Cutting-Edge Solutions for Age-related Macular Degeneration (AMD):

What is age-related macular degeneration (AMD)?

Age-related macular degeneration (AMD) is a progressive eye disease that affects the macula, the central portion of the retina responsible for sharp, detailed vision. It is the leading cause of vision loss among people aged 50 and up. AMD primarily affects the ability to see fine detail, read, drive, and recognize faces, all of which have a significant impact on one’s quality of life. The two main types of AMD are dry (atrophic) and wet (neovascular).

Dry AMD, the most common type, accounts for roughly 80-90% of cases. It occurs as the macula thins over time, resulting in a gradual loss of central vision. The presence of drusen, or yellow deposits beneath the retina, is a sign of dry AMD. Wet AMD, while less common, is more severe and can result in rapid vision loss. It is defined by the formation of abnormal blood vessels beneath the retina that leak fluid or blood, causing damage to the macula.

Aging, genetics, smoking, hypertension, high cholesterol, and long-term UV light exposure are all risk factors for AMD. Early detection and monitoring are critical in managing AMD because timely intervention can slow its progression and help maintain visual function.

Conventional Management and Treatment for Age-related Macular Degeneration (AMD)

The goal of conventional AMD management and treatment is to slow the disease’s progression, manage symptoms, and preserve vision for as long as possible. The treatment strategy varies depending on whether the patient has dry or wet AMD.

Dry AMD Management

1. Nutritional Supplements – AREDS and AREDS2 Formulations The Age-Related Eye Disease Study (AREDS) found that specific high-dose vitamin and mineral formulations could slow the progression of dry AMD. Vitamin C, E, zinc, copper, lutein, and zeaxanthin are all part of the AREDS2 formula. Patients with intermediate or advanced dry AMD should take these supplements to reduce their risk of developing severe vision loss.
2. Lifestyle Modifications – Healthy Diet: Consuming green leafy vegetables, fish, nuts, and fruits can promote eye health. These foods contain antioxidants and omega-3 fatty acids, which are beneficial to retinal health.

• Smoking Cessation: Smoking greatly increases the risk of AMD progression. To protect their vision, patients are strongly encouraged to stop smoking.
• Regular Exercise: Physical activity can improve overall health and lower the risk of AMD progression by regulating blood pressure and cholesterol levels.

1. Low Vision Aids – Magnifying Devices: Magnifying glasses, specialized reading lights, and electronic reading devices can enhance patients’ remaining vision.

• Vision Rehabilitation: Occupational therapy and vision rehabilitation services teach patients how to adjust to vision loss and effectively use assistive devices.

Wet AMD Management

1. Anti-VEGF Injections – Mechanism: Vascular endothelial growth factor (VEGF) is a key factor in the formation of abnormal blood vessels in wet AMD. Anti-VEGF medications prevent this growth, which reduces fluid leakage and bleeding.

• Medicines: Common anti-VEGF agents include ranibizumab (Lucentis), aflibercept (Eylea), and bevacizumab (Avastin). These medications are injected directly into the eye and usually require monthly or bimonthly treatments.
• Efficacy: Anti-VEGF therapy has proven to be extremely effective in stabilizing or improving vision in many patients with wet AMD. Regular monitoring and treatment are required to maintain the results.

1. Photodynamic Therapy (PDT) – Mechanism: PDT uses a photosensitizing agent (verteporfin) and a laser to target and destroy abnormal blood vessels in the retina.

• Procedure: Verteporfin is administered intravenously and activated with a laser directed at the retina. This treatment selectively damages abnormal blood vessels while preserving healthy tissue.
• Application: PDT is less commonly used these days due to the effectiveness of anti-VEGF therapy, but it may still be considered in certain cases or in combination with anti-VEGF injections.

1. Laser Therapy – Mechanism: Laser photocoagulation seals leaking blood vessels and protects the macula from further damage.

• Procedure: The laser is focused directly on the abnormal blood vessels, causing them to coagulate and shrink.
• Limitations: This treatment is typically reserved for specific cases of wet AMD in which the abnormal vessels are distant from the fovea (the central part of the macula). It is less commonly used because it can cause damage to surrounding retinal tissue and anti-VEGF therapy is superior.

Monitoring and Follow-up

• Regular Eye Exams: Patients with AMD require regular monitoring by an ophthalmologist to assess disease progression and treatment efficacy. Optical coherence tomography (OCT) and fluorescein angiography are popular imaging techniques for evaluating the retina and making treatment decisions.
• Self-Monitoring: Patients should use tools like the Amsler grid to detect any changes in their central vision as soon as possible. Any new distortions or vision loss should be reported to an eye care provider right away.

Conventional AMD management aims to slow disease progression, preserve vision, and improve quality of life by combining medical treatments, lifestyle changes, and supportive care.

Modern Therapies for Age-Related Macular Degeneration (AMD)

AMD treatments are constantly evolving to improve efficacy, reduce treatment burden, and address unmet needs in both dry and wet forms of the disease. These advancements include novel drug therapies, gene therapy, regenerative medicine, and advanced technological interventions.

Novel Drug Therapies

1. Long-Acting Anti-VEGF Agents – Brolucizumab (Beovu): Brolucizumab is a newer anti-VEGF agent with a longer duration of action, allowing for fewer injections compared to previous treatments. Clinical trials have shown that it is effective for maintaining vision and reducing retinal fluid with fewer injections.

• Port Delivery System (PDS) and Ranibizumab: The PDS is an innovative implantable device that delivers ranibizumab in a continuous manner, potentially extending the time between treatments to six months or more. This system lowers the treatment burden for patients with wet AMD.

1. Complement Inhibitors – Mechanism: Dry AMD is linked to the complement system, which is a part of the immune response. Complement inhibitors seek to modulate this pathway in order to prevent or slow disease progression.

• Pegcetacoplan (APL-2): Pegcetacoplan is a complement C3 inhibitor that is currently in clinical trials to treat geographic atrophy, a severe form of dry AMD. Early results indicate that it may slow the progression of retinal damage.

Gene Therapy

1. Subretinal Gene Therapy – Mechanism: Delivering a functional copy of a defective gene directly to retinal cells. This approach aims to address the genetic causes of AMD.

• RGX-314: This gene therapy candidate contains a gene that codes for a therapeutic anti-VEGF protein. RGX-314, administered as a subretinal injection, has shown promise in reducing the need for frequent anti-VEGF injections in patients with wet AMD.

1. Intravitreal Gene Therapy – ADVM-022: This intravitreal gene therapy delivers an anti-VEGF protein. The goal of this treatment is to provide long-term VEGF suppression with a single injection. Clinical trials are underway to assess its safety and efficacy.

Regenerative Medicine.

1. Stem Cell Therapy – Mechanism: The goal of stem cell therapy is to replace damaged retinal cells with healthy, functioning cells derived from stem cells. This method has the potential to restore vision to patients with advanced AMD.

• Human Embryonic Stem Cell-Derived Retinal Pigment Epithelium (RPE) Cells: Clinical trials are underway to study the transplantation of RPE cells derived from human embryonic stem cells. Early findings suggest that this therapy is safe and may improve vision in patients with geographic atrophy.

1. Induced Pluripotent Stem Cells (iPSCs) – Mechanism: iPSCs are adult cells that have been reprogrammed to an embryonic-like state. They can differentiate into any cell type, including retinal cells. This technology has the potential to develop personalized regenerative treatments for AMD.

• Applications: Researchers are working to develop RPE cells and photoreceptors from iPSCs for retina transplantation. These treatments seek to replace damaged cells and restore visual function.