When treating a glaucoma patient with topical hypotensive therapy, how do we know which medications are working and which medications should be discontinued in favor of a more effective option? One strategy historically used has been the monocular trial, where a new medication is initiated in a single eye, and, at the follow-up visit, the pressure of the two eyes is compared. The strategy makes perfect sense; however, glaucoma management is not always so simple.
Probably the best value that a monocular trial can provide is with respect to local side effects. If a patient is noting that a drop makes the eye itch, causes hyperemia, blurred vision, or some other local problem, continuing the agent in just one eye and comparing the outcome may be informative.
But what about efficacy? In order for a monocular trial to work the way we would like it to, a number of conditions must be met. The pressure in the eyes must be initially be equal, but it also must fluctuate similarly throughout the day. The eyes must respond similarly to the medication. And there must not be any contralateral crossover effect (which is certainly not the case with beta blockers). Corneal thickness and biomechanics have both been shown to influence IOP lowering, and these variables are not always the same between the two eyes.1
Realini2 and Bhorade et al3 both evaluated the monocular trial in separate studies and found the approach to be less than ideal. While Bhorade found that the monocular trial was not great for determining the IOP response to a PGA, she at least was able to report that the two fellow eyes responded similarly to PGAs (r=0.81). In general, using more pre- and post-treatment visits helped. Realini showed that there was only a weak correlation (0.33) between the short-term response to a medication and the long-term response, indicating that any short-term assessment of a medication could fall short.
In summary, each patient is unique, has a unique eye, and each eye and each patient may respond uniquely to any medication. If we want to play the odds, we will pick medications that have been shown in large prospective trials to be efficacious. We will then manage from that standpoint without becoming derailed by an individual’s short term IOP response. Ultimately, we will judge the efficacy of a medication by structural and functional stability, and long-term pressure reduction, evaluated over many visits.
1. Agarwal DR, Ehrlich JR, Shimmyo M, Radcliffe NM. The relationship between corneal hysteresis and the magnitude of intraocular pressure reduction with topical prostaglandin therapy.
Br J Ophthalmol. 2012;96:254-257.
2. Realini TD. A Prospective, randomized, investigator-masked evaluation of the monocular trial in ocular hypertension or open-angle glaucoma.
3. Bhorade AM, Wilson BS, Gordon MO, et al; Ocular Hypertension Treatment Study Group. The utility of the monocular trial: data from the ocular hypertension treatment study.
Dr. Nathan M. Radcliffe is the director of the glaucoma service and a clinical assistant professor at New York Univeristy Langone Ophthalmology Associates and is a cataract and glaucoma surgeon at the New York Eye Surgery Center.