Age Related Macular Degeneration

AbstractProlonged life expectancies contribute to the increasing prevalence of age-related macular degeneration (AMD) that is already the leading cause of severe vision loss among the elderly in developed countries. In dry AMD, the disease culminates into vast retinal atrophy, whereas the wet form is characterized by retinal edema and sudden vision loss due to neovascularization originating from the choroid beneath the Bruch’s membrane. There is no treatment for dry AMD and despite intravitreal injections of anti-vascular endothelial growth factor (VEGF) that suppress the neovessel formation, also wet AMD needs new therapies to prevent the disease progression and to serve patients lacking of positive response to current medicines. Knowledge on disease mechanisms is a prerequisite for the drug development, which is hindered by the multifactorial nature of AMD. Numerous distinguished publications have revealed AMD mechanisms at the cellular and molecular level and in this multi-author review, we take a bit broader look at the topic with some novel aspects.

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Mechanism of Inflammation in Age-Related Macular Degeneration

Mediators of Inflammation ◽

10.1155/2012/546786 ◽

2012 ◽

Vol 2012 ◽

pp. 1-16 ◽

Cited By ~ 59

Author(s):

Francesco Parmeggiani ◽

Mario R. Romano ◽

Ciro Costagliola ◽

Francesco Semeraro ◽

Carlo Incorvaia ◽

...

Keyword(s):

Macular Degeneration ◽

Microglial Activation ◽

Vision Loss ◽

Dietary Habits ◽

The United States ◽

Age Related Macular Degeneration ◽

Age Related ◽

Oxidized Lipoproteins ◽

Severe Vision Loss

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.

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Hypoxic drive caused type 3 neovascularization in a preclinical model of exudative age-related macular degeneration

Human Molecular Genetics ◽

10.1093/hmg/ddz159 ◽

2019 ◽

Vol 28 (20) ◽

pp. 3475-3485 ◽

Cited By ~ 2

Author(s):

Lijuan Zhang ◽

Xuan Cui ◽

Yangjun Han ◽

Karen Sophia Park ◽

Xiaohong Gao ◽

...

Keyword(s):

Macular Degeneration ◽

Vision Loss ◽

Age Related Macular Degeneration ◽

Preclinical Model ◽

Metabolic Demand ◽

Exudative Amd ◽

Type 3 Neovascularization ◽

Age Related ◽

Severe Vision Loss ◽

Type 3

Abstract Hypoxia associated with the high metabolic demand of rods has been implicated in the pathology of age-related macular degeneration (AMD), the most common cause of adult blindness in the developed world. The majority of AMD-associated severe vision loss cases are due to exudative AMD, characterized by neovascularization. To further investigate the causes and histopathology of exudative AMD, we conditionally induced hypoxia in a novel preclinical AMD model (Pde6gcreERT2/+;Vhl−/−) by targeting Vhl and used multimodal imaging and immunohistochemistry to track the development of hypoxia-induced neovascularization. In addition to developing a preclinical model that phenocopies exudative AMD, our studies revealed that the photoreceptor hypoxic response initiates and drives type 3 neovascularization, mainly in the outer retina. Activation of the VHL-HIF1a-VEGF-EPO pathway in the adult retina led to long-term neovascularization, retinal hemorrhages and compromised retinal layers. Our novel preclinical model would accelerate the testing of therapies that use metabolomic approaches to ameliorate AMD.

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PREVALENSI AGE RELATED MACULAR DEGENERATION DI POLIKLINIK MATA BLU RSUP Prof. Dr. R. D. KANDOU MANADO PERIODE JANUARI 2013 – OKTOBER 2015

e-CliniC ◽

10.35790/ecl.4.1.2016.10968 ◽

2016 ◽

Vol 4 (1) ◽

Author(s):

Clarissa E. Tany ◽

Vera Sumual ◽

J. S. M. Saerang

Keyword(s):

