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Original Contribution |

Reproducibility of Optical Coherence Tomography in Multiple Sclerosis FREE

Deanna Cettomai, BS; Mathew Pulicken, MBBS, MHS; Eliza Gordon-Lipkin, BS; Amber Salter, MPH; Teresa C. Frohman, BA; Amy Conger, BA; Xiao Zhang, PhD; Gary Cutter, PhD; Laura J. Balcer, MD, MSCE; Elliot M. Frohman, MD, PhD; Peter A. Calabresi, MD
[+] Author Affiliations

Author Affiliations: Department of Neurology, The Johns Hopkins School of Medicine, Baltimore, Maryland (Mss Cettomai and Gordon-Lipkin and Drs Pulicken and Calabresi); Departments of Neurology and Ophthalmology, The University of Texas Southwestern Medical Center, Dallas (Mss Salter, Frohman, and Conger and Dr Frohman); Department of Biostatistics, University of Alabama, Birmingham (Drs Zhang and Cutter); and Departments of Neurology and Ophthalmology, University of Pennsylvania School of Medicine, Philadelphia (Dr Balcer).


Arch Neurol. 2008;65(9):1218-1222. doi:10.1001/archneur.65.9.1218.
Text Size: A A A
Published online

Background  Optical coherence tomography (OCT) is a promising new method of quantifying axon thickness in the retinal nerve fiber layer (RNFL) that has been used predominantly by ophthalmologists to monitor glaucoma. Optical coherence tomography is being considered as a potential outcome measure in multiple sclerosis (MS) clinical trials, but no data exist on the reproducibility of this technique in MS centers.

Objective  To determine the reproducibility of OCT measurement of mean RNFL thickness in the undilated eyes of healthy control subjects and patients with MS.

Design  Prospective analysis of 4 healthy controls to determine interrater, intrarater, and longitudinal reproducibility. Cross-sectional analysis of 3 cohorts of patients with MS (n = 396) and healthy controls (n = 153).

Setting  Multiple sclerosis clinics at 3 academic medical centers.

Patients or Other Participants  Healthy controls and patients with MS.

Main Outcome Measure  Thickness of RNFL.

Results  We found excellent agreement with respect to interrater (intraclass correlation [ICC], 0.89), intrarater (ICC, 0.98), and intervisit (ICC, 0.91) results. Mean RNFL thickness did not vary significantly among research centers for patients with MS (93, 92, and 90 μm) or among healthy controls (103, 105, and 104 μm) by site.

Conclusions  We demonstrate that mean RNFL thickness can be reproducibly measured by trained technicians in an MS center using the OCT-3 model. The RNFL measures from cohorts of age-matched controls and patients with MS from 3 different research centers were remarkably similar.

Figures in this Article

Optical coherence tomography (OCT) is a noninvasive high-resolution technique that uses near-infrared light to generate cross-sectional tomographic images of tissues,1 including the retinal nerve fiber layer (RNFL).2 Optical coherence tomography is used to monitor retinal ganglion cell axon loss in glaucoma, diabetic retinopathy, traumatic optic neuropathy, chiasmal lesions, and optic neuritis.313

Recently, OCT has been studied in patients with multiple sclerosis (MS) (hereinafter referred to as MS patients), of whom 80% experience visual impairment.14,15 Decreased RNFL thickness has been demonstrated in patients with a history of optic neuritis.7,12,16,17 Two studies showed that the eyes without optic neuritis among MS patients have decreased RNFL thickness compared with the eyes of control subjects, suggesting that retinal ganglion cell axonal loss occurs separately from acute optic neuritis in MS patients.16,18 In addition, RNFL thickness correlates with low-contrast visual acuity and contrast sensitivity.16 This suggests that OCT can be used to monitor axonal injury and visual dysfunction in MS and may be a useful outcome measure in clinical trials.8,12,13,16,19

