Understanding Eye Drops
Chat Highlights
July 6, 2005

On Wednesday, July 6, 2005, Dr. Jonathan Myers a glaucoma specialist at Wills, and the glaucoma chat group discussed "Understanding Eye Drops"

Moderator:  Tonight's topic is "Understanding Eye Drops."

Dr. Jonathan Myers:  I know that many of the people in this group have a lot of experience with eye drops for glaucoma.  What sort of questions or concerns would you like to discuss?

Moderator:  Dr. Myers, when you were in the chat room in 2003, you asked us to name the glaucoma eye drops we were using.  Xalatan seemed to be mentioned the most. Do you think that has changed?

Dr. Jonathan Myers:  Xalatan remains the single-most commonly prescribed eye drop for glaucoma.  The reason for Xalatan's success is that it is among the most powerful eye drops, yet has few and infrequent side effects.

P:  A clinical trial conducted at the University of Arizona Health Sciences Center and reported in the Journal of Glaucoma found that patients with glaucoma or elevated eye pressure are able to reduce their pressure more significantly with Lumigan (bimatoprost ophthalmic solution) than with Xalatan (latanoprost ophthalmic solution).  Have other studies confirmed that?

Dr. Jonathan Myers:  There have now been just a few quality studies comparing Xalatan and Lumigan.  In general, they are nearly equivalent.  However, at some time points within these studies, Lumigan has had the edge.  Lumigan, however, is more likely to cause redness and irritation than Xalatan.  That has limited its success over Xalatan.

P:  How long does it take for an eye drop to take effect after use has begun?

Dr. Jonathan Myers:  The prostaglandins -- Lumigan, Xalatan, and Travatan -- have both a short- and a long-term onset.  They seem to lower pressure even after the first dose.  Some patients, however, show a delayed response.

P:  Does the medication decrease the pressure the more it is used?

Dr. Jonathan Myers:  It seems that these medications may remodel the extracellular matrix in the ciliary body, allowing more fluid to drain from the eye.  So, some patients may take weeks to show the full effects of these medications.  Other medications, like beta- blockers (e.g. timolol), Alphagan, and Trusopt have a more rapid onset of complete action.

P:  Which medications used to treat glaucoma lower the pressure in the eyes by decreasing the amount of fluid produced by the eyes?

Dr. Jonathan Myers:  Fluid-reducing eye drops include Alphagan (brimonidine), Trusopt (dorzolamide), and Azopt (brinzolamide), as well as beta-blockers such as timolol, Timoptic, Istalol, Betoptic, Ocupress, OptiPranolol, Betagan, etc.

P:  Which medications lower the pressure by increasing the outflow of fluid?

Dr. Jonathan Myers:  The medications that increase outflow of fluid from the eye include the prostaglandins --Travatan, Xalatan, and Lumigan -- pilocarpine, and to a small extent, perhaps Alphagan (dual action).  Pilocarpine is not used as much anymore, because there are newer agents with fewer side effects.  Pilocarpine causes some people to have blurry vision, reduced night vision, and headaches.

P:  After I used Alphagan for one week, my intraocular pressure dropped from 18 to 17 mm Hg in one eye and from 23 to 20 mm Hg in the other eye.  Will the pressure continue to drop as I use it more or will it stay at that level?

Dr. Jonathan Myers:  After a week of consistent usage, most people have reached their maximum response to Alphagan.  There are exceptions, but generally, by a week the drug is fully absorbed.

P:  For some patients, don't glaucoma eye drops become less effective after a while?

Dr. Jonathan Myers:  Many drugs lose their effect over time, including the beta blockers, such as timolol, and Alphagan.  It is unclear to what extent the prostaglandins lose their effect over time.  So far, studies have shown that they have less of a tendency to do that.  However, in general, that is a difficult question, as some glaucoma becomes more difficult to control with time.

Moderator:  Isn't Alphagan an adrenergic agonist?  Is that the same class as Xalatan?  What's the difference between the two?

Dr. Jonathan Myers:  Alphagan is an adrenergic agonist.  Xalatan and the other prostaglandin analogs work by a different mechanism.  Alphagan, or brimonidine (generic), binds to alpha-two receptors, reducing aqueous formation.  Xalatan and the other prostaglandin analogs enhance certain proteinases that affect fluid outflow from the eye.

P:  How many different drops can be used by a patient at one time?

Dr. Jonathan Myers:  Clinicians try to minimize the medications needed, while adequately controlling pressure. For some patients, one agent is enough.  However, many need two or even three.  Nationally, at least half of all patients are on more than one medication.  If more than two medications are needed, it may be worth considering laser trabeculoplasty (ALT/SLT) for open-angle glaucoma, to reduce the medication burden.

