Treatments for dry age-related macular degeneration: therapeutic avenues, clinical trials and future directions

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the developed world. The identification of the central role of vascular endothelial growth factor (VEGF) in the pathogenesis of neovascular AMD and the introduction of anti-VEGF agents as gold-standard treatment, have drastically changed its prognosis—something yet to be seen in dry AMD. Several therapeutic avenues with a wide variability of targets are currently being investigated in dry AMD. The approaches being investigated to reduce the rate of disease progression include, (1) drugs with antioxidative properties, (2) inhibitors of the complement cascade, (3) neuroprotective agents, (4) visual cycle inhibitors, (5) gene therapy and (6) cell-based therapies. A number of early phase clinical trials have provided promising results, with many more ongoing and anticipated in the near future. In this review, we aim to provide an update of the interventional trials to date and future prospects for the treatment of dry AMD.

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The role of future treatments in the management of neovascular age-related macular degeneration in Europe

European Journal of Ophthalmology ◽

10.1177/11206721211018348 ◽

2021 ◽

pp. 112067212110183

Author(s):

Laurent Kodjikian ◽

Carl Joe Mehanna ◽

Salomon-Yves Cohen ◽

François Devin ◽

Sam Razavi ◽

...

Keyword(s):

Clinical Trials ◽

Macular Degeneration ◽

Age Related Macular Degeneration ◽

Phase Iii ◽

Vascular Endothelial ◽

Real World Data ◽

Phase Iii Clinical Trials ◽

Age Related ◽

Injection Frequency ◽

Endothelial Growth Factor

Anti-vascular endothelial growth factor (VEGF) agents have transformed the management of patients with neovascular age-related macular degeneration (nAMD) over the past two decades. However, as more long-term real-world data become available, it is clear that treatment outcomes are inferior to those reported in large, controlled clinical trials. This is largely driven by undertreatment, that is, not maintaining a consistent injection frequency to achieve sustained VEGF suppression, whether due to patient non-compliance, an important injection burden, or non/incomplete anatomical response. Newer therapeutic advances under evaluation hold promise in achieving more, for less. We review the latest drugs currently in or having successfully finished phase III clinical trials, and determine their potential place in the management of patients with nAMD in Europe.

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Gene therapy for neovascular age-related macular degeneration: rationale, clinical trials and future directions

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2020-316195 ◽

2020 ◽

pp. bjophthalmol-2020-316195 ◽

Cited By ~ 1

Author(s):

Thales Antonio Cabral de Guimaraes ◽

Michalis Georgiou ◽

James W B Bainbridge ◽

Michel Michaelides

Keyword(s):

Gene Therapy ◽

Clinical Trials ◽

Macular Degeneration ◽

Age Related Macular Degeneration ◽

Current Status ◽

Routes Of Administration ◽

Age Related ◽

Potential Safety ◽

Early Phase Clinical Trials ◽

Endothelial Growth Factor

Age-related macular degeneration (AMD) is one of the leading causes of irreversible blindness in the developed world. Antivascular endothelial growth factor therapy has transformed the management and outcome of neovascular AMD (nAMD), although the need for repeated intravitreal injections—even lifelong—and the related complications, high drug costs, frequent clinic visits and repeated imaging have resulted in an enormous burden both to healthcare systems and patients. The application of gene therapy approaches for sustained delivery of a range of antiangiogenic proteins has the promise of helping to address these aforementioned challenges. A number of early phase clinical trials of gene therapy in nAMD have provided encouraging results, with many more ongoing or anticipated. There remain significant areas of controversy, including regarding the optimal treatment targets, routes of administration and potential safety concerns. In this review we aim to provide an update of the current status of gene therapy for nAMD and briefly discuss future prospects.

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Therapies for Neovascular Age-Related Macular Degeneration: Current Approaches and Pharmacologic Agents in Development

BioMed Research International ◽

10.1155/2013/830837 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 28

Author(s):

Mostafa Hanout ◽

Daniel Ferraz ◽

Mehreen Ansari ◽

Natasha Maqsood ◽

Saleema Kherani ◽

...

Keyword(s):

Macular Degeneration ◽

Vascular Diseases ◽

Age Related Macular Degeneration ◽

Treatment Modalities ◽

Vascular Endothelial ◽

New Therapies ◽

Age Related ◽

Early Phase Clinical Trials ◽

Endothelial Growth Factor ◽

Pharmacologic Agents

As one of the leading causes of blindness, age-related macular degeneration (AMD) has remained at the epicenter of clinical research in ophthalmology. During the past decade, focus of researchers has ranged from understanding the role of vascular endothelial growth factor (VEGF) in the angiogenic cascades to developing new therapies for retinal vascular diseases. Anti-VEGF agents such as ranibizumab and aflibercept are becoming increasingly well-established therapies and have replaced earlier approaches such as laser photocoagulation or photodynamic therapy. Many other new therapeutic agents, which are in the early phase clinical trials, have shown promising results. The purpose of this paper is to briefly review the available treatment modalities for neovascular AMD and then focus on promising new therapies that are currently in various stages of development.