Retrospective Study ◽

Macular Degeneration ◽

Medical Records ◽

Vision Loss ◽

Central Area ◽

Age Related Macular Degeneration ◽

Common Cause ◽

Age Related ◽

History Of ◽

Male Patients

Abstract: Age–related macular degeneration (AMD) is a visual impairment in central area of the retina (macula) that tends to be progressive. In developing countries, AMD becomes the most common cause of irreversible vision loss in people aged ≥50 years. This study aimed to obtain the prevalence of AMD in Department of Opthalmology at Prof. Dr. R. D. Kandou Hospital Manado from January 2013 to October 2015. This was a descriptive retrospective study using medical records of Department of Opthalmology. The results showed that there were 41 patients diagnosed as AMD. Based on sexes, AMD occured more frequent in male patients as many as 28 paients (68.3%). This disease was dominated by patients aged 61-70 years old as many as 16 patients (39%). There were 10 patients (24.4%) that had history of hypertension.Keywords: prevalence, AMD Abstrak: Age–related macular degeneration (AMD) adalah suatu gangguan penglihatan sentral retina (makula) yang bersifat progresif. Di negara berkembang AMD menjadi penyebab terbanyak hilangnya penglihatan yang ireversibel pada individu di atas 50 tahun. Penelitian ini bertujuan untuk mengetahui prevalensi AMD di Poliklinik Mata BLU RSUP Prof. Dr. R. D. Kandou Manado periode Januari 2013-Oktober 2015. Jenis penelitian ini deskriptif retrospektif dengan memanfaatkan data rekam medik di Poliklinik Mata BLU RSUP Prof. Dr. R. D. Kandou Manado. Hasil penelitian memperlihatkan 41 pasien dengan diagnosis AMD. Berdasarkan jenis kelamin, AMD lebih banyak dialami oleh jenis kelamin laki-laki sebanyak 28 orang (68,3%), sedangkan untuk rentang umur didominasi oleh umur 61-70 tahun yaitu sebanyak 16 orang (39%). Terdapat 10 orang (24,4%) dengan riwayat hipertensi.Kata kunci: prevalensi, AMD

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Aflibercept Treatment and Treatment Algorithms in Wet-Form (Neovascular) Age-Related Macular Degeneration

Güncel Retina Dergisi (Current Retina Journal) ◽

10.37783/crj-0033 ◽

2017 ◽

pp. 198-205

Keyword(s):

Macular Degeneration ◽

Vision Loss ◽

Age Related Macular Degeneration ◽

Vascular Endothelial ◽

Neovascular Amd ◽

Treatment Algorithms ◽

Age Related ◽

Severe Vision Loss ◽

Degenerative Disorder ◽

Endothelial Growth Factor

Age-related macular degeneration (AMD) commonly develops after the age of 50. AMD is a progressive degenerative disorder of the macula in which central vision becomes impaired and leading cause of blindness. Severe vision loss occurs in the late stages of the disease. Untreated wet-form (neovascular) AMD leads to a rapid loss of vision in the affected eye. Many studies have shown vascular endothelial growth factor (VEGF) as a key mediator in wet-form (neovascular) AMD. This review mentions the aflibercept treatment and treatment algorithms in wet-form (neovascular) age-related macular degeneration.

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Age-Related Macular Degeneration: Pathogenesis, Genetic Background, and the Role of Nutritional Supplements

Journal of Chemistry ◽

10.1155/2014/317536 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 4

Author(s):

Marilita M. Moschos ◽

Eirini Nitoda ◽

Irini P. Chatziralli ◽

Constantinos A. Demopoulos

Keyword(s):

Macular Degeneration ◽

Genetic Background ◽

Vision Loss ◽

Nutritional Supplements ◽

Age Related Macular Degeneration ◽

Light Radiation ◽

Age Related ◽

Severe Vision Loss ◽

And Oxidative Stress

Age-related macular degeneration (ARMD) is the leading cause of severe vision loss and blindness worldwide, mainly affecting people over 65 years old. Dry and wet ARDM are the main types of the disease, which seem to have a multifactorial background. The aim of this review is to summarize the mechanisms of ARMD pathogenesis and exhibit the role of diet and nutritional supplements in the onset and progression of the disease. Environmental factors, such as smoking, alcohol, and, diet appear to interact with mutations in nuclear and mitochondrial DNA, contributing to the pathogenesis of ARMD. Inflammatory mediators and oxidative stress, induced by the daily exposure of retina to high pressure of oxygen and light radiation, have been also associated with ARMD lesions. Other than medical and surgical therapies, nutritional supplements hold a significant role in the prevention and treatment of ARMD, eliminating the progression of macular degeneration.

