October 2008
Volume 49, Issue 10
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Eye Movements, Strabismus, Amblyopia and Neuro-ophthalmology  |   October 2008
Retinal Peripapillary Nerve Fiber Layer Thickness in Neuromyelitis Optica
Author Affiliations
  • Harold Merle
    From the Services d’Ophtalmologie et
  • Stéphane Olindo
    de Neurologie, Centre Hospitalier Universitaire de Fort de France, Hôpital Pierre Zobda-Quitman, Fort de France, Martinique, French West Indies.
  • Angélique Donnio
    From the Services d’Ophtalmologie et
  • Raymond Richer
    From the Services d’Ophtalmologie et
  • Didier Smadja
    de Neurologie, Centre Hospitalier Universitaire de Fort de France, Hôpital Pierre Zobda-Quitman, Fort de France, Martinique, French West Indies.
  • Philippe Cabre
    de Neurologie, Centre Hospitalier Universitaire de Fort de France, Hôpital Pierre Zobda-Quitman, Fort de France, Martinique, French West Indies.
Investigative Ophthalmology & Visual Science October 2008, Vol.49, 4412-4417. doi:10.1167/iovs.08-1815
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      Harold Merle, Stéphane Olindo, Angélique Donnio, Raymond Richer, Didier Smadja, Philippe Cabre; Retinal Peripapillary Nerve Fiber Layer Thickness in Neuromyelitis Optica. Invest. Ophthalmol. Vis. Sci. 2008;49(10):4412-4417. doi: 10.1167/iovs.08-1815.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

purpose. To measure the thickness of retinal peripapillary nerve fibers throughout the course of neuromyelitis optica (NMO).

methods. This study was of a cross-sectional design, examining the thickness of the retinal peripapillary nerve fiber layer by optical coherence tomography, in patients with NMO (n = 15; 30 eyes), patients with multiple sclerosis (MS; n = 15; 30 eyes), and a control group (n = 23; 46 eyes). The thicknesses were acquired according to protocol with the fast RNFL (Retinal Nerve Fiber Layer) procedure. The study of visual function includes for each eye a determination of refraction, measurement of visual acuity, measurement of contrast vision, an analysis of color vision, and a frequency-doubling technology perimetry (FDTP). The main outcome measurements were the thickness of the retinal peripapillary nerve fibers, visual acuity, and scores of contrast vision.

results. The average thickness of retinal peripapillary nerve fibers was respectively in the NMO, MS, and control group: 65.44 ± 24.19, 83.85 ± 24.12, and 106.24 ± 12.46 μm (P = 0.01). The average thickness of retinal peripapillary nerve fibers correlated to visual acuity, the scores of contrast vision, the scores of FDTP, and the number of episodes per patient (r = −0.58, P = 0.03).

conclusions. This is the first study to produce measurements of the thickness of retinal peripapillary nerve fibers during optic neuropathies of NMO. The optic neuropathies of NMO are also accompanied by an acute and chronic axonal loss, as clearly illustrated by the OCT.

