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Vol. 31. Issue 6.
Pages 379-388 (July - August 2016)
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Vol. 31. Issue 6.
Pages 379-388 (July - August 2016)
Original article
DOI: 10.1016/j.nrleng.2014.09.001
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Analysis of macular and nerve fibre layer thickness in multiple sclerosis patients according to severity level and optic neuritis episodes
Análisis del grosor macular y de capa de fibras nerviosas en pacientes con esclerosis múltiple en relación con su nivel de gravedad y antecedentes previos de neuritis óptica
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A. Soler Garcíaa, F. Padilla Parradob, L.C. Figueroa-Ortizc, A. González Gómeza, A. García-Bend, E. García-Bene, J.M. García-Camposa,c,
Corresponding author
jmgarcia@uma.es

Corresponding author.
a Servicio de Oftalmología, Hospital Universitario Virgen de la Victoria, Málaga, Spain
b Servicio de Neurología, Hospital Universitario Virgen de la Victoria, Málaga, Spain
c Área de Oftalmo-Biología, Centro de Investigaciones Médico-Sanitarias, Universidad de Málaga, Málaga, Spain
d Servicio de Oftalmología, Hospital General de Galicia, Santiago de Compostela, A Coruña, Spain
e Servicio de Oftalmología, Complejo Asistencial de Burgos, Hospital General Yagüe, Burgos, Spain
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Figures (2)
Tables (10)
Table 1. Characteristics of patients with, and controls without, MS.
Table 2. RNFL thickness in patients with MS and controls.
Table 3. RNFL thickness in controls and MS patients without optic neuritis.
Table 4. RNFL thickness in the patient group, broken down by clinical form of MS.
Table 5. RNFL thickness in MS patients without optic neuritis, broken down by clinical form of MS.
Table 6. RNFL thickness broken down by EDSS level.
Table 7. RNFL thickness by EDSS level in the group of MS patients without optic neuritis.
Table 8. RNFL thickness in patients with and without optic neuritis.
Table 9. Retinal thickness in the central 1000- and 3000-μm-diameter areas by EDSS level.
Table 10. Retinal thickness in the central 1000- and 3000-μm-diameter areas in patients with and without optic neuritis.
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Abstract
Introduction

Quantitative assessment of macular and nerve fibre layer thickness in multiple sclerosis patients with regard to expanded disability status scale (EDSS) and presence or absence of previous optic neuritis episodes.

Methods

We recruited 62 patients with multiple sclerosis (53 relapsing-remitting and 9 secondary-progressive) and 12 disease-free controls. All patients underwent an ophthalmological examination, including quantitative analysis of the nerve fibre layer and macular thickness using optical coherence tomography. Patients were classified according to EDSS as A (lower than 1.5), B (between 1.5 and 3.5), and C (above 3.5).

Results

Mean nerve fibre layer thickness in control, A, B, and C groups was 103.35±12.62, 99.04±14.35, 93.59±15.41, and 87.36±18.75μm respectively, with statistically significant differences (P<.05). In patients with no history of optic neuritis, history of episodes in the last 3 to 6 months, or history longer than 6 months, mean nerve fibre layer thickness was 99.25±13.71, 93.92±13.30 and 80.07±15.91μm respectively; differences were significant (P<.05). Mean macular thickness in control, A, B, and C groups was 220.01±12.07, 217.78±20.02, 217.68±20.77, and 219.04±24.26μm respectively. Differences were not statistically significant.

Conclusions

The mean retinal nerve fibre layer thickness in multiple sclerosis patients is related to the EDSS level. Patients with previous optic neuritis episodes have a thinner retinal nerve fibre layer than patients with no history of these episodes. Mean macular thickness is not correlated to EDSS level.

Keywords:
Macular thickness
Nerve fibre layer
Multiple sclerosis
Expanded disability status scale
Optic neuritis
Resumen
Introducción

Evaluar cuantitativamente el grosor macular y de la capa de fibras nerviosas en pacientes con esclerosis múltiple en relación con la escala expandida del estado de discapacidad (EDSS) con o sin antecedentes previos de neuritis óptica.

