Effect of Pilocarpine Hydrochloride on the Schlemm Canal in Healthy Eyes and Eyes With Open-Angle Glaucoma.

IMPORTANCE The in vivo effect of pilocarpine hydrochloride on the Schlemm canal may help explain its pharmacologic mechanism of action and better indicate its clinical use. OBJECTIVE To investigate the effect of pilocarpine on the structure of the Schlemm canal in vivo in healthy eyes and eyes with glaucoma. DESIGN, SETTING, AND PARTICIPANTS In this case-control study, healthy individuals and patients with open-angle glaucoma were prospectively enrolled between September 1, 2013, and June 30, 2014, after a complete ophthalmologic examination at a tertiary glaucoma referral practice. Eighty-one serial, horizontal, enhanced depth imaging optical coherence tomographic B-scans (interval between B-scans, approximately 35 µm) of the nasal corneoscleral limbus were performed before and 1 hour after topical administration of pilocarpine, 1%, in 1 eye of healthy volunteers and pilocarpine, 2%, in 1 eye of patients with glaucoma. Fifty B-scans in the overlapping area (circumferential length, approximately 1.7 mm) between the 2 sets of serial scans (before and after pilocarpine administration) were selected for analysis based on the structures of aqueous and blood vessels as landmarks. The cross-sectional area of the Schlemm canal was measured in each selected B-scan. Volume of the Schlemm canal was calculated using commercially available 3-dimensional reconstruction software. MAIN OUTCOMES AND MEASURES Mean cross-sectional area of the Schlemm canal. RESULTS Enhanced depth imaging optical coherence tomographic scans of the Schlemm canal were performed successfully before and after administration of pilocarpine, 1%, in 9 healthy eyes (9 individuals) and pilocarpine, 2%, in 10 eyes with glaucoma (10 patients) (mean [SD] age, 31.9 [7.8] and 68.7 [13.2] years, respectively). Following pilocarpine administration, mean (SD) intraocular pressure decreased from 14.3 (1.3) to 13.7 (1.1) mm Hg in healthy eyes (P = .004) and from 17.5 (6.0) to 16.6 (6.1) mm Hg in eyes with glaucoma (P = .01). The mean (SD) cross-sectional area of the Schlemm canal increased by 21% (4667 [1704] to 5647 [1911] µm2) in healthy eyes (P < .001) and by 24% (3737 [679] to 4619 [692] µm2) in eyes with glaucoma (P < .001) (mean difference in percent increase, 2.2%; 95% CI, -8.5% to 12.9%). The mean (SD) volume of the Schlemm canal in the overlapping area increased from 8 004 000 (2 923 000) to 9 685 000 (3 277 000) µm3 in healthy eyes (P < .001) and from 6 468 000 (1 170 000) to 7 970 000 (1 199 000) µm3 in eyes with glaucoma (P < .001). CONCLUSIONS AND RELEVANCE These data suggest that pilocarpine expands the Schlemm canal in eyes with and without glaucoma. No differences in the effect were identified between the 2 groups. Enhanced depth imaging optical coherence tomography may be useful in investigating the effect of pharmacologic agents on the Schlemm canal.

[1]  I. Grierson,et al.  The effects of topical pilocarpine on the morphology of the outflow apparatus of the baboon (Papio cynocephalus). , 1979, Investigative ophthalmology & visual science.

[2]  Marinko V Sarunic,et al.  Imaging the ocular anterior segment with real-time, full-range Fourier-domain optical coherence tomography. , 2008, Archives of ophthalmology.

[3]  E. Lütjen-Drecoll,et al.  Morphologic changes in the outflow pathways of bovine eyes treated with corticosteroids. , 2010, Investigative ophthalmology & visual science.

[4]  M. Flocks,et al.  Studies on the mode of action of pilocarpine on aqueous outflow. , 1957, American journal of ophthalmology.

[5]  R. Ritch,et al.  In vivo evaluation of focal lamina cribrosa defects in glaucoma. , 2012, Archives of ophthalmology.

[6]  F. Paulsen,et al.  The structure of the trabecular meshwork, its connections to the ciliary muscle, and the effect of pilocarpine on outflow facility in mice. , 2014, Investigative ophthalmology & visual science.

[7]  E. Lütjen-Drecoll Structural factors influencing outflow facility and its changeability under drugs. A study in Macaca arctoides. , 1973, Investigative ophthalmology.

[8]  D. Coleman,et al.  Pilocarpine. Effect on the anterior chamber and lens thickness. , 1972, Archives of ophthalmology.

[9]  P. Kaufman,et al.  Aqueous humor dynamics in the owl monkey with comparison to cynomolgus. , 1985, Current eye research.

[10]  D. Kook,et al.  Ultrastructural and biochemical evaluation of the porcine anterior chamber perfusion model. , 2006, Investigative ophthalmology & visual science.

[11]  D. Coleman,et al.  Pilocarpine-induced lens changes. An ultrasonic biometric evaluation of dose response. , 1974, Archives of ophthalmology.

[12]  P. Kaufman,et al.  Acute and chronic structural effects of pilocarpine on monkey outflow tissues. , 1998, Transactions of the American Ophthalmological Society.

[13]  R. Spaide,et al.  Enhanced depth imaging spectral-domain optical coherence tomography. , 2008, American journal of ophthalmology.

[14]  J. Jonas,et al.  Optical coherence tomography-assisted enhanced depth imaging of central serous chorioretinopathy. , 2013, Investigative ophthalmology & visual science.

[15]  R. Ritch,et al.  Enhanced depth imaging optical coherence tomography of optic nerve head drusen. , 2013, Ophthalmology.

[16]  J. Rohen,et al.  The relation between the ciliary muscle and the trabecular meshwork and its importance for the effect of miotics on aqueous outflow resistance , 2004, Albrecht von Graefes Archiv für klinische und experimentelle Ophthalmologie.

[17]  S. Smith,et al.  An increased effect of pilocarpine on the pupil by application of the drug in oil. , 1978, The British journal of ophthalmology.

[18]  Hiroshi Ishikawa,et al.  Identification and assessment of Schlemm's canal by spectral-domain optical coherence tomography. , 2010, Investigative ophthalmology & visual science.

[19]  Robert Ritch,et al.  Enhanced depth imaging optical coherence tomography of deep optic nerve complex structures in glaucoma. , 2012, Ophthalmology.

[20]  I. Grierson,et al.  The trabecular wall of Schlemm's canal: a study of the effects of pilocarpine by scanning electron microscopy. , 1979, The British journal of ophthalmology.

[21]  Grant Wm,et al.  Clinical measurements of aqueous outflow. , 1951 .

[22]  Bo Wang,et al.  Morphometric analysis of aqueous humor outflow structures with spectral-domain optical coherence tomography. , 2012, Investigative ophthalmology & visual science.

[23]  Sina Farsiu,et al.  Pilocarpine-induced dilation of Schlemm's canal and prevention of lumen collapse at elevated intraocular pressures in living mice visualized by OCT. , 2014, Investigative ophthalmology & visual science.

[24]  A. Loewenstein,et al.  Enhanced depth imaging optical coherence tomography: choroidal thickness and correlations with age, refractive error, and axial length. , 2012, Ophthalmic surgery, lasers & imaging : the official journal of the International Society for Imaging in the Eye.