Neuromyelitis optica (NMO) and multiple sclerosis (MS) are inflammatory, demyelinating diseases of the central nervous system. NMO is a rare condition that selectively attacks optic nerves and the spinal cord. 1 The evolution of NMO is remitting and severe, and in most cases, results in blindness, paraplegia, or quadriplegia. 2 3 The manifestations of MS are more heterogeneous, but close to 80% of patients experience visual problems of some sort during the course of the disease. 4 Representing an integral part of the handicap, the modification of visual function throughout the course of these neurologic diseases is only determined by visual acuity with the aid of the Snellen scale. Recently, the tests that explore the sensitivity of spatial contrast (Sloan and Pelli-Robson charts) or the sensitivity in temporal contrast (frequency doubling technology perimetry [FDTP]) brought to light a deficit in visual function that would go undetected by a simple measurement of visual acuity. 5 6 Although considered a primitively demyelinating disease, an axonal loss could precede, accompany, and represent a predictive factor of the progression of neurologic deficits observed throughout the course of NMO. 7 Imaging by nuclear magnetic resonance (MRI), currently used to highlight the zones of demyelination, established a connection between the axonal cerebral deficit and the progression of the handicap. 8 However, the MRI does not appear to be efficient when it comes to the axonal deficit of the optic nerve, as it cannot prove any initial atrophy of the optic nerve due to the absence of a sufficient resolution. In its most recent conception, tomography by optical coherence or OCT is a noninvasive technique that allows the measurement of the thickness of retinal peripapillary nerve fibers (retinal nerve fiber layer [RNFL]) that appear to lack myelin. OCT lends itself to a principal founded on the basis of interferometry. It uses an infrared laser of 800 μm. The resolution is in the range of 7 to 10 μm, and the measurements are reproducible. 9 After the Wallerian degeneration of the axons, the ganglionic cells or their axons are attacked, and the result is reflected by OCT as a reduction in the thickness of the RNFL. 10  
The goal of our study was to measure the thickness of retinal peripapillary nerve fibers throughout the course of NMO and to determine how visual function is affected. We compare our results with those obtained in a group of patients with MS and with those of a control group. 
Material and Methods
Our study was performed at the University Hospital Center of Fort de France, Martinique. All the patients in the study were of Afro-Caribbean origin (both parents). None of the patients had a history of familial, infectious, vascular, or compressive optic neuropathy, whether connected to general afflictions, toxicity, or deficiency. All the patients were seronegative for HIV and HTLV-1. The diagnosis of NMO was attained according to the diagnostic criterions proposed in 1999 by Wingerchuck et al. 11 and revised in 2006 12 (Table 1) . The revised criteria imply the presence of two absolute criterions, and of two or three major criterions. The absolute criterions are the existence of monoptical or bilateral optical neuritis and of an acute myelopathy. The major criterions are a normal MRI at the beginning of the disease, an extended hypersignal of more than three vertebral segments on the medullary MRI, and positive anti-NMO antibodies. 13 We retained 15 patients who satisfied both the absolute and major criterions. We excluded two female patients whose general health and visual acuity (reduced to a simple perception of light) would not permit them to participate in the tests. 
The diagnosis of acute myelitis was determined before the presence of a medullary impairment, including sensory or motor complications of the sphincter, with a maximum deficit occurring in less than 4 weeks. An ocular or medullary episode was defined as the appearance or the worsening of symptoms for at least 24 hours. Brief manifestations attributed to the Uhthoff phenomenon were not taken into account. A second episode occurred at least 1 month after the beginning of the preceding episode. 14 The overall handicap of the disease was determined by the Kürtzke scale, which spans from 0 to 10 (expanded disability status scale [EDSS]). 15 We calculated the index of the handicap’s progression as equal to the ratio EDSS/duration of the disease (in years). The visual handicap was determined by the Kürtzke scale (EDSS) with the visual function from 0 to 6. 15 The index of visual progression, equal to the ratio EDSS visual/duration of the disease (years) was calculated. Patients affected by MS (n = 15) satisfied the McDonald diagnostic criteria and presented with at least one episode of optic neuropathy. 16 The number of ganglionic cells and the thickness of the retinal peripapillary nerve fibers decreased with age. We paired each patient of the NMO group with a patient from the MS group, as well as with 1 or 2 control subjects, and matched according to age and sex. 17 Our control group was composed of 23 patients who had no medical history and were without ophthalmic or neurologic disease. No control patients showed refractive anomalies of more than 2 D. All the patients in the control group had a visual acuity of at least 20/20 in each eye. 
