with CRD had no identified sequence changes. This report of 42 novel mutations brings the growing number of identified likely pathogenic sequence changes in ABCR to approximately 250.

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.

Intraocular lenses in age-related macular degeneration.

PubMed

Grzybowski, Andrzej; Wasinska-Borowiec, Weronika; Alio, Jorge L; Amat-Peral, Pedro; Tabernero, Juan

2017-09-01

The aim of this work is to review the lenses, assessing their advantages and disadvantages. We describe a total of seven types of intraocular lenses (IOLs) recommended for age-related macular degeneration (AMD). We used the PubMed web platform to search for implantable devices in various stages of AMD. We searched for both prospective and retrospective studies and also case reports. Clinical results in AMD patients have been described for a total of seven types of IOLs recommended for AMD: an implantable miniature telescope (IMT), IOL-VIP System, Lipshitz macular implant (LMI), sulcus-implanted Lipshitz macular implant, LMI-SI, Fresnel Prism Intraocular Lens, iolAMD and Scharioth Macula Lens. We conclude that to objectively ascertain the effectiveness and safety of these lenses, further independent clinical studies with longer follow-up data are necessary prior to the general use of these optical devices.

[Non-pharmacologic therapy of age-related macular degeneration, based on the etiopathogenesis of the disease].

PubMed

Fischer, Tamás

2015-07-12

It has a great therapeutic significance that the disorder of the vascular endothelium, which supplies the affected ocular structures, plays a major role in the development of age-related macular degeneration. Chronic inflammation is closely linked to diseases associated with endothelial dysfuncition and age-related macular degeneration is accompanied by a general inflammatory response. The vascular wall including those in chorioids may be activated by several repeated and/or prolonged mechanical, physical, chemical, microbiological, immunologic and genetic factors causing a protracted host defence response with a consequent vascular damage, which leads to age-related macular degeneration. Based on this concept, age-related macular degeneration is a local manifestation of the systemic vascular disease. This recognition should have therapeutic implications because restoration of endothelial dysfunction can stabilize the condition of chronic vascular disease including age-related macular degeneration, as well. Restoration of endothelial dysfunction by non-pharmacological or pharmacological interventions may prevent the development or improve endothelial dysfunction resulting in prevention or improvement of age-related macular degeneration. Non-pharmacological interventions which may have beneficial effect in endothelial dysfunction include (1) smoking cessation; (2) reduction of increased body weight; (3) adequate physical activity; (4) appropriate diet (a) proper dose of flavonoids, polyphenols and kurcumin; (b) omega-3 long-chain polyunsaturated fatty acids: docosahexaenoic acid and eicosapentaenoic acid; (c) carotenoids, lutein and zeaxanthins), (d) management of dietary glycemic index, (e) caloric restriction, and (5) elimination of stressful lifestyle. Non-pharmacological interventions should be preferable even if medicaments are also used for the treatment of endothelial dysfunction.

Superior cervical gangliectomy induces non-exudative age-related macular degeneration in mice.

PubMed

Dieguez, Hernán H; Romeo, Horacio E; González Fleitas, María F; Aranda, Marcos L; Milne, Georgia A; Rosenstein, Ruth E; Dorfman, Damián

2018-02-07

Non-exudative age-related macular degeneration, a prevalent cause of blindness, is a progressive and degenerative disease characterized by alterations in Bruch's membrane, retinal pigment epithelium, and photoreceptors exclusively localized in the macula. Although experimental murine models exist, the vast majority take a long time to develop retinal alterations and, in general, these alterations are ubiquitous, with many resulting from non-eye-specific genetic manipulations; additionally, most do not always reproduce the hallmarks of human age-related macular degeneration. Choroid vessels receive sympathetic innervation from the superior cervical ganglion, which, together with the parasympathetic system, regulates blood flow into the choroid. Choroid blood flow changes have been involved in age-related macular degeneration development and progression. At present, no experimental models take this factor into account. The aim of this work was to analyze the effect of superior cervical gangliectomy (also known as ganglionectomy) on the choroid, Bruch's membrane, retinal pigment epithelium and retina. Adult male C57BL/6J mice underwent unilateral superior cervical gangliectomy and a contralateral sham procedure. Although superior cervical gangliectomy induced ubiquitous choroid and choriocapillaris changes, it induced Bruch's membrane thickening, loss of retinal pigment epithelium melanin content and retinoid isomerohydrolase, the appearance of drusen-like deposits, and retinal pigment epithelium and photoreceptor atrophy, exclusively localized in the temporal side. Moreover, superior cervical gangliectomy provoked a localized increase in retinal pigment epithelium and photoreceptor apoptosis, and a decline in photoreceptor electroretinographic function. Therefore, superior cervical gangliectomy recapitulated the main features of human non-exudative age-related macular degeneration, and could become a new experimental model of dry age-related macular degeneration, and

Diagnosis of non-exudative (DRY) age related macular degeneration by non-invasive photon-correlation spectroscopy.

PubMed

Fankhauser, Franz Ii; Ott, Maria; Munteanu, Mihnea

2016-01-01

Photon-correlation spectroscopy (PCS) (quasi-elastic light scattering spectroscopy, dynamic light scattering spectroscopy) allows the non-invasively reveal of local dynamics and local heterogeneities of macromolecular systems. The capability of this technique to diagnose the retinal pathologies by in-vivo investigations of spatial anomalies of retinas displaying non-exudative senile macular degeneration was evaluated. Further, the potential use of the technique for the diagnosis of the macular degeneration was analyzed and displayed by the Receiver Operating Curve (ROC). The maculae and the peripheral retina of 73 normal eyes and of 26 eyes afflicted by an early stage of non-exudative senile macular degeneration were characterized by time-correlation functions and analyzed in terms of characteristic decay times and apparent size distributions. The characteristics of the obtained time-correlation functions of the eyes afflicted with nonexudative macular degeneration and of normal eyes differed significantly, which could be referred to a significant change of the nano- and microstructure of the investigated pathologic maculas. Photon-correlation spectroscopy is able to assess the macromolecular and microstructural aberrations in the macula afflicted by non-exudative, senile macular degeneration. It has been demonstrated that macromolecules of this disease show a characteristic abnormal behavior in the macula.

Gene-diet interactions in age-related macular degeneration

USDA-ARS?s Scientific Manuscript database

Age-related macular degeneration (AMD) is a prevalent blinding disease, accounting for roughly 50% of blindness in developed nations. Very significant advances have been made in terms of discovering genetic susceptibilities to AMD as well as dietary risk factors. To date, nutritional supplementation...

The Experience of Age-Related Macular Degeneration

ERIC Educational Resources Information Center

Wong, Elaine Y. H.; Guymer, Robyn H.; Hassell, Jennifer B.; Keeffe, Jill E.

2004-01-01

This qualitative article describes the impact of age-related macular degeneration (ARMD) among 15 participants: how a person makes sense of ARMD, the effect of ARMD on the person's quality of life, the psychological disturbances associated with the limitations of ARMD, and the influence of ARMD on social interactions. Such in-depth appreciation of…

Nanotechnology-based drug delivery treatments and specific targeting therapy for age-related macular degeneration.

PubMed

Lin, Tai-Chi; Hung, Kuo-Hsuan; Peng, Chi-Hsien; Liu, Jorn-Hon; Woung, Lin-Chung; Tsai, Ching-Yao; Chen, Shih-Jen; Chen, Yan-Ting; Hsu, Chih-Chien

2015-11-01

Nanoparticles combined with cells, drugs, and specially designed genes provide improved therapeutic efficacy in studies and clinical setting, demonstrating a new era of treatment strategy, especially in retinal diseases. Nanotechnology-based drugs can provide an essential platform for sustaining, releasing and a specific targeting design to treat retinal diseases. Poly-lactic-co-glycolic acid is the most widely used biocompatible and biodegradable polymer approved by the Food and Drug Administration. Many studies have attempted to develop special devices for delivering small-molecule drugs, proteins, and other macromolecules consistently and slowly. In this article, we first review current progress in the treatment of age-related macular degeneration. Then, we discuss the function of vascular endothelial growth factor (VEGF) and the pharmacological effects of anti-VEGF-A antibodies and soluble or modified VEGF receptors. Lastly, we summarize the combination of antiangiogenic therapy and nanomedicines, and review current potential targeting therapy in age-related macular degeneration. Copyright © 2015. Published by Elsevier Taiwan.

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

Variability of disease activity in patients treated with ranibizumab for neovascular age-related macular degeneration.

PubMed

Enders, P; Scholz, P; Muether, P S; Fauser, S

2016-08-01

PurposeTo analyze choroidal neovasularization (CNV) activity and recurrence patterns in patients with neovascular age-related macular degeneration (nAMD) treated with ranibizumab, and the correlation with individual intraocular vascular endothelial growth factor (VEGF) suppression time (VST).MethodsPost-hoc analysis of data from a prospective, non-randomized clinical study. Patients with nAMD treated with ranibizumab on a pro re nata regimen. Disease activity was analyzed monthly by spectral-domain optical coherence tomography and correlated with VSTs.ResultsOverall, 73 eyes of 73 patients were included in the study with a mean follow-up of 717 days (range: 412-1239 days). Overall, the mean CNV-activity-free interval was 76.5 days (range: 0-829 days). The individual range of the length of dry intervals was high. A total of 42% of patients had a range of more than 90 days. Overall, 16% of patients showed persistent activity. And 12% stayed dry after the initial ranibizumab treatment. No significant correlation was found between the CNV-recurrence pattern and VST (P=0.12).ConclusionsCNV activity in nAMD is irregular, which is reflected in the range of the duration of dry intervals and late recurrences. The biomarker VST solely seems not to be sufficient to explain recurrence pattern of CNV in all AMD patients.

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

CLINICAL AND ELECTROPHYSIOLOGICAL EVALUATION AFTER INTRAVITREAL ZIV-AFLIBERCEPT FOR EXUDATIVE AGE-RELATED MACULAR DEGENERATION.

PubMed

de Oliveira Dias, João Rafael; de Andrade, Gabriel Costa; Kniggendorf, Vinicius Ferreira; Novais, Eduardo Amorim; Maia, André; Meyer, Carsten; Watanabe, Sung Eun Song; Farah, Michel Eid; Rodrigues, Eduardo Büchele

2017-08-01

To evaluate the 6-month safety and efficacy of ziv-aflibercept intravitreal injections for treating exudative age-related macular degeneration. Fifteen patients with unilateral exudative age-related macular degeneration were enrolled. The best-corrected visual acuity was measured and spectral domain optical coherence tomography was performed at baseline and monthly. Full-field electroretinography and multifocal electroretinography were obtained at baseline and 4, 13, and 26 weeks after the first injection. All patients received three monthly intravitreal injections of ziv-aflibercept (1.25 mg) followed by as-needed treatment. Between baseline and 26 weeks, the mean logMAR best-corrected visual acuity improved (P = 0.00408) from 0.93 ± 0.4 (20/200) to 0.82 ± 0.5 (20/160) logarithm of the minimum angle of resolution, respectively; the central retinal thickness decreased significantly (P = 0.0007) from 490.3 ± 155.1 microns to 327.9 ± 101.5 microns; the mean total macular volume decreased significantly (P < 0.0001) from 9.51 ± 1.36 mm to 8.08 ± 1.34 mm, and the a-wave implicit time increased, with no differences in the other full-field electroretinography parameters. The average multifocal electroretinography macular responses within the first central 15° showed significantly (P < 0.05) increased P1 amplitudes at 26 weeks. No systemic or ocular complications developed. Intravitreal ziv-aflibercept significantly improved the best-corrected visual acuity, multifocal electroretinography amplitudes, central retinal thickness, and total macular volume from baseline to 26 weeks. No retinal toxicity on full-field electroretinography or adverse events occurred during the follow-up period.

Development of facile drug delivery platform of ranibizumab fabricated PLGA-PEGylated magnetic nanoparticles for age-related macular degeneration therapy.

PubMed

Yan, Jian; Peng, Xifeng; Cai, Yulian; Cong, Wendong

2018-06-01

The present anti-angiogenic therapies for neovascular age-related macular degeneration require effective drug delivery systems for transfer drug molecules. Ranibizumab is an active humanized monoclonal antibody that counteracts active forms of vascular endothelial growth factor A in the neovascular age-related macular degeneration therapy. The development of ranibizumab-related therapies, we have designed the effective drug career with engineered magnetic nanoparticles (Fe 3 O 4 ) as a facile platform of ranibizumab delivery for the treatment of neovascular age-related macular degeneration. Ranibizumab conjugated iron oxide (Fe 3 O 4 )/PEGylated poly lactide-co-glycolide (PEG-PLGA) was successfully designed and the synthesized materials are analyzed different analytical techniques. The microscopic techniques (Scanning Electron Microscopy (SEM) & Transmission Electron Microscopy (TEM)) are clearly displayed that spherical nanoparticles into the PEG-PLGA matrix and presence of elements and chemical interactions confirmed by the results of energy dispersive X-ray analysis (EDX) and Fourier trans-form infrared (FTIR) spectroscopic methods. The in vitro anti-angiogenic evaluation of Fe 3 O 4 /PEG-PLGA polymer nanomaterial efficiently inhibits the tube formation in the Matrigel-based assay method by using human umbilical vein endothelial cells. Ranibizumab treated Fe 3 O 4 /PEG-PLGA polymer nanomaterials not disturbed cell proliferation and the results could not display the any significant differences in human endothelial cells. The present investigated results describe that Fe 3 O 4 /PEG-PLGA polymer nanomaterials can be highly favorable and novel formulation for the treatment of neovascular age-related macular degeneration. Copyright © 2018 Elsevier B.V. All rights reserved.

Qualitative assessment of online information about age-related macular degeneration available in Portuguese

PubMed Central

Agi, Jorge; Kasahara, Niro; Lottenberg, Claudio Luiz

2018-01-01

ABSTRACT Objective: To evaluate the quality of online information on age-related macular degeneration available in Portuguese. Methods: The search term “age-related macular degeneration” was used to browse the web using four different search engines. The first 40 websites appearing on match lists provided by each search engine were recorded and those listed in at least three tab pages selected. The Sandvik Severity Index was used as to assess website quality. Results: Quality of information available on selected websites was rated average (mean Sandvik Score 7.08±2.23). Conclusion: Most websites disseminating information about age-related macular degeneration were of average quality. The need to readjust web-based information to target lay public and promote increased understanding was emphasized. PMID:29898089

Cost-Effectiveness of Bevacizumab and Ranibizumab for Newly Diagnosed Neovascular Macular Degeneration (An American Ophthalmological Society Thesis)

PubMed Central

Stein, Joshua D.; Newman-Casey, Paula Anne; Mrinalini, Tavag; Lee, Paul P.; Hutton, David W.

2013-01-01

Purpose: To determine the most cost-effective treatment for patients with newly diagnosed neovascular macular degeneration: monthly or as-needed bevacizumab injections, or monthly or as-needed ranibizumab injections. Methods: Using a Markov model with a 20-year time horizon, we compared the incremental cost-effectiveness of treating a hypothetical cohort of 80-year-old patients with newly diagnosed neovascular macular degeneration using monthly bevacizumab, as-needed bevacizumab, monthly ranibizumab, or as-needed ranibizumab. Data came from the Comparison of Age-Related Macular Degeneration Treatment Trial (CATT), the Medicare Fee Schedules, and the medical literature. Results: Compared with as-needed bevacizumab, the incremental cost-effectiveness ratio of monthly bevacizumab is $242,357 per quality-adjusted life year (QALY). Monthly ranibizumab gains an additional 0.02 QALYs vs monthly bevacizumab at an incremental cost-effectiveness ratio of more than $10 million per QALY. As-needed ranibizumab was dominated by monthly bevacizumab. In sensitivity analyses assuming a willingness to pay of $100,000 per QALY, the annual risk of serious vascular events would have to be at least 2.5 times higher with bevacizumab than that observed in the CATT trial for as-needed ranibizumab to have an incremental cost-effectiveness ratio of <$100,000 per QALY. In another sensitivity analysis, even if every patient receiving bevacizumab experienced declining vision by one category (eg, from 20/25–20/40 to 20/50–20/80) after 2 years but all patients receiving ranibizumab retained their vision level, as-needed ranibizumab would have an incremental cost-effectiveness ratio of $97,340 per QALY. Conclusion: Even after considering the potential for differences in risks of serious adverse events and therapeutic effectiveness, bevacizumab confers considerably greater value than ranibizumab for the treatment of neovascular macular degeneration. PMID:24167325

Cost-effectiveness of bevacizumab and ranibizumab for newly diagnosed neovascular macular degeneration (an American Ophthalmological Society thesis).

PubMed

Stein, Joshua D; Newman-Casey, Paula Anne; Mrinalini, Tavag; Lee, Paul P; Hutton, David W

2013-09-01

To determine the most cost-effective treatment for patients with newly diagnosed neovascular macular degeneration: monthly or as-needed bevacizumab injections, or monthly or as-needed ranibizumab injections. Using a Markov model with a 20-year time horizon, we compared the incremental cost-effectiveness of treating a hypothetical cohort of 80-year-old patients with newly diagnosed neovascular macular degeneration using monthly bevacizumab, as-needed bevacizumab, monthly ranibizumab, or as-needed ranibizumab. Data came from the Comparison of Age-Related Macular Degeneration Treatment Trial (CATT), the Medicare Fee Schedules, and the medical literature. Compared with as-needed bevacizumab, the incremental cost-effectiveness ratio of monthly bevacizumab is $242,357 per quality-adjusted life year (QALY). Monthly ranibizumab gains an additional 0.02 QALYs vs monthly bevacizumab at an incremental cost-effectiveness ratio of more than $10 million per QALY. As-needed ranibizumab was dominated by monthly bevacizumab. In sensitivity analyses assuming a willingness to pay of $100,000 per QALY, the annual risk of serious vascular events would have to be at least 2.5 times higher with bevacizumab than that observed in the CATT trial for as-needed ranibizumab to have an incremental cost-effectiveness ratio of <$100,000 per QALY. In another sensitivity analysis, even if every patient receiving bevacizumab experienced declining vision by one category (eg, from 20/25-20/40 to 20/50-20/80) after 2 years but all patients receiving ranibizumab retained their vision level, as-needed ranibizumab would have an incremental cost-effectiveness ratio of $97,340 per QALY. Even after considering the potential for differences in risks of serious adverse events and therapeutic effectiveness, bevacizumab confers considerably greater value than ranibizumab for the treatment of neovascular macular degeneration.

Durable recovery of the macular architecture and functionality of a diagnosed age-related macular degeneration 1 year after a single intravitreal injection of dobesilate

PubMed Central

Cuevas, P; Outeiriño, L A; Azanza, C; Giménez-Gallego, G

2013-01-01

Among the age-related diseases that affect vision, age-related macular degeneration is the most frequent cause of blindness in patients older than 60 years. In this communication, we report the full anatomical and functional recovery of a patient diagnosed with wet age-related macular degeneration 1 year after a single intravitreal injection of dobesilate. PMID:24225910

Variability of disease activity in patients treated with ranibizumab for neovascular age-related macular degeneration

PubMed Central

Enders, P; Scholz, P; Muether, P S; Fauser, S

2016-01-01

Purpose To analyze choroidal neovasularization (CNV) activity and recurrence patterns in patients with neovascular age-related macular degeneration (nAMD) treated with ranibizumab, and the correlation with individual intraocular vascular endothelial growth factor (VEGF) suppression time (VST). Methods Post-hoc analysis of data from a prospective, non-randomized clinical study. Patients with nAMD treated with ranibizumab on a pro re nata regimen. Disease activity was analyzed monthly by spectral-domain optical coherence tomography and correlated with VSTs. Results Overall, 73 eyes of 73 patients were included in the study with a mean follow-up of 717 days (range: 412–1239 days). Overall, the mean CNV-activity-free interval was 76.5 days (range: 0–829 days). The individual range of the length of dry intervals was high. A total of 42% of patients had a range of more than 90 days. Overall, 16% of patients showed persistent activity. And 12% stayed dry after the initial ranibizumab treatment. No significant correlation was found between the CNV-recurrence pattern and VST (P=0.12). Conclusions CNV activity in nAMD is irregular, which is reflected in the range of the duration of dry intervals and late recurrences. The biomarker VST solely seems not to be sufficient to explain recurrence pattern of CNV in all AMD patients. PMID:27197870

Prophylactic laser in age-related macular degeneration: the past, the present and the future.

PubMed

Findlay, Quan; Jobling, Andrew I; Vessey, Kirstan A; Greferath, Ursula; Phipps, Joanna A; Guymer, Robyn H; Fletcher, Erica L

2018-05-01

The presence of drusen in the posterior eye is a hallmark feature of the early stages of age-related macular degeneration and their size is an indicator of risk of progression to vision-threatening forms of the disease. Since the initial observations that laser treatment can resolve drusen, there has been great interest in whether laser treatment can be used to reduce the progression of age-related macular degeneration. In this article, we review the development of lasers for the treatment of those with age-related macular degeneration. We provide an overview of the clinical trial results that demonstrated drusen resolution but that had mixed effects on progression of disease. In addition, we provide a summary of the recent developments in pulsed lasers that are designed to reduce the energy applied to the posterior eye to provide the therapeutic effects of conventional continuous wave lasers while reducing the secondary tissue effects.

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.

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.

Long-term intraocular pressure changes in patients with neovascular age-related macular degeneration treated with ranibizumab.

PubMed

Menke, Marcel N; Salam, Adzura; Framme, Carsten; Wolf, Sebastian

2013-01-01

To investigate the long-term effects of multiple intravitreal injections (IVTs) of ranibizumab (Lucentis) on intraocular pressure (IOP) in patients with neovascular age-related macular degeneration. In 320 eyes, IOP measurements were performed at baseline prior to injection and compared with IOP measurements of the last visit. Correlations between mean IOP change and total number of IVTs, visual acuity or patient age were tested. The mean IOP increase was 0.8 ± 3.1 mm Hg (p < 0.0001). Seven eyes showed final IOP values between 22 and 25 mm Hg. The mean follow-up was 22.7 ± 14.1 months. No further correlations between IOP change and number of IVTs, visual acuity or patient age have been found. This study demonstrated a statistically significant IOP increase in patients treated with repeated injections of ranibizumab. However, IOP increase required no glaucoma treatment during the study. Therefore, repeated injections with ranibizumab can be considered safe with regard to long-term IOP changes in patients without ocular hypertension or glaucoma. Copyright © 2013 S. Karger AG, Basel.

Embryonic stem cell trials for macular degeneration: a preliminary report.

PubMed

Schwartz, Steven D; Hubschman, Jean-Pierre; Heilwell, Gad; Franco-Cardenas, Valentina; Pan, Carolyn K; Ostrick, Rosaleen M; Mickunas, Edmund; Gay, Roger; Klimanskaya, Irina; Lanza, Robert

2012-02-25

It has been 13 years since the discovery of human embryonic stem cells (hESCs). Our report provides the first description of hESC-derived cells transplanted into human patients. We started two prospective clinical studies to establish the safety and tolerability of subretinal transplantation of hESC-derived retinal pigment epithelium (RPE) in patients with Stargardt's macular dystrophy and dry age-related macular degeneration--the leading cause of blindness in the developed world. Preoperative and postoperative ophthalmic examinations included visual acuity, fluorescein angiography, optical coherence tomography, and visual field testing. These studies are registered with ClinicalTrials.gov, numbers NCT01345006 and NCT01344993. Controlled hESC differentiation resulted in greater than 99% pure RPE. The cells displayed typical RPE behaviour and integrated into the host RPE layer forming mature quiescent monolayers after transplantation in animals. The stage of differentiation substantially affected attachment and survival of the cells in vitro after clinical formulation. Lightly pigmented cells attached and spread in a substantially greater proportion (>90%) than more darkly pigmented cells after culture. After surgery, structural evidence confirmed cells had attached and continued to persist during our study. We did not identify signs of hyperproliferation, abnormal growth, or immune mediated transplant rejection in either patient during the first 4 months. Although there is little agreement between investigators on visual endpoints in patients with low vision, it is encouraging that during the observation period neither patient lost vision. Best corrected visual acuity improved from hand motions to 20/800 (and improved from 0 to 5 letters on the Early Treatment Diabetic Retinopathy Study [ETDRS] visual acuity chart) in the study eye of the patient with Stargardt's macular dystrophy, and vision also seemed to improve in the patient with dry age-related macular

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.

SOCIETAL COSTS ASSOCIATED WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION IN THE UNITED STATES.

PubMed

Brown, Melissa M; Brown, Gary C; Lieske, Heidi B; Tran, Irwin; Turpcu, Adam; Colman, Shoshana

2016-02-01

The purpose of this study was to use a cross-sectional prevalence-based health care economic survey to ascertain the annual, incremental, societal ophthalmic costs associated with neovascular age-related macular degeneration. Consecutive patients (n = 200) with neovascular age-related macular degeneration were studied. A Control Cohort included patients with good (20/20-20/25) vision, while Study Cohort vision levels included Subcohort 1: 20/30 to 20/50, Subcohort 2: 20/60 to 20/100, Subcohort 3: 20/200 to 20/400, and Subcohort 4: 20/800 to no light perception. An interviewer-administered, standardized, written survey assessed 1) direct ophthalmic medical, 2) direct nonophthalmic medical, 3) direct nonmedical, and 4) indirect medical costs accrued due solely to neovascular age-related macular degeneration. The mean annual societal cost for the Control Cohort was $6,116 and for the Study Cohort averaged $39,910 (P < 0.001). Study Subcohort 1 costs averaged $20,339, while Subcohort 4 costs averaged $82,984. Direct ophthalmic medical costs comprised 17.9% of Study Cohort societal ophthalmic costs, versus 74.1% of Control Cohort societal ophthalmic costs (P < 0.001) and 10.4% of 20/800 to no light perception subcohort costs. Direct nonmedical costs, primarily caregiver, comprised 67.1% of Study Cohort societal ophthalmic costs, versus 21.3% ($1,302/$6,116) of Control Cohort costs (P < 0.001) and 74.1% of 20/800 to no light perception subcohort costs. Total societal ophthalmic costs associated with neovascular age-related macular degeneration dramatically increase as vision in the better-seeing eye decreases.

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…

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.

Approach of Turkish ophthalmologists to micronutrition in age-related macular degeneration.

PubMed

Muhammed, Şahin; Yüksel, Harun; Şahin, Alparslan; Cingü, Abdullah Kürşat; Türkcü, Fatih Mehmet; Özkurt, Zeynep Gürsel; Çaça, İhsan

2015-01-01

To evaluate the knowledge and behaviors of ophthalmologists in Turkey concerning micronutrition support in patients with age related macular degeneration (ARMD). This study involved 1,845 ophthalmologists. A scientific poll was sent to all participants by email. The survey covered the following: demographic features, subspecialty knowledge about micronutrition preference for prescribing micronutrition to age related macular degeneration patients, and the reason for this preference. If a participant indicated that he or she prescribed micronutrition, the participant was also asked to indicate the source of the treatment and supplemental treatments. Of 1,845 ophthalmologists, 249 responded to the survey. Of the respondents, 9% (22) never, 43% (107) sometimes, 37% (92) frequently, and 11% (27) always used micronutrition. The most frequent prescribing subgroup was general ophthalmology (22%), followed by the retina-uvea subspecialty (13.9%). The micronutrition prescribing ratio was 54.8% in retina-uvea specialists when the "frequent" and "always" responses were combined. There was no statistically significant difference between subgroups with respect to prescribing micronutrition. Among the ophthalmologists prescribing micronutrition, 57.1% of them did not use the Age-Related Eye Disease Study-1 (AREDS) criteria, and only 31.3% prescribe micronutrition according to AREDS criteria. The results for the general ophthalmologist and retina-uvea specialist subgroups were similar, 56.3% vs 20.2%, and 54.1% vs 36.1%, respectively. Micronutrition was not recommended for the following reasons: expensive (55.4%), low patient expectancy (40%), no effect (30%), and low patient drug compliance (25.4%). Moreover, 55.2% of the clinicians recommended physical activities, dietary changes, and smoking cessation; 7.3% did not recommend these behavioral changes. This survey demonstrated that micronutrition preference in age related macular degeneration was low in ophthalmologists in Turkey

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

PubMed

Lupidi, Marco; Cerquaglia, Alessio; Chhablani, Jay; Fiore, Tito; Singh, Sumit Randhir; Cardillo Piccolino, Felice; Corbucci, Roberta; Coscas, Florence; Coscas, Gabriel; Cagini, Carlo

2018-04-01

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

Treatment of dry age-related macular degeneration with dobesilate

PubMed Central

Cuevas, P; Outeiriño, L A; Angulo, J; Giménez-Gallego, G

2012-01-01

The authors present anatomical and functional evidences of dry age-macular degeneration improvement, after intravitreal treatment with dobesilate. Main outcomes measures were normalisation of retinal structure and function, assessed by optical coherence tomography, fundus-monitored microperimetry, electrophysiology and visual acuity. The effect might be related to the normalisation of the outer retinal architecture. PMID:22729337

Feasibility of a novel remote daily monitoring system for age-related macular degeneration using mobile handheld devices: results of a pilot study.

PubMed

Kaiser, Peter K; Wang, Yi-Zhong; He, Yu-Guang; Weisberger, Annemarie; Wolf, Stephane; Smith, Craig H

2013-10-01

This pilot study evaluated the feasibility of the Health Management Tool (HMT), a novel computing system using mobile handheld devices, to remotely monitor retinal visual function daily in patients with neovascular age-related macular degeneration treated with ranibizumab. Patients with neovascular age-related macular degeneration in at least 1 eye (newly diagnosed or successfully treated < 1 year) and eligible for ranibizumab therapy were enrolled in this 16-week, prospective, open-label, single-arm study. Patients performed a shape discrimination hyperacuity test (myVisionTrack [mVT]) daily on the HMT device (iPhone 3GS) remotely and at all clinic visits. Data entered into HMT devices were collected in the HMT database, which also sent reminders for patients to take mVT. Among 160 patients from 24 U.S. centers enrolled in the study (103 [64%] ≥ 75 years of age), 84.7% on average complied with daily mVT testing and ≈ 98.9% complied with at least weekly mVT testing. The HMT database successfully uploaded more than 17,000 mVT assessment values and sent more than 9,000 reminders. Elderly patients with neovascular age-related macular degeneration were willing and able to comply with daily self-testing of retinal visual function using mobile handheld devices in this novel system of remote vision monitoring.

Prevention of age-related macular degeneration-like retinopathy by rapamycin in rats.

PubMed

Kolosova, Nataliya G; Muraleva, Natalia A; Zhdankina, Anna A; Stefanova, Natalia A; Fursova, Anzhela Z; Blagosklonny, Mikhail V

2012-08-01

Age-related macular degeneration, a neurodegenerative and vascular retinal disease, is the most common cause of blindness in the Western countries. Evidence accumulates that target of rapamycin is involved in aging and age-related diseases, including neurodegeneration. The target of rapamycin inhibitor, rapamycin, suppresses the senescent cell phenotype and extends life span in diverse species, including mice. Rapamycin decreases senescence-associated phenotypes in retinal pigment epithelial cells in culture. Herein, we investigated the effect of rapamycin on spontaneous retinopathy in senescence-accelerated OXYS rats, an animal model of age-related macular degeneration. Rats were treated with either 0.1 or 0.5 mg/kg rapamycin, which was given orally as a food mixture. In a dose-dependent manner, rapamycin decreased the incidence and severity of retinopathy. Rapamycin improved some (but not all) histological abnormalities associated with retinopathy. Thus, in retinal pigment epithelial cell layers, rapamycin decreased nuclei heterogeneity and normalized intervals between nuclei. In photoreceptor cells, associated neurons, and radial glial cells, rapamycin prevented nuclear and cellular pyknosis. More important, rapamycin prevented destruction of ganglionar neurons in the retina. Rapamycin did not exert any adverse effects on the retina in control disease-free Wistar rats. Taken together, our data suggest the therapeutic potential of rapamycin for treatment and prevention of retinopathy. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

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.

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

Assessment of the long-term visual and anatomical outcomes of ranibizumab to treat neovascular age-related macular degeneration.

PubMed

Küçük, Bekir; Kadayıfçılar, Sibel; Eldem, Bora

2018-01-01

To investigate the long-term visual and anatomical outcomes of patients who underwent intravitreal ranibizumab monotherapy to treat neovascular age-related macular degeneration (AMD) and followed-up for at least 2y. A total of 74 eyes of 74 patients who underwent ranibizumab monotherapy for neovascular AMD were included in this retrospective study. The average patient age was 72.1±6.5 (range, 57-85)y, the average follow-up time 46.2±13.1 (range, 24-75)mo, and the average number of visits 24.1±9.5 (range, 8-48). The mean number of injections in year 1 was 4.5, 1.6 in year 2, 0.9 in year 3, 0.4 on year 4, and 0.1 in the following years. Within the entire follow-up period, the mean number of injections was 7.6±4.4 (range, 2-21). The mean visual acuity was 48.1±15 (range, 15-76) letters at baseline and 45.7±19 (range, 7-75) at year 5. The mean central macular thickness was 303±78 (range, 178-552) µm at baseline and 251±51 (range, 138-359) µm at year 5. Scars developed in 47 (63.5%) eyes at the end of the follow-up period, and atrophy was evident in 6 (8.1%) eyes. Ranibizumab monotherapy can stabilize visual acuity for a mean period of 4y in patients with neovascular AMD.

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.

Psychosocial Intervention for Age-Related Macular Degeneration: A Pilot Project

ERIC Educational Resources Information Center

Wahl, Hans-Werner; Kammerer, Annette; Holz, Frank; Miller, Daniel; Becker, Stefanie; Kaspar, Roman; Himmelsbach, Ines

2006-01-01

This study evaluated an emotion-focused and a problem-focused intervention designed for patients with age-related macular degeneration. It found a limited decrease in depression in the emotion-focused group and an increase in active problem orientation and in adaptation to vision loss in the problem-focused group.

[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.

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.

[Combination surgery for wet age-related macular degeneration and chronic peripheral uveitis].

PubMed

Zapuskalov, I V; Krivosheina, O I; Khoroshikh, Yu I

2016-01-01

To develop a combination surgery for wet age-related macular degeneration and concurrent chronic peripheral uveitis that would include intravitreal injection of Lucentis and cryocerclage of the peripheral retina. A total of 75 patients were examined and divided into 2 groups: the main group (37 patients) and the controls (38 patients). Patients from the main group underwent the new combination surgery, while the controls received intravitreal Lucentis alone (peripheral uveitis was managed therapeutically). It has been found that the new combination method provides a significant and stable improvement in visual acuity (by a factor of 10) and a decrease in the area of central scotoma (by a factor of 2.95) in the postoperative period. The period needed for recovery in the central retinal thickness is also 1.6 times shorter. The new combination surgery for wet age-related macular degeneration and concurrent chronic peripheral uveitis provides rapid reduction of inflammation in the extreme periphery of the fundus and a 1.5 times faster (as compared to traditional methods) primary restoration of topographic anatomy of the retina in the macular region.

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

A value-based medicine comparison of interventions for subfoveal neovascular macular degeneration.

PubMed

Brown, Gary C; Brown, Melissa M; Brown, Heidi C; Kindermann, Sylvia; Sharma, Sanjay

2007-06-01

To perform a value-based medicine analysis of clinical trials that evaluate the interventions of laser photocoagulation, intravitreal pegaptanib therapy, and photodynamic therapy (PDT) with verteporfin for the treatment of classic subfoveal choroidal neovascularization. Reference case cost-utility analysis using value-based medicine principles, which use patient-based utility values and standardized, input variable criteria. Data from participants in the Macular Photocoagulation Study, Pegaptanib for Neovascular Age-Related Macular Degeneration Study, and the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy Study. Visual data were converted to a value-based format using time tradeoff utility analysis values from patients with macular degeneration. Costs were obtained from 2005 Medicare data. Outcomes (quality-adjusted life-years [QALYs]) and costs were discounted at a 3% annual rate. Interventional QALYs gained, percent improvement in quality of life, and dollars spent per QALY gained. Laser photocoagulation confers a 4.4% (P = 0.03 versus pegaptanib therapy) improvement in quality of life for the reference case, whereas pegaptanib therapy confers a 5.9% improvement and PDT confers an 8.1% (P = 0.0002 versus pegaptanib therapy) improvement. The cost-utility associated with laser photocoagulation is $8179, that for pegaptanib therapy is $66978, and that for PDT is $31544. All sensitivity analyses remain within the conventional standards of cost-effectiveness. Photodynamic therapy confers greater patient value than intravitreal pegaptanib therapy and laser photocoagulation for the treatment of classic subfoveal choroidal neovascularization. Despite the fact that laser photocoagulation is the most cost-effective intervention, both PDT and pegaptanib therapy deliver greater value, and thus are both preferred over laser photocoagulation. Using an economic measure, photodynamic therapy is the preferred treatment among these 3 interventions.

Treat-and-extend versus every-other-month regimens with aflibercept in age-related macular degeneration.

PubMed

Haga, Akira; Kawaji, Takahiro; Ideta, Ryuichi; Inomata, Yasuya; Tanihara, Hidenobu

2018-05-01

To compare the 1-year outcomes of treat-and-extend (TAE) and every-other-month (2M) regimens with intravitreal aflibercept in Japanese wet age-related macular degeneration (AMD) patients. Prospective, multicenter, randomized clinical trial. The primary outcome measure was the proportion of eyes in which the best-corrected visual acuity (BCVA) was maintained at week 52 [with a loss of <0.3 logarithm of minimum angular of resolution (logMAR) units]. The secondary outcome measures were the mean change from baseline in the central retinal thickness (CRT) and the number of injections. Forty-one patients were enrolled. The mean changes in the BCVA from baseline in the TAE and 2M were -0.32 ± 0.27 and -0.26 ± 0.30 logMAR units (p = 0.46). The TAE group was noninferior to the 2M group in BCVA maintenance. The mean CRT changes from baseline in the TAE and 2M were -161 ± 133 and -157 ± 90 μm (p = 0.73). The mean number of injections in the TAE and 2M were 7.5 ± 1.2 (range, 7-12) and 8.0 ± 0.0 (p < 0.0001). Treat-and-extend (TAE) regimen with aflibercept improved the BCVA and CRT to the same extent as 2M regimen, with a reduced number of injections. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Foveal-Sparing Scotomas in Advanced Dry Age-Related Macular Degeneration

ERIC Educational Resources Information Center

Sunness, Janet S.; Rubin, Gary S.; Zuckerbrod, Abraham; Applegate, Carol A.

