Stability of corneal polarization axis measurements for scanning laser polarimetry

OBJECTIVE: Corneal polarization axis (CPA) has been reported to affect retardation measurements obtained with scanning laser polarimetry. The purpose of this investigation was to evaluate the longitudinal stability of CPA measurements. DESIGN: Prospective, noncomparative case series. PARTICIPANTS: Persons with normal corneas were enrolled; eyes with less than 1 year of follow-up from the initial CPA measurement were excluded. INTERVENTION: We constructed a noninvasive slit-lamp-mounted device incorporating two crossed linear polarizers and an optical retarder to measure the slow axis of corneal birefringence, or CPA. MAIN OUTCOME MEASURES: Corneal polarization axis measurements. RESULTS: Seventy-one eyes of 40 individuals (23 female, 17 male) were enrolled in this investigation (mean age, 42.9 +/- 13.6 years; range, 22-85 years). Initial CPA measurements (mean, 24.0 +/- 18.0 degrees nasally downward; range, 67 degrees downward to 13 degrees nasally upward) were strongly associated (R2 = 0.88; P < 0.0001) with repeat CPA measurements (mean, 20.9 +/- 14.6 degrees nasally downward; range, 59 degrees nasally downward to 14 degrees nasally upward). The mean change in CPA was 4.1 +/- 3.2 degrees (range, 0-13 degrees ). Corneal polarization axis stability was statistically associated with the mean (initial and repeat) CPA (R2 = 0.1; P = 0.009), but not associated with age (R2 = 0.0003; P = 0.9) or gender (R2 = 0.03; P = 0.2). CONCLUSIONS: Corneal polarization axis measurements have good 1-year stability. These data suggest that CPA should not contribute significantly to longitudinal measurements of retinal nerve fiber layer thickness obtained with scanning laser polarimetry.     

Effect of corneal polarization axis on assessment of retinal nerve fiber layer thickness by scanning laser polarimetry

PURPOSE: Scanning laser polarimetry uses an anterior segment compensating device that assumes a fixed axis of corneal birefringence, which we call the corneal polarization axis. The purpose of this investigation was to establish the distribution of corneal polarization axes among a population of normal eyes and to evaluate the relationship between corneal polarization axis and posterior segment retardation. METHODS: We constructed a noninvasive slit lamp-mounted device incorporating two crossed linear polarizers and an optical retarder in order to measure the slow axis of corneal birefringence. Normal subjects underwent corneal polarization axis measurement. A subset of eyes underwent scanning laser polarimetry of the peripapillary retinal nerve fiber layer (n = 32) and macula (n = 29), and retardation measurements were evaluated in each group. RESULTS: One hundred eighteen eyes of 63 normal subjects (35 female, 28 male) underwent corneal polarization axis measurement (mean age, 45.5 +/- 17.1 years). Six eyes (5.1%) demonstrated unmeasurable corneal polarization. In the remaining 112 eyes, the mode of the corneal polarization axis distribution was 10 to 20 degrees nasally downward (range, 90 degrees nasally downward to 54 degrees nasally upward). A significant (P <.0001) correlation was observed between fellow eyes (R(2) =.52), with a mean difference of 11.2 +/- 10.5 degrees (range, 0-52 degrees). Corneal polarization axis was significantly associated (R(2) =.52-.84) with retinal nerve fiber layer and macula summary retardation parameters (average thickness, ellipse average, superior and inferior average, superior and total integral; P <.0001 for all groups). CONCLUSIONS: The mean corneal polarization axis among normal corneas is nasally downward; however, considerable intraindividual and interindividual variability exists. The linear relationship between corneal polarization axis and posterior segment retardation parameters is responsible, in part, for the wide distribution of retinal nerve fiber layer thickness data generated by scanning laser polarimetry.     

