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Christopher T. Leffler, MD, MPH

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Chaudhary et al¹ studied monocular trials of glaucoma medications. It has been claimed that monocular trials estimate effectiveness better than binocular trials by reducing spontaneous intraocular pressure (IOP) variation, which is correlated between fellow eyes (correlated variation) using contralateral eye control.^2-5 Correlated variation sources include tonometer calibration, operator technique, diurnal fluctuation, and systemic factors (eg, blood pressure). Classic theory estimates the initially treated eye response between the baseline (1) and monocular trial visit (2) as (B₂ – B₁) – (A₂ – A₁), with A indicating the contralateral eye and B indicating the initially treated eye.

Classic theory is undermined by medicinal crossover to the untreated eye and spontaneous IOP variation, which is not correlated between fellow eyes. Uncorrelated variation might arise, for example, from a momentary intrathoracic pressure increase. Subtracting the contralateral IOP change eliminates correlated variation, but exaggerates uncorrelated variation.³

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