Faculty Bibliography

PURPOSE: We developed a method to normalize optical coherence tomography (OCT) signal profiles from two spectral-domain (SD) OCT devices so that the comparability between devices increases. METHODS: We scanned 21 eyes from 14 healthy and 7 glaucoma subjects with two SD-OCT devices on the same day, with equivalent cube scan patterns centered on the fovea (Cirrus HD-OCT and RTVue). Foveola positions were selected manually and used as the center for registration of the corresponding images. A-scan signals were sampled 1.8 mm from the foveola in the temporal, superior, nasal, and inferior quadrants. After oversampling and rescaling RTVue data along the Z-axis to match the corresponding Cirrus data format, speckle noise reduction and amplitude normalization were applied. For comparison between normalized A-scan profiles, mean absolute difference in amplitude in percentage was measured at each sampling point. As a reference, the mean absolute difference between two Cirrus scans on the same eye also was measured. RESULTS: The mean residual of the A-scan profile amplitude was reduced significantly after signal normalization (12.7% vs. 6.2%, P < 0.0001, paired t-test). All four quadrants also showed statistically significant reduction (all P < 0.0001). Mean absolute difference after normalization was smaller than the one between two Cirrus scans. No performance difference was detected between health and glaucomatous eyes. CONCLUSIONS: The reported signal normalization method successfully reduced the A-scan profile differences between two SD-OCT devices. This signal normalization processing may improve the direct comparability of OCT image analysis and measurement on various devices.

PURPOSE: Ocular imaging devices provide quantitative structural information that might improve glaucoma progression detection. This study examined scanning laser polarimetry (SLP) population-derived versus individual-derived cut-off criteria for detecting progression. METHODS: Forty-eight healthy, glaucoma suspect and glaucoma subjects, providing 76 eyes were used. All subjects had reliable visual field (VF) and SLP scans acquired at the same visits from >/=4 visits. VF progression was defined by guided progression analysis (GPA) and by the VF index. SLP measurements were analysed by fast mode (FM) GPA, compared with the population rate of progression, and extended mode (EM) GPA, compared with the individual variability. The agreement between progression detection methods was measured. RESULTS: Poor agreement was observed between progression defined by VF and FM and EM. The difference in temporal-superior-nasal-inferior-temporal (TSNIT) average rate of change between VF defined progressors and non-progressors for both FM (p=0.010) and EM (p=0.015) was statistically significant. CONCLUSIONS: There is poor agreement between VF and SLP progression regardless of the use of population derived or individual variability criteria. The best SLP progression detection method could not be ascertained, therefore, acquiring three SLP scans per visit is recommended.

PURPOSE: To assess the association between single nucleotide polymorphisms (SNPs) of the gene region containing cyclin-dependent kinase inhibitor 2B antisense noncoding RNA (CDKN2B-AS1) and glaucoma features among primary open-angle glaucoma (POAG) patients. DESIGN: Retrospective observational case series. METHODS: We studied associations between 10 CDKN2B-AS1 SNPs and glaucoma features among 976 POAG cases from the Glaucoma Genes and Environment (GLAUGEN) study and 1971 cases from the National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) consortium. For each patient, we chose the feature from the eye with the higher value. We created cohort-specific multivariable models for glaucoma features and then meta-analyzed the results. RESULTS: For 9 of the 10 protective CDKN2B-AS1 SNPs with minor alleles associated with reduced disease risk (eg, the G allele at rs2157719), POAG patients carrying these minor alleles had smaller cup-to-disc ratio (0.05 units smaller per G allele at diagnosis; 95% CI: -0.08, -0.03; P = 6.23E-05) despite having higher intraocular pressure (IOP) (0.70 mm Hg higher per G allele at DNA collection; 95% CI: 0.40, 1.00; P = 5.45E-06). For the 1 adverse rs3217992 SNP with minor allele A associated with increased disease risk, POAG patients with A alleles had larger cup-to-disc ratio (0.05 units larger per A allele at diagnosis; 95% CI: 0.02, 0.07; P = 4.74E-04) despite having lower IOP (-0.57 mm Hg per A allele at DNA collection; 95% CI: -0.84, -0.29; P = 6.55E-05). CONCLUSION: Alleles of CDKN2B-AS1 SNPs, which influence risk of developing POAG, also modulate optic nerve degeneration among POAG patients, underscoring the role of CDKN2B-AS1 in POAG.