P:  Is there ever any reason to use two glaucoma medications of the same class?

Dr. Jonathan Myers:  It is a rare case, indeed, that would require two medications from the same class.  Right now I'm hard pressed to say why one would do that, but every patient is different, and perhaps there is a good reason for someone out there.

P:  If a patient is using several different eye drops, how would the doctor know which one is losing its effectiveness?

Dr. Jonathan Myers:  Knowing which drugs are effective and to what extent can become very, very complicated.  You may have heard of monocular trials, in which a new drug is started in one eye at a time, and the other eye is used as a "control" to assess the pressure effect.  Well, you can also do a monocular discontinuation trial, stopping one medication in one eye to assess the effectiveness. In practice, we docs probably do not do this often enough.  Juggling medications, however, can become confusing for patients and requires extra visits to measure the pressure.

P:  Does Cosopt also reduce the amount of fluid in the eye?

Dr. Jonathan Myers:  Cosopt, a combination of Trusopt (a carbonic anhydrase inhibitor) and Timoptic (a beta blocker), reduces fluid production by the eye, reducing pressure.  Both medications reduce the production of fluid.

P:  Are beta-blockers available as generic drugs?

Dr. Jonathan Myers:  Beta-blockers, like Timoptic, are now available in generic form (timolol).  The generic forms tend to be just as effective and are often much cheaper, which helps those for whom cost is a problem.

P:  Does refrigerating Lumigan harm its effectiveness?

Dr. Jonathan Myers:  To my knowledge, refrigeration will not harm any of the current eye drugs.  Refrigeration does extend shelf life. Xalatan has only about a three-month shelf life without refrigeration.  So, until the bottle is opened, it should be refrigerated. Once opened, Xalatan really can't last long enough to go bad, so there's no need to refrigerate it.  Some patients like to refrigerate eye drops so that they can feel the drop when it makes contact with the eye.

P:  Are two drops of Alphagan the most that can be used to lower pressure?

Dr. Jonathan Myers:  Alphagan is FDA approved for three-times-a-day dosing.  However, most patients do almost as well with twice-a-day dosing.  Because of that, in Europe it was approved for twice-daily dosing (every 12 hours).  If it is unclear if twice a day is sufficient, we often check the pressure at the end of the day, after an early morning dose, to see if the medication is lasting long enough. If the pressure is high, then it is worth trying three times a day dosing.

P:  Can Xalatan cause increased growth of eyelashes as well as increased hair growth on other parts of their body, such as the face and legs. Is that common?

Dr. Jonathan Myers:  Increased eyelash growth is a common side effect with Xalatan, Lumigan and Travatan.  Usually, such growth is confined to the lashes.  Rarely, it can affect the cheeks. I have not yet seen it occur all over the body, but anything is possible.

P:  Xalatan does have a side effect that concerns me, which is its ability to change the color of the iris in some cases. Is it known whether the change in eye color will have any negative effect on vision later on?  Do you think the increase of melanin that Xalatan causes (or may cause) plays a role in the medication's ability to lower IOP?

Dr. Jonathan Myers:  The change in iris color caused by the prostaglandin analogs has been studied quite a bit.  The eye color change is most common in hazel, green, or mixed-color eyes, and uncommon in solid blue or dark brown eyes. The change in color results from increased melanin granules and appears to be cosmetic only.  So far, no definite tie to the intraocular-pressure-lowering effect has been demonstrated, although that remains a possibility.

We now have about 10 years of experience with Xalatan and more than 15 years with Rescula, a weaker prostaglandin analog first licensed in Japan.  To date, no long-term trends for vision loss have been shown with these agents.  Serious side effects, both to vision and to the whole patient, seem to be rare with the prostaglandin analogs.  That accounts, in part, for their huge popularity in the last three to six years.

P:  Why don't ophthalmologists ever discuss depression caused by some glaucoma eye drops?  Depression is a listed side effect for several of them.  (Most glaucoma patients don't know that can be a side effect.)

Dr. Jonathan Myers:  That is a really important point.  Doctors, in general, probably should spend more time discussing medication side effects with patients.  Depression has been reported with the beta- blockers and the carbonic anhydrase inhibitors (Trusopt, Azopt), although that is rare.  So, especially in patients with a history of depression or a new episode of depression, it's important to bring this up.  Alphagan can cause fatigue, but it's unclear whether it ever causes depression.

P:  I have been using one drop of Xalatan once a day for several years.  My IOP has been running 17 mm Hg. Recently, after cataract surgery, my IOP was 20 mm Hg.  Today, seven days later, my IOP was 16 mm Hg.  Can I expect a further drop?