2008-01-01

Foveal-sparing scotomas are common in advanced dry macular degeneration (geographic atrophy). Foveal preservation may be present for a number of years. Despite good visual acuity, these patients have reduced reading rates. Magnification may not be effective if the text becomes too large to "fit" within the central spared area. (Contains 2 tables…

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

VITRECTOMY FOR INTERMEDIATE AGE-RELATED MACULAR DEGENERATION ASSOCIATED WITH TANGENTIAL VITREOMACULAR TRACTION: A CLINICOPATHOLOGIC CORRELATION.

PubMed

Ziada, Jean; Hagenau, Felix; Compera, Denise; Wolf, Armin; Scheler, Renate; Schaumberger, Markus M; Priglinger, Siegfried G; Schumann, Ricarda G

2018-03-01

To describe the morphologic characteristics of the vitreomacular interface in intermediate age-related macular degeneration associated with tangential traction due to premacular membrane formation and to correlate with optical coherence tomography (OCT) findings and clinical data. Premacular membrane specimens were removed sequentially with the internal limiting membrane from 27 eyes of 26 patients with intermediate age-related macular degeneration during standard vitrectomy. Specimens were processed for immunocytochemical staining of epiretinal cells and extracellular matrix components. Ultrastructural analysis was performed using transmission electron microscopy. Spectral domain optical coherence tomography images and patient charts were evaluated in retrospect. Immunocytochemistry revealed hyalocytes and myofibroblasts as predominant cell types. Ultrastructural analysis demonstrated evidence of vitreoschisis in all eyes. Myofibroblasts with contractile properties were observed to span between folds of the internal limiting membrane and vitreous cortex collagen. Retinal pigment epithelial cells or inflammatory cells were not detected. Mean visual acuity (Snellen) showed significant improvement from 20/72 ± 20/36 to 20/41 ± 20/32 (P < 0.001) after a mean follow-up period of 19 months (median, 17 months). During this period, none of the eyes required anti-vascular endothelial growth factor therapy. Fibrocellular premacular proliferation in intermediate age-related macular degeneration predominantly consists of vitreous collagen, hyalocytes, and myofibroblasts with contractile properties. Vitreoschisis and vitreous-derived cells appear to play an important role in traction formation of this subgroup of eyes. In patients with intermediate age-related macular degeneration and contractile premacular membrane, release of traction by vitrectomy with internal limiting membrane peeling results in significantly functional and anatomical improvement.

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...

Feasibility of telemedicine in detecting diabetic retinopathy and age-related macular degeneration.

PubMed

Vaziri, Kamyar; Moshfeghi, Darius M; Moshfeghi, Andrew A

2015-03-01

Age-related macular degeneration and diabetic retinopathy are important causes of visual impairment and blindness in the world. Because of recent advances and newly available treatment modalities along with the devastating consequences associated with late stages of these diseases, much attention has been paid to the importance of early detection and improving patient access to specialist care. Telemedicine or, more specifically, digital retinal imaging utilizing telemedical technology has been proposed as an important alternative screening and management strategy to help meet this demand. In this paper, we perform a literature review and analysis that evaluates the validity and feasibility of telemedicine in detecting diabetic retinopathy and age-related macular degeneration. Understanding both the progress and barriers to progress that have been demonstrated in these two areas is important for future telemedicine research projects and innovations in telemedicine technology.

IRay therapy as an adjuvant therapy in newly diagnosed patients with neovascular age-related macular degeneration.

PubMed

Brand, Christopher; Arnoldussen, Mark

2018-04-17

To determine the safety and efficacy at 12 months of follow-up after stereotactic radiotherapy in combination therapy with intravitreal ranibizumab injections in treatment naïve patients with neovascular age-related macular degeneration. Retrospective data analysis in patients who received stereotactic radiotherapy (IRay Therapy) during the induction phase of intravitreal ranibizumab injections and a monotherapy control group. The baseline VA in the IRay and control group was 59.87 and 59.12 letters respectively. The real world visual acuity outcomes for the IRay group showed a mean gain of +3.0 letters at 12 months. The historical control group had a mean change of - 0.3 letters. The average number of injections for the IRay group and control group over 12 months was 4.45 and 5.64, respectively with three loading injections. Excluding the loading phase, the difference over 12 months was a 45.2% reduction in injections (P < 0.001). The number of subjects in the IRay group that didn't require further injections following the loading phase was 45.5 vs. 24.0% control group (P = 0.005). The difference in mean change in central macular thickness from baseline is significant at 6 (P = 0.010) and 12 months (P < 0.01). There were no safety concerns with the IRay therapy group. Stereotactic radiotherapy in the induction phase of intravitreal injections of ranibizumab for treatment naïve patients with neovascular age-related macular degeneration, resulted in improved visual outcome, statistically fewer injections and statistically drier macular at 12 months, compared to historical controls treated with monotherapy intravitreal ranibizumab injections.

A hypothesis for treating inflammation and oxidative stress with hydrogen sulfide during age-related macular degeneration.

PubMed

George, Akash K; Singh, Mahavir; Homme, Rubens Petit; Majumder, Avisek; Sandhu, Harpal S; Tyagi, Suresh C

2018-01-01

Age-related macular degeneration (AMD) is a leading cause of blindness and is becoming a global crisis since affected people will increase to 288 million by 2040. Genetics, age, diabetes, gender, obesity, hypertension, race, hyperopia, iris-color, smoking, sun-light and pyroptosis have varying roles in AMD, but oxidative stress-induced inflammation remains a significant driver of pathobiology. Eye is a unique organ as it contains a remarkable oxygen-gradient that generates reactive oxygen species (ROS) which upregulates inflammatory pathways. ROS becomes a source of functional and morphological impairments in retinal pigment epithelium (RPE), endothelial cells and retinal ganglion cells. Reports demonstrated that hydrogen sulfide (H 2 S) acts as a signaling molecule and that it may treat ailments. Therefore, we propose a novel hypothesis that H 2 S may restore homeostasis in the eyes thereby reducing damage caused by oxidative injury and inflammation. Since H 2 S has been shown to be a powerful antioxidant because of its free-radicals' inhibition properties in addition to its beneficial effects in age-related conditions, therefore, patients may benefit from H 2 S salubrious effects not only by minimizing their oxidant and inflammatory injuries to retina but also by lowering retinal glutamate excitotoxicity.

Protect Your Eyes: Age-Related Macular Degeneration (AMD) Facts and Prevention Tips

MedlinePlus

PROTECT YOUR EYES Age-Related Macular Degeneration ( AMD ) FACTS & PREVENTION TIPS A LEADING CAUSE OF VISION LOSS IN THE U.S . AMD is a ... Black 2% Other 89% White As the population ages, the number of cases is expected to increase ...

Early changes in macular optical coherence tomography parameters after Ranibizumab intravitreal injection in patients with exsudative age-related macular degeneration.

PubMed

de Almeida, Nicole Antunes; de Souza, Osias Francisco

2018-01-01

Evaluation of the impact of different macular optical coherence parameters on visual acuity as early as 1 day after injection of ranibizumab in patients with subfoveal exsudative age-related macular degeneration. This was an interventional, non randomized, open label prospective study, where we evaluated 20 eyes of 20 patients affected by exudative age-related macular degeneration. These patients were treated with injections of ranibizumab between February 2013 and January 2015. The primary endpoint of this study was to evaluate the early changes in optical coherence tomography parameters (retinal thickness, central and total retinal volume) and impact on best-corrected visual acuity (BCVA) obtained by logarithm of minimum resolution using ETDRS protocol in patients treated with a single dose intravitreal injection of ranibizumab (0.5 mg/0.05 mL) during the first month of follow. The patients were evaluated on the first day, them at 7 and 30 days after the treatment. The National Eye Institute Visual Functioning Questionnaire was applied during the study period to assess early perception of ranibizumab injection effectiveness. The adverse events were monitored throughout the study. Central retinal thickness values at 1 (464.0 ± 97.8 µm), 7 (379.9 ± 107.8 µm) and 30 days (365.5 ± 95.1 µm) after ranibizumab injection showed a statically significant reduction when compared with baseline results ( P  = 0.01, P  = 0.001, P  = 0.001, respectively). Similar alterations were observed in central and total retinal volume, which were detected early on the first day of evaluation, after the measurement at baseline (central: 0.36 ± 0.07 vs. 0.40 ± 0.10 mm 3 , P  = 0.01; total: 9.62 ± 1.10 vs. 9.99 ± 2.56 mm 3 , P  = 0.002) and remained steady at 7 ( P  = 0.001, P  = 0.002, respectively) and 30 days ( P  = 0.001, P  = 0.004, respectively) with slight variations without losing their gains in these parameters. The best

Treatment outcomes after 3 years in neovascular age-related macular degeneration using a treat-and-extend regimen.

PubMed

Rayess, Nadim; Houston, S K Steven; Gupta, Omesh P; Ho, Allen C; Regillo, Carl D

2015-01-01

To determine 3-year treatment outcomes after 1 to 3 years of ranibizumab or bevacizumab therapy using a treat-and-extend regimen in patients with neovascular age-related macular degeneration (AMD). Retrospective, interventional, consecutive case series. We treated 212 eyes from 196 patients diagnosed with treatment-naive neovascular AMD between January 2009 and March 2013; they were treated with either ranibizumab or bevacizumab for a minimum of 1 year, using a treat-and-extend regimen. The main outcome measures were change from baseline best-corrected Snellen visual acuity (BCVA), proportion of eyes losing <3 BCVA lines, proportion of eyes gaining ≥ 3 BCVA lines, change from baseline central retinal thickness, and mean number of injections at 1, 2 and 3 years of follow-up. The mean follow-up period was 1.88 years (median, 2 years). At baseline, mean BCVA was 20/139; it improved to 20/79 (P < 0.001) after 1 year of treatment and was maintained at 20/69 and 20/64 at 2 and 3 years follow-up (P < 0.001), respectively. At baseline, mean central retinal thickness was 351 μm and significantly decreased to 285 μm, 275 μm and 276 μm at 1, 2 and 3 years of follow-up (P < 0.001), respectively. Patients received, on average, 7.6, 5.7 and 5.8 injections over years 1, 2 and 3 of treatment, respectively. At final follow-up, 94% of eyes had lost <3 lines BCVA, and 34.4% of eyes had gained ≥ 3 lines BCVA. The treat-and-extend regimen is effective in achieving and maintaining visual and anatomic improvements in patients with neovascular AMD for up to 3 years of treatment. Copyright © 2015 Elsevier Inc. 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...

Estimated cases of blindness and visual impairment from neovascular age-related macular degeneration avoided in Australia by ranibizumab treatment.

PubMed

Mitchell, Paul; Bressler, Neil; Doan, Quan V; Dolan, Chantal; Ferreira, Alberto; Osborne, Aaron; Rochtchina, Elena; Danese, Mark; Colman, Shoshana; Wong, Tien Y

2014-01-01

Intravitreal injections of anti-vascular endothelial growth factor agents, such as ranibizumab, have significantly improved the management of neovascular age-related macular degeneration. This study used patient-level simulation modelling to estimate the number of individuals in Australia who would have been likely to avoid legal blindness or visual impairment due to neovascular age-related macular degeneration over a 2-year period as a result of intravitreal ranibizumab injections. The modelling approach used existing data for the incidence of neovascular age-related macular degeneration in Australia and outcomes from ranibizumab trials. Blindness and visual impairment were defined as visual acuity in the better-seeing eye of worse than 6/60 or 6/12, respectively. In 2010, 14,634 individuals in Australia were estimated to develop neovascular age-related macular degeneration who would be eligible for ranibizumab therapy. Without treatment, 2246 individuals would become legally blind over 2 years. Monthly 0.5 mg intravitreal ranibizumab would reduce incident blindness by 72% (95% simulation interval, 70-74%). Ranibizumab given as needed would reduce incident blindness by 68% (64-71%). Without treatment, 4846 individuals would become visually impaired over 2 years; this proportion would be reduced by 37% (34-39%) with monthly intravitreal ranibizumab, and by 28% (23-33%) with ranibizumab given as needed. These data suggest that intravitreal injections of ranibizumab, given either monthly or as needed, can substantially lower the number of cases of blindness and visual impairment over 2 years after the diagnosis of neovascular age-related macular degeneration.

High Dose Intravitreal Bevacizumab for Refractory Pigment Epithelial Detachment in Age-related Macular Degeneration.

PubMed

Lee, Dong Kyu; Kim, Soon Hyun; You, Yong Sung; Kwon, Oh Woong

2016-08-01

Intravitreal anti-vascular endothelial growth factor (anti-VEGF) is the first choice of treatment for age-related macular degeneration. However, quite a few eyes treated using conventional dose anti-VEGF (CDAV) have persistent pigment epithelial detachment (PED) on optical coherence tomography. This study investigated the efficacy and safety of high dose anti-VEGF (HDAV) for refractory PED. In this retrospective study, 31 eyes of neovascular age-related macular degeneration patients with persistent PED findings despite six or more intravitreal injections of CDAV (bevacizumab 1.25 mg or ranibizumab 2.5 mg) were analyzed. Changes in visual outcome, central foveal thickness, and PED height were compared before and after HDAV (bevacizumab 5.0 mg) for these refractory PED cases. The mean age of patients was 67.7 years. The number of CDAV injections was 12.1. The number of HDAV injections was 3.39. Best-corrected visual acuity in logarithm of the minimum angle of resolution before and after HDAV was 0.49 and 0.41 (p < 0.001), respectively. Central foveal thickness before and after HDAV was 330.06 and 311.10 µm (p = 0.125), respectively. PED height before and after HDAV was 230.28 and 204.07 µm (p = 0.014), respectively. There were no serious adverse reactions in all the eyes. Increasing the dose of bevacizumab in refractory PED may be a possible treatment option.

ASSOCIATION OF DRUSEN VOLUME WITH CHOROIDAL PARAMETERS IN NONNEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PubMed

Balasubramanian, Siva; Lei, Jianqin; Nittala, Muneeswar G; Velaga, Swetha B; Haines, Jonathan; Pericak-Vance, Margaret A; Stambolian, Dwight; Sadda, SriniVas R

2017-10-01

The choroid is thought to be relevant to the pathogenesis of nonneovascular age-related macular degeneration, but its role has not yet been fully defined. In this study, we evaluate the relationship between the extent of macular drusen and specific choroidal parameters, including thickness and intensity. Spectral domain optical coherence tomography images were collected from two distinct, independent cohorts with nonneovascular age-related macular degeneration: Amish (53 eyes of 34 subjects) and non-Amish (40 eyes from 26 subjects). All spectral domain optical coherence tomography scans were obtained using the Cirrus HD-OCT with a 512 × 128 macular cube (6 × 6 mm) protocol. The Cirrus advanced retinal pigment epithelium analysis tool was used to automatically compute drusen volume within 3 mm (DV3) and 5 mm (DV5) circles centered on the fovea. The inner and outer borders of the choroid were manually segmented, and the mean choroidal thickness and choroidal intensity (i.e., brightness) were calculated. The choroidal intensity was normalized against the vitreous and nerve fiber layer reflectivity. The correlation between DV and these choroidal parameters was assessed using Pearson and linear regression analysis. A significant positive correlation was observed between normalized choroidal intensity and DV5 in the Amish (r = 0.42, P = 0.002) and non-Amish (r = 0.33, P = 0.03) cohorts. Also, DV3 showed a significant positive correlation with normalized choroidal intensity in both the groups (Amish: r = 0.30, P = 0.02; non-Amish: r = 0.32, P = 0.04). Choroidal thickness was negatively correlated with normalized choroidal intensity in both Amish (r = -0.71, P = 0.001) and non-Amish (r = -0.43, P = 0.01) groups. Normalized choroidal intensity was the most significant constant predictor of DV in both the Amish and non-Amish groups. Choroidal intensity, but not choroidal thickness, seems to be associated with drusen volume in Amish and non-Amish populations. These

Outcomes when Switching from a pro re nata Regimen to a Treat and Extend Regimen Using Aflibercept in Neovascular Age-Related Macular Degeneration.

PubMed

Giannakaki-Zimmermann, Helena; Ebneter, Andreas; Munk, Marion R; Wolf, Sebastian; Zinkernagel, Martin S

2016-01-01

To investigate outcomes in patients with neovascular age-related macular degeneration (AMD) switched from a pro re nata regimen (PRN) to a treat and extend regimen (TER) under aflibercept. Thirty-two patients were observed over 2 years: the first year on PRN and the second year on TER. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were evaluated. Intra- and subretinal fluid as well as the number of visits and injections were assessed. Both regimens resulted in a stable BCVA. Patients in TER had a significant decrease of CRT after 1 year compared to 1 year of treatment on PRN (p < 0.0001). TER resulted in significantly less visits; however, significantly more injections were observed over the course of 1 year compared to PRN (10.25 vs. 7.5, p < 0.0001 and 5.97 vs. 7.5, p = 0.0002, respectively). A switch from PRN to TER in patients treated with aflibercept for AMD appears to be safe. © 2016 S. Karger AG, Basel.

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

A Proinflammatory Function of Toll-Like Receptor 2 in the Retinal Pigment Epithelium as a Novel Target for Reducing Choroidal Neovascularization in Age-Related Macular Degeneration.

PubMed

Feng, Lili; Ju, Meihua; Lee, Kei Ying V; Mackey, Ashley; Evangelista, Mariasilvia; Iwata, Daiju; Adamson, Peter; Lashkari, Kameran; Foxton, Richard; Shima, David; Ng, Yin Shan

2017-10-01

Current treatments for choroidal neovascularization, a major cause of blindness for patients with age-related macular degeneration, treat symptoms but not the underlying causes of the disease. Inflammation has been strongly implicated in the pathogenesis of choroidal neovascularization. We examined the inflammatory role of Toll-like receptor 2 (TLR2) in age-related macular degeneration. TLR2 was robustly expressed by the retinal pigment epithelium in mouse and human eyes, both normal and with macular degeneration/choroidal neovascularization. Nuclear localization of NF-κB, a major downstream target of TLR2 signaling, was detected in the retinal pigment epithelium of human eyes, particularly in eyes with advanced stages of age-related macular degeneration. TLR2 antagonism effectively suppressed initiation and growth of spontaneous choroidal neovascularization in a mouse model, and the combination of anti-TLR2 and antivascular endothelial growth factor receptor 2 yielded an additive therapeutic effect on both area and number of spontaneous choroidal neovascularization lesions. Finally, in primary human fetal retinal pigment epithelium cells, ligand binding to TLR2 induced robust expression of proinflammatory cytokines, and end products of lipid oxidation had a synergistic effect on TLR2 activation. Our data illustrate a functional role for TLR2 in the pathogenesis of choroidal neovascularization, likely by promoting inflammation of the retinal pigment epithelium, and validate TLR2 as a novel therapeutic target for reducing choroidal neovascularization. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Machine learning based detection of age-related macular degeneration (AMD) and diabetic macular edema (DME) from optical coherence tomography (OCT) images

PubMed Central

Wang, Yu; Zhang, Yaonan; Yao, Zhaomin; Zhao, Ruixue; Zhou, Fengfeng

2016-01-01

Non-lethal macular diseases greatly impact patients’ life quality, and will cause vision loss at the late stages. Visual inspection of the optical coherence tomography (OCT) images by the experienced clinicians is the main diagnosis technique. We proposed a computer-aided diagnosis (CAD) model to discriminate age-related macular degeneration (AMD), diabetic macular edema (DME) and healthy macula. The linear configuration pattern (LCP) based features of the OCT images were screened by the Correlation-based Feature Subset (CFS) selection algorithm. And the best model based on the sequential minimal optimization (SMO) algorithm achieved 99.3% in the overall accuracy for the three classes of samples. PMID:28018716

Macular Atrophy Development and Subretinal Drusenoid Deposits in Anti-Vascular Endothelial Growth Factor Treated Age-Related Macular Degeneration.

PubMed

Zarubina, Anna V; Gal-Or, Orly; Huisingh, Carrie E; Owsley, Cynthia; Freund, K Bailey

2017-12-01

To explore the association between presence of subretinal drusenoid deposits (SDD) at baseline in eyes with neovascular age-related macular degeneration (nAMD) with the development of macular atrophy (MA) during anti-vascular endothelial growth factor (VEGF) therapy. There were 74 eyes without pre-existing MA receiving anti-VEGF therapy for nAMD for 2 years or longer analyzed. At least two image modalities that included spectral-domain optical coherence tomography, near-infrared reflectance, fluorescein angiography, and color fundus photos were used to assess for SDD presence, phenotype (dot and ribbon), and location, neovascularization type, and MA. Logistic regression models using generalized estimating equations assessed the association between SDD and the development of MA adjusting for age, neovascularization type, and choroidal thickness. SDD were present in 46 eyes (63%) at baseline. MA developed in 38 eyes (51%) during the mean of 4.7 ± 1.2 years of follow-up. Compared with eyes without SDD, those with SDD at baseline were 3.0 times (95% confidence interval [CI] 1.1-8.5, P = 0.0343) more likely to develop MA. Eyes with SDD present in the inferior macula and inferior extramacular fields at baseline were 3.0 times and 6.5 times more likely to develop MA at follow-up than eyes without SDD in these locations (95% CI 1.0-8.9, P = 0.0461 and 95% CI 1.3-32.4, P = 0.0218, respectively). MA development was not associated with a specific SDD phenotype. MA frequently developed in eyes during anti-VEGF treatment. SDD were independently associated with MA development. The extension of SDD into the inferior fundus, particularly in the inferior extramacular field, conferred higher odds of subsequent MA development.

Macular Atrophy Development and Subretinal Drusenoid Deposits in Anti-Vascular Endothelial Growth Factor Treated Age-Related Macular Degeneration

PubMed Central

Zarubina, Anna V.; Gal-Or, Orly; Huisingh, Carrie E.; Owsley, Cynthia

2017-01-01

Purpose To explore the association between presence of subretinal drusenoid deposits (SDD) at baseline in eyes with neovascular age-related macular degeneration (nAMD) with the development of macular atrophy (MA) during anti-vascular endothelial growth factor (VEGF) therapy. Methods There were 74 eyes without pre-existing MA receiving anti-VEGF therapy for nAMD for 2 years or longer analyzed. At least two image modalities that included spectral-domain optical coherence tomography, near-infrared reflectance, fluorescein angiography, and color fundus photos were used to assess for SDD presence, phenotype (dot and ribbon), and location, neovascularization type, and MA. Logistic regression models using generalized estimating equations assessed the association between SDD and the development of MA adjusting for age, neovascularization type, and choroidal thickness. Results SDD were present in 46 eyes (63%) at baseline. MA developed in 38 eyes (51%) during the mean of 4.7 ± 1.2 years of follow-up. Compared with eyes without SDD, those with SDD at baseline were 3.0 times (95% confidence interval [CI] 1.1–8.5, P = 0.0343) more likely to develop MA. Eyes with SDD present in the inferior macula and inferior extramacular fields at baseline were 3.0 times and 6.5 times more likely to develop MA at follow-up than eyes without SDD in these locations (95% CI 1.0–8.9, P = 0.0461 and 95% CI 1.3–32.4, P = 0.0218, respectively). MA development was not associated with a specific SDD phenotype. Conclusions MA frequently developed in eyes during anti-VEGF treatment. SDD were independently associated with MA development. The extension of SDD into the inferior fundus, particularly in the inferior extramacular field, conferred higher odds of subsequent MA development. PMID:29196768

Predictors of drusen reduction after subthreshold infrared (810 nm) diode laser macular grid photocoagulation for nonexudative age-related macular degeneration.

PubMed

Rodanant, Nuttawut; Friberg, Thomas R; Cheng, Lingyun; Aurora, Ajay; Bartsch, Dirk; Toyoguchi, Mitsuko; Corbin, Patricia S; El-Bradey, Mohamed H; Freeman, William R

2002-10-01

To determine the predictors of drusen reduction in eyes with nonexudative age-related macular degeneration (ARMD) treated with subthreshold infrared (810 nm) diode laser macular grid photocoagulation. Additionally, to determine the relationship of laser-induced drusen reduction and best-corrected visual acuity (BCVA) 18 months after laser treatment. Randomized controlled clinical trial. Fifty patients (100 eyes) with bilateral nonexudative ARMD were enrolled at two centers. One eye of each patient was randomized to the observation; the other eye was treated with 48 subthreshold (invisible end point) applications of infrared (810 nm) diode laser in a macular grid pattern. The eyes that received subthreshold laser treatment were compared with the eyes that received no treatment. The baseline fundus characteristics (number, size, and distribution of drusen, as well as focal hyperpigmentation) from two macula areas (central 1500 micro diameter, pericentral 1500 micro ring area) on stereo color photographs, the number of laser-induced lesions, and the area of laser induced retinal pigment epithelial (RPE) lesions on fluorescein angiography 3 months after treatment were studied as predictors of major drusen reduction (> or = 50% drusen reduction from baseline) 18 months after laser treatment. BCVA at baseline and 18 months later was compared in observation eyes and in laser-treated eyes. Eighteen months after randomization, 24 (48%) of 50 eyes treated with subthreshold laser had major drusen reduction compared with three (6%) of 50 observation eyes (P =.00001). At 3 months post-treatment in laser-treated eyes with major drusen reduction, the mean number of laser-induced lesions on fluorescein angiography was 30.7 and the mean area of RPE change was 0.81 mm(2) compared with 14.8 laser-induced lesions and 0.35 mm(2) area of RPE change in eyes without major drusen reduction (P =.0001 and P =.0003, respectively). At baseline, fundus characteristics were not significantly

LASER RESENSITIZATION OF MEDICALLY UNRESPONSIVE NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: Efficacy and Implications.

PubMed

Luttrull, Jeffrey K; Chang, David B; Margolis, Benjamin W L; Dorin, Giorgio; Luttrull, David K

2015-06-01

Drug tolerance is the most common cause of treatment failure in neovascular age-related macular degeneration. "Low-intensity/high-density" subthreshold diode micropulse laser (SDM) has been reported effective for a number of retinal disorders without adverse effects. It has been proposed that SDM normalizes retinal pigment epithelial function. On this basis, it has been postulated that SDM treatment might restore responsiveness to anti-vascular endothelial growth factor drugs in drug-tolerant eyes. Subthreshold diode micropulse laser treatment was performed in consecutive eyes unresponsive to all anti-vascular endothelial growth factor drugs, including at least three consecutive ineffective aflibercept injections. Monthly aflibercept was resumed 1 month after SDM treatment. Thirteen eyes of 12 patients, aged 73 to 97 years (average, 84 years), receiving 16 to 67 (average, 34) anti-vascular endothelial growth factor injections before SDM treatment were included and followed for 3 months to 7 months (average, 5 months) after SDM treatment. After SDM treatment and resumption of aflibercept, 92% (12 of 13) of eyes improved, with complete resolution of macular exudation in 69% (9 of 13). Visual acuity remained unchanged. Central and maximum macular thicknesses significantly improved. Subthreshold diode micropulse laser treatment restored drug response in drug-tolerant eyes with neovascular age-related macular degeneration. Based on these findings, a theory of SDM action is proposed, suggesting a wider role for SDM as retinal reparative/protective therapy.

Potential of Induced Pluripotent Stem Cells (iPSCs) for Treating Age-Related Macular Degeneration (AMD).

PubMed

Fields, Mark; Cai, Hui; Gong, Jie; Del Priore, Lucian

2016-12-08

The field of stem cell biology has rapidly evolved in the last few decades. In the area of regenerative medicine, clinical applications using stem cells hold the potential to be a powerful tool in the treatment of a wide variety of diseases, in particular, disorders of the eye. Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are promising technologies that can potentially provide an unlimited source of cells for cell replacement therapy in the treatment of retinal degenerative disorders such as age-related macular degeneration (AMD), Stargardt disease, and other disorders. ESCs and iPSCs have been used to generate retinal pigment epithelium (RPE) cells and their functional behavior has been tested in vitro and in vivo in animal models. Additionally, iPSC-derived RPE cells provide an autologous source of cells for therapeutic use, as well as allow for novel approaches in disease modeling and drug development platforms. Clinical trials are currently testing the safety and efficacy of these cells in patients with AMD. In this review, the current status of iPSC disease modeling of AMD is discussed, as well as the challenges and potential of this technology as a viable option for cell replacement therapy in retinal degeneration.

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.

Mortality after a cerebrovascular event in age-related macular degeneration patients treated with bevacizumab ocular injections.

PubMed

Hanhart, Joel; Comaneshter, Doron S; Vinker, Shlomo

2018-04-16

To analyse the mortality associated with intravitreal injections of bevacizumab for age-related macular degeneration (AMD) in patients previously diagnosed with stroke or transient ischaemic attack (TIA). We reviewed bevacizumab-treated AMD patients with a diagnosis of stroke or TIA prior to their first bevacizumab injection (n = 948). Those patients, naïve to any anti-vascular endothelial growth factor (anti-VEGF) at the time of stroke/TIA, were then compared to age- and gender-matched patients who had a stroke/TIA at the same time and had never been exposed to anti-VEGF. Survival analysis was performed using adjusted Cox regression. The main outcome measure was survival. Adjusted variables were age, smoking, alcohol abuse, hypertension, diabetes mellitus, obesity, ischaemic heart disease, congestive heart failure and liver cancer. Age and gender distribution of bevacizumab-treated patients and controls were similar (mean age: 83.4 versus 83.7 years, p = 0.3; 51.7% males versus 52.5% males, p = 0.7). The adjusted mortality in patients who received bevacizumab within 3 months after stroke/TIA was significantly different than in patients non-exposed to bevacizumab (OR = 6.92, 95%, CI 1.88-25.43, p < 0.01). Within 6 months after stroke/TIA, the difference in adjusted mortality showed a strong trend (OR = 2.00, 95%, CI 0.96-4.16, p = 0.064). Within 12 months, it was insignificant (OR = 1.30, 95%, CI 0.75-2.26, p = 0.348). We found increased mortality within three months after a cerebrovascular event in patients treated with bevacizumab for AMD compared to patients for whom there was no record of a prescription to any anti-VEGF agent. © 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Does Vertical Reading Help People with Macular Degeneration: An Exploratory Study

PubMed Central

Calabrèse, Aurélie; Liu, Tingting; Legge, Gordon E.

2017-01-01

Individuals with macular degeneration often develop a Preferred Retinal Locus (PRL) used in place of the impaired fovea. It is known that many people adopt a PRL left of the scotoma, which is likely to affect reading by occluding text to the right of fixation. For such individuals, we examined the possibility that reading vertical text, in which words are rotated 90° with respect to the normal horizontal orientation, would be beneficial for reading. Vertically oriented words would be tangential to the scotoma instead of being partially occluded by it. Here we report the results of an exploratory study that aimed at investigating this hypothesis. We trained individuals with macular degeneration who had PRLs left of their scotoma to read text rotated 90° clockwise and presented using rapid serial visual presentation (RSVP). Although training resulted in improved reading of vertical text, the training did not result in reading speeds that appreciably exceeded reading speeds following training with horizontal text. These results do not support the hypothesis that people with left PRLs read faster with vertical text. PMID:28114373

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.

[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.

An 8-year follow-up of anti-vascular endothelial growth factor treatment with a treat-and-extend modality for neovascular age-related macular degeneration.

PubMed

Berg, Karina; Roald, Anca B; Navaratnam, Jesintha; Bragadóttir, Ragnheiður

2017-12-01

To investigate long-term visual results of treatment with anti-vascular endothelial growth factor (VEGF) agents for neovascular age-related macular degeneration (nAMD) following a treat-and-extend regimen. Retrospective review of 155 patients who initiated treatment with bevacizumab for nAMD in one eye. At the final 8-year visit, 40 patients (26%) remained for follow-up. Mean change in best-corrected visual acuity (BCVA) was calculated compared to baseline values. Mean BCVA improved significantly from baseline during the first year of treatment, with -0.11 logMAR units equivalent to 6.1 approximate Early Treatment Diabetic Retinopathy Study (approxETDRS) letters (p = <0.001). Mean BCVA was still significantly improved after 4 years of treatment for the entire group of patients and after 6 years of treatment for the subgroup of 40 patients who remained at the final 8-year visit. Thereafter, BCVA gradually declined and at 8 years, there was a mean change of 0.05 logMAR units equivalent to 2.1 approxETDRS letters below baseline (p = 0.530). Mean number of injections during the first year was 6.1 ± 2.8 and during year 8 was 5.4 ± 3.5. At 5 years, fundus autofluorescence showed some degree of macular atrophy in all eyes. At the final 8-year visit, 87.5% of the eyes had stable neovascular lesions with no fluid on optical coherence tomography (OCT). In an everyday clinical setting, treatment of nAMD patients with a treat-and-extend modality provided improvement and stability of vision for several years. After 8 years of follow-up, there was a decline in visual acuity (VA) that could be explained by macular atrophic development. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

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.

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,

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 ...

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

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.

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.

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

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

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.

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

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.

Relationship between reticular pseudodrusen and choroidal thickness in intermediate age-related macular degeneration: response.

PubMed

Ho, Chi Yd; Lek, Jia J; Aung, Khin Z; McGuinness, Myra B; Luu, Chi D; Guymer, Robyn H

2018-05-07

We thank Invernizzi, Nguyen and Gillies 1 for their interest in our paper "Relationship between reticular pseudodrusen and choroidal thickness in intermediate age-related macular degeneration". 2 . This article is protected by copyright. All rights reserved.

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.

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

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

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.

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

Mouse genetics and proteomic analyses demonstrate a critical role for complement in a model of DHRD/ML, an inherited macular degeneration

PubMed Central

Garland, Donita L.; Fernandez-Godino, Rosario; Kaur, Inderjeet; Speicher, Kaye D.; Harnly, James M.; Lambris, John D.; Speicher, David W.; Pierce, Eric A.

2014-01-01

Macular degenerations, inherited and age related, are important causes of vision loss. Human genetic studies have suggested perturbation of the complement system is important in the pathogenesis of age-related macular degeneration. The mechanisms underlying the involvement of the complement system are not understood, although complement and inflammation have been implicated in drusen formation. Drusen are an early clinical hallmark of inherited and age-related forms of macular degeneration. We studied one of the earliest stages of macular degeneration which precedes and leads to the formation of drusen, i.e. the formation of basal deposits. The studies were done using a mouse model of the inherited macular dystrophy Doyne Honeycomb Retinal Dystrophy/Malattia Leventinese (DHRD/ML) which is caused by a p.Arg345Trp mutation in EFEMP1. The hallmark of DHRD/ML is the formation of drusen at an early age, and gene targeted Efemp1R345W/R345W mice develop extensive basal deposits. Proteomic analyses of Bruch's membrane/choroid and Bruch's membrane in the Efemp1R345W/R345W mice indicate that the basal deposits comprise normal extracellular matrix (ECM) components present in abnormal amounts. The proteomic analyses also identified significant changes in proteins with immune-related function, including complement components, in the diseased tissue samples. Genetic ablation of the complement response via generation of Efemp1R345W/R345W:C3−/− double-mutant mice inhibited the formation of basal deposits. The results demonstrate a critical role for the complement system in basal deposit formation, and suggest that complement-mediated recognition of abnormal ECM may participate in basal deposit formation in DHRD/ML and perhaps other macular degenerations. PMID:23943789

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.

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.

Identification of spectral phenotypes in age-related macular degeneration patients

NASA Astrophysics Data System (ADS)

Davis, Bert; Russell, Steven; Abramoff, Michael; Nemeth, Sheila C.; Barriga, E. Simon; Soliz, Peter

2007-02-01

The purpose of this study is to show that there exists a spectral characteristic that differentiates normal macular tissue from various types of genetic-based macular diseases. This paper demonstrates statistically that hyperspectral images of macular and other retinal tissue can be used to spectrally differentiate different forms of age-related macular degeneration. A hyperspectral fundus imaging device has been developed and tested for the purpose of collecting hyperspectral images of the human retina. A methodology based on partial least squares and ANOVA has been applied to determine the hyperspectral representation of individual spectral characteristics of retinal features. Each discrete tissue type in the retina has an identifiable spectral shape or signature which, when combined with spatial context, aids in detection of pathological features. Variations in the amount and distribution of various ocular pigments or the inclusion of additional biochemical substances will allow detection of pathological conditions prior to traditional histological presentation. Fundus imaging cameras are ubiquitous and are one of the most common imaging modalities used in documenting a patient's retinal state for diagnosis, e.g. remotely, or for monitoring the progression of an ocular disease. The added diagnostic information obtained with only a minor retro-fit of a specialized spectral camera will lead to new diagnostic information to the clinical ophthalmologist or eye-care specialist.

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.

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.

Chromatic multifocal pupillometer for objective perimetry in patients with macular degeneration (Conference Presentation)

NASA Astrophysics Data System (ADS)

Rotenstreich, Ygal; Ben-Ner, Daniel; Mahajna, Mohamad; Chibel, Ron; Sher, Ifat

2016-03-01

Purpose: To objectively assess visual field (VF) defects and retinal cell function in healthy subjects and patients with macular degeneration using a chromatic multifocal pupillometer. Methods: A multifocal chromatic pupillometer (MCP) was used to record pupillary responses (PR) of 17 healthy subjects and 5 Best Vitelliform macular dystrophy patients. Blue and red light stimuli (peak 485nm and 620nm, respectively) were presented at light intensities of 400 and 1000 cd/m2, respectively at 76 different points in a 16.2 degree VF. The PR of patients were compared with their findings on Humphrey's 24-2 perimetry, optical coherence tomography and the PR obtained from healthy subjects. Results: Patients demonstrated reduced percentage of pupillary contraction and slower maximal contraction velocity, more than two standard errors (SE) away from the mean of healthy subjects in response to red light in majority of VF locations. In response to blue light, the percentage of pupillary contraction was lower (by over two SE) compared with normal controls only in central locations. The latency of maximal contraction velocity was shorter in patients compared with healthy subjects in response to both colors. Conclusions: This study demonstrated the advantage of using MCP-based objective VF to assess central scotoma in macular degeneration. Our finding also suggests that chromatic perimetry may differentiate between PR mediated by cones and rods, and can specifically detect defects in macular cones. Different parameters of PR such as latency of maximal contraction velocity may shed light on the pathophysiology of different blinding diseases.