Enhanced imaging algorithm for scanning laser polarimetry with variable corneal compensation

PURPOSE: To describe and investigate a method of improving assessment of retinal nerve fiber layer (RNFL) morphology with scanning laser polarimetry (SLP) with variable corneal compensation (VCC). METHODS: By neutralizing anterior segment birefringence with a variable compensator, the current VCC method allows direct measurement of RNFL retardation. In the new method, enhanced corneal compensation (ECC), the variable compensator was set to introduce a "bias" birefringence. This bias was removed mathematically for each individual pixel to produce the RNFL image. In 177 eyes of healthy subjects, patients with glaucoma, and subjects with ocular hypertension, retardation images were obtained with both VCC and ECC. RESULTS: In the tested eyes, images obtained with ECC showed the expected RNFL appearance better than those obtained with VCC. In addition, the typical scan score, which quantifies the amount of atypia, was higher with ECC than with VCC. The amount of residual anterior segment birefringence dropped significantly with ECC in the various groups. Measurements of peripapillary RNFL retardation showed reduced temporal and nasal values with ECC, whereas superior and inferior values were not significantly different between VCC and ECC. The dynamic range appeared to have increased with ECC. The accuracy of the TSNIT (temporal, superior, nasal, inferior, temporal) average and inferior average for detecting glaucoma was higher with ECC than with VCC. CONCLUSIONS: RNFL morphology may be better assessed with the presented ECC method than with standard VCC. ECC may be implemented in the current VCC systems by means of a software upgrade. It may enhance the clinical utility of the GDx VCC in glaucoma management.     

Scanning laser polarimetry in monkey eyes using variable corneal polarization compensation

PURPOSE: To determine if scanning laser polarimetry (SLP) using variable anterior segment birefringence compensation can provide meaningful retinal nerve fiber layer (RNFL) thickness measurements in monkey eyes. METHODS: A scanning laser polarimeter (GDx; Laser Diagnostic Technologies, San Diego, CA) was modified so that anterior segment birefringence could be compensated on an eye-specific basis. Six eyes of three adult Cynomolgus (Macaca fascicularis) monkeys were imaged. The authors determined the corneal polarization magnitude (CPM) and corneal polarization axis (CPA) in these eyes, and compared them with the fixed values in the commercial scanning laser polarimeter. Individually compensated RNFL images, using eye-specific CPM and CPA, were then obtained to determine if the resulting retardation profiles reflected the expected RNFL appearance observed with stereoscopic optic disc photographs. Two of the imaged monkeys had experimental glaucoma of the right eye, which allowed comparison of RNFL thickness measures between healthy eyes and those damaged by experimental glaucoma. RESULTS: The CPM was small in each of the six eyes examined, ranging from 5.7 to 8.7 nm. The CPA ranged from -62 degrees to 78.7 degrees (nasally upward CPA values were recorded as negative; nasally downward CPA values were recorded as positive). These values are different from the values assumed by the commercially available fixed-compensator GDx. When eye-specific compensation was used, RNFL retardation profiles mimicked the expected appearance of the RNFL in all eyes. The authors also observed a substantial decrease in retardation in experimental glaucoma eyes compared with healthy fellow eyes. CONCLUSIONS: Scanning laser polarimetry using eye-specific corneal polarization compensation can provide meaningful RNFL thickness measurements in monkey eyes. Observed differences in retardation between healthy and experimental glaucoma eyes suggest that SLP may be useful for detecting and monitoring RNFL loss in experimental primate glaucoma.     

Detection of glaucoma using scanning laser polarimetry with enhanced corneal compensation

PURPOSE: To evaluate and compare the diagnostic accuracies for glaucoma detection of scanning laser polarimetry (SLP) with enhanced corneal compensation (GDx ECC) and variable corneal compensation (GDx VCC; both by Carl Zeiss Meditec, Dublin, CA), according to different levels of disease severity and presence of atypical retardation patterns. METHODS: The study included 102 eyes of 68 patients with glaucoma and 94 eyes of 55 normal subjects. All patients underwent SLP imaging with ECC and VCC methods on the same day. Severity of disease was based on the AGIS (Advanced Glaucoma Intervention Study) visual field score. An ROC regression model was fitted to evaluate the influence of disease severity and atypical retardation patterns (typical scan score [TSS]) on the diagnostic performance of the SLP parameters for both methods. RESULTS: GDx ECC performed significantly better than GDx VCC in glaucoma detection in patients with more severe atypical retardation patterns. For average disease severity and arbitrarily chosen TSS values of 20, 50, 70, and 100, the ROC curve areas for GDx ECC were 0.910, 0.935, 0.948, and 0.964. Corresponding values for GDx VCC were 0.684, 0.850, 0.920, and 0.975. For lower values of TSS and lower AGIS scores, GDx ECC performed significantly better than GDx VCC. CONCLUSIONS: GDx ECC performed significantly better than VCC for diagnosing glaucoma in patients with more severe atypical patterns of retardation and at earlier stages of disease.     

