Mauro T. Leite

Comparison of the Diagnostic Accuracies of the Spectralis, Cirrus, and RTVue Optical Coherence Tomography Devices in Glaucoma

PURPOSE To compare the diagnostic accuracies of retinal nerve fiber layer (RNFL) thickness measurements obtained with the Spectralis (Heidelberg Engineering, Dossenheim, Germany), Cirrus (Carl Zeiss Meditec, Dublin, CA), and RTVue (Optovue Inc., Fremont, CA) devices for the detection of glaucoma. DESIGN Diagnostic, case-control study. PARTICIPANTS A total of 233 (107 healthy, 126 glaucomatous) of 149 participants from the longitudinal Diagnostic Innovations in Glaucoma Study (DIGS) and from the African Descent and Glaucoma Evaluation Study (ADAGES). METHODS All participants underwent RNFL thickness imaging with the Spectralis, Cirrus, and RTVue devices in the same visit. Receiver operating characteristic (ROC) curves adjusted for age and race were obtained for quadrants (superior, nasal, inferior, temporal) and global RNFL thickness for all instruments. Areas under ROC (AUC) and sensitivities at fixed specificities (80% and 95%) were calculated and compared. MAIN OUTCOME MEASURES Comparison of diagnostic accuracy using AUCs and sensitivities at fixed specificities of 80% and 95%. RESULTS The RNFL thickness parameter with the largest AUCs was the superior quadrant for the Spectralis (0.88) and the global RNFL thickness for the Cirrus (0.88) and the RTVue (0.87). The pairwise comparison among the ROC curves showed no statistical difference for all parameters except for the nasal quadrant, which had significantly larger AUC in the Spectralis and RTVue compared with the Cirrus (P<0.03 for both comparisons). There were no significant differences in sensitivities among the best parameters from each instrument (P>0.05). The superior quadrant thickness measured with the Spectralis had sensitivity of 81.9% at a fixed specificity of 80% and 70% at a fixed specificity of 95%. The global thickness measured by the Cirrus had a sensitivity of 80.3% at a fixed specificity of 80% and 65.6% at a fixed specificity of 95%. For the RTVue, the global thickness had a sensitivity of 77.9% at a fixed specificity of 80% and 62.1% at a fixed specificity of 95%. CONCLUSIONS Although the spectral-domain optic coherence tomography (SD-OCT) instruments have different resolution and acquisition rates, their ability to detect glaucoma was similar.

Diagnosing Preperimetric Glaucoma with Spectral Domain Optical Coherence Tomography

PURPOSE To evaluate the diagnostic accuracy of spectral domain optical coherence tomography (SD-OCT) for detection of preperimetric glaucoma and compare it with the performance of confocal scanning laser ophthalmoscopy (CSLO). DESIGN Cohort study. PARTICIPANTS A cohort of 134 eyes of 88 glaucoma suspects based on the appearance of the optic disc. METHODS Patients were recruited from the Diagnostic Innovations in Glaucoma Study (DIGS). All eyes underwent retinal nerve fiber layer (RNFL) imaging with Spectralis SD-OCT (Heidelberg Engineering, Carlsbad, CA) and topographic imaging with Heidelberg Retinal Tomograph III (HRT-III) (Heidelberg Engineering) CSLO within 6 months of each other. All patients had normal visual fields at the time of imaging and were classified on the basis of history of documented stereophotographic evidence of progressive glaucomatous change in the appearance of the optic nerve occurring before the imaging sessions. MAIN OUTCOME MEASURES Areas under the receiver operating characteristic curves (AUCs) were calculated to summarize diagnostic accuracies of the SD-OCT and CSLO. Likelihood ratios (LRs) were reported using the diagnostic categorization provided by each instrument after comparison to its normative database. RESULTS Forty-eight eyes of 42 patients had evidence of progressive glaucomatous change and were included in the preperimetric glaucoma group. Eighty-six eyes of 46 patients without any evidence of progressive glaucomatous change followed untreated for an average of 14.0 ± 3.6 years were included in the control group. The parameter with the largest AUC obtained with the SD-OCT was the temporal superior RNFL thickness (0.88 ± 0.03), followed by global RNFL thickness (0.86 ± 0.03) and temporal inferior RNFL thickness (0.81 ± 0.04). The parameter with the largest AUC obtained with the CSLO was rim area (0.72 ± 0.05), followed by rim volume (0.71 ± 0.05) and linear cup-to-disk ratio (0.66 ± 0.05). Temporal superior RNFL average thickness measured by SD-OCT performed significantly better than rim area measurements from CSLO (0.88 vs. 0.72; P=0.008). Outside normal limits results for SD-OCT parameters were associated with strongly positive LRs. CONCLUSIONS The RNFL assessment with SD-OCT performed well in detecting preperimetric glaucomatous damage in a cohort of glaucoma suspects and had a better performance than CSLO.

