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Original Contribution |

Retinal Imaging by Laser Polarimetry and Optical Coherence Tomography Evidence of Axonal Degeneration in Multiple Sclerosis FREE

Maulik S. Zaveri, MS; Amy Conger, COA; Amber Salter, MS; Teresa C. Frohman, BA; Steven L. Galetta, MD; Clyde E. Markowitz, MD; Dina A. Jacobs, MD; Gary R. Cutter, PhD; Gui-Shuang Ying, PhD; Maureen G. Maguire, PhD; Peter A. Calabresi, MD; Laura J. Balcer, MD, MSCE; Elliot M. Frohman, MD, PhD
[+] Author Affiliations

Author Affiliations: Departments of Neurology (Mr Zaveri, Drs Galetta, Markowitz, Jacobs, and Balcer), Ophthalmology (Drs Galetta, Ying, Maguire, and Balcer), Biostatistics (Drs Ying and Maguire), and Epidemiology (Dr Balcer), University of Pennsylvania School of Medicine, Philadelphia; Department of Neurology, University of Texas Southwestern Medical Center, Dallas (Mss Conger, Salter, and T. C. Frohman and Dr E. M. Frohman); Department of Biostatistics, University of Alabama, Birmingham (Dr Cutter); and Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland (Dr Calabresi).


Arch Neurol. 2008;65(7):924-928. doi:10.1001/archneur.65.7.924.
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Background  Optical coherence tomography (OCT) and scanning laser polarimetry with variable corneal compensation (GDx) are similar yet provide information on different aspects of retinal nerve fiber layer (RNFL) structure (thickness values similar to histology for OCT vs birefringence of microtubules for GDx).

Objectives  To compare the ability of OCT and GDx to distinguish eyes of patients with multiple sclerosis (MS) from eyes of disease-free controls and thus identify RNFL abnormalities. We also sought to examine the capacity of these techniques to distinguish MS eyes from those without a history of optic neuritis and to correlate with visual function.

Design  Cross-sectional study.

Setting  Academic tertiary care MS center.

Participants  Eighty patients with MS (155 eyes) and 43 disease-free controls (85 eyes) underwent both OCT and GDx imaging using protocols that measure RNFL thickness.

Main Outcome Measures  Areas under the curve (AUC), adjusted for within-patient, intereye correlations, were used to compare the abilities of OCT and GDx temporal-superior-nasal-inferior-temporal average RNFL thicknesses to discriminate between MS and control eyes and to distinguish MS eyes with a history of optic neuritis. Visual function was evaluated using low-contrast letter acuity and high-contrast visual acuity.

Results  Average peripapillary RNFL thickness (360° around the optic disc) was reduced in patients with MS compared with controls for both methods. Age-adjusted AUC did not differ between OCT (0.80; 95% confidence interval [CI], 0.72-0.88) and GDx (0.78; 95% CI, 0.68-0.86; P = .38). Optical coherence tomography–measured RNFL thickness was somewhat better at distinguishing MS eyes with a history of optic neuritis from those without (OCT: AUC, 0.73; 95% CI, 0.64-0.82; GDx: AUC, 0.66; 95% CI, 0.57-0.66; P = .17). Linear correlations of RNFL thickness for OCT vs GDx were significant yet moderate (r = 0.67, P < .001); RNFL thickness measures correlated moderately and significantly with low-contrast acuity (OCT: r = 0.54, P < .001; GDx: r = 0.55, P < .001) and correlated less with high-contrast visual acuity (OCT: r = 0.44, P < .001; GDx: r = 0.32, P < .001).

Conclusions  Scanning laser polarimetry with variable corneal compensation measurements of RNFL thickness corroborates OCT evidence of visual pathway axonal loss in MS and provides new insight into structural aspects of axonal loss that relate to RNFL birefringence (microtubule integrity). These results support validity for RNFL thickness as a marker for axonal degeneration and support use of these techniques in clinical trials that examine neuroprotective and other disease-modifying therapies.