Métodos

Sesenta y dos pacientes diagnosticados de esclerosis múltiple (53 remitente recidivante y 9 secundariamente progresiva) y 12 libres de enfermedad fueron reclutados para el estudio. Se les realizó una exploración oftalmológica, incluyendo el análisis cuantitativo de la capa de fibras nerviosas retinianas y el grosor macular mediante tomografía óptica de coherencia. Los pacientes fueron clasificados según la escala EDSS en: A: inferior a 1,5; B: entre 1,5 y 3,5, y C: superior a 3,5.

Resultados

El grosor medio ± desviación estándar de la capa de fibras nerviosas en los grupos control, A, B y C fue de 103,35±12,62, 99,04±14,35, 93,59±15,41 y 87,36±18,75μm, respectivamente, con diferencias estadísticamente significativas (p<0,05). En pacientes sin una historia previa de neuritis, o con un episodio de esta patología entre 3 y 6 meses de evolución o anterior a 6 meses, el grosor medio fue de 99,25±13,71, 93,92±13,30, 80,07±15,91μm, respectivamente, con diferencias significativas (p<0,05). El grosor macular medio en el grupo control, A, B y C se situó en 220,01±12,07, 217,78±20,02, 217,68±20,77 y 219,04±24,26μm, respectivamente. Las diferencias observadas entre grupos no fueron estadísticamente significativas.

Conclusiones

El grosor medio de la capa de fibras nerviosas en pacientes con esclerosis múltiple se relaciona con el nivel en la escala EDSS. Los pacientes con historia previa de neuritis óptica cursan con una disminución del grosor de esta capa respecto a aquellos sin antecedentes de neuritis. El grosor macular no se relaciona con el grado de afectación en la EDSS.

Palabras clave:
Grosor macular
Capa de fibras nerviosas
Esclerosis múltiple
Escala expandida del estado de discapacidad
Neuritis óptica
Full Text
Introduction

Optical coherence tomography is an easy-to-perform, non-invasive technique that quantitatively analyses the thickness of the retinal nerve fibre layer (RNFL). It uses low-coherence light, which is produced by a superluminescent diode coupled with an optical fibre interferometer, at a wavelength of 843nm.1 Studies using optical coherence tomography in patients with multiple sclerosis (MS) have shown that the RNFL is thinner in these patients than in healthy individuals.2,3

In a sample of 14 patients with MS and a history of optic neuritis with complete recovery of visual acuity, Parisi et al.4 reported a 48% decrease in RNFL thickness. In the contralateral eye, which had not been affected by optic neuritis, RNFL thickness decreased a mean of 28% compared to the control group.

Most published studies have analysed the connection between RNFL thickness and grey matter fraction, brain volume, degree of brain atrophy, optic neuritis, some clinical forms of MS, visual field sensitivity, and the contrast sensitivity test.2,5–11 However, few studies have addressed the relationship between RNFL thickness and the expanded disability status scale (EDSS) and these include patients with no history of optic neuritis.12–14

The purpose of our study was to quantitatively analyse macular and RNFL thickness in patients with MS both with and without a history of optic neuritis, and to assess their association with certain clinical forms of MS and EDSS scores.

Material and methods

We conducted a retrospective study including 62 patients diagnosed with MS (53 with relapsing-remitting MS and 9 with secondary-progressive MS) and a control group of 12 patients without the disease. In compliance with the Declaration of Helsinki, confidentiality of the results was guaranteed and all patients were apprised of the characteristics of the study before signing informed consent forms.

The patients were recruited from the neurology department at Hospital Universitario Virgen de la Victoria in Málaga, Spain, between February 2012 and January 2013. Controls were randomly selected from the patients with no eye disorders or systemic diseases who visited the ophthalmology polyclinic and who met the following criteria: visual acuity 10/10 on a Snellen chart, intraocular pressure <21mmHg, and absence of anterior or posterior segment abnormalities. The MS diagnosis was confirmed by the neurology department based on clinical examinations and neuroimaging studies.