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…

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

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.

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.

Compromised Integrity of Central Visual Pathways in Patients With Macular Degeneration.

PubMed

Malania, Maka; Konrad, Julia; Jägle, Herbert; Werner, John S; Greenlee, Mark W

2017-06-01

Macular degeneration (MD) affects the central retina and leads to gradual loss of foveal vision. Although, photoreceptors are primarily affected in MD, the retinal nerve fiber layer (RNFL) and central visual pathways may also be altered subsequent to photoreceptor degeneration. Here we investigate whether retinal damage caused by MD alters microstructural properties of visual pathways using diffusion-weighted magnetic resonance imaging. Six MD patients and six healthy control subjects participated in the study. Retinal images were obtained by spectral-domain optical coherence tomography (SD-OCT). Diffusion tensor images (DTI) and high-resolution T1-weighted structural images were collected for each subject. We used diffusion-based tensor modeling and probabilistic fiber tractography to identify the optic tract (OT) and optic radiations (OR), as well as nonvisual pathways (corticospinal tract and anterior fibers of corpus callosum). Fractional anisotropy (FA) and axial and radial diffusivity values (AD, RD) were calculated along the nonvisual and visual pathways. Measurement of RNFL thickness reveals that the temporal circumpapillary retinal nerve fiber layer was significantly thinner in eyes with macular degeneration than normal. While we did not find significant differences in diffusion properties in nonvisual pathways, patients showed significant changes in diffusion scalars (FA, RD, and AD) both in OT and OR. The results indicate that the RNFL and the white matter of the visual pathways are significantly altered in MD patients. Damage to the photoreceptors in MD leads to atrophy of the ganglion cell axons and to corresponding changes in microstructural properties of central visual pathways.

Preliminary in vitro and in vivo assessment of a new targeted inhibitor for choroidal neovascularization in age-related macular degeneration.

PubMed

Li, Wenbo; Dong, Lijie; Ma, Minwang; Hu, Bojie; Lu, Zhenyu; Liu, Xun; Liu, Juping; Li, Xiaorong

2016-01-01

Choroidal neovascularization (CNV) in age-related macular degeneration usually causes blindness. We established a novel targeted inhibitor for CNV in age-related macular degeneration. The inhibitor CR2-sFlt 1 comprises a CR2-targeting fragment and an anti-vascular endothelial growth factor (VEGF) domain (sFlt 1). The targeting of CR2-sFlt 1 was studied using the transwell assay in vitro and frozen sections in vivo using green fluorescent labeling. Transwell assay results showed that CR2-sFlt 1 migrated to the interface of complement activation products and was present in the retinal tissue of the CR2-sFlt 1-treated CNV mice. Treatment effects were assessed by investigating the VEGF concentration in retinal pigmented epithelial cell medium and the thickness of the CNV complex in the mice treated with CR2-sFlt 1. CR2-sFlt 1 significantly reduced the VEGF secretion from retinal pigmented epithelial cells in vitro and retarded CNV progress in a mouse model. Expression analysis of VEGF and VEGFRs after CR2-sFlt 1 intervention indicated the existence of feedback mechanisms in exogenous CR2-sFlt 1, endogenous VEGF, and VEGFR interaction. In summary, we demonstrated for the first time that using CR2-sFlt 1 could inhibit CNV with clear targeting and high selectivity.

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.

Age-related macular degeneration: beyond anti-angiogenesis.

PubMed

Kent, David L

2014-01-06

Recently, anti-vascular endothelial growth factor therapies for neovascular age-related macular degeneration have been developed. These agents, originally developed for their anti-angiogenic mechanism of action, probably also work through an anti-permeability effect in preventing or reducing the amount of leakage from submacular neovascular tissue. Other treatment modalities include laser photocoagulation, photodynamic therapy with verteporfin, and submacular surgery. In reality, these latter treatments can be similarly categorized as anti-angiogenic because their sole aim is destroying or removing choroidal neovascularization (CNV). At the cellular level, CNV resembles stereotypical tissue repair that consists of several matricellular components in addition to neovascularization. In the retina, the clinical term CNV is a misnomer since the term may more appropriately be referred to as aberrant submacular repair. Furthermore, CNV raises a therapeutic conundrum: To complete or correct any reparative process in the body, angiogenesis becomes an essential component. Anti-angiogenic therapy, in all its guises, arrests repair and causes the hypoxic environment to persist, thus fueling pro-angiogenesis and further development of CNV as a component of aberrant repair. However, we realize that anti-vascular endothelial growth factor therapy preserves vision in patients with age-related macular degeneration, albeit temporarily and therefore, repeated treatment is needed. More importantly, however, anti-angiogenic therapy demonstrates that we can at the very least tolerate neovascular tissue beneath the macula and preserve vision in contrast to our historical approach of total vascular destruction. In this clinical scenario, it may be possible to look beyond anti-angiogenesis if our goal is facilitating submacular repair without destroying the neurosensory retina. Thus, in this situation of neovascular tolerance, it may be timely to consider treatments that facilitate

Laser treatment in patients with bilateral large drusen: the complications of age-related macular degeneration prevention trial.

PubMed

2006-11-01

To evaluate the efficacy and safety of low-intensity laser treatment in the prevention of visual acuity (VA) loss among participants with bilateral large drusen. Multicenter randomized clinical trial. One eye of each participant was assigned to treatment, and the contralateral eye was assigned to observation. A total of 1052 participants who had > or =10 large (>125 microm) drusen and VA> or =20/40 in each eye enrolled through 22 clinical centers. The initial laser treatment protocol specified 60 barely visible burns applied in a grid pattern within an annulus between 1500 and 2500 mum from the foveal center. At 12 months, eyes assigned to treatment that had sufficient drusen remaining were retreated with 30 burns by targeting drusen within an annulus between 1000 and 2000 mum from the foveal center. Proportion of eyes at 5 years with loss of > or =3 lines of VA from baseline. Secondary outcome measures included the development of choroidal neovascularization or geographic atrophy (GA), change in contrast threshold, change in critical print size, and incidence of ocular adverse events. At 5 years, 188 (20.5%) treated eyes and 188 (20.5%) observed eyes had VA scores > or = 3 lines worse than at the initial visit (P = 1.00). Cumulative 5-year incidence rates for treated and observed eyes were 13.3% and 13.3% (P = 0.95) for choroidal neovascularization and 7.4% and 7.8% (P = 0.64) for GA, respectively. The contrast threshold doubled in 23.9% of treated eyes and in 20.5% of observed eyes (P = 0.40). The critical print size doubled in 29.6% of treated eyes and in 28.4% of observed eyes (P = 0.70). Seven treated eyes and 14 observed eyes had an adverse event of a > or =6-line loss in VA in the absence of late age-related macular degeneration or cataract. As applied in the Complications of Age-Related Macular Degeneration Prevention Trial, low-intensity laser treatment did not demonstrate a clinically significant benefit for vision in eyes of people with bilateral large

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.

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.

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

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…

AMO Teledioptric System for age-related macular degeneration

NASA Astrophysics Data System (ADS)

Chou, Jim-Son; Ting, Albert C.

1994-05-01

A 2.5 X magnification system consisting of a two-zone intraocular implant and a spectacle was developed, tested, and clinically tried by fifty patients with cataract ad age-related macular degeneration. Optical bench testing results and clinical data confirmed that the field of view of the system was 2.6 times wider than an equivalent external telescope. The study also demonstrated that the implant itself was clinically equivalent to a standard monofocal intraocular lens for cataract. The clinical study indicated that higher magnification without compromising the compactness and optical quality was needed as the disease progressed. Also, a sound vision rehabilitation process is important to provide patients the full benefits of the system.

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.).

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.

Time to first treatment: The significance of early treatment of exudative age-related macular degeneration.

PubMed

Rauch, Renate; Weingessel, Birgit; Maca, Saskia M; Vecsei-Marlovits, Pia V

2012-07-01

To determine whether the time span between initial symptoms and treatment with ranibizumab in patients with neovascular age-related macular degeneration has an effect on visual outcome. In this retrospective study, 45 patients with exudative age-related macular degeneration were split into 3 groups depending on the duration of visual symptoms--Group I: <1 month, Group II: 1 month to 6 months, and Group III: >6 months. Best-corrected visual acuity, clinical ophthalmologic examination, and central retinal thickness as measured by optical coherence tomography were recorded at baseline and 2 months later. Fluorescein angiography was performed at baseline. Treatment consisted of 2 intravitreal injections of 1.25 mg of ranibizumab at baseline and after 4 weeks. The mean time span between initial symptoms and treatment was 59 ± 62 days. In all groups, a reduction of retinal thickness was observed. Shorter disease duration, as estimated by persistence of visual symptoms, was correlated with a better visual outcome after treatment. Patients in Group I demonstrated a significant increase in best-corrected visual acuity (P = 0.007). Patients of Group II (P = 0.095) and Group III (P = 0.271) still achieved a visual improvement in best-corrected visual acuity, albeit not significant. The mean change in best-corrected visual acuity was 0.08 ± 0.1 in all patients and was not statistically significant between groups (P = 0.87). Duration of visual symptoms <1 month before treatment is associated with a better visual outcome. Treatment of new-onset wet age-related macular degeneration should be initiated as soon as possible.

Nursing actions that create a sense of good nursing care in patients with wet age-related macular degeneration.

PubMed

Emsfors, Åsa; Christensson, Lennart; Elgán, Carina

2017-09-01

To identify and describe nursing actions performed by nurses that create a sense of good nursing care in patients with wet age-related macular degeneration. People who suffer from wet age-related macular degeneration risk central vision loss. Treatment with antivascular endothelial growth factor is the only available option at present that preserves vision and no definitive cure currently exists. Patients feel that they are compelled to accept this treatment because they might otherwise become blind. An explorative and descriptive design based on the critical incident technique was used. Interviews with 16 Swedish patients who all had received intravitreal treatment for wet age-related macular degeneration. Two main areas of good nursing care were identified: 'Being perceived as an individual' and 'Being empowered'. The first area was divided into two categories: being respectful and being engaged. Being respectful was observed when nurses had a benevolent attitude towards their patients and answered questions kindly and politely. Patients saw themselves as individuals when nurses were available for conversation and focused on them. The second area was divided into two categories: encouraging participation and creating confidence. Encouraging participation refers to when nurses provided information continuously. Nurses instilled confidence and trust in their patients by keeping promises and by being honest. A respectful interaction between patients and caregivers is necessary for patients to obtain beneficial health care. Patient interviews revealed important information about nursing actions that created a sense of good nursing care in patients with wet age-related macular degeneration. Nurses acknowledged people as individuals and created trust by building partnerships and sharing decision-making. To address each patient's concerns, nurses need to prioritise each patient's narrative and participation by documenting agreements in their medical record. © 2017 John

Progress toward the maintenance and repair of degenerating retinal circuitry.

PubMed

Vugler, Anthony A

2010-01-01

Retinal diseases such as age-related macular degeneration and retinitis pigmentosa remain major causes of severe vision loss in humans. Clinical trials for treatment of retinal degenerations are underway and advancements in our understanding of retinal biology in health/disease have implications for novel therapies. A review of retinal biology is used to inform a discussion of current strategies to maintain/repair neural circuitry in age-related macular degeneration, retinitis pigmentosa, and Type 2 Leber congenital amaurosis. In age-related macular degeneration/retinitis pigmentosa, a progressive loss of rods/cones results in corruption of bipolar cell circuitry, although retinal output neurons/photoreceptive melanopsin cells survive. Visual function can be stabilized/enhanced after treatment in age-related macular degeneration, but in advanced degenerations, reorganization of retinal circuitry may preclude attempts to restore cone function. In Type 2 Leber congenital amaurosis, useful vision can be restored by gene therapy where central cones survive. Remarkable progress has been made in restoring vision to rodents using light-responsive ion channels inserted into bipolar cells/retinal ganglion cells. Advances in genetic, cellular, and prosthetic therapies show varying degrees of promise for treating retinal degenerations. While functional benefits can be obtained after early therapeutic interventions, efforts should be made to minimize circuitry changes as soon as possible after rod/cone loss. Advances in retinal anatomy/physiology and genetic technologies should allow refinement of future reparative strategies.

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.

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

An intravenous microdose of bevacizumab for the treatment of pigment epithelial detachment associated to age-related macular degeneration refractory to intravitreal bevacizumab: a case report.

PubMed

Wu, Lihteh; Evans, Teodoro

2011-01-01

The purpose of this study was to report the visual and anatomical outcomes of an intravenous microdose of 10 mg of bevacizumab in a patient with a vascularized pigment epithelial detachment (PED) associated with exudative age-related macular degeneration refractory to several intravitreal bevacizumab injections. Interventional case report and literature review. A 62-year-old female patient with a PED secondary to age-related macular degeneration was treated with 9 consecutive intravitreal injections of 2.5 mg of bevacizumab. Despite an initial response where the PED decreased in size, the subretinal fluid reabsorbed and the visual acuity improved; after the seventh injection, the PED started to grow in size again causing a drop in visual acuity. After an intravenous injection of 10 mg of bevacizumab, the patient experienced an improvement in visual acuity and a flattening of her PED. An intravenous injection of a microdose of bevacizumab appears to have resolved the PED with a sustained improvement of visual acuity.

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…

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

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.

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.

Yellow corneal ring associated with vitamin supplementation for age-related macular degeneration

PubMed Central

Eller, Andrew W; Gorovoy, Ian R; Mayercik, Vera A

2012-01-01

Purpose To report the first described cases of peripheral yellow corneal rings secondary to vitamin supplementation for age-related macular degeneration (ARMD). Design Retrospective single-center case series. Participants The eyes of four patients taking vitamin supplementation for ARMD were examined at University of Pittsburgh Medical Center (UPMC) Department of Ophthalmology between January 2010 and April 2011. Methods We reviewed the medical records of four patients with peripheral corneal rings receiving vitamin supplementation for ARMD. Main Outcome Measures the presence of peripheral yellow corneal rings, skin findings, and serum carotene levels. Results Each patient had circumferential yellow peripheral corneal rings and exhibited subtle yellowing of the skin most notable on the palms. Serum carotene levels were normal in two of the three cases and markedly elevated in the last case in which it was measured. Conclusion It is unclear at this time how to counsel patients with this ocular finding. We suspect that these rings are more common than generally appreciated as they can have a subtle appearance or may be misdiagnosed as arcus senilis. We suggest that a formal study be performed on a cohort of patients taking macular degeneration vitamin supplementation that specifically screens for yellow rings and measures serum carotene levels when they are identified. PMID:22330962

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.

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

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...

Angiographic Cystoid Macular Edema and Outcomes in the Comparison of Age-Related Macular Degeneration Treatments Trials.

PubMed

Shah, Neepa; Maguire, Maureen G; Martin, Daniel F; Shaffer, James; Ying, Gui-Shuang; Grunwald, Juan E; Toth, Cynthia A; Jaffe, Glenn J; Daniel, Ebenezer

2016-04-01

To describe morphologic and visual outcomes in eyes with angiographic cystoid macular edema (CME) treated with ranibizumab or bevacizumab for neovascular age-related macular degeneration (nAMD). Prospective cohort study within a randomized clinical trial. A total of 1185 CATT study subjects. Baseline fluorescein angiography (FA) images of all CATT study eyes were evaluated for CME. Grading of other characteristics on optical coherence tomography (OCT) and photographic images at baseline and during 2-year follow-up was completed by readers at the CATT Reading Centers. Three groups were created on the basis of baseline CME and intraretinal fluid (IRF) status: (1) CME, (2) IRF without CME, (3) neither CME nor IRF. Visual acuity (VA) and total central retinal thickness (CRT) on OCT at baseline, year 1, and year 2. Among 1131 participants with images of sufficient quality for determining CME and IRF at baseline, 92 (8.1%) had CME, 766 (67.7%) had IRF without CME, and 273 (24.1%) had neither. At baseline, eyes with CME had worse mean VA (letters) than eyes with IRF without CME and eyes with neither CME nor IRF (52 vs. 60 vs. 66 letters, P < 0.001); higher mean total CRT (μm) on OCT (514 vs. 472 vs. 404, P < 0.001); and greater hemorrhage, retinal angiomatous proliferation (RAP) lesions, and classic choroidal neovascularization (CNV). All groups showed improvement in VA at follow-up; however, the CME group started and ended with the worst VA among the 3 groups. Central retinal thickness, although higher at baseline for the CME group, was similar at 1 and 2 years follow-up for all groups. More eyes with CME (65.3%) developed scarring during 2 years of follow-up compared with eyes with IRF without CME (43.8%) and eyes with neither CME nor IRF (32.5%; P < 0.001). In CATT, eyes with CME had worse baseline and follow-up VA, although all groups showed similar rates of improvement in VA during 2 years of follow-up. Cystoid macular edema seems to be a marker for poorer visual

The role of anti-inflammatory agents in age-related macular degeneration (AMD) treatment

PubMed Central

Wang, Y; Wang, V M; Chan, C-C

2011-01-01

Although age-related macular degeneration (AMD) is not a classic inflammatory disease like uveitis, inflammation has been found to have an important role in disease pathogenesis and progression. Innate immunity and autoimmune components, such as complement factors, chemokines, cytokines, macrophages, and ocular microglia, are believed to be heavily involved in AMD development. Targeting these specific inflammatory molecules has recently been explored in an attempt to better understand and treat AMD. Although antivascular endothelial growth factor therapy is the first line of defence against neovascular AMD, anti-inflammatory agents such as corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), immunosuppressive agents (eg, methotrexate and rapamycin), and biologics (eg, infliximab, daclizumab, and complement inhibitors) may provide an adjunct or alternative mechanism to suppress the inflammatory processes driving AMD progression. Further investigation is required to evaluate the long-term safety and efficacy of these drugs for both neovascular and non-neovascular AMD. PMID:21183941

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.…

The Effect of an Educational Program for Persons with Macular Degeneration: A Pilot Study

ERIC Educational Resources Information Center

Smith, Theresa Marie; Thomas, Kimberly; Dow, Katherine

2009-01-01

Macular degeneration is the leading cause of vision loss in the United States for persons aged 60 and older. Compared to individuals without disabilities, individuals with low vision demonstrate a 15% to 30% higher dependence on others to perform activities of daily living. In addition, low vision can adversely affect a person's quality of life.…

Imaging polarimetry in patients with neovascular age-related macular degeneration

PubMed Central

Elsner, Ann E.; Weber, Anke; Cheney, Michael C.; VanNasdale, Dean A.; Miura, Masahiro

2007-01-01

Imaging polarimetry was used to examine different components of neovascular membranes in age-related macular degeneration. Retinal images were acquired with a scanning laser polarimeter. An innovative pseudo-color scale, based on cardinal directions of color, displayed two types of image information: relative phases and magnitudes of birefringence. Membranes had relative phase changes that did not correspond to anatomical structures in reflectance images. Further, membrane borders in depolarized light images had significantly higher contrasts than those in reflectance images. The retinal birefringence in neovascular membranes indicates optical activity consistent with molecular changes rather than merely geometrical changes. PMID:17429494

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...

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.

Biochemical Measurements of Free Opsin in Macular Degeneration Eyes: Examining the 11-CIS Retinal Deficiency Hypothesis of Delayed Dark Adaptation (An American Ophthalmological Society Thesis).

PubMed

Hanneken, Anne; Neikirk, Thomas; Johnson, Jennifer; Kono, Masahiro

2017-08-01

To test the hypothesis that delayed dark adaptation in patients with macular degeneration is due to an excess of free unliganded opsin (apo-opsin) and a deficiency of the visual chromophore, 11 -cis retinal, in rod outer segments. A total of 50 human autopsy eyes were harvested from donors with and without macular degeneration within 2-24 hrs. postmortem. Protocols were developed which permitted dark adaptation of normal human eyes after death and enucleation. Biochemical methods of purifying rod outer segments were optimized and the concentration of rhodopsin and apo-opsin was measured with UV-visible scanning spectroscopy. The presence of apo-opsin was calculated by measuring the difference in the rhodopsin absorption spectra before and after the addition of 11 -cis retinal. A total of 20 normal eyes and 16 eyes from donors with early, intermediate and advanced stages of macular degeneration were included in the final analysis. Dark adaptation was achieved by harvesting whole globes in low light, transferring into dark (light-proof) canisters and dissecting the globes using infrared light and image converters for visualization. Apo-opsin was readily detected in positive controls after the addition of 11 -cis retinal. Normal autopsy eyes showed no evidence of apo-opsin. Eyes with macular degeneration also showed no evidence of apo-opsin, regardless of the severity of disease. Methods have been developed to study dark adaptation in human autopsy eyes. Eyes with age-related macular degeneration do not show a deficiency of 11 -cis retinal or an excess of apo-opsin within rod outer segments.

Aqueous vascular endothelial growth factor and aflibercept concentrations after bimonthly intravitreal injections of aflibercept for age-related macular degeneration.

PubMed

Sawada, Tomoko; Wang, Xiying; Sawada, Osamu; Saishin, Yoshitsugu; Ohji, Masahito

2018-01-01

Clinical evidence supports the efficacy of bimonthly aflibercept injection for age-related macular degeneration. The study aimed to evaluate aqueous vascular endothelial growth factor and aflibercept concentrations and the efficacy of bimonthly aflibercept in patients with age-related macular degeneration. This study is a prospective, interventional case series. Enrolled were 35 eyes with exudative age-related macular degeneration from 35 patients. Patients received three bimonthly intravitreal aflibercept without loading doses. We collected the aqueous humor just before each injection, measured vascular endothelial growth factor and aflibercept concentrations by enzyme-linked immunosorbent assay and measured best-corrected visual acuity and central retinal subfield thickness before and after the injections. Aqueous vascular endothelial growth factor and aflibercept concentrations were measured. The vascular endothelial growth factor concentration was 135.4 ± 60.5 pg/mL (mean ± standard deviation, range 60.6-323.4) at baseline and below the lowest detectable limit in all eyes at month 2 and in 32 eyes at month 4 (P < 0.001 [month 2] and P < 0.001 [month 4]). The mean aflibercept concentration was 20.3 ng/mL at month 2 and 28.0 ng/mL at month 4. The mean logarithm of the minimum angle of resolution visual acuity improved from 0.50 ± 0.36 at baseline to 0.36 ± 0.40 at month 6 (P < 0.001). The mean central retinal subfield thickness decreased from 353 ± 100 μm at baseline to 236 ± 45 μm at month 6 (P < 0.001). Bimonthly aflibercept injections without loading doses may be considered a treatment option for age-related macular degeneration. © 2017 Royal Australian and New Zealand College of Ophthalmologists.

Color vision in an elderly patient with protanopic genotype and successfully treated unilateral age-related macular degeneration.

PubMed

Kitakawa, Takaaki; Hayashi, Takaaki; Tsuzuranuki, Satoshi; Kubo, Akiko; Tsuneoka, Hiroshi

2011-12-01

We investigated differences in color discrimination between the fellow eye and the affected eye successfully treated for unilateral age-related macular degeneration (AMD) in a 69-year-old male patient with protanopia. His best-corrected visual acuity (BCVA) was 1.2 in the right eye (RE) and 0.2 in the left eye (LE). Fundus and angiographic findings showed classic choroidal neovascularization (CNV) secondary to AMD in the LE. BCVA of the LE improved to 0.4, and CNV resolved by 15 months after initiating combined anti-vascular endothelial growth factor and photodynamic therapies. After CNV closure, the Farnsworth dichotomous was performed, showing confusion patterns of the protan axis in either eye. The Farnsworth-Munsell 100-hue test showed a total error score of 520 in the LE, much higher than the score of 348 in the RE. Complete genotypes of the long-wavelength-sensitive (L-) cone and middle-wavelength-sensitive (M-) cone opsin genes were determined by polymerase chain reaction, revealing that the patient had a single 5' L-M 3' hybrid gene (encoding an M-cone opsin), with this genotype responsible for protanopia (the L-cone opsin gene was non-functional), instead of the L-cone and M-cone opsin gene arrays. Poorer color vision discrimination in the LE than the RE remained present despite closure of CNV. The presence and type of congenital color vision defect can be confirmed using molecular genetic testing even if complications of acquired retinal diseases such as AMD are identified.

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.

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

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.

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.

EFFECT OF SYSTEMIC BETA-BLOCKERS, ACE INHIBITORS, AND ANGIOTENSIN RECEPTOR BLOCKERS ON DEVELOPMENT OF CHOROIDAL NEOVASCULARIZATION IN PATIENTS WITH AGE-RELATED MACULAR DEGENERATION.

PubMed

Thomas, Akshay S; Redd, Travis; Hwang, Thomas

2015-10-01

Recent studies have suggested that the use of systemic beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers can induce regression of choroidal neovascularization in rodent models. The purpose of this study is to evaluate if these agents have a protective effect against the development of choroidal neovascularization in patients with age-related macular degeneration. In this single-center retrospective case-control study, the charts of 250 patients with neovascular age-related macular degeneration were compared with those of 250 controls with dry age-related macular degeneration. Charts were reviewed for current and past use of beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers. Frequency tables were generated, and associations were examined using chi-square tests, t-tests, and multivariate logistic regression. There was no statistically significant difference between rates of beta-blocker use (P = 0.57), angiotensin-converting enzyme inhibitors use (P = 0.20), or angiotensin receptor blockers use (P = 0.61) between the 2 groups. Additionally, there was no statistically significant difference between rates of use of combinations of the above drugs between the two groups. Although there is growing evidence that beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers can induce regression of choroidal neovascularization in rodent models, these medications do not seem to confer a protective effect against the development of choroidal neovascularization in patients with age-related macular degeneration.

REDUCED CHORIOCAPILLARIS FLOW IN EYES WITH TYPE 3 NEOVASCULARIZATION AND AGE-RELATED MACULAR DEGENERATION.

PubMed

Borrelli, Enrico; Souied, Eric H; Freund, K Bailey; Querques, Giuseppe; Miere, Alexandra; Gal-Or, Orly; Sacconi, Riccardo; Sadda, SriniVas R; Sarraf, David

2018-04-30

To study choriocapillaris (CC) flow in eyes with Type 3 neovascularization (NV) and age-related macular degeneration, using optical coherence tomography angiography analysis. In this multicenter, retrospective, observational study, we collected data from 21 patients with unilateral Type 3 NV and age-related macular degeneration, based on clinical examination, structural optical coherence tomography, and fluorescein angiography when available. An additional group of 20 nonneovascular age-related macular degeneration eyes with unilateral Type 1 or Type 2 NV due to age-related macular degeneration was included for comparison. En face optical coherence tomography angiography imaging (3 × 3 mm scans) with quantitative microvascular analysis of the CC was performed. Main outcome measures were: 1) the percent nonperfused choriocapillaris area; and 2) the average CC signal void size. We included 21 patients with unilateral Type 3 NV (15 female, 71.5%) and 20 patients with unilateral Type 1 or 2 NV (9 female, 45.0% P = 0.118). Mean ± SD age was 82.1 ± 7.4 years in the unilateral Type 3 patients and 78.3 ± 8.1 in unilateral Type 1/2 NV subjects (P = 0.392). The percent nonperfused choriocapillaris area was 56.3 ± 8.1% in eyes with Type 3 NV and 51.9 ± 4.3% in the fellow eyes (P = 0.016). The average signal void size was also increased in those eyes with Type 3 NV (939.9 ± 680.9 μm), compared with the fellow eyes (616.3 ± 304.2 μm, P = 0.039). The number of signal voids was reduced in the Type 3 NV eyes (604.5 ± 282.9 vs. 747.3 ± 195.8, P = 0.046). The subfoveal choroidal thickness was 135.9 ± 54.2 μm in eyes with Type 3 NV and 167.2 ± 65.4 μm in the fellow eyes (P = 0.003). In addition, the fellow eyes of patients with unilateral Type 3 NV displayed more significant CC flow abnormalities versus the fellow eyes with unilateral Type 1/2 NV (percent nonperfused choriocapillaris area = 51.9 ± 4.3% vs. 46.0 ± 2.1%, respectively, P < 0.0001; and average signal

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

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.

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.

Emerging vascular endothelial growth factor antagonists to treat neovascular age-related macular degeneration.

PubMed

Hussain, Rehan M; Ciulla, Thomas A

2017-09-01

Evolving anti-vascular endothelial growth factor (VEGF) treatments for neovascular age-related macular degeneration (nAMD) include long acting agents, combination strategies involving new pathways, topical agents, sustained-release, and genetic therapy strategies. Areas covered: Brolucizumab and abicipar pegol have smaller molecular size, facilitating higher concentrations and potentially longer duration than current anti-VEGF agents. Agents being combined with anti-VEGFs include OPT-302 (to inhibit VEGF-C and VEGF-D); pegpleranib and rinucumab (to inhibit platelet derived growth factor, PDGF - but both failed to show consistently improved visual outcomes compared to anti-VEGF monotherapy); and RG7716, ARP-1536 and nesvacumab (to activate the Tie-2 tyrosine kinase receptor, which reduces permeability). X-82 is an oral anti-VEGF and anti-PDGF being tested in phase 2 studies. Topical anti-VEGF ± anti-PDGF drugs under study include pazopanib, PAN-90806, squalamine lactate, regorafinib, and LHA510. Sustained-release anti-VEGF delivery treatments, such as the ranibizumab Port Delivery System, GB-102, NT-503, hydrogel depot, Durasert, and ENV1305 aim to reduce the burden of frequent injections. Gene therapies with new viral vectors hold the potential to induce sustained expression of anti-angiogenic proteins via the retina's cellular apparatus, and include AVA-101/201, ADVM-202/302, AAV2-sFLT01, RGX314, and Retinostat. Expert opinion: There are many emerging anti-VEGF treatments that aim to improve visual outcomes and reduce the treatment burden of nAMD.

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.

Optical Coherence Tomography Monitoring Strategies for A-VEGF-Treated Age-Related Macular Degeneration: An Evidence-Based Analysis.

PubMed

Pron, G

2014-01-01

New anti-angiogenesis pharmacotherapies have dramatically altered treatment of age-related macular degeneration (AMD), the leading cause of blindness in older adults. Monthly intraocular injections however, are extremely burdensome to ophthalmologists, patients, and their families. Repeated injections also increase risks of complications or adverse events. Although the pharmacokinetics of anti-vascular endothelial growth factor (A-VEGF) drugs are fairly well known, an individuals' AMD presentation and their pharmacodynamics or response to the drug has been shown to be extremely variable. Therefore treating everyone on the same fixed or standard regimen has potential for undertreating or overtreating patients, and drug costs are not trivial. To review monitoring strategies and to evaluate the role of optical coherence tomography (OCT) in guiding management of A-VEGF-treated neovascular AMD (n-AMD) patients. Systematic reviews of biographic databases for studies published between 2008 and February 2013 involving A-VEGF-treated n-AMD patients monitored in longitudinal follow-up. Studies were grouped according to varying treatments, monitoring schedules, and re-treatment protocols reported for n-AMD patients treated with A-VEGF. Several outcomes were evaluated across strategies including visual acuity (VA), retinal anatomy, re-treatment criteria and frequencies of clinical follow-up, OCT imaging investigations, and intravitreal injections. Results were summarized qualitatively, as heterogeneity in study objectives and methods precluded formal meta-analysis. A systematic review identified 18 randomized controlled trials (RCTs) and 20 observational studies involving A-VEGF treatment employing various monitoring and as-needed (PRN) re-treatment protocols. Several maintenance strategies were unsuccessful, resulting in lower VA gains and stabilization than monthly injections in A-VEGF-treated n-AMD. These included fixed quarterly treatment; fixed quarterly monitoring and

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.

Transplantation of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells in Macular Degeneration.

PubMed

Mehat, Manjit S; Sundaram, Venki; Ripamonti, Caterina; Robson, Anthony G; Smith, Alexander J; Borooah, Shyamanga; Robinson, Martha; Rosenthal, Adam N; Innes, William; Weleber, Richard G; Lee, Richard W J; Crossland, Michael; Rubin, Gary S; Dhillon, Baljean; Steel, David H W; Anglade, Eddy; Lanza, Robert P; Ali, Robin R; Michaelides, Michel; Bainbridge, James W B

2018-06-05

Transplantation of human embryonic stem cell (hESC)-derived retinal pigment epithelial (RPE) cells offers the potential for benefit in macular degeneration. Previous trials have reported improved visual acuity (VA), but lacked detailed analysis of retinal structure and function in the treated area. Phase 1/2 open-label dose-escalation trial to evaluate safety and potential efficacy (clinicaltrials.gov identifier, NCT01469832). Twelve participants with advanced Stargardt disease (STGD1), the most common cause of macular degeneration in children and young adults. Subretinal transplantation of up to 200 000 hESC-derived RPE cells with systemic immunosuppressive therapy for 13 weeks. The primary end points were the safety and tolerability of hESC-derived RPE cell administration. We also investigated evidence of the survival of transplanted cells and measured retinal structure and function using microperimetry and spectral-domain OCT. Focal areas of subretinal hyperpigmentation developed in all participants in a dose-dependent manner in the recipient retina and persisted after withdrawal of systemic immunosuppression. We found no evidence of uncontrolled proliferation or inflammatory responses. Borderline improvements in best-corrected VA in 4 participants either were unsustained or were matched by a similar improvement in the untreated contralateral eye. Microperimetry demonstrated no evidence of benefit at 12 months in the 12 participants. In one instance at the highest dose, localized retinal thinning and reduced sensitivity in the area of hyperpigmentation suggested the potential for harm. Participant-reported quality of life using the 25-item National Eye Institute Visual Function Questionnaire indicated no significant change. Subretinal hyperpigmentation is consistent with the survival of viable transplanted hESC-derived RPE cells, but may reflect released pigment in their absence. The findings demonstrate the value of detailed analysis of spatial correlation of

TREATMENT OF NEOVASCULAR AGE-RELATED MACULAR DEGENERATION PATIENTS WITH VASCULAR ENDOTHELIAL GROWTH FACTOR INHIBITORS IN EVERYDAY PRACTICE: Identification of Health Care Constraints in Germany-The PONS Study.

PubMed

Ehlken, Christoph; Wilke, Thomas; Bauer-Steinhusen, Ulrike; Agostini, Hansjürgen T; Hasanbasic, Zoran; Müller, Sabrina

2018-06-01

The PONS study was conceived to analyze the extent of nonpersistence (NP) and nonadherence (NA) in the treatment of patients with neovascular age-related macular degeneration in everyday clinical practice in Germany. Further objectives were to identify factors that can affect NP and NA and to analyze clinical outcomes under everyday conditions. Nonpersistence (no contact with doctor for at least 3 months) and NA (no treatment or follow-up for at least 6 weeks) as well as clinical data were analyzed up to 24 months retrospectively and 12 months prospectively in 480 patients with neovascular age-related macular degeneration in 23 treatment centers. Patients were interviewed for factors possibly affecting NP and NA. One third of patients fulfilled criteria of NA in the first 3 months and two thirds after 6 months. The NP was 18.8% after 12 months. Treatment exclusively at one center, a higher number of patients with neovascular age-related macular degeneration at the treating center, and fixed appointments were associated with a lower risk for NP. An initial gain in visual acuity after upload was not preserved after 12 months (mean change -0.5 Early Treatment Diabetic Retinopathy Study letters). Whereas visual acuity declined by 7.5 Early Treatment Diabetic Retinopathy Study letters in patients with good baseline visual acuity >20/40, visual acuity improved by 8.5 letters in patients with baseline visual acuity of ≤20/200. Only 7.5% of patients underwent an optical coherence tomography scan after 3 upload injections, and only 2.0 optical coherence tomographies were performed in the first 12 months. The NP and NA were high in our study population and are likely to have contributed to a suboptimal clinical outcome compared with randomized clinical trials. Shortcomings in the management of patients with neovascular age-related macular degeneration, including restrictions in the timely and adequate follow-up (including optical coherence tomography) and retreatment

The Difference that Age Makes: Cultural Factors that Shape Older Adults' Responses to Age-Related Macular Degeneration

ERIC Educational Resources Information Center

Mogk, Marja

2008-01-01

This article suggests that approaching vision loss from age-related macular degeneration from a sociocultural perspective, specifically considering perceptions of aging, blindness, disability, and generational viewpoints and norms, may be critical to understanding older adults' responses to vision loss and visual rehabilitation.

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

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.

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.

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.

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.

Patient Awareness of Cataract and Age-related Macular Degeneration among the Korean Elderly: A Population-based Study.

PubMed

Lee, Hankil; Jang, Yong Jung; Lee, Hyung Keun; Kang, Hye Young

2017-12-01

Age-related eye disease is often considered part of natural aging. Lack of awareness of eye conditions can result in missed treatment. We investigated the rates of awareness of cataract and age-related macular degeneration, the most common age-related eye-diseases, and the associated factors among elderly Koreans. We identified 7,403 study subjects (≥40 years old) with cataract or age-related macular degeneration based on ophthalmic examination results during the 5th Korean National Health and Nutrition Examination Survey conducted between 2010 and 2012. We assessed whether patients were aware of their eye condition based on a previous diagnosis by a physician. The average awareness rate over the 3-year study period was 23.69% in subjects with cataract and 1.45% in subjects with age-related macular degeneration. Logistic regression analysis showed that patients with cataract were more likely to recognize their condition if they had myopia (odds ratio, 2.08), hyperopia (odds ratio, 1.33), family history of eye disease (odds ratio, 1.44), or a past eye examination (odds ratio, 4.07-29.10). The presence of diabetes mellitus was also a significant predictor of patient awareness of cataract (odds ratio, 1.88). Poor patient recognition of eye disease among the Korean elderly highlights the seriousness of this potential public health problem in our aging society. Pre-existing eye-related conditions and diabetes were significant predictors of awareness; therefore, patients in frequent contact with their doctors have a greater chance of detecting eye disease. © 2017 The Korean Ophthalmological Society

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

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.