Figures in this Article

The anterior visual pathways are a common site for axonal degeneration in multiple sclerosis (MS).1 Even in the absence of a history of acute optic neuritis (ON), eyes of patients with MS have reduced numbers of retinal ganglion cell axons in pathologic studies.1 Ocular imaging techniques, including optical coherence tomography (OCT) and scanning laser polarimetry with variable corneal compensation (GDx), have demonstrated retinal nerve fiber layer (RNFL) thinning in MS,29 ON,1013 and other forms of optic neuropathy.1420

Optical coherence tomography and GDx measures of RNFL thickness are reliable21,22 and correlate well with histomorphometric findings in primate and human studies.2325 Retinal nerve fiber layer thinning by OCT is associated with visual dysfunction in MS and ON24,713 and correlates with brain atrophy and disease subtype.5,6 These unique structure-function correlations make the anterior visual pathways an attractive model for studying neuroprotective therapies.9 Used with increasing frequency in research studies, OCT and GDx provide noninvasive assessments of RNFL thickness, require only seconds to complete, and, because both are often available at academic centers, can be used in MS clinical trials to quantify axonal loss.

Despite these similarities, there are fundamental differences in the methodologies used by OCT and GDx to image the RNFL.9,1418 Optical coherence tomography uses interference patterns of backscattered near-infrared light, analogous to B-scan ultrasound, to determine RNFL thickness and yields measurements (in micrometers) that are within 5 to 6 μm of histologic parameters.9,14,23,24 Scanning laser polarimetry quantifies shifts in polarization of near-infrared light (phase retardation) that are induced by RNFL birefringence, a tissue property that depends on the integrity of retinal ganglion cell axon microtubules and neurofilaments.26,27 An estimate of RNFL thickness is then calculated using the phase retardation and birefringence.

Scanning laser polarimetry thus has the capacity not only to corroborate OCT findings of RNFL thinning, but may also provide insight into structural damage that may precede or occur in the absence of RNFL thinning by OCT.27 A comparison of these techniques will be useful for validating the role of RNFL thickness as a marker for axonal loss in MS and will demonstrate how OCT and GDx may yield complementary information on RNFL abnormalities.

The purpose of this investigation was to compare the ability of GDx and OCT measures of RNFL thickness to discriminate eyes of patients with MS from those of disease-free controls and thus identify RNFL abnormalities in MS. We also sought to examine the capacity of these techniques to distinguish between MS eyes with and without a history of ON and to correlate with scores for low-contrast letter acuity, an emerging clinical measure that correlates with magnetic resonance imaging lesion burden and captured treatment effects in recent MS trials.28

PATIENTS

Patients and healthy controls participated as part of an ongoing multicenter investigation of vision in MS. Analyses included individuals who had undergone both OCT and GDx in the same testing session and do not overlap with previously published reports.3 Patients with comorbid ocular conditions not related to MS were excluded. A history (months to years before enrollment) of acute ON was determined by self-report and physician report and confirmed by medical record review. Eyes with ongoing ON or an episode within 3 months of testing were not included. Optic disc swelling was not noted among any participants.

Disease-free controls were recruited from staff and patients' families and had no history of ocular or neurologic disease. Control eyes were excluded if best-corrected high-contrast Snellen visual acuities were worse than 20/20. Protocols were approved by institutional review boards and participants provided written informed consent. The study was conducted in accordance with Health Insurance Portability and Accountability Act guidelines.

RETINAL IMAGING

Participants underwent measurement of RNFL thickness for both eyes using OCT (OCT-3, OCT 4.0 software; Carl Zeiss Meditec, Dublin, California) and GDx with variable corneal compensation (software version 5.5.1, Carl Zeiss Meditec). The fast RNFL thickness scan protocol was used for OCT (computes the average of 3 circumferential scans for 360° around the optic disc; 256 axial scans; diameter, 3.4 mm). Good-quality OCT scans were defined by a signal strength of 7 or greater (maximum, 10) and uniform brightness across the scan circumference. As in previous studies,3 scanning was completed without the use of pharmacologic dilation if the pupils were large enough to permit imaging (generally ≥ 5 mm). Average RNFL thickness for 360° around the optic disc was recorded as the OCT summary measure.

