Faculty Bibliography
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Comparison of retinal nerve fiber layer thickness measurement bias and imprecision across three spectral-domain optical coherence tomography devices
PURPOSE: We compared retinal nerve fiber layer (RNFL) bias and imprecision among three spectral-domain optical coherence tomographs (SD-OCT). METHODS: A total of 152 eyes of 83 subjects (96 healthy and 56 glaucomatous eyes) underwent peripapillary RNFL imaging using at least 2 of the following 3 SD-OCT devices on the same day: Cirrus HD-OCT (optic nerve head [ONH]) cube 200 x 200 protocol), RTVue-100 (ONH protocol [12 radial lines and 13 concentric circles]), and 3D OCT-1000 (3D Scan 256 x 256 protocol). Calibration equations, bias and imprecision of RNFL measurements were calculated using structural equation models. RESULTS: The calibration equations for healthy and glaucoma RNFL thickness measurements among the 3 devices were: Cirrus = 2.136 + 0.831*RTVue; Cirrus = -15.521 + 1.056*3D OCT-1000; RTVue = -21.257 + 1.271*3D OCT-1000. Using Cirrus bias as an arbitrary reference, RTVue bias was 1.20 (95% CI 1.09-1.32, P < 0.05) times larger and 3D OCT-1000 was 0.95 (0.87-1.03, P > 0.05) times smaller. Relative to 3D OCT-1000, the RTVue bias was 1.27 (1.13-1.42, P < 0.05). RTVue imprecision (healthy eyes 7.83, 95% CI 6.43-9.58; glaucoma cases 5.71, 4.19-7.64) was statistically significantly higher than both Cirrus (healthy eyes 3.23, 2.11-4.31; glaucoma cases 3.53, 0.69-5.24) and 3D OCT-1000 (healthy eyes 4.07, 3.11-5.35; glaucoma cases 5.33, 3.77-7.67) in healthy eyes. The imprecision also was significantly higher for RTVue measurements in healthy compared to glaucomatous eyes. None of the other comparisons was statistically significant. CONCLUSIONS: RTVue-100 showed higher imprecision (or higher measurement variability) than Cirrus HD-OCT and 3D OCT-1000 RNFL measurements. Three-dimensional cube scanning with post-hoc data sampling may be a factor reducing imprecision.
PMCID:3390182
PMID: 22538423
ISSN: 0146-0404
CID: 1885382
Ganglion cell loss in relation to visual disability in multiple sclerosis
PURPOSE: We used high-resolution spectral-domain optical coherence tomography (SD-OCT) with retinal segmentation to determine how ganglion cell loss relates to history of acute optic neuritis (ON), retinal nerve fiber layer (RNFL) thinning, visual function, and vision-related quality of life (QOL) in multiple sclerosis (MS). DESIGN: Cross-sectional study. PARTICIPANTS: A convenience sample of patients with MS (n = 122; 239 eyes) and disease-free controls (n = 31; 61 eyes). Among MS eyes, 87 had a history of ON before enrollment. METHODS: The SD-OCT images were captured using Macular Cube (200x200 or 512x128) and ONH Cube 200x200 protocols. Retinal layer segmentation was performed using algorithms established for glaucoma studies. Thicknesses of the ganglion cell layer/inner plexiform layer (GCL+IPL), RNFL, outer plexiform/inner nuclear layers (OPL+INL), and outer nuclear/photoreceptor layers (ONL+PRL) were measured and compared in MS versus control eyes and MS ON versus non-ON eyes. The relation between changes in macular thickness and visual disability was also examined. MAIN OUTCOME MEASURES: The OCT measurements of GCL+IPL and RNFL thickness; high contrast visual acuity (VA); low-contrast letter acuity (LCLA) at 2.5% and 1.25% contrast; on the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and 10-Item Neuro-Ophthalmic Supplement composite score. RESULTS: Macular RNFL and GCL+IPL were significantly decreased in MS versus control eyes (P<0.001 and P = 0.001) and in MS ON versus non-ON eyes (P<0.001 for both measures). Peripapillary RNFL, macular RNFL, GCL+IPL, and the combination of macular RNFL+GCL+IPL were significantly correlated with VA (P
PMCID:3631566
PMID: 22365058
ISSN: 0161-6420
CID: 174640
The optic nerve head as a robust biomechanical system
Purpose. Understanding the effects of IOP on the optic nerve head (ONH) is important in understanding glaucoma and ONH structure and function. The authors tested the hypothesis that the ONH is a robust biomechanical structure wherein various factors combine to produce a relatively stable response to IOP. Methods. The authors generated two populations of 100,000 ONH numerical models each with randomly selected values, but controlled distributions, either uniform or Gaussian, of ONH geometry and mechanical properties. The authors predicted the lamina cribrosa displacement (LCD), scleral canal expansion (SCE), and the stresses (forces) and deformations (strains) produced by a 10 mm Hg increase in IOP. The authors analyzed the distributions of the responses. Results. The responses were distributed nonuniformly, with the majority of the models having a response within a small region, often less than 30% of the size of the overall response region. This concentration of responses was more marked in the Gaussian population than in the uniform population. All the responses were positively skewed. Whether a particular case was typical or not depended on the response used for classification and on whether the decision was made using one-dimensional or two-dimensional criteria. Conclusions. Despite wide variations in ONH characteristics and responses to IOP, some responses were much more common than others. This supports conceiving of the eye as a robust structure, particularly for LCD and SCE, which is tolerant to variations in tissue geometry and mechanical properties. The authors also provide the first estimates of the typical mechanical response of the ONH to variations in IOP over a large population of ONHs.