A value-based medicine analysis of ranibizumab for the treatment of subfoveal neovascular macular degeneration.

PubMed

Brown, Melissa M; Brown, Gary C; Brown, Heidi C; Peet, Jonathan

2008-06-01

To assess the conferred value and average cost-utility (cost-effectiveness) for intravitreal ranibizumab used to treat occult/minimally classic subfoveal choroidal neovascularization associated with age-related macular degeneration (AMD). Value-based medicine cost-utility analysis. MARINA (Minimally Classic/Occult Trial of the Anti-Vascular Endothelial Growth Factor Antibody Ranibizumab in the Treatment of Neovascular AMD) Study patients utilizing published primary data. Reference case, third-party insurer perspective, cost-utility analysis using 2006 United States dollars. Conferred value in the forms of (1) quality-adjusted life-years (QALYs) and (2) percent improvement in health-related quality of life. Cost-utility is expressed in terms of dollars expended per QALY gained. All outcomes are discounted at a 3% annual rate, as recommended by the Panel on Cost-effectiveness in Health and Medicine. Data are presented for the second-eye model, first-eye model, and combined model. Twenty-two intravitreal injections of 0.5 mg of ranibizumab administered over a 2-year period confer 1.039 QALYs, or a 15.8% improvement in quality of life for the 12-year period of the second-eye model reference case of occult/minimally classic age-related subfoveal choroidal neovascularization. The reference case treatment cost is $52652, and the cost-utility for the second-eye model is $50691/QALY. The quality-of-life gain from the first-eye model is 6.4% and the cost-utility is $123887, whereas the most clinically simulating combined model yields a quality-of-life gain of 10.4% and cost-utility of $74169. By conventional standards and the most commonly used second-eye and combined models, intravitreal ranibizumab administered for occult/minimally classic subfoveal choroidal neovascularization is a cost-effective therapy. Ranibizumab treatment confers considerably greater value than other neovascular macular degeneration pharmaceutical therapies that have been studied in randomized

Development and Pilot Evaluation of a Psychosocial Intervention Program for Patients with Age-Related Macular Degeneration

ERIC Educational Resources Information Center

Birk, Tanja; Hickl, Susanne; Wahl, Hans-Werner; Miller, Daniel; Kammerer, Annette; Holz, Frank; Becker, Stefanie; Volcker, Hans E.

2004-01-01

Purpose: The psychosocial needs of patients suffering from severe visual loss associated with advanced age-related macular degeneration (ARMD) are generally ignored in the clinical routine. The aim of this study was to develop and evaluate a psychosocial intervention program for ARMD patients. This intervention program was based on six modules…

Effects of Repeated Intravitreal Aflibercept Injection on the Corneal Endothelium in Patients With Age-Related Macular Degeneration: Outcomes From the RE-VIEW Study.

PubMed

Lass, Jonathan H; Benetz, Beth Ann; Menegay, Harry J; Tsipis, Constantinos P; Cook, Jane Caty; Boyer, David S; Singer, Michael; Erickson, Kristine; Saroj, Namrata; Vitti, Robert; Chu, Karen W; Moini, Hadi; Soo, Yuhwen; Cheng, Yenchieh

2018-05-01

The effects of repeated intravitreal aflibercept injection (IAI) on the corneal endothelium were studied in patients with unilateral neovascular age-related macular degeneration. RE-VIEW was a phase 4, open-label, single-arm, multicenter study. Patients received IAI every 8 weeks after 3 monthly doses. Slit-lamp biomicroscopy was performed at all study visits. The central corneal endothelial health was evaluated by specular microscopy in the treated versus untreated fellow eyes at baseline and weeks 24 and 52. No slit-lamp abnormalities were noted in 154 enrolled patients (eyes). Baseline versus 52-week mean (±SD) endothelial morphometric values (n = 118) for the treated versus untreated fellow eyes were respectively as follows: endothelial cell density was 2410 ± 364 versus 2388 ± 384 cells/mm at baseline and remained unchanged at 2401 ± 353 versus 2376 ± 364 cells/mm at 52 weeks (P = 0.87); the coefficient of variation was 33.5 ± 4.4% versus 34.0 ± 5.0% at baseline and remained unchanged at 34.2 ± 4.7% versus 34.1 ± 4.9% at 52 weeks (P = 0.18); the percentage of hexagonal cells was 59.5 ± 5.8% versus 59.6 ± 6.4% at baseline and remained unchanged at 59.5 ± 6.0% versus 59.5 ± 5.8% at 52 weeks (P = 0.96). Repeated IAI for 52 weeks had no apparent corneal endothelial toxicity noted on specular microscopy in patients treated for neovascular age-related macular degeneration.

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.

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...

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

Gene therapy with recombinant adeno-associated vectors for neovascular age-related macular degeneration: 1 year follow-up of a phase 1 randomised clinical trial.

PubMed

Rakoczy, Elizabeth P; Lai, Chooi-May; Magno, Aaron L; Wikstrom, Matthew E; French, Martyn A; Pierce, Cora M; Schwartz, Steven D; Blumenkranz, Mark S; Chalberg, Thomas W; Degli-Esposti, Mariapia A; Constable, Ian J

2015-12-12

Neovascular, or wet, age-related macular degeneration causes central vision loss and represents a major health problem in elderly people, and is currently treated with frequent intraocular injections of anti-VEGF protein. Gene therapy might enable long-term anti-VEGF therapy from a single treatment. We tested the safety of rAAV.sFLT-1 in treatment of wet age-related macular degeneration with a single subretinal injection. In this single-centre, phase 1, randomised controlled trial, we enrolled patients with wet age-related macular degeneration at the Lions Eye Institute and the Sir Charles Gairdner Hospital (Nedlands, WA, Australia). Eligible patients had to be aged 65 years or older, have age-related macular degeneration secondary to active subfoveal choroidal neovascularisation, with best corrected visual acuity (BCVA) of 3/60-6/24 and 6/60 or better in the other eye. Patients were randomly assigned (3:1) to receive either 1 × 10(10) vector genomes (vg; low-dose rAAV.sFLT-1 group) or 1 × 10(11) vg (high-dose rAAV.sFLT-1 group), or no gene-therapy treatment (control group). Randomisation was done by sequential group assignment. All patients and investigators were unmasked. Staff doing the assessments were masked to the study group at study visits. All patients received ranibizumab at baseline and week 4, and rescue treatment during follow-up based on prespecified criteria including BCVA measured on the Early Treatment Diabetic Retinopathy Study (EDTRS) scale, optical coherence tomography, and fluorescein angiography. The primary endpoint was ocular and systemic safety. This trial is registered with ClinicalTrials.gov, number NCT01494805. From Dec 16, 2011, to April 5, 2012, we enrolled nine patients of whom eight were randomly assigned to receive either intervention (three patients in the low-dose rAAV.sFLT-1 group and three patients in the high-dose rAAV.sFLT-1 group) or no treatment (two patients in the control group). Subretinal injection of r

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

Tachyphylaxis Following Intravitreal Bevacizumab for Exudative Age-Related Macular Degeneration

PubMed Central

Forooghian, Farzin; Cukras, Catherine; Meyerle, Catherine B.; Chew, Emily Y.; Wong, Wai T.

2009-01-01

Purpose To describe tachyphylaxis to intravitreal bevacizumab (IVB) in patients with exudative age-related macular degeneration (AMD). Methods 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 which had previously demonstrated a therapeutic response in the same time interval. Results Five patients (6 eyes) were identified as developing tachyphylaxis following repeated treatment with IVB. High-dose IVB (2.50mg) did not restore therapeutic response in these patients. Bilateral tachyphylaxis to IVB was seen following an episode of unilateral post-injection 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). Conclusion Tachyphylaxis can occur following 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. PMID:19516114

Evolution of Geographic Atrophy in Participants Treated with Ranibizumab for Neovascular Age-related Macular Degeneration

PubMed Central

Thavikulwat, Alisa T.; Jacobs-El, Naima; Kim, Jane S.; Agrón, Elvira; Hasan, Jesia; Meyerle, Catherine B.; Valent, David; Cukras, Catherine A.; Wiley, Henry E.; Wong, Wai T.; Chew, Emily Y.

2016-01-01

Purpose To evaluate the risk factors, incidence, and rate of progression of geographic atrophy (GA) in eyes with neovascular age-related macular degeneration (nAMD) treated with ranibizumab. Design Post-hoc analysis of a prospective clinical study. Participants 69 participants with nAMD in at least one eye. Methods Participants were prospectively treated in the study eye with 0.5 mg intravitreal ranibizumab. Study eyes received 4 monthly injections followed by pro re nata injections until a fluid-free macula was achieved on optical coherence tomography. Risk factors assessed included baseline demographics, treatment, and ocular characteristics on imaging. Eyes were evaluated on fundus autofluorescence (FAF) for GA. The rate of GA area growth in study and fellow eyes was analyzed by linear regression of square-root transformed areas. Main Outcome Measures Development of new-onset GA and rate of GA area growth measured on ocular imaging, including FAF images of the study eyes. Results Sixty-nine participants (mean age 78.8±7.8 years) with an average of 40.0±13.6 months of follow-up were analyzed. Twenty-two of 69 study eyes (32%) were treatment naïve. During their first year of the study, participants received an average of 9.2±3.3 injections in the study eye. Of 63 study eyes with quality baseline images, 22 (35%) had pre-existing GA. Of the remaining 41 eyes, 7 (17%) developed new-onset GA during study follow-up. Those who developed new GA were older (all ≥79 years old) and had received fewer study injections on average (6.9 vs. 10.4 injections at 1 year) compared to those who did not develop new GA. Of the 12 treatment naïve study eyes without GA at baseline, 1 (8.3%) developed new GA during the study. In 21 study eyes with quantifiable GA area, eyes with GA present at baseline (16/21) enlarged by 0.34±0.26 mm/year, compared to 0.19±0.12 mm/year in eyes developing new-onset GA (5/21). Conclusions While 17% of study eyes without GA present at baseline

Evolution of Geographic Atrophy in Participants Treated with Ranibizumab for Neovascular Age-related Macular Degeneration.

PubMed

Thavikulwat, Alisa T; Jacobs-El, Naima; Kim, Jane S; Agrón, Elvira; Hasan, Jesia; Meyerle, Catherine B; Valent, David; Cukras, Catherine A; Wiley, Henry E; Wong, Wai T; Chew, Emily Y

2017-01-01

To evaluate the risk factors, incidence, and rate of progression of geographic atrophy (GA) in eyes with neovascular age-related macular degeneration (nAMD) treated with ranibizumab. Post-hoc analysis of a prospective clinical study. 69 participants with nAMD in at least one eye. Participants were prospectively treated in the study eye with 0.5 mg intravitreal ranibizumab. Study eyes received 4 monthly injections followed by pro re nata injections until a fluid-free macula was achieved on optical coherence tomography. Risk factors assessed included baseline demographics, treatment, and ocular characteristics on imaging. Eyes were evaluated on fundus autofluorescence (FAF) for GA. The rate of GA area growth in study and fellow eyes was analyzed by linear regression of square-root transformed areas. Development of new-onset GA and rate of GA area growth measured on ocular imaging, including FAF images of the study eyes. Sixty-nine participants (mean age 78.8±7.8 years) with an average of 40.0±13.6 months of follow-up were analyzed. Twenty-two of 69 study eyes (32%) were treatment naïve. During their first year of the study, participants received an average of 9.2±3.3 injections in the study eye. Of 63 study eyes with quality baseline images, 22 (35%) had pre-existing GA. Of the remaining 41 eyes, 7 (17%) developed new-onset GA during study follow-up. Those who developed new GA were older (all ≥79 years old) and had received fewer study injections on average (6.9 vs. 10.4 injections at 1 year) compared to those who did not develop new GA. Of the 12 treatment naïve study eyes without GA at baseline, 1 (8.3%) developed new GA during the study. In 21 study eyes with quantifiable GA area, eyes with GA present at baseline (16/21) enlarged by 0.34±0.26 mm/year, compared to 0.19±0.12 mm/year in eyes developing new-onset GA (5/21). While 17% of study eyes without GA present at baseline receiving ranibizumab developed new GA, the role of ranibizumab in the development

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.

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

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...

The Minnesota Grading System of eye bank eyes for age-related macular degeneration.

PubMed

Olsen, Timothy W; Feng, Xiao

2004-12-01

The Minnesota Grading System (MGS) is a method to evaluate human eye bank eyes and determine the level of age-related macular degeneration (AMD), by using criteria and definitions from the Age-Related Eye Disease Study (AREDS). Donor eyes (108 pairs) from the Minnesota Lions Eye Bank were cut circumferentially at the pars plana to remove the anterior segment. A 1000 +/- 2.5-microm ruby sphere was placed on the optic nerve as a size reference. A digital, high-resolution, color macular photograph was taken through a dissecting microscope. The neurosensory retina was removed from one globe of the pair. The underlying retinal pigment epithelium was rephotographed, localizing the fovea with a proportional triangle. A grid was superimposed in the macular photographs and images were graded according to AREDS criteria. Twenty pairs were dissected bilaterally and graded for symmetry. Eighty-eight globes were graded into one of four MGS categories. Nineteen (95%) of 20 globes had symmetric grades. The MGS provides a methodology to grade donor tissue from eye bank eyes to correspond to the AREDS classification system. Donor tissue may be used for subsequent molecular analysis, including genomics and proteomics.

Optical Coherence Tomography Monitoring Strategies for A-VEGF—Treated Age-Related Macular Degeneration: An Evidence-Based Analysis

PubMed Central

Pron, G

2014-01-01

Background New anti-angiogenesis pharmacotherapies have dramatically altered treatment of age-related macular degeneration (AMD), the leading cause of blindness in older adults. Monthly intraocular injections however, are extremely burdensome to ophthalmologists, patients, and their families. Repeated injections also increase risks of complications or adverse events. Although the pharmacokinetics of anti–vascular endothelial growth factor (A-VEGF) drugs are fairly well known, an individuals’ AMD presentation and their pharmacodynamics or response to the drug has been shown to be extremely variable. Therefore treating everyone on the same fixed or standard regimen has potential for undertreating or overtreating patients, and drug costs are not trivial. Objectives To review monitoring strategies and to evaluate the role of optical coherence tomography (OCT) in guiding management of A-VEGF–treated neovascular AMD (n-AMD) patients. Data Sources Systematic reviews of biographic databases for studies published between 2008 and February 2013 involving A-VEGF–treated n-AMD patients monitored in longitudinal follow-up. Review Methods Studies were grouped according to varying treatments, monitoring schedules, and re-treatment protocols reported for n-AMD patients treated with A-VEGF. Several outcomes were evaluated across strategies including visual acuity (VA), retinal anatomy, re-treatment criteria and frequencies of clinical follow-up, OCT imaging investigations, and intravitreal injections. Results were summarized qualitatively, as heterogeneity in study objectives and methods precluded formal meta-analysis. Results A systematic review identified 18 randomized controlled trials (RCTs) and 20 observational studies involving A-VEGF treatment employing various monitoring and as-needed (PRN) re-treatment protocols. Several maintenance strategies were unsuccessful, resulting in lower VA gains and stabilization than monthly injections in A-VEGF–treated n-AMD. These

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.

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

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…

Outcome of 5-Year Treatment of Neovascular Age-Related Macular Degeneration With Intravitreal Anti-VEGF Using "Treat and Extend" Regimen.

PubMed

Jaki Mekjavic, Polona; Zaletel Benda, Polona

2018-01-01

The aim of this study is twofold. First , to evaluate the long-term outcome of anti-vascular endothelial growth factor (anti-VEGF) treatment in a clinical setting using the "treat-and-extend regimen" (TER) in patients with neovascular age-related macular degeneration (nAMD). Second , to determine the proportion of patients treated with anti-VEGF with good visual acuity (VA), i.e., vision sufficient to maintain a high level of independence. We conducted a single center retrospective review of patients with treatment-naive nAMD who were treated with anti-VEGF. Patients were treated with anti-VEGF intravitreal injections according to the TER. Patients started treatment with monthly injections of either bevacizumab (1.25 mg/0.05 mL) or ranibizumab (0.5 mg/0.05 mL) until there were no signs present of choroidal neovascularization (CNV) activity. CNV activity was determined from fundus examination and SD-OCT imaging. Follow-up administration of intravitreal injections was extended by 2-week intervals, up to a total of 14 weeks, provided no signs of CNV activity were detected. In some patients, the first treatment was replaced with aflibercept (2 mg/0.05 mL). On the basis of the inclusion criterion for the study, that patients had to be treated for 5 years, a total of 101 patients were included in the study. In all patients, one eye was treated for a 5-year period, and thus we studied 101 eyes. Best corrected VA was analyzed at baseline and each year during the 5-year follow-up. VA improved initially after year 1 of the treatment. VA decreased in the subsequent 4 years of treatment, but remained significantly higher from year 1 to year 3 of the treatment compared to baseline values. Patients with good VA followed a similar trend: the proportion increased in the first year, and thereafter gradually decreased during the course of the 5-year follow up. At year 5, the number of patients with good VA decreased to baseline values. TER with anti-VEGF for n

Incidence of Intraocular Pressure Elevation following Intravitreal Ranibizumab (Lucentis) for Age-related Macular Degeneration.

PubMed

Reis, Gustavo Msm; Grigg, John; Chua, Brian; Lee, Anne; Lim, Ridia; Higgins, Ralph; Martins, Alessandra; Goldberg, Ivan; Clement, Colin I

2017-01-01

The aim of this article is to evaluate the rate of patients developing sustained elevated intraocular pressure (IOP) after ranibizumab (Lucentis) intravitreal (IVT) injections. This is a retrospective study. Charts of 192 consecutive patients receiving Lucentis for age-related macular degeneration (AMD) were retrospectively reviewed. We enrolled patients with at least two IOP measurements between injections. Elevated IOP was defined as >21 mm Hg with an increase of at least 20% from baseline. Noninjected contralateral eyes of the same patient cohort were used as control. Primary outcome was defined as elevated IOP. Secondary outcomes were presence and type of glaucoma, number of injections, and time to IOP elevation. Elevated IOP occurred at a significantly higher rate in eyes receiving IVT ranibizumab (7.47%; n = 9) compared with control (0.93%; n = 1). Patients with preexisting glaucoma or ocular hypertension (OHT) were more likely to develop elevated IOP after IVT ranibizumab injection. Intravitreal ranibizumab injections are associated with sustained IOP elevation in some eyes. Reis GMSM, Grigg J, Chua B, Lee A, Lim R, Higgins R, Martins A, Goldberg I, Clement CI. The Incidence of Intraocular Pressure Elevation following Intravitreal Ranibizumab (Lucentis) for Age-related Macular Degeneration. J Curr Glaucoma Pract 2017;11(1):3-7.

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.

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

[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.

Three-month outcome of ziv-aflibercept for exudative age-related macular degeneration.

PubMed

Mansour, Ahmad M; Chhablani, Jay; Antonios, Rafic S; Yogi, Rohit; Younis, Muhammad H; Dakroub, Rola; Chahine, Hasan

2016-12-01

In vitro and in vivo studies did not detect toxicity to the retinal pigment epithelium cells using intravitreal ziv-aflibercept. Our purpose is to ascertain the 3-month safety and efficacy in wet age-related macular degeneration (AMD) treated with intravitreal ziv-aflibercept. Prospectively, consecutive patients with wet AMD underwent ziv-aflibercept intravitreal injection (1.25 mg/0.05 mL) from March 2015 to November 2015. Monitoring of best-corrected visual acuity, intraocular inflammation, cataract progression and by spectral domain optical coherence tomography were carried out at baseline day 1, 1 week, 1 month, 2 months and 3 months after injections. 30 eyes were treated (22 Caucasians, 8 Indians; 16 men, 14 women; 14 right eyes and 16 left eyes) with mean age of 74.3 years with 11 treatment-naïve cases and 19 having had treatment-non-naïve. Best-corrected visual acuity improved from baseline logMAR 1.08-0.74 at 1 week, 0.72 at 1 month, 0.67 at 2 months and 0.71 at 3 months (p<0.001 for all time periods). Central macular thickness in microns decreased from 332.8 to 302.0 at 1 week, 244.8 at 1 month, 229.0 at 2 months and 208.2 at 3 months (p<0.001 for all time periods). There were no signs of intraocular inflammation, or change in lens status or increase in intraocular pressure throughout the study. Off label use of ziv-aflibercept improves visual acuity, without detectable ocular toxicity and offers a cheaper alternative to the same molecule aflibercept, especially in low/middle-income countries and in countries where aflibercept (Eylea) is not available. NCT02486484. 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/.

SCARB1 rs5888 is associated with the risk of age-related macular degeneration susceptibility and an impaired macular area.

PubMed

Stanislovaitiene, Daiva; Zaliuniene, Dalia; Krisciukaitis, Algimantas; Petrolis, Robertas; Smalinskiene, Alina; Lesauskaite, Vita; Tamosiunas, Abdonas; Lesauskaite, Vaiva

2017-01-01

Age-related macular degeneration (ARMD), a progressive retinal disease, is responsible for an impaired central vision in about 180 million people worldwide. Current options for ARMD prevention and treatment are limited due to an incomplete understanding of disease etiopathogenesis. We aimed to test the hypothesis that the single nucleotide polymorphism rs5888 of SCARB1 gene reflecting lipid and antioxidant micronutrient metabolism pathways is associated with ARMD susceptibility and to evaluate if there is any relation between SCARB1 rs5888 and the macular lesion area. The prospective case-control study included patients with ARMD (n = 215) and the reference group (n = 238) drawn from a random sample of the Lithuanian population (n = 1436). The genotyping test of SCARB1 rs5888 was carried out using the real-time polymerase chain reaction method. Regression analysis adjusted by gender and age demonstrated that SCARB1 rs5888 TT genotype significantly decreased the odds for ARMD development (OR: 0.61, 95%; CI: 0.380-0.981, p = 0.04). A smoking habit and leading an outdoor life are associated with larger macular lesion areas in ARMD patients (0.54 (0.00-39.06) vs. 3.09 (0.02-19.30) and 0.27 (0.00-34.57) vs. 0.75 (0.00-39.06), respectively). In late stage ARMD subjects with CT genotype, the macular lesion area was larger than in TT carriers (7.64 (0.49-39.06) mm 2 vs. 5.02 (0.03-37.06) mm 2 , p = 0.006). SCARB1 rs5888 and environmental oxidative stress have a prominent role in ARMD susceptibility, early ARMD progression to advanced stage disease and even in the outcome of the disease-an area of macular lesion.

EFFECT OF INTRAVITREAL RANIBIZUMAB ON GANGLION CELL COMPLEX AND PERIPAPILLARY RETINAL NERVE FIBER LAYER IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION USING SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY.

PubMed

Zucchiatti, Ilaria; Cicinelli, Maria V; Parodi, Maurizio Battaglia; Pierro, Luisa; Gagliardi, Marco; Accardo, Agostino; Bandello, Francesco

2017-07-01

To analyze the changes in ganglion cell complex and peripapillary retinal nerve fiber layer thickness, in central macular thickness and choroidal thickness on spectral domain optical coherence tomography in patients with neovascular age-related macular degeneration treated with intravitreal ranibizumab injections. All consecutive patients with untreated neovascular age-related macular degeneration received loading phase of three monthly intravitreal ranibizumab, followed by retreatments on a pro re nata protocol for 12 months. changes in ganglion cell complex and retinal nerve fiber layer at the end of follow-up. Secondary outcome: changes in best-corrected visual acuity, central macular thickness, and choroidal thickness at the end of follow-up. Choroidal thickness was measured at 500 μm, 1000 μm, and 1,500 μm intervals nasally, temporally, superiorly, and inferiorly to the fovea, respectively, on horizontal and vertical line scans centered on the fovea. Twenty-four eyes were included. Ganglion cell complex and peripapillary retinal nerve fiber layer thickness did not show statistically significant changes through 12 months (55.6 ± 18.5 and 81.9 ± 9.9 μm at baseline, 52.7 ± 19.3 and 84.6 ± 15.5 μm at month 12, P > 0.05). Central macular thickness showed progressive decrease from baseline to month 12, with maximum reduction at month 3 (P < 0.001). Statistically significant reduction in choroidal thickness was registered in the nasal 500, 1000, and 1,500 μm from the fovea, corresponding to the papillomacular region (from 169.6 ± 45.3 to 153.9 ± 46.9, P < 0.001). Intravitreal ranibizumab injections did not affect retinal nerve fiber layer and ganglion cell complex thickness in 1-year follow-up. Choroidal thickness in papillomacular area and central macular thickness was significantly reduced at the end of treatment. Further studies, with larger sample, longer follow-up, and greater number of injections, are warranted.

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...

Abnormal dark-adapted electroretinogram in Best's vitelliform macular degeneration.

PubMed

Lachapelle, P; Quigley, M G; Polomeno, R C; Little, J M

1988-10-01

It is generally well accepted that in Best's vitelliform macular degeneration (BVMD) the electroretinogram (ERG) is normal whereas the electro-oculogram (EOG) is markedly abnormal. We describe a patient in whom BVMD was suspected on the basis of the clinical findings, EOG and family history (one of her daughters had the typical vitelliform lesion). However, her dark-adapted ERG was markedly abnormal. Similar anomalies were found in the dark-adapted ERG of the daughter. While the temporal features of the various ERG waves were well preserved, a substantial decrease in the amplitude of specific segments of the ERG signal was observed. A similar decrease in the amplitude of the oscillatory potentials was also found. We believe that this unusual combination of BVMD and abnormal dark-adapted ERG may be due to the reported reduced penetrance and variable expressivity of the BVMD gene(s).

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

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.

Senile macular changes in the black African.

PubMed Central

Gregor, Z.; Joffe, L.

1978-01-01

One thousand black African and 380 white Caucasian patients over the age of 50 were examined for evidence of age-related macular changes, namely, drusen, pigment epithelial atrophy, and disciform macular degeneration. Drusen and pigment epithelial changes were found to occur twice as commonly in Caucasians as in Africans; there was a much greater difference in the prevalence of disciform macular degeneration between the 2 groups. The cause of the differences remains unexplained. PMID:687553

Submacular hemorrhage in neovascular age-related macular degeneration: A synthesis of the literature.

PubMed

Stanescu-Segall, Dinu; Balta, Florian; Jackson, Timothy L

2016-01-01

Large submacular hemorrhage, an uncommon manifestation of neovascular age-related macular degeneration, may also occur with idiopathic polypoidal choroidal vasculopathy. Submacular hemorrhage damages photoreceptors owing to iron toxicity, fibrin meshwork contraction, and reduced nutrient flux, with subsequent macular scarring. Clinical and experimental studies support prompt treatment, as tissue damage can occur within 24 hours. Without treatment the natural history is poor, with a mean final visual acuity (VA) of 20/1600. Reported treatments include retinal pigment epithelial patch, macular translocation, pneumatic displacement, intravitreal or subretinal tissue plasminogen activator, intravitreal anti-vascular endothelial growth factor (VEGF) drugs, and combinations thereof. In the absence of comparative studies, we combined eligible studies to assess the VA change before and after each treatment option. The greatest improvement occurred after combined pars plana vitrectomy, subretinal tissue plasminogen activator, intravitreal gas, and anti-vascular endothelial growth factor treatment, with VA improving from 20/1000 to 20/400. The best final VA occurred using combined intravitreal tissue plasminogen activator, gas, and anti-vascular endothelial growth factor therapy, with VA improving from 20/200 to 20/100. Both treatments had an acceptable safety profile, but most studies were small, and larger randomized controlled trials are needed to determine both safety and efficacy. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

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.

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. )

INTRAVITREAL DEXAMETHASONE IMPLANT AS ADJUVANT TREATMENT FOR BEVACIZUMAB- AND RANIBIZUMAB-RESISTANT NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A Prospective Pilot Study.

PubMed

Barikian, Anita; Salti, Haytham; Safar, Ammar; Mahfoud, Ziyad R; Bashshur, Ziad F

2017-07-01

To study the benefit of intravitreal dexamethasone implant in the management of neovascular age-related macular degeneration resistant to bevacizumab and ranibizumab. Patients with persistent macular fluid on optical coherence tomography despite monthly treatment with at least three consecutive bevacizumab injections followed by at least three ranibizumab injections were prospectively enrolled. A single dexamethasone implant was administered followed by intravitreal ranibizumab 1 week later. Ranibizumab was continued afterward on an as-needed basis. Main outcomes were improvement in central retinal thickness and best-corrected visual acuity. Nineteen patients (19 eyes) were enrolled. There was no significant change in best-corrected visual acuity over 6 months. Greatest reduction in mean central retinal thickness, from 295.2 μm to 236.2 μm, occurred 1 month after dexamethasone implant (P < 0.0001). By Month 6, mean central retinal thickness was 287.3 μm (P = 0.16). Eyes with only intraretinal fluid (13 eyes) achieved a fluid-free macula. Eyes with predominantly subretinal fluid (6 eyes) did not improve central retinal thickness and continued monthly ranibizumab. Mean baseline intraocular pressure was 13.2 mmHg, which peaked at 15.6 mmHg by Month 2 (P = 0.004). Intravitreal dexamethasone implant improved only macular intraretinal fluid in eyes with neovascular age-related macular degeneration resistant to bevacizumab and ranibizumab. However, this treatment had a limited duration.

The Role of mf-ERG in the Diagnosis and Treatment of Age-Related Macular Degeneration: Electrophysiological Features of AMD.

PubMed

Moschos, Marilita M; Nitoda, Eirini

2018-01-01

Age-related macular cegeneration (AMD) is the leading cause of visual dysfunction worldwide, affecting 9-25% of individuals between 65 and 75 years old. We have reviewed the published articles investigating the role of multifocal electroretinogram (mf-ERG) in the diagnosis and treatment of AMD. Visual evoked potentials have revealed decreased amplitudes and higher latencies in patients with AMD, while the degeneration of photoreceptors and abnormalities of retinal pigment epithelium can be identified by electro-oculogram recordings. Moreover, ERG can detect the functional abnormalities observed in AMD and evaluate each therapeutic approach. The record of local electrophysiological responses coming from different retinal areas can be accurately performed by mfERG. The accuracy of mfERG in detecting the degeneration of photoreceptors, as well the disturbances of macular function, could be useful both in the early diagnosis of AMD and the assessment of treatment efficacy.

Macular Pigment and Lutein Supplementation in ABCA4-associated Retinal Degenerations

PubMed Central

Aleman, Tomas S.; Cideciyan, Artur V.; Windsor, Elizabeth A. M.; Schwartz, Sharon B.; Swider, Malgorzata; Chico, John D.; Sumaroka, Alexander; Pantelyat, Alexander Y.; Duncan, Keith G.; Gardner, Leigh M.; Emmons, Jessica M.; Steinberg, Janet D.; Stone, Edwin M.; Jacobson, Samuel G.

2008-01-01

PURPOSE To determine macular pigment (MP) optical density (OD) in patients with ABCA4-associated retinal degenerations (ABCA4-RD) and the response of MP and vision to supplementation with lutein. METHODS Stargardt disease or cone-rod dystrophy patients with foveal fixation and with known or suspected disease-causing mutations in the ABCA4 gene were included. MPOD profiles were measured with heterochromatic flicker photometry. Serum carotenoids, visual acuity, foveal sensitivity and retinal thickness were quantified. Changes in MPOD and central vision were determined in a subset of patients receiving oral supplementation with lutein for 6 months. RESULTS MPOD in patients ranged from normal to markedly abnormal. As a group, ABCA4-RD patients had reduced foveal MPOD and there was strong correlation with retinal thickness. Average foveal tissue concentration of MP, estimated by dividing MPOD by retinal thickness, was normal in patients whereas serum concentration of lutein and zeaxanthin was significantly lower than normal. After oral lutein supplementation for 6 months, 91% of the patients showed significant increases in serum lutein and 63% of the patient eyes showed a significant augmentation in MPOD. The retinal responders tended to be female, and have lower serum lutein and zeaxanthin, lower MPOD and greater retinal thickness at baseline. Responding eyes had significantly lower baseline MP concentration compared to non-responding eyes. Central vision was unchanged after the period of supplementation. CONCLUSIONS MP is strongly affected by the stage of ABCA4 disease leading to abnormal foveal architecture. MP could be augmented by supplemental lutein in some patients. There was no change in central vision after 6 months of lutein supplementation. Long-term influences on the natural history of this supplement on macular degenerations require further study. PMID:17325179

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.

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/.

Coronary Artery Disease and Reticular Macular Disease, a Subphenotype of Early Age-Related Macular Degeneration.

PubMed

Cymerman, Rachel M; Skolnick, Adam H; Cole, William J; Nabati, Camellia; Curcio, Christine A; Smith, R Theodore

2016-11-01

Reticular macular disease (RMD) is the highest risk form of early age-related macular degeneration and also specifically confers decreased longevity. However, because RMD requires advanced retinal imaging for adequate detection of its characteristic subretinal drusenoid deposits (SDD), it has not yet been completely studied with respect to coronary artery disease (CAD), the leading cause of death in the developed world. Because CAD appears in middle age, our purpose was to screen patients aged 45-80 years, documented either with or without CAD, to determine if CAD is associated with RMD. A prospective cohort study of patients with documented CAD status and no known retinal disease in a clinical practice setting at one institution. Subjects and Controls: A number of 76 eyes from 38 consecutive patients (23 with documented CAD, 15 controls documented without CAD; 47.4% female; mean age 66.7 years). Patients were imaged with near-infrared reflectance/spectral domain optical coherence tomography and assessed in masked fashion by two graders for the presence of SDD lesions of RMD and soft drusen. Presence or absence of RMD/SDD and soft drusen. RMD was more frequent in patients with CAD versus those without (Relative Risk [RR] = 2.1, CI = 1.08-3.95, P = 0.03). There was no association of CAD with soft drusen. A specific relationship between CAD and RMD suggests common systemic causes for both and warrants further study.

Age-related macular degeneration: using morphological predictors to modify current treatment protocols.

PubMed

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

2018-03-01

To assess predictors of treatment response in neovascular age-related macular degeneration (AMD) in an attempt to develop a patient-centric treatment algorithm. We conducted a systematic search using PubMed, EMBASE and Web of Science for prognostic indicators/predictive factors with the key words: 'age related macular degeneration', 'neovascular AMD', 'choroidal neovascular membrane (CNV)', 'anti-vascular endothelial growth factor (anti-VEGF)', 'aflibercept', 'ranibizumab', 'bevacizumab', 'randomized clinical trials', 'post-hoc', 'prognostic', 'predictive', 'response' 'injection frequency, 'treat and extend (TAE), 'pro re nata (PRN)', 'bi-monthly' and 'quarterly'. We only included studies that had an adequate period of follow-up (>1 year), a single predefined treatment regimen with a predetermined re-injection criteria, an adequate number of patients, specific morphological [optical coherence tomography (OCT)] criteria that predicted final visual outcomes and injection frequency and did not include switching from one drug to the other. We were able to identify seven prospective studies and 16 retrospective studies meeting our inclusion criteria. There are several morphological and demographic prognostic indicators that can predict response to therapy in wet AMD. Smaller CNV size, subretinal fluid (SRF), retinal angiomatous proliferation (RAP) and response to therapy at 12 weeks (visual, angiographic or OCT) can all predict good visual outcomes in patients receiving anti-VEGF therapy. Patients with larger CNV, older age, pigment epithelial detachment (PED), intraretinal cysts (IRC) and vitreomacular adhesion (VMA) achieved less visual gains. Patients having VMA/VMT required more intensive treatment with increased treatment frequency. Patients with both posterior vitreous detachment (PVD) and SRF require infrequent injections. Patients with PED are prone to recurrences of fluid activity with a reduction in visual acuity (VA). A regimen that involves less intensive

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.

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.

L-Sulforaphane confers protection against oxidative stress in an in vitro model of age-related macular degeneration.

PubMed

Dulull, Nabeela Khadija; Dias, Daniel Anthony; Thrimawithana, Thilini Rasika; Kwa, Faith Ai Ai

2018-01-25

In age-related macular degeneration, oxidative damage and abnormal neovascularization in the retina are caused by the upregulation of vascular endothelium growth factor and reduced expression of Glutathione-S-transferase genes. Current treatments are only palliative. Compounds from cruciferous vegetables (e.g. L-Sulforaphane) have been found to restore normal gene expression levels in diseases including cancer via the activity of histone deacetylases and DNA methyltransferases, thus retarding disease progression. To examine L-Sulforaphane as a potential treatment to ameliorate aberrant levels of gene expression and metabolites observed in age-related macular degeneration. The in vitro oxidative stress model of AMD was based on the exposure of Adult Retinal Pigment Epithelium-19 cell line to 200µM hydrogen peroxide. The effects of L-Sulforaphane on cell proliferation were determined by MTS assay. The role of GSTM1, VEGFA, DNMT1 and HDAC6 genes in modulating these effects were investigated using quantitative real-time polymerase chain reaction. The metabolic profiling of L-Sulforaphane-treated cells via gas-chromatography mass-spectrometry was established. Significant differences between control and treatment groups were validated using one-way ANOVA, student t test and post-hoc Bonferroni statistical tests (p<0.05). L-Sulforaphane induced a dose-dependent increase in cell cell proliferation in the presence of hydrogen peroxide by upregulating Glutathione-S-Transferase µ1 gene expression. Metabolic profiling revealed that L-Sulforaphane increased levels of 2-monopalmitoglycerol, 9, 12, 15,-(Z-Z-Z)-Octodecatrienoic acid, 2-[Bis(trimethylsilyl)amino]ethyl bis(trimethylsilyl)-phosphate and nonanoic acid but decreased β-alanine levels in the absence or presence of hydrogen peroxide, respectively. This study supports the use of L-Sulforaphane to promote regeneration of retinal cells under oxidative stress conditions. Copyright© Bentham Science Publishers; For any

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.

Early initial clinical experience with intravitreal aflibercept for wet age-related macular degeneration.

