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Assessment of oxygen saturation (O2Sat) in the optic nerve head (ONH) under controlled intraocular pressure (IOP) elevations may facilitate the detection of early phase glaucoma. Objective of this research is to quantify O2Sat in response to acute IOP elevations in the ONH of cynomolgus monkey Hyperspectral imaging (HSI) was used to test the hypothesis that O 2Sat distribution resulting from graded IOP elevations in retinal vessels and the ONH can be detected by HSI technique. Assessment of percent O 2Sat in retinal vessels and the ONH was carried out using least-squares curve fit of experimental spectral curves calibrated with reference curves. A previous algorithm for relative O2Sat calculation was improved by correction for blood volume which allowed comparison of O 2Sat in vessels and in the ONU, and tested on a multi-spectral imaging (MSI) system to reduce the time required to collect imagery from human subjects. Linear relationship was found between relative and calculated percent O 2Sat. The effects of IOP on the O2Sat were visualized in saturation maps. Retinal arteries showed nonsignificant reduction in O 2Sat between IOPs of 10 and 30 mm Hg (P = 0.805) and significant reductions at 45 and 55 mm Hg (P = 0.01, P < 0.0001 respectively); veins showed incremental reduction in O2Sat at each elevation of IOP. The responses in the rim of the ONH were similar to those in the artery, with the exception of the temporal cup, which only showed significant reduction in O2Sat at 55 min Hg. Models of oxygen diffusion out of the retinal artery, and of oxygen diffusion between paired arterioles and venules suggest that a further measurement of retinal arterial blood velocity is necessary Results are consistent with early studies that optic nerve fiber layer and prelaminar neural tissues may become ischemic at low level of perfusion pressure. Findings of O2Sat at graded IOP elevations in experimental glaucoma and direct measurements of blood flow will be necessary to further assess the importance of these findings. The HSI and MSI techniques are useful in diagnosing conditions, monitoring treatments, and studying the mechanisms of the diseases / acase@tulane.edu

Iontophoresis, the application of low-level electrical current to promote movement of a substance across a boundary, was investigated in conjunction with topically applied eye medicines with easy to determine effect times through noninvasive methods (dilation/reversal, and intraocular pressure [IOP] lowering [glaucoma] medications) to assess their effect on tissues of the anterior segment of the eye Initial study focused on chemical stability of ophthalmic medications subjected to applied electrical currents. Twenty-four tested drugs (dilators, constrictors, IOP-reducing drugs, and anesthetics) underwent eleven iontophoretic treatment levels (10muA-20mA) for durations of two minutes. Macroscopic observations, pH level, HPLC profiles, and solution resistivity were noted. All tested drugs remained chemically stable in the current density range of interest (&le;1.25mA/cm2); a subset of fourteen drugs displayed minimal changes through all currents Four of these drugs were used for subsequent in vivo testing in adult rabbits: phenylephrine hydrochloride, pilocarpine hydrochloride, timolol hemihydrate, and brimonidine tartrate. Three iontophoretic treatment conditions were investigated for dilation/reversal (0.5mA for 60sec, 1mA for 30sec, and 1mA for 60sec), and one treatment condition for IOP lowering drugs (1mA for 60sec), lontophoretic current was delivered via a TENS electrode atop a closed eyelid after one drop of drug was administered topically to the eye. No significant difference was observed between iontophoretically treated and untreated eyes in time-to-effect for dilation using phenylephrine hydrochloride (p=0.22, n=8) or reversal using pilocarpine hydrochloride (p=0.32, n=8), or for maximum obtained pupil size (p=0.51, n=8). A significant reduction in time-to-effect was observed iontophoretically for the IOP lowering medication timolol hemihydrate (p=0.05, n=2), but not for brimonidine tartrate (p=0.15, n=3) The in vitro iontophoretic method employed in this study successfully verified chemical stability after current application for 14 of the 24 tested drugs, of which 4 drugs were subsequently tested for iontophoretic use in vivo. The particular in vivo iontophoretic method employed in this study, while designed around constraints of patient acceptance associated with eventual deployment to human clinical use, was unsuccessful at achieving efficiency that would justify further development. Future refinements to the in vivo method may alter this assessment / acase@tulane.edu

Primary open angle glaucoma is a group of diseases responsible for a progressive optic neuropathy that is characterized by cupping of the optic nerve head, thinning of the neuroretinal rim, atrophy of the optic nerve fibers, and visual field loss. It may afflict as many as 67 million people worldwide. It is often, but not always, associated with an increase in intraocular pressure (IOP). There is still no clear etiological understanding of why extensive remodeling of the lamina cribrosa occurs. It is likely that it is multi-factorial and interdependent on several events. The work contained herein investigated the possibility that ischemia in the optic nerve head may trigger the release of biochemical factors from support cells that weaken the lamina cribrosa and lead to neural compression and death through mechanical means Long term studies on low oxygen and nutrient studies revealed that rabbit scleral fibroblasts had higher levels of active MMP-2 in 5% O2 than in 21% O2, and in groups without a medium change than in groups with a regular medium change. Short term studies on other ocular cell types found no difference in total MMP-2. Both studies provided a basis for developing better in vitro models of ischemia Cellular solid models provided a means to relate laminar microstructure to continuum-level properties. Macro-scale stress was amplified above normal levels of IOP in the lamina cribrosa but the stress levels were less than in the peripapillary sclera and in the sclera far from the scleral canal. The most important parameter in determining the IOP-induced stress and strain in the lamina cribrosa was the stiffness of the laminar microstructure relative to the sclera. Predicted strains in a normal lamina, for an increase in IOP of 15 mm Hg to 50 mm Hg, ranged from approximately 0.5 to 5% based on different model parameters. Data obtained from nanoindentation tests suggested that the lamina cribrosa stiffness does little to resist the opening of the scleral canal. Additional work should target the peripapillary sclera and scleral canal to determine if changes in their microstructure could be an important part of glaucomatous damage / acase@tulane.edu

