Variance components in confocal scanning laser tomography measurements of neuro-retinal rim area and the effect of repeated measurements on the power to detect loss over time.

PURPOSE: To estimate the variation in measurements of neuro-retinal rim area (NRA) determined by confocal scanning laser tomography and consequences for clinical follow-up. METHODS: Altogether, 24 healthy subjects were randomized on -320 µm, Moorfields and Standard NRA plane strategies. Additionally, NRA was measured in 32 glaucoma subjects. Variance components for subjects, visits and measurements were estimated with analysis of variance. Sample sizes required to detect a 6.0 × 10-2  mm2 NRA change were estimated assuming a significance level of 0.05 and a power of 0.8. Consequences for independent group, and paired comparison design, respectively, were analysed. Further, precision in estimates within subjects over time was investigated. RESULTS: The variation of NRA among subjects was considerably larger than the variation among visits and measurements. For glaucoma subjects, the variation among visits and measurements were of the same order but larger than in healthy subjects. It was found that independent group comparisons require inconveniently large sample sizes. Within-subject paired comparisons over time require sample sizes of below 15 subjects. The estimated variations for glaucoma subjects imply that 54 months of follow-up is required for detection of change from baseline. CONCLUSIONS: The variance for subjects is substantial in relation to those for visits and measurements. Cross-sectional independent group comparisons of levels of NRA are unsuitable, due to considerable subject variation. Levels of NRA differences within subjects between visits can be estimated with acceptable precision. Neuro-retinal rim area (NRA) measurement can be used for long-term follow-up of glaucoma progression.

Optic nerve head and fibre layer imaging for diagnosing glaucoma.

BACKGROUND: The diagnosis of glaucoma is traditionally based on the finding of optic nerve head (ONH) damage assessed subjectively by ophthalmoscopy or photography or by corresponding damage to the visual field assessed by automated perimetry, or both. Diagnostic assessments are usually required when ophthalmologists or primary eye care professionals find elevated intraocular pressure (IOP) or a suspect appearance of the ONH. Imaging tests such as confocal scanning laser ophthalmoscopy (HRT), optical coherence tomography (OCT) and scanning laser polarimetry (SLP, as used by the GDx instrument), provide an objective measure of the structural changes of retinal nerve fibre layer (RNFL) thickness and ONH parameters occurring in glaucoma. OBJECTIVES: To determine the diagnostic accuracy of HRT, OCT and GDx for diagnosing manifest glaucoma by detecting ONH and RNFL damage. SEARCH METHODS: We searched several databases for this review. The most recent searches were on 19 February 2015. SELECTION CRITERIA: We included prospective and retrospective cohort studies and case-control studies that evaluated the accuracy of OCT, HRT or the GDx for diagnosing glaucoma. We excluded population-based screening studies, since we planned to consider studies on self-referred people or participants in whom a risk factor for glaucoma had already been identified in primary care, such as elevated IOP or a family history of glaucoma. We only considered recent commercial versions of the tests: spectral domain OCT, HRT III and GDx VCC or ECC. DATA COLLECTION AND ANALYSIS: We adopted standard Cochrane methods. We fitted a hierarchical summary ROC (HSROC) model using the METADAS macro in SAS software. After studies were selected, we decided to use 2 x 2 data at 0.95 specificity or closer in meta-analyses, since this was the most commonly-reported level. MAIN RESULTS: We included 106 studies in this review, which analysed 16,260 eyes (8353 cases, 7907 controls) in total. Forty studies (5574 participants) assessed GDx, 18 studies (3550 participants) HRT, and 63 (9390 participants) OCT, with 12 of these studies comparing two or three tests. Regarding study quality, a case-control design in 103 studies raised concerns as it can overestimate accuracy and reduce the applicability of the results to daily practice. Twenty-four studies were sponsored by the manufacturer, and in 15 the potential conflict of interest was unclear.Comparisons made within each test were more reliable than those between tests, as they were mostly based on direct comparisons within each study.The Nerve Fibre Indicator yielded the highest accuracy (estimate, 95% confidence interval (CI)) among GDx parameters (sensitivity: 0.67, 0.55 to 0.77; specificity: 0.94, 0.92 to 0.95). For HRT measures, the Vertical Cup/Disc (C/D) ratio (sensitivity: 0.72, 0.60 to 0.68; specificity: 0.94, 0.92 to 0.95) was no different from other parameters. With OCT, the accuracy of average RNFL retinal thickness was similar to the inferior sector (0.72, 0.65 to 0.77; specificity: 0.93, 0.92 to 0.95) and, in different studies, to the vertical C/D ratio.Comparing the parameters with the highest diagnostic odds ratio (DOR) for each device in a single HSROC model, the performance of GDx, HRT and OCT was remarkably similar. At a sensitivity of 0.70 and a high specificity close to 0.95 as in most of these studies, in 1000 people referred by primary eye care, of whom 200 have manifest glaucoma, such as in those who have already undergone some functional or anatomic testing by optometrists, the best measures of GDx, HRT and OCT would miss about 60 cases out of the 200 patients with glaucoma, and would incorrectly refer 50 out of 800 patients without glaucoma. If prevalence were 5%, e.g. such as in people referred only because of family history of glaucoma, the corresponding figures would be 15 patients missed out of 50 with manifest glaucoma, avoiding referral of about 890 out of 950 non-glaucomatous people.Heterogeneity investigations found that sensitivity estimate was higher for studies with more severe glaucoma, expressed as worse average mean deviation (MD): 0.79 (0.74 to 0.83) for MD < -6 db versus 0.64 (0.60 to 0.69) for MD ≥ -6 db, at a similar summary specificity (0.93, 95% CI 0.92 to 0.94 and, respectively, 0.94; 95% CI 0.93 to 0.95; P < 0.0001 for the difference in relative DOR). AUTHORS' CONCLUSIONS: The accuracy of imaging tests for detecting manifest glaucoma was variable across studies, but overall similar for different devices. Accuracy may have been overestimated due to the case-control design, which is a serious limitation of the current evidence base.We recommend that further diagnostic accuracy studies are carried out on patients selected consecutively at a defined step of the clinical pathway, providing a description of risk factors leading to referral and bearing in mind the consequences of false positives and false negatives in the setting in which the diagnostic question is made. Future research should report accuracy for each threshold of these continuous measures, or publish raw data.