PubMed

Ferrone, Philip J; Anwar, Farihah; Naysan, Jonathan; Chaudhary, Khurram; Fastenberg, David; Graham, Kenneth; Deramo, Vincent

2014-06-01

Age-related macular degeneration (AMD) is a degenerative process that leads to severe vision loss. Wet AMD is defined by choroidal neovascularisation, leading to the accumulation of subretinal fluid (SRF), macular oedema (ME), and pigment epithelium detachments (PED). Purpose To evaluate the initial clinical experience of conversion from bevacizumab or ranibizumab to aflibercept in wet AMD patients. Records of 250 consecutive wet AMD patients were retrospectively reviewed. Of 250 patients, 29 were naive (with no previous treatment), and 221 were previously treated with bevacizumab (1/3) or ranibizumab (2/3). On average, converted patients received 14 injections every 6 weeks on a treat-and-extend regimen with Avastin or Lucentis before being converted to aflibercept every 7 weeks on average (no loading dose) for three doses. For the purposes of this study, we concentrated on the patients converted to aflibercept since the number of naive patients was too small to draw any conclusion from. Snellen (as logMar) visual acuities, and optical coherence tomography (OCT) were compared predrug and postdrug conversion. Converted patients did not show a significant difference in visual acuity or average OCT thickness from preconversion values; however, small improvements in ME (p=0.0001), SRF (p=0.0001), and PED (p=0.008) grading were noted on average after conversion to aflibercept. No significant difference in visual outcome or average OCT thickness was observed when switched from bevacizumab or ranibizumab q6 week to aflibercept 7-week dosing, on average. Mild anatomic improvements did occur in converted patients with regard to ME, SRF and PED improvement, on average, after conversion to aflibercept, and aflibercept was injected less frequently. No serious adverse reactions, including ocular infections or inflammation, as well as ocular and systemic effects were noted. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted

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.

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.

THICKNESS OF THE MACULA, RETINAL NERVE FIBER LAYER, AND GANGLION CELL-INNER PLEXIFORM LAYER IN THE AGE-RELATED MACULAR DEGENERATION: The Repeatability Study of Spectral Domain Optical Coherence Tomography.

PubMed

Shin, Il-Hwan; Lee, Woo-Hyuk; Lee, Jong-Joo; Jo, Young-Joon; Kim, Jung-Yeul

2018-02-01

To determine the repeatability of measuring the thickness of the central macula, retinal nerve fiber layer, and ganglion cell-inner plexiform layer (GC-IPL) using spectral domain optical coherence tomography (Cirrus HD-OCT) in eyes with age-related macular degeneration. One hundred and thirty-four eyes were included. The measurement repeatability was assessed by an experienced examiner who performed two consecutive measurements using a 512 × 128 macular cube scan and a 200 × 200 optic disk cube scan. To assess changes in macular morphology in patients with age-related macular degeneration, the patients were divided into the following three groups according to the central macular thickness (CMT): A group, CMT < 200 μm; B group, 200 μm ≤ CMT < 300 μm; and C group, CMT > 300 μm. Measurement repeatability was assessed using test-retest variability, a coefficient of variation, and an intraclass correlation coefficient. The mean measurement repeatability for the central macular, retinal nerve fiber layer, and GC-IPL thickness was high in the B group. The mean measurement repeatability for both the central macula and retinal nerve fiber layer thickness was high in the A and C groups, but was lower for the GC-IPL thickness. The measurement repeatability for GC-IPL thickness was high in the B group, but low in the A group and in the C group. The automated measurement repeatability for GC-IPL thickness was significantly lower in patients with age-related macular degeneration with out of normal CMT range. The effect of changes in macular morphology should be considered when analyzing GC-IPL thicknesses in a variety of ocular diseases.

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.

Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: Two-year results of the ANCHOR study.

PubMed

Brown, David M; Michels, Mark; Kaiser, Peter K; Heier, Jeffrey S; Sy, Judy P; Ianchulev, Tsontcho

2009-01-01

The 2-year, phase III trial designated Anti-vascular endothelial growth factor (VEGF) Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization (CNV) in Age-related Macular Degeneration (ANCHOR) compared ranibizumab with verteporfin photodynamic therapy (PDT) in treating predominantly classic CNV. Multicenter, international, randomized, double-masked, active-treatment-controlled clinical trial. Patients with predominantly classic, subfoveal CNV not previously treated with PDT or antiangiogenic drugs. Patients were randomized 1:1:1 to verteporfin PDT plus monthly sham intraocular injection or to sham verteporfin PDT plus monthly intravitreal ranibizumab (0.3 mg or 0.5 mg) injection. The need for PDT (active or sham) retreatment was evaluated every 3 months using fluorescein angiography (FA). The primary, intent-to-treat efficacy analysis was at 12 months, with continued measurements to month 24. Key measures included the percentage losing <15 letters from baseline visual acuity (VA) score (month 12 primary efficacy outcome measure), percentage gaining >or=15 letters from baseline, and mean change over time in VA score and FA-assessed lesion characteristics. Adverse events were monitored. Of 423 patients (143 PDT, 140 each in the 2 ranibizumab groups), the majority (>or=77% in each group) completed the 2-year study. Consistent with results at month 12, at month 24 the VA benefit from ranibizumab was statistically significant (P<0.0001 vs. PDT) and clinically meaningful: 89.9% to 90.0% of ranibizumab-treated patients had lost <15 letters from baseline (vs. 65.7% of PDT patients); 34% to 41.0% had gained >or=15 letters (vs. 6.3% of PDT group); and, on average, VA was improved from baseline by 8.1 to 10.7 letters (vs. a mean decline of 9.8 letters in PDT group). Changes in lesion anatomic characteristics on FA also favored ranibizumab (all comparisons P<0.0001 vs. PDT). Overall, there was no imbalance among groups in rates of serious ocular and

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...

Sham radiation in clinical trials assessing radiotherapy for exudative age-related macular degeneration.

PubMed

Marcus, D M; Camp, M W; Sheils, W C; McIntosh, S B; Leibach, D B; Johnson, M H; Samy, C N

1999-01-01

To evaluate the effectiveness of sham radiation treatments in masking patients to their randomization group in the Radiation of Age-Related Macular Degeneration (ROARMD) Study. Patients with choroidal neovascularization complicating age-related macular degeneration were randomized to a treatment (RAD) group that received external beam irradiation (seven treatment sessions) or to a control (SHAM) group that received sham radiation (one sham treatment session). During a telephone survey, 62 of 73 randomized patients responded to the following questions: Do you think you received radiation? Why do you feel that way? Did the vision in your study eye worsen after enrollment? Eighty-one percent of the RAD group and 59% of the SHAM group thought that they had received radiation. In patients who thought that their vision had stabilized or improved, 82% thought that they had received radiation. In patients who thought that their vision was worse, only 39% thought that they had received radiation. In 54% of patients, subjective perception of vision influenced their guess as to whether they received radiation. Subjective patient perception of visual outcome was the most influential variable for masking. Variation between radiation treatment and sham session techniques, such as equipment used and duration of treatments, played a lesser role in the masking of patients. Seven treatment days correlated with a higher number of patients who thought that they had received radiation. Although our procedures do not strictly mask the two groups, one sham radiation session was effective in keeping patients guessing their randomization group.

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.

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.

cGAS drives noncanonical-inflammasome activation in age-related macular degeneration.

PubMed

Kerur, Nagaraj; Fukuda, Shinichi; Banerjee, Daipayan; Kim, Younghee; Fu, Dongxu; Apicella, Ivana; Varshney, Akhil; Yasuma, Reo; Fowler, Benjamin J; Baghdasaryan, Elmira; Marion, Kenneth M; Huang, Xiwen; Yasuma, Tetsuhiro; Hirano, Yoshio; Serbulea, Vlad; Ambati, Meenakshi; Ambati, Vidya L; Kajiwara, Yuji; Ambati, Kameshwari; Hirahara, Shuichiro; Bastos-Carvalho, Ana; Ogura, Yuichiro; Terasaki, Hiroko; Oshika, Tetsuro; Kim, Kyung Bo; Hinton, David R; Leitinger, Norbert; Cambier, John C; Buxbaum, Joseph D; Kenney, M Cristina; Jazwinski, S Michal; Nagai, Hiroshi; Hara, Isao; West, A Phillip; Fitzgerald, Katherine A; Sadda, SriniVas R; Gelfand, Bradley D; Ambati, Jayakrishna

2018-01-01

Geographic atrophy is a blinding form of age-related macular degeneration characterized by retinal pigmented epithelium (RPE) death; the RPE also exhibits DICER1 deficiency, resultant accumulation of endogenous Alu-retroelement RNA, and NLRP3-inflammasome activation. How the inflammasome is activated in this untreatable disease is largely unknown. Here we demonstrate that RPE degeneration in human-cell-culture and mouse models is driven by a noncanonical-inflammasome pathway that activates caspase-4 (caspase-11 in mice) and caspase-1, and requires cyclic GMP-AMP synthase (cGAS)-dependent interferon-β production and gasdermin D-dependent interleukin-18 secretion. Decreased DICER1 levels or Alu-RNA accumulation triggers cytosolic escape of mitochondrial DNA, which engages cGAS. Moreover, caspase-4, gasdermin D, interferon-β, and cGAS levels were elevated in the RPE in human eyes with geographic atrophy. Collectively, these data highlight an unexpected role of cGAS in responding to mobile-element transcripts, reveal cGAS-driven interferon signaling as a conduit for mitochondrial-damage-induced inflammasome activation, expand the immune-sensing repertoire of cGAS and caspase-4 to noninfectious human disease, and identify new potential targets for treatment of a major cause of blindness.

HISTOLOGY OF GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION: A Multilayer Approach.

PubMed

Li, Miaoling; Huisingh, Carrie; Messinger, Jeffrey; Dolz-Marco, Rosa; Ferrara, Daniela; Freund, K Bailey; Curcio, Christine A

2018-05-03

To systematically characterize histologic features of multiple chorioretinal layers in eyes with geographic atrophy, or complete retinal pigment epithelium (RPE) and outer retinal atrophy, secondary to age-related macular degeneration, including Henle fiber layer and outer nuclear layer; and to compare these changes to those in the underlying RPE-Bruch membrane-choriocapillaris complex and associated extracellular deposits. Geographic atrophy was delimited by the external limiting membrane (ELM) descent towards Bruch membrane. In 13 eyes, histologic phenotypes and/or thicknesses of Henle fiber layer, outer nuclear layer, underlying supporting tissues, and extracellular deposits at four defined locations on the non-atrophic and atrophic sides of the ELM descent were assessed and compared across other tissue layers, with generalized estimating equations and logit models. On the non-atrophic side of the ELM descent, distinct Henle fiber layer and outer nuclear layer became dyslaminated, cone photoreceptor inner segment myoids shortened, photoreceptor nuclei and mitochondria translocated inward, and RPE was dysmorphic. On the atrophic side of the ELM descent, all measures of photoreceptor health declined to zero. Henle fiber layer/outer nuclear layer thickness halved, and only Müller cells remained, in the absence of photoreceptors. Sub-RPE deposits remained, Bruch membrane thinned, and choriocapillaris density decreased. The ELM descent sharply delimits an area of marked gliosis and near-total photoreceptor depletion clinically defined as Geographic atrophy (or outer retinal atrophy), indicating severe and potentially irreversible tissue damage. Degeneration of supporting tissues across this boundary is gradual, consistent with steady age-related change and suggesting that RPE and Müller cells subsequently respond to a threshold of stress. Novel clinical trial endpoints should be sought at age-related macular degeneration stages before intense gliosis and thick

Aspirin use and early age-related macular degeneration: a meta-analysis.

PubMed

Kahawita, Shyalle K; Casson, Robert J

2014-02-01

The aim of this review was to evaluate the evidence for an association between Aspirin use and early age-related macular degeneration (ARMD). A literature search was performed in 5 databases with no restrictions on language or date of publication. Four studies involving 10292 individuals examining the association between aspirin and ARMD met the inclusion criteria. Meta-analysis was carried out by Cochrane Collaboration Review Manager 5.2 software (Cochrane Collaboration, Copenhagen, Denmark). The pooled odd ratios showed that Aspirin use was associated with early ARMD (pooled odds ratio 1.43, 95% CI 1.09-1.88). There is a small but statistically significant association between Aspirin use and early ARMD, which may warrant further investigation. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

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

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

Earlier therapeutic effects associated with high dose (2.0 mg) Ranibizumab for treatment of vascularized pigment epithelial detachments in age-related macular degeneration

PubMed Central

Chan, C K; Abraham, P; Sarraf, D; Nuthi, A S D; Lin, S G; McCannel, C A

2015-01-01

Summary statement Intravitreal high dose (2 mg) ranibizumab may lead to quicker resolution of choroidal neovascularization (CNV) and associated retinal pigment epithelial detachment in eyes with exudative age-related macular degeneration, although it may possibly correlate with RPE tears in certain cases. Purpose This prospective study compared the outcomes of 0.5 vs 2.0 mg intravitreal ranibizumab injections (RI) for treating vascularized pigment epithelial detachment (vPED) due to age-related macular degeneration. Methods Patients with vPED were randomized to receive 2.0 vs 0.5 mg RI monthly for 12 months or for 4 months and then repeated on a pro-re nata basis. Optical coherence tomography, fundus photography, and fluorescein and indocyanine-green angiography were obtained at baseline and subsequent specific intervals. Outcome measures were best-corrected standardized visual acuities, central 1-mm thickness, surface area (SA), greatest linear diameter (GLD), heights (PED and CNV), and amount of subretinal fluid (SRF) and cystoid macular edema (CME). Results Both groups yielded reductions of the central 1-mm thickness, PED and CNV SA and PED height and GLD, SRF, and CME. Vision improvement and reduction in SRF and PED height occurred earlier for eyes receiving the 2.0 mg dose. Cataract progression was similar but RPE tears developed more often with the 2.0 mg dose. Conclusions There were similar visual and anatomical outcomes at the end of the study; however, the higher dose yielded more rapid reductions and more complete resolution of the PED, although there was possible increased tendency for an RPE tear with the higher dose. PMID:25277305

Psychosocial Adaptation to Visual Impairment and Its Relationship to Depressive Affect in Older Adults with Age-Related Macular Degeneration

ERIC Educational Resources Information Center

Tolman, Jennifer; Hill, Robert D.; Kleinschmidt, Julia J.; Gregg, Charles H.

2005-01-01

Purpose: In this study we examined psychosocial adaptation to vision loss and its relationship to depressive symptomatology in legally blind older adults with age-related macular degeneration (ARMD). Design and Methods: The 144 study participants were outpatients of a large regional vision clinic that specializes in the diagnosis and treatment of…

Changes in Fundus Autofluorescence after Anti-vascular Endothelial Growth Factor According to the Type of Choroidal Neovascularization in Age-related Macular Degeneration.

PubMed

Lee, Ji Young; Chung, Hyewon; Kim, Hyung Chan

2016-02-01

To describe the changes of fundus autofluorescence (FAF) in patients with age-related macular degeneration before and after intravitreal injection of anti-vascular endothelial growth factor according to the type of choroidal neovascularization (CNV) and to evaluate the correlation of FAF with spectral domain optical coherence tomography (SD-OCT) parameters and vision. This was a retrospective study. Twenty-one treatment-naïve patients with neovascular age-related macular degeneration were included. Study eyes were divided into two groups according to the type of CNV. Fourteen eyes were type 1 CNV and seven eyes were type 2 CNV. All eyes underwent a complete ophthalmologic examination, including an assessment of best-corrected visual acuity, SD-OCT, fluorescein angiography, and FAF imaging, before and 3 months after intravitreal anti-vascular endothelial growth factor injection. Gray scales of FAF image for CNV areas, delineated as in fluorescein angiography, were analyzed using the ImageJ program, which were adjusted by comparison with normal background areas. Correlation of changes in FAF with changes in SD-OCT parameters, including CNV thickness, photoreceptor inner and outer segment junction disruption length, external limiting membrane disruption length, central macular thickness, subretinal fluid, and intraretinal fluid were analyzed. Eyes with both type 1 and type 2 CNV showed reduced FAF before treatment. The mean gray scales (%) of type 1 and type 2 CNV were 52.20% and 42.55%, respectively. The background values were 106.72 and 96.86. After treatment, the mean gray scales (%) of type 1 CNV and type 2 CNV were changed to 57.61% (p = 0.005) and 57.93% (p = 0.008), respectively. After treatment, CNV thickness, central macular thickness, and inner and outer segment junction disruption length were decreased while FAF increased. FAF was noted to be reduced in eyes with newly diagnosed wet age-related macular degeneration, but increased after anti

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.

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

Characterisation of a C1qtnf5 Ser163Arg Knock-In Mouse Model of Late-Onset Retinal Macular Degeneration

PubMed Central

Shu, Xinhua; Luhmann, Ulrich F. O.; Aleman, Tomas S.; Barker, Susan E.; Lennon, Alan; Tulloch, Brian; Chen, Mei; Xu, Heping; Jacobson, Samuel G.; Ali, Robin; Wright, Alan F.

2011-01-01

A single founder mutation resulting in a Ser163Arg substitution in the C1QTNF5 gene product causes autosomal dominant late-onset retinal macular degeneration (L-ORMD) in humans, which has clinical and pathological features resembling age-related macular degeneration. We generated and characterised a mouse “knock-in” model carrying the Ser163Arg mutation in the orthologous murine C1qtnf5 gene by site-directed mutagenesis and homologous recombination into mouse embryonic stem cells. Biochemical, immunological, electron microscopic, fundus autofluorescence, electroretinography and laser photocoagulation analyses were used to characterise the mouse model. Heterozygous and homozygous knock-in mice showed no significant abnormality in any of the above measures at time points up to 2 years. This result contrasts with another C1qtnf5 Ser163Arg knock-in mouse which showed most of the features of L-ORMD but differed in genetic background and targeting construct. PMID:22110650

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.

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...

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.

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.

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

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...

Verteporfin therapy in age-related macular degeneration (VAM): an open-label multicenter photodynamic therapy study of 4,435 patients.

PubMed

Bessler, Neil M

2004-08-01

To provide broad clinical experience and to gather safety data on photodynamic therapy with verteporfin (Visudyne, Novartis AG, Basel, Switzerland), also termed verteporfin therapy, in patients with predominantly classic subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). The Verteporfin in Age-related Macular Degeneration (VAM) Study was designed to provide expanded access to verteporfin therapy after beneficial results for these cases were reported but before regulatory approval in North America. This open-label multicenter study from September 1999 through June 2000 enrolled among 222 centers patients 50 years or older in the United States, or 40 years or older in Canada, with age-related macular degeneration and subfoveal CNV with a lesion composition that was predominantly classic CNV on fluorescein angiography. Corrected visual acuity with habitual eyewear in the office setting was 20/40 to 20/200, inclusive. All patients received verteporfin therapy and returned for follow-up every 3 months. At those follow-up examinations, additional courses of treatment were recommended if any fluorescein leakage from CNV was identified. Safety information was collected from patient self-reporting, questioning (in person and by telephone), and physician evaluation. Safety was assessed by evaluating the effect of treatment on corrected distance visual acuity and by evaluating adverse events. A total of 4,435 patients were enrolled of whom 4,051 (91%) completed the study after receiving 6,701 treatments. Most patients received only one treatment in VAM before regulatory approval of verteporfin in the United States and Canada. Three hundred patients (6.8%) experienced an adverse event considered by the treating ophthalmologist to be associated with treatment, including 115 (2.6%) with abnormal or decreased vision, of whom 25 (0.6%) experienced acute severe visual acuity decrease, and 14 (0.3%) with transient infusion-related back

The cost-utility of photodynamic therapy in eyes with neovascular macular degeneration--a value-based reappraisal with 5-year data.

PubMed

Brown, Gary C; Brown, Melissa M; Campanella, Joseph; Beauchamp, George R

2005-10-01

To assess the value conferred by photodynamic therapy (PDT) and the cost-utility of PDT for the treatment of classic, subfoveal choroidal neovascularization associated with age-related macular degeneration (ARMD). Average cost-utility analysis utilizing clinical trial data, patient-based time tradeoff utility preferences, and a third party insurer cost perspective. Five-year visual acuity data from the TAP (Treatment of Age-related Macular Degeneration With Photodynamic Therapy) Investigation were modeled into a 12-year, value-based, reference case, cost-utility model utilizing year 2004 Medicare costs and an outcome of dollar/QALY (dollars/quality-adjusted life-year). Discounting of outcomes and costs using net present value analysis with a 3% annual rate was performed as recommended by the Panel for Cost-Effectiveness in Health and Medicine. PDT with verteporfin (Visudyne) dye for classic subfoveal choroidal neovascularization confers an 8.1% quality of life (value) improvement over the 12-year life expectancy of the reference case, while during the last 8 years the value improvement is 9.5%. The average cost-utility of the intervention is dollar 31,103/QALY (quality-adjusted life-year). Extensive one-way sensitivity analysis values range from dollar 20,736/QALY if treatment efficacy is increased by 50% to dollar 62,207 if treatment efficacy is decreased by 50%, indicating robustness of the model. PDT using verteporfin dye to treat classic subfoveal choroidal neovascularization is a very cost-effective treatment by conventional standards. The marked improvement in cost-effectiveness compared with a previous report results from the facts that the treatment benefit increasingly accrues during 5 years of follow-up while the number of yearly treatments diminishes markedly during that time.

Incidence of choroidal neovascularization in the fellow eye in the comparison of age-related macular degeneration treatments trials.

PubMed

Maguire, Maureen G; Daniel, Ebenezer; Shah, Ankoor R; Grunwald, Juan E; Hagstrom, Stephanie A; Avery, Robert L; Huang, Jiayan; Martin, Revell W; Roth, Daniel B; Castellarin, Alessandro A; Bakri, Sophie J; Fine, Stuart L; Martin, Daniel F

2013-10-01

To assess the influence of drug; dosing regimen; and traditional, nontraditional, and genetic risk factors on the incidence of choroidal neovascularization (CNV) in the fellow eye of patients treated for CNV with ranibizumab or bevacizumab. Cohort study of patients enrolled in a multicenter, randomized clinical trial. Patients with no CNV in the fellow eye at the time of enrollment in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT). Eligibility criteria for the clinical trial required that study eyes have evidence on fluorescein angiography and optical coherence tomography of CNV secondary to age-related macular degeneration (AMD) and visual acuity between 20/25 and 20/320. Treatment for the study eye was assigned randomly to either ranibizumab or bevacizumab and to 3 different regimens for dosing over a 2-year period. The genotypes for 4 single nucleotide polymorphisms (SNPs) associated with risk of AMD were determined. Only patients without CNV in the fellow eye at baseline were considered at risk. The CATT ophthalmologists examined patients every 4 weeks through 2 years and recorded treatment for CNV in the fellow eye. Development of CNV in the fellow eye. Among 1185 CATT participants, 727 (61%) had no CNV in the fellow eye at enrollment. At 2 years, CNV had developed in 75 (20.6%) of 365 patients treated with ranibizumab and in 60 (16.6%) of 362 patients treated with bevacizumab (absolute difference, 4.0%; 95% confidence interval [CI], -1.7% to 9.6%; P = 0.17). The risk ratio for pro re nata dosing relative to monthly dosing was 1.1 (95% CI, 0.8-1.6). Greater elevation of the retinal pigment epithelium and fluid in the foveal center of the study eye were associated with increased incidence of CNV in the fellow eye. Incidence was not associated with genotype on rs1061170 (CFH), rs10490924 (ARMS2), rs11200638 (HTRA1), and rs2230199 (C3; P>0.35). Through 2 years, there was no statistically significant difference between ranibizumab and

Risk factors for choroidal neovascularization and geographic atrophy in the complications of age-related macular degeneration prevention trial.

PubMed

2008-09-01

To determine risk factors for choroidal neovascularization (CNV) and of geographic atrophy (GA) in eyes with large drusen. Cohort study within a multicenter, randomized clinical trial of laser treatment for the prevention of vision loss from advanced age-related macular degeneration. One thousand fifty-two participants with 10 or more large drusen (>or=125 microm) and visual acuity of 20/40 or better in each eye. At baseline, participants provided a brief medical history. Trained readers evaluated baseline color photographs for drusen characteristics and pigmentary abnormalities. One eye of each participant was assigned to laser treatment and the contralateral eye was assigned to observation. The Complications of Age-Related Macular Degeneration Prevention Trial (CAPT) Reading Center readers identified CNV and endpoint GA from color photographs and fluorescein angiograms obtained during follow-up visits scheduled for 5 or 6 years. Estimates of relative risks (RRs) and 95% confidence intervals (CIs) were obtained from survival analyses of observed and treated eyes, considered separately and combined. Development of CNV and of endpoint GA. Choroidal neovascularization developed in 141 observed eyes and 141 treated eyes, including 57 patients affected bilaterally. Statistically significant risk factors for CNV in the multivariate model for all eyes were older age (RR, 2.81 [95% CI, 1.33-5.94] for >79 years vs. 50-59 years), cigarette smoking (RR, 1.98 [95% CI, 1.16-3.39] for current vs. never), and focal hyperpigmentation (RR, 1.84 [95% CI, 1.22-2.76] for >or=250 microm vs. none). Among eyes free of GA at baseline, endpoint GA developed in 61 observed eyes and in 58 treated eyes, including 29 patients affected bilaterally. Statistically significant risk factors for GA in the multivariate model for all eyes were older age (RR, 6.39 [95% CI, 1.64-24.9] for >79 years vs. 50-59 years), greater retinal area covered by drusen (RR, 5.10 [95% CI, 2.57-10.1] for >or=25% vs

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.

Canine Retina Has a Primate Fovea-Like Bouquet of Cone Photoreceptors Which Is Affected by Inherited Macular Degenerations

PubMed Central

Guziewicz, Karina E.; Iwabe, Simone; Swider, Malgorzata; Scott, Erin M.; Savina, Svetlana V.; Ruthel, Gordon; Stefano, Frank; Zhang, Lingli; Zorger, Richard; Sumaroka, Alexander; Jacobson, Samuel G.; Aguirre, Gustavo D.

2014-01-01

Retinal areas of specialization confer vertebrates with the ability to scrutinize corresponding regions of their visual field with greater resolution. A highly specialized area found in haplorhine primates (including humans) is the fovea centralis which is defined by a high density of cone photoreceptors connected individually to interneurons, and retinal ganglion cells (RGCs) that are offset to form a pit lacking retinal capillaries and inner retinal neurons at its center. In dogs, a local increase in RGC density is found in a topographically comparable retinal area defined as the area centralis. While the canine retina is devoid of a foveal pit, no detailed examination of the photoreceptors within the area centralis has been reported. Using both in vivo and ex vivo imaging, we identified a retinal region with a primate fovea-like cone photoreceptor density but without the excavation of the inner retina. Similar anatomical structure observed in rare human subjects has been named fovea-plana. In addition, dogs with mutations in two different genes, that cause macular degeneration in humans, developed earliest disease at the newly-identified canine fovea-like area. Our results challenge the dogma that within the phylogenetic tree of mammals, haplorhine primates with a fovea are the sole lineage in which the retina has a central bouquet of cones. Furthermore, a predilection for naturally-occurring retinal degenerations to alter this cone-enriched area fills the void for a clinically-relevant animal model of human macular degenerations. PMID:24599007

DYNAMISM OF DOT SUBRETINAL DRUSENOID DEPOSITS IN AGE-RELATED MACULAR DEGENERATION DEMONSTRATED WITH ADAPTIVE OPTICS IMAGING.

PubMed

Zhang, Yuhua; Wang, Xiaolin; Godara, Pooja; Zhang, Tianjiao; Clark, Mark E; Witherspoon, C Douglas; Spaide, Richard F; Owsley, Cynthia; Curcio, Christine A

2018-01-01

To investigate the natural history of dot subretinal drusenoid deposits (SDD) in age-related macular degeneration, using high-resolution adaptive optics scanning laser ophthalmoscopy. Six eyes of four patients with intermediate age-related macular degeneration were studied at baseline and 1 year later. Individual dot SDD within the central 30° retina were examined with adaptive optics scanning laser ophthalmoscopy and optical coherence tomography. A total of 269 solitary SDD were identified at baseline. Over 12.25 ± 1.18 months, all 35 Stage 1 SDD progressed to advanced stages. Eighteen (60%) Stage 2 lesions progressed to Stage 3 and 12 (40%) remained at Stage 2. Of 204 Stage 3 SDD, 12 (6.4%) disappeared and the rest remained. Twelve new SDD were identified, including 6 (50%) at Stage 1, 2 (16.7%) at Stage 2, and 4 (33.3%) at Stage 3. The mean percentage of the retina affected by dot SDD, measured by the adaptive optics scanning laser ophthalmoscopy, increased in 5/6 eyes (from 2.31% to 5.08% in the most changed eye) and decreased slightly in 1/6 eye (from 10.67% to 10.54%). Dynamism, the absolute value of the areas affected by new and regressed lesions, ranged from 0.7% to 9.3%. Adaptive optics scanning laser ophthalmoscopy reveals that dot SDD, like drusen, are dynamic.

The goal of value-based medicine analyses: comparability. The case for neovascular macular degeneration.

PubMed

Brown, Gary C; Brown, Melissa M; Brown, Heidi C; Kindermann, Sylvia; Sharma, Sanjay

2007-01-01

To evaluate the comparability of articles in the peer-reviewed literature assessing the (1) patient value and (2) cost-utility (cost-effectiveness) associated with interventions for neovascular age-related macular degeneration (ARMD). A search was performed in the National Library of Medicine database of 16 million peer-reviewed articles using the key words cost-utility, cost-effectiveness, value, verteporfin, pegaptanib, laser photocoagulation, ranibizumab, and therapy. All articles that used an outcome of quality-adjusted life-years (QALYs) were studied in regard to (1) percent improvement in quality of life, (2) utility methodology, (3) utility respondents, (4) types of costs included (eg, direct healthcare, direct nonhealthcare, indirect), (5) cost bases (eg, Medicare, National Health Service in the United Kingdom), and (6) study cost perspective (eg, government, societal, third-party insurer). To qualify as a value-based medicine analysis, the patient value had to be measured using the outcome of the QALYs conferred by respective interventions. As with value-based medicine analyses, patient-based time tradeoff utility analysis had to be utilized, patient utility respondents were necessary, and direct medical costs were used. Among 21 cost-utility analyses performed on interventions for neovascular macular degeneration, 15 (71%) met value-based medicine criteria. The 6 others (29%) were not comparable owing to (1) varying utility methodology, (2) varying utility respondents, (3) differing costs utilized, (4) differing cost bases, and (5) varying study perspectives. Among value-based medicine studies, laser photocoagulation confers a 4.4% value gain (improvement in quality of life) for the treatment of classic subfoveal choroidal neovascularization. Intravitreal pegaptanib confers a 5.9% value gain (improvement in quality of life) for classic, minimally classic, and occult subfoveal choroidal neovascularization, and photodynamic therapy with verteporfin confers

THE GOAL OF VALUE-BASED MEDICINE ANALYSES: COMPARABILITY. THE CASE FOR NEOVASCULAR MACULAR DEGENERATION

PubMed Central

Brown, Gary C.; Brown, Melissa M.; Brown, Heidi C.; Kindermann, Sylvia; Sharma, Sanjay

2007-01-01

Purpose To evaluate the comparability of articles in the peer-reviewed literature assessing the (1) patient value and (2) cost-utility (cost-effectiveness) associated with interventions for neovascular age-related macular degeneration (ARMD). Methods A search was performed in the National Library of Medicine database of 16 million peer-reviewed articles using the key words cost-utility, cost-effectiveness, value, verteporfin, pegaptanib, laser photocoagulation, ranibizumab, and therapy. All articles that used an outcome of quality-adjusted life-years (QALYs) were studied in regard to (1) percent improvement in quality of life, (2) utility methodology, (3) utility respondents, (4) types of costs included (eg, direct healthcare, direct nonhealthcare, indirect), (5) cost bases (eg, Medicare, National Health Service in the United Kingdom), and (6) study cost perspective (eg, government, societal, third-party insurer). To qualify as a value-based medicine analysis, the patient value had to be measured using the outcome of the QALYs conferred by respective interventions. As with value-based medicine analyses, patient-based time tradeoff utility analysis had to be utilized, patient utility respondents were necessary, and direct medical costs were used. Results Among 21 cost-utility analyses performed on interventions for neovascular macular degeneration, 15 (71%) met value-based medicine criteria. The 6 others (29%) were not comparable owing to (1) varying utility methodology, (2) varying utility respondents, (3) differing costs utilized, (4) differing cost bases, and (5) varying study perspectives. Among value-based medicine studies, laser photocoagulation confers a 4.4% value gain (improvement in quality of life) for the treatment of classic subfoveal choroidal neovascularization. Intravitreal pegaptanib confers a 5.9% value gain (improvement in quality of life) for classic, minimally classic, and occult subfoveal choroidal neovascularization, and photodynamic therapy

The Impact of Supplemental Antioxidants on Visual Function in Nonadvanced Age-Related Macular Degeneration: A Head-to-Head Randomized Clinical Trial.

PubMed

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

2017-10-01

The purpose of this study was to evaluate the impact of supplemental macular carotenoids (including versus not including meso-zeaxanthin) in combination with coantioxidants on visual function in patients with nonadvanced age-related macular degeneration. In this study, 121 participants were randomly assigned to group 1 (Age-Related Eye Disease Study 2 formulation with a low dose [25 mg] of zinc and an addition of 10 mg meso-zeaxanthin; n = 60) or group 2 (Age-Related Eye Disease Study 2 formulation with a low dose [25 mg] of zinc; n = 61). Visual function was assessed using best-corrected visual acuity, contrast sensitivity (CS), glare disability, retinal straylight, photostress recovery time, reading performance, and the National Eye Institute Visual Function Questionnaire-25. Macular pigment was measured using customized heterochromatic flicker photometry. There was a statistically significant improvement in the primary outcome measure (letter CS at 6 cycles per degree [6 cpd]) over time (P = 0.013), and this observed improvement was statistically comparable between interventions (P = 0.881). Statistically significant improvements in several secondary outcome visual function measures (letter CS at 1.2 and 2.4 cpd; mesopic and photopic CS at all spatial frequencies; mesopic glare disability at 1.5, 3, and 6 cpd; photopic glare disability at 1.5, 3, 6, and 12 cpd; photostress recovery time; retinal straylight; mean and maximum reading speed) were also observed over time (P < 0.05, for all), and were statistically comparable between interventions (P > 0.05, for all). Statistically significant increases in macular pigment at all eccentricities were observed over time (P < 0.0005, for all), and the degree of augmentation was statistically comparable between interventions (P > 0.05). Antioxidant supplementation in patients with nonadvanced age-related macular degeneration results in significant increases in macular pigment and improvements in CS and other measures of

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…

Reentrant spiral waves of spreading depression cause macular degeneration in hypoglycemic chicken retina

PubMed Central

Santos, Laura M.; Mattiace, Linda A.; Costa, Manoel L.; Ferreira, Luciano C.; Benabou, Kelly; Kim, Ana H.; Abrahams, John; Bennett, Michael V. L.; Rozental, Renato

2012-01-01

Spreading depression (SD), a slow diffusion-mediated self-sustained wave of depolarization that severely disrupts neuronal function, has been implicated as a cause of cellular injury in a number of central nervous system pathologies, including blind spots in the retina. Here we show that in the hypoglycemic chicken retina, spontaneous episodes of SD can occur, resulting in irreversible punctate lesions in the macula, the region of highest visual acuity in the central region of the retina. These lesions in turn can act as sites of origin for secondary self-sustained reentrant spiral waves of SD that progressively enlarge the lesions. Furthermore, we show that the degeneration of the macula under hypoglycemic conditions can be prevented by blocking reentrant spiral SDs or by blocking caspases. The observation that spontaneous formation of reentrant spiral SD waves leads to the development of progressive retinal lesions under conditions of hypoglycemia establishes a potential role of SD in initiation and progression of macular degeneration, one of the leading causes of visual disability worldwide. PMID:22308470

Low power vs standard power transpupillary thermotherapy in patients with age-related macular degeneration and subfoveal choroidal neovascularization ineligible for photodynamic therapy.

PubMed

Hogan, A C; Kilmartin, D J

2006-06-01

To assess the effect of standard power vs low power transpupillary thermotherapy (TTT) in patients with active subfoveal choroidal neovascularization secondary to age-related macular degeneration ineligible for photodynamic therapy (PDT) by original treatment of age-related macular degeneration with photodynamic therapy (TAP) study group recommendations. Retrospective review of 79 patients with active predominantly occult subfoveal choroidal neovascularization or predominantly classic subfoveal choroidal neovascularization but Snellen visual acuity <20/200. All patients were treated with TTT administered via a Mainster wide field fundus contact lens with a retinal power/diameter coefficient of 248 mW/mm in the standard power (n=27) and 181 mW/mm in the low power group (n=52). The primary outcome was stabilization (<1 Snellen line change) or improvement (two or more Snellen lines) in visual acuity. Clinical and fluorescein angiographic resolution of overlying exudation was documented. At 24 month follow-up, 17 patients (63%) in the standard power and 36 patients (69%) in the low power group achieved stable or improved vision. Improved vision (mean three lines) was observed in 22% of the standard power and 23% of the low power group. Overlying exudation was reduced clinically with minimal or no leakage on fluorescein angiogram in 85% of standard power and 90% of low power group. Subgroup analysis in the low power group demonstrated a visual benefit in patients with subfoveal lesions, which had any classic component. Low power TTT is as effective as standard power in stabilizing or improving vision and reducing overlying exudation in patients with active subfoveal choroidal neovascularization ineligible for PDT.

Polarization sensitive changes in the human macula associated with normal aging and age-related macular degeneration

NASA Astrophysics Data System (ADS)

VanNasdale, Dean Allan, Jr.