The ophthalmological examination of all participants included: a visual acuity test using a Snellen chart (values expressed in decimals), intraocular pressure determination with a Perkins applanation tonometer, and an eye fundus examination with a non-contact biomicroscopy with a Volk 84D lens.

Clinical diagnosis of a previous episode of optic neuritis involved the following clinical findings: visual acuity loss associated with painful eye movements, visual field defects, colour vision defects, afferent pupillary defect, and poor performance on the contrast sensitivity test, with either apparently normal or oedematous papilla. We excluded the patients who less than 3 months prior to the study experienced an episode of optic neuritis.

We used the EDSS15 to assess neurological impairment. This quantitative scale ranges from 0 (normal) to 10 (death due to MS) in 0.5 unit increments. Scoring is based on a functional scale that assesses pyramidal, cerebellar, brainstem, sensitivity, bowel and bladder, visual, and mental functions, as well as difficulties in walking, communicating, and swallowing. Visual function included 7 grades: 0: normal; 1: scotoma with visual acuity better than 20/30 (corrected); 2: worse eye with scotoma with maximal visual acuity (corrected) between 20/30 and 20/59; 3: worse eye with large scotoma, or moderate decrease in fields, but with maximal visual acuity (corrected) between 20/60 and 20/99; 4: worse eye with marked decrease of fields and maximal visual acuity (corrected) between 20/100 and 20/200; 5: worse eye with maximal visual acuity (corrected) less than 20/200; and 6: grade 5 plus maximal visual acuity of better eye of 20/60 or less.

To study macular and RNFL thickness, we used the Stratus OCT 3000 optical coherence tomography system (Zeiss Humphrey Systems, Dublin, CA, USA) and 2 scan acquisition protocols: Macular Thickness Map, which performs 6 6-mm radial scans in 9seconds, and the Fast RNFL Thickness, which performs 3 3.4-mm diameter circular scans in a single 1.92-second scan (Figs. 1 and 2).

Figure 1.

Macular thickness in a patient who experienced an episode of optic neuritis in the right eye more than 6 months previously. Measurements within the central 1000-, 3000-, and 6000-μm-diameter areas.

(0.1MB).
Figure 2.

Quantitative analysis of RNFL thickness in a patient who experienced an episode of optic neuritis in the right eye more than 6 months previously. Thickness in all clock-hour sectors and quadrants is expressed in microns.

(0.2MB).

The Retinal Thickness/Volume Tabular protocol was used to quantitatively analyse macular thickness. This protocol yielded 2 circular maps for measuring macular thickness in the 1000-, 3000-, and 6000-μm-diameter areas centred on the fovea, although we analysed thickness only in the 1000- and 3000-μm-diameter areas.

RNFL thickness was determined with the RNFL Thickness Average protocol, which quantitatively analysed thickness in 4 sectors or quadrants. In our study, we included mean RNFL thickness in the 4 sectors as well as RNFL thickness in each sector (superior, inferior, temporal, and nasal).

Data were gathered using FileMaker version 10 for Windows.

Data analysis was performed using SPSS statistical software version 15.0 for Windows. We used the parametric ANOVA test to compare the means between groups. The comparative analysis of quantitative variables was performed with the Pearson bivariate correlation test. Statistical significance was set at P<.05.

Results

In our sample, 36.5% of the participants were men, and 63.5% were women. Mean age±SD was 36.50±8.92 years in the patient group and 32.7±8.33 years in the control group. Disease progression time was 81.54±74.81 months. MS was relapsing-remitting in 85.4% of the patients (53/62) and secondary-progressive in 14.6% (9/62); 70.96% of the patients (44/62) were treated with immunomodulatory drugs (interferon beta).

Eleven patients had a single relapse, 20 had 2, 9 had 3, 10 had 4, and 12 had 5 relapses. Visual acuity was 0.91±0.21 in the patient group and 1.02±0.18 in the control group (Table 1).

Table 1.

Characteristics of patients with, and controls without, MS.

