Lowering IOP With Medical Therapy in Patients With Glaucoma

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Fixed Combinations

Patients often require multiple medications to achieve target pressure control. For example, in the Ocular Hypertension Treatment Study (OHTS),^[3] 40% of subjects randomized to the treatment arm required more than 1 medication to reach their target. As discussed above, patients are commonly placed on a prostaglandin first and then have a single additional drug added. However, a 2-drug regimen still does not achieve target IOP in some patients, and physicians must address the possibility of adding a third drug. In such instances, fixed-drug combinations make multiple drug regimens more convenient. Fixed combinations that are currently available in the United States include timolol 0.5%/dorzolamide 2.0% and timolol 0.5%/brimonidine 0.2%. Other countries have approved fixed combinations of prostaglandins plus timolol 0.5%: timolol 0.5%/latanoprost 0.005%, timolol 0.5%/travoprost 0.005%, and timolol 0.5%/bimatoprost 0.03%.

Strengths of Fixed Combinations

The importance of making multiple drug regimens convenient to patients cannot be overemphasized. Glaucoma treatment is chronic, and patients usually do not appreciate a clear therapeutic benefit. In fact, they are often more aware of the side effects and cost burdens of treatment than of any benefit. With that in mind, a fixed combination offers convenience (fewer drops instilled per day), a cost savings, and a decrease in the daily topical preservative load. Fixed combinations also help avoid medication washout, which occurs when patients on multiple drugs instill their various medications with too short an interval between drops and end up with a significant washout effect.^[41] Moreover, although the large clinical trials showed the fixed combination timolol/dorzolamide to be equivalent to the unfixed combination (at most timepoints), "real-world" studies demonstrated improved IOP lowering for the fixed combination vs the unfixed combination.^[42,43] Comparisons of the fixed combination timolol/brimonidine vs unfixed combination have not yet been published. An interesting property that has been noted with regard to the fixed combination timolol/brimonidine, however, is that the allergy rate appears to be lower than that of brimonidine 0.2% alone,^[44] which may have to do with the timolol component.^[45]

Weaknesses of Fixed Combinations

Among the obvious limitations of fixed combinations is the inability to tailor individualized therapy as flexibly as with the component drugs. This rigidity may prevent the optimal dosing frequency or timing of some components (for example, having to use a beta-blocker twice daily when once daily may be sufficient). The side effects of the components may be additive, and drug interactions are often compounded with combinations of therapy. Still, these limitations are probably outweighed by the convenience of dosing for most patients.