PMCID:3357115
PMID: 22427598
ISSN: 0146-0404
CID: 1885402
Detection and diagnosis of glaucoma: ocular imaging
PMCID:3979474
PMID: 22562848
ISSN: 0146-0404
CID: 1885392
Optical coherence tomography: future trends for imaging in glaucoma
Optical coherence tomography captures a major role in clinical assessment in eye care. Innovative hardware and software improvements in the technology would further enhance its usefulness. In this review, we present several promising initiatives currently in development or early phase of assessment that we expect to have a future impact on optical coherence tomography.
PMCID:3348373
PMID: 22488265
ISSN: 1538-9235
CID: 1885422
Clinical application of ocular imaging
The broadening frontier of technology used in ocular imaging is continuously affecting the landscape of clinical eye care. With each wave of enhanced imaging modalities, the field faces the difficulties of optimally incorporating these devices into the clinic. Ocular imaging devices have been widely incorporated into clinical management after their diagnostic capabilities have been documented in a wide range of ocular disease. In this review, we are presenting the main commercially available devices for imaging of the posterior segment of the eye.
PMCID:3348430
PMID: 22488266
ISSN: 1538-9235
CID: 1885412
Variation in optical coherence tomography signal quality as an indicator of retinal nerve fibre layer segmentation error
PURPOSE: Commercial optical coherence tomography (OCT) systems use global signal quality indices to quantify scan quality. Signal quality can vary throughout a scan, contributing to local retinal nerve fibre layer segmentation errors (SegE). The purpose of this study was to develop an automated method, using local scan quality, to predict SegE. METHODS: Good-quality (global signal strength (SS) >/= 6; manufacturer specification) peripapillary circular OCT scans (fast retinal nerve fibre layer scan protocol; Stratus OCT; Carl Zeiss Meditec, Dublin, California, USA) were obtained from 6 healthy, 19 glaucoma-suspect and 43 glaucoma subjects. Scans were grouped based on SegE. Quality index (QI) values were computed for each A-scan using software of our own design. Logistic mixed-effects regression modelling was applied to evaluate SS, global mean and SD of QI, and the probability of SegE. RESULTS: The difference between local mean QI in SegE regions and No-SegE regions was -5.06 (95% CI -6.38 to 3.734) (p<0.001). Using global mean QI, QI SD and their interaction term resulted in the model of best fit (Akaike information criterion=191.8) for predicting SegE. Global mean QI >/= 20 or SS >/= 8 shows little chance for SegE. Once mean QI<20 or SS<8, the probability of SegE increases as QI SD increases. CONCLUSIONS: When combined with a signal quality parameter, the variation of signal quality between A-scans provides significant information about the quality of an OCT scan and can be used as a predictor of segmentation error.
