Age-related macular degeneration (MD) is a progressive eye condition that damages the macula, the central part of the retina responsible for sharp, detailed vision. MD is the leading cause of permanent vision loss in older adults. It is classified into two main types: dry (atrophic) and wet (neovascular). The dry form is more common, involving the slow breakdown of light-sensitive cells. The wet form is less frequent but more aggressive, characterized by the growth of abnormal, leaky blood vessels beneath the retina. Newer, more effective therapies are urgently needed to stabilize or restore vision.
Recent Advances in Anti-VEGF Medications
The standard treatment for wet macular degeneration has been the injection of drugs designed to block vascular endothelial growth factor (VEGF), a protein that promotes the growth and leakage of the abnormal blood vessels. While these anti-VEGF injections have saved the sight of millions, the need for frequent, often monthly, appointments creates a substantial treatment burden for patients and caregivers. Recent advancements focus on creating agents with a longer duration of action or a dual mechanism to reduce the number of required doctor visits.
A significant breakthrough is the introduction of a bispecific antibody that targets two distinct disease pathways simultaneously. This new drug, known as faricimab, targets both VEGF-A and angiopoietin-2 (Ang-2). Ang-2 is a signaling protein that works with VEGF to destabilize blood vessels, promoting leakage and inflammation. Neutralizing both proteins offers a more comprehensive approach to stabilizing the retinal environment.
The dual-targeting mechanism translates into extended treatment intervals for many patients. Clinical trials show that a significant proportion of patients can maintain vision stability with injections administered every three or four months, following an initial loading phase. This is a substantial improvement over older therapies, which often required injections every four to eight weeks. The focus on durability also includes new high-dose formulations, such as an 8 mg version of aflibercept, designed to allow extended dosing schedules up to every four months.
Innovative drug delivery methods also reduce the frequency of in-office injections. One method is a port delivery system (PDS), a small, surgically implanted device that continuously releases pre-filled anti-VEGF medication directly into the eye. The device is designed to be refilled at the doctor’s office, potentially every six months or longer, replacing the need for repeated monthly injections. This focus on extended durability is reshaping the treatment paradigm toward sustained therapeutic effect.
Treatments for Geographic Atrophy
Geographic atrophy (GA) is the advanced form of dry macular degeneration, characterized by the irreversible loss of retinal pigment epithelium (RPE) cells and overlying photoreceptors. For decades, there were no approved medical treatments to slow the progression of this condition. This landscape changed with the recent approval of a new drug class that addresses the underlying biological drivers of GA.
The pathology of geographic atrophy is linked to the overactivation of the complement cascade, part of the body’s innate immune system. In GA, this system mistakenly targets and destroys healthy retinal cells, leading to characteristic patches of atrophy. The newest treatments for GA are complement inhibitors that modulate this destructive process.
One approved treatment selectively binds to and inhibits the C3 protein and its fragment, C3b, central components of the complement cascade. By blocking C3, the drug acts as a broad regulator, preventing the cascade’s destructive downstream effects on retinal tissue. This mechanism slows the rate at which atrophic lesions expand across the macula.
Clinical trials demonstrated that regular administration of this inhibitor, either monthly or every other month, slowed the growth of GA lesions. Monthly treatments showed a reduction in lesion growth of up to 22% over a 24-month period in one study. This treatment slows the rate of disease progression, but does not reverse damage that has already occurred. The drug is administered as an injection into the eye, and continuous treatment is important to preserve remaining healthy vision.
Highly Innovative Emerging Therapies
Beyond currently approved medications, innovative therapies are in development, aiming to provide permanent or regenerative solutions for macular degeneration. These cutting-edge approaches include gene therapy and regenerative medicine, which address the disease at a fundamental cellular or genetic level.
Gene therapy represents a promising future for treating wet macular degeneration by potentially eliminating the need for injections. This technique involves delivering genetic material, often using a harmless adeno-associated virus, into the retina during a single surgical procedure. The introduced genes reprogram retinal cells to continuously produce their own long-lasting anti-VEGF therapeutic agent. The goal is to turn the eye into a self-sustaining drug factory, providing an enduring therapeutic effect without the need for repeated office visits.
For dry macular degeneration, regenerative medicine, particularly stem cell therapy, is being explored to restore lost vision. This approach focuses on replacing the damaged retinal pigment epithelium (RPE) cells lost in geographic atrophy. Researchers grow new, healthy RPE cells from induced pluripotent stem cells in the laboratory. These cells are then surgically transplanted into the macula to replace the diseased layer, providing metabolic support for the remaining photoreceptors.
These emerging therapies are currently in various stages of clinical trials and are not yet standard clinical practice. Gene therapy is moving closer to approval, while stem cell transplantation faces challenges related to cell survival, integration, and immune rejection. Both fields represent the next generation of treatment, offering the possibility of a functional cure or a single-procedure treatment for macular degeneration.