Faculty Bibliography

Glaucoma is a leading cause of blindness that leads to characteristic changes in the optic nerve head (ONH) region, such as nasalization of vessels. It is unknown whether the spatial location of this vessel shift inside the ONH occurs within the lamina cribrosa (LC) or the prelaminar tissue. The purpose of this study was to compare the location of the central retinal vessel trunk (CRVT) in the LC and prelaminar tissue in living healthy and glaucomatous eyes. We acquired 3-dimensional ONH scans from 119 eyes (40 healthy, 29 glaucoma suspect, and 50 glaucoma) using optical coherence tomography (OCT). The CRVT location was manually delineated in separate projection images of the LC and prelamina. We found that the CRVT in glaucoma suspect and glaucomatous eyes was located significantly more nasally compared to healthy eyes at the level of the prelamina. There was no detectable difference found in the location of the CRVT at the level of the LC between diagnostic groups. While the nasal location of the CRVT in the prelamina has been associated with glaucomatous axonal death, our results suggest that the CRVT in the LC is anchored in the tissue with minimal variation in glaucomatous eyes.

Photoacoustic (PA) imaging detects acoustic signals generated by thermal expansion of a light-excited tissue or contrast agents. PA signal amplitude and image quality directly depend on the light fluence at the target depth. With conventional PA imaging systems, approximately 30% energy of incident light at the near-infrared region would be lost due to reflection on the skin surface. Such light loss directly leads to a reduction of PA signal and image quality. A new light delivery scheme that collects and redistributes reflected light energy was recently suggested, which is called the light catcher. In our previous study, proof of concept using a finite-element simulation model was shown and a laboratory-built prototype of the light catcher was applied on tissue-mimicking phantoms. In this paper, we present an elaborate prototype of a high-frequency PA probe with the light catcher fabricated using 3-D printing technology, which is conformal to a subcutaneous tumor in mice. The in vivo usefulness of the developed prototype was evaluated in a mouse tumor model. Equipped with the light catcher, PA signal amplitude from the clinical photosensitizer injected into the mouse tumor was enhanced by 33.7%, which is approximately equivalent to the percent light loss due to reflection on the skin.

The purpose of this study was to characterize and determine the efficacy of a long-term, non-invasive gel/microsphere (GMS) eye drop for glaucoma. This novel drug delivery system is comprised of a thermoresponsive hydrogel carrier and drug-loaded polymer microspheres. In vitro release of brimonidine from the GMS drops and gel properties were quantified. A single brimonidine-loaded GMS drop was administered to 5 normotensive rabbits and intraocular pressure (IOP) was monitored for 28 days. Here we report that IOP reduction in rabbits receiving a single brimonidine GMS drop was comparable to that of rabbits receiving twice daily, standard brimonidine drops. GMS drops were retained in the inferior fornix in all animals for the length of the study. Our results suggest in vivo efficacy over 28 days from a single GMS drop and a potential decrease in systemic absorption, based on a lack of substantial IOP effects on the fellow untreated eye, compared to brimonidine twice-daily eye drops. To our knowledge, this represents the first long-term, drug-releasing depot that can be administered as a traditional eye drop.

Purpose: Although collagen microstructural crimp is a major determinant of ocular biomechanics, no direct measurements of optic nerve head (ONH) crimp have been reported. Our goal was to characterize the crimp period of the lamina cribrosa (LC) and peripapillary sclera (PPS) at low and normal IOPs. Methods: ONHs from 11 sheep eyes were fixed at 10-, 5-, or 0-mm Hg IOP and crimp periods measured manually from coronal cryosections imaged with polarized light microscopy (PLM). Using linear mixed-effect models, we characterized the LC and PPS periods, and how they varied with distance from the scleral canal edge. Results: A total of 17,374 manual collagen crimp period measurements were obtained with high repeatability (1.9 mum) and reproducibility (4.7 mum). The periods were smaller (P < 0.001) and less variable in the LC than in the PPS: average (SD) of 13.8 (3.1) mum in the LC, and 31.0 (10.4) mum in the PPS. LC crimp period did not vary with distance from the scleral canal wall (P > 0.1). PPS period increased with the square root of the distance to the canal (P < 0.0001). Conclusions: Small, uniform crimp periods within the sheep LC and immediately adjacent PPS may indicate that these tissues are setup to prevent large or heterogeneous deformations that insult the neural tissues within the canal. An increasing more variable period with distance from the canal provides a smooth transition of mechanical properties that minimizes stress and strain concentrations.

