Julie E. Whitcomb

Ex vivo porcine iris stiffening due to drug stimulation.

The purpose of this study was to quantify how the elastic modulus of the ex vivo iris changes following stimulation by pilocarpine (PILO), phenylephrine (PE), and tropicamide (TROP). Irides (n = 20) were dissected from porcine eyes within 4 h post-mortem and tested uniaxially. Either the entire iris or sector thereof was used. The samples were stretched up to 40% Green strain. The radial modulus was calculated from the linear portion of the stress-strain curve, and the azimuthal modulus was fitted to a model treating the iris as a collection of circular elastic bands. One of the three drugs (n = 6 or 7) of interest was added (80 microg/ml) to the bath surrounding the tissue, and the test was repeated. Changes in pupil diameter of free-floating samples and isometric force of mounted samples confirmed that the tissue was responsive to the drugs. The untreated iris modulus for cut sections in radial extension was 4.0 +/- 0.9 kPa (mean +/- s.d., n = 20), and treated iris modulus was 7.7 +/- 2.0 kPa (PILO, n = 7), 6.9 +/- 2.2 kPa (PE, n = 6), and 8.4 +/- 1.7 kPa (TROP, n = 7). Intact irides (n = 10) gave similar trends but values approximately 25% higher, presumably due to support from the nominally unloaded tissue. The azimuthal modulus of the untreated iris was 2.97 +/- 1.3 kPa (n = 5), and that of the treated iris (PILO) was 5.34 +/- 2.1 kPa. Although PILO, PE, and TROP work by different mechanisms, all three had similar results - an increase of modulus by a factor of two. These results suggest that in most normal situations the iris remains compliant at all pupil diameters.

The Posterior Location of the Dilator Muscle Induces Anterior Iris Bowing during Dilation, Even in the Absence of Pupillary Block

PURPOSE To examine the effect of the posterior location of the dilator on iris anterior curvature during dilation. METHODS An in vivo human study, an ex vivo porcine experiment, and an in silico computational model were performed in parallel. Iris anterior curvature was measured in vivo before and after dilation by time-domain slit lamp optical coherence tomography (SL-OCT). All patients (n = 7) had undergone laser peripheral iridotomy to eliminate any pupillary block due to primary angle-closure glaucoma. In the ex vivo experiments, isolated porcine irides (n = 30) were secured at the periphery and immersed in an oxygenated Krebs-Ringer buffer. Dilation was induced pharmaceutically by the addition of 2.5% phenylephrine and 1% tropicamide. An in-house optical coherence tomography (OCT) system was used to obtain iris images before and after dilation. A finite element model was also developed based on typical geometry of the iris from the initial OCT image. The iris was modeled as a neo-Hookean solid, and the active muscle component was applied only to the region specified as the dilator. RESULTS An increase in curvature and a decrease in chord length after dilation were observed in both experiments. In both the in vivo and ex vivo experiments, the curvature-to-chord length ratio increased significantly during dilation. Computer simulations agreed well with the experimental results only when the proper anatomic position of dilator was used. CONCLUSIONS The posterior location of the dilator contributes to the anterior iris bowing via a nonpupillary block dependent mechanism.

Spatial Heterogenity of Iris Elasticity Measured by Indentation

Angle-closure glaucoma, pigment dispersion syndrome, and intraoperative floppy iris syndrome (IFIS) are all ocular disorders that involve abnormal morphologies of the iris. In angle-closure glaucoma, for example, the iris bows anteriorly and impedes the natural flow of the fluid (aqueous humor), which then increases the intraocular pressure (IOP) leading to vision loss. The iris contour is determined by a combination of external stresses arising from the flow of the aqueous humor [1] and internal stresses due to the passive and active components of the constituent tissues. We have previously shown that the iris has a mechanical asymmetry [2] and that posterior positioning of the dilator muscle within the iris contributes to the anterior bowing during dilation [3]; however, the relative contributions of the individual components of the iris are unknown.Copyright

Mechanical Properties of the Iris Dilator and Stroma Using Nanoindentation

In certain disorders of the eye such as angle-closure glaucoma [1], pigment dispersion syndrome [2], and intra-operative floppy iris syndrome [3] the contour of the iris plays an important role. The active iris contour is determined by a combination of external stresses arising from the flow of the aqueous humor and internal stresses due to the passive and active components of the constituent tissues. For example, in angle closure, the iris bows anteriorly, and the abnormal shape and position of the iris are directly related to the blockage of aqueous humor outflow, increasing the intraocular pressure. While the interaction between the aqueous humor and iris has been studied [4], little is known about the effect of the components of the iris on the contour. The iris is composed of stroma, pigment epithelial cells, and two constituent muscles, the sphincter iridis and dilator pupillae (Fig1).Copyright

The effect of the posterior location of the dilator on the iris concavity

Aqueous humor (AH) constantly flows in the anterior eye to provide avascular tissues, notably the lens and cornea, with oxygen and nutrients. If AH outflow is impeded, the normal intraocular pressure could reach to dangerous levels. In angle closure, the abnormal shape and position of the iris is directly related to the blockage of the outflow. In particular, when the peripheral iris moves forward, it may narrow or close the angle between the iris and cornea, where most of AH leaves the anterior eye.Copyright

IRIS stiffening following drug stimulation

Glaucoma is a general term for the deterioration of the optic nerve head usually associated with an increase of intraocular pressure (IOP). Certain types of glaucoma are associated directly with the displacement of the iris from its normal morphology [1]. For example, angle closure glaucoma and pigment dispersion syndrome involve abnormal anterior or posterior displacement of the iris, respectively [2]. In angle closure, the abnormal position of the peripheral iris blocks aqueous humor access to the outflow pathway (trabecular meshwork), increasing the IOP. Although there has been a considerable amount of ultrastructural characterization of the iris [3], to our knowledge, there as been little done on the mechanical characterization of the iris other than a previous study by Heys and Barocas on passive bovine irides [4]. To have a complete understanding of these it requires that we understand the mechanical properties of the iris in both its passive and stimulated states. Mechanical analysis of the iris requires the consideration of its two constituent muscles, the inner sphincter iridis and the outer dilator pupillae, see Fig. 1. The sphincter iridis is innervated parasympathetically whereas the dilator is innervated sympathetically.Copyright