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Comment by Luciano Quaranta on:

68907 Validity of the Monocular Trial of Intraocular Pressure-Lowering at Different Time Points in Patients Starting Topical Glaucoma Medication, King AJ; Rotchford AP, JAMA ophthalmology, 2016; 134: 742-747

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When medical treatment is initiated in a patient affected by glaucoma, individual response to prescribed agent is extremely important. To better characterize individual response to medications, a monocular trial test (MTT) was first suggested by Drance et al.¹ Basically, it consists of administering medical agents unilaterally for a short period, leaving the fellow eye untreated, until a constant hypotensive effect is achieved. MTT rationale is that IOP is not constant, but fluctuates in the short (during the day) and in the long (day-by-day) term. It has been postulated that IOP reduction in the treated eye reflects both therapeutic effect and IOP fluctuations; on the other hand, untreated eye exhibits only spontaneous IOP changes, allowing for a correction of IOP data in the treated eye.

In this study, King et al. demonstrated the use of MTT in glaucoma and ocular hypertension naïve patients may provide a significantly more accurate estimate of the real therapeutic response to a prostaglandin analogue (travoprost). Moreover, MTT may be effective in estimating therapeutic response also when pre-treatment and post-treatment IOPs are measured at different timepoints. According to these results, MTT may not only overwhelm the regression to the mean of IOP values, but also partially correct for short-term and long-term fluctuations.

MTT assumes that diurnal IOP fluctuations are equal, or at least very similar, in both eyes. On this basis, IOP values of the treated eye can be corrected for the measurements of the fellow eye. While a quite similar diurnal IOP rhythm in both eyes of King et al.'s cohort can be inferred from the paper, this probably does not apply to all glaucoma patients. Indeed, IOP may vary in an asymmetric fashion, both in healthy and glaucomatous subjects.^2-5 Dinn et al. performed diurnal IOP curves on treated and untreated glaucoma patients and found that the probability of having an absolute change < 2 mmHg between fellow eyes was 68% to 90% (untreated subjects) and 72% to 82% (treated subjects) for all time-points.² These results indicate that the concordance of diurnal IOP fluctuation between fellow eyes in glaucoma patients is fairly high, but not perfect.

Just like asymmetric IOP fluctuations can be recorded during a diurnal IOP curve, asymmetric IOP fluctuations can be encountered from one visit to another, days or months apart.^6,7 In a retrospective study by Realini et al., 21 of 42 healthy subjects and 24 of 38 glaucoma patients (50% and 63.2%) exhibited an asymmetric IOP fluctuation of at least 3 mmHg from one visit to another, representing a 15% change from baseline.6 In terms of absolute magnitude, asymmetric IOP fluctuation measured 3.7 ± 1.2 mmHg in healthy subjects and 4.0 ± 1.2 mmHg in glaucoma patients. MTT does not take into account asymmetric fluctuation in the long term, assuming that long-term fluctuation is equal in both eyes. Besides these data, the effect of medical treatment on IOP fluctuation is not completely known,⁸ and it cannot be excluded an effect of medical agents on 24-hour IOP rhythm of the treated eye, both in the short and in the long term. Interestingly, King et al. underlined that the treatment in their study did not demonstrate any effect on diurnal IOP pattern, probably as deduced from diurnal IOP curves.

A well-recognized limit of MTT is the assumption there is no contralateral pharmacological effect determined by systemic absorption of the prescribed agent. This assumption limits the use of MTT with several pharmacological classes. While the contralateral effect due to β-blocker agents has been well described,^9,10 little or no effect has been described for prostaglandin analogues.¹¹

All these factors should be taken into account when interpreting MTT and the results of this study. MTT could be a useful test in glaucoma practice, when all these assumptions are verified. However, this probably implies as many clinical efforts that overwhelm the advantages of the test.

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