Measuring retinal nerve fiber layer birefringence, retardation, and thickness using wide-field, high-speed polarization sensitive spectral domain OCT.

PURPOSE: We presented a novel polarization sensitive optical coherence tomography (PS-OCT) system for measuring retinal nerve fiber layer (RNFL) birefringence, retardation, and thickness, and report on the repeatability of acquiring these quantities. METHODS: A new PS-OCT system, measuring at 840 nm, was developed that supports scan angles of up to 40° × 40° with an A-scan rate of 70 kHz. To test the performance and reproducibility, we measured 10 eyes of 5 healthy human volunteers five times each. All volunteers were imaged further with scanning laser polarimetry (SLP). The obtained RNFL birefringence, retardation, and thickness maps were averaged, and standard deviation maps were calculated. For quantitative comparison between the new PS-OCT and SLP, a circumpapillary evaluation within 2 annular segments (superior and inferior to the optic disc) was performed. RESULTS: High quality RNFL birefringence, retardation, and thickness maps were obtained. Within the superior and inferior segments, the mean retardation for individual eyes ranged from 20° to 28.9° and 17.2° to 28.2°, respectively. The quadrant precision over the 5 consecutive measurements for each subject, calculated for the average retardation obtained within the superior and inferior quadrants ranged from 0.16° to 0.69°. The mean birefringence ranged from 0.106°/µm to 0.141°/µm superior and 0.101°/µm to 0.135°/µm inferior, with a quadrant precision of 0.001°/µm to 0.007°/µm. The mean RNFL thickness varied from 114 to 150 µm superior, and 111 to 140.9 µm inferior (quadrant precision ranged from 3.6 to 11.9 µm). CONCLUSIONS: The new PS-OCT system showed high image quality and reproducibility, and, therefore, might be a valuable tool for glaucoma diagnosis.

Glaucoma diagnostic performance of GDxVCC and spectralis OCT on eyes with atypical retardation pattern.

