not admit to poor compliance even if directly asked.123 Patients who admit they forget to take their medications generally are telling the truth; those who swear they never miss a dose may or may not be telling the truth. No matter how well they think they know their patients, physicians are unable to identify those who are defaulting from antiglaucoma treatment.124,125

Somewhat surprisingly, compliance (or lack thereof ) is not

associated with age, marital status, socioeconomic level, race, occupation, education level, or intelligence level.119,124,125 However,

increased frequency of missed appointments, lack of understanding of the disease, dissatisfaction with physician or clinic, increased waiting times to see the physician, disinterest in one’s health, and unstable family condition are associated with increased rates of poor compliance. Interestingly, even an excellent understanding of glaucoma and its potential for blindness does not guarantee good compliance; in one study, only two-thirds of the glaucoma patients who seemed to have an adequate understanding of their condition were compliant.126 Conversely, of those in the same study who did not understand their condition, only one-third were compliant.

From 3% to 7% of patients do not even fill the prescriptions given to them by the physician.127 Many do not understand the chronic nature of glaucoma therapy and may take the drops only for some fixed period such as a month or until the first bottle runs out. The continued use of a prescribed medication is referred to as persistence. As it is with most asymptomatic, chronic diseases, the persistence with glaucoma medications is surprisingly poor with, at best, only about 50% still refilling their prescriptions at 1 year.128 Two recent surveys of large medication insurance plans show that persistence is best (although not terrific) for the prostaglan-

din group of agents and significantly poorer with the rest of the antiglaucoma agents.128,129

Another problem relates to the fact that patients do not always know a satisfactory technique for administering eyedrops.130 This is particularly true of ointments. The doctor often assumes (incorrectly) that the patient will somehow, perhaps intuitively, know how to administer drops or ointments to themselves. Patients with poor vision may not be able to distinguish the different eyedrop containers without color-coded caps or other markings. Elderly patients or those with difficulty using their hands may not be physically able to administer drops to themselves or may have great difficulty with some bottle designs. The small bottles associated with prostaglandin analogs may be particularly difficult for those with arthritic fingers. Patients may assume that if one drop is good, then two or even more may be better. Patients with busy or erratic lifestyles may not be able to keep to a regular dosing schedule.

General suggestions for medical treatment of glaucoma

How is the physician to achieve a safe and effective medical regimen for glaucoma based on the preceding discussion of the pharmacology of topical ocular drugs? It is impossible to develop guidelines that cover the medical treatment of all varieties of glaucoma in all stages of severity. The list summarized in Box 22-4 gives general suggestions for the long-term treatment of some of the more common forms of chronic glaucoma, especially POAG or angle-closure glaucoma after iridotomy.131

Box 22-4  General suggestions for medical treatment of glaucoma

    1. Establish a target pressure.

   2. Adjust the treatment program to the patient and his/her lifestyle.   3. Initiate or change therapy through a therapeutic trial in one eye.

   4. When therapy is ineffective, substitute rather than add drugs.

  5. Continually monitor the assumptions related to the target pressure and change as indicated.

  6. Ask about and monitor potential ocular and systemic side effects.

   7. Simplify and reduce treatment when possible.

  8. Teach patients the proper technique for instilling eyedrops.

   9. Provide written directions.

10. Communicate with the patient’s family physician.11. Ask about problems with the medical regimen.

12. Consider defaulting as an explanation for the failure of medical treatment.

13. Educate patient about his/her illness and its treatment.

14. Stop treatment periodically to determine continuing effectiveness.

15. Measure IOP at different times of the day and at different intervals after the last administration of medication.

16. Recommend that the patient comparison shop for medication.

Establish a target pressure

The first step is to establish a target pressure, which is determined by the initial IOP level when the diagnosis was made, the degree of optic nerve damage, and the general health of the patient. The lower the initial IOP, the older the patient, the more advanced the optic nerve damage, and the presence of cardiovascular disease or diabetes, the lower the target pressure must be set.

Two examples may help to put this guideline in perspective. A 42-year-old man with an initial IOP of 32 mmHg, a 0.6 disc diameter cup, a small arcuate scotoma, and no other health problems may be able to tolerate pressures in the low 20s for many years. On the other hand, this individual has many years to live with his disease. Conversely, an 85-year-old woman with diabetes mellitus, an initial IOP of 23 mmHg, an 0.8 disc diameter cup, and an altitudinal visual field defect will probably require an IOP of 17 mmHg or lower to prevent further optic nerve damage. A 94-year-old man with moderate glaucoma, only modest visual field loss and multiple systemic diseases may die before his glaucoma robs him of functional vision; he may not require such aggressive therapy.

