Luciana M. Alencar

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.

Detection of glaucoma progression with stratus OCT retinal nerve fiber layer, optic nerve head, and macular thickness measurements.

PURPOSE To evaluate and compare the ability of optical coherence tomography (OCT) retinal nerve fiber layer (RNFL), optic nerve head, and macular thickness parameters to detect progressive structural damage in glaucoma. METHODS This observational cohort study included 253 eyes of 253 patients. Images were obtained annually with the Stratus OCT (Carl Zeiss Meditec, Inc., Dublin, CA) along with optic disc stereophotographs and standard automated perimetry (SAP) visual fields. The median follow-up time was 4.01 years. Progression was determined by the Guided Progression Analysis software for SAP (Carl Zeiss Meditec, Inc.) and by masked assessment of optic disc stereophotographs performed by expert graders. Random coefficient models and receiver operating characteristic (ROC) curves were used to evaluate the relationship between change in Stratus OCT parameters over time and progression as determined by SAP and/or stereophotographs. RESULTS From the 253 eyes, 31 (13%) showed progression over time by stereophotographs and/or SAP. Mean rates of change in average RNFL thickness were significantly higher for progressors compared with nonprogressors (-0.72 mum/y vs. 0.14 mum/y; P = 0.004), with sensitivity of 77% for specificity of 80%. RNFL parameters performed significantly better than ONH and macular thickness measurements in discriminating progressors from nonprogressors. The parameters with the largest ROC curve areas for each scanning area were inferior RNFL thickness (0.84), cup area (0.66), and inferior inner macula thickness (0.64). CONCLUSIONS Stratus OCT RNFL parameters discriminated between eyes progressing by visual fields or optic disc photographs and eyes that remained stable by these methods and performed significantly better than ONH and macular thickness parameters in detecting change over time.

Prediction of Functional Loss in Glaucoma From Progressive Optic Disc Damage

OBJECTIVE To evaluate the ability of progressive optic disc damage detected by assessment of longitudinal stereophotographs to predict future development of functional loss in those with suspected glaucoma. METHODS The study included 639 eyes of 407 patients with suspected glaucoma followed up for an average of 8.0 years with annual standard automated perimetry visual field and optic disc stereophotographs. All patients had normal and reliable standard automated perimetry results at baseline. Conversion to glaucoma was defined as development of 3 consecutive abnormal visual fields during follow-up. Presence of progressive optic disc damage was evaluated by grading longitudinally acquired simultaneous stereophotographs. Other predictive factors included age, intraocular pressure, central corneal thickness, pattern standard deviation, and baseline stereophotograph grading. Hazard ratios for predicting visual field loss were obtained by extended Cox models, with optic disc progression as a time-dependent covariate. Predictive accuracy was evaluated using a modified R(2) index. RESULTS Progressive optic disc damage had a hazard ratio of 25.8 (95% confidence interval, 16.0-41.7) and was the most important risk factor for development of visual field loss with an R(2) of 79%. The R(2)s for other predictive factors ranged from 6% to 26%. CONCLUSIONS Presence of progressive optic disc damage on stereophotographs was a highly predictive factor for future development of functional loss in glaucoma. These findings suggest the importance of careful monitoring of the optic disc appearance and a potential role for longitudinal assessment of the optic disc as an end point in clinical trials and as a reference for evaluation of diagnostic tests in glaucoma.

Detection of progressive retinal nerve fiber layer loss in glaucoma using scanning laser polarimetry with variable corneal compensation.

PURPOSE To evaluate the ability of scanning laser polarimetry with variable corneal compensation to detect progressive retinal nerve fiber layer (RNFL) loss in glaucoma patients and patients suspected of having the disease. METHODS This was an observational cohort study that included 335 eyes of 195 patients. Images were obtained annually with the GDx VCC scanning laser polarimeter, along with optic disc stereophotographs and standard automated perimetry (SAP) visual fields. The median follow-up time was 3.94 years. Progression was determined using commercial software for SAP and by masked assessment of optic disc stereophotographs performed by expert graders. Random coefficient models were used to evaluate the relationship between RNFL thickness measurements over time and progression as determined by SAP and/or stereophotographs. RESULTS From the 335 eyes, 34 (10%) showed progression over time by stereophotographs and/or SAP. Average GDx VCC measurements decreased significantly over time for both progressors as well as non-progressors. However, the rate of decline was significantly higher in the progressing group (-0.70 microm/year) compared to the non-progressing group (-0.14 microm/year; P=0.001). Black race and male sex were significantly associated with higher rates of RNFL loss during follow-up. CONCLUSIONS The GDx VCC scanning laser polarimeter was able to identify longitudinal RNFL loss in eyes that showed progression in optic disc stereophotographs and/or visual fields. These findings suggest that this technology could be useful to detect and monitor progressive disease in patients with established diagnosis of glaucoma or suspected of having the disease.