PURPOSE: To investigate the impact of typical scan score (TSS) on discriminating glaucomatous and healthy eyes by scanning laser polarimetry and spectral domain optical coherence tomography (SD-OCT) in 32 peripapillary sectors. PATIENTS AND METHODS: One hundred two glaucoma patients and 32 healthy controls underwent standard automated perimetry, 24-hour intraocular pressure profile, optic disc photography, GDxVCC, and SD-OCT measurements. For controls, only very typical scans (TSS=100) were accepted. Glaucoma patients were divided into 3 subgroups (very typical: TSS=100; typical: 99≥TSS≥80, atypical: TSS<80). Receiver operating characteristic curves were constructed for mean retinal nerve fiber layer values, sector data, and nerve fiber indicator (NFI). Sensitivity was estimated at ≥90% specificity to compare the discriminating ability of each imaging modality. RESULTS: For discrimination between healthy and glaucomatous eyes with very typical scans, the NFI and inferior sector analyses 26 to 27 demonstrated the highest sensitivity at ≥90% specificity in GDxVCC and SD-OCT, respectively. For the typical and atypical groups, sensitivity at ≥90% specificity decreased for all 32 peripapillary sectors on an average by 10.9% and 17.9% for GDxVCC and by 4.9% and 0.8% for SD-OCT. For GDxVCC, diagnostic performance of peripapillary sectors decreased with lower TSS, especially in temporosuperior and inferotemporal sectors (sensitivity at ≥90% specificity decreased by 55.3% and by 37.8% in the atypical group). CONCLUSIONS: Diagnostic accuracy is comparable for SD-OCT and GDxVCC if typical scans (TSS=100) are investigated. Decreasing TSS is associated with a decrease in diagnostic accuracy for discriminating healthy and glaucomatous eyes by scanning laser polarimetry. NFI is less influenced than the global or sector retinal nerve fiber layer thickness. The TSS score should be included in the standard printout. Diagnostic accuracy of SD-OCT is barely influenced by low TSS.

Comparison of scanning laser polarimetry and optical coherence tomography in preperimetric glaucoma.

PURPOSE: This study was performed to compare the effectiveness of scanning laser polarimetry with variable corneal compensation (GDx VCC) and optical coherence tomography (Stratus OCT) for the detection of loss of the retinal nerve fiber layer (RNFL) in preperimetric glaucomatous eyes. METHODS: Sixty subjects with preperimetric glaucoma (60 eyes) and 60 normal subjects (60 eyes) were included. We measured the RNFL thickness with GDx VCC and Stratus OCT and analyzed the results by 12 clock hour RNFL measurements. The area under the receiver-operating characteristic curve was calculated, and the data from all clock hour segments were compared using regression analyses. RESULTS: The mean RNFL thickness for GDx VCC were 49.00 ± 17.23 µm and 59.4 ± 8.38 µm (p < 0.01), and for Stratus OCT, they were 86.43 ± 20.49 µm and 106.61 ± 9.57 µm (p < 0.01) in the patients with preperimetric glaucoma and normal group, respectively. The mean RNFL thickness for the clock hour evaluations were significantly different between the patients with preperimetric glaucoma and the normal group (p < 0.05). In preperimetric glaucoma, the area under the receiver-operating characteristic curve was the highest for the 12 clock hour RNFL thickness for GDx VCC (0.905) and the 7 clock hour RNFL thickness for Stratus OCT (0.903). GDx VCC and Stratus OCT RNFL measurements had significantly high correlations in the superior and inferior quadrants (r >0.750) and low correlation at the nasal quadrant (r = 0.210). CONCLUSIONS: Both GDx VCC and Stratus OCT instruments had similar correlations at each clock hour segment, and both were useful in the early detection of patients with preperimetric glaucoma.

Detecting glaucomatous progression using GDx with variable and enhanced corneal compensation using Guided Progression Analysis.