Structure-Function relationships using the Cirrus Spectral Domain Optical Coherence Tomograph and Standard Automated Perimetry

Purpose:To evaluate the relationship between glaucomatous structural damage assessed by the Cirrus Spectral Domain OCT (SDOCT) and functional loss as measured by standard automated perimetry (SAP). Methods:Four hundred twenty-two eyes (78 healthy, 210 suspects, 134 glaucomatous) of 250 patients were recruited from the longitudinal Diagnostic Innovations in Glaucoma Study and from the African Descent and Glaucoma Evaluation Study. All eyes underwent testing with the Cirrus SDOCT and SAP within a 6-month period. The relationship between parapapillary retinal nerve fiber layer thickness (RNFL) sectors and corresponding topographic SAP locations was evaluated using locally weighted scatterplot smoothing and regression analysis. SAP sensitivity values were evaluated using both linear as well as logarithmic scales. We also tested the fit of a model (Hood) for structure-function relationship in glaucoma. Results:Structure was significantly related to function for all but the nasal thickness sector. The relationship was strongest for superotemporal RNFL thickness and inferonasal sensitivity (R2=0.314, P<0.001). The Hood model fitted the data relatively well with 88% of the eyes inside the 95% confidence interval predicted by the model. Conclusions:RNFL thinning measured by the Cirrus SDOCT was associated with correspondent visual field loss in glaucoma.

Agreement among spectral-domain optical coherence tomography instruments for assessing retinal nerve fiber layer thickness.

PURPOSE To assess the agreement of parapapillary retinal nerve fiber layer (RNFL) thickness measurements among 3 spectral-domain optical coherence tomography (SD-OCT) instruments. DESIGN Observational, cross-sectional study. METHODS Three hundred thirty eyes (88 with glaucoma, 206 glaucoma suspects, 36 healthy) from 208 individuals enrolled in the Diagnostic Innovations in Glaucoma Study (DIGS) were imaged using RTVue, Spectralis and Cirrus in a single visit. Agreement among RNFL thickness measurements was assessed using Bland-Altman plots. The influence of age, axial length, disc size, race, spherical equivalent, and disease severity on the pairwise agreements between different instruments was assessed by regression analysis. RESULTS Although RNFL thickness measurements between different instruments were highly correlated, Bland-Altman analyses indicated the presence of fixed and proportional biases for most of the pairwise agreements. In general, RTVue measurements tended to be thicker than Spectralis and Cirrus measurements. The agreement in average RNFL thickness measurements between RTVue and Spectralis was affected by age (P = .001) and spherical equivalent (P < .001), whereas the agreement between Spectralis and Cirrus was affected by axial length (P = .004) and spherical equivalent (P < .001). Disease severity influenced the agreement between Spectralis and both RTVue and Cirrus (P = .001). Disc area and race did not influence the agreement among the devices. CONCLUSIONS RNFL thickness measurements obtained by different SD-OCT instruments were not entirely compatible and therefore they should not be used interchangeably. This may be attributable in part to differences in RNFL detection algorithms. Comparisons with histologic measurements could determine which technique is most accurate.

Effect of disease severity on the performance of Cirrus spectral-domain OCT for glaucoma diagnosis.

PURPOSE To evaluate the effect of disease severity on the diagnostic accuracy of the Cirrus Optical Coherence Tomograph (Cirrus HD-OCT; Carl Zeiss Meditec, Inc., Dublin, CA) for glaucoma detection. METHODS One hundred thirty-five glaucomatous eyes of 99 patients and 79 normal eyes of 47 control subjects were recruited from the longitudinal Diagnostic Innovations in Glaucoma Study (DIGS). The severity of the disease was graded based on the visual field index (VFI) from standard automated perimetry. Imaging of the retinal nerve fiber layer (RNFL) was obtained using the optic disc cube protocol available on the Cirrus HD-OCT. Pooled receiver operating characteristic (ROC) curves were initially obtained for each parameter of the Cirrus HD-OCT. The effect of disease severity on diagnostic performance was evaluated by fitting an ROC regression model, with VFI used as a covariate, and calculating the area under the ROC curve (AUCs) for different levels of disease severity. RESULTS The largest pooled AUCs were for average thickness (0.892), inferior quadrant thickness (0.881), and superior quadrant thickness (0.874). Disease severity had a significant influence on the detection of glaucoma. For the average RNFL thickness parameter, AUCs were 0.962, 0.932, 0.886, and 0.822 for VFIs of 70%, 80%, 90%, and 100%, respectively. CONCLUSIONS Disease severity had a significant effect on the diagnostic performance of the Cirrus HD-OCT and thus should be considered when interpreting results from this device and when considering the potential applications of this instrument for diagnosing glaucoma in the various clinical settings.

