Regular Aspirin Use Linked to Increased Risk of AMD

Staff
2/23/2013

Regular aspirin use appears to be associated with an increased risk of neovascular age-related macular degeneration, and it appears to be independent of a history of cardiovascular disease and smoking, according to a report published online by JAMA Internal Medicine.

Aspirin is one of the most widely used medications in the world and is commonly used in the prevention of cardiovascular disease, such as myocardial infarction and ischemic stroke. While a recent study suggested that regular aspirin use was associated with AMD, particularly the more visually devastating neovascular form, other studies have reported inconsistent findings. Smoking is also a preventable risk factor for AMD, the authors write in the study background.

Gerald Liew, PhD, of the University of Sydney, Australia, and colleagues examined whether regular aspirin use (defined as once or more per week in the past year) was associated with a higher risk of developing AMD by conducting a prospective analysis of data from an Australian study that included four examinations during a 15-year period. Of 2,389 participants, 257 individuals (10.8 percent) were regular aspirin users.
After the 15-year follow-up, 63 individuals (24.5 percent) developed incident neovascular AMD, according to the results.

“The cumulative incidence of neovascular AMD among nonregular aspirin users was 0.8 percent at five years, 1.6 percent at 10 years, and 3.7 percent at 15 years; among regular aspirin users, the cumulative incidence was 1.9 percent at five years, 7 percent at 10 years and 9.3 percent at 15 years, respectively,” the authors note. “Regular aspirin use was significantly associated with an increased incidence of neovascular AMD.”

The authors note that any decision concerning whether to stop aspirin therapy is “complex and needs to be individualized.”

“Currently, there is insufficient evidence to recommend changing clinical practice, except perhaps in patients with strong risk factors for neovascular AMD (e.g., existing late AMD in the fellow eye) in whom it may be appropriate to raise the potentially small risk of incident neovascular AMD with long-term aspirin therapy,” the authors conclude. 

Fetal Light Exposure Key to Eye Development
New research published in Nature concludes that not only does the eye depend on light to see, it needs light to develop normally during pregnancy.

Scientists say the unexpected finding offers a new basic understanding of fetal eye development and ocular diseases caused by vascular disorders—in particular retinopathy of prematurity. The research, led by scientists at Cincinnati Children’s Hospital Medical Center and the University of California, San Francisco, appeared online Jan. 16 ahead of print publication.

“This fundamentally changes our understanding of how the retina develops,” says study co-author Richard Lang, PhD, a researcher in the Division of Pediatric Ophthalmology at Cincinnati Children’s Hospital Medical Center. “We have identified a light-response pathway that controls the number of retinal neurons. This has downstream effects on developing vasculature in the eye and is important because several major eye diseases are vascular diseases.”

Dr. Lang is a principal investigator on the ongoing research along with project collaborator, David Copenhagen, PhD, a scientist in the departments of ophthalmology and physiology at UCSF. The scientists say their current study, conducted in mouse models, includes several unexpected findings.

“Several stages of mouse eye development occur after birth,” says Dr. Copenhagen. “Because of this, we had always assumed that if light played a role in the development of the eye, it would also happen only after birth.”

But researchers in the current study found that activation of the newly described light-response pathway must happen during pregnancy to activate the carefully choreographed program that produces a healthy eye. Specifically, they say it is important for a sufficient number of photons to enter the mother’s body by late gestation, or about 16 days into a mouse pregnancy.

Researchers were also surprised to learn that photons of light activate a protein called melanopsin directly in the fetus—not the mother—to help initiate normal development of blood vessels and retinal neurons in the eye. 

One purpose of the light-response pathway is to suppress the number of blood vessels that form in the retina. These vessels are critical to retinal neurons, which require large amounts of oxygen to form and to function. When retinopathy of prematurity occurs in infants, retinal vessels grow almost unchecked. This continued expansion puts intense pressure on the developing eye and in extreme cases causes severe damage and blindness.

The research team led by Drs. Lang and Copenhagen conducted several experiments in laboratory mouse models that allowed them to identify the light-response pathway’s specific components and function.

Mice were reared in the dark and in a normal day-night cycle beginning at late gestation to observe the comparative effects on vascular development of the eye. The researchers verified the function of the light response pathway by mutating an opsin gene in mice called Opn4 that produces melanopsin, in essence preventing activation of the photo pigment.