Comparison of Retinal Nerve Fiber Layer and Optic Disc Imaging for Diagnosing Glaucoma in Patients Suspected of Having the Disease

PURPOSE To compare retinal nerve fiber layer (RNFL) and optic disc topographic imaging for detection of optic nerve damage in patients suspected of having glaucoma. DESIGN Observational cohort study. PARTICIPANTS A cohort of 82 patients suspected of having glaucoma based on the appearance of the optic nerve. METHODS All patients were imaged using the GDx VCC scanning laser polarimeter and HRT (software version 3.0) confocal scanning laser ophthalmoscope. All patients had normal standard automated perimetry visual fields at the time of imaging and were classified based on 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 (ROC) curves were used to evaluate the diagnostic accuracies of GDx VCC and the HRT. RESULTS Forty eyes with progressive glaucomatous optic nerve change were included in the glaucoma group, and 42 eyes without any evidence of progressive damage to the optic nerve followed untreated for an average time of 8.97+/-3.08 years were included in the normal group. The area under the ROC curve for the best parameter from GDx VCC (nerve fiber indicator [NFI]) was significantly larger than that of the best parameter from the HRT (rim volume) (0.83 vs. 0.70; P = 0.044). The NFI parameter also had a larger ROC curve area than that of the contour line-independent parameter glaucoma probability score (0.83 vs. 0.68; P = 0.023). Assuming borderline results as normal, the Moorfields regression analysis classification had a sensitivity of 48% for specificity of 69%. For a similar specificity (70%), the parameter NFI had a significantly larger sensitivity (83%) (P = 0.003). CONCLUSIONS Retinal nerve fiber layer imaging with GDx VCC had a superior performance versus topographic optic disc assessment with the HRT for detecting early damage in patients suspected of having glaucoma. For glaucoma diagnosis, these results suggest that GDx VCC may offer advantage over the HRT when these tests are combined with clinical examination of the optic nerve.

The Relationship between Intraocular Pressure and Progressive Retinal Nerve Fiber Layer Loss in Glaucoma

PURPOSE To evaluate the relationship between intraocular pressure (IOP) and progressive retinal nerve fiber layer (RNFL) loss, as measured by scanning laser polarimetry with enhanced corneal compensation (GDx ECC), in a cohort of glaucoma patients and individuals suspected of having the disease followed over time. DESIGN Observational cohort study. PARTICIPANTS The study included 344 eyes of 204 patients recruited from the Diagnostic Innovations in Glaucoma Study (DIGS). There were 98 eyes (28%) with a diagnosis of glaucoma and 246 (72%) were considered glaucoma suspects at baseline. METHODS Images were obtained annually with the GDx ECC scanning laser polarimeter, along with stereophotographs and SAP. The study included a total of 1211 GDx ECC visits with an average of 3.5 visits per eye. Progression was determined by the Guided Progression Analysis software for SAP and by masked assessment of stereophotographs performed by expert graders. MAIN OUTCOME MEASURES Random coefficient models were used to evaluate the relationship between IOP and RNFL thickness measurements over time in progressors and nonprogressors. Models were adjusted for baseline diagnosis and central corneal thickness. RESULTS For all 344 eyes, the overall rate of change for the GDx ECC average thickness at an average IOP of 17 mmHg was -0.25 microm per year (P = 0.002). Each 1-mmHg higher IOP was associated with an additional loss of 0.05 microm per year of RNFL (P = 0.001). Twenty-nine eyes (8%) showed progression on SAP and/or optic disc stereophotographs. These eyes had a significantly higher rate of RNFL change (-0.95 microm/year) than nonprogressors (-0.17 microm/year; P = 0.001). For progressors, each 1-mmHg higher IOP was associated with an additional loss of 0.13 microm per year of RNFL. CONCLUSIONS Higher levels of IOP during follow-up were significantly related to higher rates of progressive RNFL loss detected by the GDx ECC. These findings suggest that the GDx ECC may be helpful in monitoring progression and estimating rates of change in patients with glaucoma or suspected of having the disease. Also, they may contribute to a better understanding of the relationship between IOP and structural deterioration in glaucoma. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

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.

