Lower limits of intraocular pressure in glaucoma clinical trials.

Purpose: To determine the association of the lower limit of intraocular pressure (IOP) specified in the inclusion criteria to baseline and active treatment visit IOPs for monotherapy treatments.

Methods: A review of clinical trial articles evaluating currently used topical glaucoma medicines. Articles were published between January 1995 and December 2011.

Results: This study included 37 monotherapy treatment arms from 15 studies. There were 18 prostaglandin analogs, 8 β-blockers, 8 carbonic anhydrase inhibitors, 2 α-agonists, and 1 unoprostone. For all studies included generally there was a stepwise increase in the baseline 8 AM and diurnal IOP of approximately 1 mm Hg for each 1 mm Hg increase in entry criteria. This was true for all treatment arms together, with or without a PM entry criterion (P<0.0001). However, the inclusion of an afternoon entry criterion time point did not seem to affect average IOP at baseline for the 8 AM and diurnal IOP. The treated reductions from baseline were not statistically different based on morning or afternoon entry criteria for either the 8 AM or diurnal IOPs (P≥0.07).

Conclusions: Progressively higher 8 AM entry criteria IOPs at untreated baseline may influence, depending on design, in a linear manner the 8 AM and diurnal baseline IOPs of glaucoma studies at baseline. However, this effect was not observed in the treated reductions from baseline. Further, the addition of an afternoon entry criterion time point does not seem to change baseline 8 AM and diurnal IOPs.