  Patients  Controls 
n  62  12 
  Relapsing-remitting: 53 (85.4%)   
  Secondary-progressive: 9 (16.6%)   
Eyes (n124  24 
Age, years (mean±SD)  36.50±8.92  32.7±8.33 
Disease duration, months (mean±SD)  81.54±4.81  – 
EDSS score (mean±SD)  2.46±2.04  – 
VA (mean±SD)  0.91±0.21  1.02±0.18 
IOP (mean±SD)  16.3±1.4  16.7±0.9 

VA, visual acuity; SD, standard deviation; EDSS, expanded disability status scale; n, number; IOP: intraocular pressure.

We found statistically significant differences in mean RNFL thickness (P=.02) and in RNFL thickness in the temporal (P=.02) and inferior (P=.01) sectors between patients and controls (Table 2). After excluding the patients who had experienced an episode of optic neuritis, differences were significant only for the temporal sector (P<.05) (Table 3).

Table 2.

RNFL thickness in patients with MS and controls.

RNFL thicknessEyes  Mean  SD  95% confidence interval for the mean
          Lower limit  Upper limit 
Mean thickness  Patients  124  94.5418  16.2078  91.6488  97.4348 
  Controls  24  103.3590  12.6272  97.4493  109.2687 
Superior sector  Patients  124  118.3740  23.1557  114.2408  122.5072 
  Controls  24  124.5000  17.6888  116.2214  132.7786 
Inferior sector  Patients  124  115.5203  22.1323  111.5698  119.4708 
  Controls  24  131.9500  18.4375  123.3209  140.5791 
Nasal sector  Patients  124  83.1545  23.4430  78.9700  87.3389 
  Controls  24  82.8500  18.1609  74.3504  91.3496 
Temporal sector  Patients  124  61.2276  15.6476  58.4346  64.0207 
  Controls  24  74.0000  13.1589  67.8414  80.1586 

Comparison of mean thickness and thickness in each sector of the RNFL. Values are expressed in microns. 95% confidence intervals for means±SD.

Table 3.

RNFL thickness in controls and MS patients without optic neuritis.

RNFL thicknessEyes  Mean  SD  95% confidence interval for the mean
          Lower limit  Upper limit 
Mean thickness  Patients  88  99.4891  13.1589  96.5940  102.3842 
  Controls  24  103.3590  12.6272  97.4493  109.2687 
Superior sector  Patients  88  123.2989  21.3623  118.7459  127.8518 
  Controls  24  124.5000  17.6888  116.2214  132.7786 
Inferior sector  Patients  88  121.6782  18.7135  117.6898  125.6666 
  Controls  24  131.9500  18.4375  123.3209  140.5791 
Nasal sector  Patients  88  64.3793  14.7334  61.2392  67.5194 
  Controls  24  74.0000  13.1589  67.8414  80.1586 
Temporal sector  Patients  88  88.0690  22.3808  83.2990  92.8390 
  Controls  24  82.8500  18.1609  74.3504  91.3496 

Comparison of mean thickness and thickness in each sector of the RNFL. Values are expressed in microns. 95% confidence intervals for means±SD.

Table 4, which analyses mean RNFL thickness and RNFL thickness in each sector by the clinical form of MS, shows a decrease in thickness in the patients with secondary-progressive MS compared to those with relapsing-remitting MS; however, these differences were not statistically significant. When excluding those patients with a history of optic neuritis, the differences were still not significant (Table 5).

Table 4.

RNFL thickness in the patient group, broken down by clinical form of MS.

RNFL thicknessEyes  Mean  SD  95% confidence interval for the mean
          Lower limit  Upper limit 
Mean thickness  Relapsing-remitting  106  94.6412  16.7450  91.4620  97.8204 
  Secondary-progressive  18  93.7679  11.6233  87.0567  100.4790 
Superior sector  Relapsing-remitting  106  118.7982  23.9732  114.2467  123.3497 
  Secondary-progressive  18  115.0714  15.6227  106.0511  124.0918 
Inferior sector  Relapsing-remitting  106  115.5780  22.7340  111.2617  119.8942 
  Secondary-progressive  18  115.0714  17.4067  105.0211  125.1218 
Nasal sector  Relapsing-remitting  106  83.3486  24.2496  78.7446  87.9526 
  Secondary-progressive  18  81.6429  16.4157  72.1647  91.1210 
Temporal sector  Relapsing-remitting  106  61.4404  15.7041  58.4588  64.4219 
  Secondary-progressive  18  59.5714  15.6731  50.5220  68.6208 

Comparison of mean thickness and thickness in each sector of the RNFL. Values are expressed in microns. 95% confidence intervals for means±SD.

