Pilocarpine:The Frequency Dogma

Abstract

Pilocarpine, a cholinergic agonist, reduces intraocular pressure by stimulating postsynaptic muscarinic receptors in the ciliary muscle causing it to contract. Pilocarpine preparations have been used since the 1870s, but the need to administer them frequently everyday has made them unsuitable for many patients.1 The optimal strength and frequency of administration of pilocarpine for control of intraocular pressure has not been scientifically defined. The purpose of this investigation, was to evaluate the effect of varying frequency of pilocarpine hydrochloride 2% on IOP. This study was approved by the Wills Eye Institute Institutional Review Board (IRB#08-914E). Informed consent was obtained prior to the initial screening evaluation. This was a prospective analysis of patients aged 18 years or older with open angle glaucoma or open angle glaucoma suspects. Patients were selected from glaucoma service of Wills Eye Institute. Patients were either naive to glaucoma therapy or administering topical medications other than long acting miotics. Patients were excluded from the study if they had coexisting ocular pathology, recent ocular surgery, or ocular inflammation or ocular infection within 3 months prior to the screening visit, previously recorded allergy to pilocarpine, pregnant women or nursing mothers. The study included 15 patients with demographic data detailed in Table 1. At the start of the study the following attributes were checked: visual acuity, color of the iris (blue, brown or hazel), size of the pupil, IOP measurement by Goldmann applanation tonometer (P0), gonioscopy for nature of the chamber angle, slit-lamp biomicroscopy using a +66D lens for cup-to-disk ratio, depth of the cup and degree of pallor of the disk and visual field by Humphrey field analyzer (Carl Zeiss Meditec, Inc.). A 4 minutes pressure tracing was obtained with a needle recorder attached to the indentation tonometer while it was gently applied to the cornea. Its position on the cornea was maintained until a smooth tracing for 4 minutes was obtained. The P0 and the change in scale reading during the 4 minutes were then used to obtain the coefficient of outflow facility (C) from tonographic Tables.2 All medications were stopped for thirty days. On the fourth day, intraocular pressure was measured at 9 am, 12 pm and 5 pm to determine the daily variation off treatment. Pilocarpine 2% was started in both eyes on the fifth day. On day 5 through 8, each patient was instructed to take pilocarpine once daily in the right eye at 10 pm, and twice daily in the left eye (10 am and 10 pm). On days 9 through 11, pilocarpine was again administered once daily in the right eye at 10 pm, but was increased to four times daily in left eye (8 am, 1 pm, 6 pm and 10 pm). On days 12 through 15 the program was reversed, pilocarpine being given four times daily in the right eye and once daily in the left eye. On days 16 through 18 the program was again reversed, pilocarpine now being used four times daily in the left eye and once daily in the right eye. On the last three days of the study, 19 through 22, this was again reversed, pilocarpine now being used four times daily in the right eye and once in the left eye. Following the 10 pm dosage on day 22 no medication was used for three days. Intraocular pressure was taken at 9 am, 12 pm and 5 pm on days 4, 8, 11, 15, 18, 22 and 25. Thus the frequencies employed were one, two and four times daily in each patient, and intervals tested were 1, 2, 4, 7, 11, 14, 19, 59, 62 and 67 hours post-therapy. The total duration of the study was twenty-five days. Study protocol is described in Table 2. The mean IOP with different frequency of administration of pilocarpine 2% are shown in Table 3. The coefficient of outflow ranged from 0.50 to 0.30. Statistical analysis revealed that four times daily administration resulted in significantly lower tension compared to daily or twice daily treatment. The mean IOP obtained with twice daily treatment was slightly lower when compared to the mean IOP on once daily treatment. However, the difference was not statistically significant. There was no significant difference in the mean IOP between the two periods of no treatment. Table 4 summarizes the mean IOP taken at 9 am, 12 pm, and 5 pm on different frequencies of pilocarpine 2%. On Table 1: Patient demographics