Scanning laser polarimetry with variable corneal compensation was also performed to measure RNFL thickness. These scans were centered on the optic disc using a scan circle of 3.2 mm; the mean of 3 measurements was used. Adequate scan quality was defined as Q(GDx) values of 7 or greater. The temporal-superior-nasal-inferior-temporal average RNFL thickness was used as the summary parameter for GDx.

VISUAL FUNCTION TESTING

Low-contrast letter acuity testing was performed for each eye separately using retroilluminated low-contrast Sloan letter charts (1.25% contrast at 2 m; Precision Vision, LaSalle, Illinois).28 High-contrast visual acuity was assessed using retroilluminated Early Treatment Diabetic Retinopathy Study charts at 3.2 m. The number of letters identified correctly (maximum of 70 per chart) were recorded for each eye for low- and high-contrast acuity.28 Testing was performed by trained technicians experienced in examination of patients for research studies, and patients wore their habitual glasses or contact lenses for distance correction. Standardized protocols, including written scripts and instructions, were followed for testing.

STATISTICAL ANALYSIS

Analyses were performed using Stata, version 10.0 (Stata Corp, College Station, Texas), and SAS (SAS Institute, Cary, North Carolina). Both eyes of patients and controls were included when eligible; analyses were adjusted for potential correlations between eyes of the same participant. While ophthalmologic studies sometimes include only 1 eye per participant, methods used in this study maximize available data (in the case of MS, both eyes may be affected) while accounting for within-patient, intereye correlations.

The capacity of RNFL thickness by OCT and GDx to discriminate MS from control eyes was summarized by areas under the curves (AUCs). Similar analyses were performed for distinguishing eyes with a history of ON from those without. To accommodate the correlation between eyes of the same patient, bootstrap sampling was performed for AUC analyses by stratifying eyes on their disease state (MS vs control, ON vs non-ON) and drawing patients with replacement from each stratum. Confidence intervals for AUC were calculated based on the 2.5th percentile and 97.5th percentile from 2000 replications of bootstrap estimates.29 Areas under the curve for OCT and GDx were compared using the bootstrap method to generate the variance and covariance of the estimates of the 2 correlated AUCs.30

The relationship of GDx and OCT parameters with visual function in MS eyes was examined using Pearson linear correlation coefficients and generalized estimating equation techniques accounting for age and adjusting for within-patient, intereye correlations. Type 1 error for significance was set at α = 0.05 for all analyses.

Clinical data for 80 patients with MS (155 eyes) and 43 disease-free controls (85 eyes) are summarized in Table 1. Characteristics were similar to the US MS population for sex (80% female) and age; most patients had relapsing-remitting MS (85%). Patients with MS were older than controls; analyses comparing eyes in these groups, therefore, included age adjustment. Retinal nerve fiber layer thickness was reduced in MS eyes compared with control eyes (Table 1). Consistent with reports for glaucoma and band atrophy, RNFL thickness values for GDx (polarimetric micrometers) were lower than those for OCT based on differences in imaging paradigms.9

Table Graphic Jump LocationTable 1. Characteristics of Eyes of Patients With MS and Disease-free Controls

Adjusting for age and within-patient, intereye correlations, the capacity to distinguish MS eyes from control eyes did not differ between OCT and GDx temporal-superior-nasal-inferior-temporal average RNFL thickness (P = .38) (Table 2). Optical coherence tomography and GDx were also similar in their capacities to discriminate eyes with a history of ON from those without. Linear correlations for OCT vs GDx RNFL thickness were moderate and significant for MS eyes both with and without ON (Figure).

Place holder to copy figure label and caption
Figure.

