Techniques modified to prevent IFIS in tamsulosin users

The use of tamsulosin to treat prostate enlargement and urinary symptoms has recently been linked with an elevated risk of complications after cataract surgery. New Primary Care Optometry News Editorial Board member John A. Hovanesian, MD, FACS, interviewed David F. Chang, MD, about identifying the condition and management strategies.

David F. Chang

John A. Hovanesian

John A. Hovanesian, MD, FACS: Intraoperative floppy iris syndrome (IFIS) has changed the way we think about cataract surgery, and you brought its attention to the world first. Tell us how it came about.

David F. Chang, MD: This was an interesting association that was first suspected by another ophthalmologist in northern California. John R. Campbell, MD, and his staff actually made the connection. He was concerned that some of his patients were not dilating well, and he wanted to know what was different about them. One of the staff members noted that many of those patients were taking Flomax (tamsulosin, Boehringer Ingelheim). With that information he asked me if I had seen this.

When I looked at some charts of patients I recalled with floppy irises, there definitely was a connection, although it did not seem to be everyone. So we set out to do some studies to try to determine whether tamsulosin was truly a causative factor, what other factors existed and to define exactly what this syndrome was. That was the basis of our original report and our paper in the Journal of Cataract and Refractive Surgery in 2005.

Dr. Hovanesian: Not everyone who takes Flomax develops IFIS. How often does it happen?

Dr. Chang: We have learned that there is a broad spectrum of severity to this condition, and we ought to think of it as being mild, moderate or severe. If we look at the classic triad of billowing of the iris, progressive miosis during surgery and a strong tendency for iris prolapse, the most severely affected eyes manifest all three signs. You see just the billowing in some eyes. There are some in which you see just some billowing and a little bit of miosis, and these would be characterized as being mild to moderate.

I organized a large prospective trial among 10 different centers in the country, and we consecutively enrolled more than 160 eyes of patients taking tamsulosin and having cataract surgery. When you use these types of definitions, about 90% of all patients had at least some form of IFIS, even if it was mild. A much greater percentage, though, had the moderate to severe form of IFIS.

Dr. Hovanesian: Since you brought it to the world’s attention, most of us who do cataract surgery have certainly seen this in our patients and are grateful to have at least some fair warning for those tamsulosin patients. Why is tamsulosin more prone to cause IFIS than other alpha blockers?

Dr. Chang: Originally we just saw the connection that tamsulosin is an alpha-1 blocker, and the alpha-1 receptor is well characterized in the prostate. There are three subtypes of the alpha-1 receptor: 1A, 1B and 1D, and the reason that tamsulosin is the No. 1 prescribed medication for benign prosthetic hyperplasia is that it is selective for the alpha-1A subtype. This receptor predominates in the prostate, and it makes the drug more uroselective, making patients less likely to have postural hypotension compared with the nonselective alpha blockers such as Hytrin (terazosin, Abbott Laboratories), Cardura (doxazosin, Pfizer) or Uroxatral (alfuzosin, Sanofi-Aventis). So it was interesting that in the iris, the alpha-1A subtype is also the most predominant receptor; however, if it is going to be blocked by a nonspecific drug as well, theoretically tamsulosin, terazosin, doxazosin and alfuzosin should all be about equivalent.

I have been convinced all along that this was far more common with tamsulosin than with the nonspecific alpha blockers, and there are several studies now that have supported this. The most notable is a paper that was published in Journal of Cataract and Refractive Surgery by Blouin and colleagues indicating retrospectively that the incidence of IFIS was much higher among tamsulosin cases vs. alfuzosin cases.

More recently, I have collaborated with a basic science group in Europe that has for the first time performed animal studies comparing the effects of alpha blockers on the iris dilator muscle. These experiments are similar to those in which the pharmacology of alpha blockers in the prostate were studied and they, interestingly, have shown that tamsulosin has a much greater antagonistic effect on the iris dilator muscle in rabbits than does alfuzosin.

So, on the basis of this it looks as though there are other alpha blockers that are effective for benign prostatic hyperplasia (BPH) (for example, alfuzosin is also a uroselective blocker), and it appears that these agents can treat BPH without causing IFIS to anywhere near the degree that tamsulosin does.

Before surgery

Dr. Hovanesian: When we first became aware of IFIS, the reaction was to stop the tamsulosin some time before cataract surgery. That does not seem to work very well, does it?

Dr. Chang: No. I think we have all seen situations in which patients have been off of tamsulosin for even up to several years and yet still manifest a classic, severe IFIS. So we certainly cannot rely on stopping the drug to make any difference. I routinely now do not have patients alter their BPH medications or stop them, and I would choose instead to rely on surgical strategies to help me through the case.

Dr. Hovanesian: It also does not seem to matter how long they were on tamsulosin, does it?

Dr. Chang: That is a good question. Several studies have tried to look at whether the dose or duration of the drug had some correlation with the incidence and severity of IFIS, and no one has found any. So, at one extreme we have had patients who have been off of tamsulosin for up to 3 years who still show IFIS. There is also a good anecdotal report of a patient who did not have IFIS in the first eye during surgery and then had the other eye done a month later with classic IFIS, with the notable development that he had been placed on tamsulosin 2 weeks after surgery on the first eye. That is a well-documented case in which taking tamsulosin for just 2 weeks produced a classic IFIS.

