Mayo Clinic detective work shows possible side effect in macular degeneration drug

Two major drug trials conclude there was little risk from a drug aimed at age-related macular degeneration. Yet a Mayo Clinic ophthalmologist began to note something concerning in some of her patients: an increase in pressure inside the eye. It led to a retrospective study and findings that will be presented at the American Academy of Ophthalmology in Orlando.

Sophie Bakri, M.D., had been treating patients in her clinic with Food and Drug Administration-approved ranibizumab (), when she began noticing a change in some patients.

"I was treating patients and measuring pressures, and I was surprised to see that in some of these people, their intraocular pressure was higher, and they didn't have a diagnosis of glaucoma," Dr. Bakri says. "So, why did the pressure go up? Was it from the drug itself, or the actual injection? Is this real? You don't know if it's a fluke unless you go back and look at the clinical trials. I took a closer look at the pooled data."

Intraocular pressure (IOP) is a measure of fluid pressure inside the eye. Measured in millimeters of mercury (mm/Hg), IOP that is higher than normal or above baseline (higher than 21 mm/Hg) can indicate glaucoma.

Data from the two clinical trials in many ways held the answers to Dr. Bakri's questions, but she found that knowing what to look for helps.

MARINA (Minimally Classic/OccultTrial of the Anti-Vascular Endothelial Growth Factor Antibody Ranibizumab in the Treatment of Neovascular Endothelial Age-Related Macular Degeneration) and ANCHOR (Anti-VEGF antibody for the treatment of predominantly classic Choroidal Neovascularization in Age-Related Macular Degeneration) evaluated drugs including Lucentis, for treatment of age-related and other forms of (AMD). Both were two-year studies with monthly injections of Lucentis, compared to a control group who did not receive the injection. Pooling the two studies, which followed the treatment of 1,125 eyes, Dr. Bakri was able to perform a more robust evaluation of IOP changes. Some patients received Lucentis and others unknowingly received "sham" or mimicked injections, or a laser treatment called verteporfin photodynamic therapy (PDT), which did not involve injection.

Dr. Bakri found what she suspected: a subset of patients had increased IOP.

"We still don't know if it goes up because of the drug or the pressure of the repeated monthly injections, or both," she says. The take-home finding: should be monitored in eyes receiving ranibizumab.

"A greater proportion of eyes in the groups had IOP increases regardless of the presence or absence of pre-existing risk factors, such as history of glaucoma, suspicion of glaucoma, ocular hypertension or use of a glaucoma medication," Dr. Bakri says.

A small portion, 8 percent, of all eyes across treatment groups received glaucoma medications in the study. Importantly, none of the patients needed glaucoma surgery.

"Our analysis was surprising because the increase was so prevalent and highly statistically significant," Dr. Bakri says. "Lucentis is an excellent drug that works very well, but if we use a drug, we gain long-term experience, and that's where side effects start showing up.

add to favorites email to friend print save as pdf

Related Stories

AMD drug and IOP; getting good eyeglasses to those in need

Oct 26, 2009

A first-time finding of intraocular pressure increases in patients with no personal or family history of glaucoma following anti-VEGF treatment for wet age-related macular degeneration (AMD), and a report on a simple, low-cost ...

Can further studies lower the cost of preserving vision?

Oct 04, 2006

The results of two large, randomized clinical trials published October 5, 2006, in the New England Journal of Medicine demonstrate that the drug ranibizumab is an effective treatment for neovascular macular degeneration, a comp ...

Recommended for you

Ebola kills 31 people in DR Congo: WHO

38 minutes ago

An outbreak of the Ebola virus in the Democratic Republic of Congo has killed 31 people and the epidemic remains contained in a remote northwestern region, UN the World Health Organization (WHO) said Tuesday.

Dengue fever strikes models in Japan

3 hours ago

A worsening outbreak of dengue fever in Japan has claimed its first celebrities—two young models sent on assignment to the Tokyo park believed to be its source.

Japanese researchers develop 30-minute Ebola test

3 hours ago

Japanese researchers said Tuesday they had developed a new method to detect the presence of the Ebola virus in 30 minutes, with technology that could allow doctors to quickly diagnose infection.

Senegal monitors contacts of 1st Ebola patient

15 hours ago

Senegalese authorities on Monday were monitoring everyone who was in contact with a student infected with Ebola who crossed into the country, and who has lost three family members to the disease.

Cerebral palsy may be hereditary

21 hours ago

Cerebral palsy is a neurological developmental disorder which follows an injury to the immature brain before, during or after birth. The resulting condition affects the child's ability to move and in some ...

User comments