Scatterplot of optical coherence tomography (OCT) vs scanning laser polarimetry (GDx) temporal-superior-nasal-inferior-temporal average retinal nerve fiber layer (RNFL) thickness for eyes of patients with multiple sclerosis. A, Eyes of patients with multiple sclerosis and no history of optic neuritis (ON). B, Eyes of patients with multiple sclerosis and a history of ON at least 3 months before study enrollment. Linear correlation coefficients for OCT vs GDx measures were moderate and statistically significant. Lines indicate fitted values based on univariate regression analyses.

Graphic Jump Location
Table Graphic Jump LocationTable 2. Comparison of AUC for RNFL Thickness by OCT and GDx

Retinal nerve fiber layer thickness correlated moderately and to a significant degree with low-contrast letter acuity scores (OCT: r = 0.54, P < .001; GDx temporal-superior-nasal-inferior-temporal: r = 0.55, P < .001), indicating worse vision scores in the setting of RNFL thinning. Correlations with high-contrast visual acuity were lower (OCT: r = 0.44, P < .001; GDx temporal-superior-nasal-inferior-temporal: r = 0.32, P < .001). Adjustment for age and within-patient, intereye correlations confirmed associations between reduced visual function and RNFL thinning for both GDx and OCT (P < .001, generalized estimating equation models). In these models, 2-line (10-letter) differences in low-contrast acuity were associated, on average, with 8.1 μm differences in OCT (95% confidence interval, 5.9-10.2) and 4.0 μm differences in GDx RNFL thickness (95% confidence interval, 3.0-4.9). For low-contrast letter acuity, 2-line (10-letter) differences in score have been used in recent MS trials as a criterion for clinically meaningful change based on published reliability data.31

Results for GDx-measured RNFL thickness in this study provide evidence for anterior visual pathway axonal degeneration that reflects not only thinning of RNFL axons (measured by OCT) but also implicates disruption of birefringent axonal structures, such as microtubules (detected by GDx). Both GDx and OCT capture RNFL thinning in MS eyes and correlate well with visual function. Data from this study provide additional evidence that RNFL thickness is an important marker for axonal loss and suggest that these techniques will complement visual function assessments in clinical trials of MS and ON.

The recent development of candidate neuroprotective therapies for MS and other neurodegenerative diseases has brought to the forefront the potential role for the anterior visual pathways as a model for assessing clinical outcomes and axonal integrity.9 While GDx and OCT use near-infrared light to produce measurements of RNFL thickness that are reliable,21,22 noninvasive, and correlate with visual function,24,713 differences in these techniques have provided a basis for comparative studies.1418 Optical coherence tomography yields measurements (in micrometers) that are similar to those of histologic sections.9,14,23,24 Scanning laser polarimetry captures RNFL birefringence, which is largely dependent on the interaction of light with microtubules of ganglion cell axons9,14,26,27; GDx thus offers the ability to evaluate microtubule density changes, which have been demonstrated in animal models to be detectable by GDx, even in the absence of changes in RNFL thickness as measured by OCT.27 These differing properties and measurements provided by OCT and GDx likely explain, at least in part, that correlations between OCT- and GDx-measured RNFL thickness in this and other studies are moderate in magnitude but not higher (r = 0.57-0.69 in present study; r = 0.63 in optic nerve band atrophy18; and r = 0.71-0.85 in glaucoma14,17).

Because GDx not only estimates RNFL thickness but also evaluates an important aspect of axonal viability (microtubule integrity), this technology complements OCT in examining the RNFL in MS. Technical features of GDx that differ from OCT include its use of variable corneal compensation (measurement of corneal birefringence, measured first during the scan and subtracted from RNFL birefringence) and that patients undergoing GDx need to adequately fixate on a target (difficult with poor vision, primary gaze nystagmus) so that the scan can be obtained.9 Whereas the technician performing OCT can visualize the optic disc to ensure proper scan placement, GDx does not allow for such visualization. On the other hand, elevations in RNFL thickness related to disc edema must be considered for OCT but are less problematic with GDx.9 Retinal nerve fiber layer thickness measurements are proportional but differ in magnitude between GDx and OCT, with GDx values (in polarimetric micrometers) being approximately 0.55 times those of OCT (in micrometers) in the same eyes.1418