Table 5.

RNFL thickness in MS patients without optic neuritis, broken down by clinical form of MS.

RNFL thicknessEyes  Mean  SD  95% confidence interval for the mean
          Lower limit  Upper limit 
Mean thickness  Relapsing-remitting  76  100.1324  13.8377  96.9486  103.3162 
  Secondary-progressive  12  95.4683  11.5748  88.1140  102.8226 
Superior sector  Relapsing-remitting  76  124.4933  21.8813  119.4589  129.5278 
  Secondary-progressive  12  115.8333  16.6232  105.2714  126.3953 
Inferior sector  Relapsing-remitting  76  122.2800  19.0671  117.8931  126.6669 
  Secondary-progressive  12  117.9167  16.5609  107.3943  128.4390 
Nasal sector  Relapsing-remitting  76  89.0667  22.9925  83.7766  94.3568 
  Secondary-progressive  12  81.8333  17.6214  70.6372  93.0295 
Temporal sector  Relapsing-remitting  76  64.7600  14.6995  61.3779  68.1421 
  Secondary-progressive  12  62.0000  15.3741  52.2317  71.7683 

Comparison of mean thickness and thickness in each sector of the RNFL. Values are expressed in microns. 95% confidence intervals for means±SD.

Degree of disability was established based on EDSS scores. The mean EDSS score was 2.46±2.04. We established the following ordinal scale for EDSS scores: A: <1.5; B: 1.5 to 3.5; and C: >3.5. Twenty-five patients were classified into level A, 24 into level B, and 13 into level C. In our sample, none of the patients scored above 6.5.

Table 6 shows RNFL thickness by EDSS level. The statistical analysis revealed significant differences between EDSS levels in terms of mean thickness (P=.011), and thickness in the superior (P=.017), inferior (P=.013), and temporal (P=.005) sectors.

Table 6.

RNFL thickness broken down by EDSS level.

RNFL thickness  EDSS score  Eyes  Mean  SD  95% confidence interval for the mean
          Lower limit  Upper limit 
Mean thickness  <1.5  50  99.0412  14.3548  94.9616  103.1208 
  1.5-3.5  48  93.5908  15.4139  89.1151  98.0666 
  >3.5  26  87.3688  18.7561  79.6266  95.1110 
Superior sector  <1.5  50  122.7800  20.3071  117.0088  128.5512 
  1.5-3.5  48  119.7083  24.3720  112.6314  126.7852 
  >3.5  26  107.0000  23.2737  97.3931  116.6069 
Inferior sector  <1.5  50  120.8400  20.0482  115.1423  126.5377 
  1.5-3.5  48  115.4375  20.5404  109.4732  121.4018 
  >3.5  26  105.0400  25.8803  94.3571  115.7229 
Nasal sector  <1.5  50  85.8400  24.3229  78.9275  92.7525 
  1.5-3.5  48  81.9167  21.2531  75.7454  88.0879 
  >3.5  26  80.1600  25.9577  69.4452  90.8748 
Temporal sector  <1.5  50  66.7000  15.5514  62.2803  71.1197 
  1.5-3.5  48  58.0000  14.3764  53.8255  62.1745 
  >3.5  26  56.4800  15.4734  50.0929  62.8671 

Comparison of RNFL mean thickness and thickness in each sector. Values are expressed in microns. 95% confidence intervals for means±SD.

After excluding the patients with optic neuritis, the differences between EDSS levels were significant only for mean thickness (P<.05) (Table 7).

Table 7.

RNFL thickness by EDSS level in the group of MS patients without optic neuritis.