OBJECTIVE: To compare detection of glaucoma progression with scanning laser polarimetry using two methods for corneal compensation. METHODS: Normal, glaucoma suspects and glaucoma patients with 36 months' follow-up meeting the eligibility criteria were prospectively enrolled. All subjects underwent complete eye exam, standard automated perimetry (SAP) and scanning laser polarimetry with variable and enhanced corneal compensation (GDxVCC, GDxECC). SAP progression was determined using the visual-field index (VFI). GDx progression was determined using Guided Progression Analysis software (GDxGPA) and was defined as a repeatable change on two consecutive scans compared with two baseline images using any of three strategies: ≥ 150 contiguous pixels on the image progression map (A), four or more adjacent segments on the Temporal Superior Nasal Inferior Temporal graph (B) or a significant change in slope of the summary parameter chart (C). Kappa statistics and logistic regression were used for the analysis. RESULTS: Thirteen normal, 30 glaucoma suspect and 25 glaucomatous eyes participating in the Advanced Imaging in Glaucoma Study were included. Progression was identified in six eyes (8.8%) using GDxVCC and in eight eyes (11.8%) using GDxECC. SAP progression was detected in seven (10.3%) eyes. Agreement among progression methods using GDxVCC and GDxECC was strongest for method C (kappa=0.57, p=0.002) compared with methods A (kappa=0.41, p=0.01) and B (kappa=0.41, p=0.01). The association between typical scan score (TSS) and overall or individual methods of progression was not significant using VCC or ECC (p>0.05). CONCLUSIONS: GDxGPA represents a novel approach for detection of glaucomatous progression. GDxVCC and GDxECC demonstrate moderate agreement.

Comparison of optical coherence tomography and scanning laser polarimetry measurements in patients with multiple sclerosis.

PURPOSE: To compare optical coherence tomography (OCT) and scanning laser polarimetry (GDx) measurements of the retinal nerve fiber layer (RNFL) in multiple sclerosis (MS) patients with and without optic neuritis (ON). METHODS: OCT and GDx were performed on 68 MS patients. Qualifying eyes were divided into two groups: 51 eyes with an ON history > or =6 months before (ON eyes) and 65 eyes with no history of ON (non-ON eyes). Several GDx and OCT parameters and criteria were used to define an eye as abnormal, for example, GDx nerve fiber indicator (NFI) >20 or 30, OCT average RNFL thickness, and GDx temporal-superior-nasal-inferior-temporal average (TSNIT) below 5 or 1% of the normative database of the instruments. Agreement between OCT and GDx parameters was reported as percent of observed agreement, along with the AC1 statistic. Linear regression analyses were used to examine the relationship between OCT average RNFL thickness and GDx NFI and TSNIT. RESULTS: All OCT and GDx measurements showed significantly more RNFL damage in ON than in non-ON eyes. Agreement between OCT and GDx parameters ranged from 69 to 90% (AC1 0.37 to 0.81) in ON eyes and 52 to 91% (AC1 = 0.21 to 0.90) in non-ON eyes. Best agreement was observed between OCT average RNFL thickness (p < 0.01) and NFI (>30) in ON eyes (90%, AC1 = 0.81) and between OCT average RNFL thickness (p < 0.01) and GDx TSNIT average (p < 0.01) in non-ON eyes (91%, AC1 = 0.90). In ON eyes, the OCT average RNFL thickness showed good linear correlation with NFI (R = 0.69, p < 0.0001) and TSNIT (R = 0.55, p < 0.0001). CONCLUSIONS: OCT and GDx show good agreement and can be useful in detecting RNFL loss in MS/ON eyes.

Comparison of optical coherence tomography and scanning laser polarimetry for detection of localized retinal nerve fiber layer defects.

