scholarly journals Pipeline therapies for neovascular age related macular degeneration

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Sruthi Arepalli ◽  
Peter K. Kaiser
Keyword(s):  
New York ◽  
South Korea ◽  
Macular Degeneration ◽  
San Francisco ◽  
Vision Loss ◽  
Surgical Excision ◽  
Age Related Macular Degeneration ◽  
Neovascular Amd ◽  
Age Related ◽  
Redwood City

AbstractAge related macular degeneration (AMD) is the most common cause of vision loss in the elderly population. Neovascular AMD comprises 10% of all cases and can lead to devastating visual loss due to choroidal neovascularization (CNV). There are various cytokine pathways involved in the formation and leakage from CNV. Prior treatments have included focal laser therapy, verteporfin (Visudyne, Bausch and Lomb, Rochester, New York) ocular photodynamic therapy, transpupillary thermotherapy, intravitreal steroids and surgical excision of choroidal neovascular membranes. Currently, the major therapies in AMD focus on the VEGF-A pathway, of which the most common are bevacizumab (Avastin; Genentech, San Francisco, California), ranibizumab (Lucentis; Genentech, South San Francisco, California), and aflibercept (Eylea; Regeneron, Tarrytown, New York). Anti-VEGF agents have revolutionized our treatment of wet AMD; however, real world studies have shown limited visual improvement in patients over time, largely due to the large treatment burden. Cheaper alternatives, including ranibizumab biosimilars, include razumab (Intas Pharmaceuticals Ltd., Ahmedabad, India), FYB 201 (Formycon AG, Munich, Germany and Bioeq Gmbh Holzkirchen, Germany), SB-11 (Samsung Bioepsis, Incheon, South Korea), xlucane (Xbrane Biopharma, Solna, Sweden), PF582 (Pfnex, San Diego, California), CHS3551 (Coherus BioSciences, Redwood City, California). Additionally, aflibercept biosimilars under development include FYB203 (Formycon AG, Munich, Germany and Bioeq Gmbh Holzkirchen, Germany), ALT-L9 (Alteogen, Deajeon, South Korea), MYL1710 (Momenta Pharamaceuticals, Cambridge, MA, and Mylan Pharmacueticals, Canonsburg, PA), CHS-2020 (Coherus BioSciences, Redwood City, California). Those in the pipeline of VEGF targets include abicipar pegol (Abicipar; Allergan, Coolock, Dublin), OPT-302 (Opthea; OPTHEA limited; Victoria, Melbourne), conbercept (Lumitin; Chengdu Kanghong Pharmaceutical Group, Chengdu, Sichuan), and KSI-301 (Kodiak Sciences, Palo Alto, CA). There are also combination medications, which target VEGF and PDGF, VEGF and tissue factor, VEGF and Tie-2, which this paper will also discuss in depth. Furthermore, long lasting depots, such as the ranibizumab port delivery system (PDS) (Genentech, San Francisco, CA), as well as others are under evaluation. Gene therapy present possible longer treatments options as well and are reviewed here. This paper will highlight the past approved medications as well as pipeline therapies for neovascular AMD.

Pegaptanib for Neovascular Age-Related Macular Degeneration

2020 ◽  
pp. 239-244
Author(s):  
Alan D. Penman ◽  
Kimberly W. Crowder ◽  
William M. Watkins
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
Age Related Macular Degeneration ◽  
Vascular Endothelial ◽  
Efficacy And Safety ◽  
Neovascular Amd ◽  
Ocular Neovascularization ◽  
Age Related ◽  
Discontinue Therapy ◽  
Endothelial Growth Factor

