JNNP Online First, published on February 10, 2015 as 10.1136/jnnp-2014-309704 Multiple sclerosis
RESEARCH PAPER
The temporal evolution of structural and functional measures after acute optic neuritis Fiona Costello,1,2,3 Y Irene Pan,4 E Ann Yeh,5 William Hodge,4 Jodie M Burton,1,3,6 Randy Kardon7 ▸ Additional material is published online only. To view please visit the journal online (http://dx.doi.org/10.1136/ jnnp-2014-309704). 1
Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada 2 Department of Surgery, University of Calgary, Calgary, Alberta, Canada 3 Hotchkiss Brain Institute, Calgary, Alberta, Canada 4 Department of Ophthalmology, University of Western Ontario, London, Ontario, Canada 5 Division of Neurology, Hospital for Sick Children, Department of Pediatrics (Neurology), University of Toronto, Division of Neurosciences and Mental Health, SickKids Research Institute 6 Department of Community Health, University of Calgary, Calgary, Alberta, Canada 7 Department of Ophthalmology and Visual Science, University of Iowa, Department of Veterans Affairs Medical Center, Iowa City Correspondence to Dr Fiona Costello, Department of Clinical Neurosciences, University of Calgary, Health Sciences Centre, Foothills Medical Centre, Area 4, 3350 —Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1; Fiona.Costello@ albertahealthservices.ca Received 16 October 2014 Accepted 29 December 2014
To cite: Costello F, Pan YI, Yeh EA, et al. J Neurol Neurosurg Psychiatry Published Online First: [please include Day Month Year] doi:10.1136/jnnp2014-309704
ABSTRACT Background In this prospective case series, we aimed to characterise the temporal evolution of functional and structural measures in the afferent visual pathway of patients with acute optic neuritis (ON). Methods Fifty patients with ON were followed over 12 months. Testing with spectral-domain optical coherence tomography, Early Treatment Diabetic Retinopathy Study logarithm of the minimum angle of resolution (LogMAR) visual acuity and Humphrey perimetry central 30-2 threshold (SITA strategy) was performed at baseline, 3, 6 and 12 months after symptom onset. The main outcome measure was mean peripapillary retinal nerve fibre layer (RNFL) thickness in ON eyes. Secondary outcomes included mean ganglion cell layer (GCL) thickness, LogMAR visual acuity, and Humphrey perimetry measured visual field mean deviation (VFMD). Survival analyses were performed to Kaplan-Meier curves and variables in the models were tested using the log-rank test. Results Over 12 months, RNFL and GCL values progressively declined in ON eyes, and intereye differences were significantly different across all time points. When functional recovery was defined as a VFMD better than −5.00 dB in ON eyes, the mean recovery time for the entire cohort was 3 months (survival was 48%, SE=0.09, 95% CI 0.30 to 0.64). There were significant differences in cumulative recovery when comparisons were made between genders: 3 months after symptom onset there was a higher percentage cumulative recovery for female (75%) versus male (25%) patients. Conclusions Structural and functional measures evolve over time in patients with ON. There may be sex-specific differences in recovery after an acute ON event.
