Optimal Intereye Difference Thresholds in Retinal Nerve Fiber Layer Thickness for Predicting a Unilateral Optic Nerve Lesion in Multiple Sclerosis

Rachel C. Nolan, Steven L. Galetta, Teresa C. Frohman, Elliot M. Frohman, Peter Calabresi, Carmen Castrillo-Viguera, Diego Cadavid, Laura J. Balcer

Research output: Contribution to journalArticle

Abstract

BACKGROUND: The optic nerve is a frequent site for involvement in multiple sclerosis (MS). Optical coherence tomography (OCT) detects thinning of the retinal nerve fiber layer (RNFL) in eyes of patients with MS and in those meeting criteria for clinically or radiologically isolated demyelinating syndromes. Current international diagnostic criteria for MS do not include the optic nerve as an imaging lesion site despite the high prevalence of acute optic neuritis (ON), or occult optic neuropathy, among early MS and clinically isolated syndrome patients; as well as most MS patients over the course of the disease. We sought to determine optimal thresholds for intereye difference in peripapillary RNFL thickness that are most predictive of a unilateral optic nerve lesion. METHODS: We analyzed spectral domain OCT data of 31 healthy volunteers and 124 patients with MS at a single center as part of an ongoing collaborative investigation of visual outcomes. Intereye differences in peripapillary (360°) RNFL thickness were calculated as the absolute value of the difference. First, we determined the 95th percentile value of intereye difference for the healthy volunteers. This value was applied to the convenience sample group of MS patients as a validation cohort determining how well this threshold could distinguish patients with vs without a history of unilateral ON. The relation of intereye differences in peripapillary RNFL thickness to binocular low-contrast letter acuity scores was also examined. RESULTS: Among healthy volunteer participants (n = 31), the 95th percentile value for intereye difference (upper boundary of expected for normal controls) was 6.0 μm. This value was applied to the convenience sample group of MS patients (n = 124, validation cohort). Positive predictive value, negative predictive value, sensitivity, and specificity for identifying MS patients with a history of unilateral ON were calculated for the 6-μm threshold value in a 2 × 2 table analysis with the application of χ tests (P < 0.0001). The 6-μm threshold was predictive of worse binocular low-contrast acuity scores at 2.5% (P = 0.03) and 1.25% (P = 0.002 by linear regression analyses). A receiver operating characteristic curve analysis demonstrated an optimal intereye difference threshold of 5 μm for identifying unilateral ON in the MS cohort. CONCLUSIONS: An intereye difference of 5-6 μm in RNFL thickness is a robust structural threshold for identifying the presence of a unilateral optic nerve lesion in MS.

Original languageEnglish (US)
Pages (from-to)451-458
Number of pages8
JournalJournal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society
Volume38
Issue number4
DOIs
StatePublished - Dec 1 2018

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Optic Nerve
Nerve Fibers
Multiple Sclerosis
Optic Neuritis
Healthy Volunteers
Optical Coherence Tomography
Optic Nerve Diseases
ROC Curve
Linear Models
Regression Analysis
Sensitivity and Specificity

ASJC Scopus subject areas

  • Ophthalmology
  • Clinical Neurology

Cite this

Optimal Intereye Difference Thresholds in Retinal Nerve Fiber Layer Thickness for Predicting a Unilateral Optic Nerve Lesion in Multiple Sclerosis. / Nolan, Rachel C.; Galetta, Steven L.; Frohman, Teresa C.; Frohman, Elliot M.; Calabresi, Peter; Castrillo-Viguera, Carmen; Cadavid, Diego; Balcer, Laura J.

In: Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society, Vol. 38, No. 4, 01.12.2018, p. 451-458.

Research output: Contribution to journalArticle

Nolan, Rachel C. ; Galetta, Steven L. ; Frohman, Teresa C. ; Frohman, Elliot M. ; Calabresi, Peter ; Castrillo-Viguera, Carmen ; Cadavid, Diego ; Balcer, Laura J. / Optimal Intereye Difference Thresholds in Retinal Nerve Fiber Layer Thickness for Predicting a Unilateral Optic Nerve Lesion in Multiple Sclerosis. In: Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society. 2018 ; Vol. 38, No. 4. pp. 451-458.
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abstract = "BACKGROUND: The optic nerve is a frequent site for involvement in multiple sclerosis (MS). Optical coherence tomography (OCT) detects thinning of the retinal nerve fiber layer (RNFL) in eyes of patients with MS and in those meeting criteria for clinically or radiologically isolated demyelinating syndromes. Current international diagnostic criteria for MS do not include the optic nerve as an imaging lesion site despite the high prevalence of acute optic neuritis (ON), or occult optic neuropathy, among early MS and clinically isolated syndrome patients; as well as most MS patients over the course of the disease. We sought to determine optimal thresholds for intereye difference in peripapillary RNFL thickness that are most predictive of a unilateral optic nerve lesion. METHODS: We analyzed spectral domain OCT data of 31 healthy volunteers and 124 patients with MS at a single center as part of an ongoing collaborative investigation of visual outcomes. Intereye differences in peripapillary (360°) RNFL thickness were calculated as the absolute value of the difference. First, we determined the 95th percentile value of intereye difference for the healthy volunteers. This value was applied to the convenience sample group of MS patients as a validation cohort determining how well this threshold could distinguish patients with vs without a history of unilateral ON. The relation of intereye differences in peripapillary RNFL thickness to binocular low-contrast letter acuity scores was also examined. RESULTS: Among healthy volunteer participants (n = 31), the 95th percentile value for intereye difference (upper boundary of expected for normal controls) was 6.0 μm. This value was applied to the convenience sample group of MS patients (n = 124, validation cohort). Positive predictive value, negative predictive value, sensitivity, and specificity for identifying MS patients with a history of unilateral ON were calculated for the 6-μm threshold value in a 2 × 2 table analysis with the application of χ tests (P < 0.0001). The 6-μm threshold was predictive of worse binocular low-contrast acuity scores at 2.5{\%} (P = 0.03) and 1.25{\%} (P = 0.002 by linear regression analyses). A receiver operating characteristic curve analysis demonstrated an optimal intereye difference threshold of 5 μm for identifying unilateral ON in the MS cohort. CONCLUSIONS: An intereye difference of 5-6 μm in RNFL thickness is a robust structural threshold for identifying the presence of a unilateral optic nerve lesion in MS.",
author = "Nolan, {Rachel C.} and Galetta, {Steven L.} and Frohman, {Teresa C.} and Frohman, {Elliot M.} and Peter Calabresi and Carmen Castrillo-Viguera and Diego Cadavid and Balcer, {Laura J.}",
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AU - Nolan, Rachel C.

