Linda M. Zangwill

Scanning Laser Polarimetry to Measure the Nerve Fiber Layer of Normal and Glaucomatous Eyes

PURPOSE To determine whether retardation (change in polarization) measurements of healthy subjects and glaucoma patients obtained by using a confocal scanning laser polarimeter correspond to known properties of the nerve fiber layer. METHODS A polarimeter, an optical device used to measure the change in linear polarization of light (retardation), was interfaced with a scanning laser ophthalmoscope to obtain retardation data at 65,536 locations (256 x 256 pixels) in a study of normal subjects and patients with primary open-angle glaucoma. To validate the instrument, we compared our measurements with known properties of the human retinal nerve fiber layer in 105 normal subjects. Additionally, we compared retardation measurements in eyes of 64 normal subjects and 64 age-matched glaucoma patients treated in a referral practice. RESULTS In normal eyes, mean (+/- S.D.) peripapillary retardation was highest in the superior and inferior arcuate regions and lowest in the temporal and nasal regions, 12.0 +/- 1.9, 13.1 +/- 2.0, 7.0 +/- 1.8, and 7.0 +/- 1.6 degrees, respectively. Retardation decreased toward the periphery and was lower over blood vessels. In normal eyes, retardation decreased with increasing age in the superior and inferior regions. Mean retardation was statistically significantly higher among normal eyes than glaucoma eyes in the inferior and superior regions but not in the temporal or nasal areas. CONCLUSIONS Scanning laser polarimetry provides quantitative measurements that correspond to known properties of the retinal nerve fiber layer in normal and glaucomatous eyes.

Reproducibility of nerve fiber layer thickness measurements by use of optical coherence tomography

OBJECTIVE To evaluate the reproducibility of optical coherence tomograph (OCT) retinal nerve fiber layer (RNFL) measurements in normal and glaucomatous eyes by means of the commercially available OCT 2000 instrument (Humphrey Systems, Dublin, CA). DESIGN Prospective instrument validation study. PARTICIPANTS One eye each from 10 normal subjects and 10 glaucoma patients. METHODS Twenty subjects underwent a total of eight scanning sessions during two independent visits. In each session, five circular scans centered on the optic nerve head were performed. The first two sessions were performed by two experienced technicians. Followed by a 30-minute break, a third and a fourth session was completed by the same technicians. This sequence was duplicated on a second visit. Intrasession, intersession, intervisit, and interoperator reproducibility of quadrant and global RNFL measurements were calculated by use of a components of variance model. MAIN OUTCOME MEASURES RNFL thickness. RESULTS The coefficient of variation for the mean RNFL thickness was significantly smaller (P = 0.02) in normal eyes (6.9%) than in glaucoma eyes (11.8%). The estimated root mean squared error based on the statistical model using three scans per patient was 5.8 and 8.0 micrometer for normal and glaucoma eyes, respectively. A components of variance model showed most of the variance (79%) to be due to differences between patients. Only a modest contribution to variability was found for session (1%), visit (5%), and operator (2%). CONCLUSION With the commercially available OCT, our results indicate that the RNFL measurements are reproducible for both normal and glaucomatous eyes.

Imaging of the optic disc and retinal nerve fiber layer: the effects of age, optic disc area, refractive error, and gender

We cross-sectionally examined the relationship between age, optic disc area, refraction, and gender and optic disc topography and retinal nerve fiber layer (RNFL) measurements, using optical imaging techniques. One eye from each of 155 Caucasian subjects (age range 23.0-80.8 y) without ocular pathology was included. Measurements were obtained by using the Heidelberg Retina Tomography (HRT), the GDx Nerve Fiber Analyzer, and the Optical Coherence Tomograph (OCT). The effects of age were small (R2 < 17%) and were limited to specific HRT, GDx, and OCT parameters. Disc area was significantly associated with most HRT parameters and isolated GDx and OCT parameters. Refraction and gender were not significantly associated with any optic disc or RNFL parameters. Although effects of age on the optic disc and RNFL are small, they should be considered in monitoring ocular disease. Optic disc area should be considered when cross-sectionally evaluating disc topography and, to a lesser extent, RNFL thickness.