INTRODUCTION Optic neuritis (ON) is a relatively common acquired cause of vision loss in young adults, affecting 1–5 individuals per 100 000 per year.1 The majority of ON cases are due to inflammatory demyelination, which can arise as a sporadic event, or in the setting of multiple sclerosis (MS).1–3 The natural history of typical ON has long been considered favourable, such that standardised tests of vision improve spontaneously over weeks.4 5 Yet, many patients with ON report persistent visual problems in the postacute phase including Uhthoff ’s phenomenon (worsening vision with increased body temperature), loss of contrast sensitivity, fatigue-related variability, and
impaired motion perception.1 2 6–9 Several potential pathobiological substrates have been proposed to account for visual impairment post-ON including: demyelination with suboptimal repair in the retrobulbar optic nerve, neuronal loss affecting the retinal ganglion cells, axonal injury manifesting as retinal nerve fibre layer (RNFL) thinning, or a combination of the same. Accordingly, recovery has been attributed to remyelination, development of continuous conduction through sodium channels along the demyelinated optic nerve segment and/or cortical plasticity.10 Failure with respect to any of these reparative processes could cause neuroaxonal damage in the afferent visual pathway, resulting in functional impairment post-ON.10 11 The optic nerve, when studied experimentally and clinically, represents a ‘window’ through which mechanisms of symptom onset and recovery applicable to demyelination elsewhere in the central nervous system may be explored in patients with MS.10–12 In the modern ocular imaging era, spectral-domain optical coherence tomography (SD-OCT) enables indirect quantification of neuronal (ganglion cell layer (GCL) thickness) and axonal ( peripapillary RNFL thickness) integrity in the afferent visual pathway.11 By using SD-OCT, we can capture in vivo, structural changes in RNFL and GCL thickness of the retina, which arise from retrograde axonal degeneration caused by an optic nerve injury.11 Previous time-domain OCT studies have shown that RNFL values progressively decline for up to 1 year after ON.13–18 Extensive RNFL loss has been associated with poorer functional outcomes, including worse high-contrast and lowcontrast letter acuity scores,9 11 13–19 colour vision deficits,19 20 and reduced visual field sensitivity15 16 19 in ON eyes. Yet, little is known about the longitudinal changes in SD-OCT measurements after acute ON because most of the published reports to date have been cross-sectional in design and/or have included very small patient populations.18 Prospective data in larger patient populations are needed. In the current study, we aimed to characterise the temporal evolution of functional and structural measures of afferent visual pathway integrity arising from acute ON. As a secondary objective, we used survival analyses to provide Kaplan-Meier estimates regarding the proportion of patients that achieved defined end points for recovery. We also explored whether patient characteristics including age, disease subtype, or gender affected the proportion of patients that attained recovery post-ON.
Costello F, et al. J Neurol Neurosurg Psychiatry 2015;0:1–5. doi:10.1136/jnnp-2014-309704
Copyright Article author (or their employer) 2015. Produced by BMJ Publishing Group Ltd under licence.
1
Multiple sclerosis
This prospective case series included consecutive patients with ON evaluated in the Neuro-Ophthalmology Clinic at the University of Calgary between 2010 and 2013. Institutional Review Board/Ethics Committee approval was obtained. Participants provided informed written consent.
the Macular Cube 200×200 scan. The Ganglion Layer Analysis software was used to evaluate the mean and minimum thickness of the combined GCL and inner plexiform layers (referred to as GCL thickness in this study). All OCT imaging was performed by certified ophthalmic technicians. Only studies with good fixation, a circular scan centred on the nerve head, and a signal strength ≥7 (of a possible 10) were included.
Patient population
Outcome measures
Inclusion criteria: Patients with a first clinical presentation of unilateral ON who underwent clinical evaluation within 1 month of symptom onset were included in the study. Criteria for the diagnosis of ON included: decreased visual acuity (VA), a visual field defect consistent with the diagnosis of ON, colour vision loss, a relative afferent pupil defect, and a compatible fundus examination in the ON eye. Exclusion criteria: Patients with other causes of vision loss in the ON eye, a refractive error of greater than ±6 dioptres, or those who could not participate in OCT testing were excluded. Patients with a history of relapsing–remitting MS (RRMS)21 22 were not excluded from the study, but patients with MS could not have a history of prior optic nerve injury in the ON eye. Patients underwent baseline investigations to check for potential mimics for ON (see online supplementary material), which also served as a basis for exclusion.
The main outcome measure was mean RNFL thickness in microns (mm) at baseline and at all follow-up time points. Secondary outcomes included structural measures (eg, mean GCL thickness) and functional changes (eg, foveal threshold, LogMAR VA and VFMD) from baseline to each follow-up time point. Time to recovery was measured with time-to-event analysis as defined in the Statistical Analyses. We used Kaplan-Meier estimates of survival analyses to determine the proportion of patients who achieved recovery end points by comparing age groups (20–29, 30–39, 40–49, and greater than 50 years), MS subtype (clinically isolated syndrome (CIS) vs RRMS), and genders (female vs male patients with ON).