Whether reproducibility studies completed on earlier OCT models2026 are applicable to the OCT-3 model (Carl Zeiss Meditec, Dublin, California) is unclear because foveal thickness measurements obtained using the prototype OCT scanner and OCT-3 are not directly comparable.27 The reproducibility of RNFL thickness has been examined using OCT-3 in healthy subjects and cohorts with glaucoma, ocular hypertension, macular edema, and diabetes mellitus,2834 but not in MS cohorts. These studies were performed by ophthalmologists on subjects with pharmacologically dilated pupils. All found good reproducibility of RNFL measurements. However, ocular symptoms in MS, including nystagmus, can have an important effect on visual fixation—an essential component in obtaining high-quality OCT scans—and, therefore, present unique challenges in MS patients, with the potential to decrease OCT reproducibility in this cohort. Other possible impediments to the reliable use of OCT in an MS center include the facts that neurology patients do not routinely have their pupils dilated and that neurology office staff are not trained in the use of slitlamp examination. We hypothesized that, despite these issues, OCT could be performed reproducibly in the setting of an MS center.

SUBJECTS

Interrater, intrarater, and intervisit reproducibility studies were performed at the Johns Hopkins MS Center. We examined both eyes of 4 healthy subjects recruited from the staff of the neurology department. The cross-center comparison was performed using cross-sectional data obtained from age- and sex-matched MS patients (n = 396) and healthy controls (n = 153) at the MS centers of The Johns Hopkins University (JHU), the University of Pennsylvania (U Penn), and The University of Texas Southwestern Medical Center (UTSW). We included subjects with no history of intraocular surgery, glaucoma, retinal disease, diabetes, or hypertension and who completed informed consent. All MS disease subtypes were included. Data from the initial scans of all patients and controls at each center were included in the cross-center comparison.

OPTICAL COHERENCE TOMOGRAPHY

The RNFL measurements were obtained using the OCT-3 fast RNFL thickness protocol, which performs 3 consecutive 3.4-mm-diameter circular scans centered on the optic nerve head. In addition, OCT software (OCT 4.0, version A2; Carl Zeiss Meditec) generated a mean RNFL thickness measurement for 360° around the optic disc, 4 retinal quadrants, and 12 clock hour segments (30° for each hour position).

STUDY PROTOCOL

The RNFL scans were obtained on both eyes of 4 healthy subjects by 3 technicians during 5 consecutive weekly visits. Interrater and intervisit reproducibility were obtained from these data. At visit 3, 1 investigator performed 3 consecutive RNFL scans on each eye of each subject to determine intrarater reproducibility. All scans were performed without pupil dilation. In the cross-center comparison, 1 OCT scan was obtained of each eye of the MS patients and healthy controls.

STATISTICAL ANALYSIS

We used the intraclass correlation coefficient (ICC) as a summary measure for interrater, intrarater, and intervisit agreement. The ICC represents the proportion of variance in data explained by between-subject differences; the higher the ICC (maximum value, 1.0), the better the agreement between measures of the same patient. An ICC of less than 0.40 indicates poor reproducibility; of 0.40 to 0.75, fair to good reproducibility; and of greater than 0.75, excellent reproducibility.

In this study design, there was complex nesting, which requires large sample sizes for simultaneous estimates of desired measures; thus, we used random-effects general linear models (Proc MIXED in SAS; SAS Institute Inc, Cary, North Carolina) to compare ICCs between groups of patients, observers, and longitudinally, treating certain factors as fixed and others as random, depending on the ICC being estimated. Variance homogeneity and ICC homogeneity tests were used to validate assumptions made for estimates. We used only 1 eye in each analysis to enable consistency with the literature but present values for each eye. The high correlations between eyes and the relative consistency of the results demonstrate that little additional information was available by incorporating both eyes in the same analysis.

SUBJECT CHARACTERISTICS

We studied 8 eyes of 4 healthy subjects for the interrater, intervisit, and intrarater portions of this study. There were 2 men and 2 women, and the mean (SD) age was 23 (3) years (range, 20-27 years). In the cross-center comparison, MS patients and controls across 3 centers did not differ significantly in demographic characteristics (Table 1).

