Ravi K. Yadav

Effect of Scan Quality on Diagnostic Accuracy of Spectral-Domain Optical Coherence Tomography in Glaucoma

PURPOSE To evaluate the effect of scan quality on the diagnostic accuracies of optic nerve head (ONH), retinal nerve fiber layer (RNFL), and ganglion cell complex (GCC) parameters of spectral-domain optical coherence tomography (SD OCT) in glaucoma. DESIGN Cross-sectional study. METHODS Two hundred fifty-two eyes of 183 control subjects (mean deviation [MD]: -1.84 dB) and 207 eyes of 159 glaucoma patients (MD: -7.31 dB) underwent ONH, RNFL, and GCC scanning with SD OCT. Scan quality of SD OCT images was based on signal strength index (SSI) values. Influence of SSI on diagnostic accuracy of SD OCT was evaluated by receiver operating characteristic (ROC) regression. RESULTS Diagnostic accuracies of all SD OCT parameters were better when the SSI values were higher. This effect was statistically significant (P < .05) for ONH and RNFL but not for GCC parameters. In mild glaucoma (MD of -5 dB), area under ROC curve (AUC) for rim area, average RNFL thickness, and average GCC thickness parameters improved from 0.651, 0.678, and 0.726, respectively, at an SSI value of 30 to 0.873, 0.962, and 0.886, respectively, at an SSI of 70. AUCs of the same parameters in advanced glaucoma (MD of -15 dB) improved from 0.747, 0.890, and 0.873, respectively, at an SSI value of 30 to 0.922, 0.994, and 0.959, respectively, at an SSI of 70. CONCLUSION Diagnostic accuracies of SD OCT parameters in glaucoma were significantly influenced by the scan quality even when the SSI values were within the manufacturer-recommended limits. These results should be considered while interpreting the SD OCT scans for glaucoma.

Role of Visual Field Reliability Indices in Ruling Out Glaucoma

IMPORTANCE Standard automated perimetry is the current criterion standard for assessment of visual field (VF) loss in glaucoma. The 3 commonly used reliability indices to judge the quality of standard automated perimetry results are fixation losses (FLs) and false-positive (FP) and false-negative (FN) response rates. However, the influence of reliability indices, when within the manufacturer-recommended limits, on VF classification has been sparsely studied. OBJECTIVE To evaluate the role of VF reliability indices in ruling out glaucoma. DESIGN, SETTING, AND PARTICIPANTS A cross-sectional study of 291 eyes of 291 participants referred to a tertiary eye care facility by general ophthalmologists. The participants were suspected to have glaucoma based on optic disc appearance, but the eyes were judged to be normal with physiological cupping by glaucoma experts on masked evaluation of optic disc photographs. All participants underwent VF testing with the Swedish interactive threshold algorithm standard 24-2 program. MAIN OUTCOMES AND MEASURES Logistic regression models were used to evaluate the associations between reliability indices and FP classifications on VF testing (glaucoma hemifield test as outside normal limits and pattern standard deviation with P < .05). RESULTS Median FL, FP, and FN response rates were 7%, 1%, and 2%, respectively. Among the 241 participants with reliable VF results (FL <20% and FP response rate <15%), the VF classification was normal in 188 (78.0%) and glaucoma (FP) in 53 (22.0%). Probability of FP VF classification was associated with FN response rates (odds ratio [OR], 1.36; 95% CI, 1.25-1.48, P < .001) but did not appear to be associated with FLs (OR, 0.96; 95% CI, 0.90-1.03, P = .30) or FP response rates (OR, 0.96; 95% CI, 0.83-1.12, P = .64). Predicted probability of FP VF classification was 9% (95% CI, 6%-14%), 40% (32%-49%), and 82% (68%-91%) at FN response rates of 0%, 8%, and 16%, respectively. CONCLUSIONS AND RELEVANCE This study suggests that FN response rates have an effect on the ability of automated VF assessments to rule out glaucoma. Since FN response rates are ignored by the manufacturer while flagging a test as unreliable, clinicians and researchers may benefit by realizing that FN response rates can lead to FP VF classification, even when their frequencies are small.

