Faculty Bibliography

PURPOSE: Ethyl pyruvate (EP) has pharmacologic effects that remediate cellular stress. In the organ-cultured murine lens, EP ameliorates oxidative stress, and in a rat cataract model, it attenuates cataract formation. However, corneal responses to EP have not been elucidated. In this study, the potential of EP as a therapeutic agent in corneal wound healing was determined by examining its effects on the transition of quiescent corneal stromal keratocytes into contractile myofibroblasts. METHODS: Three independent preparations of cultured human keratocytes were treated with TGF-beta1, to elicit a phenotypic transition to myofibroblasts in the presence or absence of 10 or 15 mM EP. Gene expression profiles of the 12 samples (keratocytes +/- EP +/- TGF-beta1 for three preparations) were produced by using gene microarrays. RESULTS: TGF-beta1-driven twofold changes in at least two of three experiments defined a group of 1961 genes. Genes showing twofold modulation by EP in at least two experiments appeared exclusively in myofibroblasts (857 genes), exclusively in keratocytes (409 genes), or in both phenotypes (252 genes). Analysis of these three EP-modulated groups showed that EP (1) inhibited myofibroblast proliferation with concomitant modulation of some cell cycle genes, (2) augmented the NRF2-mediated antioxidant response in both keratocytes and myofibroblasts, and (3) modified the TGF-beta1-driven transition of keratocytes to myofibroblasts by inhibiting the upregulation of a subset of profibrotic genes. CONCLUSIONS: These EP-induced phenotypic changes in myofibroblasts indicate the potential of EP as a therapeutic agent in corneal wound healing.

PURPOSE: To study optic nerve head (ONH) topography parameters measured by Stratus optical coherence tomography (OCT) in normal subjects and to analyze ONH data for differences in relation to disc size, ethnicity, and age. METHODS: Three hundred sixty-seven normal subjects underwent Stratus optical coherence tomography ONH measurement using the fast optic disc scan protocol software package 3.0. Only ONH scans meeting specific qualification criteria were included for data analysis ensuring appropriate scan quality and reliability. ONH topographic parameters of qualified scans were analyzed for differences in regards to optic disc size, age, and ethnicity. RESULTS: Two hundred and twelve qualified ONH scans were included for data analysis. Mean disc area was 2.27+/-0.41 mm and optic cup area, rim area, and horizontal integrated rim width increased with disc size, whereas vertical integrated rim area did not. Vertical integrated rim area, horizontal integrated rim width, and rim area decreased and cup area increased with age. Mean optic disc area was larger in African-Americans as compared with Hispanics or Whites and this difference was statistically significant. CONCLUSIONS: Optic cup area, rim area, and horizontal integrated rim width correlated to disc size. Vertical integrated rim area, horizontal integrated rim width, rim area, and cup area, changed with age. African-American optic discs had larger disc area measurements as compared with Whites optic discs and this difference was statistically significant.

PURPOSE: To develop a fully automated algorithm (AP) to perform a volumetric measure of the optic disc using conventional stereoscopic optic nerve head (ONH) photographs, and to compare algorithm-produced parameters with manual photogrammetry (MP), scanning laser ophthalmoscope (SLO) and optical coherence tomography (OCT) measurements. METHODS: One hundred twenty-two stereoscopic optic disc photographs (61 subjects) were analyzed. Disc area, rim area, cup area, cup/disc area ratio, vertical cup/disc ratio, rim volume and cup volume were automatically computed by the algorithm. Latent variable measurement error models were used to assess measurement reproducibility for the four techniques. RESULTS: AP had better reproducibility for disc area and cup volume and worse reproducibility for cup/disc area ratio and vertical cup/disc ratio, when the measurements were compared to the MP, SLO and OCT methods. CONCLUSION: AP provides a useful technique for an objective quantitative assessment of 3D ONH structures.

