New Research: Are Lucentis, Avastin, and Eylea Risk Factors for Increased Eye Pressure?

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The injectable drugs Eylea, Lucentis, and Avastin have revolutionized the treatment of wet age-related macular degeneration (AMD).

Nevertheless, questions continue to arise regarding the risks and complications that accompany this delivery system. At present, these drugs require monthly injections or a pro re nata [i.e., “as needed”] (PRN) regimen, with monthly controls and injections for recurrent or persistent macular bleeding.

One aspect of the injection process that causes particular concern is monitoring increased intraocular [i.e., within the eye] pressure after injection, specifically in persons who also have a history of glaucoma.

In response, a new study, currently “in press” in the American Journal of Ophthalmology, concludes that (a) a history of multiple/repeated injections was not a significant risk factor for increased or elevated intraocular pressure (IOP) in the study subjects and (b) IOP elevation was more common in eyes with retinal vein occlusion occlusion than with macular degeneration after injection.

About the Research

The study, entitled Long-Term Effects of Multiple Intravitreal Anti- Vascular Endothelial Growth Factor Injections on Intraocular Pressure, is authored by Yoon Jeon Kim; Kyung Rim Sung; Kyoung Sub Lee; Soo Geun Joe; Joo Yong Lee; June-Gone Kim; and Young Hee Yoon, from the Department of Ophthalmology, University of Ulsan, College of Medicine, Asan Medical Center, Seoul, South Korea.

The American Journal of Ophthalmology is a peer-reviewed, scientific journal that has been published monthly since 1884. The Journal publishes original research directed to ophthalmologists and visual science specialists that “describes clinical investigations, observations, and laboratory investigations.”

Eylea, Lucentis, Avastin, and Anti-Angiogenic Drugs

retina with wet AMD

Angiogenesis is a term used to describe the growth of new blood vessels and plays a crucial role in the normal development of body organs and tissue. Sometimes, however, excessive and abnormal blood vessel development can occur in diseases such as cancer (tumor growth) and AMD (retinal and macular bleeding).

Substances that stop the growth of these excessive blood vessels are called anti-angiogenic (anti=against; angio=vessel; genic=development), and anti-neovascular (anti=against; neo=new; vascular=blood vessels).

The focus of current anti-angiogenic drug treatments for wet AMD is to reduce the level of a particular protein (vascular endothelial growth factor, or VEGF) that stimulates abnormal blood vessel growth in the retina and macula; thus, these drugs, including Lucentis, Avastin, and Eylea, are classified as anti-VEGF treatments. These drugs are administered by injection directly into the eye after the surface has been numbed.

What Is Glaucoma?

The term “glaucoma” describes a group of eye diseases that can lead to blindness by damaging the optic nerve. It is one of the leading causes of vision loss and blindness.

The human eye continuously produces a fluid, called the aqueous, that must drain from the eye to maintain healthy eye pressure.

In primary open-angle glaucoma, the most common type of glaucoma, the eye’s drainage canals become blocked, and the fluid accumulation causes pressure to build within the eye. This pressure can cause damage to the optic nerve, which transmits information from the eye to the brain.

Most eye care professionals define the range of normal intraocular pressure (IOP) as between 10 and 21 mm Hg [i.e., millimeters of mercury, which is a pressure measurement]. Most persons with glaucoma have an IOP measurement of greater than 21 mm Hg.

About Retinal Vein Occlusion

A retinal vein occlusion (RVO) is a blockage [i.e., “occlusion”] of the small veins that carry blood away from the retina, the light-sensitive tissue that lines the inside surface of the eye. The retina converts incoming light into nerve signals and sends them to the brain, which interprets them as visual images.

Blockage of smaller, “branching,” veins (a branch retinal vein occlusion or BRVO) in the retina often occurs when retinal arteries that have been thickened or hardened by atherosclerosis “cross over” and place pressure on a retinal vein. A branch retinal vein occlusion is sometimes referred to as “a stroke on the retina.”

More about the Study

From a study summary in Healio Optometry, entitled History of multiple intravitreal anti-VEGF injections not associated with IOP elevation:

Researchers evaluated patients who were treated with more than three injections and were tracked for more than 12 months after their last injection. They defined intraocular pressure (IOP) elevation as an increase of 5 mmHg above the baseline measurement on two consecutive visits.

Researchers determined that the following were significant risk factors for IOP elevation after multiple anti-VEGF injections: (a) a low baseline IOP, (b) a history of glaucoma, or (c) a diagnosis of retinal vein occlusion.

“We suggest … that a ‘treat-and-extend’ dosing regimen for anti-VEGF injections is not a significant risk factor for IOP elevation,” the authors said. “Anti-VEGF therapy requires multiple injections during an extended period, but IOP elevation was noted in our current patient [group] at a low rate and extent,” they said.

From the American Journal of Ophthalmology

Here is more information about the study, excerpted from the article abstract:

Purpose: To evaluate long-term effects of multiple … anti-vascular endothelial growth factor (VEGF) injections on intraocular pressure (IOP) in eyes with neovascular age-related macular degeneration (AMD) or retinal vein occlusion (RVO).

Methods: This study enrolled patients who underwent multiple (more than three) … anti-VEGF injections and who were followed for more than 12 months after their last injection. IOP elevation was defined as an increase of 5 mmHg over the baseline measurement on two consecutive visits.

Results: 629 eyes with [wet] AMD and 95 eyes with RVO were included in the analysis. Twenty eyes with [wet] AMD (3.0%) and 7 eyes with RVO (7.4%) experienced IOP elevation after multiple anti-VEGF injections, with an overall incidence of 3.7%. A diagnosis of RVO, a history of glaucoma, and low baseline IOP were all significant risk factors for IOP elevation after multiple anti-VEGF injections.

Conclusion: A history of multiple … anti-VEGF injections was not a significant risk factor for IOP elevation in our study. IOP elevation was more common in eyes with RVO than with AMD after anti-VEGF injection.

VisionAware will continue to provide updates for ongoing macular degeneration research as they become available.