PURPOSES: To compare the ability of Stratus optical coherence tomography (Stratus OCT) and scanning laser polarimetry with variable corneal compensator (GDx VCC) in recognizing a localized retinal nerve fiber layer (RNFL) defect identified on red-free fundus photography. MATERIALS AND METHODS: Fifty-three patients with only 1 localized RNFL defect in either eye were taken RNFL thickness analysis using Stratus OCT and GDx VCC. Thirty-nine healthy subjects were used as controls and only 1 eye per subject was considered. Using red-free photography as the standard reference test, sensitivity and specificity for photographic defects, and topographic correlation with photographic defects were compared between Stratus OCT (sector average graph) and GDx VCC (deviation from normal map). Abnormal sectors at P<5% compared with their internal normative database were evaluated. RESULTS: After excluding eyes with unacceptable scan images, 38 healthy eyes and 47 glaucomatous eyes were finally included. Stratus OCT and GDx VCC showed moderate sensitivity (78.7%) and high specificity (94.7% and 89.5%, respectively), and there was no significant difference (P=1.00 and P=0.69, respectively). RNFL defects determined by Stratus OCT and GDx VCC were correlated well with photographic RNFL defects in terms of peripapillary localization and clock-hour size, and there was no significant difference between 2 imaging devices (P=0.20 and P=0.27, respectively). CONCLUSIONS: In recognizing a localized RNFL defect, overall diagnostic performance of Stratus OCT and GDx VCC with regard to their internal normative database was not significantly different. As both Stratus OCT and GDx VCC showed only moderate sensitivity, these imaging devices may not substitute red-free fundus photography in clinical practice of glaucoma diagnosis.

Influence of pupil dilation on repeatability of scanning laser polarimetry with variable and enhanced corneal compensation in different stages of glaucoma.

PURPOSE: To evaluate the influence of pupil dilation on repeatability of scanning laser polarimetry with variable (GDx-VCC) and enhanced (GDx-ECC) corneal compensation, in different stages of glaucoma. METHODS: One eye of each of 37 Caucasian participants [14 healthy and ocular hypertensive subjects with mean deviation (MD) <2 dB, 11 glaucoma patients with MD 6 to 12 dB, and 12 glaucoma patients with MD >15 dB] was imaged 5 times with both GDx-VCC and GDx-ECC, before and after pupil dilation. RESULTS: No statistically significant alteration was found for any parameter or most coefficients of variation in any group, or in the total study population, due to pupil dilation. Intraclass correlation was similar with both compensation techniques: it varied between 98.5% and 99.2% before, and 97.3% and 99.1% after pupil dilation for all participants. Intrasession variability was below 6 mum for all parameters and all groups irrespective of corneal compensation and pupil dilation. By using GDx-ECC, a statistically significant trend for higher coefficient of variation values in more severe stages of glaucoma was found, irrespective of pupil dilation (Jonckheere-Terpstra test, P<0.026, for all parameters). With GDx-VCC this trend was not seen for 2 of the 3 parameters before pupil dilation, but did appear for all parameters in mydriasis (P<0.002). CONCLUSIONS: Repeatability of GDx-VCC and GDx-ECC is similar, and is satisfactory for clinical purposes; it is only minimally influenced by pharmacological mydriasis. However, repeatability of the measurement decreases with increasing severity of glaucoma. This characteristic is better detectable with GDx-ECC than with GDx-VCC.

Scan quality effect on glaucoma discrimination by glaucoma imaging devices.

AIM: To evaluate, within ocular imaging scans of acceptable quality as determined by manufacturers' guidelines, the effects of image quality on glaucoma discrimination capabilities. METHODS: One hundred and four healthy and 75 glaucomatous eyes from the Advanced Imaging in Glaucoma Study (AIGS) were imaged with GDx-VCC, HRT II and StratusOCT. Quality score (QS>/=8), pixel standard deviation (SD/=5) were used as quality parameter cut-offs, respectively. GDx nerve fibre indicator (NFI) and HRT Moorfields regression analysis (MRA) classifications and OCT mean retinal nerve fibre layer (RNFL) thickness were used as the discriminatory parameters. Logistic regression models were used to model the dichotomous clinical classification (healthy vs glaucoma) as a function of image-quality parameters and discriminatory parameters. RESULTS: Quality parameter covariates were statistically non-significant for GDx and HRT but had an inverse effect on OCT in predicting disease (a higher SS had a lower probability of glaucoma). Age was a significant covariate for GDx and HRT, but not OCT, while ethnicity and interaction between the image quality and the institute where scans were acquired were significant covariates in the OCT models. CONCLUSION: Scan quality within the range recommended as acceptable by the manufacturer of each imaging device does not affect the glaucoma discriminating ability of GDx or HRT but does affect Stratus OCT glaucoma discrimination.