2011-12-01

The human macula occupies a relatively small, but crucial retinal area, as it is the location responsible for our most acute spatial vision and best color discrimination. Localizing important landmarks in the retina is difficult even in normal eyes where morphological inter-individual variability is high. This becomes even more challenging in the presence of sight-threatening pathology. With respect to the human macula, there remains a significant gap in the understanding of normal structure and function. Even less is known about the pathological mechanisms that occur in sight-threatening diseases including age-related macular degeneration. Because relatively little is known about normal aging changes, it is also difficult to differentiate those changes from changes associated with retinal disease. To better understand normal and pathological changes in the macula, imaging techniques using specific optical signatures are required. Structural features in the macula can be distinguished based on their intrinsic properties using specific light/tissue interactions. Because of the high degree of structural regularity in the macula, polarization sensitive imaging is potentially a useful tool for evaluating the morphology and integrity of the cellular architecture for both normal individuals and those affected by disease. In our investigations, we used polarization sensitive imaging to determining normal landmarks that are important clinically and for research investigations. We found that precision and accuracy in localizing the central macula was greatly improved through the use of polarization sensitive imaging. We also found that specific polarization alterations can be used to demonstrate systematic changes as a function of age, disproportionately affecting the central macular region. When evaluating patients with age-related macular degeneration, we found that precision and accuracy of localizing the central macula was also improved, even when significant pathology

Macular thickness after glaucoma filtration surgery.

PubMed

Sesar, Antonio; Cavar, Ivan; Sesar, Anita Pusić; Geber, Mia Zorić; Sesar, Irena; Laus, Katia Novak; Vatavuk, Zoran; Mandić, Zdravko

2013-09-01

The aim of present study was to analyze early postoperative changes in the macular area using optical coherence tomography (OCT) after uncomplicated glaucoma filtration surgery. This prospective study included 32 patients (34 eyes) with open-angle glaucoma, which underwent trabeculectomy with or without use of mitomycin C. Exclusion criteria were macular edema, uveitis, age-related macular degeneration, blurred optical media, secondary glaucoma and angle-closure glaucoma. All standard clinical examinations were made before surgery, at the 2nd day, 1 week and 1 month after surgery. Tomography of the macula was performed during every examination using Cirrus HD OCT for the analysis of central subfield thickness. Results show that thickening of the macula was slightly higher 1 week and 1 month after operation in comparison with baseline end 2nd day postoperativelly. There was no significant difference in the change of macular thickness in patients who have used topical prostaglandins compared with those who have used other topical medications. Also, there was no difference in macular changes between patients treated with or without mitomycin C. In conclusion, we found a slight subclinical increase in macular thickness after uncomplicated trabeculectomy, for which we considered that was the result in reduction of intraocular pressure after glaucoma surgery. Macular thickening after glaucoma filtering surgery could be a physiological reaction to the stress of the retina caused by a sudden reduction of intraocular pressure and it is the consequence of altered relationship between capillary pressure and interstitial fluid pressure.

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.

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.

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

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.

Relationship between slow visual processing and reading speed in people with macular degeneration

PubMed Central

Cheong, Allen MY; Legge, Gordon E; Lawrence, Mary G; Cheung, Sing-Hang; Ruff, Mary A

2007-01-01

Purpose People with macular degeneration (MD) often read slowly even with adequate magnification to compensate for acuity loss. Oculomotor deficits may affect reading in MD, but cannot fully explain the substantial reduction in reading speed. Central-field loss (CFL) is often a consequence of macular degeneration, necessitating the use of peripheral vision for reading. We hypothesized that slower temporal processing of visual patterns in peripheral vision is a factor contributing to slow reading performance in MD patients. Methods Fifteen subjects with MD, including 12 with CFL, and five age-matched control subjects were recruited. Maximum reading speed and critical print size were measured with RSVP (Rapid Serial Visual Presentation). Temporal processing speed was studied by measuring letter-recognition accuracy for strings of three randomly selected letters centered at fixation for a range of exposure times. Temporal threshold was defined as the exposure time yielding 80% recognition accuracy for the central letter. Results Temporal thresholds for the MD subjects ranged from 159 to 5881 ms, much longer than values for age-matched controls in central vision (13 ms, p<0.01). The mean temporal threshold for the 11 MD subjects who used eccentric fixation (1555.8 ± 1708.4 ms) was much longer than the mean temporal threshold (97.0 ms ± 34.2 ms, p<0.01) for the age-matched controls at 10° in the lower visual field. Individual temporal thresholds accounted for 30% of the variance in reading speed (p<0.05). Conclusion The significant association between increased temporal threshold for letter recognition and reduced reading speed is consistent with the hypothesis that slower visual processing of letter recognition is one of the factors limiting reading speed in MD subjects. PMID:17881032

The comparative effectiveness and cost-effectiveness of ranibizumab for neovascular macular degeneration revisited.

PubMed

Brown, Gary C; Brown, Melissa M; Lieske, Heidi B; Turpcu, Adam; Rajput, Yamina

2017-01-01

To compare a near decade of follow-up, newer control cohort data, use of both the societal and third party insurer cost perspectives, and integration of unilateral/bilateral therapy on the comparative effectiveness and cost-effectiveness of intravitreal ranibizumab therapy for neovascular, age-related macular degeneration (AMD). Value-Based Medicine ® , 12-year, combined-eye model, cost-utility analysis employing MARINA and HORIZON clinical trial data. Preference-based comparative effectiveness outcomes were quantified in (1) QALY (quality-adjusted life-year) gain, and (2) percent improvement in quality-of-life, while cost-effectiveness outcomes were quantified in (3) the cost-utility ratio (CUR) and financial return-on-investment (ROI) to society. Using MARINA and HORIZON trial data and a meta-analysis control cohort after 24 months, ranibizumab therapy conferred a combined-eye patient value (quality-of-life) gain of 16.3%, versus 10.4% found in 2006. The two-year direct ophthalmic medical cost for ranibizumab therapy was $46,450, a 33.8% real dollar decrease from 2006. The societal cost perspective CUR was -$242,920/QALY, indicating a $282,517 financial return-on-investment (ROI), or 12.3%/year to society for direct ophthalmic medical costs expended. The 3rd party insurer CUR ranged from $21,199/QALY utilizing all direct, medical costs, to $69,591/QALY using direct ophthalmic medical costs. Ranibizumab therapy for neovascular AMD in 2015, considering treatment of both eyes, conferred greater patient value gain (comparative effectiveness) and improved cost-effectiveness than in 2006, as well as a large monetary return-on-investment to the Gross Domestic Product and nation's wealth. The model herein integrates important novel features for neovascular age-related macular degeneration, vitreoretinal cost effectiveness analyses, including: (1) treatment of both eyes, (2) a long-term, untreated control cohort, and (3) the use of societal costs.

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.

Characteristics of choroidal neovascularization in the complications of age-related macular degeneration prevention trial.

PubMed

Maguire, Maureen G; Alexander, Judith; Fine, Stuart L

2008-09-01

To describe the characteristics of incident choroidal neovascularization (CNV) in observed and treated eyes in the Complications of Age-related Macular Degeneration Prevention Trial (CAPT). Cross-sectional descriptive study within a multicenter, randomized clinical trial. Patients who developed CNV during CAPT follow-up. Inclusion criteria for CAPT specified bilateral large drusen (>or=10 drusen at least 125 micro), visual acuity >or=20/40 in each eye, and age >or=50. Exclusion criteria included CNV and geographic atrophy >1 Macular Photocoagulation Study (MPS) disc area or within 500 micro of the foveal center. One eye of each person was selected randomly for low-intensity laser treatment and the contralateral eye was observed. Fluorescein angiography was performed at baseline, annually for >or=5 years, and whenever there were symptoms of CNV. Trained readers at the CAPT Photograph Reading Center assessed color stereo photographs and angiogram negatives to identify CNV. Choroidal neovascularization was classified by type (predominantly classic CNV, minimally classic CNV, occult only CNV, or scar), location, and area. Visual acuity was measured by certified examiners. Symmetry of characteristics between eyes of bilaterally affected patients was examined. Choroidal neovascularization developed in 282 eyes of 225 patients. At the time of detection, 192 (68%) of the lesions were occult only, 153 (54%) were subfoveal, and 157 (56%) were or=20/40 in 123 (69%) of 179 eyes with visual acuity measured at the time of detection. Choroidal neovascularization developed in both eyes in 57 patients (25%) during CAPT follow-up. Lesions in eyes of bilaterally affected patients were no more similar to each other than affected eyes in 2 different patients. When patients are monitored closely, many CNV lesions can be detected outside of the fovea and when they are relatively small. Early detection may lead to improved long-term visual acuity.

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+;…

Intravitreal dobesilate in the treatment of choroidal neovascularisation associated with age-related macular degeneration: report of two cases

PubMed Central

Cuevas, Pedro; Outeiriño, Luis; Azanza, Carlos; Giménez-Gallego, Guillermo

2012-01-01

This case report presents the effectiveness of intravitreal administration of dobesilate, a synthetic fibroblast growth factor inhibitor, in two patients showing neovascular age-related macular degeneration of the classic, and of the occult choroidal neovascularisation types, respectively. Our study demonstrates that the treatment induces the regression of both forms of this pathology, as assessed by spectral optical coherence tomography. Improvement of the lesions was accompanied of visual acuity improvement. PMID:22948997

Two-year functional and anatomical results after converting treatment resistant eyes with exudative age-related macular degeneration to aflibercept in accordance with a treat and extend protocol.

PubMed

Jørstad, Øystein Kalsnes; Faber, Rowan Thomas; Moe, Morten Carstens

2017-08-01

To study the effects of converting to aflibercept in accordance with a treat and extend (T&E) strategy in eyes with treatment resistant exudative age-related macular degeneration (AMD). Two-year prospective study of eyes with exudative AMD and persistent macular fluid despite monthly treatment with ranibizumab or bevacizumab. Eyes were converted to 2.0 mg aflibercept in accordance with a T&E protocol. Fifty eyes from 47 patients were included. At baseline, the mean central retinal thickness (CRT) was 273 μm and mean best-corrected visual acuity (BCVA) 0.25 logarithm of the minimal angle of resolution (logMAR). The mean number of aflibercept injections the first year was 9.2. After 1 year, there was a reduction in mean CRT to 228 μm (p < 0.001); 22 eyes (44%) had a dry macula; and the mean BCVA was 0.24 logMAR (p = 0.531). The mean number of aflibercept injections the second year was 8.0 (p = 0.013 compared to first year). After 2 years, 24 eyes (48%) received treatment more frequently than every eighth week. The mean CRT was 225 μm (p < 0.001 compared to baseline); 31 eyes (62%) had a dry macula; and mean BCVA was 0.32 logMAR (p = 0.005 compared to baseline). Five eyes did not complete 2 years of aflibercept treatment after failing to improve. A majority of eyes showed improved anatomic outcomes. There was a small decrease in mean BCVA after the second year of treatment. About half of the eyes required treatment more frequently than the recommended aflibercept label of an 8-week interval. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Switching from pro re nata to treat-and-extend regimen improves visual acuity in patients with neovascular age-related macular degeneration.

PubMed

Kvannli, Line; Krohn, Jørgen

2017-11-01

To evaluate the visual outcome after transitioning from a pro re nata (PRN) intravitreal injection regimen to a treat-and-extend (TAE) regimen for patients with neovascular age-related macular degeneration (AMD). A retrospective review of patients who were switched from a PRN regimen with intravitreal injections of bevacizumab, ranibizumab or aflibercept to a TAE regimen. The best corrected visual acuity (BCVA), central retinal thickness (CRT) and type of medication used at baseline, at the time of changing treatment regimen and at the end of the study were analysed. Twenty-one eyes of 21 patients met the inclusion criteria. Prior to the switch, the patients received a mean of 13.8 injections (median, 10; range, 3-39 injections) with the PRN regimen for 44 months (range, 3-100 months), which improved the visual acuity in five patients (24%). After a mean of 6.1 injections (median, 5; range, 3-14 injections) with the TAE regimen over 8 months (range, 2-16 months), the visual acuity improved in 12 patients (57%). The improvement in visual acuity during treatment with the TAE regimen was statistically significant (p = 0.005). The proportion of patients with a visual acuity of 0.2 or better was significantly higher after treatment with the TAE regimen than after treatment with the PRN regimen (p = 0.048). No significant differences in CRT were found between the two treatment regimens. Even after prolonged treatment and a high number of intravitreal injections, switching AMD patients from a PRN regimen to a strict TAE regimen significantly improves visual acuity. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

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

[Results of Re-switch from Intravitreal Aflibercept to Ranibizumab in Patients with Exudative Age-related Macular Degeneration].

PubMed

Waibel, Sören; Matthé, Egbert; Sandner, Dirk

2018-05-01

The purpose of this study was to investigate the effectiveness of re-switch from intravitreal aflibercept to ranibizumab in patients with exudative age-related macular degeneration. This retrospective case series included 17 eyes of 17 patients who had previously switched from ranibizumab to aflibercept and finally back to ranibizumab. Main outcomes were change of visual acuity (VA) and assessment of central macular thickness (CMT). Secondary outcomes included predictive factors which had a beneficial effect as VA and CMT before re-switch, number of previous injections and gender. The mean VA was 0.64 ± 0.36 logMAR before the switch, and 0.87 ± 0.40 logMAR before the re-switch, and gained with a slight but not significantly improvement up to 0.85 ± 0.58 logMAR after the re-switch (p = 0.896). The average CMT before the switch was 448.6 µm ± 181.5. This decreased to 343.8 µm ± 161.3 after the switch (p = 0.614) to 299.1 µm ± 155.8 at switchback (p = 0.133). Overall, 8 patients (47%) had an improvement of vision, whereas in 5 patients (30%) VA deteriorated. Further analysis of predictive factors revealed a mean improvement of VA in male patients after re-switch, while female patients lost VA, with statistical significance between after the switch and after the re-switch to the benefit of male patients (p = 0.016). A re-switch from aflibercept to ranibizumab may enable improvement in morphological parameters and stabilization of VA in patients with exudative age-related macular degeneration who achieved no more benefit from the initial switch. Georg Thieme Verlag KG Stuttgart · New York.

Cone photopigment in older subjects: decreased optical density in early age-related macular degeneration

NASA Astrophysics Data System (ADS)

Elsner, Ann E.; Burns, Stephen A.; Weiter, John J.

2002-01-01

We measured changes to cone photoreceptors in patients with early age-related macular degeneration. The data of 53 patients were compared with normative data for color matching measurements of long- and middle-wavelength-sensitive cones in the central macula. A four-parameter model quantified cone photopigment optical density and kinetics. Cone photopigment optical density was on average less for the patients than for normal subjects and was uncorrelated with visual acuity. More light was needed to reduce the photopigment density by 50% in the steady state for patients. These results imply that cone photopigment optical density is reduced by factors other than slowed kinetics.

Defective phagosome motility and degradation in cell nonautonomous RPE pathogenesis of a dominant macular degeneration.

PubMed

Esteve-Rudd, Julian; Hazim, Roni A; Diemer, Tanja; Paniagua, Antonio E; Volland, Stefanie; Umapathy, Ankita; Williams, David S

2018-05-22

Stargardt macular dystrophy 3 (STGD3) is caused by dominant mutations in the ELOVL4 gene. Like other macular degenerations, pathogenesis within the retinal pigment epithelium (RPE) appears to contribute to the loss of photoreceptors from the central retina. However, the RPE does not express ELOVL4 , suggesting photoreceptor cell loss in STGD3 occurs through two cell nonautonomous events: mutant photoreceptors first affect RPE cell pathogenesis, and then, second, RPE dysfunction leads to photoreceptor cell death. Here, we have investigated how the RPE pathology occurs, using a STGD3 mouse model in which mutant human ELOVL4 is expressed in the photoreceptors. We found that the mutant protein was aberrantly localized to the photoreceptor outer segment (POS), and that resulting POS phagosomes were degraded more slowly in the RPE. In cell culture, the mutant POSs are ingested by primary RPE cells normally, but the phagosomes are processed inefficiently, even by wild-type RPE. The mutant phagosomes excessively sequester RAB7A and dynein, and have impaired motility. We propose that the abnormal presence of ELOVL4 protein in POSs results in phagosomes that are defective in recruiting appropriate motor protein linkers, thus contributing to slower degradation because their altered motility results in slower basal migration and fewer productive encounters with endolysosomes. In the transgenic mouse retinas, the RPE accumulated abnormal-looking phagosomes and oxidative stress adducts; these pathological changes were followed by pathology in the neural retina. Our results indicate inefficient phagosome degradation as a key component of the first cell nonautonomous event underlying retinal degeneration due to mutant ELOVL4.

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

Clinicopathologic correlation of submacular membranectomy with retention of good vision in a patient with age-related macular degeneration.

PubMed

Rosa, R H; Thomas, M A; Green, W R

1996-04-01

We present the clinicopathologic features of the eye of a patient with age-related macular degeneration who underwent submacular membranectomy and had retention of good visual acuity for almost 4 years despite recurrent choroidal neovascularization treated with krypton laser photocoagulation and mild expansion of the laser lesion with time. Histopathologic study of the surgically removed membrane from the right eye disclosed a thin fibrovascular membrane lined by retinal pigment epithelium on one surface. Microscopic examination of the right eye obtained post mortem disclosed a 2.75-mm (horizontal) x 2.1-mm (vertical) retinal pigment epithelium defect with overlying photoreceptor cell atrophy centered on the temporal parafoveal area, and a 0.6 x 0.1-mm subretinal pigment epithelium fibrovascular membrane with an area of retinal pigment epithelial hyperplasia and vascularization from the retina 0.4 mm temporal to the fovea. Basal laminar deposit was present in the region of the fovea and nasal parafoveal area.

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

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

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

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.

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...

Epilutein for Early-Stage Age-Related Macular Degeneration: A Randomized and Prospective Study.

PubMed

Forte, Raimondo; Panzella, Lucia; Cesarano, Ida; Cennamo, Gilda; Eidenberger, Thomas; Napolitano, Alessandra

2017-01-01

The hypothesis that oral supplementation of the epilutein/lutein combination could augment the macular pigment optical density (MPOD) in patients with age-related macular degeneration (AMD) was tested. In a prospective randomized interventional study, 40 consecutive patients with early-stage AMD were recruited. After a 2-week run-in period, patients were randomly treated with a daily oral administration of 8 mg epilutein and 2 mg lutein (group 1) or 10 mg lutein (group 2) for 2 months. At baseline (BL) and 1-month (M1) and 2-month visits (M2), all patients underwent a complete ophthalmological examination, including measurement of MPOD in a 7° area (Visucam 200; Carl Zeiss Meditec, Milan, Italy). Xanthophylls were quantified in plasma, as well as the HDL, non-HDL, and erythrocyte fractions at each study visit. Twenty-one patients (mean age 69.4 ± 6.7 years, 35 eyes) were included in group 1. Mean MPOD was 0.203 ± 0.02 optical density units (ODU) at BL, and increased to 0.214 ± 0.04 ODU at M1 (p = 0.008) and 0.206 ± 0.03 ODU at M2 (p = 0.04). Sixteen patients (mean age 72.0 ± 6.3 years, 29 eyes) were included in group 2. Mean MPOD was 0.215 ± 0.03 at BL, which reduced to 0.202 ± 0.03 ODU at M1 (p = 0.003) and 0.207 ± 0.02 ODU at M2 (p < 0.001). A rise in the systemic level of total xanthophylls was observed at M1 for both groups. At M2, total xanthophylls were significantly increased only in group 1 and decreased in group 2. In patients with early-stage AMD, the administration of lutein in combination with epilutein was associated with an increased MPOD compared to the administration of lutein alone. © 2017 S. Karger AG, Basel.

Alternating Bi-Weekly Intravitreal Ranibizumab and Bevacizumab for Refractory Neovascular Age-Related Macular Degeneration with Pigment Epithelial Detachment.

PubMed

Witkin, Andre J; Rayess, Nadim; Garg, Sunir J; Maguire, Joseph I; Storey, Philip; Kaiser, Richard S; Hsu, Jason; Vander, James F; Ho, Allen C

2017-01-01

To describe visual and anatomical outcomes following bi-weekly intravitreal ranibizumab/bevacizumab injections in eyes with refractory neovascular age-related macular degeneration (AMD) and pigment epithelial detachment (PED). Retrospective, consecutive, interventional case series. Eighteen patients diagnosed with neovascular AMD that were refractory to anti-VEGF therapy and received alternating biweekly ranibizumab/bevacizumab injections were included. Patients with neovascular AMD and PED that were refractory to at least 11 monthly ranibizumab or bevacizumab injections were included in this study at a large, single retina practice. Following inclusion, patients received four bi-weekly alternating ranibizumab/bevacizumab intravitreal injections. After completing a course of four bi-weekly injections, patients were treated with variable regimens of intravitreal anti-vascular endothelial growth factor (VEGF) therapy. The primary outcomes of the study included change in visual acuity (VA) and central foveal thickness (CFT) at eight weeks follow-up. Study eyes had previously received a mean of 22 intravitreal anti-VEGF injections. At enrollment, mean VA was 20/95 and mean CFT was 455 µm. After four bi-weekly anti-VEGF injections, mean VA improved to 20/65 (p < 0.001), and mean CFT decreased to 387 µm (p = 0.029). In patients with PED, there was a mean 27.9% reduction in height (p = 0.046) at eight weeks' follow-up. Four injections of bi-weekly alternating ranibizumab/bevacizumab improved visual acuity and reduced macular thickness in a number of patients with refractory neovascular AMD and PED.

The Experience of a Randomized Clinical Trial of Closed-Circuit Television versus Eccentric Viewing Training for People with Age-Related Macular Degeneration

ERIC Educational Resources Information Center

Leat, Susan J.; Si, Francis Fengqin; Gold, Deborah; Pickering, Dawn; Gordon, Keith; Hodge, William

2017-01-01

Introduction: In addition to optical devices, closed-circuit televisions (CCTVs) and eccentric viewing training are both recognized interventions to improve reading performance in individuals with vision loss secondary to age-related macular degeneration. Both are relatively expensive, however, either in the cost of the device or in the amount of…

Outcomes in Eyes with Retinal Angiomatous Proliferation in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT).

PubMed

Daniel, Ebenezer; Shaffer, James; Ying, Gui-shuang; Grunwald, Juan E; Martin, Daniel F; Jaffe, Glenn J; Maguire, Maureen G

2016-03-01

To compare baseline characteristics, visual acuity (VA), and morphologic outcomes between eyes with retinal angiomatous proliferation (RAP) and all other eyes among patients with neovascular age-related macular degeneration (NVAMD) treated with anti-vascular endothelial growth factor (VEGF) drugs. Prospective cohort study within the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT). Patients with NVAMD. Reading center staff evaluated digital color fundus photographs, fluorescein angiography (FA) images, and optical coherence tomography (OCT) scans of eyes with NVAMD treated with either ranibizumab or bevacizumab over a 2-year period. Retinal angiomatous proliferation was identified by the intense intra-retinal leakage of fluorescein in combination with other associated features. Visual acuity; fluorescein leakage; scar; geographic atrophy (GA) on FA; retinal thickness, fluid, and subretinal hyperreflective material (SHRM) on OCT; and the number of intravitreal anti-VEGF injections at 1 and 2 years. Retinal angiomatous proliferation was present in 126 of 1183 (10.7%) study eyes at baseline. Mean VA improvement from baseline was greater (10.6 vs. 6.9 letters; P = 0.01) at 1 year, but similar at 2 years (7.8 vs. 6.2 letters; P = 0.34). At 1 year, eyes with RAP were more likely to have no fluid (46% vs. 26%; P < 0.001) on OCT, no leakage on FA (61% vs. 50%; P = 0.03), and greater reduction in foveal thickness (-240 μm vs. -161 μm; P < 0.001). They were more likely to demonstrate GA (24% vs. 15%; P = 0.01) and less likely to have scarring (17% vs. 36%; P < 0.001) or SHRM (36% vs. 48%; P = 0.01). These results were similar at 2 years. The mean change in lesion size at 1 year differed (-0.27 DA vs. 0.27 DA; P = 0.02), but was similar at 2 years (0.49 DA vs. 0.79 DA; P = 0.26). Among eyes treated PRN, eyes with RAP received a lower mean number of injections in year 1 (6.1 vs. 7.4; P = 0.003) and year 2 (5.4 vs. 6.6; P = 0.025). At both 1 and 2 years

Reprint of: Aspirin use and early age-related macular degeneration: a meta-analysis.

PubMed

Kahawita, Shyalle K; Casson, Robert J

2015-06-01

The aim of this review was to evaluate the evidence for an association between Aspirin use and early age-related macular degeneration (ARMD). A literature search was performed in 5 databases with no restrictions on language or date of publication. Four studies involving 10292 individuals examining the association between aspirin and ARMD met the inclusion criteria. Meta-analysis was carried out by Cochrane Collaboration Review Manager 5.2 software (Cochrane Collaboration, Copenhagen, Denmark). The pooled odd ratios showed that Aspirin use was associated with early ARMD (pooled odds ratio 1.43, 95% CI 1.09-1.88). There is a small but statistically significant association between Aspirin use and early ARMD, which may warrant further investigation. Copyright © 2015. Published by Elsevier Inc.

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.

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

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

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.

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.

[Comparison of Functional and Morphological Outcome after Aflibercept or Ranibizumab in Chronic Recurrent Neovascular Age-Related Macular Degeneration].

PubMed

Hoffmann, A E; Maier, M; Lohmann, C P; Feucht, N

2016-11-01

Background: To assess functional and morphological outcomes in patients with chronic recurrent neovascular age-related macular degeneration (nAMD) previously treated with ranibizumab, who were either switched from ranibizumab to aflibercept or received further ranibizumab injections. Methods: Retrospective analysis of eyes with recurrent nAMD previously treated with ranibizumab. On recurrence of the macular oedema, patients had received either 3 injections of aflibercept (2.0 mg) or ranibizumab (0.5 mg) at 4 week intervals. Patients were examined before the first injection and four weeks after the last injection. The main outcome measures included change in visual acuity (VA) in logMAR, subfoveal central retinal thickness (CRT), subretinal fluid (SRF) and height of pigment epithelial detachment (PED height), as well as the maximum height of macular subretinal fluid (SRF max) and of macular pigment epithelial detachment (PED height max) in spectral-domain optical coherence tomography (OCT). Changes in VA and OCT were compared between the two groups to investigate differences in the therapeutic effects of aflibercept and ranibizumab. Results: 60 eyes of 55 patients were included. The aflibercept group (n = 30) and the ranibizumab group (n = 30) showed no statistically significant differences in mean age (p = 0.813), number of prior injections of ranibizumab (p = 0.127) or time since last injection (p = 0.523). Mean VA logMAR improved in both groups, though only in the ranibizumab group was the difference significant (0.50 ± 0.33 to 0.44 ± 0.29 logMAR; p = 0.013; Table 1). CRT decreased in the aflibercept (p = 0.133) and ranibizumab groups (p = 0.043). PED height was reduced in both groups (aflibercept p = 0.068; ranibizumab p = 0.241). SRF, SRF max and PED height max showed statistically significant decreases in both groups. Comparison of the aflibercept and the ranibizumab groups showed no statistically

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.

Evolving Knowledge in Pharmacologic Treatments of Age-Related Macular Degeneration.

PubMed

Soubrane Daguet, Gisèle; Risard-Gasiorowski, Sarah; Massamba, Nathalie

2016-01-01

Modern retinal drug therapy is a result of the recent challenges and breakthroughs in chemistry, physics, genetics, cell biology and biotechnologies. Specific pharmaceutical and pharmacokinetic characteristics of a drug are of major importance and contribute to its ability to penetrate targeted ocular tissues in order to result in effective therapeutic concentrations. In addition, the drugs should maintain a prolonged time of activity and be safe with minimal local and systemic toxicity. The transporter vehicle or drug delivery system is crucial in order to enhance ocular tissue penetration and establish controlled drug release. Administration methods should be local, thereby reducing systemic side effects, and, ideally, treatment should be noninvasive. Within the group of so-called classic therapies, the use of pharmacologic treatments has become widespread for most severe retinal diseases. Thereby, ocular therapy of diseases like exudative age-related macular degeneration has improved markedly. Moreover, new metabolic pathways have been identified, new molecules have emerged, new synthesis technologies have been discovered, and new formulae conceived. These developments have opened new avenues for limiting disease progression. © 2016 S. Karger AG, Basel.

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

Cost-effectiveness of community versus hospital eye service follow-up for patients with quiescent treated age-related macular degeneration alongside the ECHoES randomised trial

PubMed Central

Violato, M; Dakin, H; Chakravarthy, U; Reeves, B C; Peto, T; Hogg, R E; Harding, S P; Scott, L J; Taylor, J; Cappel-Porter, H; Mills, N; O'Reilly, D; Rogers, C A; Wordsworth, S

2016-01-01

Objectives To assess the cost-effectiveness of optometrist-led follow-up monitoring reviews for patients with quiescent neovascular age-related macular degeneration (nAMD) in community settings (including high street opticians) compared with ophthalmologist-led reviews in hospitals. Design A model-based cost-effectiveness analysis with a 4-week time horizon, based on a ‘virtual’ non-inferiority randomised trial designed to emulate a parallel group design. Setting A virtual internet-based clinical assessment, conducted at community optometry practices, and hospital ophthalmology clinics. Participants Ophthalmologists with experience in the age-related macular degeneration service; fully qualified optometrists not participating in nAMD shared care schemes. Interventions The participating optometrists and ophthalmologists classified lesions from vignettes and were asked to judge whether any retreatment was required. Vignettes comprised clinical information, colour fundus photographs and optical coherence tomography images. Participants' classifications were validated against experts' classifications (reference standard). Resource use and cost information were attributed to these retreatment decisions. Main outcome measures Correct classification of whether further treatment is needed, compared with a reference standard. Results The mean cost per assessment, including the subsequent care pathway, was £411 for optometrists and £397 for ophthalmologists: a cost difference of £13 (95% CI −£18 to £45). Optometrists were non-inferior to ophthalmologists with respect to the overall percentage of lesions correctly assessed (difference −1.0%; 95% CI −4.5% to 2.5%). Conclusions In the base case analysis, the slightly larger number of incorrect retreatment decisions by optometrists led to marginally and non-significantly higher costs. Sensitivity analyses that reflected different practices across eye hospitals indicate that shared care pathways between

Cost-effectiveness of community versus hospital eye service follow-up for patients with quiescent treated age-related macular degeneration alongside the ECHoES randomised trial.

PubMed

Violato, M; Dakin, H; Chakravarthy, U; Reeves, B C; Peto, T; Hogg, R E; Harding, S P; Scott, L J; Taylor, J; Cappel-Porter, H; Mills, N; O'Reilly, D; Rogers, C A; Wordsworth, S

2016-10-24

To assess the cost-effectiveness of optometrist-led follow-up monitoring reviews for patients with quiescent neovascular age-related macular degeneration (nAMD) in community settings (including high street opticians) compared with ophthalmologist-led reviews in hospitals. A model-based cost-effectiveness analysis with a 4-week time horizon, based on a 'virtual' non-inferiority randomised trial designed to emulate a parallel group design. A virtual internet-based clinical assessment, conducted at community optometry practices, and hospital ophthalmology clinics. Ophthalmologists with experience in the age-related macular degeneration service; fully qualified optometrists not participating in nAMD shared care schemes. The participating optometrists and ophthalmologists classified lesions from vignettes and were asked to judge whether any retreatment was required. Vignettes comprised clinical information, colour fundus photographs and optical coherence tomography images. Participants' classifications were validated against experts' classifications (reference standard). Resource use and cost information were attributed to these retreatment decisions. Correct classification of whether further treatment is needed, compared with a reference standard. The mean cost per assessment, including the subsequent care pathway, was £411 for optometrists and £397 for ophthalmologists: a cost difference of £13 (95% CI -£18 to £45). Optometrists were non-inferior to ophthalmologists with respect to the overall percentage of lesions correctly assessed (difference -1.0%; 95% CI -4.5% to 2.5%). In the base case analysis, the slightly larger number of incorrect retreatment decisions by optometrists led to marginally and non-significantly higher costs. Sensitivity analyses that reflected different practices across eye hospitals indicate that shared care pathways between optometrists and ophthalmologists can be identified which may reduce demands on scant hospital resources, although

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].

[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.

The treat-and-extend injection regimen versus alternate dosing strategies in age-related macular degeneration: a systematic review and meta-analysis.

PubMed

Okada, Mali; Kandasamy, Rathika; Chong, Elaine W; McGuiness, Myra; Guymer, Robyn H

2018-06-06

To assess outcomes of the treat-and-extend (T&E) injection regimen for neovascular age related macular degeneration (AMD) as compared to either a monthly or a pro-re-nata (PRN) treatment strategy. Systematic review and meta-analysis METHODS: Studies that compared the T&E regimen with either monthly or PRN dosing for treatment-naïve AMD were included. Trial eligibility, data extraction and risk of bias were assessed according to Cochrane review methods. Estimates were pooled using random effects meta-analysis. Four eligible studies were identified, all using ranibizumab (total n=940 eyes), including two randomized controlled trials comparing T&E to monthly and two retrospective reviews comparing T&E to PRN. No studies evaluating aflibercept were identified. Improvements in vision and central retinal thickness were similar between T&E and monthly at 12 months, with a mean difference of -1.79 letters (95% CI: 3.70, 0.13) and 3.76μm (95% CI: -13.78, 21.30) in favour of monthly injections. In contrast, visual gains were higher in the T&E compared to PRN group (difference of +6.18 letters, 95% CI: 3.28, 9.08). Fewer injections were required using the T&E regimen when compared to monthly (mean of -1.6 and -6.9 injections less at 12 and 24 months respectively). A mean of 1.44 more injections was required for the T&E compared to PRN regimen at 12 months, however this was achieved with fewer visits. Despite the growing preference for the T&E regimen, there is limited head-to-head evidence comparing dosing strategies. The evidence available however, suggests that at 12 months, T&E is comparable to monthly and superior to PRN dosing for both efficacy and safety outcomes when using ranibizumab. Copyright © 2018 Elsevier Inc. All rights reserved.

Subfoveal choroidal thickness predicts macular atrophy in age-related macular degeneration: results from the TREX-AMD trial.

PubMed

Fan, Wenying; Abdelfattah, Nizar Saleh; Uji, Akihito; Lei, Jianqin; Ip, Michael; Sadda, SriniVas R; Wykoff, Charles C

2018-03-01

Our purpose was to evaluate the relationship between subfoveal choroidal thickness (SCT) and development of macular atrophy (MA) in eyes with age-related macular degeneration (AMD). This was a prospective, multicenter study. Sixty participants (120 eyes) in the TREX-AMD trial (NCT01648292) with treatment-naïve neovascular AMD (NVAMD) in at least one eye were included. SCT was measured by certified reading center graders at baseline using spectral domain optical coherence tomography (SDOCT). The baseline SCT was correlated with the presence of MA at baseline and development of incident MA by month 18. Generalized estimating equations were used to account for information from both eyes. Baseline SCT in eyes with MA was statistically significantly less than in those without MA in both the dry AMD (DAMD) (P = 0.04) and NVAMD (P = 0.01) groups. Comparison of baseline SCT between MA developers and non-MA developers revealed a statistically significant difference (P = 0.03). Receiver operating characteristic curve (ROC) analysis showed the cut-off threshold of SCT for predicting the development of MA in cases without MA at baseline was 124 μm (AUC = 0.772; Sensitivity = 0.923; Specificity = 0.5). Among eyes without MA at baseline, those with baseline SCT ≤124 μm were 4.3 times more likely to develop MA (Odds ratio: 4.3, 95% confidence interval: 1.6-12, P = 0.005) than those with baseline SCT >124 μm. Eyes with AMD and MA had less SCT than those without MA. Eyes with less baseline SCT also appear to be at higher risk to develop MA within 18 months.

THE PATHOPHYSIOLOGY OF GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION AND THE COMPLEMENT PATHWAY AS A THERAPEUTIC TARGET

PubMed Central

Schmidt-Erfurth, Ursula; van Lookeren Campagne, Menno; Henry, Erin C.; Brittain, Christopher

2017-01-01

Purpose: Geographic atrophy (GA) is an advanced, vision-threatening form of age-related macular degeneration (AMD) affecting approximately five million individuals worldwide. To date, there are no approved therapeutics for GA treatment; however, several are in clinical trials. This review focuses on the pathophysiology of GA, particularly the role of complement cascade dysregulation and emerging therapies targeting the complement cascade. Methods: Primary literature search on PubMed for GA, complement cascade in age-related macular degeneration. ClinicalTrials.gov was searched for natural history studies in GA and clinical trials of drugs targeting the complement cascade for GA. Results: Cumulative damage to the retina by aging, environmental stress, and other factors triggers inflammation via multiple pathways, including the complement cascade. When regulatory components in these pathways are compromised, as with several GA-linked genetic risk factors in the complement cascade, chronic inflammation can ultimately lead to the retinal cell death characteristic of GA. Complement inhibition has been identified as a key candidate for therapeutic intervention, and drugs targeting the complement pathway are currently in clinical trials. Conclusion: The complement cascade is a strategic target for GA therapy. Further research, including on natural history and genetics, is crucial to expand the understanding of GA pathophysiology and identify effective therapeutic targets. PMID:27902638

Safety and efficacy of intravitreal bevacizumab followed by pegaptanib maintenance as a treatment regimen for age-related macular degeneration.

PubMed

Hughes, Mark S; Sang, Delia N

2006-01-01

Vascular endothelial growth factor (VEGF)-A, both necessary and sufficient in promoting ocular neovascularization, is an attractive therapeutic target. Combining nonselective and selective VEGF blockade may provide clinical benefit with minimal risks in the treatment of neovascular age-related macular degeneration (AMD). Twenty patients with all subtypes of neovascular AMD and a broad range of baseline vision were treated with intravitreal bevacizumab followed by pegaptanib sodium for 54 weeks. Visual acuity measurements, biomicroscopy, funduscopy, fluorescein angiography, optical coherence tomography, and adverse event assessments were performed. Mean visual acuity improved from approximately 20/200 at baseline to 20/80. All patients experienced an improvement in retinal thickness, ranging from -47 to -297 microns. Adverse events were limited to transient irritation or redness. No significant elevation in intraocular pressure occurred following either bevacizumab or pegaptanib injections. Nonselective VEGF blockade with bevacizumab induction and selective VEGF165 blockade with pegaptanib as maintenance therapies may offer clinically meaningful outcomes with acceptable safety profiles in patients with AMD.

