When I was training as an ophthalmology resident in the 1990s, I remember seeing countless patients losing their vision due to a condition called age-related macular degeneration (AMD). Many of these patients developed a form of AMD known as “wet” AMD, characterized by the growth of new blood vessels underneath the retina that leaked fluid and sometimes bled suddenly, leading to catastrophic central vision loss.

Patients often found they could not recognize faces, read, or even tell the time on their watch. At the time, treatments were limited. Photodynamic therapy (PDT) was available but expensive, and I had to watch helplessly as many people went blind.

The Breakthrough: Avastin

In response to the devastating effects of AMD, pharmaceutical companies worked diligently to find a solution. One treatment that has since revolutionized ophthalmology is Avastin (bevacizumab). Originally developed as a treatment for colon cancer, Avastin has found critical applications in eye care, particularly for conditions involving abnormal blood vessel growth.

What is Avastin?

Avastin is part of a class of drugs known as anti-VEGF agents. VEGF stands for Vascular Endothelial Growth Factor, a protein produced by oxygen-deprived (ischemic) tissue that stimulates the growth of new blood vessels. The “mab” in bevacizumab indicates that it was initially derived from mouse antibodies.

While the production of VEGF is crucial for normal bodily functions, excessive VEGF can lead to abnormal blood vessel growth, which is a hallmark of several eye conditions, including wet AMD and diabetic retinopathy.

Mechanism of Action

Developed by Genentech (now part of Roche), Avastin works by inhibiting VEGF. It binds irreversibly to the protein, slowing or halting the growth of new blood vessels. Interestingly, its effectiveness in treating eye conditions was discovered accidentally by ophthalmologists at the Bascom Palmer Eye Institute in Miami, Florida.

Avastin’s Journey from Cancer to Eye Care

Initially, Avastin was approved by the FDA in 2004 for treating metastatic colorectal cancer. It worked by inhibiting angiogenesis – the formation of new blood vessels – depriving tumors of the nutrients and oxygen they need to grow. Clinical trials proved its effectiveness in combination with chemotherapy for various cancers, including lung, breast, kidney, and brain cancers.

In 2005, ophthalmologists realized that the same mechanism could benefit patients with eye conditions involving abnormal blood vessel growth. In these conditions, VEGF overproduction leads to leaky blood vessels in the retina, causing fluid accumulation, bleeding, and vision loss. Avastin reduces this fluid, controls inflammation, and halts the growth of abnormal vessels.

How is Avastin Administered?

Avastin is delivered via an intravitreal injection – a small amount of the drug is injected directly into the vitreous humor (the jelly-like substance filling most of the eyeball).

Eye Conditions Treated with Avastin

Avastin has shown effectiveness in managing several sight-threatening conditions:

1. Age-Related Macular Degeneration (Wet AMD)

Wet AMD involves abnormal blood vessel growth under the retina, causing fluid leakage and rapid vision loss. Avastin helps reduce these abnormal vessels and fluid buildup, preserving central vision.

2. Diabetic Retinopathy and Diabetic Macular Edema

Diabetic retinopathy damages retinal blood vessels due to diabetes. In advanced stages, fluid leaks into the macula (diabetic macular edema), impairing central vision. Avastin reduces this fluid and helps manage the disease.

3. Retinal Vein Occlusion

This condition occurs when a major retinal vein is blocked, causing widespread damage and fluid leakage. Avastin reduces macular edema associated with both branch and central retinal vein occlusions.

4. Neovascular Glaucoma

In this rare form of glaucoma, abnormal blood vessels grow on the iris, blocking drainage channels and increasing eye pressure. Avastin helps reduce vessel growth, giving surgeons time to perform laser treatment (PRP).

5. Retinopathy of Prematurity (ROP)

ROP affects premature infants and involves abnormal retinal blood vessel growth. Avastin can be used as an initial treatment until laser therapy (PRP) can be performed.

Benefits of Avastin

1. Effectiveness: Studies, including a 2011 New England Journal of Medicine study, found Avastin as effective as the more expensive drug Lucentis for AMD treatment.

2. Cost-Effectiveness: Avastin is significantly more affordable than other anti-VEGF medications, making it accessible to more patients, especially in resource-limited healthcare systems.

3. Versatility: Avastin is effective for multiple eye conditions, making it a versatile tool for ophthalmologists.

4. Rapid Action: Many patients notice vision improvements within weeks of starting treatment.

Potential Risks and Side Effects

While Avastin is generally safe, it does carry some risks:

1. Eye-Related Complications

• Severe eye infection (endophthalmitis)

• Retinal detachment

• Temporary increase in eye pressure

• Inflammation inside the eye

2. Systemic Side Effects

• Increased risk of blood clots (especially in patients with a history of stroke or heart attack)

• High blood pressure

• Gastrointestinal perforations

3. Allergic Reactions

Though rare, allergic reactions can occur.

Off-Label Use Controversy

Avastin’s use in ophthalmology is “off-label” in many countries, including the United States. This means it’s FDA-approved for cancer but not specifically for eye treatments.

• Proponents: Avastin’s efficacy and affordability make it indispensable for many patients.

• Critics: Concerns remain about potential risks and lack of FDA oversight.

Compounding pharmacies prepare Avastin for ophthalmic use by dividing large cancer-treatment vials into smaller doses for eye injections.

Conclusion

Avastin’s transformation from a cancer drug to a revolutionary ophthalmic treatment showcases the power of innovation and adaptability in medicine. It provides an affordable, effective solution for sight-threatening conditions like wet AMD and diabetic retinopathy, helping millions preserve their vision.

While debates about off-label use persist, extensive clinical research supports Avastin’s role in eye care. As always, patients should consult qualified ophthalmologists to weigh potential risks and benefits.

Staying informed about treatments like Avastin empowers patients to take an active role in their eye health.

References

1. CATT Research Group (2011). Ranibizumab and Bevacizumab for Neovascular Age-Related Macular Degeneration. New England Journal of Medicine, 364(20), 1897-1908.

2. CATT Research Group (2012). Ranibizumab and Bevacizumab for Treatment of Neovascular Age-related Macular Degeneration: Two-Year Results. Ophthalmology, 119(7), 1388-1398.

3. American Academy of Ophthalmology (2015). Policy Statement: Intraocular Use of Bevacizumab (Avastin).

4. Avery, R. L., et al. (2006). Intravitreal Bevacizumab (Avastin) in the Treatment of Proliferative Diabetic Retinopathy. Ophthalmology, 113(10), 1695-1705.e6.

5. Michels, S., et al. (2005). Intravitreal Bevacizumab (Avastin) for Persistent Neovascular Age-Related Macular Degeneration after Previous Treatment. Retina, 25(6), 713-720.

6. Duker, J., & Liang, M. (2024). Anti-VEGF Use in Ophthalmology. CRC Press.