PMCID:3375178
PMID: 21900227
ISSN: 1468-2079
CID: 1885432
Multipotent stem cells from trabecular meshwork become phagocytic TM cells
PURPOSE: To isolate and characterize stem cells from human trabecular meshwork (TM) and to investigate the potential of these stem cells to differentiate into TM cells. METHODS: Human trabecular meshwork stem cells (TMSCs) were isolated as side population cells by fluorescence-activated cell sorting or isolated by clonal cultures. Passaged TMSCs were compared with primary TM cells by immunostaining and quantitative RT-PCR. TMSC purity was assessed by flow cytometry and TMSC multipotency was examined by induction of neural cells, adipocytes, keratocytes, or TM cells. Differential gene expression was detected by quantitative RT-PCR, immunostaining, and immunoblotting. TM cell function was evaluated by phagocytic assay using inactivated Staphylococcus aureus bioparticles. RESULTS: Side population and clonal isolated cells expressed stem cell markers ABCG2, Notch1, OCT-3/4, AnkG, and MUC1 but not TM markers AQP1, MGP, CHI3L1, or TIMP3. Passaged TMSCs are a homogeneous population with >95% cells positive to CD73, CD90, CD166, or Bmi1. TMSCs exhibited multipotent ability of differentiation into a variety of cell types with expression of neural markers neurofilament, beta-tubulin III, GFAP; or keratocyte-specific markers keratan sulfate and keratocan; or adipocyte markers ap2 and leptin. TMSC readily differentiated into TM cells with phagocytic function and expression of TM markers AQP1, CHI3L1, and TIMP3. CONCLUSIONS: TMSCs, isolated as side population or as clones, express specific stem cell markers, are homogeneous and multipotent, with the ability to differentiate into phagocytic TM cells. These cells offer a potential for development of a novel stem cell-based therapy for glaucoma.
PMCID:3339918
PMID: 22297497
ISSN: 0146-0404
CID: 1885442
Asymmetry in hemifield macular thickness as an early indicator of glaucomatous change
PURPOSE: To investigate whether asymmetry in hemifield macular thickness can serve as an early indicator of glaucomatous structural damage using spectral domain optical coherence tomography. METHODS: Five zones in the macular thickness map were defined. Each zone included reciprocal areas in the superior and inferior hemifield. Differences in average retinal thickness (DRT) between corresponding regional pairs were measured in each of the five zones in 50 healthy eyes. An abnormality was defined as the DRT value lying outside the 95% confidence intervals. An eye was considered to yield an "abnormal macular hemifield test" (MHT) if abnormality was evident in any zone. The sensitivity and specificity for glaucoma detection of MHT and average circumpapillary retinal nerve fiber layer (cRNFL) classification were determined. RESULTS: A total of 114 healthy, 103 glaucoma-suspect, and 74 glaucomatous eyes were included. Overall, 5.8%, 36.9%, 88.4%, and 77.4% of the eyes of the healthy, glaucoma-suspect (GS), early glaucoma (EG), and advanced glaucoma (AG) groups yielded abnormal MHT results, respectively. In EG eyes, the sensitivity of an abnormal MHT result was significantly greater than that of abnormal average cRNFL classification (P=0.008). In the GS and AG groups, the sensitivity did not significantly differ between an abnormal MHT result and an average cRNFL classification (P=0.880, 0.180). Compared with sectoral cRNFL thickness measurements, MHT showed a similar level of diagnostic performance. Specificity was not different between an abnormal MHT result and an average cRNFL classification (P=0.687). CONCLUSIONS: Evaluation of asymmetry in hemifield macular thickness may serve as an assessment tool in the early diagnosis of glaucoma.
PMCID:3979493
PMID: 22247461
ISSN: 0146-0404
CID: 1885462
Optical coherence tomography as a rapid, accurate, noncontact method of visualizing the palisades of Vogt
PURPOSE: This study explored the efficacy of optical coherence tomography (OCT) as a high-resolution, noncontact method for imaging the palisades of Vogt by correlating OCT and confocal microscopy images. METHODS: Human limbal rims were acquired and imaged with OCT and confocal microscopy. The area of the epithelial basement membrane in each of these sets was digitally reconstructed, and the models were compared. RESULTS: OCT identified the palisades within the limbus and exhibited excellent structural correlation with immunostained tissue imaged by confocal microscopy. CONCLUSIONS: OCT successfully identified the limbal palisades of Vogt that constitute the corneal epithelial stem cell niche. These findings offer the exciting potential to characterize the architecture of the palisades in vivo, to harvest stem cells for transplantation more accurately, to track palisade structure for better diagnosis, follow-up and staging of treatment, and to assess and intervene in the progression of stem cell depletion by monitoring changes in the structure of the palisades.
PMCID:3339911
PMID: 22266521
ISSN: 0146-0404
CID: 1885452