Characteristics of the disease history were obtained from our database in Martinique of patients afflicted with NMO and MS. The results were gathered in a prospective manner over a period of 20 years. For each patient, in addition to an examination targeting the ocular antecedents, a complete ophthalmic examination was conducted during a period of remission, or at least 6 months before the onset of an ocular episode. The test included a precise determination of the refraction. The visual acuity was measured with the Snellen scale. The optotypes were read at 5 m and represented by capital letters in increasing size, including 12 standards of acuity, going from 20/400 to 20/20. We also used the logarithmic scale of the Early Treatment Diabetic Retinopathy Study (ETDRS) chart, composed of black optotypes on a white background, with a contrast close to 100%. The ETDRS scale is made up of 14 lines of 5 letters, and is presented at 4 m. Each letter read corresponds to 1 point scored. The score is obtained by the total letters that are read correctly (0–70). As for sensitivity to spatial contrast, we used the Pelli-Robson and Sloan charts. 18 On the Pelli-Robson test, the letters are organized in groups of three triplets of different contrast. 19 A triplet is correctly identified when two of the three letters are recognized. A superior score, or a score of 15 (converted in logarithmic units for statistical analysis), is considered normal. 20 According to Sloan, the weak contrast cards are dependent on the identification of gray letters, whose size progressively decreases. The format is similar to that of the ETDRS scale and has five letters per line. These letters appear on a back-lit, white base (Precision Vision, La Salle, IL) placed 2 m away. We used levels of contrast 1.25% and 2.5%. 5 21 22 Sensitivity to temporal contrast was explored in FDTP. The FDTP analyzes sensitivity to the temporal contrast of ganglionic cells of the magnocellular retina. The FDTP equipment (Carl Zeiss Meditec, Inc., Dublin, CA) shows stimuli as vertical light bars, as alternating with dark bars, representing those subject to the phenomenon of frequency doubling. These stimuli in 10° × 10° square form are present in 16 zones of the 20° centrally located in the visual field. The central target of 5° is round. We used the program limit N-30. 23 The results are compared to a base of normal values according to age. The results indicate for each target the limit of sensitivity in decibels and the total deviation marked, taking into account age (mean deviation [MD]), as well as the SD of the differences between the value of the limit, and of the anticipated value at the level of each point tested (pattern standard deviation [PSD]). The limit of average sensitivity of the nasal quadrant is obtained in determining the average limit of sensitivity of seven affected individuals (patients 1, 6, 7, 8, 10, 11, and 12), of the superior quadrant of the five targets (patients 2, 3, 4, 5, and 9), and of the inferior quadrant of the five targets (patients 13, 14, 15, 16, and 17; Fig. 1 ). The exploration of color vision was performed with the Farnsworth 100 Hue test. The square root of the score was used for the statistic analysis. The standard value of the score according to age was obtained from the tables devised by Verriest et al. 24  
The measurement of the thickness of retinal peripapillary nerve fibers was performed with the help of OCT (Stratus OCT, equipped with ver. 4.0 of the software; Carl Zeiss Meditec, Inc.). The results were acquired with the protocol Fast RNFL thickness. The equipment made three circular scans (resolution, 256) of 3.4 mm in diameter centered on the head of the optic nerve in 1.92 seconds. We increased the average thickness of the layer of retinal nerve fibers, as well as the average thickness in the temporal, superior, nasal, and inferior quadrants. 17 The scans obtained had a quality of input ≥7. In the case of a narrow pupil, the OCT was performed with the instillation of 1 drop of tropicamide. 
The data-processing was performed maintaining strict anonymity (Excel, Microsoft, Redmond, WA; and Statview; SAS Cary, NC). For the statistical analysis, we used χ2 for the comparing of frequencies, χ2 with the Yates correction for small sizes, and a Student’s t-test for comparison of the mean. The correlation between the thickness of retinal peripapillary nerve fibers and the clinical variables was studied by calculating the Spearman correlation coefficient (r). A multivariate analysis by logistic regression was performed to investigate the independent values associated with the average thickness of the layer of retinal nerve fibers. This study obtained approval from the Consulting Committee for the Protection of Individuals of Biomedical Research sponsored by the French Ministry of Health and was conducted in accordance with the Declaration of Helsinki. 
Results
The general characteristics of the patients belonging to the NMO group are displayed in Table 2 . The average age of patients with NMO was 41 ± 8.1 years. Fourteen patients were women and one was a man. The average age from the beginning of the onset of NMO was 34.2 ± 9.3 years. The disease progressed for 7.3 ± 4.5 years. Eleven (73.3%) patients experienced optic neuropathy at the onset of the disease. The average EDSS was 4.9 ± 1.9. The index of progression of the EDSS was 1.15 ± 1. The number of ocular episodes per patient, the number of ocular episodes during the first 2 years, and the annual rate of episodes were, respectively, 2.13 ± 1.4, 1.33 ± 0.8, and 0.36 ± 0.25. Ten (66.6%) patients had a medical history of bilateral optic neuropathy. Five (33.3%) patients had a medical history of papillitis. The average visual EDSS was 4.4 ± 2.1. The index of progression (IP) of the visual EDSS was 0.9 ± 0.75. 