Measures of RNFL thickness for OCT in the present study were similar to those in previous investigations of MS and ON.213 In 1 study of GDx,8 40% of MS eyes had an abnormal RNFL thickness but actual values were not presented. Areas under the curve were lower for our cohort compared with those in studies of glaucoma and band atrophy.1418 This is likely because, while glaucoma and band atrophy are defined by the presence of optic neuropathy, anterior visual pathway involvement and optic atrophy are not invariably present in MS and are not necessary for diagnosis. Correlations of GDx and OCT measurements with low-contrast letter acuity were similar (r = 0.55 vs 0.54) but were relatively lower for high-contrast visual acuity vs GDx (r = 0.32) and OCT (r = 0.44). The relationship of low- vs high-contrast acuity measures with changes in RNFL thickness and birefringence is also under investigation in longitudinal studies. Importantly, data from our study demonstrate that RNFL thinning by both GDx and OCT are associated with reductions in low- and high-contrast acuity scores, supporting available evidence that axonal integrity in MS is likely an important contributor to afferent visual function.213

Additional studies of RNFL quadrant-specific analyses for GDx and OCT will provide insight into patterns of axonal loss in MS. Ongoing longitudinal studies will also determine the course and relationship among RNFL microtubule disruption (captured by GDx), visual dysfunction, and RNFL thinning by OCT. Our data support a role for ocular imaging techniques such as OCT and GDx in clinical trials of ON and MS that examine neuroprotective and other disease-modifying therapies.

Correspondence: Laura J. Balcer, MD, MSCE, 3 E Gates Bldg, Department of Neurology, 3400 Spruce St, Philadelphia, PA 19104 (laura.balcer@uphs.upenn.edu).

Accepted for Publication: February 8, 2008.

Author Contributions:Study concept and design: Balcer. Acquisition of data: Conger, Salter, T. C. Frohman, Markowitz, Jacobs, and Balcer. Analysis and interpretation of data: Zaveri, Galetta, Markowitz, Cutter, Ying, Maguire, Calabresi, Balcer, and E. M. Frohman. Drafting of the manuscript: Zaveri and Balcer. Critical revision of the manuscript for important intellectual content: Conger, Salter, Frohman, Galetta, Markowitz, Jacobs, Cutter, Ying, Maguire, Calabresi, Balcer, and E. M. Frohman. Statistical analysis: Cutter, Ying, Maguire, and Balcer. Obtained funding: Calabresi and Balcer. Administrative, technical, and material support: Conger, Salter, T. C. Frohman, Markowitz, Jacobs, Balcer, and E.M. Frohman. Study supervision: T. C. Frohman, Galetta, and Balcer.

Financial Disclosure: None reported.

Funding/Support: This study was supported by grant PP1115 from the National Multiple Sclerosis Society (Dr Balcer); grant TR 3760-A-3 from the National Multiple Sclerosis Society Translational Research Partnership (Drs Calabresi and Balcer); grant K24 EY 014136 from the National Eye Institute (Dr Balcer); and grant T32NS043126-05 from the National Institute of Neurological Disorders and Stroke (Mr Zaveri).