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.

Agreement for Detecting Glaucoma Progression with the GDx Guided Progression Analysis, Automated Perimetry, and Optic Disc Photography

PURPOSE To evaluate the ability of the GDx Variable Corneal Compensation (VCC) Guided Progression Analysis (GPA) software for detecting glaucomatous progression. DESIGN Observational cohort study. PARTICIPANTS The study included 453 eyes from 252 individuals followed for an average of 46+/-14 months as part of the Diagnostic Innovations in Glaucoma Study. At baseline, 29% of the eyes were classified as glaucomatous, 67% of the eyes were classified as suspects, and 5% of the eyes were classified as healthy. METHODS Images were obtained annually with the GDx VCC and analyzed for progression using the Fast Mode of the GDx GPA software. Progression using conventional methods was determined by the GPA software for standard automated achromatic perimetry (SAP) and by masked assessment of optic disc stereophotographs by expert graders. MAIN OUTCOME MEASURES Sensitivity, specificity, and likelihood ratios (LRs) for detection of glaucoma progression using the GDx GPA were calculated with SAP and optic disc stereophotographs used as reference standards. Agreement among the different methods was reported using the AC(1) coefficient. RESULTS Thirty-four of the 431 glaucoma and glaucoma suspect eyes (8%) showed progression by SAP or optic disc stereophotographs. The GDx GPA detected 17 of these eyes for a sensitivity of 50%. Fourteen eyes showed progression only by the GDx GPA with a specificity of 96%. Positive and negative LRs were 12.5 and 0.5, respectively. None of the healthy eyes showed progression by the GDx GPA, with a specificity of 100% in this group. Inter-method agreement (AC(1) coefficient and 95% confidence intervals) for non-progressing and progressing eyes was 0.96 (0.94-0.97) and 0.44 (0.28-0.61), respectively. CONCLUSIONS The GDx GPA detected glaucoma progression in a significant number of cases showing progression by conventional methods, with high specificity and high positive LRs. Estimates of the accuracy for detecting progression suggest that the GDx GPA could be used to complement clinical evaluation in the detection of longitudinal change in glaucoma.

A Comparison of Rates of Change in Neuroretinal Rim Area and Retinal Nerve Fiber Layer Thickness in Progressive Glaucoma

PURPOSE. To evaluate and compare rates of change in neuroretinal rim area (RA) and retinal nerve fiber layer thickness (RNFLT) measurements in glaucoma patients, those with suspected glaucoma, and normal subjects observed over time. METHODS. In this observational cohort study, patients recruited from two longitudinal studies (Diagnostic Innovations in Glaucoma Study-DIGS and African Descent and Evaluation Study-ADAGES) were observed with standard achromatic perimetry (SAP), optic disc stereophotographs, confocal scanning laser ophthalmoscopy (HRT-3; Heidelberg Engineering, Heidelberg, Germany), and scanning laser polarimetry (GDx-VCC; Carl Zeiss Meditec, Inc., Dublin, CA). Glaucoma progression was determined by the Guided Progression Analysis software for standard automated perimetry [SAP] and by masked assessment of serial optic disc stereophotographs by expert graders. Random-coefficients models were used to evaluate rates of change in average RNFLT and global RA measurements and their relationship with glaucoma progression. RESULTS. At baseline, 194 (31%) eyes were glaucomatous, 347 (55%) had suspected glaucoma, and 88 (14%) were normal. Forty-six (9%) eyes showed progression by SAP and/or stereophotographs, during an average follow-up of 3.3 (+/-0.7) years. The average rate of decline for RNFLT measurements was significantly higher in the progressing group than in the nonprogressing group (-0.65 vs. -0.11 microm/y, respectively; P < 0.001), whereas RA decline was not significantly different between these groups (-0.0058 vs. -0.0073 mm(2)/y, respectively; P = 0.727). The areas under the receiver operating characteristic (ROC) curves used to discriminate progressing versus nonprogressing eyes were 0.811 and 0.507 for the rates of change in the RNFLT and RA, respectively (P < 0.001). CONCLUSIONS. The ability to discriminate eyes with progressing glaucoma by SAP and/or stereophotographs from stable eyes was significantly greater for RNFLT than for RA measurements.