The Tell Tale Heart

I recently received this question. This makes now the third patient who had these symptoms after an injection of Lucentis® or Avastin®.

“I received Lucentis for the fifth time. I had three in a row and then three months later one dose. After the fifth dose I became very red and my heart was racing. I went back into the doctor's office and my blood pressure had sky rocketed. They wouldn't tell me my BP until it came down to 162/80. They said Lucentis did not cause this. My BP is normal always.”

My answer:

I wrote in another blog (see Nov 28¹ and 30², 2007) about a patient who had exactly the same symptoms namely a racing heart, high blood pressure, and a pink flush. In that blog, I ascribed these symptoms to anxiety but I think I was wrong. Patients who are anxious may feel faint after an injection. A faint is called a vaso-vagal reaction and is associated with a slow pulse, low blood pressure, and clammy skin. We usually have the patient put his head down so they blood can reach the brain even with the low blood pressure and the feeling soon passes. I don’t think these patients had a typical fainting spell. They also describe the symptoms occurring after the injection when the anxiety should be decreasing.

I now think that these reactions were either due to the phenylephrine eye drops used to dilate the eye or more likely, epinephrine in the local anesthetic solution. Both of these medications can increase the heart rate and blood pressure. Epinephrine can also cause flushed skin. Epinephrine is often used in a local anesthetic injection because it constricts blood vessels. The anesthetic then will stay around at the injection site longer because it is not absorbed by the blood vessels. The constricted blood vessels will also bleed less. Eye doctors may be tempted to use epinephrine in their local anesthetic to reduce the risk of unsightly subconjunctival hemorrhage. The conjunctiva of the eye though is very vascular and will readily absorb epinephrine after its injection. Epinephrine in the blood stream causes, you guessed it, an increased heart rate, blood pressure, and flushing. We don’t use epinephrine in our local anesthetic, mainly I confess due to the intelligence of our nurses, and have not seen this reaction.

Therefore I would recommend that doctors do not use epinephrine in their local anesthetic and use just one drop of 2.5% phenylephrine to dilate the eye. Patients may want to ask the doctor or nurse to makes sure that no epinephrine is in the local anesthetic.

1. Folk JC. Query: Worried About Stroke. November 28, 2007. http://www.medrounds.org/amd/2007/11/query-worried-about-stroke.html

2. Folk JC. Anxiety and the Injection Procedure. November 30, 2008. http://www.medrounds.org/amd/2007/11/anxiety-and-injection-procedure.html

Not Responding to Treatment

I received this question recently:

“My father is suffering from AMD he has been receiving Avastin injections every 6 weeks (about 7 treatments so far) and his doctor never says he sees much improvement and he will probably need it for the rest of his life! Should we consider a different drug?(Lucentis for example) or another doctor?”

Here are possible answers:

1. I would have the doctor recheck the OCT to make sure he doesn’t have other problems in the eye like vitreous traction on the macula or an epi-retinal membrane that may need surgery.

2. I would first try Lucentis®. It works a little quicker than Avastin® but doesn’t seem to last as long. Whenever one of these drugs isn’t working, we try the other and sometimes it works better.

3. If the doctor wants to keep using Avastin, then maybe he/she should see your dad back in four weeks to make sure he isn’t missing the improvement in the fluid. Maybe your dad needs injections more often than every six weeks.

4. If your dad is not getting vision improvement and the doctor doesn’t see any reduction in the fluid, your dad may have older mature vessels that don’t respond well to these drugs. He and the doctor could consider stopping the injections to see if the vision worsens. If the vision doesn’t change much without the injections, then I would just follow him to make sure he doesn’t get worse.

5. The doctor could also consider an ancillary treatment along with the Lucentis like PDT with intraocular Kenalog along with either Avastin or Lucentis.

Unfortunately, your dad probably doesn’t have a high chance of vision improvement probably because the abnormal vessels have been there awhile. The Kenalog can increase the pressure in his eye too but usually it’s temporary so I would try one or more of the procedures listed above before giving up.

Thanks. JCF

Reader Question: Lucentis and risk of stroke?

I received this question recently:

My mom is 54 years old, she had a stroke (clot blood) one year ago and started to get treatment after 1 month of the stroke. She does not have blood pressure, cholesterol or diabetes mellitus. The major causes according to the doctors are smoking and hormone (Estrogens) which she has taken for many years because she had no uterus since 1994.

She is taking one tablet daily of dipyridamole. She was treated with laser+cortisone injection two times and she had one injection of Avastin. After 10 months of treatment a little of vascular growth have started and the main sign was that the eye is full with edema. Because of that doctors decided to give her Lucentis, and she had the first one two weeks ago.

My questions are: Is there a possibility that my mother will has a new stroke by taking Lucentis? How many Lucentis injection do you think she’ll need?

My answer:
First she should stop smoking and probably the estrogen but I will leave that up to her doctors to decide. Anyone with AMD, especially wet AMD, should stop smoking.

There is no proof that Lucentis causes an increased risk of strokes. So far, the percentage of strokes and heart attacks in the various trials was about the same between the Lucentis and placebo groups. The concern is that Lucentis is part of another drug called Avastin which does increase the risk of strokes when given intravenously for colon cancer. I don’t think we can really implicate Lucentis or Avastin for that matter, on this basis since the Avastin dose used intravenously is 300 times the dose used in the eye.

Genentech, in a “Dear Doctor” letter on January 24, 2007, stated that a planned interim analysis of the accruing data in the SAILOR study showed a higher risk of strokes, (1.2%) in the group receiving 0.5mg of Lucentis than in the group receiving 0.3mg (0.3%). People with a history of a previous stroke were at higher risk. Both groups of patients had been followed an average of 230 days or a little less than eight months. Doctors were not too worried about this letter because the follow-up was short and the overall risk of stroke seemed fairly low. We have not heard from Genentech since that letter so I’m guessing that the increased rate of stroke didn’t continue or wasn’t significant. The latest results from the Sailor study results will be presented at ARVO this April.

A recent article found that the risk of ischemic stroke was about 3.5% a year in Medicare patients whether they had AMD or not. Patients who had a history of a heart attack or stroke had a 35% risk of having another stroke in the following year. The average age of this group of patients was 80.5 years so they were on average much older than your mother and hopefully that means your mother’s risk is lower than 35%.

The bottom line is that we really don’t know but Lucentis is probably pretty safe. The people we are most concerned about however are those like your mother who has already had a stroke. I would encourage her doctors to use Lucentis as infrequently as possible. I would also try to determine how important the vision is in her affected eye. For instance, if the affected eye has very poor vision, the doctors don't think it will get much better even with treatment, and the other eye is very good, then it would be reasonable to forgo more treatment for this eye.


1. Alexander SL, et al., “Annual Rates of Arterial Thromboembolic Events in Medicare Neovascular Age-Related Macular Degeneration Patients.” Ophthalmology 2007;114:2174-2178.