The characteristics of patients who made up the MS group are likewise represented in Table 2 . MS had developed earlier (30.4 ± 11.4 years), progressed for a longer period (10.6 ± 9.3 years), and had also progressed more rapidly in general—for example (IP EDSS MS 0.45 ± 0.4 versus IP EDSS NMO 1.15 ± 1, P = 0.04) than on the ocular level (IP EDSS visual MS 0.27 ± 0.63 versus IP EDSS NMO 0.9 ± 0.75, P = 0.032). The control group was made up of 23 patients. The average age of the patients in this control group was 40 ± 8.2 years. It also comprised 22 women and 1 man. 
Table 3displays the results of the measurement of the thickness of the retinal peripapillary nerve fibers and of the tests of visual function. All the results obtained in the NMO and MS groups are significantly different from those obtained from the control group (P < 0.0001, P = 0.007). The average thickness of the retinal peripapillary nerve fibers was less in the NMO group than in the MS group: 65.44 ± 24.19 μm versus 83.85 ± 24.12 μm (P = 0.01). The average thickness of the retinal peripapillary nerve fibers in the control group was 106.24 ± 12.46 μm. The thickness was less in all quadrants of the same magnitude, but the difference was not significant in the superior quadrants, nor in the nasal quadrants (Fig. 2)
We compared the average thickness of the retinal peripapillary nerve fibers in eyes that did not have a history of optic neuropathy. In the NMO group (n = 5) and in the MS group (n = 7), the average thickness was, respectively, 89.28 ± 24.73 μm and 89.7 ± 18.33 μm, versus 106.24 ± 12.46 μm in the control group (P = 0.04). The NMO or MS clinical status was not an independent risk factor directly correlated to the average thickness of the layer of the retinal nerve fibers in multivariate analysis. 
The average visual acuity was 20/50 in the NMO group and 20/30 in the MS group (P = 0.0035). The ETDRS scores and the tests of the sensitivities of the spatial contrasts (Pelli-Robson, Sloan 1.25% and 2.5%) were less in the NMO group than in the MS and control groups. The results of the FDTP were equally less high in the NMO group, but the difference was not significant. 
There was a significant correlation between the average thickness of retinal peripapillary nerve fibers and the Snellen visual acuity (r = 0.65, P = 0.0006), the EDTRS visual acuity (r = 0.64, P = 0.0026), the score of the Pelli-Robson test (r = 0.65, P = 0.0014), the score of the Sloan test 1.25% (r = 0.71, P = 0.0011), and the score of the Sloan test 2.5% (r = 0.74, P = 0.0005). An equally significant correlation was found in the results of the FDTP. There was no correlation regarding the results of the Hue 100 test (Table 4) . The average thickness of the retinal peripapillary nerve fibers between the eyes of each patient correlated with the visual EDSS (r = −0.63, P = 0.02), and the number of episodes per patient (r = −0.58, P = 0.03). There was no correlation between the average thickness of the retinal peripapillary nerve fibers between the eyes of each patient and the overall handicap (EDSS), the age of the onset, and the length of the disease. 
We have determined a threshold value of 20/200 for the visual activity and of 52 μm for the RNFL. 3 The value 52 μm corresponds to the average RNFL when the visual acuity was inferior or equal to 20/200. The presence of a visual acuity inferior or equal to 20/200 predicted NMO with a 53% sensibility, 79% specificity, and a Youden plot of 0.31. An average RNFL of 52 μm predicted an NMO with a 50% sensibility, 94% specificity, and a Youden plot of 0.44. The visual acuity measurement and the RNFL study have close sensibility; nevertheless, the RNFL study is more specific. 
Discussion
NMO is a rare, demyelinating disease that principally affects females, and has a global distribution and a bad prognosis. For a long time, it was considered to be a variant of MS. 25 However, certain clinical, immunologic, and histologic characteristics now distinguish it from MS, such as the brain reserves at the beginning of the disease, the frequent association (10%–40%) with autoimmune diseases, or the presence of immunoglobulin G (NMO-IgG), an antibody to aquaporin 4. 26 Visual function is severely affected and is characterized by a significant incidence of ocular episodes and thus by the severity of the degradation of visual function. 11 The average time for progression of blindness in the first eye is 2 years; for an episode in the second eye, 1 year; and for blindness in the second eye, 13 years. As a rule, two episodes are sufficient to lead to definitive vision loss. 3 The percentage of bilateral blindness is 41% in the series in Papais-Alvarenga et al. 27  
The measurement of the thickness of retinal peripapillary nerve fibers associated with OCT was performed only in cases of optic neuropathy in MS. This study reports the first results obtained regarding optic neuropathies of NMO. We observed a reduction of the thickness of peripapillary retinal nerve fibers in NMO. The significant reduction of the average thickness of the retinal peripapillary nerve fibers in the NMO group were strongly linked to visual acuity. In the multivariate analysis, the NMO status did not appear as an independent factor when it came to axonal involvement. 
