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 ◽  
◽  
◽  
...  

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.

2019 ◽  
Vol 4 (1) ◽  
pp. e000398 ◽  
Author(s):  
Saira Khanna ◽  
Rahul Komati ◽  
David A Eichenbaum ◽  
Ishani Hariprasad ◽  
Thomas A Ciulla ◽  
...  

Age-related macular degeneration is the leading cause of vision loss in the developed world, with the expected number of affected elderly individuals reaching 17.8 million. Antivascular endothelial growth factor (anti-VEGF) injection therapy has been instrumental in treating a disease process that was previously thought to be untreatable. Over the past two decades, landmark studies have demonstrated the efficacy of different anti-VEGF medications and investigated the optimal dosing regimen and delivery mechanism to increase overall vision and minimise patient burden. In this review, we outline landmark neovascular age-related macular degeneration clinical trials that have demonstrated level 1 evidence for its usage or have contributed to the understanding of how to dose these agents.


Author(s):  
Alan D. Penman ◽  
Kimberly W. Crowder ◽  
William M. Watkins

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.


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.


2020 ◽  
Vol 77 (5) ◽  
pp. 779-780 ◽  
Author(s):  
Anu Kauppinen

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.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2035
Author(s):  
Bo Yang ◽  
Ge Li ◽  
Jiaxin Liu ◽  
Xiangyu Li ◽  
Shixin Zhang ◽  
...  

Age-related macular degeneration (AMD) is a degenerative eye disease that is the leading cause of irreversible vision loss in people 50 years and older. Today, the most common treatment for AMD involves repeated intravitreal injections of anti-vascular endothelial growth factor (VEGF) drugs. However, the existing expensive therapies not only cannot cure this disease, they also produce a variety of side effects. For example, the number of injections increases the cumulative risk of endophthalmitis and other complications. Today, a single intravitreal injection of gene therapy products can greatly reduce the burden of treatment and improve visual effects. In addition, the latest innovations in nanotherapy provide the best drug delivery alternative for the treatment of AMD. In this review, we discuss the development of nano-drug delivery systems and gene therapy strategies for AMD in recent years. In addition, we discuss some novel targeting strategies and the potential application of these delivery methods in the treatment of AMD. Finally, we also propose that the combination of CRISPR/Cas9 technology with a new non-viral delivery system may be promising as a therapeutic strategy for the treatment of AMD.


2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Eui Chun Kang ◽  
Hyoung Jun Koh

Herein, we review the association between vitreomacular adhesion (VMA) and neovascular age-related macular degeneration (AMD). Meta-analyses have shown that eyes with neovascular AMD are twice as likely to have VMA as normal eyes. VMA in neovascular AMD may induce inflammation, macular traction, decrease in oxygenation, sequestering of vascular endothelial growth factor (VEGF), and other cytokines or may directly stimulate VEGF production. VMA may also interfere with the treatment effects of anti-VEGF therapy, which is the standard treatment for neovascular AMD, and releasing VMA can improve the treatment response to anti-VEGF treatment in neovascular AMD. We also reviewed currently available methods of relieving VMA.


Author(s):  
Sruthi Arepalli ◽  
Peter K. Kaiser

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.


Author(s):  
Alan D. Penman ◽  
Kimberly W. Crowder ◽  
William M. Watkins

The Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular AMD (MARINA) study was a randomized, double-blind, sham-controlled clinical trial to determine whether intravitreal administration of ranibizumab (an anti-vascular endothelial growth factor [VEGF] agent) prevents vision loss and improves mean visual acuity in patients with minimally classic or occult choroidal neovascularization related to age-related macular degeneration (AMD). Ranibizumab therapy was associated with clinically and statistically significant benefits in visual acuity and the amount of angiographic leakage from choroidal neovascularization during two years of follow-up, with low rates of serious adverse events.


2013 ◽  
Vol 06 (01) ◽  
pp. 58 ◽  
Author(s):  
Michael W Stewart ◽  

Vascular endothelial growth factor (VEGF) plays a central role in the development of several chorioretinal vascular disorders including exudative age-related macular degeneration (AMD). Detailed understanding of VEGF biochemistry has led to the development of four drugs which specifically inhibit its actions. Bevacizumab and ranibizumab have been the dominant ophthalmic anti-VEGF drugs for seven years and their regular use has significantly decreased vision loss. In late 2011, aflibercept, a high-affinity, fusion protein that acts as a soluble VEGF receptor, was approved for the treatment of exudative AMD. Phase three trials showed that monthly and bimonthly aflibercept maintained vision in 95 % of patients, improved average visual acuity by +8.3 to +9.4 letters, and thinned the macula comparably to monthly ranibizumab. Since its approval, aflibercept has been shown to decrease retinal edema and subretinal fluid, and flatten retinal pigment epithelial detachments in eyes that have responded incompletely to frequent ranibizumab and bevacizumab injections. Aflibercept’s longer duration of action coupled with its comparable unit price (versus ranibizumab) promise to decrease the total cost of treatment.


Age-related macular degeneration (AMD) is a chronic and degenerative disease that causes vision loss. Although anti-vascular endothelial growth factor (Anti-VEGF) drugs are the mainstay of treatment in cases of age-related AMD, there is no similar response to treatment in each patient. In the case of non-response, the treatment approach for the cause must be regulated. Although there is no consensus on the concept of response to treatment, the use of alternative anti-VEGF in cases where drug efficacy is weak is quite common.


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