Detection of early glaucomatous structural damage with confocal scanning laser tomography.

PURPOSE The authors determine which optic disc topographic parameters obtained by the Heidelberg Retina Tomograph (HRT, Heidelberg Engineering, Heidelberg, Germany) are most useful in detecting individuals with early glaucomatous visual field loss. METHODS Ninety-nine eyes of 49 healthy individuals and 50 age-matched individuals with early glaucomatous visual field loss were included. Three images were obtained and the mean topography image was created and used in the analyses. The HRT discriminant analysis function (software version 2.01) was applied and compared to the Fisher linear discriminant function developed in this population. Analysis was repeated after stratifying by disc area (< 2 mm2 or 2-3 mm2). RESULTS There were statistically significant differences between the healthy and glaucomatous groups for all optic disc topographic parameters (p < 0.05) measured. These differences remained after the analysis was repeated controlling for disc size, except for height variation contour. Applying the HRT discriminant function to this study population resulted in sensitivity and specificity of 62% and 94%, respectively. The sensitivity was 83% while specificity remained high (91%) for larger disc sizes. Using this data, additional discriminant functions that differentiated similarly between the two groups were found. The best formula used cup-shape measure (third moment), rim area, height variation contour, and retinal nerve fiber layer thickness and had a sensitivity and specificity of 78% and 88%, respectively. CONCLUSIONS Several different discriminant analysis formulas are capable of detecting early glaucomatous visual field loss in a comparable manner. The characteristics of the study population are likely to influence the discriminating power of these various formulas.

Corneal thickness as a risk factor for visual field loss in patients with preperimetric glaucomatous optic neuropathy.

PURPOSE To determine whether central corneal thickness (CCT) is a risk factor for visual field loss development among patients diagnosed with preperimetric glaucomatous optic neuropathy (GON). DESIGN Observational cohort study. METHODS The study included 98 eyes of 98 patients with GON, with a mean follow-up time of 4.3 +/- 2.7 years. Diagnosis of GON was based on masked assessment of optic disk stereophotographs. All patients had normal standard automated perimetry visual fields at baseline. Criteria for visual field abnormality were derived from a prior study. Several clinical factors (CCT, intraocular pressure, vertical cup-to-disk ratio, refraction, age, gender, family history of glaucoma, high blood pressure, cardiovascular disease, and migraine) were investigated to ascertain whether there is an association with development of repeatable visual field loss. Cox proportional hazards models were used to obtain hazard ratios (HR) and identify factors that predicted which individuals developed glaucomatous visual field loss during the follow-up period. RESULTS Thirty-four patients (35%) developed repeatable visual field abnormality during follow-up. In multivariate analysis, risk factors that predicted the development of visual field loss were a thinner CCT (adjusted HR = 1.62/40 microm thinner; P =.023; 95% confidence interval [CI]: 1.07-2.45), higher baseline intraocular pressure (adjusted HR = 1.07/mm Hg; P =.022; 95% CI: 1.01-1.14), and larger baseline vertical cup-to-disk ratio (adjusted HR = 1.63/0.1 larger; P =.009; 95% CI: 1.13-2.35). The mean +/- standard deviation CCT of GON patients who developed visual field loss was 543 +/- 36 microm compared with 565 +/- 35 microm of those who did not develop visual field abnormalities (P =.005, Student t test). CONCLUSIONS Central corneal thickness is a risk factor for development of visual field loss among patients diagnosed with preperimetric GON. It is important to consider CCT when establishing target intraocular pressure of patients with GON.