Several authors have shown that patients with MS have a reduction in the thickness of peripapillary retinal nerve fibers. Parisi et al. 28 report a thickness of 59.79 ± 10.80 μm in patients after an episode of optic neuropathy. This first study, unlike those that followed, was performed with first-generation OCT and comprised 14 patients with MS. Trip et al. 10 confirms these first results, finding in 25 patients who had a medical history of isolated optic neuropathy or one associated with MS, a mean RNFL thickness of 68.7 ± 18.8 μm. The most important series is that in Fischer et al. 22 who examined 90 patients with MS. It also reports a reduction in the thickness of retinal peripapillary nerve fibers in patients with at least one episode of optic neuropathy. The reduction in the thickness of retinal peripapillary nerve fibers appeared after an episode of optic neuropathy in 11% of the cases before 3 months, in 85% of the cases between 3 and 6 months, and in 4% of the cases after 6 months. This decline predominated in the temporal quadrant where the papillomacular fibers are located. 29  
The surface measurement of the section of the optical nerve in the MRI and of the amplitude of the visual evoked potentials reveal atrophy of the optical nerve resulting in an axonal loss that continued for at least 1 year after the occurrence of acute optic neuropathy. 30 31 Recently, Trip et al. 32 established that the reduction of the thickness of retinal peripapillary nerve fibers was directly related to optic nerve atrophy as seen in the MRI. As suggested on retinography and confirmed by histologic analysis for many years, the axonal loss of the afferent visual system is now firmly linked to the progression of MS. 33 Like the neuropathies of MS, the optic neuropathies observed in NMO are accompanied by axonal loss. In contrast to Fischer et al., 22 we found no correlation between the thickness of retinal peripapillary nerve fibers and magnitude of handicap (EDSS) of NMO, presumably due to the small sample size. 
We also found that the thickness of the retinal peripapillary nerve fibers was reduced in eyes that had absolutely no medical history of optic neuropathy. As noted in our MS group and by Fisher et al, 22 in Adelphe eyes, or in patients without an ophthalmic history, these results suggest the possibility of a chronic axonal injury that is unrelated to any sort of acute episode. 
Histologic injuries of the optical nerve in NMO were different from those usually seen in MS. The optic nerve appeared to be of a grayish color and soft. There was also an infiltration of eosinophilic and polynuclear neutrophilic inflammatory cells. The vessels was thickened and hyalinated. We also saw necrotic lesions and atrophy never before seen in MS. 34 As Vernant et al. 35 demonstrated, lesions can spread as far as the optic chiasm and surpass it. The lesions dominate the center of the nerve, sometimes stemming from the central cavitation. 36 The same type of lesion is observed at the medullary level, as well as in the gray and white matter. 36 All these lesions are characterized by a rosette pattern of immunoglobulins, immune complexes, and complement around the blood vessels. This distribution is superimposed on the normal expression of aquaporin 4 on astrocytes. 37  
Widely used to treat glaucoma and retinal disease, OCT is an objective, noninvasive method that permits in vivo to measure the thickness of retinal peripapillary nerve fibers. The actual thickness of the nerve fibers (histologic images) would be from 4% to 12% greater than the thickness resulting from OCT. 38 The measurements are quick and simple to perform, even in patients who are severely affected. Compared to visual field testing, the examination requires limited cooperation. Unlike MRI, OCT can be easily repeated and at a lower cost. Optic neuropathies of NMO are singled out in our study by low visual acuity (ETDRS, 31 ± 24); however, the thickness of the retinal peripapillary nerve fibers appears to correlate with the results of visual contrast tests. A correlation between the thickness of retinal peripapillary nerve fibers and the results of the contrast vision tests has already been established: The loss of 1 line on the weak visual contrast tests (Sloan 1.25%, Sloan 2.5%, and Pelli-Robson) is accompanied by an average reduction of 4 μm of the thickness of retinal peripapillary nerve fibers. 22 In our study, the deficiencies of the FDTP correlated with the thickness of retinal peripapillary nerve fibers. Our results are in accordance with those of Trip et al. 10 (obtained with a Humphrey perimeter; Carl Zeiss Meditec, Inc.). 
In a disease in which axonal loss is paramount and for which no effective treatment is known, OCT may be a new and efficient method for surveillance of the axonal structure of the optic nerve. OCT can complement other tests of visual function that are currently being used, such as visual acuity, contrast sensitivity, visual fields and visual evoked potentials. It may also complement MRI findings, and like MRI, OCT might prove useful in the evaluation of various therapies for NMO. 
 