METHODS Study design
Clinical assessment Participants underwent visual testing 1, 3, 6 and 12 months after initial presentation, as per the preplanned protocol of the study (FC, JMB, WH). Best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) high-contrast VA equivalent was expressed as the logarithm of the minimum angle of resolution (LogMAR VA).23 Visual field mean deviation (VFMD) and foveal threshold (measured in decibels (dB)) were determined with Humphrey perimetry (Carl Zeiss Meditec, Dublin, California, USA), using the Central 30-2 Threshold (SITA strategy). Visual field test results were used if the false-positive and false-negative errors measured less than 33% and fixation losses measured less than 20%.
Optical coherence tomography Retinal imaging was performed with Cirrus HD-OCT (model 4000, software V.6.0; Carl Zeiss Meditec). Peripapillary RNFL thickness measures were obtained using the Optic Disc 200×200 protocol. Macular assessments were performed with
Table 1 Patient demographics and clinical characteristics
Mean age (years) (SD) Sex Mean disease duration (months) (SD) Median (months) Minimum (months) Maximum (months) Patients with RRMS Number treated with DMT Number treated with corticosteroids Number with MRI lesions at baseline
Total
Female
Male
35.9 (8.6)
35.7 (8.9) 42 28.9 (34.5) 12 6 180 15 (36%) 5 (12%) 11 (26%) 36 (86%)
37.4 (7.2) 8 28.9 (30.1) 12 3 180 4 (50%) 1 (13%) 3 (38%) 5 (63%)
28.9 (33.5) 12 3 180 19 (38%) 6 (12%) 14 (28%) 41 (82%)
Disease duration, time from the diagnosis of multiple sclerosis measured in months (n=19 patients); DMT, disease-modifying therapy; MRI, MRI lesions as defined per the CHAMPS study24; RRMS, relapsing–remitting multiple sclerosis.21 22
2
Statistical analyses Descriptive summary statistics were generated to describe variables. Continuous variables were summarised using mean with SD or median with range if the continuous variables displayed a non-Gaussian distribution. Significance of skewness and kurtosis were checked for each study variable’s distribution. Student t test was used to determine significance of difference in the change of structural measures from baseline to different follow-up points. Multiple regression models were used to analyse predictors of change in measures of structure and function with selected clinical characteristics adjusted including: age, sex, disease duration, disease-modifying drug use and acute treatment with high-dose corticosteroids. Survival analyses were performed to Kaplan-Meier curves and variables in the models were tested using the log-rank test. For the purpose of the survival analysis, successful recovery in ON eyes was defined as (1) functional: a VFMD better than −5.00 dB or (2) structural: a mean RNFL thickness greater than 72 mm. Previous time-domain OCT studies have shown an RNFL decrement of approximately 20% after ON.13 15 Therefore, we defined ‘structural recovery’ as an RNFL thickness equal to or greater than 80% of that of measured in the non-optic neuritis (NON) eyes of our patients at baseline (90.3 mm×0.80=72 mm). All data analysis was performed using STATAV.9.02 (College Station, StataCorp, Texas, USA) (YIP, WH, EAY, RK), and level of significance was set at 0.05.
RESULTS Patient demographics and clinical characteristics The patient demographics and clinical features at presentation are included in table 1. Fifty (n=50) patients with ON were included in the study. The majority of patients (84%) were women with a mean age of 36 years. Thirty-eight per cent (n=19) of patients carried the diagnosis of RRMS.21 22 The mean and median time to OCT testing in ON eyes from symptom onset were: 18 and 17 days, respectively (SD=7.4; minimum=3 days; maximum=30 days).
