Geographic Atrophy and Syfovre

Geographic Atrophy and Syfovre™

Advanced AMD, Geographic Atrophy, and Syfovre: Finally a Treatment Option for this Blinding Condition

Geographic atrophy, a form of age-related macular degeneration (AMD), is a chronic and progressive eye condition that leads to the gradual loss of central vision. While there is currently no cure for geographic atrophy, recent advancements in medical research have introduced a potential treatment called Syfovre. This page aims to explore geographic atrophy, its impact on vision, and the emerging therapy of Syfovre, offering hope to individuals affected by this debilitating condition.

Geographic atrophy is a form of advanced age-related macular degeneration. Unlike the more common "wet" AMD, which is characterized by abnormal blood vessel growth in the retina, geographic atrophy involves the gradual degeneration of the retinal cells in the macula. As the cells deteriorate, patches of atrophy, or thinning, occur in the macula, leading to the loss of central vision. For affected patients, this can have a profound effect on visual function, making it difficult to read, recognize faces, and perform everyday tasks.

The exact causes of geographic atrophy remain unknown. However, several risk factors have been identified, including advanced age, genetic predisposition, smoking, high blood pressure, and obesity. Studies have also suggested that chronic inflammation and oxidative stress play significant roles in the development and progression of the condition.

In the early stages of geographic atrophy, individuals may not experience any noticeable symptoms. However, as the disease progresses, the following symptoms may arise:

  1. Blurred or distorted central vision
  2. Difficulty recognizing faces
  3. Reduced ability to read or perform close-up tasks
  4. Decreased contrast sensitivity
  5. Impaired color perception
  6. Scotomas (areas of vision loss)
  7. Increased sensitivity to glare

It is important to note that geographic atrophy does not typically cause total blindness since it only affects the central vision. However, the loss of central vision can significantly impact daily activities and quality of life.

Early detection and diagnosis are crucial in managing geographic atrophy effectively. Ophthalmologists employ various tests, including a comprehensive eye examination, visual acuity tests, optical coherence tomography (OCT), and fundus autofluorescence imaging, to assess the extent and progression of the disease.

Introducing Syfovre (pegcetacoplan):

The culmination of decades of research, pegcetacoplan (trade name Syfovre) was recently approved by the FDA, and is the first and only treatment option for geographic atrophy. Syfovre offers hope to individuals affected by this progressive condition.

How Syfovre Works:

Pegcetacoplan targets the complement system, a part of the immune system involved in inflammation. Complement overactivation has been linked to the development and progression of geographic atrophy. Pegcetacoplan works by specifically inhibiting a protein called C3, which plays a crucial role in the complement cascade. In short, pegcetacoplan slows down an overactive immune system that damages the macula and results in geographic atrophy.

Mechanism of Action:

Geographic atrophy involves chronic inflammation and damage to the retinal cells in the macula. Pegcetacoplan binds to C3 protein, preventing its activation and subsequent downstream complement system activation. By inhibiting this inflammatory response, pegcetacoplan aims to reduce the damage to retinal cells, slow down the progression of geographic atrophy, and potentially preserve visual function.

Clinical Trials and Efficacy:

Well-designed clinical trials demonstrated the safety and effectiveness of pegcetacoplan in treating geographic atrophy. The Phase 3 clinical trial, known as the DERBY and OAKS studies, showed promising results. The trials demonstrated that pegcetacoplan significantly reduced the rate of geographic atrophy progression compared to the control group, as assessed by changes in the total area of atrophy over time. Specifically, patients treated with monthly Syfovre had a 20% slower rate of progression of atrophy.

Importantly, pegcetacoplan has shown a favorable safety profile, with most adverse events reported as mild or moderate and manageable. Long-term studies are still ongoing to further evaluate the safety and efficacy of this investigational drug. Most risks can be minimized, and it is important to discuss all risks with your doctor before treatment is initiated.

Collaboration and Advancements:

The progress made in developing pegcetacoplan would not be possible without collaborative efforts among pharmaceutical companies, researchers, and clinicians. The collective commitment to understanding the underlying mechanisms of geographic atrophy and finding innovative treatments has propelled this field forward. We at RCSD are proud to collaborate with multiple pharmaceutical companies to study pegcecacoplan and other medications, and to provide exciting investigational treatment options to our patients.


Geographic atrophy is a progressive eye condition that causes central vision loss, impacting the quality of life for affected individuals. Pegcetacoplan, a newly FDA-approved drug targeting the complement system, significantly slows the progression of geographic atrophy by reducing inflammation and damage to the retina. The development of pegcetacoplan represents a significant advancement in the pursuit of effective treatments for geographic atrophy, offering hope for improved management and preservation of visual function for those affected by this condition.

What is geographic atrophy?

In most cases, dry age-related macular degeneration (AMD) is generally benign. However, in later, more advanced stages, dry AMD may progress into geographic atrophy (GA), which is one of the leading causes of blindness in the world. GA involves the development and growth of lesions that target the retinal pigment epithelium (RPE), a tissue layer found beneath the retina that is essential to the retina’s metabolic processes. The RPE may become atrophic and dysfunctional, causing blind spots in your vision.

One of the primary hallmarks of dry AMD is the development and accumulation of drusen under the retina. Drusen are small, yellowish deposits of cellular debris that build up over time. With GA, there is an excessive amount of drusen accumulation, which can cause RPE cells to die and inhibit their functionality. This eventually leads to the death of the retina’s photoreceptor cells, contributing to a significant loss of central vision. Up until recently, there was no treatment available for this devastating disease. However, thanks to the tireless research efforts conducted across the world, the U.S. Food and Drug Administration (FDA) approved the first and only treatment for geographic atrophy in March 2023.

The main symptom of GA is loss of central vision, which can cause difficulties with performing a wide range of visual activities, such as reading, driving, and seeing faces. Other common symptoms include seeing in low-light conditions, colors appearing washed out or dull, and decreased visual acuity. Another symptom to be aware of is the development of scotomas, which are blind spots in or near the central field of vision. In addition, if left unaddressed, permanent vision loss may occur.

GA is characterized by the presence of drusen, which is what retina specialists use to identify and monitor the condition’s progression. However, the formation of drusen is very common and does not always indicate a problem.

The FDA has approved Syfovre™ (pegcetacoplan injection) for GA. This is significant, as there had been no approved treatments for patients previously. Safe and effective, Syfovre, an injectable medication, has been shown to slow lesion growth, with its effects increasing over time.

As an advanced stage of dry AMD, patients with GA are advised to follow the same preventive measures, including getting regular exercise, consuming an eye-healthy diet, and avoiding smoking. In some cases, your doctor may recommend that you take nutritional supplements, specifically an AREDS 2 vitamin, which is a combination of high-dose antioxidants and carotenoids. It’s also strongly recommended that patients with any form of macular degeneration monitor their vision daily using an Amsler grid.

Before the FDA approval of Syforvre™, the prognosis for GA was poor, as the disease is a chronic and progressive condition. While the results vary among patients, GA progression often leads to an extensive decrease in visual acuity.

However, although not a cure for GA, Syforvre™ offers hope to many. Having undergone extensive clinical trials, Syfovre™ was found to effectively slow lesion growth, with its effects increasing over time. While this medication cannot cure or reverse any existing damage caused by GA lesion growth, it has been shown to effectively help keep the condition from getting worse. Syfovre™ is safe for most patients, with the most common adverse reactions including ocular discomfort, floaters, conjunctival hemorrhage (excessive bleeding in the eye’s outer membrane), and the development of wet, or neovascular AMD. Dosage frequency is flexible and can be administered every 25 to 60 days, depending on the patient’s specific case.