PURPOSE: To develop and test a novel signal enhancement method for optical coherence tomography (OCT) images based on the high dynamic range (HDR) imaging concept. METHODS: Three virtual channels, which represent low, medium, and high signal components, were produced for each OCT signal dataset. The dynamic range of each signal component was normalized to the full gray scale range. Finally, the three components were recombined into one image using various weights. Fourteen eyes of 14 healthy volunteers were scanned multiple times using time-domain (TD)-OCT before and while preventing blinking in order to produce a wide variety of signal strength (SS) images on the same eye scanned on the same day. For each eye, a pair of scans with the highest and lowest SS with successful retinal nerve fiber layer (RNFL) segmentation was selected to test the signal enhancement effect. In addition, spectral-domain (SD)-OCT images with poor signal qualities were also processed. RESULTS: Mean SS of good and poor quality scans were 9.0 +/- 1.1 and 4.4 +/- 0.9, respectively. TD-OCT RNFL thickness showed significant differences between good and poor quality scans on the same eye (mean difference 11.9 +/- 6.0 mum, P < 0.0001, paired t-test), while there was no significant difference after signal enhancement (1.7 +/- 6.2 mum, P = 0.33). However, HDR had weaker RNFL compensation effect on images with SS less than or equal to 4, while it maintained good compensation effect on images with SS greater than 4. Successful signal enhancement was also confirmed subjectively on SD-OCT images. CONCLUSION: The HDR imaging successfully restored OCT signal and image quality and reduced RNFL thickness differences due to variable signal level to the level within the expected measurement variability. This technique can be applied to both TD- and SD-OCT images.

PURPOSE: To compare prospectively detection of progressive retinal nerve fiber layer thickness (RNFL) atrophy identified using time-domain optical coherence tomography with visual field progression using standard automated perimetry in glaucoma suspect and preperimetric glaucoma patients or perimetric glaucoma patients. DESIGN: Prospective, longitudinal clinical trial. METHODS: Eligible eyes with 2 years or more of follow-up underwent time-domain optical coherence tomography and standard automated perimetry every 6 months. The occurrence of visual field progression was defined as the first follow-up visit reaching a significant (P < .05) negative visual field index slope over time. RNFL progression or improvement was defined as a significant negative or positive slope over time, respectively. Specificity was defined as the number of eyes with neither progression nor improvement, divided by the number of eyes without progression. Cox proportional hazard ratios were calculated using univariate and multivariate models with RNFL loss as a time-dependent covariate. RESULTS: Three hundred ten glaucoma suspect and preperimetric glaucoma eyes and 177 perimetric glaucoma eyes were included. Eighty-nine eyes showed visual field progression and 101 eyes showed RNFL progression. The average time to detect visual field progression in those 89 eyes was 35 +/- 13 months, and the average time to detect RNFL progression in those 101 eyes was 36 +/- 13 months. In multivariate Cox models, average and superior RNFL losses were associated with subsequent visual field index loss in the entire cohort (every 10-mum loss; hazard ratio, 1.38; P = .03; hazard ratio, 1.20; P = .01; respectively). Among the entire cohort of 487 eyes, 42 had significant visual field index improvement and 55 had significant RNFL improvement (specificity, 91.4% and 88.7%, respectively). CONCLUSIONS: Structural progression is associated with functional progression in glaucoma suspect and glaucomatous eyes. Average and superior RNFL thickness may predict subsequent standard automated perimetry loss.