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Role of amyloid β-peptide in the pathogenesis of age-related macular degeneration

BMJ Open Ophthalmology ◽

10.1136/bmjophth-2021-000774 ◽

2021 ◽

Vol 6 (1) ◽

pp. e000774

Author(s):

Minwei Wang ◽

Shiqi Su ◽

Shaoyun Jiang ◽

Xinghuai Sun ◽

Jiantao Wang

Keyword(s):

Mitochondrial Dysfunction ◽

Macular Degeneration ◽

Vision Loss ◽

Cell Structure ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Amyloid Β ◽

Age Related Macular Degeneration ◽

Amyloid Β Peptide ◽

Age Related

Age-related macular degeneration (AMD) is the most common eye disease in elderly patients, which could lead to irreversible vision loss and blindness. Increasing evidence indicates that amyloid β-peptide (Aβ) might be associated with the pathogenesis of AMD. In this review, we would like to summarise the current findings in this field. The literature search was done from 1995 to Feb, 2021 with following keywords, ‘Amyloid β-peptide and age-related macular degeneration’, ‘Inflammation and age-related macular degeneration’, ‘Angiogenesis and age-related macular degeneration’, ‘Actin cytoskeleton and amyloid β-peptide’, ‘Mitochondrial dysfunction and amyloid β-peptide’, ‘Ribosomal dysregulation and amyloid β-peptide’ using search engines Pubmed, Google Scholar and Web of Science. Aβ congregates in subretinal drusen of patients with AMD and participates in the pathogenesis of AMD through enhancing inflammatory activity, inducing mitochondrial dysfunction, altering ribosomal function, regulating the lysosomal pathway, affecting RNA splicing, modulating angiogenesis and modifying cell structure in AMD. The methods targeting Aβ are shown to inhibit inflammatory signalling pathway and restore the function of retinal pigment epithelium cells and photoreceptor cells in the subretinal region. Targeting Aβ may provide a novel therapeutic strategy for AMD.

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Mingjing granule, a traditional Chinese medicine in the treatment of neovascular age-related macular degeneration: study protocol for a randomized controlled trial

Trials ◽

10.1186/s13063-021-05025-x ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Yamin Li ◽

Lina Liang ◽

Torkel Snellingen ◽

Kai Xu ◽

Yun Gao ◽

...

Keyword(s):

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Macular Degeneration ◽

Vision Loss ◽

Age Related Macular Degeneration ◽

Case Report Form ◽

Link Type ◽

Anti Vegf ◽

Age Related ◽

Function Test

Abstract Background Neovascular age-related macular degeneration (nAMD) is the most common cause of irreversible vision loss and blindness among the older people aged 50 and over. Although anti-vascular endothelial growth factor (anti-VEGF) therapies have resulted in improving patient outcomes, there are limitations associated with these treatments. In China, traditional Chinese medicine (TCM) has been used to treat eye diseases for more than 2000 years. Previous studies have shown that TCM may be beneficial for nAMD patients. However, explicit evidence has not been obtained. The purpose of the present trial is to examine the efficacy and safety of the Mingjing granule, a compound Chinese herbal medicine, for nAMD patients. Methods/design This is a double-blind, placebo-controlled, randomized trial of Mingjing granule as an add-on to intravitreous ranibizumab for nAMD. One hundred eighty nAMD patients from six hospitals in China will be enrolled according to the inclusion and exclusion criteria and randomly allocated into two groups, 90 in each. All participants will receive a 24-week treatment and then be followed up for another 24 weeks. The primary outcome is the mean change of best-corrected visual acuity at week 24 and 48 as compared to the baseline. The secondary outcomes include mean change in central retinal thickness, area of retinal hemorrhage and exudation, and TCM syndrome score, mean number of intravitreal ranibizumab injection, and total cost of the treatment. Indexes of safety include blood regular test, urine regular test, liver function test, renal function test, and electrocardiogram from baseline to weeks 24 and 48. Qualitative control and some standard operating processes will be formed throughout the trial. Any ocular or systemic adverse events will be treated suitably, and related data will be recorded accurately and completely in the case report form. Discussion Based on previous empirical and animal laboratory studies, this study will address the question of whether Mingjing granule could contribute to improving efficacy, safety, and efficiency with need for fewer intravitreal injections of anti-VEGF, improving compliance and visual outcomes in the management of persons with nAMD. Trial registration Chinese Clinical Trial Registry (http://www.chictr.org.cn), ChiCTR2000035990. Registered on 21 August 2020.

