Glaucoma Medications
Chat Highlights
December 7, 2011

On Wednesday, December 7, 2011, Dr. Anand Mantravadi, a glaucoma specialist at Wills, and the glaucoma chat group discussed "Glaucoma Medications".

Moderator: Tonight our topic is “Glaucoma Medications”. We are joined again by Dr. Anand Mantravadi.

P: Would you please run through the classifications of glaucoma medications and explain how each one helps in lowering eye pressure?

Dr. Anand Mantravadi: There are several classes of glaucoma medications available that work on different aspects of aqueous humor dynamics to lower eye pressure as follows:

1. Drugs that affect aqueous humor inflow or decrease aqueous production: include beta blockers, alpha-receptor agonists, and carbonic anhydrase inhibitors
2. Drugs that affect trabecular outflow: such as pilocarpine
3. Drugs that increase what is known as uveo-scleral outflow: prostaglandins like latanoprost, travoprost, and bimatoprost.

P: Can a drop from each drug family be simultaneous prescribed to lower intraocular pressure?

Dr. Anand Mantravadi: Generally, it is nice to have complementary mechanisms of action. That being said, more than one medication belonging to the same class (particularly the drugs that decrease aqueous humor formation) can be prescribed.

P: Is there a maximum number of glaucoma eye drops a patient can use at once?

Dr. Anand Mantravadi: The term "maximal medical therapy" has a broad meaning. There are patients who maybe on many medications (i.e. four different drops), and controlled well; however, there are patients who maybe on many medications and not be well controlled.

P: Are the same drugs prescribed for those with ocular hypertension as well as those with glaucoma?

Dr. Anand Mantravadi: Yes.

P: Is it typical to develop allergies or immunities/tolerances to some medications?

Dr. Anand Mantravadi: It is indeed possible to develop an allergy or "immunity" or "tachyphylaxis" (meaning a medication can lose its effect with time) to any of the medications. Some medications have a higher overall allergy incidence, but it can be very individualized.

P: If a patient has both ocular and systemic hypertension but nocturnal low systemic pressure, how can a medication be given to lower IOP?

Dr. Anand Mantravadi: If one has ocular hypertension, and one wishes to lower eye pressure while minimizing nocturnal dips in systemic blood pressure, one can avoid the beta blocker class and choose another class of medication such as the prostaglandin.

P: Can Dorzolamide and timolol and be prescribed simultaneously? Is it a combo drug?

Dr. Anand Mantravadi: Yes, it is made in a fixed combination drug (both medications together in the same bottle).

P: What sort of systemic effects are of particular concern when taking drops? I am most concerned about Timolol, being a beta-blocker.

Dr. Anand Mantravadi: Every drop has a certain profile of possible side effects. Beta blockers can exacerbate asthma/COPD, or slow heart rate, along with exercise intolerance. Also impotence is rarely possible.

P: Should glaucoma medications be refrigerated when not in use?

Dr. Anand Mantravadi: Generally speaking, most manufacturers don't mandate refrigeration.

P: Can a beta blocker eye drop be taken at night with a night time oral medication to lower blood pressure?

Dr. Anand Mantravadi: Beta blockers can be prescribed up to twice daily topically, but generally once in the morning is sufficient to observe the effect.

P: Do you have your patients practice punctal occlusion? Can it really make a difference?

Dr. Anand Mantravadi: Absolutely. Let’s look into how much of a drop actually stays in the eye. The pocket of your eyelid can generally hold seven to nine micro liters and maximally up to 30 micro liters of a drop. A commercial drop size ranges from 25-55 micro liters. Therefore one half of the drop can spill out from the lids. Punctal occlusion prevents passage of the excess drop into your tear ducts, and improves the effective time on the eye, enhancing possible penetration of the drug, and therefore effectiveness.

P: Should a bottle of glaucoma eye drops be discarded after three months once opened?

Dr. Anand Mantravadi: I'm not aware of a hard-line three month time period once opened. I would generally defer to the manufacturer recommendations that may have tested the stability of the compound with time.

P: I've been on glaucoma medications for ten years. I am currently on Lumigan, Combigan, and Restatsis and keep getting blebhartis from the preservatives. I also have terrible dry eye. What are your thoughts on getting compound medicines without preservatives?

Dr. Anand Mantravadi: The role of preservatives and associated problems of the ocular surface like dry eye is an area of intense research. It's a double edged sword, in that the medications are effective, but can exacerbate dry eye, and possible eyelid problems. Fixed combination medications without preservatives are currently not available in the United States.

P: Do generic drops have the same effectiveness?

Dr. Anand Mantravadi: The short answer is we are not hundred percent sure. The active ingredient is the same, and in general a generic must prove to be similar in efficacy. That being said, for some individuals, the generic does not work as well, and for others it does. It's very individualized.

P: Some drops have directions with specifics as to temperature when storing. What happens if the temperature rises and you forget? Do they lose potency? If the drops are exposed to a higher temperature than directed, then later exposed to a lower temperature, will this be of any help? Drops are so expensive!

Dr. Anand Mantravadi: These drops have those recommendations usually because of rigorous testing during the process of development. Extremes of temperature may possibly affect the drop efficacy.

P: ROCK inhibitor AR-12286 by Aerie Pharmaceuticals is said to be in Phase 2. What makes this drug different than the others already on the market?

Dr. Anand Mantravadi: ROCKi s a rho-kinase inhibitor. Research is ongoing on Rho-kinase inhibitors which is believed to affect the trabecular meshwork, making it more amenable to aqueous outflow.

P: Are there any drugs in the developmental pipeline that would work to combat pseudoexfoliation specifically? Is there any known way the debris accumulation could be lessened or dissolved?

