Anxiety and the Injection Procedure

We received this comment about the anxiety of the injections procedure.

“And, speaking strictly to the anxiety aspect of intraocular injections (not the BP spikes) -- for the first year or so of treatments, we made sure my mother took 0.5 - 1.0 mg Ativan [lorazepam] at least an hour before treatment. Eventually, the procedure became so familiar that a tranquilizer assist is no longer needed. Also... consciously developing a jolly, bantering interaction between my mother and the nurses has led to her looking forward to each visit in a way that doesn't leave much room for anxiety.”

Thanks for their comment and kudos to them for coming up with a good plan. Although it shouldn’t hurt, no one can really look forward to an injection in the eye. So doctors, patients, and families should try to make this as good an experience as possible.

Query: Worried About Stroke

We received the following comment:

“I have had the exact treatment and result as anonymous. I had two Visudyne - the second left a hole in my vision. I had three Lucentis with good results for six months. Vision started to get wavy again and I had a fourth Lucentis this week. I am just 55 but worried about stroke. During injection my blood pressure shot up and my pulse was high and I turned hot pink?"

I think the reaction during the injection was more anxiety than anything else since I doubt that the Lucentis could have reached the bloodstream that quickly or had such a rapid effect. Another possibility could have been an allergic reaction to one of the drops or anesthetic given before the injection. Any hives or itching would support an allergic reaction.

We all worry about stroke but there is no definite evidence that it is increased with the use of intraocular Lucentis or Avastin for that matter. We know that intravenous Avastin causes an increased risk of stroke but that is at three hundred times the dose that is given into the eye. The intravenous Avastin is also given every two weeks in patients with metastatic colon cancer instead of every month or six weeks. The best guess is that these drugs, when used in the eye, can increase the risk of stroke, but that increase in the risk is minimal.

The person who left the comment should get his/her blood pressure checked. I can’t tell is he still has good vision in both or just one eye. It sounds like thought, that the Lucentis is keeping the vision good. I think if there is future evidence of leakage or fluid, I would keep getting the injections. Your doctor should monitor your blood pressure and pulse and try to keep you as calm as possible.

Treatments for Dry AMD

I recently attended The Direct Dry AMD Meeting sponsored by Duke University. Ninety percent of people with AMD have the dry form and can lose vision from loss of photoreceptors and RPE. The cells are often lost in circular patches called geographic atrophy of the RPE. The patches usually start outside the center of the macula but then enlarge and coalesce. See eye with dry AMD below:

Currently there is no proven therapy to retard or stop the progression of atrophy. The beneficial affect of AREDS vitamins is mainly due to reducing the risk of developing the wet form of AMD and not in reducing the progression of atrophy. There are some trials that are now testing treatments aimed at slowing or stopping the progression of dry AMD:

Neurotech USA has developed a small tube that contains living cells and can be surgically implanted into the eye. The cells live in the tube and manufacture ciliary neurotrophic factor which is secreted into the eye. The hope is that this factor will retard the loss of cells in dry AMD. A Phase II study is underway and will involve a total of 48 patients although 12 of them will have a sham operation as a control. These patients will be followed for 18 months to see if the device has any affect on dry AMD.

Sirion Therapeutics is sponsoring a trial to evaluate fenretinide for the treatment of dry AMD. The drug is given orally and binds to retinol (vitamin A) which prevents it from entering the outer retina. This may seem counterproductive since retinol is needed to make rhodopsin which is the molecule that absorbs light and starts the process of seeing. Byproducts of rhodopsin metabolism however are toxic to the cell and patients with AMD often have an accumulation of these toxic byproducts. Reducing the amount of retinol entering the RPE seems to reduce the amount of these toxins. So perhaps depriving the eye of an excess of retinol may help retard the progression of AMD. Preliminary results of the 225 patients placed on fenretinide are expected in late 2008.

Othera Pharmaceuticals, Inc., is developing OT-551, which they describe simply as a small molecule that has anti-inflammatory, anti-oxidant, and anti-angiogenic properties. The molecule is given as an eye drop and Othera says it then penetrates back to the retina and choroid. OT-551 is being tested in two small studies on patients who have AMD.

The National Eye Institute is sponsoring a trial testing an eyedrop, OT-551, made by Othera Pharmaceuticals. The eyedrop has anti-oxidant, anti-inflammatory, and anti-angiogenic properties which could be beneficial in slowing the progression of dry AMD.

References

Lectures at the Direct AMD Meeting, October 25-27, 2007. Duke University., Durham, NC

Fluorescein Angiography in Pregnancy

I received the following question recently:

“..does anyone know if fluorescein is safe to use during pregnancy?”

The answer is that no one knows. Sodium fluorescein is a chemical dissolved in water that is injected into an arm vein. The photographs are taken using special filters which cause the chemical to absorb light at one wavelength and emit it at another one. The emitted light can be captured digitally or on film. A fluorescein angiogram is a good test to visualize normal and abnormal blood vessels in the eye as well as leakage from these vessels. It’s commonly used in people with AMD, diabetes, or other retinal vascular disease. Fluorescein does cross the placenta.

The only extensive article is referenced below (twice since the same article was published twice). This article resulted from compilation of a questionnaire survey of retinal specialists so it’s difficult to gauge the accuracy of the information. Nevertheless the specialists reported that they had performed an angiogram on a total of 116 pregnant patients. Three of the 116 had nausea during the procedure and an additional 4 had nausea and vomiting. One of the subsequent children was born with an undescended testicle and one had syndactayly (toes or fingers fused together).

Forty one of the 116 women had the angiogram during the first trimester of the pregnancy when there is the most risk of developmental malformations. Four fetal deaths occurred in these 41 women. Two were thought to be due to complications of severe eclampsia and not the fluorescein; one occurred months after the fluorescein angiogram; and one occurred three days after the fluorescein in a healthy woman who had been four weeks pregnant. The authors concluded that fluorescein angiography was safe in pregnancy because fetal deaths are not uncommon in severe eclampsia and there were only two mild malformations. Greenberg and Lewis later criticized the article stating that no firm conclusions could be reached from such a study.

Most retinal experts don’t perform fluorescein angiography on pregnant women. Almost always the diagnosis can be made from the clinical exam, plain color photography, and optic coherence tomography none of which involve any drug. The risk of congenital malformations or spontaneous abortions is probably low with fluorescein angiography but no one can say that it’s completely safe.

References

1. Halperin LS, Olk RJ, Soubrane G, Coscas G. Safety of fluorescein angiography during pregnancy. Am J Ophthalmol. 1990 May 15;109(5):563-6.
2. Olk RJ, Halperin LS, Soubrane G, Coscas G. Fluorescein angiography--is it safe to use in a pregnant patient? Eur J Ophthalmol. 1991 Apr-Jun;1(2):103-6.
3. Greenberg F, Lewis RA. Safety of fluorescein angiography during pregnancy. Am J Ophthalmol. 1990 Sep 15;110(3):323-5.