AU - Galetta, Steven L.

AU - Frohman, Teresa C.

AU - Frohman, Elliot M.

AU - Calabresi, Peter

AU - Castrillo-Viguera, Carmen

AU - Cadavid, Diego

AU - Balcer, Laura J.

PY - 2018/12/1

Y1 - 2018/12/1

N2 - BACKGROUND: The optic nerve is a frequent site for involvement in multiple sclerosis (MS). Optical coherence tomography (OCT) detects thinning of the retinal nerve fiber layer (RNFL) in eyes of patients with MS and in those meeting criteria for clinically or radiologically isolated demyelinating syndromes. Current international diagnostic criteria for MS do not include the optic nerve as an imaging lesion site despite the high prevalence of acute optic neuritis (ON), or occult optic neuropathy, among early MS and clinically isolated syndrome patients; as well as most MS patients over the course of the disease. We sought to determine optimal thresholds for intereye difference in peripapillary RNFL thickness that are most predictive of a unilateral optic nerve lesion. METHODS: We analyzed spectral domain OCT data of 31 healthy volunteers and 124 patients with MS at a single center as part of an ongoing collaborative investigation of visual outcomes. Intereye differences in peripapillary (360°) RNFL thickness were calculated as the absolute value of the difference. First, we determined the 95th percentile value of intereye difference for the healthy volunteers. This value was applied to the convenience sample group of MS patients as a validation cohort determining how well this threshold could distinguish patients with vs without a history of unilateral ON. The relation of intereye differences in peripapillary RNFL thickness to binocular low-contrast letter acuity scores was also examined. RESULTS: Among healthy volunteer participants (n = 31), the 95th percentile value for intereye difference (upper boundary of expected for normal controls) was 6.0 μm. This value was applied to the convenience sample group of MS patients (n = 124, validation cohort). Positive predictive value, negative predictive value, sensitivity, and specificity for identifying MS patients with a history of unilateral ON were calculated for the 6-μm threshold value in a 2 × 2 table analysis with the application of χ tests (P < 0.0001). The 6-μm threshold was predictive of worse binocular low-contrast acuity scores at 2.5% (P = 0.03) and 1.25% (P = 0.002 by linear regression analyses). A receiver operating characteristic curve analysis demonstrated an optimal intereye difference threshold of 5 μm for identifying unilateral ON in the MS cohort. CONCLUSIONS: An intereye difference of 5-6 μm in RNFL thickness is a robust structural threshold for identifying the presence of a unilateral optic nerve lesion in MS.

AB - BACKGROUND: The optic nerve is a frequent site for involvement in multiple sclerosis (MS). Optical coherence tomography (OCT) detects thinning of the retinal nerve fiber layer (RNFL) in eyes of patients with MS and in those meeting criteria for clinically or radiologically isolated demyelinating syndromes. Current international diagnostic criteria for MS do not include the optic nerve as an imaging lesion site despite the high prevalence of acute optic neuritis (ON), or occult optic neuropathy, among early MS and clinically isolated syndrome patients; as well as most MS patients over the course of the disease. We sought to determine optimal thresholds for intereye difference in peripapillary RNFL thickness that are most predictive of a unilateral optic nerve lesion. METHODS: We analyzed spectral domain OCT data of 31 healthy volunteers and 124 patients with MS at a single center as part of an ongoing collaborative investigation of visual outcomes. Intereye differences in peripapillary (360°) RNFL thickness were calculated as the absolute value of the difference. First, we determined the 95th percentile value of intereye difference for the healthy volunteers. This value was applied to the convenience sample group of MS patients as a validation cohort determining how well this threshold could distinguish patients with vs without a history of unilateral ON. The relation of intereye differences in peripapillary RNFL thickness to binocular low-contrast letter acuity scores was also examined. RESULTS: Among healthy volunteer participants (n = 31), the 95th percentile value for intereye difference (upper boundary of expected for normal controls) was 6.0 μm. This value was applied to the convenience sample group of MS patients (n = 124, validation cohort). Positive predictive value, negative predictive value, sensitivity, and specificity for identifying MS patients with a history of unilateral ON were calculated for the 6-μm threshold value in a 2 × 2 table analysis with the application of χ tests (P < 0.0001). The 6-μm threshold was predictive of worse binocular low-contrast acuity scores at 2.5% (P = 0.03) and 1.25% (P = 0.002 by linear regression analyses). A receiver operating characteristic curve analysis demonstrated an optimal intereye difference threshold of 5 μm for identifying unilateral ON in the MS cohort. CONCLUSIONS: An intereye difference of 5-6 μm in RNFL thickness is a robust structural threshold for identifying the presence of a unilateral optic nerve lesion in MS.

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