https://orcid.org/0000-0002-8108-2903
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ABSTRACT
Introduction
Wet age-related macular degeneration (w-AMD) is a leading cause of visual impairment globally, with its prevalence expected to rise alongside increasing life expectancy. The current standard treatment involves frequent intravitreal injections of anti-VEGF agents, which although revolutionary, pose significant burdens on both patients and healthcare services.
Areas covered
This review explores current and emerging pharmaceutical treatments for w-AMD, focusing on their pharmacokinetics, pharmacodynamics, efficacy, and safety. Promising developments include extending treatment intervals with newer anti-VEGF agents like brolucizumab and faricimab, biosimilars offering cost-effective options, and exploring innovative drug delivery methods such as subretinal gene therapy. Combination therapies, gene therapies, and novel agents like KSI-301 and OPT-302 show potential for improving treatment outcomes and reducing treatment burden.
Expert opinion
While current treatments for w-AMD have significantly advanced with the advent of anti-VEGF therapies, their limitations in terms of treatment burden and incomplete responses have spurred research into diverse alternative approaches. These innovative strategies offer hope for improving patient outcomes and reducing healthcare burdens, suggesting a promising future for w-AMD management.
Article highlights
Age-related macular degeneration manifests in three forms: dry, geographic atrophy and w-AMD. The hallmark of w-AMD is choroidal neovascular membrane (CNV), which again is of three types.
The current mainstay of treatment of w-AMD is anti-VEGF agents which are administered intravitreally on a regular basis.
This regular invasive procedure presents a treatment burden for patients, as well as service and economic pressures for healthcare providers. Additionally, some patients do not respond adequately to these agents.
Novel therapies under development aim to provide longer-lasting effects, fewer injections and less invasive administration, leading to less burden on healthcare providers, improving patient comfort and better outcomes.
Promising agents include new drug delivery mechanisms such as refillable depot injection, topical treatment, and subretinal gene therapy. In addition, newer agents have been focusing on previously untargeted pathogenic mediators.
Abbreviations
| AMD | = | Age-related macular degeneration |
| AAV8 | = | Adeno-associated virus |
| Ang-1 | = | Angiopoietin-1 |
| Ang-2 | = | Angiopoietin-2 |
| AREDS | = | Age-Related Eye Disease Study |
| BCVA | = | Best corrected visual acuity |
| cDNA | = | Complementary Deoxyribonucleic acid |
| CNV | = | Choroidal neovascular membrane |
| CST | = | Central subfield thickness |
| EMA | = | European Medicines Agency |
| ETDRS | = | Early Treatment Diabetic Retinopathy Study |
| FDA | = | Food and Drug Administration |
| GA | = | Geographic atrophy |
| MHRA | = | Medicines and Healthcare products Regulatory Agency |
| MPS | = | Macular Photocoagulation Study |
| PDS | = | Port Delivery System |
| PDT | = | Photodynamic therapy |
| PEG | = | Polyethylene glycol |
| PlGF | = | Placental Growth Factor |
| PRN | = | Pro Re Nata |
| RPE | = | Retinal pigment epithelium |
| SANA | = | Systemic Avastin for Neovascular AMD |
| TAP | = | Treatment of Age-related Macular Degeneration with Photodynamic Therapy |
| TKI | = | Tyrosine kinase inhibitor |
| VEGF | = | Vascular Endothelial Growth Factor |
| VEGFR | = | Vascular Endothelial Growth Factor Receptor |
| w-AMD | = | Wet age-related macular degeneration |
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.