Structural changes after ON OCT testing was performed at 1 (n=46), 3 (n=42), 6 (n=46) and 12 months (n=49; table 2). Mean peripapillary RNFL measures were initially elevated in ON eyes (111.3 mm) relative to NON eyes (90.3 mm) reflecting mild optic disc oedema at the Costello F, et al. J Neurol Neurosurg Psychiatry 2015;0:1–5. doi:10.1136/jnnp-2014-309704
Multiple sclerosis Table 2 Serial changes in optical coherence tomography measurements and visual function measures in ON eyes and non-affected (NON) eyes of patients with ON Structural
Functional
mRNFL
tRNFL
mGCL
MV
FT
LogMAR BCVA
VFMD
Time
ON
NON
ON
NON
ON
NON
ON
NON
ON
NON
ON
NON
ON
NON
1
111.3 39.7 84.9 16.5 79.2 14.9 75.3 13.7
90.3 14.9 90.1 13.8 90.5 14.3 90.4 14.3
64.5 19.3 54.6 13.1 50.5 13.1 47.4 12.4
61.8 12.4 62.8 15.4 63.3 15.5 63.5 16.3
73.4 7.9 67.0 8.4 66.5 9.0 64.6 9.0
77.0 8.6 77.2 9.2 77.7 9.6 77.9 9.4
10.0 0.5 9.8 0.5 9.6 0.5 9.5 0.5
9.9 0.5 10.0 0.6 10.0 0.5 10.0 0.5
25.4 12.1 32.1 7.8 35.0 2.7 34.2 7.8
36.3 1.8 36.9 2.0 37.6 1.9 37.2 1.6
−12.5 10.7 −4.9 6.8 −2.9 3.8 −3.0 5.6
−1.8 1.9 −1.3 1.3 −1.2 1.4 −0.6 1.4
1.2 1.7 0.3 0.9 0.04 0.1 0.09 0.3
0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0
3 6 12
Mean SD Mean SD Mean SD Mean SD
BCVA, best-corrected visual acuity; FT, foveal threshold measured in decibels (dB); LogMAR BCVA, logarithm of the minimum angle of resolution best-corrected Early Treatment Diabetic Retinopathy Study high-contrast letter acuity; mGCL, mean ganglion cell layer thickness measured in mm; mGCL, minimum ganglion cell layer thickness measured in mm; mRNFL, mean retinal nerve fibre layer thickness measured in microns (mm); MV, macular volume measured in mm3; ON, optic neuritis; Time, time from symptom onset measured in months; tRNFL, temporal RNFL thickness measured in mm; VFMD, visual field mean deviation measured in dB.
time of the acute event. Over the 12-month follow-up period, RNFL (and GCL) values decreased significantly ( p
RESEARCH PAPER
The temporal evolution of structural and functional measures after acute optic neuritis Fiona Costello,1,2,3 Y Irene Pan,4 E Ann Yeh,5 William Hodge,4 Jodie M Burton,1,3,6 Randy Kardon7 ▸ Additional material is published online only. To view please visit the journal online (http://dx.doi.org/10.1136/ jnnp-2014-309704). 1
Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada 2 Department of Surgery, University of Calgary, Calgary, Alberta, Canada 3 Hotchkiss Brain Institute, Calgary, Alberta, Canada 4 Department of Ophthalmology, University of Western Ontario, London, Ontario, Canada 5 Division of Neurology, Hospital for Sick Children, Department of Pediatrics (Neurology), University of Toronto, Division of Neurosciences and Mental Health, SickKids Research Institute 6 Department of Community Health, University of Calgary, Calgary, Alberta, Canada 7 Department of Ophthalmology and Visual Science, University of Iowa, Department of Veterans Affairs Medical Center, Iowa City Correspondence to Dr Fiona Costello, Department of Clinical Neurosciences, University of Calgary, Health Sciences Centre, Foothills Medical Centre, Area 4, 3350 —Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1; Fiona.Costello@ albertahealthservices.ca Received 16 October 2014 Accepted 29 December 2014
To cite: Costello F, Pan YI, Yeh EA, et al. J Neurol Neurosurg Psychiatry Published Online First: [please include Day Month Year] doi:10.1136/jnnp2014-309704
ABSTRACT Background In this prospective case series, we aimed to characterise the temporal evolution of functional and structural measures in the afferent visual pathway of patients with acute optic neuritis (ON). Methods Fifty patients with ON were followed over 12 months. Testing with spectral-domain optical coherence tomography, Early Treatment Diabetic Retinopathy Study logarithm of the minimum angle of resolution (LogMAR) visual acuity and Humphrey perimetry central 30-2 threshold (SITA strategy) was performed at baseline, 3, 6 and 12 months after symptom onset. The main outcome measure was mean peripapillary retinal nerve fibre layer (RNFL) thickness in ON eyes. Secondary outcomes included mean ganglion cell layer (GCL) thickness, LogMAR visual acuity, and Humphrey perimetry measured visual field mean deviation (VFMD). Survival analyses were performed to Kaplan-Meier curves and variables in the models were tested using the log-rank test. Results Over 12 months, RNFL and GCL values progressively declined in ON eyes, and intereye differences were significantly different across all time points. When functional recovery was defined as a VFMD better than −5.00 dB in ON eyes, the mean recovery time for the entire cohort was 3 months (survival was 48%, SE=0.09, 95% CI 0.30 to 0.64). There were significant differences in cumulative recovery when comparisons were made between genders: 3 months after symptom onset there was a higher percentage cumulative recovery for female (75%) versus male (25%) patients. Conclusions Structural and functional measures evolve over time in patients with ON. There may be sex-specific differences in recovery after an acute ON event.