In recent years there has been a great deal of interest in the use of fluorescent particles to quantify ocular blood flow. The extraction and analysis of data from the markers, however, are tedious and subjective. This has limited the utility of particle-tracking techniques, and has suggested the need for a means of automating these time-consuming tasks. The objectives of this research are: to develop a fluorescent particle suitable for imaging the ocular fundus; to develop and validate computer software to automate the extraction of data from particle-tracking sessions; to evaluate the reproducibility of the software; to use the software to map hemodynamic parameters in the normal rabbit fundus; and to evaluate the software as a tool for detecting pathological changes in retinal blood flow In developing fluorescent microsphere imaging, we evaluated and optimized single- and multiple-dye polystyrene microspheres as tools for imaging retinal and choroidal blood flow. These particles are injected systemically and excited transcorneally using the lasers of the scanning laser ophthalmoscope. The ophthalmoscope then creates a video image of the particle emissions. By tailoring the excitation and emission spectra of the particles, we can selectively image blood flow at various depths and in various tissues of the ocular fundus We developed a series of computer programs with which videotapes of these imaging sessions can be automatically evaluated. After detecting the positions of particles, we generated maps of relative volumetric blood flow in the entire field of view of the ophthalmoscope. Further, we developed routines for quantifying particle motions and used the information to map absolute blood velocities in the fundus. We combined this information with our maps of vessel diameters to measure absolute blood flow rates in large vessel segments; this provided a scale with which we mapped absolute flow rates across the entire ocular fundus We then tested these techniques by imaging particles in the eyes of four rabbits. Each rabbit was evaluated three times, including one session in which we induced abnormal flow. In a series of ANOVA tests, we demonstrated the ability of the software to distinguish normal from pathological ocular blood flows / acase@tulane.edu

The design and testing of an ocular Shack-Hartmann aberrometer is presented. The aberrometer objectively measures optical aberrations in the human eye in vivo. The sensor was successfully tested for measurements of refractive error (sphere and cylinder) and spherical aberration. Vignetting limits the measurement range of the wavefront to a range of -10 D to +15 D. Large refractive errors and decentration of the measurement induce aberrations in the test wavefront. Analytical tools to correct for these systematic errors were developed. A clinical study was conducted assessing visual performance in 158 eyes of 89 subjects before and after LARK refractive surgery. The main results of the study were that refractive surgery corrects refractive errors very accurately. A slight regression in refraction during the 12 months after surgery was noted. Measurements of ocular aberrations using the Shack-Hartmann aberrometer revealed that refractive surgery introduced large amounts of higher order aberrations, mainly spherical aberration and coma. The amount of aberrations changed significantly during the 12 months wound healing period. The dark adapted pupil diameter of the eye increased significantly during the first 6 months after surgery. The changes in ocular aberrations and pupil diameter were correlated to changes in contrast sensitivity in the human eye. The analysis of corneal topography showed that while the anterior corneal curvature changed due to surgery, we also saw a change in the posterior corneal curvature as a biomechanical response to surgery. A Customized Eye Model was designed and tested based on the clinical measurements. The model used conic surfaces and modeled defocus and spherical aberration. This computer eye model was then used in optical lens design software to calculate an optimal Customized Ablation Pattern for individual eyes.

<p> Refractive development has been shown to be influenced by optical defocus in the eye and the interpretation of this signal appears to be localized in the retina. Optical defocus is not uniform across the retina and has been suggested as a potential cause of myopia development. Specifically hyperopic focus, i.e. focusing light behind the retina, may signal the eye to elongate, causing myopia. This non-uniform hyperopic signal appears to be due to the retinal shape. Ultimately, these signals are detected by the retina in an as yet undetermined manner. The purpose of this thesis is to examine the retinal profile using a novel method developed at Indiana University and then to examine retinal structural changes across the retina associated with myopia. </p><p> Myopes exhibited more prolate retinas than hyperopes/emmetropes using the SD OCT. Using the SD OCT, this profile difference was detectable starting at 5 degrees from the fovea, which was closer than previously reported in the literature. These results agreed significantly with results found from peripheral refraction and peripheral axial length at 10 degrees. Overall, the total retina was thinner for myopes than hyperopes/emmetropes. It was also statistically significantly thinner for the Outer Nuclear Layer (ONL), Inner Nuclear Layer (INL) and Outer Plexiform Layer (OPL) but not for other retinal layers such as the Ganglion Layer. Thinning generally occurred outside of 5 degrees. </p><p> The SD OCT method provided a nearly 10 fold increase in sensitivity which allowed for detection of profile changes closer to the fovea. The location of the retinal changes may be interesting as the layers that showed significant differences in thickness are also layers that contain cells believed to be associated with refractive development (amacrine, bipolar, and photoreceptor cells.) The reason for the retinal changes cannot be determined with this study, but possible theories include stretch due to axial elongation, neural remodeling due to blur, and/or direct influence on refractive development due to neural cell densities.</p>