Peripapillary Retinal Nerve Fiber Layer Assessment of Spectral Domain Optical Coherence Tomography and Scanning Laser Polarimetry to Diagnose Preperimetric Glaucoma

Purpose To compare the abilities of peripapillary retinal nerve fiber layer (RNFL) parameters of spectral domain optical coherence tomograph (SDOCT) and scanning laser polarimeter (GDx enhanced corneal compensation; ECC) in detecting preperimetric glaucoma. Methods In a cross-sectional study, 35 preperimetric glaucoma eyes (32 subjects) and 94 control eyes (74 subjects) underwent digital optic disc photography and RNFL imaging with SDOCT and GDx ECC. Ability of RNFL parameters of SDOCT and GDx ECC to discriminate preperimetric glaucoma eyes from control eyes was compared using area under receiver operating characteristic curves (AUC), sensitivities at fixed specificities and likelihood ratios (LR). Results AUC of the global average RNFL thickness of SDOCT (0.786) was significantly greater (p<0.001) than that of GDx ECC (0.627). Sensitivities at 95% specificity of the corresponding parameters were 20% and 8.6% respectively. AUCs of the inferior, superior and temporal quadrant RNFL thickness parameters of SDOCT were also significantly (p<0.05) greater than the respective RNFL parameters of GDx ECC. LRs of outside normal limits category of SDOCT parameters ranged between 3.3 and 4.0 while the same of GDx ECC parameters ranged between 1.2 and 2.1. LRs of within normal limits category of SDOCT parameters ranged between 0.4 and 0.7 while the same of GDx ECC parameters ranged between 0.7 and 1.0. Conclusions Abilities of the RNFL parameters of SDOCT and GDx ECC to diagnose preperimetric glaucoma were only moderate. Diagnostic abilities of the RNFL parameters of SDOCT were significantly better than that of GDx ECC in preperimetric glaucoma.

Retinal nerve fiber layer measurements by scanning laser polarimetry with enhanced corneal compensation in healthy subjects.

Purpose:To evaluate the (i) effects of biological (age and axial length) and instrument-related [typical scan score (TSS) and corneal birefringence] parameters on the retinal nerve fiber layer (RNFL) measurements and (ii) repeatability of RNFL measurements with the enhanced corneal compensation (ECC) protocol of scanning laser polarimetry (SLP) in healthy subjects. Methods:In a cross-sectional study, 140 eyes of 73 healthy subjects underwent RNFL imaging with the ECC protocol of SLP. Linear mixed modeling methods were used to evaluate the effects of age, axial length, TSS, and corneal birefringence on RNFL measurements. One randomly selected eye of 48 subjects from the cohort underwent 3 serial scans during the same session to determine the repeatability. Results:Age significantly influenced all RNFL measurements. RNFL measurements decreased by 1 µm for every decade increase in age. TSS affected the overall average RNFL measurement (&bgr;=−0.62, P=0.003), whereas residual anterior segment retardance affected the superior quadrant measurement (&bgr;=1.14, P=0.01). Axial length and corneal birefringence measurements did not influence RNFL measurements. Repeatability, as assessed by the coefficient of variation, ranged between 1.7% for the overall average RNFL measurement and 11.4% for th nerve fiber indicator. Conclusions:Age significantly affected all RNFL measurements with the ECC protocol of SLP, whereas TSS and residual anterior segment retardance affected the overall average and the superior average RNFL measurements, respectively. Axial length and corneal birefringence measurements did not influence any RNFL measurements. RNFL measurements had good intrasession repeatability. These results are important while evaluating the change in structural measurements over time in glaucoma patients.