INTRODUCTION Optic neuritis (ON) is a relatively common acquired cause of vision loss in young adults, affecting 1–5 individuals per 100 000 per year.1 The majority of ON cases are due to inflammatory demyelination, which can arise as a sporadic event, or in the setting of multiple sclerosis (MS).1–3 The natural history of typical ON has long been considered favourable, such that standardised tests of vision improve spontaneously over weeks.4 5 Yet, many patients with ON report persistent visual problems in the postacute phase including Uhthoff ’s phenomenon (worsening vision with increased body temperature), loss of contrast sensitivity, fatigue-related variability, and
impaired motion perception.1 2 6–9 Several potential pathobiological substrates have been proposed to account for visual impairment post-ON including: demyelination with suboptimal repair in the retrobulbar optic nerve, neuronal loss affecting the retinal ganglion cells, axonal injury manifesting as retinal nerve fibre layer (RNFL) thinning, or a combination of the same. Accordingly, recovery has been attributed to remyelination, development of continuous conduction through sodium channels along the demyelinated optic nerve segment and/or cortical plasticity.10 Failure with respect to any of these reparative processes could cause neuroaxonal damage in the afferent visual pathway, resulting in functional impairment post-ON.10 11 The optic nerve, when studied experimentally and clinically, represents a ‘window’ through which mechanisms of symptom onset and recovery applicable to demyelination elsewhere in the central nervous system may be explored in patients with MS.10–12 In the modern ocular imaging era, spectral-domain optical coherence tomography (SD-OCT) enables indirect quantification of neuronal (ganglion cell layer (GCL) thickness) and axonal ( peripapillary RNFL thickness) integrity in the afferent visual pathway.11 By using SD-OCT, we can capture in vivo, structural changes in RNFL and GCL thickness of the retina, which arise from retrograde axonal degeneration caused by an optic nerve injury.11 Previous time-domain OCT studies have shown that RNFL values progressively decline for up to 1 year after ON.13–18 Extensive RNFL loss has been associated with poorer functional outcomes, including worse high-contrast and lowcontrast letter acuity scores,9 11 13–19 colour vision deficits,19 20 and reduced visual field sensitivity15 16 19 in ON eyes. Yet, little is known about the longitudinal changes in SD-OCT measurements after acute ON because most of the published reports to date have been cross-sectional in design and/or have included very small patient populations.18 Prospective data in larger patient populations are needed. In the current study, we aimed to characterise the temporal evolution of functional and structural measures of afferent visual pathway integrity arising from acute ON. As a secondary objective, we used survival analyses to provide Kaplan-Meier estimates regarding the proportion of patients that achieved defined end points for recovery. We also explored whether patient characteristics including age, disease subtype, or gender affected the proportion of patients that attained recovery post-ON.
Costello F, et al. J Neurol Neurosurg Psychiatry 2015;0:1–5. doi:10.1136/jnnp-2014-309704
Copyright Article author (or their employer) 2015. Produced by BMJ Publishing Group Ltd under licence.