Table Graphic Jump LocationTable 1. Demographic Characteristics of MS Patients and Healthy Control Cohorts
RNFL THICKNESS

The ICCs were first calculated by combining data from each eye of each subject and indicated excellent agreement (Table 2). Quadrant ICCs ranged from 0.66 to 0.98 and were slightly lower than mean RNFL ICCs, which ranged from 0.89 to 0.98. Intrarater ICCs were highest (Figure 1), and intervisit ICCs were also high (Figure 2). Although still acceptable, interrater ICCs were the lowest (Figure 3). This approach effectively averaged the eyes of each subject, which are highly correlated, and may have slightly overestimated ICCs. When the analyses were repeated considering each eye separately (Table 3), ICCs remained high but with wider confidence intervals. Mean (SD) RNFL thickness was remarkably similar among centers for the MS patient and healthy subject cohorts (Figure 4).

Place holder to copy figure label and caption
Figure 1.

Intrarater reproducibility. Mean retinal nerve fiber layer (RNFL) thicknesses from 3 optical coherence tomographic scans of each eye (E-1 and E-2) of healthy control subjects (HC-A to HC-D) obtained by the same rater on the same day.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Intervisit reproducibility. Mean retinal nerve fiber layer (RNFL) thicknesses of each eye (E-1 and E-2) of healthy control subjects (HC-A to HC-D) obtained by 3 raters (A, B, and C) at 5 weekly visits.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.

Interrater reproducibility. Mean retinal nerve fiber layer (RNFL) thicknesses of each eye (E-1 and E-2) of healthy control subjects (HC-A to HC-D) obtained by 3 different raters.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 4.

Cross-center comparison. Mean retinal nerve fiber layer (RNFL) thicknesses from patients with multiple sclerosis (A) and healthy control subjects (B) at 3 research centers. JHU indicates The Johns Hopkins University; U Penn, University of Pennsylvania; and UTSW, The University of Texas Southwestern Medical Center.

Graphic Jump Location
Table Graphic Jump LocationTable 2. Optical Coherence Tomographic RNFL Thickness ICCs Calculated Using Both Eyes of Each Subject
Table Graphic Jump LocationTable 3. Optical Coherence Tomographic RNFL Thickness ICCs Calculated for Each Eye Separately

We found that all RNFL measurements showed excellent ICCs when examined for intrarater, interrater, and intervisit reproducibility. Intrarater reproducibility was stronger than intervisit reproducibility, indicating that reproducibility within a given eye on a given day is greater than reproducibility within a given eye on different days.21,30 Quadrant thicknesses were more variable than were mean RNFL thickness. The lower ICC for quadrants suggests that quadrantic analyses, although potentially more sensitive to subtle changes, will decrease power in clinical trials owing to poorer reproducibility. However, mean RNFL thicknesses are sensitive to abnormalities in MS patients and highly reproducible, making them appropriate to use for comparisons. The major limitation of this portion of our investigation was the small sample size studied.

Our data (Tables 2 and 3) are comparable to previously reported ICCs. One study measuring intervisit reproducibility30 reported a mean RNFL thickness ICC of 0.83 and ICCs for quadrant thicknesses ranging from 0.62 to 0.81, whereas another group examining intrarater reproducibility33 found a mean RNFL thickness ICC of 0.95with quadrant thickness ICCs varying from 0.79 to 0.97. Finally, a recent study of patients with glaucoma34 found an intrarater mean RNFL thickness ICC of 0.98 and an intervisit mean RNFL thickness ICC of 0.96.

The most reproducible RNFL measurement in our study was mean thickness, which correlates with previously published results.3032 Averaging the mean RNFL thicknesses from several consecutive scans increased the ICC in one report. However, results from averaged and nonaveraged data were similar, indicating that a single scan can provide reliable results.30 Several groups previously reported quadrant thickness reproducibility. Four studies found that the nasal quadrant was the most variable,25,3234 and another found the greatest variability in the superior quadrant, followed by the nasal quadrant.31 Our results indicate that the nasal quadrant thickness was the most reproducible, whereas superior quadrant thickness was the least reproducible. However, the mean superior quadrant thickness of our healthy subjects was much greater than the mean nasal quadrant thickness (superior, 139 μm, and nasal, 85 μm). A previous study35 found that macular sector thickness variation increased with increasing macular thickness. This seems to indicate that a similar phenomenon may be seen with RNFL quadrant thicknesses, thus potentially explaining the decreased reproducibility of the superior quadrant in our study.