Table 1.
 
Criteria of Wingerchuk et al. 11 for the Diagnosis of NMO
Table 1.
 
Criteria of Wingerchuk et al. 11 for the Diagnosis of NMO
Absolute criteria Optic neuritis
Acute myelitis
No evidence of clinical disease outside the optic nerve or spinal cord
Supportive criteria Major
Negative brain MRI at onset (criteria of Paty et al. 13 )
Spinal cord MRI with signal abnormality extending over ≥3 vertebral segments
CSF pleiocytosis of >50 WBC/mm3 or >5 neutrophils/mm3
Minor
Bilateral optic neuritis
Severe optic neuritis with fixed visual acuity of less than 20/200 in at least one eye
Severe, fixed, episode-related weakness (MRC grade ≤ 2) in one or more limbs
Figure 1.
 
Illustration of the stimulus zones of FDTP. The FDTP device (Carl Zeiss Meditec, Inc., Dublin, CA) presents the stimuli as clear vertical bars alternating with other darkened bars subject to the frequency-doubling phenomenon. These stimuli in a square-shaped form of 10° × 10° are presented in 16 zones of the 20° central to the visual field. The 5° central target is round.
Figure 1.
 
Illustration of the stimulus zones of FDTP. The FDTP device (Carl Zeiss Meditec, Inc., Dublin, CA) presents the stimuli as clear vertical bars alternating with other darkened bars subject to the frequency-doubling phenomenon. These stimuli in a square-shaped form of 10° × 10° are presented in 16 zones of the 20° central to the visual field. The 5° central target is round.
Table 2.
 
Demographic Characteristics of Patients from the NMO Group and from the MS Group
Table 2.
 
Demographic Characteristics of Patients from the NMO Group and from the MS Group
NMO (n = 15, 30 eyes) MS (n = 15, 30 eyes) P
Age (y) 41 ± 8.1 40.4 ± 11.2 0.9 NS
Female/male ratio (% F) 14/1 (93%) 14/1 (93%) 0.99 NS
Age at onset (y) 34.2 ± 9.3 30.4 ± 11.4 0.38 NS
Duration of the disease (y) 7.3 ± 4.5 10.6 ± 9.3 0.27 NS
Ocular presenting symptom 11/15 (73.3%) 7/15 (46.6%) 0.99 NS
EDSS 4.9 ± 1.9 3.4 ± 2.6 0.09 NS
IP of EDSS 1.15 ± 1 0.45 ± 0.4 0.04
Episodes/patient (n) 2.13 ± 1.4 1.6 ± 0.7 0.2 NS
Episodes/patient in the first 2 years (n) 1.33 ± 0.8 1.07 ± 0.7 0.33 NS
Annual relapsing rate 0.36 ± 0.25 0.39 ± 0.51 0.84 NS
Retrobulbar optic neuritis 13/15 (86.6%) 12/15 (80%) 0.99 NS
Papillitis 5/15 (33.3%) 3/15 (20%) 0.99 NS
Binocular impairment 10/15 (66.6%) 7/15 (46.6%) 0.82 NS
Visual EDSS 4.4 ± 2.1 1.5 ± 1.8 0.0013
Visual IP 0.9 ± 0.75 0.27 ± 0.63 0.032
Table 3.
 
Thickness of Retinal Peripapillary Nerve Fibers, the Results of Contrast Vision Tests, and the Results of FDTP for Eyes of Patients from the NMO, MS, and Control Groups
Table 3.
 
Thickness of Retinal Peripapillary Nerve Fibers, the Results of Contrast Vision Tests, and the Results of FDTP for Eyes of Patients from the NMO, MS, and Control Groups
NMO (n = 15, 30 Eyes) MS (n = 15, 30 Eyes) Disease-Free Controls (n = 23, 46 Eyes) P *
Visual acuity (Snellen) 20/50 20/30 20/20 0.0035
Visual acuity ETDRS 31 ± 24 47 ± 16 59.89 ± 7.43 0.0037
Pelli-Robson chart 0.96 ± 0.64 1.34 ± 0.5 1.71 ± 0.13 0.0213
Sloan chart 1.25% 3.31 ± 7.17 10.33 ± 11.38 22.26 ± 9.28 0.0031
Sloan chart 2.5% 9.17 ± 13.19 18.3 ± 14.79 34.17 ± 5.22 0.0096
MD (FDTP) −7.13 ± 6.98 −4.19 ± 3.91 0.72 ± 1.52 0.13 NS
PSD (FDTP) 6.87 ± 4.8 6.01 ± 3.08 3.5 ± 0.69 0.64 NS
Nasal sensitivity (FDTP) 20.79 ± 10.27 24.07 ± 6.8 32.38 ± 7.56 0.33 NS
Superior sensitivity (FDTP) 20.17 ± 10.14 25.57 ± 6.44 31.72 ± 2.52 0.057 NS
Inferior sensitivity (FDTP) 21.82 ± 9.33 25.72 ± 6.17 32.42 ± 2.32 0.22 NS
100 Hue 171 ± 148 174 ± 169 60 ± 31 0.26 NS
Overall average RNFL thickness 65.44 ± 24.19 83.85 ± 24.12 106.24 ± 12.46 0.01
Temporal quadrant RNFL 39.46 ± 12.69 50.2 ± 17.38 69.43 ± 12.65 0.01
Superior quadrant RNFL 82 ± 37.92 105.4 ± 34.54 135.56 ± 21.07 0.06 NS
Nasal quadrant RNFL 57.82 ± 22.43 66.53 ± 23.91 81.71 ± 18.36 0.15 NS
Inferior quadrant RNFL 82.5 ± 33.3 113.1 ± 33.97 138.41 ± 20.12 0.004
Figure 2.
 
