Faculty Bibliography

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.

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.

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.

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.

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.

AIMS: To determine the retinal nerve fibre layer (RNFL) thickness at which visual field (VF) damage becomes detectable and associated with structural loss. METHODS: In a prospective cross-sectional study, 72 healthy and 40 glaucoma subjects (one eye per subject) recruited from an academic institution had VF examinations and spectral domain optical coherence tomography (SD-OCT) optic disc cube scans (Humphrey field analyser and Cirrus HD-OCT, respectively). Comparison of global mean and sectoral RNFL thicknesses with VF threshold values showed a plateau of threshold values at high RNFL thicknesses and a sharp decrease at lower RNFL thicknesses. A 'broken stick' statistical model was fitted to global and sectoral data to estimate the RNFL thickness 'tipping point' where the VF threshold values become associated with the structural measurements. The slope for the association between structure and function was computed for data above and below the tipping point. RESULTS: The mean RNFL thickness threshold for VF loss was 75.3 mum (95% CI: 68.9 to 81.8), reflecting a 17.3% RNFL thickness loss from age-matched normative value. Above the tipping point, the slope for RNFL thickness and threshold value was 0.03 dB/mum (CI: -0.02 to 0.08) and below the tipping point, it was 0.28 dB/mum (CI: 0.18 to 0.38); the difference between the slopes was statistically significant (p<0.001). A similar pattern was observed for quadrant and clock-hour analysis. CONCLUSIONS: Substantial structural loss ( approximately 17%) appears to be necessary for functional loss to be detectable using the current testing methods.