In this study, we did not dilate pupils and found no effect on the quality of the data, which is in keeping with a previous report.30 Another study investigating whether the technicians' experience affected reproducibility found that inexperienced technicians could generate useful measurements.25 In our study, 2 technicians had 8 months of OCT-3 experience, whereas 1 technician had 1 month of experience (D.C., M.P., and E.G.-L.). We found that all 3 technicians generated reproducible data.

Other groups have shown higher variation in patients with glaucoma and diabetes compared with healthy subjects.31,36 To our knowledge, the reproducibility of OCT in MS patients has not been reported previously. Our cross-sectional study was limited because different patients were studied at each site. Although not ideal, the only feasible way to compare large, geographically distant cohorts was to use age-matched subjects with similar demographic characteristics as found in our cohorts. Despite the potential for ocular abnormalities of MS to interfere with obtaining high-quality OCT scans, our cross-sectional data obtained from 3 research centers examining separate MS cohorts were virtually identical. This suggests that RNFL measurements are reproducible within diverse MS patient groups, which is encouraging for the potential use of OCT-3as an outcome measure in clinical trials. Use of a single model of the same machine also offers advantages over magnetic resonance images obtained using many different models and machine types.

Validation of OCT as an imaging biomarker in MS is important because several aspects of the information it generates are unique. Imaging the RNFL allows direct measurement of the unmyelinated axons of the central nervous system.37 The capacity to image central nervous system axons quickly and noninvasively, to minimize expense, and to correlate structural abnormalities with visual dysfunction add to the appeal of OCT as an imaging biomarker and outcome measure in clinical trials.16

We have demonstrated that OCT RNFL thicknesses obtained in an MS clinic show excellent interrater, intrarater, and intervisit reproducibility in healthy controls. In addition, RNFL measurements from MS and control cohorts from 3 different academic MS centers were remarkably similar. This makes OCT an attractive potential outcome measure for clinical trials of axonal-protective therapeutics and as a potential marker for disease progression in MS patients.

Correspondence: Peter A. Calabresi, MD, Pathology Bldg, Ste 627, The Johns Hopkins Hospital, 600 N Wolfe St, Baltimore, MD 21287 (calabresi@jhmi.edu).

Accepted for Publication: March 11, 2008.

Author Contributions:Study concept and design: Cettomai, Pulicken, Gordon-Lipkin, E. M. Frohman, and Calabresi. Acquisition of data: Cettomai, Pulicken, Gordon-Lipkin, Salter, T. C. Frohman, Conger, and E. M. Frohman. Analysis and interpretation of data: Cettomai, Zhang, Cutter, Balcer, and Calabresi. Drafting of the manuscript: Cettomai, Pulicken, and E. M. Frohman. Critical revision of the manuscript for important intellectual content: Cettomai, Gordon-Lipkin, Salter, T. C. Frohman, Conger, Zhang, Cutter, Balcer, E. M. Frohman, and Calabresi. Statistical analysis: Conger, Zhang, Cutter, and Balcer. Obtained funding: Cettomai and Calabresi. Administrative, technical, and material support: Cettomai, Pulicken, Gordon-Lipkin, Salter, and E. M. Frohman. Study supervision: Cettomai, Pulicken, T. C. Frohman, E. M. Frohman, and Calabresi.

Financial Disclosure: None reported.

Funding/Support: This study was supported by grant TR3760-A3 from the National Multiple Sclerosis Society (Dr Calabresi), The Nancy Davis Foundation (Dr Calabresi), and the American Academy of Neurology Medical Student Research Scholarship (Ms Cettomai).