1
Multiple sclerosis
This prospective case series included consecutive patients with ON evaluated in the Neuro-Ophthalmology Clinic at the University of Calgary between 2010 and 2013. Institutional Review Board/Ethics Committee approval was obtained. Participants provided informed written consent.
the Macular Cube 200×200 scan. The Ganglion Layer Analysis software was used to evaluate the mean and minimum thickness of the combined GCL and inner plexiform layers (referred to as GCL thickness in this study). All OCT imaging was performed by certified ophthalmic technicians. Only studies with good fixation, a circular scan centred on the nerve head, and a signal strength ≥7 (of a possible 10) were included.
Patient population
Outcome measures
Inclusion criteria: Patients with a first clinical presentation of unilateral ON who underwent clinical evaluation within 1 month of symptom onset were included in the study. Criteria for the diagnosis of ON included: decreased visual acuity (VA), a visual field defect consistent with the diagnosis of ON, colour vision loss, a relative afferent pupil defect, and a compatible fundus examination in the ON eye. Exclusion criteria: Patients with other causes of vision loss in the ON eye, a refractive error of greater than ±6 dioptres, or those who could not participate in OCT testing were excluded. Patients with a history of relapsing–remitting MS (RRMS)21 22 were not excluded from the study, but patients with MS could not have a history of prior optic nerve injury in the ON eye. Patients underwent baseline investigations to check for potential mimics for ON (see online supplementary material), which also served as a basis for exclusion.
The main outcome measure was mean RNFL thickness in microns (mm) at baseline and at all follow-up time points. Secondary outcomes included structural measures (eg, mean GCL thickness) and functional changes (eg, foveal threshold, LogMAR VA and VFMD) from baseline to each follow-up time point. Time to recovery was measured with time-to-event analysis as defined in the Statistical Analyses. We used Kaplan-Meier estimates of survival analyses to determine the proportion of patients who achieved recovery end points by comparing age groups (20–29, 30–39, 40–49, and greater than 50 years), MS subtype (clinically isolated syndrome (CIS) vs RRMS), and genders (female vs male patients with ON).
METHODS Study design
Clinical assessment Participants underwent visual testing 1, 3, 6 and 12 months after initial presentation, as per the preplanned protocol of the study (FC, JMB, WH). Best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) high-contrast VA equivalent was expressed as the logarithm of the minimum angle of resolution (LogMAR VA).23 Visual field mean deviation (VFMD) and foveal threshold (measured in decibels (dB)) were determined with Humphrey perimetry (Carl Zeiss Meditec, Dublin, California, USA), using the Central 30-2 Threshold (SITA strategy). Visual field test results were used if the false-positive and false-negative errors measured less than 33% and fixation losses measured less than 20%.
Optical coherence tomography Retinal imaging was performed with Cirrus HD-OCT (model 4000, software V.6.0; Carl Zeiss Meditec). Peripapillary RNFL thickness measures were obtained using the Optic Disc 200×200 protocol. Macular assessments were performed with
Table 1 Patient demographics and clinical characteristics
Mean age (years) (SD) Sex Mean disease duration (months) (SD) Median (months) Minimum (months) Maximum (months) Patients with RRMS Number treated with DMT Number treated with corticosteroids Number with MRI lesions at baseline
Total
Female
Male
35.9 (8.6)
35.7 (8.9) 42 28.9 (34.5) 12 6 180 15 (36%) 5 (12%) 11 (26%) 36 (86%)
37.4 (7.2) 8 28.9 (30.1) 12 3 180 4 (50%) 1 (13%) 3 (38%) 5 (63%)
28.9 (33.5) 12 3 180 19 (38%) 6 (12%) 14 (28%) 41 (82%)
Disease duration, time from the diagnosis of multiple sclerosis measured in months (n=19 patients); DMT, disease-modifying therapy; MRI, MRI lesions as defined per the CHAMPS study24; RRMS, relapsing–remitting multiple sclerosis.21 22
2
Statistical analyses Descriptive summary statistics were generated to describe variables. Continuous variables were summarised using mean with SD or median with range if the continuous variables displayed a non-Gaussian distribution. Significance of skewness and kurtosis were checked for each study variable’s distribution. Student t test was used to determine significance of difference in the change of structural measures from baseline to different follow-up points. Multiple regression models were used to analyse predictors of change in measures of structure and function with selected clinical characteristics adjusted including: age, sex, disease duration, disease-modifying drug use and acute treatment with high-dose corticosteroids. Survival analyses were performed to Kaplan-Meier curves and variables in the models were tested using the log-rank test. For the purpose of the survival analysis, successful recovery in ON eyes was defined as (1) functional: a VFMD better than −5.00 dB or (2) structural: a mean RNFL thickness greater than 72 mm. Previous time-domain OCT studies have shown an RNFL decrement of approximately 20% after ON.13 15 Therefore, we defined ‘structural recovery’ as an RNFL thickness equal to or greater than 80% of that of measured in the non-optic neuritis (NON) eyes of our patients at baseline (90.3 mm×0.80=72 mm). All data analysis was performed using STATAV.9.02 (College Station, StataCorp, Texas, USA) (YIP, WH, EAY, RK), and level of significance was set at 0.05.
