Robert W. Knighton

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.

Simultaneous acquisition of sectional and fundus ophthalmic images with spectral-domain optical coherence tomography.

A high-speed spectral-domain optical coherence tomography (OCT) system was built to image the human retina in vivo. A fundus image similar to the intensity image produced by a scanning laser ophthalmoscope (SLO) was generated from the same spectra that were used for generating the OCT sectional images immediately after the spectra were collected. This function offers perfect spatial registration between the sectional OCT images and the fundus image, which is desired in ophthalmology for monitoring data quality, locating pathology, and increasing reproducibility. This function also offers a practical way to detect eye movements that occur during the acquisition of the OCT image. The system was successfully applied to imaging human retina in vivo.

Revealing Henle's Fiber Layer Using Spectral Domain Optical Coherence Tomography

PURPOSE Spectral domain optical coherence tomography (SD-OCT) uses infrared light to visualize the reflectivity of structures of differing optical properties within the retina. Despite their presence on histologic studies, traditionally acquired SD-OCT images are unable to delineate the axons of photoreceptor nuclei, Henles fiber layer (HFL). The authors present a new method to reliably identify HFL by varying the entry position of the SD-OCT beam through the pupil. METHODS Fifteen eyes from 11 subjects with normal vision were prospectively imaged using 1 of 2 commercial SD-OCT systems. For each eye, the entry position of the SD-OCT beam through the pupil was varied horizontally and vertically. The reflectivity of outer retinal layers was measured as a function of beam position, and thicknesses were recorded. RESULTS The reflectivity of HFL was directionally dependent and increased with eccentricity on the side of the fovea opposite the entry position. When HFL was included in the measurement, the thickness of the outer nuclear layer (ONL) of central horizontal B-scans increased by an average of 52% in three subjects quantified. Four cases of pathology, in which alterations to the normal macular geometry affected HFL intensity, were identified. CONCLUSIONS The authors demonstrated a novel method to distinguish HFL from true ONL. An accurate measurement of the ONL is critical to clinical studies measuring photoreceptor layer thickness using any SD-OCT system. Recognition of the optical properties of HFL can explain reflectivity changes imaged in this layer in association with macular pathology.

Scanning laser polarimetry with variable corneal compensation and optical coherence tomography in normal and glaucomatous eyes

PURPOSE To evaluate the relationship between visual function and retinal nerve fiber layer (RNFL) measurements obtained with scanning laser polarimetry with variable corneal compensation (SLP-VCC) and optical coherence tomography (OCT). DESIGN Cross-sectional analysis of normal and glaucomatous eyes in a tertiary care academic referral practice. METHODS A commercial GDx nerve fiber analyzer was modified to enable the measurement of corneal polarization axis and magnitude so that compensation for corneal birefringence was eye specific. Complete examination, SLP with fixed corneal compensation (FCC) and variable corneal compensation (VCC), optical coherence tomography (OCT) imaging of the peripapillary RNFL, and automated achromatic perimetry were performed in all subjects. Exclusion criteria were visual acuity less than 20/40, diseases other than glaucoma, and unreliable perimetry. RESULTS Fifty-nine patients (59 eyes; 29 normal, 30 glaucomatous) were enrolled (mean age, 56.7 +/- 20.3 years, range, 20-91). All eyes with glaucoma had associated visual field loss (average mean defect, -8.4 +/- 5.8 dB). Using SLP-FCC, nine of 12 retardation parameters (75%) were significantly less in glaucomatous eyes. Using SLP-VCC, 11of 12 retardation parameters (92%) were significantly less in glaucomatous eyes. Multiple regression models constructed for each retardation parameter with visual field demonstrated that the following VCC parameters were statistically significant whereas FCC parameters were not: ellipse average (FCC, P =.28, VCC, P =.001), superior average (FCC, P =.38, VCC, P <.001), inferior average (FCC, P =.10, VCC, P =.008), average thickness (FCC, P =.30, VCC, P =.031), and superior integral (FCC, P =.43, VCC, P =.001). Similar results were obtained for multiple regression models constructed with OCT-derived RNFL thickness: ellipse average (FCC, P =.99, VCC, P =.002), superior average (FCC, P =.90, VCC, P <.001), inferior average (FCC, P =.61, VCC, P =.007), and superior integral (FCC, P =.92, VCC, P <.001). CONCLUSIONS Compared with fixed compensation, mean-based SLP parameters generated with SLP-VCC have greater correlation with visual function and RNFL thickness assessments obtained with OCT.