Huang  DSwanson  EALin  CP  et al.  Optical coherence tomography. Science 1991;254 (5035) 1178- 1181
PubMed
Jaffe  GJCaprioli  J Optical coherence tomography to detect and manage retinal disease and glaucoma. Am J Ophthalmol 2004;137 (1) 156- 169
PubMed
Kanamori  ANakamura  MEscano  MFSeya  RMaeda  HNegi  A Evaluation of the glaucomatous damage on retinal nerve fiber layer thickness measured by optical coherence tomography. Am J Ophthalmol 2003;135 (4) 513- 520
PubMed
Medeiros  FAZangwill  LMBowd  CWeinreb  RN Comparison of the GDx VCC scanning laser polarimeter, HRT II confocal scanning laser ophthalmoscope, and Stratus OCT optical coherence tomograph for the detection of glaucoma. Arch Ophthalmol 2004;122 (6) 827- 837
PubMed
Medeiros  FAMoura  FCVessani  RMSusanna  R  Jr Axonal loss after traumatic optic neuropathy documented by optical coherence tomography. Am J Ophthalmol 2003;135 (3) 406- 408
PubMed
Monteiro  MLLeal  BCRosa  AABronstein  MD Optical coherence tomography analysis of axonal loss in band atrophy of the optic nerve. Br J Ophthalmol 2004;88 (7) 896- 899
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
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
Massin  PGirach  AErginay  AGaudric  A Optical coherence tomography: a key to the future management of patients with diabetic macular oedema. Acta Ophthalmol Scand 2006;84 (4) 466- 474
PubMed
Costa  RASkaf  MMelo  LA  Jr  et al.  Retinal assessment using optical coherence tomography. Prog Retin Eye Res 2006;25 (3) 325- 353
PubMed
Savini  GBellusci  CCarbonelli  M  et al.  Detection and quantification of retinal nerve fiber layer thickness in optic disc edema using stratus OCT. Arch Ophthalmol 2006;124 (8) 1111- 1117
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  GMunoz-Negrete  F Optical coherence tomography in optic neuritis [letter]. Ophthalmology 2007;114 (1) 200
PubMed
McDonald  WIBarnes  D The ocular manifestations of multiple sclerosis, I: abnormalities of the afferent visual system. J Neurol Neurosurg Psychiatry 1992;55 (9) 747- 752
PubMed
Warner  JLessell  S Neuro-ophthalmology of multiple sclerosis. Clin Neurosci 1994;2 (3-4) 180- 188
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- 332
PubMed
Trip  SASchlottmann  PGJones  SJ  et al.  Optic nerve atrophy and retinal nerve fiber layer thinning following optic neuritis: evidence that axonal loss is a substrate of MRI-detected atrophy. Neuroimage 2006;31 (1) 286- 293
PubMed
Pulicken  MGordon-Lipkin  EBalcer  LJFrohman  ECutter  GCalabresi  PA Optical coherence tomography and disease subtype in multiple sclerosis. Neurology 2007;69 (22) 2085- 2092
PubMed
Sergott  RC Optical coherence tomography: measuring in-vivo axonal survival and neuroprotection in multiple sclerosis and optic neuritis. Curr Opin Ophthalmol 2005;16 (6) 346- 350
PubMed
Koozekanani  DRoberts  CKatz  SEHerderick  EE Intersession repeatability of macular thickness measurements with the Humphrey 2000 OCT. Invest Ophthalmol Vis Sci 2000;41 (6) 1486- 1491
PubMed
Schuman  JSPedut-Kloizman  THertzmark  E  et al.  Reproducibility of nerve fiber layer thickness measurements using optical coherence tomography. Ophthalmology 1996;103 (11) 1889- 1898
PubMed
Massin  PVicaut  EHaouchine  BErginay  APaques  MGaudric  A Reproducibility of retinal mapping using optical coherence tomography. Arch Ophthalmol 2001;119 (8) 1135- 1142
