Harsha L. Rao

Comparison of Different Spectral Domain Optical Coherence Tomography Scanning Areas for Glaucoma Diagnosis

PURPOSE To evaluate retinal nerve fiber layer (RNFL), optic nerve head (ONH), and macular thickness measurements for glaucoma detection using the RTVue spectral domain optical coherence tomograph. DESIGN Diagnostic, case-control study. PARTICIPANTS One hundred forty eyes of 106 glaucoma patients and 74 eyes of 40 healthy subjects from the Diagnostic Innovations in Glaucoma Study (DIGS). METHODS All patients underwent ocular imaging with the commercially available RTVue. Optic nerve head, RNFL thickness, and macular thickness scans were obtained during the same visit. Receiver operating characteristic (ROC) curves and sensitivities at fixed specificities (80% and 95%) were calculated for each parameter. MAIN OUTCOME MEASURES Areas under the ROC curves (AUC) and sensitivities at fixed specificities of 80% and 95%. RESULTS The AUC for the RNFL parameter with best performance, inferior quadrant thickness, was significantly higher than that of the best-performing ONH parameter, inferior rim area (0.884 vs 0.812, respectively; P = 0.04). There was no difference between ROC curve areas of the best RNFL thickness parameters and the best inner macular thickness measurement, ganglion cell complex root mean square (ROC curve area = 0.870). CONCLUSIONS The RTVue RNFL and inner retinal macular thickness measurements had good ability to detect eyes with glaucomatous visual field loss and performed significantly better than ONH parameters.

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.

Retinal nerve fiber layer and macular inner retina measurements by spectral domain optical coherence tomograph in Indian eyes with early glaucoma

PurposeTo compare the diagnostic abilities of peripapillary retinal nerve fiber layer (RNFL) and macular inner retina (MIR) measurements by spectral domain optical coherence tomography (SD–OCT) in Indian eyes early glaucoma.MethodsIn an observational, cross-sectional study, 125 eyes of 64 normal subjects and 91 eyes of 59 early glaucoma patients underwent RNFL and MIR imaging with SD–OCT. Glaucomatous eyes had characteristic optic nerve and RNFL abnormalities and correlating visual field defects and a mean deviation of better than or equal to -6 dB on standard automated perimetry. Areas under the receiver operating characteristic curves (AUC), sensitivities at a fixed specificity and likelihood ratios (LRs) were estimated for all RNFL and MIR parameters.ResultsThe AUCs for the RNFL parameters ranged from 0.537 for the temporal quadrant thickness to 0.821 for the inferior quadrant RNFL thickness. AUCs for the MIR parameters ranged from 0.603 for the superior minus inferior MIR thickness average to 0.908 for ganglion cell complex focal loss volume (GCC–FLV). AUC for the best MIR parameter (GCC–FLV) was significantly better (P<0.001) than that of the best RNFL parameter (inferior quadrant thickness). The sensitivities of these parameters at high specificity of 95%, however, were comparable (52.7% vs58.2%). Evaluation of the LRs showed that outside normal limits results of most of the RNFL and MIR parameters were associated with large effects on the post-test probability of disease.ConclusionMIR parameters with RTVue SD–OCT were as good as the RNFL parameters to detect early glaucoma.

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.

Effect of Spectrum Bias on the Diagnostic Accuracy of Spectral-Domain Optical Coherence Tomography in Glaucoma

PURPOSE To evaluate the influence of a control group on the diagnostic accuracy of spectral-domain optical coherence tomography (SD-OCT) in early glaucoma. METHODS In a diagnostic, case-control study, 119 eyes of 60 normal subjects with no findings suspicious for glaucoma (control cohort 1); 76 eyes of 41 subjects referred by general ophthalmologists as glaucoma suspects based on optic disc morphology, but found by glaucoma experts to be normal but with physiological variations in their optic nerves (control cohort 2); and 65 eyes of 46 early-glaucoma patients (cases) underwent imaging of the optic nerve head (ONH), retinal nerve fiber layer (RNFL), and ganglion cell complex (GCC) by SD-OCT. RESULTS Areas under the receiver operating characteristic curves (AUC) of ONH parameters discriminating glaucomatous eyes from normal eyes of control cohort 2 were significantly lesser (P < 0.001) than those discriminating glaucomatous eyes from normal eyes of control cohort 1. AUCs of RNFL parameters discriminating glaucomatous eyes from normal eyes of control cohorts 2 and 1 were comparable. Although the AUCs of GCC thickness parameters were comparable, AUCs of GCC focal and global loss volume in control cohort 2 (0.684 and 0.671. respectively) were significantly less (P < 0.05) than in control cohort 1 (0.881 and 0.841, respectively). CONCLUSIONS The effectiveness of most SD-OCT parameters in detecting glaucoma significantly decreased when evaluated against a clinically relevant control group with suspicious-looking optic nerves compared with that against a control group consisting of normal subjects with no findings suspicious for glaucoma.