RESULTS Patient demographics and clinical characteristics The patient demographics and clinical features at presentation are included in table 1. Fifty (n=50) patients with ON were included in the study. The majority of patients (84%) were women with a mean age of 36 years. Thirty-eight per cent (n=19) of patients carried the diagnosis of RRMS.21 22 The mean and median time to OCT testing in ON eyes from symptom onset were: 18 and 17 days, respectively (SD=7.4; minimum=3 days; maximum=30 days).
Structural changes after ON OCT testing was performed at 1 (n=46), 3 (n=42), 6 (n=46) and 12 months (n=49; table 2). Mean peripapillary RNFL measures were initially elevated in ON eyes (111.3 mm) relative to NON eyes (90.3 mm) reflecting mild optic disc oedema at the Costello F, et al. J Neurol Neurosurg Psychiatry 2015;0:1–5. doi:10.1136/jnnp-2014-309704
Multiple sclerosis Table 2 Serial changes in optical coherence tomography measurements and visual function measures in ON eyes and non-affected (NON) eyes of patients with ON Structural
Functional
mRNFL
tRNFL
mGCL
MV
FT
LogMAR BCVA
VFMD
Time
ON
NON
ON
NON
ON
NON
ON
NON
ON
NON
ON
NON
ON
NON
1
111.3 39.7 84.9 16.5 79.2 14.9 75.3 13.7
90.3 14.9 90.1 13.8 90.5 14.3 90.4 14.3
64.5 19.3 54.6 13.1 50.5 13.1 47.4 12.4
61.8 12.4 62.8 15.4 63.3 15.5 63.5 16.3
73.4 7.9 67.0 8.4 66.5 9.0 64.6 9.0
77.0 8.6 77.2 9.2 77.7 9.6 77.9 9.4
10.0 0.5 9.8 0.5 9.6 0.5 9.5 0.5
9.9 0.5 10.0 0.6 10.0 0.5 10.0 0.5
25.4 12.1 32.1 7.8 35.0 2.7 34.2 7.8
36.3 1.8 36.9 2.0 37.6 1.9 37.2 1.6
−12.5 10.7 −4.9 6.8 −2.9 3.8 −3.0 5.6
−1.8 1.9 −1.3 1.3 −1.2 1.4 −0.6 1.4
1.2 1.7 0.3 0.9 0.04 0.1 0.09 0.3
0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0
3 6 12
Mean SD Mean SD Mean SD Mean SD
BCVA, best-corrected visual acuity; FT, foveal threshold measured in decibels (dB); LogMAR BCVA, logarithm of the minimum angle of resolution best-corrected Early Treatment Diabetic Retinopathy Study high-contrast letter acuity; mGCL, mean ganglion cell layer thickness measured in mm; mGCL, minimum ganglion cell layer thickness measured in mm; mRNFL, mean retinal nerve fibre layer thickness measured in microns (mm); MV, macular volume measured in mm3; ON, optic neuritis; Time, time from symptom onset measured in months; tRNFL, temporal RNFL thickness measured in mm; VFMD, visual field mean deviation measured in dB.
time of the acute event. Over the 12-month follow-up period, RNFL (and GCL) values decreased significantly ( p