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

Plasma long-chain omega-3 polyunsaturated fatty acids and macular pigment in subjects with family history of age-related macular degeneration: the Limpia Study.

PubMed

Merle, Bénédicte M J; Buaud, Benjamin; Korobelnik, Jean-François; Bron, Alain; Delyfer, Marie-Noëlle; Rougier, Marie-Bénédicte; Savel, Hélène; Vaysse, Carole; Creuzot-Garcher, Catherine; Delcourt, Cécile

2017-12-01

In numerous epidemiological studies, omega-3 polyunsaturated fatty acids (PUFAs) have been associated with a decreased risk of age-related macular degeneration (AMD). Beyond their structural, functional and neuroprotective roles, omega-3 PUFAs may favour the retinal accumulation of lutein and zeaxanthin and thus increase macular pigment optical density (MPOD). We examined the associations of MPOD with plasma omega-3 PUFAs in subjects with family history of AMD. The Limpia study is a double-blind, placebo-controlled, prospective randomized clinical trial performed in 120 subjects. Subjects with at least one parent treated for neovascular AMD, aged 40-70, with a best corrected visual acuity (BCVA) >20/25, free of late AMD and other major eye conditions and with no use of supplement containing lutein or zeaxanthin the preceding year were recruited in Bordeaux and Dijon, France. At baseline, MPOD within 1° of eccentricity was measured by modified Heidelberg retinal analyser (Heidelberg, Germany) and plasma omega-3 PUFAs by gas chromatography. Medical history and lifestyle data were collected from a standardized questionnaire. Associations of MPOD with plasma omega-3 PUFAs were assessed at the baseline examination, using mixed linear models adjusted for age, gender, centre, body mass index, smoking, plasma high-density lipoprotein (HDL) cholesterol and lutein+zeaxanthin. After multivariate adjustment, high MPOD was significantly associated with higher level of plasma docosapentaenoic acid (DPA) (β = 0.029, 95% CI: 0.003, 0.055; p = 0.03). Plasma alpha linolenic, eicosapentaenoic and docosahexaenoic acids were not significantly associated with MPOD. In the Limpia study, high MPOD within 1° was significantly associated with higher plasma levels of omega-3 DPA. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

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 ...

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.

Three-dimensional image reconstruction of macula from stratus optical coherence tomography (OCT) for diagnosis of macular degeneration

NASA Astrophysics Data System (ADS)

Arinilhaq; Widita, R.

2016-03-01

Diagnosis of macular degeneration using a Stratus OCT with a fast macular thickness map (FMTM) method produced six B-scan images of macula from different angles. The images were converted into a retinal thickness chart to be evaluated by normal distribution percentile of data so that it can be classified as normal thickness of macula or as experiencing abnormality (e.g. thickening and thinning). Unfortunately, the diagnostic images only represent the retinal thickness in several areas of the macular region. Thus, this study is aims to obtain the entire retinal thickness in the macula area from Status OCT's output images. Basically, the volumetric image is obtained by combining each of the six images. Reconstruction consists of a series of processes such as pre-processing, segmentation, and interpolation. Linear interpolation techniques are used to fill the empty pixels in reconstruction matrix. Based on the results, this method is able to provide retinal thickness maps on the macula surface and the macula 3D image. Retinal thickness map can display the macula area which experienced abnormalities. The macula 3D image can show the layers of tissue in the macula that is abnormal. The system built cannot replace ophthalmologist in decision making in term of diagnosis.

Retinal Ultrastructure of Murine Models of Dry Age-related Macular Degeneration (AMD)

PubMed Central

Ramkumar, Hema L.; Zhang, Jun; Chan, Chi-Chao

2010-01-01

Age-related macular degeneration (AMD) is the most prevalent form of irreversible blindness worldwide in the elderly population. The pathology of dry AMD consists of degeneration of photoreceptors and the RPE, lipofuscin (A2E) accumulation, and drusen formation. Mice have been widely used for generating models that simulate human AMD features for investigating the pathogenesis, treatment and prevention of the disease. Although the mouse has no macula, focal atrophy of photorecptors and RPE, lipofuscin accumulation, and increased A2E can develop in aged mouse eyes. However, drusen are rarely seen in mice because of their simpler Bruch’s membrane and different process of lipofuscin extrusion compared with humans. Thus, analyzing basal deposits at the ultrastructural level and understanding the ultrastructural pathologic differences between various mouse AMD models are critical to comprehending the significance of research findings and response to possible therapeutic options for dry AMD. Based on the multifactorial pathogenesis of AMD, murine dry AMD models can be classified into three groups. First, genetically engineered mice that target genes related to juvenile macular dystrophies are the most common models, and they include abcr−/− (Stargardt disease), transgenic ELOVL4 (Stargardt-3 dominant inheritary disease), Efemp1R345W/R345W (Doyne honeycomb retinal dystrophy), and Timp3S156C/S156C (Sorsby fundus dystrophy) mice. Other murine models target genes relevant to AMD, including inflammatory genes such as Cfh−/−, Ccl2−/−, Ccr2−/−, Cx3cr1−/−, and Ccl2−/−/cx3cr1−/−, oxidative stress associated genes such as Sod1−/− and Sod2 knockdown, metabolic pathway genes such as neprilysin −/− (amyloid β), transgenic mcd/mcd (cathepsin D), Cp−/−/Heph−/Y (ferroxidase ceruloplasmin/hepaestin, iron metabolism), and transgenic ApoE4 on high fat and high cholesterol diet (lipid metabolism). Second, mice have also been immunologically

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

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

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

cGAS drives non-canonical inflammasome activation in age-related macular degeneration

PubMed Central

Kerur, Nagaraj; Fukuda, Shinichi; Banerjee, Daipayan; Kim, Younghee; Fu, Dongxu; Apicella, Ivana; Varshney, Akhil; Yasuma, Reo; Fowler, Benjamin J.; Baghdasaryan, Elmira; Marion, Kenneth M.; Huang, Xiwen; Yasuma, Tetsuhiro; Hirano, Yoshio; Serbulea, Vlad; Ambati, Meenakshi; Ambati, Vidya L.; Kajiwara, Yuji; Ambati, Kameshwari; Bastos-Carvalho, Ana; Ogura, Yuichiro; Terasaki, Hiroko; Oshika, Tetsuro; Kim, Kyung Bo; Hinton, David R.; Leitinger, Norbert; Cambier, John C.; Buxbaum, Joseph D.; Kenney, M. Cristina; Jazwinski, S. Michal; Nagai, Hiroshi; Hara, Isao; West, A. Phillip; Fitzgerald, Katherine A.; Sadda, SriniVas R.; Gelfand, Bradley D.; Ambati, Jayakrishna

2017-01-01

Geographic atrophy is a blinding form of age-related macular degeneration characterized by death of the retinal pigmented epithelium (RPE). In this disease, the RPE displays evidence of DICER1 deficiency, resultant accumulation of endogenous Alu retroelement RNA, and NLRP3 inflammasome activation. How the inflammasome is activated in this untreatable disease is largely unknown. Here we demonstrate that RPE degeneration in human cell culture and in mouse models is driven by a non-canonical inflammasome pathway that results in activation of caspase-4 (caspase-11 in mice) and caspase-1, and requires cyclic GMP-AMP synthase (cGAS)-dependent interferon-β (IFN-β) production and gasdermin D-dependent interleukin-18 (IL-18) secretion. Reduction of DICER1 levelsor accumulation of Alu RNA triggers cytosolic escape of mitochondrial DNA, which engages cGAS. Moreover, caspase-4, gasdermin D, IFN-β, and cGAS levels are elevated in the RPE of human eyes with geographic atrophy. Collectively, these data highlight an unexpected role for cGAS in responding to mobile element transcripts, reveal cGAS-driven interferon signaling as a conduit for mitochondrial damage-induced inflammasome activation, expand the immune sensing repertoire of cGAS and caspase-4 to non-infectious human disease, and identify new potential targets for treatment of a major cause of blindness. PMID:29176737

Automated Segmentation Methods of Drusen to Diagnose Age-Related Macular Degeneration Screening in Retinal Images.

PubMed

Kim, Young Jae; Kim, Kwang Gi

2018-01-01

Existing drusen measurement is difficult to use in clinic because it requires a lot of time and effort for visual inspection. In order to resolve this problem, we propose an automatic drusen detection method to help clinical diagnosis of age-related macular degeneration. First, we changed the fundus image to a green channel and extracted the ROI of the macular area based on the optic disk. Next, we detected the candidate group using the difference image of the median filter within the ROI. We also segmented vessels and removed them from the image. Finally, we detected the drusen through Renyi's entropy threshold algorithm. We performed comparisons and statistical analysis between the manual detection results and automatic detection results for 30 cases in order to verify validity. As a result, the average sensitivity was 93.37% (80.95%~100%) and the average DSC was 0.73 (0.3~0.98). In addition, the value of the ICC was 0.984 (CI: 0.967~0.993, p < 0.01), showing the high reliability of the proposed automatic method. We expect that the automatic drusen detection helps clinicians to improve the diagnostic performance in the detection of drusen on fundus image.

Ranibizumab and bevacizumab for neovascular age-related macular degeneration.

PubMed

Martin, Daniel F; Maguire, Maureen G; Ying, Gui-shuang; Grunwald, Juan E; Fine, Stuart L; Jaffe, Glenn J

2011-05-19

Clinical trials have established the efficacy of ranibizumab for the treatment of neovascular age-related macular degeneration (AMD). In addition, bevacizumab is used off-label to treat AMD, despite the absence of similar supporting data. In a multicenter, single-blind, noninferiority trial, we randomly assigned 1208 patients with neovascular AMD to receive intravitreal injections of ranibizumab or bevacizumab on either a monthly schedule or as needed with monthly evaluation. The primary outcome was the mean change in visual acuity at 1 year, with a noninferiority limit of 5 letters on the eye chart. Bevacizumab administered monthly was equivalent to ranibizumab administered monthly, with 8.0 and 8.5 letters gained, respectively. Bevacizumab administered as needed was equivalent to ranibizumab as needed, with 5.9 and 6.8 letters gained, respectively. Ranibizumab as needed was equivalent to monthly ranibizumab, although the comparison between bevacizumab as needed and monthly bevacizumab was inconclusive. The mean decrease in central retinal thickness was greater in the ranibizumab-monthly group (196 μm) than in the other groups (152 to 168 μm, P=0.03 by analysis of variance). Rates of death, myocardial infarction, and stroke were similar for patients receiving either bevacizumab or ranibizumab (P>0.20). The proportion of patients with serious systemic adverse events (primarily hospitalizations) was higher with bevacizumab than with ranibizumab (24.1% vs. 19.0%; risk ratio, 1.29; 95% confidence interval, 1.01 to 1.66), with excess events broadly distributed in disease categories not identified in previous studies as areas of concern. At 1 year, bevacizumab and ranibizumab had equivalent effects on visual acuity when administered according to the same schedule. Ranibizumab given as needed with monthly evaluation had effects on vision that were equivalent to those of ranibizumab administered monthly. Differences in rates of serious adverse events require further

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.

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.

Patterns of Early and Delayed Visual Response to Ranibizumab Treatment for Neovascular Age-Related Macular Degeneration.

PubMed

Stoller, Glenn L; Kokame, Gregg T; Dreyer, Richard F; Shapiro, Howard; Tuomi, Lisa L

2016-05-12

Understanding the range of temporal responses to ranibizumab is critical for the assessment of individualized treatment regimens for neovascular age-related macular degeneration. To examine patterns of visual and anatomical response to ranibizumab treatment. This study is a retrospective subanalysis of HARBOR (a phase 3, double-masked, multicenter, randomized, active treatment-controlled study of the efficacy and safety of 0.5 mg and 2.0 mg ranibizumab administered monthly or on an as-needed basis (PRN) in patients with subfoveal neovascular age-related macular degeneration). A total of 1097 patients with neovascular age-related macular degeneration were randomized to intravitreal ranibizumab, 0.5 or 2.0 mg, administered monthly or as needed (PRN) with monthly monitoring. Of the 1097 patients, 1057 were included in the analysis for early responders (best-corrected visual acuity [BCVA] obtained at baseline and month 3), and 988 patients were included in the analysis for delayed responders (BCVA obtained at baseline, month 3, and month 12). The HARBOR study began July 7, 2009, with the primary 12-month end point completed on August 5, 2011, ongoing to 24 months. Data analysis for the subgroup was performed from January 4, 2013, through December 17, 2015. Patients were categorized based on BCVA outcomes as early 15-letter responders (gained ≥15 letters from baseline at month 3) or delayed 15-letter responders (did not gain ≥15 letters from baseline at month 3 but did so at month 12). Changes from baseline in BCVA and central foveal thickness (CFT). In total, 266 early and 135 delayed 15-letter responders were identified. In the 0.5-mg monthly, 0.5-mg PRN, 2.0-mg monthly, and 2.0-mg PRN treatment groups, 63 (24.0%) of 263, 65 (24.6%) of 264, 68 (25.7%) of 265, and 70 (26.4%) of 265 patients were early responders, respectively, and 40 (16.3%) of 246, 31 (12.6%) of 247, 35 (14.1%) of 248, and 29 (11.7%) of 247 patients were delayed responders, respectively. By month

Influence of the Vitreoretinal Interface on the Treatment with Anti-VEGF for Exudative Age-Related Macular Degeneration.

PubMed

Gil, Pedro; Gil, João; Oliveira, Nuno; Laíns, Inês; Camilo, Eduardo Nery Rossi; Fonseca, Cristina; Raimundo, Miguel; Cachulo, Maria da Luz; Silva, Rufino

2018-05-07

To investigate the influence of the vitreoretinal interface on the outcomes of different ranibizumab regimens for exudative age-related macular degeneration. We conducted a retrospective subanalysis of 2 prospective clinical trials. Patients were treated with ranibizumab for 12 months according to 3 different regimens: pro-re-nata (PRN), treat and extend (T&E), and monthly. Vitreoretinal interface was assessed for absence (group ON) or presence (group OFF) of posterior vitreous detachment (PVD). We included 64 eyes from 64 patients. Visual improvement was poorer for group ON (0.3 ± 10.7 letters) than for group OFF (9.2 ± 13.3; p = 0.007). A significant difference in letters of improvement between groups was observed in the PRN cohort (ON: -5.0 ± 12.9; OFF: 11.4 ± 11.9; p = 0.003), but not in the cohorts with monthly (ON: 5.7 ± 7.8; OFF: 7.9 ± 15.2; p = 0.735) or T&E (ON: 4.3 ± 4.3; OFF: 7.8 ± 11.1; p = 0.424) treatment. The negative impact of absence of PVD is regimen dependent, with monthly dosing providing similar outcomes to PVD patients. In the absence of PVD (group ON), PRN should be avoided, and T&E might be an alternative. © 2018 S. Karger AG, Basel.

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.

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.

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.

Autofluorescence Lifetimes in Geographic Atrophy in Patients With Age-Related Macular Degeneration.

PubMed

Dysli, Chantal; Wolf, Sebastian; Zinkernagel, Martin S

2016-05-01

To investigate fluorescence lifetime characteristics in patients with geographic atrophy (GA) in eyes with age-related macular degeneration and to correlate the measurements with clinical data and optical coherence tomography (OCT) findings. Patients with GA were imaged with a fluorescence lifetime imaging ophthalmoscope. Retinal autofluorescence lifetimes were measured in a short and a long spectral channel (498-560 nm and 560-720 nm). Mean retinal fluorescence lifetimes were analyzed within GA and the surrounding retina, and data were correlated with best corrected visual acuity and OCT measurements. Fluorescence lifetime maps of 41 eyes of 41 patients (80 ± 7 years) with GA were analyzed. Mean lifetimes within areas of atrophy were prolonged by 624 ± 276 ps (+152%) in the short spectral channel and 418 ± 186 ps (+83%) in the long spectral channel compared to the surrounding tissue. Autofluorescence lifetime abnormalities in GA occurred with particular patterns, similar to those seen in fundus autofluorescence intensity images. Within the fovea short mean autofluorescence lifetimes were observed, presumably representing macular pigment. Short lifetimes were preserved even in the absence of foveal sparing but were decreased in patients with advanced retinal atrophy in OCT. Short lifetimes in the fovea correlated with better best corrected visual acuity in both spectral channels. This study established that autofluorescence lifetime changes in GA present with explicit patterns. We hypothesize that the short lifetimes seen within the atrophy may be used to estimate damage induced by atrophy and to monitor disease progression in the context of natural history or interventional therapeutic studies.

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.

Topical application of a G-Quartet aptamer targeting nucleolin attenuates choroidal neovascularization in a model of age-related macular degeneration.

PubMed

Leaderer, Derek; Cashman, Siobhan M; Kumar-Singh, Rajendra

2015-11-01

Choroidal neovascularization (CNV) associated with the 'wet' form of age related macular degeneration (AMD) is one of the most common causes of central vision loss among the elderly. The 'wet' form of AMD is currently treated by intravitreal delivery of anti-VEGF agents. However, intravitreal injections are associated with complications and long-term inhibition of VEGF leads to macular atrophy. Thus, there is currently an unmet need for the development of therapies for CNV that target molecules other than VEGF. Here, we describe nucleolin as a novel target for the 'wet' form of AMD. Nucleolin was found on the surface of endothelial cells that migrate from the choroid into the subretinal space in the laser-induced model of 'wet' AMD. AS1411 is a previously described G-quartet oligonucleotide that has been shown to bind nucleolin. We found that AS1411 inhibited the formation of tubes by human umbilical vein endothelial cells (HUVECs) by approximately 27.4% in vitro. AS1411 co-localized with the site of laser induced CNV in vivo. Intravitreally injected AS1411 inhibited laser-induced CNV by 37.6% and attenuated infiltration of macrophages by 40.3%. Finally, topical application of AS1411 led to a 43.4% reduction in CNV. Our observations have potential implications for the development of therapies for CNV and specifically for the 'wet' form of AMD. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

EFFICACY AND SAFETY OF INTRAVITREAL AFLIBERCEPT AND RANIBIZUMAB IN ASIAN PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: Subgroup Analyses From the View Trials.

PubMed

Wong, Tien Yin; Cheung, Chui Ming Gemmy; Lai, Timothy Y Y; Chen, Shih-Jen; Lee, Won Ki; Yoon, Young Hee; Iida, Tomohiro; Tueckmantel, Claudia; Sowade, Olaf; Ogura, Yuichiro

2017-12-26

To assess the treatment effect of intravitreal aflibercept and ranibizumab in Asian patients with neovascular age-related macular degeneration. We evaluated data from VIEW 1 and VIEW 2, comparing functional and morphologic outcomes at Week 96 between intravitreal aflibercept 2 mg monthly (2q4) or 2 mg bimonthly after 3 initial monthly doses (2q8) versus ranibizumab 0.5 mg monthly among Asian patients (n = 269) and between Asian and white patients (n = 2044). In Asian patients, there were no significant differences between intravitreal aflibercept 2q4 and 2q8 compared with ranibizumab in mean gain in best-corrected visual acuity (10.23 and 8.35 vs. 8.51 letters). Reduction in central retinal thickness was greater for intravitreal aflibercept 2q4 (150.43 μm, P = 0.0075) and 2q8 (148.15 μm, P = 0.0126) than ranibizumab (119.46 μm). The proportion of dry retinas was greater for intravitreal aflibercept 2q4 (65.7%, P < 0.01) than ranibizumab (41.7%). There were no differences in outcomes between Asian and white patients. Serious treatment-emergent ocular adverse events occurred in <8% of treated eyes, evenly distributed across subgroups. In Asian patients with neovascular age-related macular degeneration, functional and morphologic outcomes were largely similar between intravitreal aflibercept and ranibizumab groups, and to results seen in white patients.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

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.

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.

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

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.

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.

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.

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.

Prevalence and incidence of blindness and other degrees of sight impairment in patients treated for neovascular age-related macular degeneration in a well-defined region of the United Kingdom.

PubMed

Buckle, M; Lee, A; Mohamed, Q; Fletcher, E; Sallam, A; Healy, R; Stratton, I; Tufail, A; Johnston, R L

2015-03-01

This study aimed to evaluate the incidence and prevalence of blindness, sight impairment, and other visual acuity (VA) states in patients receiving ranibizumab for neovascular age-related macular degeneration (nAMD) in Gloucestershire. Serial VA and injection data for all treatment-naive patients receiving their first intravitreal injections of ranibizumab for nAMD in the Gloucestershire National Health Service Ophthalmology department between 2008 and 2010 were extracted from an electronic medical record system. The prevalence of blindness (VA in the better-seeing eye ≤25 Early Treatment Diabetic Retinopathy Study (ETDRS) letters) at the time of first intravitreal injection was 0.8%, increasing to 3.5% after 3 years. The prevalence of sight impairment (VA in the better-seeing eye 26-39 ETDRS letters) increased from 4.1% at baseline to 5.5% after 3 years. The incidence of initiating ranibizumab treatment for nAMD in people aged ≥50 years in Gloucestershire was 111 people per 100 000 population in 2009, and 97 people in 2010. The incidence of patients meeting the visual criteria for blindness and sight impairment registration from treated nAMD in people aged ≥50 years in Gloucestershire was 3.5 and 9.7 people, respectively per 100 000 population in 2010. This is the first real-world study on the incidence and prevalence of eligibility for blindness and sight impairment registration in treated nAMD in the UK based on VA data. The incidence and prevalence of eligibility for certification of blindness or sight impairment in patients treated with ranibizumab for nAMD is low in Gloucestershire, with only 3.6% of the incident population progressing to blindness in 2010.

DICER1/Alu RNA dysmetabolism induces Caspase-8–mediated cell death in age-related macular degeneration

PubMed Central

Kim, Younghee; Tarallo, Valeria; Kerur, Nagaraj; Yasuma, Tetsuhiro; Gelfand, Bradley D.; Bastos-Carvalho, Ana; Hirano, Yoshio; Yasuma, Reo; Mizutani, Takeshi; Fowler, Benjamin J.; Li, Shengjian; Kaneko, Hiroki; Bogdanovich, Sasha; Ambati, Balamurali K.; Hinton, David R.; Hauswirth, William W.; Hakem, Razqallah; Wright, Charles; Ambati, Jayakrishna

2014-01-01

Geographic atrophy, an advanced form of age-related macular degeneration (AMD) characterized by death of the retinal pigmented epithelium (RPE), causes untreatable blindness in millions worldwide. The RPE of human eyes with geographic atrophy accumulates toxic Alu RNA in response to a deficit in the enzyme DICER1, which in turn leads to activation of the NLRP3 inflammasome and elaboration of IL-18. Despite these recent insights, it is still unclear how RPE cells die during the course of the disease. In this study, we implicate the involvement of Caspase-8 as a critical mediator of RPE degeneration. Here we show that DICER1 deficiency, Alu RNA accumulation, and IL-18 up-regulation lead to RPE cell death via activation of Caspase-8 through a Fas ligand-dependent mechanism. Coupled with our observation of increased Caspase-8 expression in the RPE of human eyes with geographic atrophy, our findings provide a rationale for targeting this apoptotic pathway in this disease. PMID:25349431

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.

Macular Morphology and Visual Acuity in the Second Year of the Comparison of Age-Related Macular Degeneration Treatments Trials.

PubMed

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

2016-04-01

To describe the association between morphologic features on fundus photography (FP), fluorescein angiography (FA), and optical coherence tomography (OCT) and visual acuity (VA) in the second year of the Comparison of Age-related Macular Degeneration Treatments Trials (CATT). Prospective cohort study within a randomized clinical trial. Participants in the CATT. Study eye eligibility required angiographic and OCT evidence of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) and VA between 20/25 and 20/320. Treatment was assigned randomly to ranibizumab or bevacizumab with 3 different dosing regimens over a 2-year period. Fluid type, location, and thickness; retina and subretinal tissue complex thickness on OCT; size and lesion composition on FP and FA; and VA. Among 1185 CATT participants, 993 (84%) had fluid on OCT at baseline and completed 2 years of follow-up. At 2 years, intraretinal fluid (IRF), subretinal fluid (SRF), sub-retinal pigment epithelium (RPE) fluid, and subretinal tissue complex thickness decreased in all treatment groups. Ranibizumab monthly was best able to resolve each type of fluid. Eyes with SRF in the foveal center on OCT had better mean VA than eyes with no SRF (72.8 vs. 66.6 letters; P = 0.006). Eyes with IRF in the foveal center had worse mean VA than eyes without IRF (59.9 vs. 70.9 letters; P < 0.0001). Eyes with retinal thickness <120 μm had worse VA compared with eyes with retinal thickness 120 to 212 and >212 μm (59.4 vs. 71.3 vs. 70.3 letters; P < 0.0001). At 2 years, the mean VA (letters) of eyes varied substantially by the type of subfoveal pathology on FP and FA: 70.6 for no pathology; 74.1 for fluid only; 73.3 for CNV or pigment epithelial (RPE) detachment; 68.4 for nongeographic atrophy; and 62.9 for geographic atrophy, hemorrhage, RPE tear, or scar (P < 0.0001). The associations between VA and morphologic features identified through year 1 were maintained or strengthened during year 2. Eyes

Incomplete cortical reorganization in macular degeneration.

PubMed

Liu, Tingting; Cheung, Sing-Hang; Schuchard, Ronald A; Glielmi, Christopher B; Hu, Xiaoping; He, Sheng; Legge, Gordon E

2010-12-01

Activity in regions of the visual cortex corresponding to central scotomas in subjects with macular degeneration (MD) is considered evidence for functional reorganization in the brain. Three unresolved issues related to cortical activity in subjects with MD were addressed: Is the cortical response to stimuli presented to the preferred retinal locus (PRL) different from other retinal loci at the same eccentricity? What effect does the role of age of onset and etiology of MD have on cortical responses? How do functional responses in an MD subject's visual cortex vary for task and stimulus conditions? Eight MD subjects-four with age-related onset (AMD) and four with juvenile onset (JMD)-and two age-matched normal vision controls, participated in three testing conditions while undergoing functional magnetic resonance imaging (fMRI). First, subjects viewed a small stimulus presented at the PRL compared with a non-PRL control location to investigate the role of the PRL. Second, they viewed a full-field flickering checkerboard compared with a small stimulus in the original fovea to investigate brain activation with passive viewing. Third, they performed a one-back task with scene images to investigate brain activation with active viewing. A small stimulus at the PRL generated more extensive cortical activation than at a non-PRL location, but neither yielded activation in the foveal cortical projection. Both passive and active viewing of full-field stimuli left a silent zone at the posterior pole of the occipital cortex, implying a lack of complete cortical reorganization. The silent zone was smaller in the task requiring active viewing compared with the task requiring passive viewing, especially in JMD subjects. The PRL for MD subjects has more extensive cortical representation than a retinal region with matched eccentricity. There is evidence for incomplete functional reorganization of early visual cortex in both JMD and AMD. Functional reorganization is more prominent

Incomplete Cortical Reorganization in Macular Degeneration

PubMed Central

Cheung, Sing-Hang; Schuchard, Ronald A.; Glielmi, Christopher B.; Hu, Xiaoping; He, Sheng; Legge, Gordon E.

2010-01-01

Purpose. Activity in regions of the visual cortex corresponding to central scotomas in subjects with macular degeneration (MD) is considered evidence for functional reorganization in the brain. Three unresolved issues related to cortical activity in subjects with MD were addressed: Is the cortical response to stimuli presented to the preferred retinal locus (PRL) different from other retinal loci at the same eccentricity? What effect does the role of age of onset and etiology of MD have on cortical responses? How do functional responses in an MD subject's visual cortex vary for task and stimulus conditions? Methods. Eight MD subjects—four with age-related onset (AMD) and four with juvenile onset (JMD)—and two age-matched normal vision controls, participated in three testing conditions while undergoing functional magnetic resonance imaging (fMRI). First, subjects viewed a small stimulus presented at the PRL compared with a non-PRL control location to investigate the role of the PRL. Second, they viewed a full-field flickering checkerboard compared with a small stimulus in the original fovea to investigate brain activation with passive viewing. Third, they performed a one-back task with scene images to investigate brain activation with active viewing. Results. A small stimulus at the PRL generated more extensive cortical activation than at a non-PRL location, but neither yielded activation in the foveal cortical projection. Both passive and active viewing of full-field stimuli left a silent zone at the posterior pole of the occipital cortex, implying a lack of complete cortical reorganization. The silent zone was smaller in the task requiring active viewing compared with the task requiring passive viewing, especially in JMD subjects. Conclusions. The PRL for MD subjects has more extensive cortical representation than a retinal region with matched eccentricity. There is evidence for incomplete functional reorganization of early visual cortex in both JMD and AMD

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.

Quality of life in age-related macular degeneration: a review of the literature

PubMed Central

Mitchell, Jan; Bradley, Clare

2006-01-01

Background The Age-related Macular Degeneration Alliance International commissioned a review of the literature on quality of life (QoL) in macular degeneration (MD) with a view to increasing awareness of MD, reducing its impact and improving services for people with MD worldwide. Method A systematic review was conducted using electronic databases, conference proceedings and key journal hand search checks. The resulting 'White Paper' was posted on the AMD Alliance website and is reproduced here. Review MD is a chronic, largely untreatable eye condition which leads to loss of central vision needed for tasks such as reading, watching TV, driving, recognising faces. It is the most common cause of blindness in the Western world. Shock of diagnosis, coupled with lack of information and support are a common experience. Incidence of depression is twice that found in the community-dwelling elderly, fuelled by functional decline and loss of leisure activities. Some people feel suicidal. MD threatens independence, especially when comorbidity exacerbates functional limitations. Rehabilitation, including low vision aid (LVA) provision and training, peer support and education, can improve functional and psychological outcomes but many people do not receive services likely to benefit them. Medical treatments, suitable for only a small minority of people with MD, can improve vision but most limit progress of MD, at least for a time, rather than cure. The White Paper considers difficulties associated with inappropriate use of health status measures and misinterpretation of utility values as QoL measures: evidence suggests they have poor validity in MD. Conclusion There is considerable evidence for the major damage done to QoL by MD which is underestimated by health status and utility measures. Medical treatments are limited to a small proportion of people. However, much can be done to improve QoL by early diagnosis of MD with good communication of prognosis and continuing support

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

Subretinal Hyperreflective Material in the Comparison of Age-Related Macular Degeneration Treatments Trials.

PubMed

Willoughby, Alex S; Ying, Gui-Shuang; Toth, Cynthia A; Maguire, Maureen G; Burns, Russell E; Grunwald, Juan E; Daniel, Ebenezer; Jaffe, Glenn J

2015-09-01

To evaluate the association of subretinal hyperreflective material (SHRM) with visual acuity (VA), geographic atrophy (GA), and scar in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT). Prospective cohort study within a randomized clinical trial. The 1185 CATT participants. Masked readers graded scar and GA on fundus photography and fluorescein angiography and graded SHRM on time-domain and spectral-domain (SD) optical coherence tomography (OCT) throughout 104 weeks. Measurements of SHRM height and width in the fovea, within the center 1 mm(2), or outside the center 1mm(2) were obtained on SD OCT images at 56 (n = 76) and 104 (n = 66) weeks. Presence of SHRM, as well as location and size, and associations with VA, scar, and GA. Among CATT participants, the percentage with SHRM at enrollment was 77%, decreasing to 68% at 4 weeks after treatment and to 54% at 104 weeks. At 104 weeks, scar was present more often in eyes with persistent SHRM than in eyes with SHRM that resolved (64% vs. 31%; P < 0.0001). Among eyes with detailed evaluation of SHRM at weeks 56 (n = 76) and 104 (n = 66), mean VA letter score was 73.5 (standard error [SE], 2.8), 73.1 (SE, 3.4), 65.3 (SE, 3.5), and 63.9 (SE, 3.7) when SHRM was absent, present outside the central 1 mm(2), present within the central 1 mm(2) but not the foveal center, or present at the foveal center (P = 0.02), respectively. When SHRM was present, the median maximum height under the fovea, within the central 1 mm(2) including the fovea and anywhere within the scan, was 86 μm, 120 μm, and 122 μm, respectively. Visual acuity was decreased with greater SHRM height and width (P < 0.05). In eyes with neovascular age-related macular degeneration (AMD), SHRM is common and often persists after anti-vascular endothelial growth factor treatment. At 2 years, eyes with scar were more likely to have SHRM than other eyes. Greater SHRM dimensions were associated with worse VA. In eyes with neovascular AMD

Cytokine concentration in aqueous humour of eyes with exudative age-related macular degeneration.

PubMed

Jonas, Jost B; Tao, Yong; Neumaier, Michael; Findeisen, Peter

2012-08-01

To measure the concentration of cytokines in the aqueous humour of eyes with exudative age-related macular degeneration (AMD). The clinical interventional study included a study group of 18 patients with exudative AMD and a control group of 20 patients undergoing routine cataract surgery. Age did not vary significantly (p = 0.36) between study group (80.8 ± 6.4 years) and control group (77.0 ± 9.9 years), nor did gender (p = 0.75). During the interventions, aqueous humour samples were obtained, in which the concentration of cytokines was measured using a solid-phase chemiluminescence immunoassay. Macular thickness was measured by optical coherence tomography (OCT). In the study group as compared to the control group, significantly higher concentrations were measured for epithelial growth factor (EGF) (p = 0.017), human growth factor (HGF) (p= 0.048), intercellular adhesion molecule-1 (ICAM1) (p = 0.028), interleukin 12p40 (IL12p40) (p = 0.009), interleukin 1a2 (IL1a2) (p = 0.01), interleukin 3 (IL3) (p = 0.02), interleukin 6 (IL6) (p = 0.006), interleukin 8 (IL8) (p = 0.02), monocyte chemoattractant protein-1 (MCP-1) (p = 0.048), monokine induced by interferon gamma (MIG) (p = 0.016), matrix metalloproteinase 9 (MMP9) (p = 0.004) and plasminogen activator inhibitor 1 (PAI1) (p = 0.006). Macular thickness was significantly associated with the concentrations of EGF (p = 0.001), HGF (p = 0.02), ICAM1 (p = 0.001), interleukin 12p40 (p = 0.006), IL 1a2 (p = 0.002), MIG (p = 0.001), MMP9 (p < 0.001) and PAI1 (p = 0.01). Interleukin 6 and MCP-1 showed significant associations with the height of retinal pigment epithelium detachment. Numerous cytokines are associated with the presence and the amount of exudative AMD. © 2012 The Authors. Acta Ophthalmologica © 2012 Acta Ophthalmologica Scandinavica Foundation.

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.

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

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

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

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.

Cost-effectiveness of treating wet age-related macular degeneration at the Kuopio University Hospital in Finland based on a two-eye Markov transition model.

PubMed

Vottonen, Pasi; Kankaanpää, Eila

2016-11-01

Wet age-related macular degeneration (AMD) is the leading cause of blindness worldwide, which can be treated with regular intraocular anti-vascular endothelial growth factor (VEGF) injections. In this study, we wanted to evaluate whether less frequent injections of aflibercept would make it more cost-effective when compared with ranibizumab and low priced bevacizumab. We used a two-eye model to simulate the progression and the treatment of the disease. We selected an 8-year period, 3-month cycles and five health states based on the visual acuity of the better-seeing eye. The transition probabilities and utilities attached to the health states were gathered from previous studies. We conducted the analysis from the hospital perspective and we used the health care costs obtained from Kuopio University Hospital. The costs of intraocular adverse events were taken into account. The incremental cost-effectiveness ratio (ICER) with 3% discount rate (€/QALY) for aflibercept compared with monthly bevacizumab was 1 801 228 and when compared with ranibizumab given as needed, the ICER was minus 3 716 943. The sensitivity analysis showed that a change of 20% of the estimated model parameters or a longer follow-up period did not influence these conclusions. A two-eye Markov transition model was developed to analyse the cost-effectiveness of wet AMD treatment, as quality of life years (QALYs) are largely based on the visual acuity of the better-seeing eye. Monthly injected bevacizumab was the most cost-effective treatment and monthly ranibizumab the least effective. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Tamoxifen Provides Structural and Functional Rescue in Murine Models of Photoreceptor Degeneration

PubMed Central

Wang, Xu; Ma, Wenxin; Gonzalez, Shaimar R.; Kretschmer, Friedrich; Badea, Tudor C.

2017-01-01

Photoreceptor degeneration is a cause of irreversible vision loss in incurable blinding retinal diseases including retinitis pigmentosa (RP) and atrophic age-related macular degeneration. We found in two separate mouse models of photoreceptor degeneration that tamoxifen, a selective estrogen receptor modulator and a drug previously linked with retinal toxicity, paradoxically provided potent neuroprotective effects. In a light-induced degeneration model, tamoxifen prevented onset of photoreceptor apoptosis and atrophy and maintained near-normal levels of electroretinographic responses. Rescue effects were correlated with decreased microglial activation and inflammatory cytokine production in the retina in vivo and a reduction of microglia-mediated toxicity to photoreceptors in vitro, indicating a microglia-mediated mechanism of rescue. Tamoxifen also rescued degeneration in a genetic (Pde6brd10) model of RP, significantly improving retinal structure, electrophysiological responses, and visual behavior. These prominent neuroprotective effects warrant the consideration of tamoxifen as a drug suitable for being repurposed to treat photoreceptor degenerative disease. SIGNIFICANCE STATEMENT Photoreceptor degeneration is a cause of irreversible blindness in a number of retinal diseases such as retinitis pigmentosa (RP) and atrophic age-related macular degeneration. Tamoxifen, a selective estrogen receptor modulator approved for the treatment of breast cancer and previously linked to a low incidence of retinal toxicity, was unexpectedly found to exert marked protective effects against photoreceptor degeneration. Structural and functional protective effects were found for an acute model of light-induced photoreceptor injury and for a genetic model for RP. The mechanism of protection involved the modulation of microglial activation and the production of inflammatory cytokines, highlighting the role of inflammatory mechanisms in photoreceptor degeneration. Tamoxifen may be

One-year real-world outcomes in patients receiving fixed-dosing aflibercept for neovascular age-related macular degeneration.