Both mice reared under dark conditions from late gestation, and those with mutated Opn4, exhibited nearly identical promiscuous expansion of hyaloid vessels and abnormal retinal vascular growth. The unchecked vascular growth was driven by the protein vascular endothelial growth factor. When the light response pathway is properly engaged, it modulates VEGF to help prevent promiscuous vascular growth, according to researchers. The melanopsin protein is present in both mice and humans during pregnancy. Dr. Lang said the research team is continuing to study how the light-response pathway might influence the susceptibility of pre-term infants to retinopathy of prematurity and also be related to other diseases of the eye.

Blue Mountains: Early Predictor of Glaucoma Found
A new study finds that certain changes in blood vessels in the retina can be an early warning that a person is at increased risk for glaucoma.
Using diagnostic photos and other data from the Australian Blue Mountains Eye Study, the researchers showed that patients who had abnormally narrow retinal arteries when the study began were also those who were most likely to have glaucoma at its 10-year end point. If confirmed by future research, this finding could give ophthalmologists a new way to identify and treat those who are most vulnerable to vision loss from glaucoma. The study was recently published online by Ophthalmology.

The findings of the new study, led by Paul Mitchell, MD, PhD, of the Centre for Vision Research, University of Sydney, support the concept that abnormal narrowing of retinal blood vessels is an important factor in the earliest stages of open-angle glaucoma. Tracking nearly 2,500 participants, the study found that the open-angle glaucoma risk at the 10-year mark was about four times higher in patients whose retinal arteries had been narrowest when the study began, compared with those who had the widest arteries. 

None of the participants had a diagnosis of open-angle glaucoma at the study’s outset. Compared with the study group as a whole, the patients who were diagnosed with OAG by the 10-year mark were older, had higher blood pressure or higher intraocular pressure at the study’s baseline, and were more likely to be female. Study results were adjusted for age, family history of glaucoma, smoking, diabetes, hypertension and other relevant factors.

“Our results suggest that a computer-based imaging tool designed to detect narrowing of the retinal artery caliber, or diameter, could effectively identify those who are most at risk for open-angle glaucoma,” said Dr. Mitchell. “Such a tool would also need to account for blood pressure and other factors that can contribute to blood vessel changes. Early detection would allow ophthalmologists to treat patients before optic nerve damage occurs and would give us the best chance of protecting their vision.”

Study Cautions on VEGF-Blocking Therapies
Increasingly aggressive therapies that block vascular endothelial growth factor could have a harmful effect on the ciliary body, according to a study in Investigative Ophthalmology & Visual Science.

“Very little is known about the factors that regulate the integrity and function of [the ciliary body] in the adult,” said author Patricia A. D’Amore, PhD, of Schepens Eye Research Institute/Massachusetts Eye and Ear. “Our finding indicates that VEGF-A is at least one of the molecules that play a role in keeping the ciliary body healthy and functioning properly.”

In the study, Expression and role of VEGF-A in the Ciliary Body, investigators simulated the VEGF-A activity in adult mice and found that blocking the protein decreased the intraocular pressure, an unexpected side effect that impaired the ciliary body.

Several anti-VEGF-A therapies are currently being widely and successfully used for the treatment of eye diseases like wet macular degeneration, diabetic macular edema and retinopathy of prematurity. Dr. D’Amore agrees that there is no evidence to indicate that the manner in which these drugs are being administered interferes with the ciliary body. “However, there is a move toward developing methods to continuously deliver anti-VEGF to the eye and to have drugs that are more potent inhibitors of VEGF,” she said. “I would be concerned that more aggressive VEGF inhibition in the eye would have deleterious effects on the ciliary body.”

The research team’s investigation of anti-VEGF-A on the ciliary body was the result of prior studies that found blocking VEGF can lead to the degeneration of capillary beds, particularly capillaries that have specializations called fenestrations like the ones found in the ciliary body. These include whole-body VEGF blockade in anti-cancer therapies that damage the capillaries of the kidney and the effect anti-VEGF has had on the thyroid function in people treated locally for brain tumors.

The results of the new IOVS study suggest further research, including clinical trials, should be considered. “I am hoping that revealing the possible negative side effects of VEGF inhibition in the eye will motivate research into new ways to block edema and blood vessel growth in the eye that does not require continuous inhibition of intraocular VEGF,” said Dr. D’Amore.  REVIEW