The options for the topical medical therapy of glaucoma have greatly increased during the past 3 decades. The introduction of new classes of medication, often with several choices within a class, lower IOP more effectively than ever before. The evaluation of a drug, however, still focuses on three characteristics. The first is efficacy or the agent's ability to lower IOP, although questions remain as to the significance of mean, peak, or variability of IOP. The second is safety—that is, the side effects of a drug that may affect systemic or ocular function. The third is tolerability, as in side effects that may not be a safety concern but may still bother the patient.
The challenge is to individualize therapy to maximize its efficacy while minimizing concerns about safety and tolerability. In today's health care environment, physicians must also take cost into account. When addressing this parameter, however, it is vital to consider costeffectiveness (ie, the impact of cost savings on the eventual outcome of the therapy on the disease, not just the cost of the medication).
A FOCUSED APPROACH
Clinicians no longer have the option of putting a patient on all of the classes of medications. In general, the first drug achieves the greatest decrease in IOP. A second additive drop is often a reasonable option, but a third or fourth drop rarely demonstrates substantial additional IOP lowering.1 Furthermore, when patients must use multiple eye drops, as much as half of a drug can be lost to the washout effect when they only wait 30 seconds between each drop's instillation.2
It is therefore imperative to maximize the benefit of the first drop. Usually, this medication is a prostaglandin analogue due to the drugs' excellent efficacy, safety profile, and once-daily dosing. There are differences among the available agents, and it is important to optimize therapy based on its efficacy and tolerability. Primary therapy is the best chance to treat the patient successfully. Therapy with multiple drops decreases adherence and increases the potential for side effects.
GENERIC ALTERNATIVES
The introduction of generic latanoprost represents a paradigm change in single-drop therapy. Obviously, the most prominent benefit of generic medications is cost savings.3 The amount saved is dependent on specific drug plans, however, and may not be as great as anticipated compared with the branded alternatives.
Any cost savings must be weighed against concerns regarding generic ophthalmic medications. Specifically, manufacturers are not required to demonstrate bioequivalence for ophthalmic drops or equal efficacy in lowering IOP for generic drugs' approval.4 The composition of the solution contains the active ingredient, but all other components, called excipients, are not tested to be sure that they are the same as in the branded agent. Additionally, with multiple generic agents available of unknown comparability, it is likely that different generics will be dispensed over time and based on the site of dispensing. Thus, if some generics are better than others, there is no assurance that a patient will receive the best. Lastly, in the case of latanoprost, the composition of the bottle may well play a role in drug availability. This may explain the finding that at least one generic form of latanoprost has been shown to be less effective at lowering IOP than Xalatan (Pfizer Inc.).5
The availability of generic latanoprost allows clinicians the potential to provide more cost-effective medical therapy, but it also complicates the clinical care system. Constant surveillance of efficacy and tolerability is required to ensure that the clinical characteristics of the generic agent are equivalent to those of branded alternatives.
ADDITIVE THERAPY
Although monotherapy is highly desirable, additive medical therapy is often necessary to achieve the target IOP or if there is evidence of progressive glaucomatous damage despite treatment with a single agent. Unfortunately, the clinical studies to help guide decisions for second-line therapy are not nearly as useful as those for monotherapy. In general, any drug produces a lesser decrease in IOP when used as additive therapy than when used as monotherapy. Moreover, if administering multiple types of drops at the same time, the patient should wait at least 5 minutes between the drops' instillation to prevent the washout of the first drop. In addition, the side-effect profile may be worse than for monotherapy because of the cumulative impact of multiple drugs. Finally, a drug's efficacy as a second-line agent may be different than expected when it is used as monotherapy. It is important to be sure that the second-line agent adds sufficient IOP lowering over the full 24 hours to justify its use. There are differences among classes as to their ability to lower the IOP when added to a prostaglandin analogue as well as differences in efficacy, particularly at night.
In addition, to more rapidly obtain greater IOP lowering with second-line drops, practitioners are increasingly considering the use of fixed-combination agents, particularly when justified by the presence of severe disease or markedly elevated IOP. The drawback of starting two agents simultaneously is that there is no way to determine the relative efficacy of each agent or to identify the specific cause of a side effect. If the combined agent can produce a substantial decrease in IOP that is greater than would be expected with any single agent used in additivity and produces no identified side effects, however, its use can be justified to allow fewer visits and more rapid IOP control in certain cases. Three or more adjustments made to a drop regimen can almost double costs that year, so fewer visits and changes in therapy can save money.6 In cases of mild disease or modestly elevated IOP, it is certainly desirable to evaluate the characteristics of each drug before instituting the fixed combination.
Fixed combinations have advantages, including a single copayment. In addition, compared with separate drops, a fixed combination reduces the patient's exposure to preservatives and eliminates the need to wait between instilling the two drug components of the drop. The patient's adherence may also improve, because he or she will be using one bottle instead of two.
CONCLUSION
It remains vital to individualize medical glaucoma therapy. In doing so, clinicians must bear in mind not only the immediate monetary cost to the patient of their drops, but also the cost-effectiveness of all aspects of therapy on the overall success of treatment
Ronald L. Gross, MD, is a professor of ophthalmology at Baylor College of Medicine in Houston. He is a consultant to, is on the speakers' bureaus of, and has received clinical research support from Alcon Laboratories, Inc., and Allergan, Inc. Dr. Gross may be reached at (713) 798-6100.
Ryan D. Vincent, MD, is the glaucoma fellow at Baylor College of Medicine in Houston for the 2010-to-2011 academic year. He acknowledged no financial interest in the product or company mentioned herein. Dr. Vincent may be reached at (713) 798-6100; rvincent@bcm.edu.