Enhanced corneal compensation for scanning laser polarimetry on eyes with atypical polarisation pattern

AIM: To investigate the potential advantage of an enhanced corneal compensation algorithm (ECC) compared with variable corneal compensation (VCC) in the analysis of scanning laser polarimetric (SLP) images with atypical retardation pattern (ARP). METHODS: SLP-VCC images with ARP (typical scan score (TSS) <80) of one eye of each of 27 glaucoma patients and 19 healthy subjects were compared with the corresponding SLP-ECC images obtained at the same session. RESULTS: ARP was present in 10.4% of the normals and 15.5% of the glaucoma patients imaged with SLP-VCC over 9 months. In both groups TSS was higher for ECC than for VCC (p<0.001). In glaucoma TSNIT, superior and inferior average thickness values were significantly lower, and TSNIT (measuring ellipse around the optic nerve head in the four (temporal, superior, nasal, inferior) quadrants) standard deviation was significantly higher with ECC than with VCC (p<0.001). In the normal group nerve fibre indicator (NFI) was lower with ECC than with VCC (p=0.007). TSNIT average was smaller and TSNIT standard deviation was higher with ECC (p<0.001). Superior and inferior average thickness did not differ between VCC and ECC in the normal group. CONCLUSIONS: The new ECC software substantially improves polarimetric image analysis on eyes showing atypical polarisation pattern.     

Relationship between scanning laser polarimetry with enhanced corneal compensation and with variable corneal compensation

PURPOSE: To evaluate the structure-function relationships between retinal sensitivity measured by Humphrey visual field analyzer (HVFA) and the retinal nerve fiber layer (RNFL) thickness measured by scanning laser polarimetry (SLP) with variable corneal compensation (VCC) and enhanced corneal compensation (ECC) in glaucomatous and healthy eyes. METHODS: Fifty-three eyes with an atypical birefringence pattern (ABP) based on SLP-VCC (28 glaucomatous eyes and 25 normal healthy eyes) were enrolled in this cross-sectional study. RNFL thickness was measured by both VCC and ECC techniques, and the visual field was examined by HVFA with 24-2 full-threshold program. The relationships between RNFL measurements in superior and inferior sectors and corresponding retinal mean sensitivity were sought globally and regionally with linear regression analysis in each group. Coefficients of the determination were calculated and compared between VCC and ECC techniques. RESULTS: In eyes with ABP, R2 values for the association between SLP parameters and retinal sensitivity were 0.06-0.16 with VCC, whereas they were 0.21-0.48 with ECC. The association of RNFL thickness with retinal sensitivity was significantly better with ECC than with VCC in 5 out of 8 regression models between SLP parameters and HVF parameters (P<0.05). CONCLUSIONS: The strength of the structure-function association was higher with ECC than with VCC in eyes with ABP, which suggests that the ECC algorithm is a better approach for evaluating the structure-function relationship in eyes with ABP.     