Telemedicine services facilitate the evaluation, diagnosis, and management of the remote patient. Telemedicine has rapidly flourished in the United States and has improved access to care, outcomes, and patient satisfaction. However, the use of telemedicine in ophthalmology is currently in its infancy and has yet to gain wide acceptance. Current models of telemedicine in ophthalmology are largely performed via "store and forward" methods, but remote monitoring and interactive modalities exist. Although studies have examined the effects of telemedicine, few reports have characterized its current status. We perform a descriptive analysis of the current state of teleophthalmology in the United States. We describe the use of teleophthalmology in the hospital and outpatient settings. We also review the applications to retinopathy of prematurity, diabetic retinopathy, age-related macular degeneration, and glaucoma, as well as anticipated barriers and hurdles for the future adoption of teleophthalmology. With ongoing advances in teleophthalmology, these models may provide earlier detection and more reliable monitoring of vision-threatening diseases.

Purpose: Evaluation of the effect of prelaminar tissue thickness on visualization of the lamina cribrosa (LC) using optical coherence tomography (OCT). Methods: The optic nerve head (ONH) region was scanned using OCT. The quality of visible LC microstructure was assessed subjectively using a grading system and objectively by analyzing the signal intensity of each scan's superpixel components. Manual delineations were made separately and in 3-dimensions quantifying prelaminar tissue thickness, analyzable regions of LC microstructure, and regions with a visible anterior LC (ALC) boundary. A linear mixed effect model quantified the association between tissue thickness and LC visualization. Results: A total of 17 healthy, 27 glaucoma suspect, and 47 glaucomatous eyes were included. Scans with thicker average prelaminar tissue measurements received worse grading scores (P = 0.007), and superpixels with low signal intensity were associated significantly with regions beneath thick prelaminar tissue (P < 0.05). The average prelaminar tissue thickness in regions of scans where the LC was analyzable (214 mum) was significantly thinner than in regions where the LC was not analyzable (569 mum; P < 0.001). Healthy eyes had significantly thicker average prelaminar tissue measurements than glaucoma or glaucoma suspect eyes (both P < 0.001), and glaucoma suspect eyes had significantly thicker average prelaminar tissue measurements than glaucoma eyes (P = 0.008). Significantly more of the ALC boundary was visible in glaucoma eyes (63% of ONH) than in healthy eyes (41%; P = 0.005). Conclusions: Thick prelaminar tissue was associated with impaired visualization of the LC. Healthy subjects generally had thicker prelaminar tissue, which potentially could create a selection bias against healthy eyes when comparing LC structures.

PURPOSE: To assess the effect of the previously reported optical coherence tomography (OCT) signal normalization method on reducing the discrepancies in image appearance among spectral-domain OCT (SD-OCT) devices. METHODS: Healthy eyes and eyes with various retinal pathologies were scanned at the macular region using similar volumetric scan patterns with at least two out of three SD-OCT devices at the same visit (Cirrus HD-OCT, Zeiss, Dublin, CA; RTVue, Optovue, Fremont, CA; and Spectralis, Heidelberg Engineering, Heidelberg, Germany). All the images were processed with the signal normalization. A set of images formed a questionnaire with 24 pairs of cross-sectional images from each eye with any combination of the three SD-OCT devices either both pre- or postsignal normalization. Observers were asked to evaluate the similarity of the two displayed images based on the image appearance. The effects on reducing the differences in image appearance before and after processing were analyzed. RESULTS: Twenty-nine researchers familiar with OCT images participated in the survey. Image similarity was significantly improved after signal normalization for all three combinations (P