Evangelou  NKonz  DEsiri  MM  et al.  Size-selective neuronal changes in the anterior optic pathways suggest a differential susceptibility to injury in multiple sclerosis. Brain 2001;124 (pt 9) 1813- 1820
PubMed
Parisi  VManni  GSpadaro  M  et al.  Correlation between morphological and functional retinal impairment in multiple sclerosis patients. Invest Ophthalmol Vis Sci 1999;40 (11) 2520- 2527
PubMed
Fisher  JBJacobs  DAMarkowitz  CE  et al.  Relation of visual function to retinal nerve fiber layer thickness in multiple sclerosis. Ophthalmology 2006;113 (2) 324- 334
PubMed
Sepulcre  JMurie-Fernandez  MSalinas-Alaman  A  et al.  Diagnostic accuracy of retinal abnormalities in predicting disease activity in MS. Neurology 2007;68 (18) 1488- 1494
PubMed
Gordon-Lipkin  EChodkowski  BReich  DS  et al.  Retinal nerve fiber layer is associated with brain atrophy in multiple sclerosis. Neurology 2007;69 (16) 1603- 1609
PubMed
Pulicken  MGordon-Lipkin  EBalcer  LJFrohman  EMCutter  GCalabresi  PA Optical coherence tomography and disease subtype in multiple sclerosis. Neurology 2007;69 (22) 2085- 2092
PubMed
Henderson  APDTrip  SASchlottmann  PG  et al.  An investigation of the retinal nerve fibre layer in progressive multiple sclerosis using optical coherence tomography. Brain 2008;131 (pt 1) 277- 287
PubMed
Della Mea  GBacchetti  SZappieri  M  et al.  Nerve fiber layer analysis with GDx with a variable corneal compensator in patients with multiple sclerosis. Ophthalmologica 2007;221 (3) 186- 189
PubMed
Frohman  EMCostello  FStüve  O  et al.  Modeling axonal degeneration within the anterior visual system: implications for demonstrating neuroprotection in multiple sclerosis. Arch Neurol 2008;65 (1) 26- 35
PubMed
Trip  SASchlottmann  PGJones  SJ  et al.  Retinal nerve fiber layer axonal loss and visual dysfunction in optic neuritis. Ann Neurol 2005;58 (3) 383- 391
PubMed
Costello  FCoupland  SHodge  W  et al.  Quantifying axonal loss after optic neuritis with optical coherence tomography. Ann Neurol 2006;59 (6) 963- 969
PubMed
Noval  SContreras  IRebolleda  GMuñoz-Negrete  FJ Optical coherence tomography versus automated perimetry for follow-up of optic neuritis. Acta Ophthalmol Scand 2006;84 (6) 790- 794
PubMed
Steel  DHWaldock  A Measurement of the retinal nerve fibre layer with scanning laser polarimetry in patients with previous demyelinating optic neuritis. J Neurol Neurosurg Psychiatry 1998;64 (4) 505- 509
PubMed
Leung  CKChan  WChong  KK  et al.  Comparative study of retinal nerve fiber layer measurement by StratusOCT and GDx VCC, I: correlation analysis in glaucoma. Invest Ophthalmol Vis Sci 2005;46 (9) 3214- 3220
PubMed
Brusini  PSalvetat  MLZeppieri  M  et al.  Comparison between GDx VCC scanning laser polarimetry and Stratus OCT optical coherence tomography in the diagnosis of chronic glaucoma. Acta Ophthalmol Scand 2006;84 (5) 650- 655
PubMed