Prospective evaluation of factors associated with post-LASIK corneal birefringence with scanning laser polarimetry

PURPOSE: To identify factors that affect corneal birefringence, such as the corneal polarization axis (CPA) and corneal polarization magnitude (CPM), after laser in situ keratomileusis (LASIK) using scanning laser polarimetry with a variable corneal polarization compensator. METHODS: The CPA and CPM from 42 patients (42 eyes) who underwent LASIK and 24 normal untreated subjects (24 eyes) were measured 1 week before and 1 week after LASIK. Changes in the CPA and CPM after LASIK were studied using Student t test and Pearson correlation coefficient. RESULTS: In the LASIK group, the post-LASIK CPA and CPM significantly changed, whereas both values did not change in normal subjects. Among 5 candidate factors [preoperative CPA (pre-CPA), preoperative CPM (pre-CPM), age, change in corneal curvature, and ablation depth], the change in CPA was significantly correlated with the pre-CPA (r=-0.793) and pre-CPM (r=0.339). The change in CPM was correlated with the pre-CPA (r=-0.455) and pre-CPM (r=-0.411). Over 83% case of postoperative corneal birefringence can be explained by only 2 parameters with regression analysis. CONCLUSIONS: The pre-CPA and pre-CPM are strongly associated with LASIK-induced changes in CPA and CPM. Variations in age, changes in corneal curvature, and ablation depth do not contribute to changes in either parameter.     

Fourier analysis of scanning laser polarimetry measurements with variable corneal compensation in glaucoma

PURPOSE: To apply Fourier analysis to the retinal nerve fiber layer (RNFL) thickness measurements obtained with scanning laser polarimetry (SLP), by using variable corneal compensation, and to evaluate the ability of this method to discriminate glaucomatous from normal eyes. METHODS: The study included one eye each of 55 patients with glaucoma and 52 healthy subjects. RNFL thickness measurements were obtained with a modified commercial scanning laser polarimeter (GDx Nerve Fiber Analyzer; Laser Diagnostic Technologies, Inc., San Diego, CA) so that corneal birefringence could be corrected on a subject-specific variable basis. The shape of the RNFL thickness double-hump pattern was analyzed by Fourier analysis of polarimetry data. Fourier coefficients and GDx parameters were compared between the two groups. A linear discriminant function was developed to identify and combine the most useful Fourier coefficients to separate the two groups. Receiver operating characteristic (ROC) curves were obtained for each measurement, and sensitivity values (at fixed specificities) were calculated. RESULTS: The Fourier-based linear discriminant function (LDF Fourier) resulted in a sensitivity of 84% for a specificity set at 92%. For similar specificity, the GDx software-provided parameters had sensitivities ranging from 24% to 69%. The area under ROC curve for the LDF Fourier was 0.949, significantly larger than the ROC curve area for the single best GDx software-provided parameter, superior average (0.870). CONCLUSIONS: The combination of Fourier RNFL thickness measures in an LDF, obtained using SLP with variable corneal compensation, improved the ability to discriminate glaucomatous from healthy eyes, compared with the GDx software-provided parameters.     

Low specificity of scanning laser polarimetry

PURPOSE: Scanning laser polarimetry is used to assess the peripapillary retinal nerve fiber layer. This study evaluates scanning laser polarimetry in normal subjects. SUBJECTS AND METHODS: 28 eyes of 28 normal subjects (age range 21-48 years, mean age 36.5 years) had scanning laser polarimetry (NFA-GDx, Laser Diagnostic Technologies, San Diego, Calif., USA). All subjects had normal eye examinations, refractive errors with spherical equivalents <5 D and astigmatism <2 D, normal intraocular pressures, no history of diseases affecting the visual field or nerve fiber layer, and normal white-on-white automated perimetry (Octopus 101, program G2). The mean image of three good-quality measurements with the scanning laser polarimeter was included. RESULTS: 36% of the normal subjects (10/28) had at least one NFA parameter outside normal (p < 0.05). The parameters most frequently found to be outside normal were symmetry (21%, 6/28) and superior ratio (17%, 5/28). CONCLUSIONS: Scanning laser polarimetry is often used for early detection of glaucomatous damage in glaucoma suspects. This study found a specificity of only 64% and indicates that the actual selection of parameters is not adequate. Especially the parameters symmetry and superior ratio should be reevaluated in order to achieve a higher specificity.     