Comparison of Different Spectral Domain OCT Scanning Protocols for Diagnosing Preperimetric Glaucoma

PURPOSE To compare the ability of spectral-domain optical coherence tomography (SDOCT) retinal nerve fiber layer (RNFL), optic nerve head (ONH), and macular measurements to detect preperimetric glaucomatous damage. METHODS The study included 142 eyes from 91 patients suspected of having the disease based on the appearance of the optic disc. All eyes had normal visual fields before the imaging session. Forty-eight eyes with progressive glaucomatous damage were included in the preperimetric glaucoma group. Ninety-four eyes without any evidence of progressive glaucomatous damage and followed untreated for 12.8 ± 3.6 years were used as controls. Areas under the receiver operating characteristic curves (AUC) were calculated to summarize diagnostic accuracies of the parameters. RESULTS The three RNFL parameters with the largest AUCs were average RNFL thickness (0.89 ± 0.03), inferior hemisphere average thickness (0.87 ± 0.03), and inferior quadrant average thickness (0.85 ± 0.03). The three ONH parameters with the largest AUCs were vertical cup-to-disc ratio (0.74 ± 0.04), rim area (0.72 ± 0.05), and rim volume (0.72 ± 0.05). The three macular parameters with the largest AUCs were GCC average thickness (0.79 ± 0.04), GCC inferior thickness (0.79 ± 0.05), and GCC superior thickness (0.76 ± 0.05). Average RNFL thickness performed better than vertical cup-to-disc ratio (0.89 vs. 0.74; P = 0.007) and GCC average thickness (0.89 vs. 0.79; P = 0.015). CONCLUSIONS SDOCT RNFL measurements performed better than ONH and macular measurements for detecting preperimetric glaucomatous damage in a cohort of glaucoma suspects. (ClinicalTrials.gov number, NCT00221897.).

Combining Structural and Functional Measurements to Improve Detection of Glaucoma Progression using Bayesian Hierarchical Models

PURPOSE To present and evaluate a new methodology for combining longitudinal information from structural and functional tests to improve detection of glaucoma progression and estimation of rates of change. METHODS This observational cohort study included 434 eyes of 257 participants observed for an average of 4.2 ± 1.1 years and recruited from the Diagnostic Innovations in Glaucoma Study (DIGS). The subjects were examined annually with standard automated perimetry, optic disc stereophotographs, and scanning laser polarimetry with enhanced corneal compensation. Rates of change over time were measured using the visual field index (VFI) and average retinal nerve fiber layer thickness (TSNIT average). A bayesian hierarchical model was built to integrate information from the longitudinal measures and classify individual eyes as progressing or not. Estimates of sensitivity and specificity of the bayesian method were compared with those obtained by the conventional approach of ordinary least-squares (OLS) regression. RESULTS The bayesian method identified a significantly higher proportion of the 405 glaucomatous and suspect eyes as having progressed when compared with the OLS method (22.7% vs. 12.8%; P < 0.001), while having the same specificity of 100% in 29 healthy eyes. In addition, the bayesian method identified a significantly higher proportion of eyes with progression by optic disc stereophotographs compared with the OLS method (74% vs. 37%; P = 0.001). CONCLUSIONS A bayesian hierarchical modeling approach for combining functional and structural tests performed significantly better than the OLS method for detection of glaucoma progression. (ClinicalTrials.gov number, NCT00221897.).

Effect of disease severity and optic disc size on diagnostic accuracy of RTVue spectral domain optical coherence tomograph in glaucoma.