Association Between Quantitative Nerve Fiber Layer Measurement and Visual Field Loss in Glaucoma

PURPOSE To evaluate the association between quantitative nerve fiber layer measurements and visual field loss in patients with primary open-angle glaucoma. METHODS Quantitative retinal nerve fiber layer measurements were obtained in 53 patients with primary open-angle glaucoma by using confocal scanning laser ophthalmoscopy (cross-section area) and confocal scanning laser polarimetry (retardation ratio). For each eye, three images were obtained with each instrument. An image that was the mean of those three was created and used in all analyses. We investigated the association between global, regional, and hemifield differences in retinal nerve fiber layer measurements and visual field loss with linear regression techniques. RESULTS The retardation ratio decreased with increasing mean visual field loss, measured both globally and regionally; R2 (the amount of variation explained by the model) ranged from 8% to 21%. Retinal nerve fiber layer cross-section area was not significantly associated with global measures of visual field loss. The inferior visual field mean deviation increased with decreasing superior retinal nerve fiber layer cross-section area (R2 = 8.2%, P = .04); superior visual field mean deviation was not associated with inferior retinal nerve fiber layer cross-section area (R2 = 2.6%, P = .25). Hemifield differences in visual field mean deviation increased with increasing hemifield differences in retinal nerve fiber layer cross-section area (R2 = 20.0%, P < .001), but not with retardation ratio (R2 = 0.9%, P = .48). CONCLUSIONS Quantitative measures of the retinal nerve fiber layer using both confocal scanning laser ophthalmoscopy and confocal scanning laser polarimetry were correlated with visual field loss in glaucoma patients.

Reproducibility of RTVue retinal nerve fiber layer thickness and optic disc measurements and agreement with Stratus optical coherence tomography measurements.

PURPOSE To evaluate RTVue spectral-domain optical coherence tomography (OCT) (Optovue Inc, Fremont, California, USA) reproducibility and to assess agreement with Stratus time-domain OCT (Carl Zeiss Meditec, Dublin, California, USA) measurements. DESIGN Observational clinical study. METHODS Scans were obtained from both eyes of all participants 3 times using the RTVue nerve head map 4-mm diameter protocol and once using Stratus OCT within the same session. RTVue reproducibility and agreement with Stratus OCT were evaluated for retinal nerve fiber layer (RNFL) and optic disc measurements. RESULTS Thirty healthy participants (60 eyes) and 38 glaucoma patients (76 eyes) were included in the study. RTVue reproducibility was good in both healthy participants and patients. For average RNFL thickness, the intraclass correlation coefficients in healthy eyes and patient eyes were 0.97 whereas for rim area they were 0.97 and 0.96, respectively. The correlation between RTVue and Stratus measurements generally was good, especially for average RNFL thickness (healthy eyes and patient eyes, r(2) = 0.82 and 0.86, respectively) and rim volume (healthy eyes and patient eyes, r(2) = 0.78 and 0.76, respectively). Bland-Altman plots showed good agreement between the instruments, with better agreement for average RNFL thickness (95% limits of agreement in healthy eyes and patient eyes, -8.6 to 12 microm and -5.6 to -14.8 microm, respectively) than optic disc parameters. Cup-to-disc ratio 95% limits of agreement in healthy eyes and patient eyes were -0.3 to 0.4 and -0.2 to 0.3, respectively. Optic disc measurements with RTVue were smaller than those with Stratus OCT (eg, disc area was on average 0.4 mm(2) smaller and rim area was 0.3 mm(2) smaller with RTVue). CONCLUSIONS Reproducibility of RTVue RNFL and optic disc measurements was excellent in both groups. The level of agreement between RTVue and Stratus measurements suggests that RTVue has the potential to detect glaucomatous structural changes.

Agreement between Spectral-Domain and Time-Domain OCT for measuring RNFL thickness.

