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Pearls in Medical Management of Glaucoma

Mark

Dr. Mark Werner,M.D.

 

Glaucoma is a disease of the optic nerve with a particular pattern of peripheral vision defects and morphologic changes.  The vast majority of patients suffer from damage because the intraocular pressure is too high for their optic nerve.  The only treatment we have that is currently effective in stabilizing the disease involves lowering of intraocular pressure.  Therapies can be separated into medicine, laser, and surgery.  Young children are generally treated primarily with surgery, as their disease may be often cured with an intervention with minimal long-term consequences, and medical therapy is more difficult.  Some cases of angle closure may be treated effectively with laser iridotomy.  There may be a role for primary laser trabeculoplasty in some patients with open-angle glaucoma 1.  However, the majority of patients with glaucoma are first treated medically.  This review focuses on open angle glaucomas in adults.  Some ocular conditions (i.e. angle closure, uveitis) associated with glaucoma have specific medical therapies which will not be addressed here.
               

Medical therapy may carry very little risk for the patient, as long as relevant contraindications are respected.  Medical therapy may be effective in a high percentage of patients, as was demonstrated in the CIGTS study 2 (though some patients were given a low-risk laser trabeculoplasty in conjunction).  Surgery may be highly effective in many patients; however, a significant minority of patients may have a rocky postoperative course, potentialy require more surgery, and even lose vision.  For this reason, surgery is usually undertaken after medical therapy has failed.  There are specific challenges associated with medical therapy.  The astute clinician can often identify barriers to successful medical management and intervene successfully to avoid other interventions. 

Noncompliance is a big issue, and often unappreciated by the treating clinician3.  In order to elicit a history of noncompliance, a nonjudgmental approach is essential4.  If the doctor seems understanding and cooperative, as opposed to confrontational and authoritative, the patient is more likely to be forthcoming in admitting lapses in therapy.  Questions such as “How often do you miss your medication?” are more effective than “Do you miss your medication?”  Apparent ineffectiveness of a medication may be the first sign of noncompliance.  Pharmacy refill histories may now be elicited with the use of some newer electronic systems.  Signs such as eyelash growth or redness due to prostaglandin use, as well as pupillary miosis with pilocarpine therapy, may indicate objectively that the patient is actually using their medication.
Proper patient education is essential to good compliance.  Each patient should understand the goal of therapy, the proper dosing schedule, and the need for continued treatment and monitoring.  Prescriptions should be kept up to date, and patients should know to call several days before running out of a medicine.
Proper technique for eye drop placement should be taught as well.  Alan Robin, Gary Novack and colleagues recently demonstrated a high level of difficulty with drop placement among chronic glaucoma patients, particularly in the elderly and those with advanced vision loss 5.  The clinician or ancillary staff should demonstrate the proper head and hand positioning and observe the patient place drops in the exam chair.  Latanoprost has a dosing aid available which may help some patients.  If the patient fails to demonstrate proper drop placement, either someone else must place eye drops for the patient, or surgical and laser treatments must be considered along with their attendant risks.

Cost of medications can be prohibitive for some patients.  Obtaining a history of out-of-pocket expenses associated with medications, as well as insurance coverage for generic and brand name medications, will help tailor therapy and also foster a good doctor-patient relationship.  Limiting drop use to the minimum necessary also may help patients afford necessary medications.  Blind eyes can often be weaned off of eye medications.  Timolol solution may be just as effective given once in the morning as twice daily dosing in many cases 6.  Topical beta blockers may not have as much benefit when added to systemic beta blockers 7.  The advantage of adding a third or fourth medication may also be negligible8, and one of the weaker medicines may often be stopped on a trial basis.  Patients with unilateral glaucoma or ocular hypertension may be overtreated in one or both eyes; in some cases medications can be cautiously withdrawn under observation.  On the other hand, it should also be considered that patients on at least one medication may be more likely to take their disease seriously and follow up appropriately 9.  Expensive combination drops may have been prescribed without first assessing the efficacy of the cheaper individual component medicines. 

Patients may run out of eye drops each month before they can obtain another bottle of medicine.  Providing an occasional sample bottle can supplement a patient’s medication supply enough to bridge the gap.  In addition, review of proper drop placement may help patients to avoid wasting eye drop solution.  Keeping drops refrigerated can alert patients when a drop first hits their eye to prevent wastage.  Having another person place the drops can also help patients conserve drops, if this is an option.
Simplifying a regimen may help some patients comply better with therapy.  Once daily dosing is associated with improved compliance10.  Prostaglandin analogues and beta blockers may both be given once daily.  Beta blockers are quite efficacious and often inexpensive, but are contraindicated in patients with reactive airway disease, bradyarrhythmias, and perhaps depression.  Protaglandins are very potent in lowering IOP, but they can sometimes permanently darken iris color. 

