Doctor of Philosophy, University of Texas Austin (2011)
Lei Xing, Postdoctoral Faculty Sponsor
The primary goal of this study was the fabrication, long-term stability, and measured release of a marker dye from a micro-patterned drug delivery device using (i) mechanical puncture and (ii) photodisruption with an ophthalmic Nd:YAG laser.A drug delivery device was made from a transparent bio-compatible polymer. The device consisted of two 2.6?mm diameter reservoirs containing 10% Na fluorescein dye. The device was implanted in the rabbit's eye (n?=?2) with the cap of the device facing toward the exterior of the eye. Once the animals recovered from the implant surgery, 100% anhydrous glycerol was topically applied to the eye at the implantation site to decrease light scattering in the conjunctiva and sclera. The dye was released from one of the reservoir either using a 28?G ½ needle or an ophthalmic Q-switched Nd:YAG laser. A fluorescence spectrophotometer (FS) with fiber optic probe was used to measure the half-life of the dye in the eye. Measurements of fluorescence intensity were collected until the measurements return to baseline and histology was done on the tissue surrounded the device.None of the devices leaked of 10% Na fluorescein dye after implant. The ablation threshold of the drug delivery device was between 6 and 10?mJ to create 100-500?µm holes. The half-life measurement of the dye was found to be 13 days at the vitreous chamber after measuring the fluorescence intensity through the dilated cornea. Histology study showed minimal immune and foreign body response such as mild inflammation.This study established that the drug delivery device seemed to elicit minimal inflammatory response and retained its fluidic content until it was released with relatively longer retention time (half-life). Thus, similar device could be used for controlled release of drugs for certain ocular diseases.
View details for DOI 10.1002/lsm.21149
View details for Web of Science ID 000299076500006
View details for PubMedID 22127811
Light scattering in the normally white sclera prevents diagnostic imaging or delivery of a focused laser beam to a target in the underlying choroid layer. In this study, we examine optical clearing of the sclera and changes in blood flow resulting from the application of glycerol to the sclera of rabbits. Recovery dynamics are monitored after the application of saline. The speed of clearing for injection delivery is compared to the direct application of glycerol through an incision in the conjunctiva. Although, the same volume of glycerol was applied, the sclera cleared much faster (5 to 10 s) with the topical application of glycerol compared to the injection method (3 min). In addition, the direct topical application of glycerol spreads over a larger area in the sclera than the latter method. A diffuse optical spectroscopy system provided spectral analysis of the remitted light every two minutes during clearing and rehydration. Comparison of measurements to those obtained from phantoms with various absorption and scattering properties provided estimates of the absorption coefficient and reduced scattering coefficient of rabbit eye tissue.
View details for DOI 10.1117/1.3599985
View details for Web of Science ID 000294453800046
View details for PubMedID 21806288
Previous studies demonstrated a decrease in fluorescence intensity as tissue temperature increased. In vitro samples were increased from room temperature and in vivo canine liver from body temperature. This study investigated variations in fluorescence intensity with temperatures starting at 14°C and compared in vivo and in vitro results for consistency.A fiber optic-based noninvasive system was used to characterize the temperature effect on tissue fluorescence in hamster dorsal skin in vivo, and in sclera and cornea of enucleated pig eyes in vitro. As tissue was allowed to progress through the temperature range of 14-42°C, the spectra of auto-fluorescence with respect to temperature was sampled every 1-2 minutes. A pulsed nitrogen laser was used to excite fluorescence through a fiber optic probe with a source-detector aperture separation of 370?µm.Fluorescence intensity decreased as temperature increased from 14 to 42°C in a phantom containing Rhodamine B dye. Results from both in vivo and in vitro tissue followed the same trend of decreasing intensity as tissue temperature increased from 14°C. Spectral intensity lineshape changed around 450?nm due to absorption from tissue.Cooling a tissue increased fluorescence intensity of skin in vivo, in all experiments. In vitro results were consistent with in vivo measurements.
View details for DOI 10.1002/lsm.21023
View details for Web of Science ID 000286440300006
View details for PubMedID 21254141
The objective of this article is to quantify the effect of hyper-osmotic agent (glycerol) on blood velocity in hamster skin blood vessels measured with a dynamic imaging technique, laser speckle contrast imaging (LSCI).In this study a dorsal skin-flap window was implanted on the hamster skin. The hyper-osmotic drug, that is, glycerol was delivered to the skin through the open dermal end of the window model. A two-dimensional map of blood flow of skin blood vessels was obtained from the speckle contrast (SC) images.Preliminary studies demonstrated that hyper-osmotic agents such as glycerol not only make tissue temporarily transparent, but also reduce blood flow. The blood perfusion was measured every 3 minutes for 36-66 minutes after diffusion of anhydrous glycerol. Blood flow in small capillaries was found to be reduced significantly within 3-9 minutes. Blood flow in larger blood vessels (i.e., all arteries and veins) decreased over time and some veins had significantly reduced blood flow within 36 minutes. At 24 hours, there was a further reduction in capillary blood perfusion whereas larger blood vessels regained flow compared to an hour after initial application of glycerol.Blood flow velocity and vessel diameter of the micro-vasculatures of hamster skin were reduced by the application of 100% anhydrous glycerol. At 24 hours, capillary perfusion remained depressed.
View details for DOI 10.1002/lsm.20803
View details for Web of Science ID 000269710800004
View details for PubMedID 19670326