Dr. Jonathan Myers:  IOP reduction after cataract surgery is common. In patients with early or mild glaucoma, the pressure often drops after cataract surgery.  However, in patients requiring two or more medications, or with advanced glaucoma, the pressure may increase after cataract surgery, sometimes dramatically.

For this reason, some patients are better off having combined cataract and glaucoma surgery to protect the pressure.  However, with cataract surgery alone, the recuperation tends to be quicker and the complications fewer, so in many cases cataract surgery alone may be the best choice.

P:  My IOP came down after cataract surgery and has stayed down for 18 months, enough so that I don't need drops.

Dr. Jonathan Myers:  In my experience, the time course of the IOP reduction reaches a maximum within one month after surgery in most cases.  A drop of 2 to 5 points is typical, although occasionally we see more.  The effect of cataract surgery on IOP has been compared to that of laser trabeculoplasty (ALT/SLT) and may be related to the inflammation around the time of surgery.

P:  In advanced glaucoma, why would cataract surgery cause an increase in IOP?

Dr. Jonathan Myers:  During cataract surgery, some microscopic fragments of the lens, some of the liquids used, and inflammatory debris may clog the natural drainage channel.  In advanced glaucoma, the drainage channel has reduced capacity and seems more easily overwhelmed at the time of cataract surgery.  Rarely, pressure spikes may reach 40, 50, or even 60 mm Hg. Usually these spikes are short-lived; rarely they require semi-emergent glaucoma surgery.

P:  Then why doesn't the IOP also increase in early glaucoma after cataract surgery?

Dr. Jonathan Myers:  In early glaucoma, it may be that the drainage channel still has sufficient reserve capacity to handle the increased load.  We're not really sure.  Since IOP spikes are not that common, and since no one wants to risk their patients, there have not been any "definitive" studies

P:  After cataract surgery on my right eye on May 2 this year, I used prednisolone (Pred Forte), Acular, and Zymar in the right eye, and timolol in both eyes.  After seven weeks, my lower eyelids puffed up.  There was no pain, no itching.  Could the several drops have caused the swelling?

Dr. Jonathan Myers:  Seven weeks is a bit surprising.  Usually by that point, patients are off most drops, so it's hard to be sure.  Allergies to eye drops, however, are a common cause of swelling.

P:  My doctor says I have inflammation after the cataract surgery, hence the extended course of Pred Forte and Acular.  I am concerned about using steroids that long.  How else could I handle the inflammation?

Dr. Jonathan Myers:  Occasionally, prolonged inflammation may require long courses of treatment, even several months.  In most cases, the most worrisome side effects -- increased intraocular pressure, cataract, and infection -- can be monitored.  The risk of infection is very, very small.  If you've had cataract surgery, then you don't have to worry about cataract. If you've had glaucoma surgery, then IOP increases are very uncommon.  Inflammation itself, if not treated, can lead to increased IOP and cataracts, so you are usually better off controlling the inflammation, but I understand your concern.

P:  Is there a medication stronger than Acular for eye discomfort?

Dr. Jonathan Myers:  Acular, a topical nonsteroidal eye drop, can help with allergies or certain types of eye pain.  It is often used after LASIK to reduce eye pain.  Other medications in this class include Voltaren and Ocufen.  There is a new entry in this class, Zybrom, which is approved for only twice-daily (as opposed to four times daily) use. It's not clear that it is stronger.

P:  Is the size of a drop pretty constant, given viscosity, so that there are about 20 drops per ml, whatever the shape of the bottle and nozzle?

Dr. Jonathan Myers:  Eye drop size varies with viscosity and bottle design.  All eye drops are larger than the eyelid can retain, so the extra amount runs out.  That is okay, since it only takes a tiny amount to get a sufficient effect on the eye.

Eye-drop size is closely considered by drug and insurance companies, in terms of drops per bottle and the number of bottles allowed.  That has the unfortunate effect that some patients, who sometimes miss getting the drop in the eye, run out of drops before they are allowed to refill the prescription.  And some insurance companies and pharmacies won't let them refill, because it's not "time" yet!

Moderator:  Dr. Myers, thanks for coming tonight, even with your hectic schedule.  Patients here still have lots of questions on this topic, so maybe you will return when time permits.

Dr. Jonathan Myers:  I'd be happy to return.  Sorry again for my delayed arrival, and thanks to everyone for participating.

On July 13, Dr. Wilson discussed "The Role of Blood Flow in Glaucoma" in the Chat room. Click here for highlights of that meeting.

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