Correction for corneal polarization axis improves the discriminating power of scanning laser polarimetry

PURPOSE Corneal polarization axis (CPA) has been reported to affect retardation measurements obtained with scanning laser polarimetry (SLP). The purpose of this investigation was to prospectively determine whether correction for CPA improves the discriminating power of SLP for detection of mild-to-moderate glaucoma. DESIGN Cross-sectional analysis of normal and glaucomatous eyes. METHODS We constructed a noninvasive slit-lamp-mounted device incorporating two crossed linear polarizers and an optical retarder to measure the slow axis of corneal polarization. Complete ocular examination, standard automated perimetry, SLP imaging, and CPA measurements were performed on normal and glaucomatous eyes. One eye/subject was enrolled; if both eyes of a patient were eligible for the study, the right eye was selected. For each of the 13 SLP parameters, logistic regression was used to determine if including CPA in the model influenced the ability to discriminate between normal and glaucomatous eyes. RESULTS Forty-three normal eyes (average visual field mean defect, -0.53 +/- 1.4 dB) and 33 glaucomatous eyes (average visual field mean defect, -5.93 +/- 6.5 dB) were enrolled. CPA was significantly correlated with summary retardation parameters (average thickness and integral values) in normal (r = 0.72-0.83, P <.001 for all values) and glaucomatous eyes (r = 0.43-0.62, P =.013 to <.001). Including CPA in the model improved the ability to discriminate between normal and glaucomatous eyes for five retardation parameters quantifying retinal nerve fiber layer (RNFL) thickness (range of P values: 0.045-0.001). For inferior average thickness, area under the receiver operating characteristic (ROC) curve increased significantly (P =.002) from 0.70 to 0.78 after accounting for CPA; with a sensitivity set at 80% specificity improved from 33% to 72%. Correlations between visual field corrected pattern standard deviation and average thickness, ellipse average, superior average, and inferior average significantly increased (range of P values,.018-.001) after adjustment for CPA (r = -0.35 and -0.45, -0.38 and -0.47, -0.46 and -0.57, and -0.42 and -0.49, respectively). CONCLUSIONS Correction for CPA significantly increases the correlation between retinal nerve fiber layer structural damage and visual function and significantly improves the discriminating power of SLP for detection of mild-to-moderate glaucoma.

Analytical methods for scanning laser polarimetry

Scanning laser polarimetry (SLP), a technology for glaucoma diagnosis, uses imaging polarimetry to detect the birefringence of the retinal nerve fiber layer. A simple model of SLP suggests an algorithm for calculating birefringence that, unlike previous methods, uses all of the data available in the images to achieve better signal-to-noise ratio and lower sensitivity to depolarization. The uncertainty of the calculated retardance is estimated and an appropriate averaging strategy to reduce uncertainty is demonstrated. Averaging over a large area of the macula of the eye is used in a new method for determining anterior segment birefringence.

Light scattering and form birefringence of parallel cylindrical arrays that represent cellular organelles of the retinal nerve fiber layer

The retinal nerve fiber layer (RNFL) comprises bundles of unmyelinated axons that run across the surface of the retina. The cylindrical organelles of the RNFL (axonal membranes, microtubules, neurofilaments, and mitochondria) as seen by electron microscopy were modeled as parallel cylindrical arrays in order to gain insight into their optical properties. Arrays of thin fibrils were used to represent organelles that are thin relative to wavelength, and the model took into account interference effects that may arise from spatial order. Angular and spectral light-scattering functions were calculated for the backscattering hemisphere. Scattering was much larger from axonal membranes than from microtubules or neurofilaments. Spectra from 400 to 700 nm show that scattering increases at shorter wavelengths for both axonal membranes and microtubules. At 560 nm, scattering from mitochondria modeled as thick cylinders was approximately the same as that from microtubules but showed little wavelength dependence. The model reveals differences in backscattered polarization ratios that may permit experimental discrimination between microtubule and membrane mechanisms for the RNFL reflectance. Calculated backscattering exceeds measured values by at least 1 order of magnitude, but calculated form birefringence for microtubule arrays is approximately the same as measured birefringence.