Dr. Anand Mantravadi: I am not aware of a pharmacologic agent that can specifically reduce the process of exfoliation. Most medications are geared at the effect of exfoliation and the elevated IOP.

P: I thought I read somewhere on this website that there was a pharmacy in San Jose, California that made compound glaucoma drops?

Dr. Anand Mantravadi: Yes, there are compounding pharmacies that can prepare preservative free versions of some medications that are not commercially readily available in specific instances.

P: If an allergy develops, could changing drops for a few months or years and then changing back be a possibility? Or do you tend to stay away from medications patients have previously developed allergies to?

Dr. Anand Mantravadi: Depending on the nature of the allergy, I tend to avoid agents that have been tried in the past that have invoked an allergic response.

P: Do you know of research being done on the effects of drops on Schlemm's canal/trabecular meshwork? Isn't that the reason the eyeball gets "clogged" and high IOP results?

Dr. Anand Mantravadi: As mentioned, there are compounds being tested that may affect the trabecular meshwork and Schlemm's canal permeability to ultimately affect IOP. These are in the study phases.

P: After an initial diagnosis of NTG what conditions would cause a doctor to recommend laser rather than drops to start?

Dr. Anand Mantravadi: Studies have demonstrated that SLT can be equally safe and effective as starting a medication, and as initial therapy, it can be a good option. Drops are also a good option for initial therapy. The pros and cons of each need to be weighed, and an individualized treatment plan chosen which will differ from person to person.

P: Is it possible to develop a tolerance to a glaucoma medication so that it no longer works?

Dr. Anand Mantravadi: Yes.

P: Are there any other new drugs on the horizon?

Dr. Anand Mantravadi: Possibly. There are preservative free versions of some of the drug classes currently available. Rho Kinase inhibitors and adenosine compounds are in the research phases. There is a significant amount of research on various methods of drug delivery rather than drops that may prove to be a major advance. Only time will tell.

P: Do you see any hope in the future for not having to rely on eye drops?

Dr. Anand Mantravadi: I hope that there will be advances in drug delivery. Perhaps a long acting depot medication, or something implantable, that releases medication slowly. A major difficulty in the treatment of glaucoma is having to rely on the medication that has costs, and many have difficulties incorporating and remembering to take their drops. Another way to deliver medication would be a major step for glaucoma care.

P: Are there any medications to reduce scarring after trabulectomy.

Dr. Anand Mantravadi: Prednisolone and topical steroids can reduce scarring or "fibrosis' in the early stages following trabeculectomy. If scarring has developed, some anti-metabolites such as 5-Fluoro-uracil or mitomycin can be used along with a procedure called “bleb needling” to break up scar tissue.

P: Some drops have side effects like Lumigan and skin darkening. Is this because a drop spills out on installation? Are there any medications to lower IOP in ointment form?

Dr. Anand Mantravadi: The exact reason why prostaglandins can in some susceptible people induce pigment changes is not well understood. This can be minimized by preventing excess of the medication from contacting the periocular skin. There is a more viscous version of the betablocker class that is in a gel-forming solution that can increase contact time with the eye.

P: Have you ever witnessed a patient having a normal-range IOP by substituting medication for a healthy lifestyle (i.e. exercise, eating right, and meditating).

Dr. Anand Mantravadi: Physiologic well being can lower IOP and is encouraged. As far as eye pressure, I haven't personally seen someone eliminate a drop due to a lifestyle change, but this will definitely benefit other aspects of one's well being and overall fitness.

P: One of my medications, Azopt, has to be shaken. Is it possible that that towards the end of the bottle the medication is not as effective? I seemed to have experienced that with my Pred-Forte. I do shake when the directions indicate this.

Dr. Anand Mantravadi: Azopt and Pred-Forte are suspensions. I'm not sure about the effectiveness at the end of the bottle, but that could be possible.

P: Can you elaborate the pros and cons of preservative free medicines?

Dr. Anand Mantravadi: Many tolerate preservatives just fine. Some people have difficulties with preservatives commonly found in topical medications. There are different preservatives used such as BAK, Sofzia, and Purite.
If preservatives are thought to be worsening the ocular surface, like making dry eye worse, then a medication with a different preservative can be tried or if a beta-blocker, a preservative free version can be explored.

P: What causes disc hemorrhages and is there any medication that can eliminate this?

Dr. Anand Mantravadi: There is no medication that can "eliminate" a disc hemorrhage. Disc hemorrhages are thought to be a negative prognostic factor for glaucoma. In other words, the presence of recurrent disc hemorrhage may suggest that more intensive IOP control may be required.

P: What about effects of drops on the actual optic disk/nerve? Are there any studies that you know of that help regenerate nerves via eye drops?

Dr. Anand Mantravadi: I am not aware of current studies testing medications on tissue regeneration to be used topically for glaucoma at this time.

P: Thanks. I keep seeing ads for Restasis. Can you explain why it would be used instead of drops? Is it more effective?

Dr. Anand Mantravadi: Restasis is an “immunomodulator” that can increase tear production in people with dry eye, usually with some inflammatory component. The treatment for dry eye includes warm compresses, artificial tears (preferably preservative free) and sometimes thicker versions for night time, fish oil, flax seed oil and omega fatty acids. Treating and managing blepharitis is helpful for dry eye.

Moderator: Just one more question. What about tears in between drops?

Dr. Anand Mantravadi: I would wait at least five and preferably ten minutes following instillation of a medication with punctal occlusion before placing a tear.

Moderator: Thank you Dr. Anand for a very informative chat and thank you chatters for such good questions!

Dr. Anand Mantravadi: Thanks and have a great night.

Click here for the most recent glaucoma chat highlights and links to the chat archives.

Click here for upcoming glaucoma chat events.