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Editors Selection IGR 11-2

Intraocular Pressure: Day-to-day IOP variability

Comment by Tony Realini on:

50233 Day-to-day variability in intraocular pressure in glaucoma and ocular hypertension, Rotchford AP; Uppal S; Lakshmanan A et al., British Journal of Ophthalmology, 2012; 96: 967-970

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Dr. Rotchford and colleagues recently made a valuable contribution to the ongoing debate regarding the clinical utility of the monocular drug trial in evaluating the efficacy of newly-initiated IOP-lowering therapy. In this current study, the team has conducted a post hoc analysis of data from that trial to estimate the day-to-day variability in IOP among subjects with ocular hypertension and glaucoma. Briefly, IOP was assessed at 0800, 1100 and 1600 on three different days before initiating therapy and on three different days after initiating therapy. Agreement of IOP in the same eye at the same time of day on the three pre-treatment visits was assessed using the intraclass correlation coefficient (ICC); the same analysis was conducted separately on the on-treatment visits. For the first-treated eye (that is, the eye undergoing the monocular trial in the original study), ICC values were uniformly in the good to excellent range. However, as the authors rightly point out, the ICC has limitations and does not fully characterize IOP variability. The investigators looked more closely at variability, using the coefficient of repeatability (CR) as a within-subject estimate of IOP variability at the same time across days. Pretreatment, the CR ranged from 5.3 to 6.9 mmHg at the three measured time points, and on-treatment CR values ranged from 4.1 to 4.8 mmHg. Interpreting a CR is straightforward: a CR of 5.3 mmHg means that 95% of repeated measurements on the same subject on the same time of day would be expected to fall within this range.

Standardizing the time of day of IOP measurements does not eliminate spontaneous variability of IOP

Phrased in a clinical context, when IOP is measured on two different days at 0800, any difference in the two measurements < 5.3 mmHg would be indistinguishable from spontaneous, nontherapeutic IOP fluctuation. Clearly, a spontaneous IOP change of that magnitude could easily mimic a successful monocular trial if it occurred in the trial eye ‐ even if the drug being trialed had no effect on IOP; and similarly, if it occurred in the fellow eye during a monocular trial, the trial may appear not to have been successful even if the drug did lower IOP in the trial eye, as the therapeutic benefit in the treated eye was masked by a spontaneous IOP drop of similar magnitude in the fellow eye. These findings support our own and the work of others, demonstrating that standardizing the time of day of IOP measurements does not eliminate spontaneous variability of IOP.

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