Pilocarpine’s effects on the blood-aqueous barrier of the human eye as assessed by high-resolution, contrast magnetic resonance imaging Thomas F. Freddo a, * , Samuel Patz b , Yevgeniy Arshanskiy b a Department of Ophthalmology and Pathology, Boston University School of Medicine, 715 Albany Street, L-905, 02118-2307 Boston, MA, USA b Department of Radiology, New England Medical Center, 750 Washington St, Boston MA, 02111, USA Received 18 March 2005; accepted in revised form 1 July 2005 Available online 19 September 2005 Abstract The purpose of this research was to reassess the effects of topical pilocarpine on the integrity of the blood-aqueous barrier, using high resolution, magnetic resonance imaging, and the standard intravenous contrast agent gadolinium dimeglumine. It has long been known that topical pilocarpine gives rise to an increase in protein levels in the anterior chamber of the eye. This protein scatters light and is referred to clinically as ‘flare’. Prior studies concluded that pilocarpine-induced flare resulted from disruption of the blood-aqueous barrier. These studies relied upon indirect methods that precluded direct visualization of the posterior chamber of the eye. Five normal, human volunteers (age 22–40) received a single drop of 3% pilocarpine in one eye, following baseline measurements of pupil size and anterior chamber ‘flare’. These measurements were repeated every 15 min for 45 min. The subject was then positioned in the magnet and the eye that received pilocarpine was taped closed and covered with a 3 in.-diameter receive-only surface coil. The open contralateral eye focused on a target to maintain fixation of the imaged eye. A baseline image of the eye was obtained and the contrast agent was administered intravenously. A series of additional images was obtained during the following 60 min to track the movement of contrast material from the bloodstream into the tissues and compartments of the eye. Percent enhancement was calculated from selected regions of interest in the images, including the ciliary body, and the anterior and posterior chambers. Within the 45 min after administration of pilocarpine, pupil size in mm decreased from (meanGS.D.) 5.7G1.5 to 2.5G0.5 (pZ0.0106). During this period, average flare/S.D. (photons msec K1 ) increased from 3.7G1.1 to 12.5G4.7 (pZ0.0151). In all cases, MRI images showed rapid enhancement of the ciliary body, followed by a progressive increase in signal in the anterior chamber but not the posterior chamber. These studies confirm that topical pilocarpine gives rise to ‘flare’ in the anterior chamber. But the lack of enhancement in the posterior chamber strongly suggests that the presence of this added protein in the anterior chamber is not the result of increased permeability of the blood-aqueous barrier of the ciliary body. These studies also introduce the novel concept that not all clinically observed flare is the result of blood-aqueous barrier compromise. q 2005 Elsevier Ltd. All rights reserved. Keywords: magnetic resonance imaging; pilocarpine; blood-aqueous barrier; human 1. Introduction The amount of plasma-derived protein in normal aqueous humor is very low, generally 1% or less of that found in plasma (Raviola, 1977). The capillaries of the ciliary body stroma are fenestrated, and therefore leak plasma proteins abundantly. Estimates of the percentage of plasma protein in the ciliary body stroma, relative to plasma, range as high as 74% (Bill, 1986). But tight junctions between the apico-lateral surfaces of non-pigmented ciliary epithelial cells normally block the diffusion of this plasma protein into the aqueous humor in the posterior chamber, thus forming a part of the blood-aqueous barrier (Raviola, 1977). Disruption of these tight junctions in anterior uveitis gives rise to elevations of aqueous humor protein levels (Freddo, 1987; Freddo and Sacks-Wilner, 1989). This additional protein causes a visible scattering of light during biomicro- scopic examination of the eye and is thus referred to clinically as flare. The physiological model of the blood-aqueous barrier available during most of the last 20 years concluded that the small amount of plasma-derived protein present in Experimental Eye Research 82 (2006) 458–464 www.elsevier.com/locate/yexer 0014-4835/$ - see front matter q 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.exer.2005.07.019 * Corresponding author. E-mail address: tfreddo@bu.edu (T.F. Freddo).