The Photostress Recovery Test in the Clinical Assessment of Visual Function

To distinguish optic nerve conduction defects from macular disease in patients with otherwise unexplained loss of central vision we first determined the best visual acuity with correction at distance in unilateral defects. The normal eye was tested first and photostressed for ten seconds by looking at an ordinary penlight held 2 to 3 cm from the eye. The time required to read three letters on three Snellen test lines just larger than the best acuity was used as the end point. In 63 eyes with maculopathy the recovery time was prolonged. Prolonged recovery time was not observed in 20 patients who had optic nerve disease.

Effect of individualized compensation for anterior segment birefringence on retinal nerve fiber layer assessments as determined by scanning laser polarimetry

PURPOSE Scanning laser polarimetry estimates retinal nerve fiber layer (RNFL) thickness through measurement of retardation of a polarized laser light passing through the naturally birefringent RNFL and cornea. The commercial instrument, the GDx Nerve Fiber Analyzer (Laser Diagnostic Technologies, Inc., San Diego, CA), uses an anterior segment compensator of fixed magnitude and slow polarization axis to eliminate the contribution of the cornea to the total signal. Previous studies have shown up to 30% of patients are not adequately compensated by this method. The aim of this study was to determine the effect of individualized anterior segment compensation using a newly designed variable compensator on estimates of retinal nerve fiber layer thickness compared with those as determined with the fixed compensator in the commercial device. DESIGN Comparative, observational case series. PARTICIPANTS Twenty-eight eyes from 14 normal participants and 24 eyes from 12 patients with bilateral glaucoma. METHODS Using information derived from a scan of the macula, a newly designed variable anterior segment compensator for the GDx was set to neutralize anterior segment birefringence. Normal participants and patients with glaucoma underwent RNFL measurements using the standard (fixed) compensator and the variable compensator. The results were compared using Hotellings generalized means test and Bonferronis adjustment for multiple comparisons. MAIN OUTCOME MEASURES Standard GDx modulation and thickness parameters as determined with the fixed and variable compensators. RESULTS All thickness values were statistically significantly lower as determined with the variable compensator, with no discernible differences in any of the modulation parameters. CONCLUSIONS Individualized anterior segment compensation lowers the RNFL thickness values as determined by scanning laser polarimetry compared with those determined with the standard fixed compensator. This may narrow the normal range and increase the discriminating ability of scanning laser polarimetry between normal and disease. However, modulation is less affected, and the modulation parameters may thus prove more useful for distinguishing between normal and glaucoma.

An optical model of the human retinal nerve fiber layer: implications of directional reflectance for variability of clinical measurements.

Purpose: The reflectance of the retinal nerve fiber layer is highly directional—that is, it depends strongly on the angles of illumination and viewing. This study explored and illustrated the implications of this directional reflectance for nerve fiber layer measurements in the human eye. Methods: The retina was modeled as a sphere centered on the optic axis of a schematic eye. Nerve fiber ribbons were projected onto the retina and cylindrical light scattering was calculated along each ribbon. The reflectance along the ribbon was then determined for the illuminating and viewing apertures of two hypothetical optical instruments, a fundus camera and a confocal scanning laser ophthalmoscope. Results were displayed as reflectance maps. Results: Uniformly illuminated nerve fiber ribbons exhibited a nonuniform reflectance pattern that was very sensitive to the location in the pupil of the instrument apertures. Ribbon reflectance at the superior and inferior disc margins varied with ribbon orientation, being higher with temporal tilt and lower with nasal tilt. Ribbons nasal to the disk could be quite dim. Conclusions: In quantitative nerve fiber layer assessment technologies, the observed reflectance depends on the configuration of the illuminating and viewing apertures of the measuring instrument and on the retinal position and orientation of each nerve fiber bundle. In clinical practice, this dependence may cause significant measurement variability that can be reduced by specific measurement maneuvers.