The average thickness of retinal peripapillary nerve fibers in the entire periphery of the papilla in the temporal, superior, nasal, and inferior quadrants in patients in the NMO, MS, and control groups. CG, control group.
Figure 2.
 
The average thickness of retinal peripapillary nerve fibers in the entire periphery of the papilla in the temporal, superior, nasal, and inferior quadrants in patients in the NMO, MS, and control groups. CG, control group.
Table 4.
 
Correlation between the Thickness of Retinal Peripapillary Nerve Fibers and Visual Function in the NMO Group
Table 4.
 
Correlation between the Thickness of Retinal Peripapillary Nerve Fibers and Visual Function in the NMO Group
Overall Average RNFL Thickness VA Snellen EDTRS Pelli-Robson Sloan 1.25% Sloan 2.5% MD PSD Nasal FDTP Superior FDTP Inferior FDTP 100 Hue
Spearman r 0.65 0.64 0.65 0.71 0.74 0.52 −0.3 0.52 0.54 0.69 0.038
P 0.0006 0.0026 0.0014 0.0011 0.0005 0.011 0.11* 0.011 0.0092 0.0008 0.87*
The authors thank all the subjects who took part in the study and Sarah Meyer, Karen Thérèse, and Eric Ventura for assistance. 
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Figure 1.
 
Illustration of the stimulus zones of FDTP. The FDTP device (Carl Zeiss Meditec, Inc., Dublin, CA) presents the stimuli as clear vertical bars alternating with other darkened bars subject to the frequency-doubling phenomenon. These stimuli in a square-shaped form of 10° × 10° are presented in 16 zones of the 20° central to the visual field. The 5° central target is round.
Figure 1.
 
Illustration of the stimulus zones of FDTP. The FDTP device (Carl Zeiss Meditec, Inc., Dublin, CA) presents the stimuli as clear vertical bars alternating with other darkened bars subject to the frequency-doubling phenomenon. These stimuli in a square-shaped form of 10° × 10° are presented in 16 zones of the 20° central to the visual field. The 5° central target is round.
Figure 2.
 
The average thickness of retinal peripapillary nerve fibers in the entire periphery of the papilla in the temporal, superior, nasal, and inferior quadrants in patients in the NMO, MS, and control groups. CG, control group.
Figure 2.
 
The average thickness of retinal peripapillary nerve fibers in the entire periphery of the papilla in the temporal, superior, nasal, and inferior quadrants in patients in the NMO, MS, and control groups. CG, control group.
Table 1.
 
Criteria of Wingerchuk et al. 11 for the Diagnosis of NMO
Table 1.
 
Criteria of Wingerchuk et al. 11 for the Diagnosis of NMO
Absolute criteria Optic neuritis
Acute myelitis
No evidence of clinical disease outside the optic nerve or spinal cord
Supportive criteria Major
Negative brain MRI at onset (criteria of Paty et al. 13 )
Spinal cord MRI with signal abnormality extending over ≥3 vertebral segments
CSF pleiocytosis of >50 WBC/mm3 or >5 neutrophils/mm3
Minor
Bilateral optic neuritis
Severe optic neuritis with fixed visual acuity of less than 20/200 in at least one eye
Severe, fixed, episode-related weakness (MRC grade ≤ 2) in one or more limbs
Table 2.
 
Demographic Characteristics of Patients from the NMO Group and from the MS Group
Table 2.
 
