IOP increase consistent with dose after glaucoma medication washout
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Stopping glaucoma medication resulted in a dose-dependent IOP increase in patients treated for open-angle glaucoma, according to data from two independent clinical trial cohorts.
“Despite the continual advent of new laser and surgical procedures, ocular hypotensive eye drops remain the mainstay of initial IOP lowering therapy for most forms of glaucoma,” Thomas V. Johnson, MD, PhD, from the Johns Hopkins Wilmer Eye Institute in Md., and colleagues wrote. “By assuming that the washout IOP is comparable to untreated IOP, we have calculated an inferred IOP reduction induced by medical glaucoma therapy.”
Johnson and colleagues enrolled 781 patients in the HORIZON trial and 619 patients in the COMPASS trial, with one eye in each patient randomized. All patients underwent tonometry before and after washout of IOP-lowering medications.
Patients in the HORIZON trial had been on one to four IOP-lowering medications, and those in the COMPASS trial had been on no medications to up to three medications, including prostaglandin analogues and beta-adrenergic antagonists. Those in the HORIZON trial had a lower IOP on medication and used more IOP medications compared with those in the COMPASS trial (P < .001).
The mean IOP for all patients was lower on medications than after washout (18 vs. 24.1 mm Hg; P < .001). The rise in IOP after medication washout was correlated with the number of medications washed out (P < .001).
Johnson and colleagues wrote that, by assuming that the washed-out IOP is comparable to untreated IOP, the corresponding decrease in IOP from adding medications ranged from 23.5% for one medication to 35.6% for four medications.
“The medicated IOP, washed-out IOP, IOP change, percent IOP rise upon medication washout and inferred IOP decrease upon medication addition were all significantly associated with number of medications washed out,” the researchers wrote. “The change following medication washout was strikingly similar for subjects enrolled in HORIZON and COMPASS.”
Predictors of greater change in IOP upon medication washout included greater number of medications (P < .001), greater washed-out unmedicated IOP (P < .001), thinner central corneal thickness as measured in micrometers (P < .001) and HORIZON as the source clinical trial (P = .004).
“As clinical trials for new glaucoma therapies are developed and conducted, understanding the expected IOP elevation following medication washout for participating subjects will increase the efficiency of planning and recruitment,” Johnson and colleagues wrote. “As new glaucoma medications, including nitric oxide donors and rho kinase inhibitors. have only recently been introduced to the market, the present data do not provide information to understand how these drops affect washout IOP.” – by Talitha Bennett
Disclosures: Johnson reports no relevant financial disclosures. Please see the full study for all other authors’ relevant financial disclosures.
Perspective
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Lisa M. Young, OD, FAAO
Discontinuing glaucoma medications (commonly referred to as a drug “washout”) may be used to reset baseline IOP, confirm a therapeutic sensitivity or explore the possibility of adverse medication side effects. Of course, there is concern about IOP spikes with possible glaucoma progression, and, indeed, sometimes post washout IOP readings defy expectation.
To further understand the potential reasons for this variability, Johnson and his colleagues analyzed washout data from two clinical trials. Based on their data, how much of an IOP increase should you anticipate during a washout period? Not surprisingly, they found that discontinuing glaucoma medications results in a dose-dependent IOP increase in treated open-angle glaucoma patients. In other words, you should expect higher IOP after washout in your patients who were on more medications.
Were washout IOP increases similar between different medication classes? As expected, they found that prostaglandin analog washouts resulted in a greater IOP elevation than a washout of other drug classes. Were there any other confounding factors that affect the washout IOP elevation? Yes, thicker central corneal thickness and history of selective laser trabeculoplasty were associated with less of an IOP elevation.
These “drug holidays” are a critical part of glaucoma management, and being able to anticipate how patients may respond without medications allows us to plan our next step accordingly.
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