PubMed
Jones  ALSheen  NJNorth  RVMorgan  JE The Humphrey optical coherence tomography scanner: quantitative analysis and reproducibility study of the normal human retinal nerve fiber layer. Br J Ophthalmol 2001;85 (6) 673- 677
PubMed
Blumenthal  EZWilliams  JMWeinreb  RNGirkin  CABerry  CCZangwill  LM Reproducibility of nerve fiber layer thickness measurements by use of optical coherence tomography. Ophthalmology 2000;107 (12) 2278- 2282
PubMed
Villain  MAGreenfield  DS Peripapillary nerve fiber layer thickness measurement reproducibility using optical coherence tomography. Ophthalmic Surg Lasers Imaging 2003;34 (1) 33- 37
PubMed
Carpineto  PCiancaglini  MZuppardi  EFalconio  GDoronzo  EMastropasqua  L Reliability of nerve fiber layer thickness measurements using optical coherence tomography in normal and glaucomatous eyes. Ophthalmology 2003;110 (1) 190- 195
PubMed
Pierre-Kahn  VTadayoni  RHaouchine  BMassin  PGaudric  A Comparison of optical coherence tomography models OCT1 and Stratus OCT for macular retinal thickness measurement. Br J Ophthalmol 2005;89 (12) 1581- 1585
PubMed
Hsu  SYTung  ICSheu  MMTsai  RK Reproducibility of peripapillary retinal nerve fiber layer and macular retinal thickness measurements using optical coherence tomography. Kaohsiung J Med Sci 2006;22 (9) 447- 451
PubMed
Lleó-Pérez  AOrtuño-Soto  ARahhal  MSMartínez-Sorian  FSanchis-Gimeno  JA Intraobserver reproducibility of retinal nerve fiber layer measurements using scanning laser polarimetry and optical coherence tomography in normal and ocular hypertensive subjects. Eur J Ophthalmol 2004;14 (6) 523- 530
PubMed
Paunescu  LASchuman  JSPrice  LL  et al.  Reproducibility of nerve fiber thickness, macular thickness and optic nerve head measurements using StratusOCT. Invest Ophthalmol Vis Sci 2004;45 (6) 1716- 1724
PubMed
Pueyo  VPolo  VLarrosa  JMMayoral  FFerreras  AHonrubia  FM Reproducibility of optic nerve head and retinal nerve fiber layer thickness measurements using optical coherence tomography. Arch Soc Esp Oftalmol 2006;81 (4) 205- 211
PubMed
Gürses-Ozden  RTeng  CVessani  RZafar  SLiebmann  JMRitch  R Macular and retinal nerve fiber layer thickness measurement reproducibility using optical coherence tomography (OCT-3). J Glaucoma 2004;13 (3) 238- 244
PubMed
Budenz  DLChang  RTHuang  XKnighton  RWTielsch  JM Reproducibility of retinal nerve fiber thickness measurements using the Stratus OCT in normal and glaucomatous eyes. Invest Ophthalmol Vis Sci 2005;46 (7) 2440- 2443
PubMed
Budenz  DLFredette  MJFeuer  WJAnderson  DR Reproducibility of peripapillary retinal nerve fiber thickness measurements with Stratus OCT in glaucomatous eyes. Ophthalmology 2008;115 (4) 661- 666.e4
PubMed10.1016/j.ophtha.2007.05.035
Browning  DJ Interobserver variability in optical coherence tomography for macular edema. Am J Ophthalmol 2004;137 (6) 1116- 1117
PubMed
Polito  ADel Borrello  MDIsola  MZemella  NBandello  F Repeatability and reproducibility of fast macular thickness mapping with Stratus optical coherence tomography. Arch Ophthalmol 2005;123 (10) 1330- 1337
PubMed
Frohman  ECostello  FZivadinov  R  et al.  Optical coherence tomography in multiple sclerosis. Lancet Neurol 2006;5 (10) 853- 863
PubMed

