Combination Therapy

The need to add more medications to the patient's regimen becomes evident when there is progression of disease or when a single drug does not sustain a reduced pressure. In the case of advancing disease, optic nerve or visual field changes may occur despite a seemingly adequate initial pressure reduction. This should prompt the addition of medications to further reduce the IOP. For patients with early glaucoma and little optic nerve damage and visual field loss, an IOP in the high teens or low 20s may suffice, while for a patient with visual field loss on one side of the horizontal meridian or the other, an IOP in the mid to high teens may be required. For a patient with advanced disease, an IOP of 12 or less might be targeted as the goal to halt disease progression.3 On the other hand, usually a clinician will recalibrate the goal IOP through a process of trial and error for any given patient. In general, if target IOP is not adequate to control the disease, the aim should be approximately 20-30% reduction in IOP when there is evidence of progressive disease.

When the IOP rises to levels previously associated with disease progression, more aggressive treatment is needed. The reason for IOP elevation may be a loss of drug efficacy or refractory disease. A loss of drug efficacy can be assessed by performing a reverse monocular drug trial, where a drug is discontinued in one eye. If the IOP rises considerably, then the drug most likely is helping and advancing disease is the culprit.4 In the case of dramatic elevations of IOP, however, it is more prudent to add or change to another drug unilaterally or bilaterally than to take one away and risk a potentially damaging IOP spike.


Many practitioners tend to add medications, assuming that more is better. Remember, however, that it is the patient who must take all of the medications. Each time patients add a new drop to their regimen, they add new potential side effects, drug or preservative allergies, and inconveniences to their daily schedule. As a general rule of thumb, additional medications are needed when disease progresses despite an already reduced IOP. Substitution is more appropriate in patients with less advanced disease who display tolerance or a loss of drug efficacy over time.

In both addition and substitution, the new medication should belong to a different drug class. For example, adding or substituting a nonselective beta blocker for a selective beta blocker will not produce a dramatic change in IOP and is usually not an appropriate choice (unless such a change is, e.g., from betaxolol to timolol for dose scheduling purposes).

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