Demographic Characteristics of Patients from the NMO Group and from the MS Group
NMO (n = 15, 30 eyes) MS (n = 15, 30 eyes) P
Age (y) 41 ± 8.1 40.4 ± 11.2 0.9 NS
Female/male ratio (% F) 14/1 (93%) 14/1 (93%) 0.99 NS
Age at onset (y) 34.2 ± 9.3 30.4 ± 11.4 0.38 NS
Duration of the disease (y) 7.3 ± 4.5 10.6 ± 9.3 0.27 NS
Ocular presenting symptom 11/15 (73.3%) 7/15 (46.6%) 0.99 NS
EDSS 4.9 ± 1.9 3.4 ± 2.6 0.09 NS
IP of EDSS 1.15 ± 1 0.45 ± 0.4 0.04
Episodes/patient (n) 2.13 ± 1.4 1.6 ± 0.7 0.2 NS
Episodes/patient in the first 2 years (n) 1.33 ± 0.8 1.07 ± 0.7 0.33 NS
Annual relapsing rate 0.36 ± 0.25 0.39 ± 0.51 0.84 NS
Retrobulbar optic neuritis 13/15 (86.6%) 12/15 (80%) 0.99 NS
Papillitis 5/15 (33.3%) 3/15 (20%) 0.99 NS
Binocular impairment 10/15 (66.6%) 7/15 (46.6%) 0.82 NS
Visual EDSS 4.4 ± 2.1 1.5 ± 1.8 0.0013
Visual IP 0.9 ± 0.75 0.27 ± 0.63 0.032
Table 3.
 
Thickness of Retinal Peripapillary Nerve Fibers, the Results of Contrast Vision Tests, and the Results of FDTP for Eyes of Patients from the NMO, MS, and Control Groups
Table 3.
 
Thickness of Retinal Peripapillary Nerve Fibers, the Results of Contrast Vision Tests, and the Results of FDTP for Eyes of Patients from the NMO, MS, and Control Groups
NMO (n = 15, 30 Eyes) MS (n = 15, 30 Eyes) Disease-Free Controls (n = 23, 46 Eyes) P *
Visual acuity (Snellen) 20/50 20/30 20/20 0.0035
Visual acuity ETDRS 31 ± 24 47 ± 16 59.89 ± 7.43 0.0037
Pelli-Robson chart 0.96 ± 0.64 1.34 ± 0.5 1.71 ± 0.13 0.0213
Sloan chart 1.25% 3.31 ± 7.17 10.33 ± 11.38 22.26 ± 9.28 0.0031
Sloan chart 2.5% 9.17 ± 13.19 18.3 ± 14.79 34.17 ± 5.22 0.0096
MD (FDTP) −7.13 ± 6.98 −4.19 ± 3.91 0.72 ± 1.52 0.13 NS
PSD (FDTP) 6.87 ± 4.8 6.01 ± 3.08 3.5 ± 0.69 0.64 NS
Nasal sensitivity (FDTP) 20.79 ± 10.27 24.07 ± 6.8 32.38 ± 7.56 0.33 NS
Superior sensitivity (FDTP) 20.17 ± 10.14 25.57 ± 6.44 31.72 ± 2.52 0.057 NS
Inferior sensitivity (FDTP) 21.82 ± 9.33 25.72 ± 6.17 32.42 ± 2.32 0.22 NS
100 Hue 171 ± 148 174 ± 169 60 ± 31 0.26 NS
Overall average RNFL thickness 65.44 ± 24.19 83.85 ± 24.12 106.24 ± 12.46 0.01
Temporal quadrant RNFL 39.46 ± 12.69 50.2 ± 17.38 69.43 ± 12.65 0.01
Superior quadrant RNFL 82 ± 37.92 105.4 ± 34.54 135.56 ± 21.07 0.06 NS
Nasal quadrant RNFL 57.82 ± 22.43 66.53 ± 23.91 81.71 ± 18.36 0.15 NS
Inferior quadrant RNFL 82.5 ± 33.3 113.1 ± 33.97 138.41 ± 20.12 0.004
Table 4.
 
Correlation between the Thickness of Retinal Peripapillary Nerve Fibers and Visual Function in the NMO Group
Table 4.
 
Correlation between the Thickness of Retinal Peripapillary Nerve Fibers and Visual Function in the NMO Group
Overall Average RNFL Thickness VA Snellen EDTRS Pelli-Robson Sloan 1.25% Sloan 2.5% MD PSD Nasal FDTP Superior FDTP Inferior FDTP 100 Hue
Spearman r 0.65 0.64 0.65 0.71 0.74 0.52 −0.3 0.52 0.54 0.69 0.038
P 0.0006 0.0026 0.0014 0.0011 0.0005 0.011 0.11* 0.011 0.0092 0.0008 0.87*
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