Figures

Place holder to copy figure label and caption
Figure 1.

Intrarater reproducibility. Mean retinal nerve fiber layer (RNFL) thicknesses from 3 optical coherence tomographic scans of each eye (E-1 and E-2) of healthy control subjects (HC-A to HC-D) obtained by the same rater on the same day.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Intervisit reproducibility. Mean retinal nerve fiber layer (RNFL) thicknesses of each eye (E-1 and E-2) of healthy control subjects (HC-A to HC-D) obtained by 3 raters (A, B, and C) at 5 weekly visits.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.

Interrater reproducibility. Mean retinal nerve fiber layer (RNFL) thicknesses of each eye (E-1 and E-2) of healthy control subjects (HC-A to HC-D) obtained by 3 different raters.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 4.

Cross-center comparison. Mean retinal nerve fiber layer (RNFL) thicknesses from patients with multiple sclerosis (A) and healthy control subjects (B) at 3 research centers. JHU indicates The Johns Hopkins University; U Penn, University of Pennsylvania; and UTSW, The University of Texas Southwestern Medical Center.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1. Demographic Characteristics of MS Patients and Healthy Control Cohorts
Table Graphic Jump LocationTable 2. Optical Coherence Tomographic RNFL Thickness ICCs Calculated Using Both Eyes of Each Subject
Table Graphic Jump LocationTable 3. Optical Coherence Tomographic RNFL Thickness ICCs Calculated for Each Eye Separately

References

Huang  DSwanson  EALin  CP  et al.  Optical coherence tomography. Science 1991;254 (5035) 1178- 1181
PubMed
Jaffe  GJCaprioli  J Optical coherence tomography to detect and manage retinal disease and glaucoma. Am J Ophthalmol 2004;137 (1) 156- 169
PubMed
Kanamori  ANakamura  MEscano  MFSeya  RMaeda  HNegi  A Evaluation of the glaucomatous damage on retinal nerve fiber layer thickness measured by optical coherence tomography. Am J Ophthalmol 2003;135 (4) 513- 520
PubMed
Medeiros  FAZangwill  LMBowd  CWeinreb  RN Comparison of the GDx VCC scanning laser polarimeter, HRT II confocal scanning laser ophthalmoscope, and Stratus OCT optical coherence tomograph for the detection of glaucoma. Arch Ophthalmol 2004;122 (6) 827- 837
PubMed
Medeiros  FAMoura  FCVessani  RMSusanna  R  Jr Axonal loss after traumatic optic neuropathy documented by optical coherence tomography. Am J Ophthalmol 2003;135 (3) 406- 408
PubMed
Monteiro  MLLeal  BCRosa  AABronstein  MD Optical coherence tomography analysis of axonal loss in band atrophy of the optic nerve. Br J Ophthalmol 2004;88 (7) 896- 899
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
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
Massin  PGirach  AErginay  AGaudric  A Optical coherence tomography: a key to the future management of patients with diabetic macular oedema. Acta Ophthalmol Scand 2006;84 (4) 466- 474
PubMed
Costa  RASkaf  MMelo  LA  Jr  et al.  Retinal assessment using optical coherence tomography. Prog Retin Eye Res 2006;25 (3) 325- 353
PubMed
Savini  GBellusci  CCarbonelli  M  et al.  Detection and quantification of retinal nerve fiber layer thickness in optic disc edema using stratus OCT. Arch Ophthalmol 2006;124 (8) 1111- 1117
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  GMunoz-Negrete  F Optical coherence tomography in optic neuritis [letter]. Ophthalmology 2007;114 (1) 200
PubMed
McDonald  WIBarnes  D The ocular manifestations of multiple sclerosis, I: abnormalities of the afferent visual system. J Neurol Neurosurg Psychiatry 1992;55 (9) 747- 752
PubMed
Warner  JLessell  S Neuro-ophthalmology of multiple sclerosis. Clin Neurosci 1994;2 (3-4) 180- 188
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- 332
PubMed
Trip  SASchlottmann  PGJones  SJ  et al.  Optic nerve atrophy and retinal nerve fiber layer thinning following optic neuritis: evidence that axonal loss is a substrate of MRI-detected atrophy. Neuroimage 2006;31 (1) 286- 293
PubMed
Pulicken  MGordon-Lipkin  EBalcer  LJFrohman  ECutter  GCalabresi  PA Optical coherence tomography and disease subtype in multiple sclerosis. Neurology 2007;69 (22) 2085- 2092
PubMed
Sergott  RC Optical coherence tomography: measuring in-vivo axonal survival and neuroprotection in multiple sclerosis and optic neuritis. Curr Opin Ophthalmol 2005;16 (6) 346- 350
PubMed
Koozekanani  DRoberts  CKatz  SEHerderick  EE Intersession repeatability of macular thickness measurements with the Humphrey 2000 OCT. Invest Ophthalmol Vis Sci 2000;41 (6) 1486- 1491
PubMed
Schuman  JSPedut-Kloizman  THertzmark  E  et al.  Reproducibility of nerve fiber layer thickness measurements using optical coherence tomography. Ophthalmology 1996;103 (11) 1889- 1898
PubMed
Massin  PVicaut  EHaouchine  BErginay  APaques  MGaudric  A Reproducibility of retinal mapping using optical coherence tomography. Arch Ophthalmol 2001;119 (8) 1135- 1142
PubMed
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