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The Positive Legacy of Vision Loss: Pathways to Posttraumatic Growth

Innovation in Aging ◽

10.1093/geroni/igaa057.2094 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 616-617

Author(s):

Corinna Tanner ◽

Michael Caserta ◽

Jia-Wen Guo ◽

Margaret Clayton ◽

Paul Bernstein ◽

...

Keyword(s):

Posttraumatic Growth ◽

Cognitive Processing ◽

Mixed Method ◽

Vision Loss ◽

Social Issues ◽

Qualitative Interviews ◽

Age Related Macular Degeneration ◽

Age Related ◽

Severe Vision Loss ◽

Age Range

Abstract This mixed method study describes posttraumatic growth (PTG) accruing form experience with vision loss caused by severe age related macular degeneration (AMD) and explores relationships between depression, social support, and cognitive processing, on the path to PTG. Research describing the psychological and social issues surrounding AMD has focused on negative outcomes. However, learning from highly challenging experiences, such as vision loss, can offer benefits. In this study, these included an increased sense of personal strength, increased spirituality, and empathy for others (all domains of PTG). 89 participants with severe vision loss (mean age = 85.3 years, age range = 74–98 years) completed the interviewer-administered composite questionnaire, which identified elements of Tedeschi and Calhoun’s model of PTG. Relationships between variables were examined using path analysis. Findings were contextualized with data from 15 qualitative interviews. Findings underscored the importance of supportive others and deliberate cognitive processing in the path to PTG.

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Functional optical coherence tomography of retinal photoreceptors

Experimental Biology and Medicine ◽

10.1177/1535370218816517 ◽

2018 ◽

Vol 243 (17-18) ◽

pp. 1256-1264 ◽

Cited By ~ 9

Author(s):

Xincheng Yao ◽

Taeyoon Son ◽

Tae-Hoon Kim ◽

Yiming Lu

Keyword(s):

Vision Loss ◽

Objective Assessment ◽

Age Related Macular Degeneration ◽

Retinal Stimulation ◽

Age Related ◽

Retinal Photoreceptors ◽

Severe Vision Loss ◽

Further Development

Age-related macular degeneration (AMD) is the leading cause of severe vision loss and legal blindness. It is known that retinal photoreceptors are the primary target of AMD. Therefore, a reliable method for objective assessment of photoreceptor function is needed for early detection and reliable treatment evaluation of AMD and other eye diseases such as retinitis pigmentosa that are known to cause photoreceptor dysfunctions. Stimulus-evoked intrinsic optical signal (IOS) changes promise a unique opportunity for objective assessment of physiological function of retinal photoreceptor and inner neurons. Instead of a comprehensive review, this mini-review is to provide a brief summary of our recent in vitro and in vivo optical coherence tomography (OCT) studies of stimulus-evoked IOS changes in animal retinas. By providing excellent axial resolution to differentiate individual retinal layers, depth-resolved OCT revealed rapid IOS response at the photoreceptor outer segment. The fast photoreceptor-IOS occurred almost right away (∼ 2 ms) after the onset of retinal stimulation, differentiating itself from slow IOS changes correlated with inner neural and hemodynamic changes. Further development of the functional IOS instruments and retinal stimulation protocols may provide a feasible solution to pursue clinical application of functional IOS imaging for objective assessment of human photoreceptors. Impact statement Retinal photoreceptors are the primary target of age-related macular degeneration (AMD) which is the leading cause of severe vision loss and legal blindness. An objective method for functional assessment of photoreceptor physiology can benefit early detection and better treatment evaluation of AMD and other eye diseases that are known to cause photoreceptor dysfunctions. This article summarizes in vitro study of IOS mechanisms and in vivo demonstration of IOS imaging of intact animals. Further development of the functional IOS imaging may provide a revolutionary solution to achieve objective assessment of human photoreceptors.

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