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.

Neurodegeneration in Type 2 Diabetes: Evidence From Spectral-Domain Optical Coherence Tomography

PURPOSE The purpose of this study was to assess changes in the neural retina in eyes with different stages of diabetic retinopathy (DR) in comparison to age-matched healthy subjects. METHODS Retrospective analysis of spectral-domain optical coherence tomography (SD-OCT) scans of 76 naïve eyes of 62 subjects with diabetes was performed. Key exclusion criteria included presence of diabetic macular edema, any other retinal disease, history of any treatment for DR, or incorrect segmentation of the retinal layers on SD-OCT scans. Eyes from diabetic patients were divided into three groups, including no DR, nonproliferative DR (NPDR), and proliferative DR (PDR). A control group of 67 eyes of 66 age-matched healthy volunteers was included for comparison. Average, minimum, and sectoral thicknesses for the ganglion cell-inner plexiform layer (GCIPL) and retinal nerve fiber layer (RNFL) were collected from both groups and compared using an ANOVA test. RESULTS Among the 76 included eyes, 43 had NPDR, 13 had PDR, and 20 had no signs of DR. Average and minimum GCIPL showed significant thinning in diabetic subjects compared with controls in all stages of DR (P < 0.05), especially involving the papillo-macula bundle. However, GCIPL thickness was similar between diabetic groups. There was no significant difference in average or sectoral RNFL thicknesses among groups; however, the minimum RNFL thickness was lower in diabetics compared with controls (P < 0.05). No relationship between GCIPL and RNFL thicknesses and duration of diabetes was present. CONCLUSIONS Early thinning on the inner retina happens in type 2 diabetes, even before visible vascular signs of DR. This supports the presence of a neurodegenerative process in eyes of patients with diabetes and warrants neuroprotective intervention to prevent chronic neurodegeneration. The SD-OCT may represent an indispensable tool for identifying early signs of neurodegeneration in diabetic patients.

Accuracy of intraocular lens power calculation formulae in children less than two years.

PURPOSE To assess the accuracy of IOL power calculation formulae in children less than 2 years of age. DESIGN Retrospective, comparative study, comprising of 128 eyes of 84 children. METHODS We analyzed records of children less than 2 years with congenital cataract who underwent primary IOL implantation. Data were analyzed for prediction error using the 4 commonly used IOL power calculation formulae. We calculated the absolute prediction error with each of the formulae and the formula that gave least variability was determined. The formula that gave the best prediction error was determined. RESULTS Mean age at surgery was 11.7 ± 6.2 months. Absolute prediction error was found to be 2.27 ± 1.69 diopters (D) with SRK II, 3.23 ± 2.24 D with SRK T, 3.62 ± 2.42 D with Holladay, and 4.61 ± 3.12 D with Hoffer Q. The number of eyes with absolute prediction error within 0.5 D was 27 (21.1%) with SRK II, 8 (6.3%) with SRK T, 12 (9.4%) with Holladay, and 5 (3.9%) with Hoffer Q. Comparison between different formulae showed that the absolute prediction error with SRK II formula was significantly better than with other formulae (P < .001). Prediction error with SRK II formula was not affected by any factor such as age (P = .31), keratometry (P = .32), and axial length (P = .27) of the patient. Axial length influenced the absolute prediction error with Holladay (P = .05) and Hoffer Q formulae (P = .002). Mean keratometry influenced prediction error (P = .03) with SRK T formula. CONCLUSION Although absolute prediction error tends to remain high with all present IOL power calculation formulae, SRK II was the most predictable formula in our series.