Background/aims: To evaluate spectral-domain (SD) optical coherence tomography (OCT) reproducibility and assess the agreement between SD-OCT and Time-Domain (TD) OCT retinal nerve fibre layer (RNFL) measurements. Methods: Three Cirrus-SD-OCT scans and one Stratus-TD-OCT scan were obtained from Diagnostic Innovations in Glaucoma Study (DIGS) healthy participants and glaucoma patients on the same day. Repeatability was evaluated using Sw (within-subject standard deviation), CV (coefficient of variation) and ICC (intraclass correlation coefficient). Agreement was assessed using correlation and Bland–Altman plots. Results: 16 healthy participants (32 eyes) and 39 patients (78 eyes) were included. SD-OCT reproducibility was excellent in both groups. The CV and ICC for Average RNFL thickness were 1.5% and 0.96, respectively, in healthy eyes and 1.6% and 0.98, respectively, in patient eyes. Correlations between RNFL parameters were strong, particularly for average RNFL thickness (R2 = 0.92 in patient eyes). Bland–Altman plots showed good agreement between instruments, with better agreement for average RNFL thickness than for sectoral RNFL parameters (for example, at 90 µm average RNFL thickness, 95% limits of agreement were −13.1 to 0.9 for healthy eyes and −16.2 to −0.3 µm for patient eyes). Conclusions: SD-OCT measurements were highly repeatable in healthy and patient eyes. Although the agreement between instruments was good, TD-OCT provided thicker RNFL measurements than SD-OCT. Measurements with these instruments should not be considered interchangeable.

Primary Open-Angle Glaucoma in Blacks: A Review

Glaucoma is one of the leading causes of blindness worldwide. Primary open-angle glaucoma (POAG) is the most prevalent form of glaucoma and has a particularly devastating impact in blacks. In the black American population, POAG prevalence is estimated to be six times as high in certain age groups compared to whites. POAG is more likely to result in irreversible blindness, appears approximately 10 years earlier and progresses more rapidly in blacks than in whites. Racial differences in optic disk parameters have been reported and show that blacks have larger optic disks than whites. This finding is robust and may account for the reported differences in other optic disk parameters. The existence of racial differences in intraocular pressure remains to be demonstrated, as conflicting findings are reported in the literature. Intraocular pressure may actually be underestimated in blacks, perhaps because they have thinner corneas. The prevalence of diabetes and hypertension is higher in blacks than in whites, and although no causal relationship has been established between POAG and each of these systemic diseases, some reports suggest that they often occur together, perhaps through an indirect relationship with intraocular pressure. Compounding the problem, there is evidence that blacks are less responsive to both drug and surgical treatment for POAG. Finally, they often have reduced accessibility to treatment and are less aware of the risks of having POAG. This article provides a comprehensive review of the current knowledge pertaining to POAG in blacks.

Using optical imaging summary data to detect glaucoma.

PURPOSE To evaluate the sensitivity and specificity for discriminating between early to moderate glaucomatous and normal eyes using summary data reports from the Heidelberg Retina Tomograph (HRT), the GDx Nerve Fiber Analyzer (GDx), and the Optical Coherence Tomograph (OCT). DESIGN Comparative cross-sectional study PARTICIPANTS One eye each of 50 normal subjects and 39 glaucoma patients with early to moderate visual field damage (mean deviation, -5.04 +/- 3.32 dB; range, -0.85 to -13.2 dB). METHODS Three experienced graders masked to patient identity and diagnosis evaluated each summary data report from the HRT, GDx, and OCT independently. MAIN OUTCOME MEASURES Each summary report was classified as either normal or glaucomatous. Sensitivity and specificity are reported for each grader, and agreement between graders is reported. RESULTS For the HRT, sensitivity and specificity ranged from 64% to 75% and 68% to 80%, respectively. Agreement (kappa +/- standard error [SE]) between observers one and two, two and three, and one and three was 0.73 +/- 0.07, 0.77 +/- 0.07, and 0.67 +/- 0.08, respectively. For the GDx, sensitivity and specificity ranged from 72% to 82% and 56% to 82%, respectively. Agreement (kappa +/- SE) between observers one and two, two and three, and one and three was 0.66 +/- 0.08, 0.66 +/- 0.08, and 0.50 +/- 0.09, respectively. For the OCT, sensitivity and specificity ranged from 76% to 79% and 68% to 81%, respectively. Agreement (kappa +/- SE) between observers one and two, two and three, and one and three was 0.73 +/- 0.07, 0.58 +/- 0.08, and 0.51 +/- 0.09, respectively. CONCLUSIONS When used alone, HRT, GDx, and OCT summary data reports can differentiate between normal and glaucomatous eyes with mild to moderate visual field loss. However, none of the instruments provided sensitivity and specificity that justify summary data reports being used as a screening tool for early to moderate glaucoma.