Adjust the treatment program to the patient and his or her lifestyle

The systemic status of the patient is a very important consideration in determining the potential benefits and problems with medical therapy. Some systemic conditions that may be affected to a significant degree by topical or systemic antiglaucoma medications include obstructive pulmonary disease, asthma, heart failure, arrhythmia, diabetes mellitus, metabolic acidosis, metabolic alkalosis, renal lithiasis, renal disease, hepatic disease, dysautonomia, mood disorders, gastrointestinal disorders, and genitourinary disorders. A careful medical history and review of systems should be obtained from every patient for whom glaucoma treatment is contemplated. The patient should be informed of the common systemic side effects and told to call the doctor if any unusual or persistent symptoms appear.

The lifestyle, occupation, avocations, personality, and social situation of the patient should also be taken into account when initiating or changing therapy. It is unlikely that a hard-driving executive will take his or her medication four times daily. Similarly, a 40- year-old truck driver prescribed miotics may be unable to work because of fluctuating myopic refractive shift. It is counterproductive to prescribe a treatment program that the patient cannot or will not follow. This only invites dissatisfaction with the physician and defaulting from the regimen.

The busier the lifestyle, the less structured the environment, and the fewer resources the patient has, the simpler the regimen should be. Try to use the patient’s most ingrained habits or activities as a tool to help him or her stick to the regimen. For example, twice-daily medication may be linked with breakfast and dinner or tooth brushing.Visual impairment may be initiated or exacerbated by the use of miotics when a patient has a lens opacity as well as glaucoma. Patients who use soft contact lenses should be warned about and monitored for the possible concentration of preservatives in the contact lens and the potential toxicity that such

Box 22-5  Initial approach to treatment of open-angle glaucoma

Medical therapy first

Most patients

Laser surgery first

Unlikely to tolerate medical therapy

Doesn’t understand need for medical therapy

Unlikely to comply (e.g., Alzheimer’s, mental retardation)

Multiple systemic medical treatments

Incisional surgery first

Same as for laser surgery but unlikely to respond to trabeculoplasty Unable to perform laser trabeculoplasty

Unlikely or unable to follow up

concentrated preservatives may pose for the ocular surface. Similarly, those patients on multiple topical medications may fall victim to preservative toxicity.

For most patients, topical medical therapy is a good place to start. Initial laser treatment should be considered for those who are unlikely to take or tolerate medical therapy; examples include patients with Alzheimer’s disease and those with advanced cardiovascular disease.Those who are unlikely to return for follow-up or are unlikely to respond to laser trabeculoplasty (e.g., failed in the fellow eye) should be considered for initial surgical intervention (Box 22-5).

Initiate or change therapy through a therapeutic trial in one eye

Because IOP fluctuates from day to day and even from hour to hour, it is difficult to assess effectiveness of therapy without a therapeutic trial in one eye. For example, a patient whose IOP is 30 mmHg in each eye is prescribed 1% pilocarpine four times daily to both eyes (Fig. 22-2). If the patient returns in 2 weeks with an IOP of 22 mmHg in both eyes, the ophthalmologist does not know whether the reduction in IOP is related to treatment or represents a spontaneous fluctuation. However, this concept has been called into question recently due to the fact that not all patients respond to a medication the same way in both eyes and to the fact that there may be cross-over effects to the untreated eye from the treated one.132 Still, the idea of a unilateral trial does have some merit and should be considered when it is not clear if the patient is responding to treatment.

In a therapeutic trial in one eye, the physician prescribes timolol twice daily or one of the other agents at appropriate dosage levels to the right (or left) eye. When the patient returns 4 weeks later with an IOP of 22 mmHg in both eyes, the ophthalmologist knows that the drug is ineffective. Conversely, if the IOP is 22 mmHg in the right eye and 30 mmHg in the left eye on repeat examination, the effect of the drug is clear. Some drugs (e.g., timolol and other -blocking agents) reduce IOP in both eyes after unilateral

Baseline

Intervention

Two weeks later

Begin 1% pilocarpine 4 times a day both eyes

Intraocular pressure 22 mmHg both eyes Drug effect not clear

Intraocular pressure 30 mmHg both eyes

Begin 1% pilocarpine 4 times a day right eye

Intraocular pressure 22 mmHg both eyes Drug clearly ineffective (No net decrease in intraocular pressure)