The VEGF Inhibition Study in Ocular Neovascularization (V.I.S.I.O.N.) study comprised two concurrent randomized, double-masked, sham-controlled clinical trials to evaluate the efficacy and safety of a second year of treatment with pegaptanib sodium (an anti-vascular endothelial growth factor [VEGF] agent) in patients with neovascular age-related macular degeneration (AMD). In combined analyses, 88% of patients were re-randomized at week 54, and 89% were assessed at week 102. At week 54, those initially assigned to pegaptanib were re-randomized to continue or discontinue therapy for 48 more weeks (8 injections). Those initially assigned to sham were re-randomized to continue sham, discontinue sham, or receive 1 of 3 pegaptanib doses. The study showed that in patients with a diverse mix of neovascular AMD presentations, treatment with pegaptanib every 6 weeks for 2 years reduced the risk of vision loss regardless of lesion composition or size; this benefit was maintained during year 2.

scholarly journals Advances in Age-related Macular Degeneration Understanding and Therapy

2017 ◽  
Vol 10 (02) ◽  
pp. 119 ◽  
Author(s):  
Joan W Miller ◽  
Saghar Bagheri ◽  
Demetrios G Vavvas ◽  
◽  
◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
Disease Process ◽  
Age Related Macular Degeneration ◽  
Great Success ◽  
Neovascular Amd ◽  
Clinical Endpoints ◽  
Age Related ◽  
Cell Death Mechanisms ◽  
Endothelial Growth Factor

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.

scholarly journals Principles of anti-VEGF dosing in the treatment of neovascular age-related macular degeneration

2019 ◽  
Vol 12 (3) ◽  
pp. 102-112
Author(s):  
I. E. Ioshin ◽  
T. Anoprieva
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
Evidence Base ◽  
Age Related Macular Degeneration ◽  
Neovascular Amd ◽  
Anti Vegf ◽  
Age Related ◽  
Optimal Dosing ◽  
Increased Risk ◽  
Dosing Regimens

Age-related macular degeneration (AMD) is a chronic progressive disease regarded as a leading cause of vision impairment in elderly people in industrial countries. Neovascular AMD is characterized by an increased risk of severe vision loss. Intravitreal injections of anti-VEGF medication has become a standard of treatment of neovascular AMD. Clinical trials demonstrate that the use of anti-VEGF helps stabilize the vision in at least 90 % of patients, while 30 to 40 % gain three or more lines of vision (15 ETDRS letters). However, observational studies suggest that there are barriers diminishing the efficacy of anti-VEGF treatment in routine clinical practice. Finding an optimal dosing regimen for anti-VEGF therapy that could maintain treatment efficacy with a lower number of injections and fewer monitoring visits could be a solution. The review discusses the evidence base regarding anti-VEGF dosing principles and analyzes current dosing regimens with regard to their benefits and limitations.

scholarly journals New and Innovative Treatments for Neovascular Age-Related Macular Degeneration (nAMD)

2021 ◽  
Vol 10 (11) ◽  
pp. 2436
Author(s):  
Prem Patel ◽  
Veeral Sheth
Keyword(s):  
Macular Degeneration ◽  
Randomized Clinical Trials ◽  
Vision Loss ◽  
Standard Of Care ◽  
Geographic Atrophy ◽  
Age Related Macular Degeneration ◽  
Neovascular Amd ◽  
Current Standard ◽  
Combination Strategies ◽  
Age Related

Age-related macular degeneration (AMD) is one of the most common causes of vision loss. Advanced forms of AMD are seen in primarily two types—neovascular AMD (nAMD) with the presence of choroid neovascularization and non-neovascular AMD (nnAMD) with geographic atrophy. Neovascular AMD is characterized by choroidal neovascularization (CNV), which leads to a cascade of complications, including exudation, leakage, and ultimately fibrosis with photoreceptor loss. Inhibition of VEGF represents the current standard of care. However, there is a tremendous gap between the outcomes in randomized clinical trials and real-world settings. New agents for nAMD might offer the potential to improve treatment outcomes and reduce treatment of frequent intravitreal injections. We summarize all the newer molecules, their pivotal clinical trial results, and their unique mechanisms of action; these include longer-acting agents, combination strategies, sustained release, and genetic therapies.

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

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.

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

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.

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

Trials ◽  
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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