PubMed

Almuhtaseb, H; Kanavati, S; Rufai, S R; Lotery, A J

2017-06-01

PurposeTo investigate 1-year visual and anatomic outcomes of intravitreal aflibercept for neovascular age-related macular degeneration (nAMD) given at a fixed 8-weekly interval.MethodsRetrospective, single-practice data analysis from an electronic medical record system of 255 eyes (223 patients) with treatment-naïve nAMD receiving 8-weekly aflibercept.ResultsMean logarithm of the minimum angle of resolution best-corrected visual acuity (BCVA) improved from 0.66 at baseline to 0.50 at month 11 (P<0.0001). Mean central retinal thickness (CRT) decreased from 311 μm at baseline to 211 μm at month 11 (P<0.0001). Our mean VA gain of eight ETDRS letters was comparable to the VIEW 1 and VIEW 2 Trials' results at the end of year 1. After loading at month 5, mean BCVA was 0.48 (P<0.0001), and mean CRT was 235 μm. At month 5, 143 eyes (56%) were inactive defined by the absence of macular haemorrhage and intraretinal fluid (IRF) and subretinal fluid (SRF) on optical coherence tomography, and 112 eyes (44%) remained active. At month 11, 136 eyes (53%) were inactive, and 119 eyes (47%) remained active. At month 11, 77% of inactive eyes after loading remained inactive, and 77% of the active eyes after loading remained active. At month 11, mean BCVA of the inactive group was 0.51, and mean BCVA of the active group was 0.48 (P=0.54).ConclusionsAflibercept administered by fixed dosing over 1 year improved VA and macular morphology in treatment-naïve eyes. Active lesions at month 11 do not have worse VA outcomes compared with inactive lesions. The macular status after loading is a reliable indicator of disease activity at the end of year 1.

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

Tele-Ophthalmology for Age-Related Macular Degeneration and Diabetic Retinopathy Screening: A Systematic Review and Meta-Analysis.

PubMed

Kawaguchi, Atsushi; Sharafeldin, Noha; Sundaram, Aishwarya; Campbell, Sandy; Tennant, Matthew; Rudnisky, Christopher; Weis, Ezekiel; Damji, Karim F

2018-04-01

To synthesize high-quality evidence to compare traditional in-person screening and tele-ophthalmology screening. Only randomized controlled trials (RCTs) were included in this systematic review and meta-analysis. The intervention of interest was any type of tele-ophthalmology, including screening of diseases using remote devices. Studies involved patients receiving care from any trained provider via tele-ophthalmology, compared with those receiving equivalent face-to-face care. A search was executed on the following databases: Medline, EMBASE, EBM Reviews, Global Health, EBSCO-CINAHL, SCOPUS, ProQuest Dissertations and Theses Global, OCLC Papers First, and Web of Science Core Collection. Six outcomes of care for age-related macular degeneration (AMD), diabetic retinopathy (DR), or glaucoma were measured and analyzed. Two hundred thirty-seven records were assessed at the full-text level; six RCTs fulfilled inclusion criteria and were included in this review. Four studies involved participants with diabetes mellitus, and two studies examined choroidal neovascularization in AMD. Only data of detection of disease and participation in the screening program were used for the meta-analysis. Tele-ophthalmology had a 14% higher odds to detect disease than traditional examination; however, the result was not statistically significant (n = 2,012, odds ratio: 1.14, 95% confidence interval (CI): 0.52-2.53, p = 0.74). Meta-analysis results show that odds of having DR screening in the tele-ophthalmology group was 13.15 (95% CI: 8.01-21.61; p < 0.001) compared to the traditional screening program. The current evidence suggests that tele-ophthalmology for DR and age-related macular degeneration is as effective as in-person examination and potentially increases patient participation in screening.

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

Correlation of Macular Focal Electroretinogram with Ellipsoid Zone Extension in Stargardt Disease

PubMed Central

Placidi, Giorgio; Calandriello, Luigi; Piccardi, Marco; Campagna, Francesca; Minnella, Angelo Maria; Savastano, Maria Cristina; Falsini, Benedetto

2017-01-01

Stargardt disease (STGD1) is the most common cause of inherited juvenile macular degeneration. This disease is characterized by a progressive accumulation of lipofuscin in the outer retina and subsequent loss of photoreceptors and retinal pigment epithelium. The aim of this study was to evaluate the relationship between cone photoreceptor function and structure in STGD1. Macular function was assessed by visual acuity measurement and focal electroretinogram (FERG) recording while spectral domain optical coherence tomography (SD-OCT) imaging was performed to evaluate the integrity of photoreceptors. FERG amplitude was significantly reduced in patients with Stargardt disease (p < 0.0001). The amplitude of FERG showed a negative relationship with interruption of ellipsoid zone (EZ) (R2 = 0.54, p < 0.0001) and a positive correlation with average macular thickness (AMT). Conversely, visual acuity was only weakly correlated with central macular thickness (CMT) (R2 = 0.12, p = 0.04). In conclusion, this study demonstrates that FERG amplitude is a reliable indicator of macular cone function while visual acuity reflects the activity of the foveal region. A precise assessment of macular cone function by FERG recording may be useful to monitor the progression of STGD1 and to select the optimal candidates to include in future clinical trials to treat this disease. PMID:28912967

Correlation of Macular Focal Electroretinogram with Ellipsoid Zone Extension in Stargardt Disease.

PubMed

Abed, Edoardo; Placidi, Giorgio; Calandriello, Luigi; Piccardi, Marco; Campagna, Francesca; Bertelli, Matteo; Minnella, Angelo Maria; Savastano, Maria Cristina; Falsini, Benedetto

2017-01-01

Stargardt disease (STGD1) is the most common cause of inherited juvenile macular degeneration. This disease is characterized by a progressive accumulation of lipofuscin in the outer retina and subsequent loss of photoreceptors and retinal pigment epithelium. The aim of this study was to evaluate the relationship between cone photoreceptor function and structure in STGD1. Macular function was assessed by visual acuity measurement and focal electroretinogram (FERG) recording while spectral domain optical coherence tomography (SD-OCT) imaging was performed to evaluate the integrity of photoreceptors. FERG amplitude was significantly reduced in patients with Stargardt disease ( p < 0.0001). The amplitude of FERG showed a negative relationship with interruption of ellipsoid zone (EZ) ( R 2 = 0.54, p < 0.0001) and a positive correlation with average macular thickness (AMT). Conversely, visual acuity was only weakly correlated with central macular thickness (CMT) ( R 2 = 0.12, p = 0.04). In conclusion, this study demonstrates that FERG amplitude is a reliable indicator of macular cone function while visual acuity reflects the activity of the foveal region. A precise assessment of macular cone function by FERG recording may be useful to monitor the progression of STGD1 and to select the optimal candidates to include in future clinical trials to treat this disease.

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.

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.

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

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.

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.

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

Baseline data from a multicenter, 5-year, prospective cohort study of Japanese age-related macular degeneration: an AMD2000 report.

PubMed

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

2018-03-01

To report research participants' baseline characteristics in the AMD2000 study, a prospective, multicenter, 5-year, observational cohort study of Japanese age-related macular degeneration (AMD). The characteristics were determined using multimodal imaging. Patients with AMD were recruited at 18 clinical sites in Japan between April 2006 and March 2009. Each patient underwent a complete ophthalmic examination, including measurement of best-corrected visual acuity (Landolt chart), indirect ophthalmoscopy, slit-lamp biomicroscopy with a contact lens, optical coherence tomography imaging, fundus photography, and fluorescein and indocyanine green angiography. Four hundred sixty participants (326 men [70.9%]) were included in the study. At enrollment, 131 eyes (28.5%) had hard drusen and 125 eyes (27.2%) had soft drusen in the macular area. A total of 455 eyes (98.9%) were diagnosed as having wet AMD, and 5 eyes (1.1%), as having dry AMD. Of the 455 eyes with wet AMD, 209 eyes (45.4%) had typical AMD, 228 eyes (49.6%) had polypoidal choroidal vasculopathy (PCV), and 18 eyes (3.9%) had retinal angiomatous proliferation. The size of choroidal neovascularization (CNV) was significantly smaller with indocyanine green angiography than with fluorescein angiography (P < 0.001). Poor baseline visual acuity was associated with cystoid macular edema, older age, scar, extrafoveal macular edema, subfoveal CNV, large branching vascular network, and hard exudates. Japanese patients with AMD are predominantly male, lack drusen, and have a high rate of PCV.

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.

[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.

Comparative Safety and Tolerability of Anti-VEGF therapy in Age-Related Macular Degeneration

PubMed Central

Modi, Yasha S.; Tanchon, Carley; Ehlers, Justis P

2015-01-01

Neovascular age-related macular degeneration (NVAMD) is one of the leading causes of blindness. Over the last decade, the treatment of NVAMD has been revolutionized by the development intravitreal anti-vascular endothelial growth factor (VEGF) therapies. Several anti-VEGF medications are used for the treatment of NVAMD. The safety and tolerability of these medications deserve review given the high prevalence of NVAMD and the significant utilization of these medications. Numerous large randomized clinical trials have not shown any definitive differential safety relative to ocular or systemic safety of these medications. Intravitreal anti-VEGF therapy does appear to impact systemic VEGF levels, but the implications of these changes remain unclear. One unique safety concern relates drug compounding and the potential risks of contamination, specifically for bevacizumab. Continued surveillance for systemic safety concerns, particularly for rare events is merited. Overall these medications are well tolerated and effective in the treatment of NVAMD. PMID:25700714

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.

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.

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.

Therapeutic potential of omega-3 fatty acids supplementation in a mouse model of dry macular degeneration.

PubMed

Prokopiou, Ekatherine; Kolovos, Panagiotis; Kalogerou, Maria; Neokleous, Anastasia; Papagregoriou, Gregory; Deltas, Constantinos; Malas, Stavros; Georgiou, Tassos

2017-01-01

To evaluate the therapeutic effects of omega-3 (ω-3) and omega-6 (ω-6) fatty acids in the CCL2 -/- model of dry age-related macular degeneration (AMD). The blood level of eicosapentaenoic acid (EPA) and arachidonic acid (AA) served to adjust the treatment dosage (AA/EPA=1-1.5). Nine-month-old animals were allocated to different groups: (A) C57BL/6 untreated , (B) CCL2 -/- untreated, (C) CCL2 -/- treated with ω-3+ω-6, and (D) CCL2 -/- treated with ω-3. Treatment was daily administered by gavage for 3 months. Fatty acids analysis was performed and retinas were histologically examined. Three-month-old wild type mice were used for comparison purposes. Real-time PCR and Western blot were performed for retinal inflammatory mediators. Increased EPA and decreased AA levels were observed in both blood and retinas in the treatment groups. The outer nuclear layer thickness was increased in groups C (45.0±3.9 µm) and D (62.8±4.9 µm), compared with groups B (65.6±3.0 µm) and A (71.1±4.2 µm), and in younger mice, it was 98.0±3.9 µm. A decrease in NF-κB expression was noted in the treatment groups. Interleukin (IL) 18 protein levels demonstrated a significant reduction in the ω-3-treated group only. Supplementation with ω-3+ω-6 or ω-3 alone (AA/EPA=1-1.5) suggests a protective mechanism in the CCL2 -/- animal model of dry AMD, with a more beneficial effect when ω-3 are used alone. Our findings indicated that inflammation is not the only determining factor; perhaps a regenerative process might be involved following administration of ω-3 fatty acids.

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

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

Age-related macular degeneration: Effects of a short-term intervention with an oleaginous kale extract--a pilot study.

PubMed

Arnold, Christin; Jentsch, Susanne; Dawczynski, Jens; Böhm, Volker

2013-01-01

Age-related macular degeneration (AMD) is a multifactorial degenerative disease of the retina, which accounts for slowly progressive visual impairment in the elderly. An increased dietary intake of xanthophylls is suggested to be inversely related to the risk of macular disease. The present study was designed as a randomized, double-blind, placebo-controlled, parallel trial examining the influence of a short-term intervention with an oleaginous extract of Brassica oleracea var. sabellica L. (kale) on plasma xanthophyll concentrations and the optical density of the macular pigment xanthophylls (MPOD). Twenty patients with non-exudative AMD were recruited for a 10-wk study period (2-wk run-in, 4-wk intervention, 4-wk washout). All participants received 50 mL of a beverage containing either an oleaginous extract of kale (kale) or refined rapeseed oil (placebo). The verum product provides 10 mg lutein and 3 mg zeaxanthin per day. The concentrations of the xanthophylls in plasma and the MPOD increased significantly in the kale group after 4 wk of intervention. The successive washout period resulted in a significant decline of the values in plasma and macula. The values at the end of the study were still significantly higher than the initial values. Nevertheless, the improvements did not persist over 4 wk of washout. The distribution of the xanthophylls in the macula seems to be more dynamic than originally assumed. Copyright © 2013 Elsevier Inc. All rights reserved.

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

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

Immune responses in age-related macular degeneration and a possible long-term therapeutic strategy for prevention.

PubMed

Nussenblatt, Robert B; Lee, Richard W J; Chew, Emily; Wei, Lai; Liu, Baoying; Sen, H Nida; Dick, Andrew D; Ferris, Frederick L

2014-07-01

To describe the immune alterations associated with age-related macular degeneration (AMD); and, based on these findings, to offer an approach to possibly prevent the expression of late disease. Perspective. Review of the existing literature dealing with epidemiology, models, and immunologic findings in patients. Significant genetic associations have been identified and reported, but environmentally induced (including epigenetic) changes are also an important consideration. Immune alterations include a strong interleukin 17 family signature as well as marked expression of these molecules in the eye. Oxidative stress as well as other homeostatic altering mechanisms occur throughout life. With this immune dysregulation there is a rationale for considering immunotherapy. Indeed, immunotherapy has been shown to affect the late stages of AMD. Immune dysregulation appears to be an underlying alteration in AMD, as in other diseases thought to be degenerative and attributable to aging. Para-inflammation and immunosenescence may importantly contribute to the development of disease. The role of complement factor H still needs to be better defined, but in light of its association with ocular inflammatory conditions such as sarcoidosis, it does not appear to be unique to AMD but rather may be a marker for retinal pigment epithelium function. With the strong interleukin 17 family signature and the need to treat early on in the disease process, oral tolerance may be considered to prevent disease progression. Published by Elsevier Inc.

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

Racial differences and other risk factors for incidence and progression of age-related macular degeneration: Salisbury Eye Evaluation (SEE) Project.

PubMed

Chang, Margaret A; Bressler, Susan B; Munoz, Beatriz; West, Sheila K

2008-06-01

To evaluate risk factors for the incidence and progression of age-related macular degeneration (AMD) in a racially heterogeneous, geriatric population. Subjects (n = 2240) aged 65 to 84 years underwent 2 examinations separated by 2 years, of which 1937 subjects (85%) were included in this report. Fundus photographs were performed at each examination and were graded by trained readers. Multivariate logistic regression models adjusted for age, sex, race, and clustering between eyes were used to evaluate risk factors for AMD incidence and progression. Smoking was a strong, dose-dependent, risk factor for progression from medium size drusen to large drusen or pigmentary abnormalities within the central 1500-microm macular zone. Smoking was also a strong risk factor for development of incident focal pigmentation within 3000 microm of the foveal center. White participants were significantly more likely than blacks to develop large drusen and focal pigmentation and to progress from medium- to large-sized drusen or pigment abnormalities within the central 1500 microm macular zone. However, whites did not have an increased risk of progression from large drusen or pigment abnormalities within the central 1500-microm perimacular zone to foveal GA or CNV when compared with blacks. Smoking and race are important risk factors for progression from medium to large drusen or to pigment abnormalities within the central 1500-microm macular zone. Limitations in the power of this study preclude assessment of the roles of smoking and race on the ultimate progression to foveal GA or CNV once central large drusen or pigment abnormalities are present.

What Effect Does Ethnicity Have on the Response to Ranibizumab in the Treatment of Wet Age-Related Macular Degeneration?

PubMed

Mohamed, Ryian; Gadhvi, Kunal; Mensah, Evelyn

2018-05-30

To compare, in a single urban population, the visual outcomes of ranibizumab monotherapy in "White" (W) and "Non-White" (NW) patients with wet age-related macular degeneration (AMD). Prospective data was collected from 434 eyes of 217 patients with wet AMD patients receiving intravitreal ranibizumab. Baseline and monthly LogMAR visual acuities were obtained. All patients received treatment under a "treat and extend policy" consisting of three monthly injections of ranibizumab, followed by individualised sequentially lengthening follow-up intervals when stable. At 24 months, the percentage of eyes that maintained or improved vision was 91% in W patients and 83% in NW patients. Correspondingly, at 24 months, the percentage of visual loss was 9% for W patients and 17% of NW patients. We found that whilst W patients required fewer overall injections (14.1) they gained an average 4 LogMAR letters of visual acuity. However, NW patients required more injections (14.6) to gain 0.5 LogMAR letters of visual acuity over the same 24 months of treatment. Individualised ranibizumab monotherapy is more effective in preserving vision for W compared to NW patients with wet AMD. © 2018 S. Karger AG, Basel.

The Long-term Natural History of Geographic Atrophy from Age-Related Macular Degeneration

PubMed Central

Sunness, Janet S.; Margalit, Eyal; Srikumaran, Divya; Applegate, Carol A.; Tian, Yan; Perry, Daniel; Hawkins, Barbara S.; Bressler, Neil M.

2008-01-01

Purpose To report the enlargement rate of geographic atrophy (GA) over time, its relationship to size of atrophy at baseline and to prior enlargement rate, and the implications for designing future treatment trials for GA. Design Prospective natural history study of GA resulting from age-related macular degeneration. Participants Two hundred twelve eyes of 131 patients were included in the analysis. Methods Annual follow-up included stereo color fundus photographs. The areas of GA were identified and measured, and the rate of enlargement of the atrophy was assessed. Sample sizes for clinical trials using systemic treatment and uniocular treatment were determined. Main Outcome Measure Rate of enlargement of the atrophy. Results The median overall enlargement rate was 2.1 mm2/year (mean, 2.6 mm2/year). Eyes with larger areas of atrophy at baseline tended to have larger enlargement rates, but knowledge of prior rates of enlargement was the most significant factor in predicting subsequent enlargement rates. There was high concordance between the enlargement rates in the 2 eyes of patients with bilateral GA (correlation coefficient, 0.76). To detect a 25% reduction in enlargement rate for a systemic treatment (α, 0.05; power, 0.80; losses to follow-up, 15%), 153 patients each in a control and treatment group would be required for a trial with a 2-year follow-up period for each patient. For a uniocular treatment, 38 patients with bilateral GA would be required, with the untreated eye serving as a control for the treated eye. Conclusions Treatment trials for GA with an outcome variable of change in enlargement rate are feasible. PMID:17270676

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/

One year results of anti-VEGF treatment in pigment epithelial detachment secondary to macular degeneration.

PubMed

Yüksel, Harun; Türkcü, Fatih M; Sahin, Alparslan; Sahin, Muhammed; Cinar, Yasin; Cingü, Abdullah K; Ari, Seyhmus; Caça, Ihsan

2013-01-01

Pigment epithelial detachment (PED) may be seen in all stages of age-related macular degeneration (ARMD) and may lead to poor prognosis. In this study, we retrospectively examined the effect of anti-VEGF treatments in ARMD patients with vascularized PED. Medical records of 15 patients with PED secondary to ARMD were reviewed retrospectively. The diagnosis of PED was made with fundoscopy, fundus fluorescein angiography and optical coherence tomography. Patients were treated with intravitreal ranibizumab or/and bevacizumab and followed up for a minimum of one year. PED height and best corrected visual acuity (BCVA) was obtained before the first intravitreal anti-VEGF injection and again at the 1st, 3rd, 6th and 12th month after the injection. The mean baseline BCVA was 0.71 ± 0.48 logarithm of the minimal angle of resolution (logMAR) unit and the mean baseline PED height was 361 ± 153 µ. The mean injection count per eye was 3.9 ± 2.9. There was a significant reduce in mean PED height (247 ± 177 µ) also in 2 eyes PED completely resolved at the end of the follow up period. The mean BCVA at 12th month (0,69 ± 0,37) were not different from the baseline record. This retrospective case series showed that intravitreal anti-VEGF therapy preserved vision and reduced PED height in PED patients in a one-year follow-up period.

Influence of vitreomacular interface on anti-vascular endothelial growth factor treatment outcomes in neovascular age-related macular degeneration

PubMed Central

Gao, Meng; Liu, LiMei; Liang, XiDa; Yu, YanPing; Liu, XinXin; Liu, Wu

2017-01-01

Abstract The aim of the study was to evaluate the influence of vitreomacular interface configuration on treatment outcomes after intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy for neovascular age-related macular degeneration (AMD). The Pubmed, Embase, and Cochrane Central Register of Controlled Trials databases were searched to identify relevant prospective or retrospective studies that evaluate the influence of vitreomacular adhesion (VMA) or vitreomacular traction (VMT) on functional and anatomical outcomes in neovascular AMD patients treated with anti-VEGF agents. The outcome measures were the mean change in best corrected visual acuity (BCVA) from baseline, the mean change in central macular thickness (CMT) from baseline, and the mean injection numbers of anti-VEGF treatment from baseline. In total, 9 studies were selected for this meta-analysis, including 2156 eyes (404 eyes in the VMA/VMT group and 1752 eyes in the non-VMA/VMT group). In neovascular AMD patients treated with anti-VEGF agents, the VMA/VMT group was associated with poorer visual acuity gains and CMT reductions at 1 year (WMD [95% CI], −6.17 [−11.91, −0.43] early treatment diabetic retinopathy study (ETDRS) letters, P = .04; WMD [95% CI], 22.19 [2.01, 42.38] μm, P = .03, respectively). There was no significant difference between 2 groups in the mean BCVA change and the CMT change over 2 years (WMD [95% CI], −5.59 [−21.19, 10.01] ETDRS letters, P = .48; WMD [95% CI], 6.56 [−24.78, 37.90] μm, P = .68, respectively). There was no significant difference in the mean injection numbers between 2 groups at 1 year (WMD [95% CI], 0.36 [−0.19, 0.90], P = .21), whereas the VMA/VMT group had a significantly higher mean injection numbers over 2 years (WMD [95% CI], 1.14 [0.11, 2.16], P = .03). The limited evidence suggests that vitreomacular interface configuration have a significant influence on the visual acuity gain and CMT reduction at 1

Prevalence of intermediate-stage age-related macular degeneration in patients with acquired immunodeficiency syndrome.

PubMed

Jabs, Douglas A; Van Natta, Mark L; Sezgin, Efe; Pak, Jeong Won; Danis, Ronald

2015-06-01

To evaluate the prevalence of intermediate-stage age-related macular degeneration (AMD) in patients with acquired immunodeficiency syndrome (AIDS). Cross-sectional study of patients with AIDS enrolled in the Longitudinal Study of the Ocular Complications of AIDS. Intermediate-stage AMD was determined from enrollment retinal photographs by graders at a centralized Reading Center, using the Age-Related Eye Disease Study grading system. Graders were masked as to clinical data. Of 1825 participants with AIDS and no ocular opportunistic infections, 9.9% had intermediate-stage AMD. Risk factors included age, with an odds ratio (OR) of 1.9 (95% confidence interval [CI] 1.6, 2.3, P < .001) for every decade of age; the prevalence of AMD ranged from 4.0% for participants 30-39 years old to 24.3% for participants ≥60 years old. Other risk factors included the human immunodeficiency virus (HIV) risk groups of injection drug use (OR = 2.4, 95% CI 1.5, 3.9, P < .001) or heterosexual contact (OR = 1.9, 95% CI 1.3, 2.8, P = .001). Compared with the HIV-uninfected population in the Beaver Dam Offspring Study, there was an approximate 4-fold increased age-adjusted prevalence of intermediate-stage AMD. Patients with AIDS have an increased age-adjusted prevalence of intermediate-stage AMD compared with that found in a non-HIV-infected cohort evaluated with similar methods. This increased prevalence is consistent with the increased prevalence of other age-related diseases in antiretroviral-treated, immune-restored, HIV-infected persons when compared to non-HIV-infected persons. Published by Elsevier Inc.

Clinical evidence of intravitreal triamcinolone acetonide in the management of age-related macular degeneration.

PubMed

Becerra, E M; Morescalchi, F; Gandolfo, F; Danzi, P; Nascimbeni, G; Arcidiacono, B; Semeraro, F

2011-02-01

Triamcinolone acetonide (TA) is one of the first pharmacologic compounds evaluated for the treatment of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). The most important effects of TA consist in the stabilisation of the blood-retinal barrier and the down-regulation of inflammation. TA also has anti-angiogenic and anti-fibrotic properties. The peculiar characteristic of being well tolerated by ocular tissues and the capability to remain active for many months after a single intravitreal injection, make this drug a safe and effective alternative. In the past decade, intravitreal injection of TA (IVTA) has emerged as a useful treatment of several ocular diseases such as uveitis, macular edema secondary to retinal vasculature disease, neovascularisation and vitreoretinopathy. In this paper, we review all the available evidence of its use in AMD as mono-therapy or in combination with other treatments, and we discuss which role TA will play in the treatment of AMD in the future. The first experiences with IVTA as monotherapy for the treatment of exudative AMD reported a positive outcome in transiently reducing the leakage from CNV. However, in the long-term follow-up, IVTA as monotherapy had no effect on the risk of severe visual acuity loss, despite a significant anti-angiogenic effect found 3 months after the treatment. Consequently, studies using the combination of IVTA and photodynamic therapy (PDT), which acts synergistically, were performed. They reported to improve vision and to reduce the number of re-treatments with PDT. A large number of publications confirmed the positive synergic role of combining TA and PDT (therapies) for the treatment of all types of CNV: classic or predominantly classic, occult or minimally classic and RAP (Retinal Angiomatous Proliferation) lesions. The advantages registered with the use of IVTA plus PDT compared to PDT alone were partially limited by the side effects, such as the rapid evolution

[Age-related macular degeneration – a challenge for public health care].

PubMed

Mantel, Irmela

2016-01-01

Age-related macular degeneration (AMD) is the predominant cause of legal blindness in the population over 50 years of age. The disorder shows exponentially increasing prevalence with age, and the late forms with their vision threatening evolution are found in approximately one third of cases. The late AMD may be purely atrophic and so far untreatable. Or it may be neovascular and exudative, for which medical treatment is available, consisting of repetitive intravitreous injections of Anti-VEGF molecules. The treatment is highly effective in blocking the growth of the pathological vessels and allowing resolution of the accompanying edema. Visual improvement is variable but often very meaningful for the patients. However, the final visual level depends mostly on early intervention. Thus, screening for the first signs of neovascular AMD is crucial for the endresult. However, the repetitive intraocular injections are an important burden for the patients. Due to the high patient numbers, the chronic care management with steadily adding new patients is a major challenge for treating institutions. Limited resources may put patients at risk of undertreatment with resulting visual loss. Various strategies have been developed to cope with the burden. In addition, the financial cost is high for the health care system. On the other hand, timely and ongoing treatment is the best investment to achieve meaningful visual improvement, which is extremely important for the quality of life and autonomy of the patients. Side effects of the treatment are limited and mostly procedure related. Systemic side effects are possible but despite the large studies not conclusive. However, care must be taken in cases of high cardiovascular risk, as thromboembolic risk increase may rarely happen. So far unsolved problems include the long term visual results, the degree of reversibility of neovascularization, and the missing treatment options of atrophic AMD. Basic and clinical research on various

Kilovoltage radiosurgery with gold nanoparticles for neovascular age-related macular degeneration (AMD): a Monte Carlo evaluation

NASA Astrophysics Data System (ADS)

Brivio, D.; Zygmanski, P.; Arnoldussen, M.; Hanlon, J.; Chell, E.; Sajo, E.; Makrigiorgos, G. M.; Ngwa, W.

2015-12-01

This work uses Monte Carlo radiation transport simulation to assess the potential benefits of gold nanoparticles (AuNP) in the treatment of neovascular age-related macular degeneration with stereotactic radiosurgery. Clinically, a 100 kVp x-ray beam of 4 mm diameter is aimed at the macula to deliver an ablative dose in a single fraction. In the transport model, AuNP accumulated at the bottom of the macula are targeted with a source representative of the clinical beam in order to provide enhanced dose to the diseased macular endothelial cells. It is observed that, because of the AuNP, the dose to the endothelial cells can be significantly enhanced, allowing for greater sparing of optic nerve, retina and other neighboring healthy tissue. For 20 nm diameter AuNP concentration of 32 mg g-1, which has been shown to be achievable in vivo, a dose enhancement ratio (DER) of 1.97 was found to be possible, which could potentially be increased through appropriate optimization of beam quality and/or AuNP targeting. A significant enhancement in dose is seen in the vicinity of the AuNP layer within 30 μm, peaked at the AuNP-tissue interface. Different angular tilting of the 4 mm beam results in a similar enhancement. The DER inside and in the penumbra of the 4 mm irradiation-field are almost the same while the actual delivered dose is more than one order of magnitude lower outside the field leading to normal tissue sparing. The prescribed dose to macular endothelial cells can be delivered using almost half of the radiation allowing reduction of dose to the neighboring organs such as retina/optic nerve by 49% when compared to a treatment without AuNP.

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

Recommended Guidelines for Use of Intravitreal Aflibercept With a Treat-and-Extend Regimen for the Management of Neovascular Age-Related Macular Degeneration in the Asia-Pacific Region: Report From a Consensus Panel.

PubMed

Koh, Adrian; Lanzetta, Paolo; Lee, Won Ki; Lai, Chi-Chun; Chan, Wai-Man; Yang, Chung-May; Cheung, Chui Ming Gemmy

2017-01-01

To summarize recommendations for the use of intravitreal aflibercept with a treat-and-extend regimen to manage neovascular age-related macular degeneration (nAMD) in the Asia-Pacific region. Although anti-vascular endothelial growth factor therapies have improved the quality of life of patients with nAMD, a leading cause of blindness and visual impairment, the high treatment frequency recommended by current guidelines places a significant burden on patients and healthcare providers. Recommended guidelines from a consensus panel. An expert panel formed a consensus on recommendations for use of intravitreal aflibercept as treatment of nAMD in the Asia-Pacific region. After 3 initial monthly doses, treatment interval could be extended by 4-week increments, to a maximum of 12 weeks, in patients with inactive disease. Conversely, in active disease, treatment intervals should be shortened, by 4 weeks, or to 4 weeks in cases of severe recurrence. Treatment could be ceased in patients with stable disease activity after 12 months of treatment at 12-week intervals, as a means to prevent over treatent and lifelong injections. These recommendations could potentially minimize the number of treatments while maintaining efficacy and improve compliance by reducing the number of clinic visits compared with existing recommendations. Copyright 2017 Asia-Pacific Academy of Ophthalmology.

[Real life visual and anatomic outcomes of aflibercept treatment for treatment-naive patients with exudative age-related macular degeneration].

PubMed

Duval, M-V; Rougier, M-B; Delyfer, M-N; Combillet, F; Korobelnik, J-F

2017-04-01

Anti-VEGF therapies have revolutionized the treatment of neovascular age-related macular degeneration (AMD). The goal of this study was to evaluate the "real life" visual and anatomical outcomes of aflibercept treatment for treatment-naive patients with exudative AMD. This was a retrospective study of patients treated with aflibercept in the department of Ophthalmology at the University Hospital of Bordeaux between November 2013 and July 2015. The follow-up period varied from 3months to 2years. All patients received an induction phase with 3monthly intravitreal injections (IVT) followed by personalized monitoring. ETDRS best-corrected visual acuity (BCVA), fundus examination and OCT were performed at each visit. Data were collected at day 0, 3 months, 6, 9, 12months, 18 and 24months. Forty-three eyes of forty patients, mean age 77.7years, were included, with a minimum of 3months follow-up. Twenty-five eyes were followed for 1year; 5 eyes for two years. At baseline, the mean BCVA was 55.7 letters. Patients received 7.5 injections on average the first year and 2.6 the 2nd year. The mean gain of visual acuity was +7.3 letters at 3 months, +6.2 letters at 12 months, and +6.8 letters at 2years. Anatomically, the OCT data showed a decline of all parameters. The central macular thickness decreased by 118.3μm at 3months, 136.4μm at 12months and 65.5μm at 2years. Aflibercept can achieve effective visual and anatomical outcomes with results, which approach the pivotal studies, despite the use of personalized protocols and longer monitoring intervals. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

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

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

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.

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.

Lamellar macular hole in X linked retinoschisis

PubMed Central

Kumar, Vinod; Goel, Neha

2016-01-01

X linked retinoschisis (XLRS) is the most common juvenile onset retinal degeneration. The disorder leads to poor vision in old age. Complications, however, can lead to earlier loss of vision in this condition. This report describes two patients of XLRS, who had presented with poor vision because of having had a lamellar macular hole at a young age. Lamellar macular holes are rare and have never been reported to cause early onset poor vision in XLRS. PMID:27170611

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

Inner Segment Remodeling and Mitochondrial Translocation in Cone Photoreceptors in Age-Related Macular Degeneration With Outer Retinal Tubulation.

PubMed

Litts, Katie M; Messinger, Jeffrey D; Freund, K Bailey; Zhang, Yuhua; Curcio, Christine A

2015-04-01

To quantify impressions of mitochondrial translocation in degenerating cones and to determine the nature of accumulated material in the subretinal space with apparent inner segment (IS)-like features by examining cone IS ultrastructure. Human donor eyes with advanced age-related macular degeneration (AMD) were screened for outer retinal tubulation (ORT) in macula-wide, high-resolution digital sections. Degenerating cones inside ORT (ORT cones) and outside ORT (non-ORT cones) from AMD eyes and unaffected cones in age-matched control eyes were imaged using transmission electron microscopy. The distances of mitochondria to the external limiting membrane (ELM), cone IS length, and cone IS width at the ELM were measured. Outer retinal tubulation and non-ORT cones lose outer segments (OS), followed by shortening of IS and mitochondria. In non-ORT cones, IS broaden. Outer retinal tubulation and non-ORT cone IS myoids become undetectable due to mitochondria redistribution toward the nucleus. Some ORT cones were found lacking IS and containing mitochondria in the outer fiber (between soma and ELM). Unlike long, thin IS mitochondria in control cones, ORT and non-ORT IS mitochondria are ovoid or reniform. Shed IS, some containing mitochondria, were found in the subretinal space. In AMD, macula cones exhibit loss of detectable myoid due to IS shortening in addition to OS loss, as described. Mitochondria shrink and translocate toward the nucleus. As reflectivity sources, translocating mitochondria may be detectable using in vivo imaging to monitor photoreceptor degeneration in retinal disorders. These results improve the knowledge basis for interpreting high-resolution clinical retinal imaging.

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.

Towards early detection of age-related macular degeneration with tetracyclines and FLIM

NASA Astrophysics Data System (ADS)

Szmacinski, Henryk; Hegde, Kavita; Zeng, Hui-Hui; Eslami, Katayoun; Puche, Adam; Lakowicz, Joseph R.; Lengyel, Imre; Thompson, Richard B.

2018-02-01

Recently, we discovered microscopic spherules of hydroxyapatite (HAP) in aged human sub-retinal pigment epithelial (sub-RPE) deposits in the retinas of aged humans (PMID: 25605911), and developed evidence that the spherules may act to nucleate the growth of sub-RPE deposits such as drusen. Drusen are clinical hallmarks of age-related macular degeneration (AMD). We found that tetracycline-family antibiotics, long known to stain HAP in teeth and bones, also stained the HAP spherules, but in general the HAP-bound fluorescence excitation and emission spectra overlapped with the well-known autofluorescence of the RPE overlying drusen, making them difficult to resolve. However, we also found that certain tetracyclines exhibited substantial increases in fluorescence lifetime upon binding to HAP, and moreover these lifetimes were substantially greater than those previously observed (Dysli, et al., 2014) for autofluorescence in the human retina in vivo. Thus we were able to image the HAP spherules by fluorescence lifetime imaging microscopy (FLIM) in cadaveric retinas of aged humans. These findings suggest that FLIM imaging of tetracycline binding to HAP could become a diagnostic tool for the development and progression of AMD.

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

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.

Treatments for dry age-related macular degeneration and Stargardt disease: a systematic review.

PubMed

Waugh, Norman; Loveman, Emma; Colquitt, Jill; Royle, Pamela; Yeong, Jian Lee; Hoad, Geraldine; Lois, Noemi

2018-05-01

Age-related macular degeneration (AMD) is the leading cause of visual loss in older people. Advanced AMD takes two forms, neovascular (wet) and atrophic (dry). Stargardt disease (STGD) is the commonest form of inherited macular dystrophy. To carry out a systematic review of treatments for dry AMD and STGD, and to identify emerging treatments where future NIHR research might be commissioned. Systematic review. We searched MEDLINE, EMBASE, Web of Science and The Cochrane Library from 2005 to 13 July 2017 for reviews, journal articles and meeting abstracts. We looked for studies of interventions that aim to preserve or restore vision in people with dry AMD or STGD. The most important outcomes are those that matter to patients: visual acuity (VA), contrast sensitivity, reading speed, ability to drive, adverse effects of treatment, quality of life, progression of disease and patient preference. However, visual loss is a late event and intermediate predictors of future decline were accepted if there was good evidence that they are strong predictors of subsequent visual outcomes. These include changes detectable by investigation, but not necessarily noticed by people with AMD or STGD. ClinicalTrials.gov, the World Health Organization search portal and the UK Clinical Trials gateway were searched for ongoing and recently completed clinical trials. The titles and abstracts of 7948 articles were screened for inclusion. The full text of 398 articles were obtained for further screening and checking of references and 112 articles were included in the final report. Overall, there were disappointingly few good-quality studies (including of sufficient size and duration) reporting useful outcomes, particularly in STGD. However we did identify a number of promising research topics, including drug treatments, stem cells, new forms of laser treatment, and implantable intraocular lens telescopes. In many cases, research is already under way, funded by industry or governments. In AMD