There are many situations that confront the optometrist as he/she decides whether to initiate therapy for ocular hypertension (OHT) or glaucoma. For ocular hypertension, the decision process is discussed in Chapter 5. In regard to glaucoma, when optic nerve and/or visual field damage associated with glaucoma is recognized and other causes of this loss are ruled out, therapy is in order. Before therapy commences, a strategy is developed based upon the stage of disease and IOP level, as well as other factors. A target intraocular pressure (IOP) range is determined and a medication selected. If therapy is not indicated, the patient is often classified as a glaucoma suspect and followed once to twice per year, depending upon the individual’s characteristics. The category of glaucoma suspect includes individuals with ocular hypertension as well as suspicious optic nerves or visual fields.
When medical therapy is initiated, the selection of the initial agent usually is decided between two classes of drugs: prostaglandins (PGs) or topical beta-blockers. PGs have replaced beta-adrenergic antagonists as the most commonly used agent for initial therapy. This is due to their ability to reduce IOP efficiently on a once-per-dosage schedule, without inducing serious side effects, as well as their dampening IOP fluctuations that may occur over a 24-hour period (diurnal curve). Beta-adrenergic antagonists do not reduce IOP as effectively, especially when viewed over a 24- hour period, and have some additional contraindications. Recent information from several clinical trials has highlighted the need for reduced target IOPs, further cementing PG’s role as first-line agents.
The initial medication selected is based upon its ability to reduce IOP, its safety profile, tolerability and patient acceptance. The drug needs to be matched to the patient. For example, a patient with a history of anterior uveitis or macula edema would not be a good candidate for PG therapy. Likewise, a patient with pulmonary disease would not be a candidate for beta-adrenergic antagonist therapy. Target IOPs must also be considered as a therapeutic agent is selected. Target pressures refer to the range of IOP that we hope will prevent further glaucomatous damage. A patient’s target IOP may change over time, either as new knowledge becomes available, indicating lower IOPs will be advantageous or if progression is confirmed. Target IOPs are a best guess of what IOP will control the condition. The best indicator to show that target IOP has been achieved is when periodic optic nerve and visual field evaluations reveal no change. If change is noted, additional reduction is necessary. Target IOPs are based on the amount of damage present and the highest IOP reading, with greater reduction required as damage worsens. Recent clinical trials have provided evidence that lower target IOPs are important, though no definitive study has shown exactly what IOPs are optimal.
The Ocular Hypertension Treatment Study (OHTS), which had a target IOP reduction of 20%, found that 4.4% of individuals in the therapy group progressed. In a study of glaucoma patients, the Early Manifest Glaucoma Trial (EMGT), in which the goal was 25% IOP reduction, 45% of patients in the therapy group progressed over time. The Collaborative Initial Glaucoma Treatment Study (CIGTS) which had a similar group of patients with early glaucoma as the EMGT, also monitored for progression. CIGTS found little change in the group whose IOP was reduced 38%. In the Advanced Glaucoma Intervention Study (AGIS), groups were broken down based on the percentage of visits in which the IOP was reduced below 18mmHg. One group with a mean IOP of 20.2mmHg showed significant deterioration, while another group with a mean IOP of 12.3mmHg appeared to be stable over an 8-year period. These studies, taken as a group, do not provide proof that IOPs need to be reduced to the low teens for all patients, but they do illustrate the need to reduce IOPs to lower levels than previously thought.
The EMGT recognized that risk factors for glaucomatous progression include higher IOP at the time of diagnosis, pseudoexfoliation, bilateral disease, disc hemorrhages, older age and worse visual field mean deviation. The AGIS found that an additional risk factor is variation in IOP over a 24-hour period. This is a separate risk that describes IOP fluctuation throughout the day, even when IOP is low at certain time points. To recognize diurnal fluctuations, we should record the time of each visit and schedule exams at varying times during the day.
Often it is helpful to begin therapy with a monocular or unilateral trial in which medication is begun in one eye for a few weeks, with the contralateral eye serving as a control. The rationale is that IOP, while often different between the two eyes, will rise and fall over the day to a similar degree. Also, the response to a medication should be similar in both eyes. Since non-responder rates vary from 8% to 25% depending on the class of medication, a monocular trial is one way to ensure the medication is effective as well as determine if side effects are occurring. Realini has questioned the use of the monocular trial, in part because the IOP reduction in one eye does not necessarily predict how the drug will perform in the other. Moreover, monocular trials require at least one additional visit. Nevertheless, many experts continue to recommend the monocular trial, recognizing its limitations but also using it as a way to control the initiation of a new drug.