New developments in scanning laser polarimetry for glaucoma

PURPOSE OF REVIEW: Scanning laser polarimetry is a technique that is used to evaluate the thickness of the retinal nerve fiber layer. It has been shown to have a high accuracy for diagnosing glaucoma. In a subset of eyes, atypical retardation patterns may be present that do not match the expected retinal nerve fiber layer appearance. This review summarizes recent advances made to reduce the frequency and severity of these patterns. In addition, recent progress in the development of algorithms for detecting progression is discussed. RECENT FINDINGS: A new measurement algorithm--enhanced corneal compensation--has been developed to improve the instrument's signal-to-noise ratio. Enhanced corneal compensation has been shown to improve the accuracy of scanning laser polarimetry for diagnosing glaucoma. In addition, enhanced corneal compensation improves the relationship between standard automated perimetry and scanning laser polarimetry measurements. Furthermore, research is being done on detecting progression in glaucoma. Recently, a method for simulating progression has been proposed, thereby diminishing the need for long-term studies to validate numerous measurement algorithms. SUMMARY: With enhanced corneal compensation, the diagnostic accuracy of scanning laser polarimetry has been further improved for glaucoma. Newly developed algorithms for detecting any progressive retinal nerve fiber layer thinning await clinical validation.     

The effect of pupil dilation on scanning laser polarimetry with variable corneal compensation.

BACKGROUND AND OBJECTIVE: The feasibility and reproducibility of scanning laser polarimetry performed through dilated pupils rather than through non-dilated pupils was tested. PATIENTS AND METHODS: One eye each of 36 subjects (12 normal, 12 suspected glaucoma, and 12 glaucoma) was scanned using a single GDx unit with variable corneal compensator (GDx-VCC; Laser Diagnostic Technologies, Inc., San Diego, CA). Two scans prior to and two scans after dilation were performed on each study eye, resetting the cornea compensation prior to each scan. The dilated eye was viewed off-center, such that the whitish focusing patch was projected on the 9-o'clock peripheral iris. After adequate anteroposterior focus, the pupil was centered and a scan was acquired. Each of 5 GDx parameters was evaluated comparing the pre-dilation and post-dilation scans. RESULTS: No statistically significant difference was found between pre-dilation and post-dilation measurements. There was a high pre-dilation to post-dilation correlation of 98%, 98%, 98%, 93%, and 95% for nerve fiber indicator, TSNIT average, TSNIT standard deviation, superior average, and inferior average, respectively. Less than 5% of the measurement variability was attributed to changes in pupil size (R2 ranging from 0.024 to 0.047). Stratifying the data by diagnostic groups yielded similar results. CONCLUSIONS: Pharmacologic mydriasis was not found to influence the retinal nerve fiber layer measurements acquired using the GDx-VCC. Results were comparable to scans achieved in the same eyes prior to dilation.     

Motion artifacts in scanning laser polarimetry

PURPOSE: The GDx (Laser Diagnostic Technologies, San Diego, CA) is a scanning laser polarimeter that measures retardation to assess retinal nerve fiber layer thickness in vivo. Eye movements during image acquisition may result in motion artifacts in the GDx image. The aims of this study were to investigate the effect of motion artifacts on the retardation values and to illustrate how motion artifacts can be identified. DESIGN: Observational case series. PARTICIPANTS: Thirty-two normal subjects and 28 glaucoma patients participated. METHODS: We imaged all 60 subjects with the GDx. Images with identified motion artifacts were compared with images without motion artifacts from the same eye and the same session. In 25 cases, the artifact was identified in the superior segment only, and the effect on the superior maximum parameter was calculated. In 26 cases, the artifact was observed in the inferior segment only, and the effect on the inferior maximum parameter was calculated. In nine cases, the artifact was observed superiorly and inferiorly, and the effect on both parameters was calculated. In all 60 cases, the effect on The Number (a summary parameter) was calculated. We also analyzed the groups of glaucoma patients and normal subjects separately. MAIN OUTCOME MEASURES: Superior maximum parameter, inferior maximum parameter, The Number parameters. RESULTS: In general, the identified motion artifacts led to an increase in retardation, reflected by an increase in the superior maximum and inferior maximum parameter by 5.9 micro m and 3.4 micro m, respectively (P < 0.001). The Number decreased by 3.4 with motion artifacts (P = 0.001). The variability of this effect was large. In one case, the motion artifact increased retardation by as much as 28.6 micro m. The effect of motion artifacts was greater in glaucoma patients than in normal subjects. CONCLUSIONS: The identified motion artifacts generally increase retardation values. This increase, however, is highly variable. Therefore, images with such motion artifacts should be viewed with caution or excluded from analysis.     