Associating drops with another common daily activity, such as brushing teeth, helps patients to establish a routine.  Patients on multiple drops can be assured that a 5 minute interval between drops is sufficient in order to accommodate a busy schedule.  If a patient is hurrying out the door, under extreme circumstances multiple drops can be placed within a shorter interval.  Simple eyelid closure may be just as effective as punctual occlusion in increasing intraocular absorption 11.  However, patients should understand that it’s better to get the drop in and go about their business than to miss a dose entirely.  Eye drop schedules may need to accommodate school or work schedules, and the clinician should try to help patients accommodate necessary schedule limitations.  When more than one medication is necessary, a combination drop may also facilitate proper usage; however, it should be demonstrated that each medication is both effective and necessary. 

Medication tolerance should be actively assessed on each patient encounter.  In patients with intolerance to multiple eye drops, benzalkonium chloride allergy should be considered, and drops with alternative preservatives considered, including preservative-free timolol vials, alphagan P with purite (Allergan Inc.), and travatan Z (Alcon labs).  Other ocular comorbidities, such as dry eyes and blepharitis, should also be addressed.  Oral agents such as methazolamide can bypass problems with topical drop use. 

Aside from preservative issues, each ocular medication carries its own side effect profile.  In addition to aforementioned contraindications, beta blockers can also cause sexual dysfunction.  Brimonidine is a frequent cause of topical allergies, whether given alone or in combination with timolol 12.  Follicular conjunctivitis, sometimes involving the bulbar and palpebral conjunctiva, as well as periocular eczematous changes may occur in severe allergic cases.  Brimonidine can also cause central nervous system depression, even involving the respiratory centers in infants 13; for this reason, brimonidine is contraindicated in young children.

In terms of the topical carbonic anhydrase inhibitors, dorzolamide-containing drops sting upon installation because of their acidity, but can often be continued once patients are reassured.  Systemic carbonic anhydrase inhibitors are frequently associated with side effects, including tingling in the extremities, weight loss, GI effects, frequent urination, kidney stones, and constitutional symptoms.  Systemic hyperosmotics can be associated with severe complications including stroke and should be used on a very limited basis.  All medication use must be carefully analyzed in a pregnant woman, as the effects on the developing fetus may be unpredictable; beta blockers may be the safest choice 14.

Proper dosing of medication should be addressed at some point with each patient.  Prostaglandins can be given at any time of day in order to improve compliance, as long as it is around the same time each day.  However, beta blockers are likely only effective during the day, and should be given on awakening in the morning 15.  Patients who work nights should place their beta blockers on awakening, even if it is in the evening.  More frequent dosing with prostaglandins should be discouraged, as efficacy decreases with more than once daily use 16.  Topical carbonic anhydrase inhibitors 17 and brimonidine are both slightly more effective given three times daily.  However, the level of compliance with a third (mid-day) dose of medication is poor.  In order to prevent patients from missing more critical doses of medicines, it may be better to stick to twice daily dosing.

 

References

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  2. Lichter PR, Musch DC, Gillespie BW, Guire KE, Janz NK, Wren PA, Mills RP; CIGTS Study Group.  Interim clinical outcomes in the Collaborative Initial Glaucoma Treatment Study comparing initial treatment randomized to medications or surgery.  Ophthalmology. 2001 Nov;108(11):1943-53.
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  12. Motolko MA.  Comparison of allergy rates in glaucoma patients receiving brimonidine 0.2% monotherapy versus fixed-combination brimonidine 0.2%-timolol 0.5% therapy. Curr Med Res Opin. 2008 Sep;24(9):2663-7. Epub 2008 Aug 7.
  13. Lai Becker M, Huntington N, Woolf AD.  Brimonidine tartrate poisoning in children: frequency, trends, and use of naloxone as an antidote.  Pediatrics. 2009 Feb;123(2):e305-11. Epub 2009 Jan 5.
  14. Ho JD, Hu CC, Lin HC.  Antiglaucoma medications during pregnancy and the risk of low birth weight: a population-based study.  Br J Ophthalmol. 2009 Oct;93(10):1283-6. Epub 2009 Jun 10.
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  17. Lupinacci AP, Netland PA, Fung KH, Evans D, Zhao Y.  Comparison of twice-daily and three-times-daily dosing of dorzolamide in ocular hypertension and primary open-angle glaucoma patients treated with latanoprost.  Adv Ther. 2008 Mar;25(3):231-9.
  18. Konstas AG, Stewart WC, Topouzis F, Tersis I, Holmes KT, Stangos NT.  Brimonidine 0.2% given two or three times daily versus timolol maleate 0.5% in primary open-angle glaucoma.  Am J Ophthalmol. 2001 Jun;131(6):729-33.

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