PURPOSE To evaluate the effect of disease severity and optic disc size on the diagnostic accuracies of optic nerve head (ONH), retinal nerve fiber layer (RNFL), and macular parameters with RTVue (Optovue, Fremont, CA) spectral domain optical coherence tomography (SDOCT) in glaucoma. METHODS 110 eyes of 62 normal subjects and 193 eyes of 136 glaucoma patients from the Diagnostic Innovations in Glaucoma Study underwent ONH, RNFL, and macular imaging with RTVue. Severity of glaucoma was based on visual field index (VFI) values from standard automated perimetry. Optic disc size was based on disc area measurement using the Heidelberg Retina Tomograph II (Heidelberg Engineering, Dossenheim, Germany). Influence of disease severity and disc size on the diagnostic accuracy of RTVue was evaluated by receiver operating characteristic (ROC) and logistic regression models. RESULTS Areas under ROC curve (AUC) of all scanning areas increased (P < 0.05) as disease severity increased. For a VFI value of 99%, indicating early damage, AUCs for rim area, average RNFL thickness, and ganglion cell complex-root mean square were 0.693, 0.799, and 0.779, respectively. For a VFI of 70%, indicating severe damage, corresponding AUCs were 0.828, 0.985, and 0.992, respectively. Optic disc size did not influence the AUCs of any of the SDOCT scanning protocols of RTVue (P > 0.05). Sensitivity of the rim area increased and specificity decreased in large optic discs. CONCLUSIONS Diagnostic accuracies of RTVue scanning protocols for glaucoma were significantly influenced by disease severity. Sensitivity of the rim area increased in large optic discs at the expense of specificity.

Comparison of Corneal Biomechanical Properties Between Healthy Blacks and Whites Using the Ocular Response Analyzer

PURPOSE To analyze and compare corneal biomechanical properties in healthy black and white subjects using the Ocular Response Analyzer (ORA) and to evaluate their relationship with other ocular parameters. DESIGN Observational cross-sectional study. METHODS One hundred eighty one eyes (46 in blacks, 135 in whites) of 119 patients (37 blacks, 82 whites) were recruited from the longitudinal Diagnostic Innovations in Glaucoma Study (DIGS) and from the African Descent and Glaucoma Evaluation Study (ADAGES) at the University of California, San Diego. Corneal curvature, axial length, central corneal thickness (CCT), corneal hysteresis (CH), and corneal resistance factor (CRF) were obtained from all participants. Univariable and multivariable regression analyses were used to evaluate the associations between ORA measurements and age, CCT, axial length, corneal curvature, and race. RESULTS Black subjects had significantly lower values of CH (9.7 mm Hg vs 10.4 mm Hg; P = .033), CRF (9.84 mm Hg vs 10.70 mm Hg; P = .028), and CCT (534 mum vs 562 mum; P = .001) compared to white subjects. A significant relationship was found between CH and CCT (R(2) = 0.25; P < .001) and between CRF and CCT (R(2) = 0.42; P < .001). After adjusting for CCT, age, axial length, and corneal curvature, the difference between blacks and whites in CH (P = .077) and CRF (P = .621) measurements lost statistical significance. CONCLUSION Black subjects tended to have lower measurements of corneal hysteresis compared to white subjects; however, this was largely explained by differences in corneal thickness. Therefore, it is unlikely that CH would have an independent effect in explaining differences in susceptibility of disease between these 2 racial groups.

Association between Corneal Biomechanical Properties and Glaucoma Severity

PURPOSE To investigate the association between corneal biomechanical parameters using the Ocular Response Analyzer (ORA) and glaucoma severity. DESIGN Observational cross-sectional study. METHODS Two hundred ninety-nine eyes of 191 patients with confirmed or suspect glaucoma were recruited at the University of California, San Diego. Corneal hysteresis (CH) and corneal resistance factor (CRF) were obtained from all participants. Standard automated perimetry was done using the 24-2 Swedish Interactive Threshold Algorithm. Retinal nerve fiber layer (RNFL) thickness measurements were obtained using GDx ECC and spectral-domain optical coherence tomography (SD-OCT). The association between ORA parameters and disease severity was evaluated using univariable and multivariable regression models. RESULTS CH and CRF were both positively associated with mean defect (MD) (R(2) = 0.03; P < .01 and R(2) = 0.10; P < .01, respectively). In multivariable analysis, the association between CRF and MD remained significant while CH to MD did not (P < .01 and P = .77). In the GDx ECC subgroup (204 eyes), there was a weak association between CH and CRF and average RNFL thickness (R(2) = 0.07; P < .01 and R(2) = 0.05; P < .01, respectively), which was not observed in the SD-OCT subgroup (146 eyes) (R(2) = 0.01; P = .30 and R(2) = 0.01; P = .21). After adjusting for central corneal thickness, age, and axial length, the relationship of CH and CRF to RNFL thickness no longer reached statistical significance. CONCLUSIONS The current study found only a weak relationship between corneal biomechanical parameters and measures of structural and functional damage in glaucoma.