Monocular treatment trial for glaucoma might not be valid

Both sides of this issue were debated during a point-counterpoint session at the Glaucoma Subspecialty Day meeting. M. Bruce Shields, MD, presented the arguments in favor of continuing monocular drug trials, and Tony Realini, MD, offered various points discrediting this practice.

First assumption

"The first assumption is that fellow eyes exhibit symmetrical spontaneous IOP fluctuations," Dr. Realini explained. "There are historical diurnal curve data, as well as data we published in 2002, demonstrating that spontaneous IOP fluctuations between fellow eyes of ocular hypertensive and glaucoma patients are dissimilar a substantial proportion of the time."

Dr. Realini cited a report from 1964 that compared diurnal curve shapes between fellow eyes of glaucoma patients and found that 45% of the subjects had different IOP curves in their fellow eyes. Another report in 1993 noted similar findings in 33% of patients with ocular hypertension and 36% with glaucoma. In his own research published in Ophthalmology in 2002, Dr. Realini found asymmetric IOP fluctuations between fellow eyes in patients with and without glaucoma.

"There are not compelling data in the literature that I am aware of showing that IOPs in fellow eyes fluctuate symmetrically," Dr. Realini said. "I am not sure anyone has ever looked, because everyone has just accepted it as a given."

Dr. Shields, the Marvin L. Sears Professor and chairman emeritus, Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, CT, acknowledged the evidence that asymmetric IOP fluctuation is supported by various studies as reported in the literature. One study, published in Ophthalmology in 2005 by J.H. Liu, A.J. Sit, and R.N. Weinreb, found that 24-hour IOP profiles in the right and left eyes of healthy individuals in a sleep study were similar. After examining the single pairs of IOP readings in individuals, the two eyes exhibited asymmetric IOP fluctuations at times. So, it may be helpful to determine mean IOP after several IOP readings over a period of time, he said.

In an editorial published in Ophthalmology in 2004, J. Piltz-Seymour and H. Jampel suggested the utility of taking multiple IOP measurements at different times during the day for a monocular treatment trial.

"Starting a medication simultaneously in both eyes would not eliminate the problem of asymmetric IOP fluctuation," Dr. Shields emphasized. "It would only reduce the chances of assessing how the drug is actually working."

Second assumption

Another assumption pertaining to the monocular drug trial is that no contralateral crossover effect is seen with a topical IOP-lowering agent. This isn't true in the case of beta blockers, noted Dr. Realini. In 2000, a report published in the American Journal of Ophthalmology showed that in eyes treated with a beta blocker there was an average IOP lowering effect of –5.9 mm Hg and the contralateral untreated eye had an IOP lowering of –1.5 mm Hg in initial one-eyed trials in the ocular hypertension treatment study.

Dr. Realini noted that with prostaglandin analogue use, the contralateral crossover effect is unlikely to occur.