Hong  SAhn  HHa  SJ  et al.  Early glaucoma detection using the Humphrey matrix perimeter, GDx VCC, Stratus OCT, and retinal nerve fiber layer photography. Ophthalmology 2007;114 (2) 210- 215
PubMed
Sehi  MUme  SGreenfield  DS  et al.  Scanning laser polarimetry with enhanced corneal compensation and optical coherence tomography in normal and glaucomatous eyes. Invest Ophthalmol Vis Sci 2007;48 (5) 2099- 2104
PubMed
Montiero  MLMoura  FC Comparison of the GDx VCC scanning laser polarimeter and the stratus optical coherence tomograph in detection of band atrophy of the optic nerve [published online ahead of print January 26, 2007]. Eye 2008;22 (5) 641- 64810.1038/sj.eye.6702694
PubMed
Contreras  INoval  SRebolleda  GMuñoz-Negrete  FJ Follow-up of nonartertitic anterior ischemic optic neuropathy with optical coherence tomography. Ophthalmology 2007;114 (12) 2338- 2344
PubMed
Chan  CKMMiller  NR Peripapillary nerve fiber layer thickness measured by optical coherence tomography in patients with no light perception from long-standing nonglaucomatous optic neuropathies. J Neuroophthalmol 2007;27 (3) 176- 179
PubMed
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PubMed
Blumenthal  EZFrenkel  S Inter-device reproducibility of the scanning laser polarimeter with variable cornea compensation. Eye 2005;19 (3) 308- 311
PubMed
Schuman  JSPedut-Koizman  TPakter  H  et al.  Optical coherence tomography and histologic measurements of nerve fiber layer thickness in normal and glaucomatous monkey eyes. Invest Ophthalmol Vis Sci 2007;48 (8) 3645- 3654
PubMed
Blumenthal  EZParikh  RSPe’er  JNaik  MKaliner  ECohen  MJPrabakaran  SKogan  MThomas  R Retinal nerve fibre layer imaging compared with histological measurements in a human eye. Eye 24 August2007;[Epub ahead of print].10.1038/sj.eye.6702942
PubMed
Weinreb  RNDreher  AWColeman  A  et al.  Histopathologic validation of Fourier-ellipsometry measurements of retinal nerve fiber layer thickness. Arch Ophthalmol 1990;108 (4) 557- 560
PubMed
Huang  XRKnighton  RW Microtubules contribute to the birefringence of the retinal nerve fiber layer. Invest Ophthalmol Vis Sci 2005;46 (12) 4588- 4593
PubMed
Fortune  BWang  LCull  GCioffi  GA Intravitreal colchicine causes decreased RNFL birefringence without altering RNFL thickness. Invest Ophthalmol Vis Sci 2008;49 (1) 255- 261
PubMed
Balcer  LJGaletta  SLCalabresi  PC  et al.  Natalizumab reduces visual loss in patients with relapsing multiple sclerosis. Neurology 2007;68 (16) 1299- 1304
PubMed
Rutter  CM Bootstrap estimation of diagnostic accuracy with patient-clustered data. Acad Radiol 2000;7 (6) 413- 419
PubMed
Margolis  DJBilker  WBoston  RLocalio  RBerlin  JA Statistical characteristics of area under receiver operating characteristic curve for a simple prognostic model using traditional and bootstrapped approaches. J Clin Epidemiol 2002;55 (5) 518- 524
PubMed
Rosser  DACousens  SNMurdoch  IEFitzke  FWLaidlaw  DA How sensitive to clinical change are ETDRS and logMAR visual acuity measurements? Invest Ophthalmol Vis Sci 2003;44 (8) 3278- 3281
PubMed