Scanning the macula for detecting glaucoma

Background: With the advent of spectral domain optical coherence tomography (SDOCT), there has been a renewed interest in macular region for detection of glaucoma. However, most macular SDOCT parameters currently are thickness parameters which evaluate thinning of the macular layers but do not quantify the extent of area over which the thinning has occurred. We therefore calculated a new macular parameter, ganglion cell complex surface abnormality ratio (GCC SAR) that represented the surface area over which the macular thickness was decreased. Purpose: To evaluate the ability of SAR in detecting perimetric and preperimetric glaucoma. Design: Retrospective image analysis. Materials and Methods: 68 eyes with perimetric glaucoma, 62 eyes with preperimetric glaucoma and 165 control eyes underwent GCC imaging with SDOCT. SAR was calculated as the ratio of the abnormal to total area on the GCC significance map. Statistical Analysis: Diagnostic ability of SAR in glaucoma was compared against that of the standard parameters generated by the SDOCT software using area under receiver operating characteristic curves (AUC) and sensitivities at fixed specificities. Results: AUC of SAR (0.91) was statistically significantly better than that of GCC average thickness (0.86, P= 0.001) and GCC global loss volume (GLV; 0.88, P= 0.01) in differentiating perimetric glaucoma from control eyes. In differentiating preperimetric glaucoma from control eyes, AUC of SAR (0.72) was comparable to that of GCC average thickness (0.70, P> 0.05) and GLV (0.72, P> 0.05). Sensitivities at specificities of 80% and 95% of SAR were comparable (P > 0.05 for all comparisons) to that of GCC average thickness and GLV in diagnosing perimetric and preperimetric glaucoma. Conclusion: GCC SAR had a better ability to diagnose perimetric glaucoma compared to the SDOCT software provided global GCC parameters. However, in diagnosing preperimetric glaucoma, the ability of SAR was similar to that of software provided global GCC parameters.

Reference Standard Test and the Diagnostic Ability of Spectral Domain Optical Coherence Tomography in Glaucoma.

Purpose:To evaluate the relationship between the reference standard used to diagnose glaucoma and the diagnostic ability of spectral domain optical coherence tomograph (SDOCT). Methods:In a cross-sectional study, 280 eyes of 175 consecutive subjects, referred to a tertiary eye care center for glaucoma evaluation, underwent optic disc photography, visual field (VF) examination, and SDOCT examination. The cohort was divided into glaucoma and control groups based on 3 reference standards for glaucoma diagnosis: first based on the optic disc classification (179 glaucoma and 101 control eyes), second on VF classification (glaucoma hemifield test outside normal limits and pattern SD with P-value of <5%, 130 glaucoma and 150 control eyes), and third on the presence of both glaucomatous optic disc and glaucomatous VF (125 glaucoma and 155 control eyes). Relationship between the reference standards and the diagnostic parameters of SDOCT were evaluated using areas under the receiver operating characteristic curve, sensitivity, and specificity. Results:Areas under the receiver operating characteristic curve and sensitivities of most of the SDOCT parameters obtained with the 3 reference standards (ranging from 0.74 to 0.88 and 72% to 88%, respectively) were comparable (P>0.05). However, specificities of SDOCT parameters were significantly greater (P<0.05) with optic disc classification as reference standard (74% to 88%) compared with VF classification as reference standard (57% to 74%). Conclusions:Diagnostic parameters of SDOCT that was significantly affected by reference standard was the specificity, which was greater with optic disc classification as the reference standard. This has to be considered when comparing the diagnostic ability of SDOCT across studies.

Comparing spectral-domain optical coherence tomography and standard automated perimetry to diagnose glaucomatous optic neuropathy.

Purpose:To compare the abilities of standard automated perimetry (SAP) and spectral-domain optical coherence tomography (SDOCT) in diagnosing eyes with glaucomatous optic neuropathy (GON). Methods:In a cross-sectional study, 280 eyes of 175 subjects referred to tertiary eye care center by general ophthalmologists for a glaucoma evaluation underwent retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) imaging with SDOCT. All subjects had at least 2 reliable and repeatable SAP. Two glaucoma experts masked to clinical and SAP results classified the optic nerves into GON and nonglaucomatous groups based on digital optic disc photographs. Ability of SDOCT parameters and SAP to discriminate GON eyes from nonglaucomatous eyes was evaluated using sensitivity, specificity, and likelihood ratios (LR). Results:Experts classified 179 eyes into GON and 101 eyes into nonglaucomatous group. Sensitivity of SAP (69.8%) was significantly lower (P<0.05) than that of inferior quadrant RNFL thickness (83.8%), average RNFL thickness (77.2%), GCC focal loss volume (FLV, 81.5%), and global loss volume (GLV, 82.6%). Specificity and positive LR of SAP (95% and14.1, respectively) were significantly greater than those of all RNFL parameters, FLV (84.2% and 5.1) and GLV (82.2% and 4.6). Negative LR of SAP (0.32) was significantly inferior to that of inferior quadrant RNFL thickness (0.22), FLV (0.22), and GLV (0.21). Conclusions:Most of the RNFL and GCC parameters of SDOCT had better sensitivities and negative LRs to diagnose GON compared with SAP. The specificities and positive LRs of most SDOCT parameters were inferior to that of SAP.

