Should You Try Combination Therapy for Wet AMD?

Wet AMD: Are You a Candidate for Combination Therapy?

Combination therapy could be an option if anti-VEGF drugs aren’t enough to treat your wet AMD. Find out more about this macular degeneration treatment.
Wet AMD: Are You a Candidate for Combination Therapy?
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If you have wet age-related macular degeneration (AMD), you’re likely seeing an eye doctor for regular injections of anti-VEGF (vascular endothelial growth factor) drugs to keep your vision stable and prevent further blood vessel damage in your eyes.

But if anti-VEGF drugs aren’t enough to keep abnormal blood vessel growth at bay — meaning, you have treatment-resistant wet AMD — you may benefit from combination therapy.

Here’s what to know about combination therapy for wet AMD.

Anti-VEGF Drugs for Wet AMD

AMD occurs when the macula — the portion of the retina at the back of the eye that provides the sharpest vision and enables you to see colors — becomes damaged.

Wet AMD, which progresses from the more common “dry” form of the condition, is caused in part by a process called choroidal neovascularization (CNV), or the formation of new blood vessels in the layer beneath the retina called the choroid. These abnormal blood vessels may leak blood or other fluids, causing damage to the macula that can lead to scarring and rapid central vision loss.

Most people with wet AMD are initially treated with injections of anti-VEGF drugs, which work well in many cases, because they target the proteins involved in the formation and progression of CNV. As the name implies, they do so by blocking production of the VEGF protein, which causes abnormal, impaired blood vessels to form from the choroid.

“The standard of care for wet macular degeneration is to start with anti-VEGF therapy, which consists of injections of medication into the eye,” says Philip Storey, MD, a retina specialist at Austin Retina Associates in Texas. “The treatments are safe and well tolerated — and very effective at improving vision.”

To start, the injections are typically given once a month. As time goes on, you may need them less frequently.

Anti-VEGF drugs help stabilize vision for 9 out of 10 people who have wet AMD, and improve vision in about 1 out of 3 people.

But for the people who don’t see improvements in their vision, combination therapy could be an option.

Combination Therapy for Wet AMD

For 50 percent of people who have wet AMD, anti-VEGF drugs aren’t enough to improve their vision to 20/40 or better.

 This is likely because, despite treatment, there is still too much fluid in the retina.

“Patients who have persistent fluid in the retina with monthly anti-VEGF injections may be good candidates for combination therapy,” Dr. Storey says.

There are different combination therapies available for wet AMD, according to Storey, including:

  • Anti-VEGF Drugs and Photodynamic Therapy (PDT) “With PDT, we inject dye into the arm, and then we shine a laser in the back of the eye, which treats the leaking blood vessel,” Storey says. Some research shows that adding PDT to anti-VEGF drugs increased visual acuity compared with anti-VEGF drugs alone. The combination can also potentially reduce the number of anti-VEGF injections needed, according to the researchers.

  • Anti-VEGF Drugs and Steroid Injections Steroids are used for a number of health conditions to ease inflammation and halt an overactive immune system. Together with anti-VEGF drugs, steroid injections may help treat wet AMD.

  • Anti-VEGF Injections and Dorzolamide-Timolol Eye Drops Dorzolamide and timolol eye drops are designed to decrease pressure in the eye and are commonly used to treat glaucoma. In wet AMD, the eye drops essentially work to enhance the effectiveness of the anti-VEGF injections.

It’s important to note that only the combination of anti-VEGF injections and PDT has been shown in clinical trials to have positive effects on wet AMD, Storey says. Even then, he adds, “I would not consider doing a combination of PDT and anti-VEGF therapy until giving at least three to six injections of anti-VEGF alone to measure clinical response.”

When you have wet AMD, it’s important to work closely with your doctor to monitor and manage your condition. As new treatment options become available, discuss with your doctor how effective your current treatment is and whether you’d be a good candidate for a new therapy.

The Takeaway

  • If anti-VEGF drugs haven’t been effective at improving your wet AMD, your doctor may prescribe combination therapy, which includes an anti-VEGF, plus another treatment.
  • Some combination therapies include anti-VEGF drugs and photodynamic therapy (PDT), and steroid injections
  • Not all combination therapies have been shown to be equally effective at treating wet AMD.
Edmund-Tsui-bio

Edmund Tsui, MD

Medical Reviewer

Edmund Tsui, MD, is an assistant professor of ophthalmology at the Jules Stein Eye Institute in the David Geffen School of Medicine at UCLA.

He earned his medical degree from Dartmouth. He completed an ophthalmology residency at the NYU Grossman School of Medicine, where he was chief resident, followed by a fellowship in uveitis and ocular inflammatory disease at the Francis I. Proctor Foundation for Research in Ophthalmology at the University of California in San Francisco.

Dr. Tsui is committed to advancing the field of ophthalmology. His research focuses on utilizing state-of-the-art ophthalmic imaging technology to improve the diagnosis and monitoring of uveitis. He is a co-investigator in several multicenter clinical trials investigating therapeutics for uveitis. He is the author of over 80 peer-reviewed publications and has given talks at national and international conferences.

Along with his clinical and research responsibilities, Tsui teaches medical students and residents. He is on the Association for Research in Vision and Ophthalmology's professional development and education committee, as well as the advocacy and outreach committee, which seeks to increase funding and awareness of vision research. He also serves on the editorial board of Ophthalmology and the executive committee of the American Uveitis Society.

Erica Patino

Author
Erica Patino is a freelance writer and editor, content strategist, and usability specialist who has worked for a variety of online health outlets, including Healthline, Sharecare, and Twill Care. She was previously a senior editor at Everyday Health. She is also the founder and editor-in-chief of Hear 2 Tell, a website that covers advances in hearing loss treatment. Patino lives in Portland, Oregon, with her husband and twin sons.
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Resources
  1. Turbert D. Anti-VEGF Treatments. American Academy of Ophthalmology. July 26, 2023.
  2. What Is Choroidal Neovascularization? BrightFocus Foundation. July 8, 2021.
  3. Injections to Treat Eye Conditions. National Eye Institute. July 8, 2022.
  4. Maguire MG et al. Five-Year Outcomes With Anti-Vascular Endothelial Growth Factor Treatment of Neovascular Age-Related Macular Degeneration: The Comparison of Age-Related Macular Degeneration Treatments Trials. Ophthalmology. August 2016.
  5. Lim TH et al. Comparison of Ranibizumab With or Without Verteporfin Photodynamic Therapy for Polypoidal Choroidal Vasculopathy. JAMA Ophthalmology. July 16, 2020.
  6. Kaya C et al. Adding a Corticosteroid or Switching to Another Anti-VEGF in Insufficiently Responsive Wet Age-Related Macular Degeneration. Clinical Ophthalmology. December 5, 2019.
  7. Sadr A et al. Topical Dorzolamide as Adjunctive Treatment With Intravitreal Bevacizumab in Bilateral Diabetic Macular Edema. Cureus. February 24, 2024.