Faculty Bibliography

PURPOSE: We sought to visualize the aqueous outflow system in 3 dimensions (3D) in living human eyes, and to investigate the use of commercially available spectral-domain optical coherence tomographic (SD-OCT) systems for this purpose. DESIGN: Prospective, observational study. PARTICIPANTS: One randomly determined eye in each of 6 normal healthy subjects was included. TESTING: We performed 3D SD-OCT imaging of the aqueous humor outflow structures with 2 devices: The Cirrus HD-OCT and the Bioptigen SDOIS. MAIN OUTCOME MEASURES: We created 3D virtual castings of Schlemm's canal (SC) and more distal outflow structures from scan data from each device. RESULTS: Virtual casting of the SC provided visualization of more aqueous vessels branching from SC than could be located by interrogating the 2-dimensional (2D) image stack. Similarly, virtual casting of distal structures allowed visualization of large and small aqueous outflow channel networks that could not be appreciated with conventional 2D visualization. CONCLUSIONS: The outflow pathways from SC to the superficial vasculature can be identified and tracked in living human eyes using commercially available SD-OCT.

PURPOSE: To investigate the effects of central corneal thickness (CCT)-associated variants on primary open-angle glaucoma (POAG) risk using single nucleotide polymorphisms (SNP) data from the Glaucoma Genes and Environment (GLAUGEN) and National Eye Institute (NEI) Glaucoma Human Genetics Collaboration (NEIGHBOR) consortia. METHODS: A replication analysis of previously reported CCT SNPs was performed in a CCT dataset (n = 1117) and these SNPs were then tested for association with POAG using a larger POAG dataset (n = 6470). Then a CCT genome-wide association study (GWAS) was performed. Top SNPs from this analysis were selected and tested for association with POAG. cDNA libraries from fetal and adult brain and ocular tissue samples were generated and used for candidate gene expression analysis. RESULTS: Association with one of 20 previously published CCT SNPs was replicated: rs12447690, near the ZNF469 gene (P = 0.001; beta = -5.08 mum/allele). None of these SNPs were significantly associated with POAG. In the CCT GWAS, no SNPs reached genome-wide significance. After testing 50 candidate SNPs for association with POAG, one SNP was identified, rs7481514 within the neurotrimin (NTM) gene, that was significantly associated with POAG in a low-tension subset (P = 0.00099; Odds Ratio [OR] = 1.28). Additionally, SNPs in the CNTNAP4 gene showed suggestive association with POAG (top SNP = rs1428758; P = 0.018; OR = 0.84). NTM and CNTNAP4 were shown to be expressed in ocular tissues. CONCLUSIONS: The results suggest previously reported CCT loci are not significantly associated with POAG susceptibility. By performing a quantitative analysis of CCT and a subsequent analysis of POAG, SNPs in two cell adhesion molecules, NTM and CNTNAP4, were identified and may increase POAG susceptibility in a subset of cases.

Several in vitro and in vivo studies have established accelerated thrombolysis using ultrasound (US) induced microbubble (MB) cavitation. However, the mechanisms underlying MB mediated sonothrombolysis are still not completely elucidated. We performed three-dimensional (3-D) volumetric optical coherence tomography (OCT) imaging before and after the application of contrast US to thrombus. The most dramatic reduction in clot volume was observed with US + MB + recombinant tissue plasminogen activator (rt-PA). Thrombus surface erosion in this group on the side of the thrombus exposed to MB and ultrasound was evident on the OCT images. This technique may assist in clarifying the mechanisms underlying sonothrombolysis, especially regarding the importance of US transducer orientation on lytic efficacy and the effects of MB cavitation on thrombus structure.

Eye movement artifacts occurring during 3-D optical coherence tomography (OCT) scanning is a well-recognized problem that may adversely affect image analysis and interpretation. A particle filtering algorithm is presented in this paper to correct motion in a 3-D dataset by considering eye movement as a target tracking problem in a dynamic system. The proposed particle filtering algorithm is an independent 3-D alignment approach, which does not rely on any reference image. 3-D OCT data is considered as a dynamic system, while the location of each A-scan is represented by the state space. A particle set is used to approximate the probability density of the state in the dynamic system. The state of the system is updated frame by frame to detect A-scan movement. The proposed method was applied on both simulated data for objective evaluation and experimental data for subjective evaluation. The sensitivity and specificity of the x-movement detection were 98.85% and 99.43%, respectively, in the simulated data. For the experimental data (74 3-D OCT 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 3-D OCT volume data and correct the eye movement without using references.

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.

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