At the outset of therapy, the patient needs to be educated in regard to the optimal time for drop instillation(s) and potential side effects. Also, it is important to demonstrate proper eyedrop instillation technique and have the patient demonstrate that he/she can properly instill the drops. If eyedrop instillation appears to be a problem, there are devices to aid instillation. Also, a companion or family member may aid in medication insertion. Finally, written dosing schedules should be provided as reminders. The first followup visit usually occurs 2 to 4 weeks after therapy commences. At each visit, ask if any side effects have occurred and when the patient last used the medication(s). Patient communication is discussed in Chapter 10. Even when written schedules are provided, some patients misunderstand how to use the medication. Questions that should be addressed at every visit include whether the patient is actually using the drug or if there are any problems or concerns. The IOP is measured to assess whether the medication is effective and pressure is at target level. If the drug is well-tolerated and effective, then the patient is followed over time, watching for medication side effects and/or progression. Patients are seen every 3 to 6 months depending on severity and type of disease. Ocular hypertensives are monitored less often, and individuals with significant loss, more often. Dilated optic nerve evaluation, imaging and visual field testing should be performed at least yearly. Testing more often is recommended in the first year after diagnosis, if a greater degree of loss is present or a question of stability arises.
An important question that should be considered early in the course of follow-up is the rate of change. If a patient is progressing rapidly, we need to recognize this and modify our approach. One way to measure rate of change is to perform perimetry on a 6- month basis for the first 2 years. This is best done with SITA visual fields and the Glaucoma Progression Analysis (GPA) software tool. If the fields are unchanged, the interval between field testing can be increased to yearly. Several fields are needed before a decision can be reached regarding stability, but once 5 fields are available, trends will emerge.
One challenge occurs when a patient does not respond or side effects develop with the initial medication. If side effects occur, what are they? Are they caused by the medication? May they be reduced if a switch occurs within the same class of drugs? An intra-class switch may work if hyperemia develops with one PG. A more difficult question is if the target IOP level is not reached with the initial medication. In this case, the IOP response needs to be evaluated. For example, if the IOP was very high and/or the damage significant, leading to a target goal of 40% reduction, and the drug provides 25% of the target reduction, then the medication appears to be effective, but a second agent is needed. On the other hand, if the reduction is 15% or less, the patient may be considered a non-responder. Inadequate responses do occur and are not often recognized, leading to unachieved target levels. We should ask if progression may occur in 15 years at the present IOP level. It may be then easier to appreciate the urgency of attempting to achieve target IOP levels.
There are different reasons why the IOP may not have been reduced with the initial agent, including lack of response or poor compliance with the clinician faced with a decision of how to proceed. Switching to a drug within the same class, such as going from one PG to another (intra-class switches) is controversial, since it is not proven that such switches work. Switch studies with PGs have shown that the medication switched to always performs better. However, one problem is that most switch studies have been conducted over only short periods, usually about 30 days. The improved efficacy may be due to the second drug’s greater response, but other possible reasons for this reduction include improved compliance or fluctuations in IOP (regression to the mean).
If the medication is effective but further reduction is needed, either because the IOP is above the target goal or progression is identified, the practitioner may choose an additional medication. If a PG is the initial agent, the second agent may be a beta-blocker, alpha agonist or topical CAI. A beta-blocker offers the convenience of once-per-day use; thus the patient would take it in the morning and take the PG at nighttime. When added to a PG, topical CAIs may be more effective at lowering IOP than beta-blockers. But, topical CAIs require twice-per-day dosage. If a patient is on a PG along with a beta-blocker or topical CAI and further IOP reduction is needed, then either of these drugs may be discontinued and a fixed-combination agent containing timolol and dorzolamide (Cosopt) begun. It is important to stress to patients taking two medications that they should wait five minutes before instilling the second agent to avoid washing the first from the eye. Also, remember to instruct patients taking beta-blockers to close their eyes or occlude their punctum for three minutes. This will reduce systemic absorption, improve efficacy and reduce side effects. Argon or Selective Laser Trabeculoplasty and filter surgery become options when the patient is progressing or the IOP is above the target level, and several medical options have been tried (see chapter 8).
In some cases, even with patients who respond well to initial therapy, the IOP may slowly rise over time. Such increases could be due to the glaucoma worsening, problems with compliance or the development of tachyphylaxis. The two questions to ask are: Is the drug effective, and is it being used? If the IOP is elevated, instill the medication and measure the IOP several hours later. Also, observe the patient’s drop instillation technique to determine if the drug is getting into the eye. And finally, the reverse monocular trial may be helpful to address whether tachyphylaxis has developed. In this trial, the drug is temporarily discontinued in one eye and continued in the other. If tolerance has developed, there will be little change in the untreated eye’s IOP over the next several weeks. However, a rising IOP proves the drug is effective and should be continued, but an additional agent is necessary.
The management of ocular hypertension and glaucoma is an art that requires the clinician to make an ongoing series of decisions and adjustments over the patient’s lifetime to ensure the IOP remains at acceptable levels and the condition does not worsen. Periodic monitoring of the optic nerve and visual fields are also necessary. The doctor needs to consider both the short and longterm view to ensure occurs throughout the lifetime of their patient.
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