PURPOSE: Time domain optical coherence tomography (TD-OCT) has been used commonly in clinical practice, producing a large inventory of circular scan data for retinal nerve fiber layer (RNFL) assessment. Spectral domain (SD)-OCT produces three-dimensional (3-D) data volumes. The purpose of this study was to create a robust technique that makes TD-OCT circular scan RNFL thickness measurements comparable with those from 3-D SD-OCT volumes. METHODS: Eleven eyes of 11 healthy subjects and 7 eyes of 7 subjects with glaucoma were enrolled. Each eye was scanned with one centered and eight displaced TD-OCT scanning circles. One 3-D SD-OCT cube scan was obtained at the same visit. The matching location of the TD-OCT scanning circle was automatically detected within the corresponding 3-D SD-OCT scan. Algorithm performance was assessed by estimating the difference between the detected scanning circle location on 3-D SD-OCT volume and the TD-OCT circle location. Global and sectoral RNFL thickness measurement errors between the two devices were also compared. RESULTS: The difference (95% confidence interval) in scanning circle center locations between TD- and SD-OCT was 2.3 (1.5-3.2) pixels (69.0 [45.0-96.0] microm on the retina) for healthy eyes and 3.1 (2.0-4.1) pixels (93.0 [60.0-123.0] microm on the retina) for glaucomatous eyes. The absolute RNFL thickness measurement difference was significantly smaller with the matched scanning circle. CONCLUSIONS: Scan location matching may bridge the gap in RNFL thickness measurements between TD-OCT circular scan data and 3-D SD-OCT scan data, providing follow-up comparability across the two generations of OCTs.

PURPOSE: The purpose of this study was to report normal macular thickness measurements and assess reproducibility of retinal thickness measurements acquired by a time-domain optical coherence tomography (OCT) (Stratus, Carl Zeiss Meditec, Inc., Dublin, CA) and three commercially available spectral/Fourier domain OCT instruments (Cirrus HD-OCT, Carl Zeiss Meditec, Inc.; RTVue-100, Optovue, Inc., Fremont, CA; 3D OCT-1000, Topcon, Inc., Paramus, NJ). METHODS: Forty randomly selected eyes of 40 normal, healthy volunteers were imaged. Subjects were scanned twice during 1 visit and a subset of 25 was scanned again within 8 weeks. Retinal thickness measurements were automatically generated by OCT software and recorded after manual correction. Regression and Bland-Altman plots were used to compare agreement between instruments. Reproducibility was analyzed by using intraclass correlation coefficients, and incidence of artifacts was determined. RESULTS: Macular thickness measurements were found to have high reproducibility across all instruments with intraclass correlation coefficients values ranging 84.8% to 94.9% for Stratus OCT, 92.6% to 97.3% for Cirrus Cube, 76.4% to 93.7% for RTVue MM5, 61.1% to 96.8% for MM6, 93.1% to 97.9% for 3D OCT-1000 radial, and 31.5% to 97.5% for 3D macular scans. Incidence of artifacts was higher in spectral/Fourier domain instruments, ranging from 28.75% to 53.16%, compared with 17.46% in Stratus OCT. No significant age or sex trends were found in the measurements. CONCLUSION: Commercial spectral/Fourier domain OCT instruments provide higher speed and axial resolution than the Stratus OCT, although they vary greatly in scanning protocols and are currently limited in their analysis functions. Further development of segmentation algorithms and quantitative features are needed to assist clinicians in objective use of these newer instruments to manage diseases.

Three-dimensional optical coherence tomography (OCT) is a new ophthalmic imaging technique offering more detailed quantitative analysis of the retinal structure. Eye movement during 3D OCT scanning, however, creates significant spatial distortions that may adversely affect image interpretation and analysis. Current software solutions must use additional reference images or B-scans to correct eye movement in a certain direction. The proposed particle filtering algorithm is an independent 3D alignment approach, which does not rely on any reference image. 3D OCT data is considered as a dynamic system, while location of A-scan is represented by the state space. A particle set is generated to approximate the probability density of the state. The state of the system is updated frame by frame to detect A-scan movement. Seventy-four 3D OCT images with eye movement were tested and subjectively evaluated by comparing them with the original images. All the images were improved after z-alignment, while 81.1% images were improved after x-alignment. The proposed algorithm is an efficient way to align 3D OCT volume data and correct the eye movement without using references.

We address a novel problem domain in the analysis of optical coherence tomography (OCT) images: the diagnosis of multiple macular pathologies in retinal OCT images. The goal is to identify the presence of normal macula and each of three types of macular pathologies, namely, macular hole, macular edema, and age-related macular degeneration, in the OCT slice centered at the fovea. We use a machine learning approach based on global image descriptors formed from a multi-scale spatial pyramid. Our local descriptors are dimension-reduced Local Binary Pattern histograms, which are capable of encoding texture information from OCT images of the retina. Our representation operates at multiple spatial scales and granularities, leading to robust performance. We use 2-class Support Vector Machine classifiers to identify the presence of normal macula and each of the three pathologies. We conducted extensive experiments on a large dataset consisting of 326 OCT scans from 136 patients. The results show that the proposed method is very effective.