Begin 1% pilocarpine 4 times a day right eye

Intraocular pressure 22 mmHg right eye, 30 mmHg left eye, Drug clearly effective (Net decrease of 8 mmHg)

administration.This may be a confounding factor in one-eye therapeutic trials. However, the contralateral effect is smaller than is the ipsilateral effect. Standard miotics can be evaluated in a few days to a week. Adrenaline (epinephrine), dipivefrin, -adrenergic agonists, carbonic anhydrase inhibitors, and -adrenergic antagonists should be evaluated after 2–4 weeks. Latanoprost and the other prostaglandins may take as long as 6 weeks to reach maximum effect.

The therapeutic trial in one eye is also useful when adding another medication (e.g., adding brimonidine or dorzolamide to a regimen of latanoprost) (Fig. 22-3). If a therapeutic trial is carried out for a few to several weeks, the ophthalmologist can determine whether the IOP reduction justifies the expense, bother, and potential side effects of the added drug.

The one-eye therapeutic trial requires more time and more visits to the office or clinic. However, the amount of information gained about drug efficacy and side effects justifies any additional time or expense on the part of the patient and physician. Therapeutic trials are not applicable in emergency situations or when glaucoma is unilateral or markedly asymmetric.

When therapy is ineffective, substitute rather than add drugs

When IOP is considered too high, there is a tendency to add drugs to the regimen rather than to find a simple, effective regimen. If IOP rises after a patient has been controlled on a medication for some time, the drug should be stopped in one eye to determine whether it is still effective (Fig. 22-4). If the drug is ineffective or only partially effective, it should be discontinued and a more potent agent either in its class or in a different class substituted. If a drug is effective but the ophthalmologist believes that a lower IOP is necessary

Intervention

Two weeks later

to prevent further damage, either a more potent drug may be substituted or a new drug can be added to the old regimen using a therapeutic trial in one eye.As a general rule, a 20–25% reduction in IOP is considered a sufficient response to justify continued treatment. However, there are situations in which a smaller reduction would be considered helpful. For example, a reduction in IOP from 19 to 17 mmHg (10.5% decrease) might warrant continued treatment in the presence of advanced optic nerve damage and visual field loss.

Continually monitor the target pressure

Determining the effectiveness of treatment requires constant monitoring of IOP, optic nerve appearance, and visual function. Deterioration in any of these parameters is a sign to consider more aggressive therapy (i.e., to set the target pressure at a lower level).

Ask about and monitor ocular and systemic side effects

Potential side effects should also be evaluated and placed in perspective by the physician–patient team. Patients will usually be forthcoming about ocular side effects. Often, however, patients do not relate systemic side effects to eyedrops. Therefore, the treating physician must be proactive and ask specifically about systemic side effects such as breathing difficulties, irregular heartbeat, gastrointestinal disturbances, fatigue, impotence, and mood or behavior changes.

Simplify and reduce treatment when possible

Patients should be treated with the lowest concentration(s), the smallest number of medicines, and the fewest number of administrations per day that have the desired therapeutic effect.133 It is important to remember that the dose–response curve for an individual patient may differ from that derived from normal volunteers or a tested population of glaucoma patients. Some individuals are sensitive to a drug, whereas others do not respond at all. In some patients, 0.5% epinephrine, 1% pilocarpine, or 0.25% timolol produces the maximum IOP reduction. Higher concentrations may not be more effective and may only increase the possibility of side effects.Treatment is usually instituted using a low concentration of a drug. If this is effective but does not produce an acceptable IOP level, the drug should be administered to both eyes and the concentration increased in a therapeutic trial in one eye (Fig. 22-5). Some antiglaucoma agents (e.g., -blocking agents or strong miotics) are capable of controlling IOP when instilled once daily. This must be proven by measuring IOP 20–26 hours after the last medication administration.

Teach patients the proper technique for instilling eyedrops

Many patients use poor technique when administering eyedrops. Poor techniques include instilling excess drops, contaminating the

dropper or bottle tip, and neglecting eyelid closure and punctal occlusion.130,134,135 Improper eyedrop administration may increase

the expenditure for medication, decrease the therapeutic response (e.g., excess drops stimulate tearing and blinking and decrease drug penetration into the eye), and enhance side effects (especially those caused by systemic absorption of the drug).