The ISNT rule in glaucoma: revisiting with spectral domain optical coherence tomography.

To evaluate the ability of the neuroretinal rim (NRR) rules determined using spectral domain optical coherence tomography (SDOCT) in diagnosing glaucoma and to study the effect of optic disc size and disease severity on the diagnostic ability of these rules.

Factors affecting the ability of the spectral domain optical coherence tomograph to detect photographic retinal nerve fiber layer defects.

Purpose To evaluate the ability of normative database classification (color-coded maps) of spectral domain optical coherence tomograph (SDOCT) in detecting wedge shaped retinal nerve fiber layer (RNFL) defects identified on photographs and the factors affecting the ability of SDOCT in detecting these RNFL defects. Methods In a cross-sectional study, 238 eyes (476 RNFL quadrants) of 172 normal subjects and 85 eyes (103 RNFL quadrants with wedge shaped RNFL defects) of 66 glaucoma patients underwent RNFL imaging with SDOCT. Logistic regression models were used to evaluate the factors associated with false positive and false negative RNFL classifications of the color-coded maps of SDOCT. Results False positive classification at a p value of <5% was seen in 108 of 476 quadrants (22.8%). False negative classification at a p value of <5% was seen in 16 of 103 quadrants (15.5%). Of the 103 quadrants with RNFL defects, 64 showed a corresponding VF defect in the opposite hemisphere and 39 were preperimetric. Higher signal strength index (SSI) of the scan was less likely to have a false positive classification (odds ratio: 0.97, p = 0.01). Presence of an associated visual field defect (odds ratio: 0.17, p = 0.01) and inferior quadrant RNFL defects as compared to superior (odds ratio: 0.24, p = 0.04) were less likely to show false negative classifications. Conclusions Scans with lower signal strengths were more likely to show false positive RNFL classifications, and preperimetric and superior quadrant RNFL defects were more likely to show false negative classifications on color-coded maps of SDOCT.

Diagnostic Abilities of Variable and Enhanced Corneal Compensation Algorithms of GDx in Different Severities of Glaucoma.

Purpose:To compare the abilities of retinal nerve fiber layer (RNFL) parameters of variable corneal compensation (VCC) and enhanced corneal compensation (ECC) algorithms of scanning laser polarimetry (GDx) in detecting various severities of glaucoma. Methods:Two hundred and eighty-five eyes of 194 subjects from the Longitudinal Glaucoma Evaluation Study who underwent GDx VCC and ECC imaging were evaluated. Abilities of RNFL parameters of GDx VCC and ECC to diagnose glaucoma were compared using area under receiver operating characteristic curves (AUC), sensitivities at fixed specificities, and likelihood ratios. Results:After excluding 5 eyes that failed to satisfy manufacturer-recommended quality parameters with ECC and 68 with VCC, 56 eyes of 41 normal subjects and 161 eyes of 121 glaucoma patients [36 eyes with preperimetric glaucoma, 52 eyes with early (MD>−6 dB), 34 with moderate (MD between −6 and −12 dB), and 39 with severe glaucoma (MD<−12 dB)] were included for the analysis. Inferior RNFL, average RNFL, and nerve fiber indicator parameters showed the best AUCs and sensitivities both with GDx VCC and ECC in diagnosing all severities of glaucoma. AUCs and sensitivities of all RNFL parameters were comparable between the VCC and ECC algorithms (P>0.20 for all comparisons). Likelihood ratios associated with the diagnostic categorization of RNFL parameters were comparable between the VCC and ECC algorithms. Conclusion:In scans satisfying the manufacturer-recommended quality parameters, which were significantly greater with ECC than VCC algorithm, diagnostic abilities of GDx ECC and VCC in glaucoma were similar.