Quantitative assessment of atypical birefringence images using scanning laser polarimetry with variable corneal compensation

PURPOSE: To define the clinical characteristics of atypical birefringence images and to describe a quantitative method for their identification. DESIGN: Prospective, comparative, clinical observational study. METHODS: Normal and glaucomatous eyes underwent complete examination, standard automated perimetry, scanning laser polarimetry with variable corneal compensation (GDx-VCC), and optical coherence tomography (OCT) of the macula, peripapillary retinal nerve fiber layer (RNFL), and optic disk. Eyes were classified into two groups: normal birefringence pattern (NBP) and atypical birefringence pattern (ABP). Clinical, functional, and structural characteristics were assessed separately. A multiple logistic regression model was used to predict eyes with ABP on the basis of a quantitative scan score generated by a support vector machine (SVM) with GDx-VCC. RESULTS: Sixty-five eyes of 65 patients were enrolled. ABP images were observed in 5 of 20 (25%) normal eyes and 23 of 45 (51%) glaucomatous eyes. Compared with eyes with NBP, glaucomatous eyes with ABP demonstrated significantly lower SVM scores (P < .0001, < 0.0001, 0.008, 0.03, and 0.03, respectively) and greater temporal, mean, inferior, and nasal RNFL thickness using GDx-VCC; and a weaker correlation with OCT generated RNFL thickness (R(2) = .75 vs .27). ABP images were significantly correlated with older age (R(2) = .16, P = .001). The SVM score was the only significant (P < .0001) predictor of ABP images and provided high discriminating power between eyes with NBP and ABP (area under the receiver operator characteristic curve = 0.98). CONCLUSIONS: ABP images exist in a subset of normal and glaucomatous eyes, are associated with older patient age, and produce an artifactual increase in RNFL thickness using GDx-VCC. The SVM score is highly predictive of ABP images.     

Structure-function relationship is stronger with enhanced corneal compensation than with variable corneal compensation in scanning laser polarimetry

PURPOSE: To compare the structure-function relationship between peripapillary retinal nerve fiber layer (RNFL) retardation, measured with scanning laser polarimetry (SLP) with both enhanced and variable corneal compensation (ECC [enhanced corneal compensation] and VCC [variable corneal compensation], respectively; features of the GDx Nerve Fiber Analyzer; Carl Zeiss Meditec, Inc., Dublin, CA), and visual field (VF) sensitivity, measured with standard automated perimetry (SAP) in normal and glaucomatous eyes and the effect of marked atypical birefringence patterns (ABPs) on this relationship. METHODS: Thirty-three healthy subjects, and 68 patients with primary open-angle glaucoma (POAG) took part in the study. ECC and VCC images were taken in one randomly selected eye of each subject. VF tests were also obtained in the same eyes. The structure-function relationship was assessed in six peripapillary sectors and their matching VF areas and was reassessed after eliminating eyes with marked ABPs. RESULTS: Correlations (Spearman's correlation coefficients, r(s)) in the structure-function relationship were generally stronger in images taken with ECC than in those taken with VCC. With ECC, the relationship was significantly more curvilinear when VF sensitivity was expressed in the standard decibel scale and more linear when VF sensitivity was expressed in an antilog scale than with VCC. When eyes with marked ABP images were removed from the analysis, the structure-function relationship with VCC improved, and no statistically significantly differences were found in the relationships between VCC and ECC. CONCLUSIONS: The structure-function relationship between RNFL retardation and SAP VF sensitivity was stronger in images obtained with the GDx ECC than with the GDx VCC (Carl Zeiss Meditec, Inc., Dublin, CA). ABPs, which appeared more markedly with VCC than with ECC, weakened the structure-function relationship.