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Recent advances in the management and understanding of macular degeneration

F1000Research ◽

10.12688/f1000research.10998.1 ◽

2017 ◽

Vol 6 ◽

pp. 519 ◽

Cited By ~ 5

Author(s):

Sepehr Bahadorani ◽

Michael Singer

Keyword(s):

Vascular Endothelial Growth Factor ◽

Macular Degeneration ◽

Age Related Macular Degeneration ◽

Vascular Endothelial ◽

Current Management ◽

Vegf Inhibitors ◽

Age Related ◽

Dry Amd ◽

Endothelial Growth Factor ◽

Wet Amd

Current management of age-related macular degeneration (AMD) is directed at intravitreal injection of vascular endothelial growth factor (VEGF) inhibitors for the treatment of wet AMD and supplementation with oral antioxidants for the treatment of dry AMD. In this article, we will review recent clinical trials for the treatment of dry and wet AMD.

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PPAR-αLigands as Potential Therapeutic Agents for Wet Age-Related Macular Degeneration

PPAR Research ◽

10.1155/2008/821592 ◽

2008 ◽

Vol 2008 ◽

pp. 1-5 ◽

Cited By ~ 6

Author(s):

Marisol del V Cano ◽

Peter L. Gehlbach

Keyword(s):

Macular Degeneration ◽

Immune Modulation ◽

Age Related Macular Degeneration ◽

Peroxisome Proliferator ◽

Vascular Endothelial ◽

Age Related ◽

Dry Amd ◽

Peroxisome Proliferator Activated Receptors ◽

Endothelial Growth Factor ◽

Wet Amd

The peroxisome proliferator-activated receptors (PPAR's) are members of the steroid/thyroid nuclear receptor, superfamily of transcription factors. There are currently three known PPAR subtypes,α,β, andγ. The PPARs are now recognized participants in a number of biological pathways some of which are implicated in the pathogenesis of age-related macular degeneration (AMD). These include immune modulation, lipid regulation, and oxidant/antioxidant pathways important to the onset and progression of “dry” AMD, and vascular endothelial growth factor (VEGF) mediated pathways that stimulate choroidal neovascularization (CNV), characteristic of “wet” AMD. PPAR-αis found in retina and also on vascular cells important to formation of CNV. At this time, however, relatively little is known about potential contributions of PPAR-αto the pathogenesis of dry and wet AMD. This review examines current literature for potential roles of PPAR-αin the pathogenesis and potential treatment of AMD with emphasis on prevention and treatment of wet AMD.

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Treat and Extend Dosing Regimen with Anti-vascular Endothelial Growth Factor Agents for Neovascular Age-related Macular Degeneration

American Journal of Ophthalmic Clinical Trials ◽

10.25259/ajoct-2-2018 ◽

2018 ◽

Vol 1 ◽

pp. 1 ◽

Cited By ~ 5

Author(s):

Karen M. Wai ◽

Rishi P. Singh

Keyword(s):

Vascular Endothelial Growth Factor ◽

Clinical Trials ◽

Growth Factor ◽

Macular Degeneration ◽

Age Related Macular Degeneration ◽

Vascular Endothelial ◽

Dosing Regimen ◽

Anti Vegf ◽

Age Related ◽

Endothelial Growth Factor

Anti-vascular endothelial growth factor (anti-VEGF) agents are the mainstay of therapy for treatment of neovascular age-related macular degeneration (nvAMD), one of the leading causes of blindness in the developed world. There have been a variety of different treatment regimens that have been examined for the administration of anti-VEGF therapies, including continuous fixed dosing, pro re nata administration, and treat and extend (TAE) protocols. There is no clear consensus on which dosing regimen optimizes visual and anatomical outcomes while accounting for factors such as cost and patient burden. Based on recent surveys in 2014 and 2017 by the American Society of Retina Specialists (ASRS), the majority of ophthalmology providers are utilizing TAE protocol for anti-VEGF dosing for the management of nvAMD. Although there are a number of clinical trials that have examined TAE dosing, the ALTAIR study is the first, large, prospective randomized controlled trial to compare two different TAE protocols utilizing the anti-VEGF agent aflibercept for nvAMD. The ALTAIR study, in conjunction with other previous clinical trials, suggests that TAE protocol with aflibercept is an effective anti-VEGF dosing regimen for patients with nvAMD as it produces good visual gains and minimizes cost and burden for the patient.

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