Figures

Place holder to copy figure label and caption
Figure.

Scatterplot of optical coherence tomography (OCT) vs scanning laser polarimetry (GDx) temporal-superior-nasal-inferior-temporal average retinal nerve fiber layer (RNFL) thickness for eyes of patients with multiple sclerosis. A, Eyes of patients with multiple sclerosis and no history of optic neuritis (ON). B, Eyes of patients with multiple sclerosis and a history of ON at least 3 months before study enrollment. Linear correlation coefficients for OCT vs GDx measures were moderate and statistically significant. Lines indicate fitted values based on univariate regression analyses.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1. Characteristics of Eyes of Patients With MS and Disease-free Controls
Table Graphic Jump LocationTable 2. Comparison of AUC for RNFL Thickness by OCT and GDx

References

Evangelou  NKonz  DEsiri  MM  et al.  Size-selective neuronal changes in the anterior optic pathways suggest a differential susceptibility to injury in multiple sclerosis. Brain 2001;124 (pt 9) 1813- 1820
PubMed
Parisi  VManni  GSpadaro  M  et al.  Correlation between morphological and functional retinal impairment in multiple sclerosis patients. Invest Ophthalmol Vis Sci 1999;40 (11) 2520- 2527
PubMed
Fisher  JBJacobs  DAMarkowitz  CE  et al.  Relation of visual function to retinal nerve fiber layer thickness in multiple sclerosis. Ophthalmology 2006;113 (2) 324- 334
PubMed
Sepulcre  JMurie-Fernandez  MSalinas-Alaman  A  et al.  Diagnostic accuracy of retinal abnormalities in predicting disease activity in MS. Neurology 2007;68 (18) 1488- 1494
PubMed
Gordon-Lipkin  EChodkowski  BReich  DS  et al.  Retinal nerve fiber layer is associated with brain atrophy in multiple sclerosis. Neurology 2007;69 (16) 1603- 1609
PubMed
Pulicken  MGordon-Lipkin  EBalcer  LJFrohman  EMCutter  GCalabresi  PA Optical coherence tomography and disease subtype in multiple sclerosis. Neurology 2007;69 (22) 2085- 2092
PubMed
Henderson  APDTrip  SASchlottmann  PG  et al.  An investigation of the retinal nerve fibre layer in progressive multiple sclerosis using optical coherence tomography. Brain 2008;131 (pt 1) 277- 287
PubMed
Della Mea  GBacchetti  SZappieri  M  et al.  Nerve fiber layer analysis with GDx with a variable corneal compensator in patients with multiple sclerosis. Ophthalmologica 2007;221 (3) 186- 189
PubMed
Frohman  EMCostello  FStüve  O  et al.  Modeling axonal degeneration within the anterior visual system: implications for demonstrating neuroprotection in multiple sclerosis. Arch Neurol 2008;65 (1) 26- 35
PubMed
Trip  SASchlottmann  PGJones  SJ  et al.  Retinal nerve fiber layer axonal loss and visual dysfunction in optic neuritis. Ann Neurol 2005;58 (3) 383- 391
PubMed
Costello  FCoupland  SHodge  W  et al.  Quantifying axonal loss after optic neuritis with optical coherence tomography. Ann Neurol 2006;59 (6) 963- 969
PubMed
Noval  SContreras  IRebolleda  GMuñoz-Negrete  FJ Optical coherence tomography versus automated perimetry for follow-up of optic neuritis. Acta Ophthalmol Scand 2006;84 (6) 790- 794
PubMed
Steel  DHWaldock  A Measurement of the retinal nerve fibre layer with scanning laser polarimetry in patients with previous demyelinating optic neuritis. J Neurol Neurosurg Psychiatry 1998;64 (4) 505- 509
PubMed
Leung  CKChan  WChong  KK  et al.  Comparative study of retinal nerve fiber layer measurement by StratusOCT and GDx VCC, I: correlation analysis in glaucoma. Invest Ophthalmol Vis Sci 2005;46 (9) 3214- 3220
PubMed
Brusini  PSalvetat  MLZeppieri  M  et al.  Comparison between GDx VCC scanning laser polarimetry and Stratus OCT optical coherence tomography in the diagnosis of chronic glaucoma. Acta Ophthalmol Scand 2006;84 (5) 650- 655
PubMed
Hong  SAhn  HHa  SJ  et al.  Early glaucoma detection using the Humphrey matrix perimeter, GDx VCC, Stratus OCT, and retinal nerve fiber layer photography. Ophthalmology 2007;114 (2) 210- 215
PubMed
Sehi  MUme  SGreenfield  DS  et al.  Scanning laser polarimetry with enhanced corneal compensation and optical coherence tomography in normal and glaucomatous eyes. Invest Ophthalmol Vis Sci 2007;48 (5) 2099- 2104
PubMed
Montiero  MLMoura  FC Comparison of the GDx VCC scanning laser polarimeter and the stratus optical coherence tomograph in detection of band atrophy of the optic nerve [published online ahead of print January 26, 2007]. Eye 2008;22 (5) 641- 64810.1038/sj.eye.6702694
PubMed
Contreras  INoval  SRebolleda  GMuñoz-Negrete  FJ Follow-up of nonartertitic anterior ischemic optic neuropathy with optical coherence tomography. Ophthalmology 2007;114 (12) 2338- 2344
PubMed
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