Dr. Hovanesian: If I have a patient contemplating surgery and we discover that tamsulosin is part of his medication regimen, how should I counsel the patient?

Dr. Chang: I usually tell people that they have been taking a drug that can make cataract surgery a little bit more difficult, but that we have some effective strategies that will allow us to do the procedure with an excellent prognosis and that it is not necessary for them to discontinue the drug. The important thing is that we know about it in advance and we can anticipate what needs to be done.

Pharmacologic approach

Dr. Hovanesian: Are there other measures to optimize the outcome?

Dr. Chang: There are a lot of different ideas for managing IFIS, and people have reported varying success with them. I would divide them into primarily three categories. One is pharmacologic, one is the use of viscoadaptive or specialized viscoelastics or ophthalmic viscosurgical devices (OVDs) and one is using some type of mechanical dilating devices at the time of surgery. It is important for surgeons to be familiar with all of the different methods. The surgeon can come up with his or her own algorithm for starting the case and then, if necessary, go to different adjunctive techniques if the pupil is not large enough.

I will address the pharmacologic approach. Samuel Masket, MD, first proposed using preoperative topical atropine, with the objective of knocking out the pupillary sphincter muscle. A wonderful approach has been intracameral alpha agonists. Richard Packard, MD, came up with the idea of intracameral phenylephrine, and later on Joel K. Shugar, MD, MSEE, did some work with intracameral epinephrine.

My experience has been that with a mild to moderate case of IFIS in which the pupil dilates reasonably well, injecting epinephrine often will improve the pupil dilation. But even if it does not, it seems to tense up the iris dilator muscle, restoring the normal rigidity to the iris during surgery and making it much less likely to prolapse and billow. This is something that you can do on virtually all patients at risk of IFIS, but I would certainly employ this in a case that I expect to manifest mild IFIS. This is a patient who is on tamsulosin but dilates well preoperatively, indicating reasonably good iris dilator muscle function.

Dr. Hovanesian: So, pharmacologic intervention would be appropriate in a mild case. Now, you mention mild vs. presumably moderate or severe cases as measured preoperatively. Is dilation the only characteristic that can indicate the level of severity?

Dr. Chang: Other than having previous experience with the opposite eye, the best way to try to predict who might have mild, moderate or severe IFIS is to evaluate how well the patient dilates immediately before surgery. The smaller the pupil, the more likely it is to be severe IFIS. Another tip is when you first inject some intracameral lidocaine, you will often see the billowing immediately. If so, you should anticipate a more severe degree of IFIS. Finally, if you have a patient who has stopped tamsulosin or is perhaps on one of the nonspecific alpha blockers, any resulting IFIS is much more likely to be moderate or mild.

Ophthalmic viscosurgical devices

Dr. Hovanesian: How about OVDs and their role?

Dr. Chang: Robert H. Osher, MD, and Douglas D. Koch, MD, were among the first to suggest using the viscoadaptive OVD Healon5 (2.3% sodium hyaluronate, Abbott Medical Optics) because it is so dense a material that it pushes back the iris and pushes the pupil open. This is an effective technique at blocking the iris from either constricting or prolapsing up to the incision. You have to alter your phaco parameters by using a low aspiration flow rate and a low vacuum, and this is not something that all surgeons are necessarily comfortable with.

Dilating devices

Dr. Hovanesian: Dilating devices are the last resort to control the iris movement. At what point during surgery, when you see that billowing and perhaps miosis develop, do you determine that you need to use one?

Dr. Chang: If you are going to use a mechanical dilating device, such as a pupil expansion ring or iris hooks, it is nice to do this before you start the capsulorrhexis so there is no danger of hooking the anterior capsular edge. This is where anticipating severe IFIS is helpful and where I probably would just go straight to mechanical devices.

One advantage of these is that, for most surgeons, they do not require a change in their technique. You do not have to wonder if it will turn into a more severe case of IFIS. This will be 100% reliable at keeping the iris open, which is certainly a consideration if you have other co-existing risk factors such as a brunescent lens or pseudoexfoliation or a patient with only one eye. Everyone can use iris retractors, and they deserve a good look.

For more information:

• David F. Chang, MD, can be reached at 762 Altos Oaks Drive, Suite 1, Los Altos, CA 94024; (650) 948-9123; fax: (650) 948-0563; e-mail: dceye@earthlink.net. Dr. Chang receives consulting fees from AMO and Alcon that are donated to the Himalayan Cataract Project.
• John A. Hovanesian, MD, FACS, is a Primary Care Optometry News Editorial Board member. He can be reached at Harvard Eye Associates, 24401 Calle De La Louisa, Suite 300, Laguna Hills, CA 92653; (949) 951-2020; fax: (949) 380-7856; e-mail: drhovanesian@harvardeye.com.

References:

• Blouin MC, Blouin J, et al. Intraoperative floppy-iris syndrome associated with alpha1-adrenoreceptors: comparison of tamsulosin and alfuzosin. J Cataract Refract Surg. 2007;33(7):1227-1234.
• Chang DF, Campbell JR. Intraoperative floppy iris syndrome associated with tamsulosin. J Cataract Refract Surg. 2005;31(4):664-673.
• Chang DF, Osher RH, Wang L, Koch DD. Prospective multicenter evaluation of cataract surgery in patients taking tamsulosin (Flomax). Ophthalmology. 2007;114(5):957-964.