RNFL thickness  EDSS score  Eyes  Mean  SD  95% confidence interval for the mean
          Lower limit  Upper limit 
Mean thickness  <1.5  38  103.6062  11.8219  99.6646  107.5479 
  1.5-3.5  34  96.4023  15.5446  91.0625  101.7420 
  >3.5  16  96.5360  10.4546  90.7464  102.3256 
Superior sector  <1.5  38  127.5405  19.0271  121.1966  133.8845 
  1.5-3.5  34  121.2000  25.9261  112.2941  130.1059 
  >3.5  16  117.7333  12.1741  110.9915  124.4751 
Inferior sector  <1.5  38  126.0000  17.6839  120.1039  131.8961 
  1.5-3.5  34  119.4286  20.0107  112.5547  126.3025 
  >3.5  16  116.2667  16.7693  106.9801  125.5532 
Nasal sector  <1.5  38  92.4324  22.0511  85.0802  99.7846 
  1.5-3.5  34  83.4286  23.2749  75.4334  91.4238 
  >3.5  16  88.1333  20.1702  76.9634  99.3032 
Temporal sector  <1.5  38  68.3784  15.1847  63.3155  73.4412 
  1.5-3.5  34  61.5714  14.2298  56.6833  66.4595 
  >3.5  16  61.0667  13.2312  53.7394  68.3939 

Comparison of RNFL mean thickness and thickness in each sector. Values are expressed in microns. 95% confidence intervals for means±SD.

Table 8 shows mean thickness and thickness of each sector in the eyes both with and without a history of optic neuritis (eyes with optic neuritis are further classified by time elapsed since the episode of optic neuritis). Mean thickness was greater in the patients with no optic neuritis than in those with a history of the disorder (onset between 3 and 6 months or more than 6 months previously). Differences between these groups were statistically significant (P<.01) for mean thickness and thickness in the 4 peripapillary sectors.

Table 8.

RNFL thickness in patients with and without optic neuritis.

RNFL thickness  ON  Eyes  Mean  SD 
Mean thickness  ON>6 months  20  80.0711  15.9168 
  ON between 3 and 6 months  16  93.9275  13.3021 
  No history of ON  88  99.2555  13.7123 
Superior sector  ON>6 months  20  103.1071  24.6160 
  ON between 3 and 6 months  16  121.8750  15.5970 
  No history of ON  88  122.9655  21.2660 
Inferior sector  ON>6 months  20  96.2857  21.4973 
  ON between 3 and 6 months  16  121.6250  16.1239 
  No history of ON  88  121.1494  19.3044 
Nasal sector  ON>6 months  20  70.1429  21.1024 
  ON between 3 and 6 months  16  82.5000  19.5375 
  No history of ON  88  87.4023  23.1373 
Temporal sector  ON>6 months  20  51.5357  14.1198 
  ON between 3 and 6 months  16  54.0000  19.4717 
  No history of ON  88  65.0115  15.0838 

Comparison of mean thickness and thickness in each sector of the RNFL. Values are expressed in microns. Mean±SD.

ON, optic neuritis.

We found no significant differences between EDSS levels in terms of mean macular thickness in either the 1000-μm-diameter area or the sectors of the 3000-μm-diameter area (Table 9).

Table 9.

Retinal thickness in the central 1000- and 3000-μm-diameter areas by EDSS level.

Retinal thickness  EDSS score  Eyes  Mean  SD  95% confidence interval for the mean
          Lower limit  Upper limit 
Macular thickness  <1.5  50  217.7800  20.0268  212.0884  223.4716 
  1.5-3.5  48  217.6875  20.7704  211.6564  223.7186 
  >3.5  26  219.0400  24.2632  209.0246  229.0554 
Superior sector  <1.5  50  265.0600  19.7116  259.4580  270.6620 
  1.5-3.5  48  259.2500  19.7263  253.5221  264.9779 
  >3.5  26  257.9600  25.4009  247.4750  268.4450 
Inferior sector  <1.5  50  261.4200  21.2786  255.3727  267.4673 
  1.5-3.5  48  257.7083  20.9649  251.6207  263.7959 
  >3.5  26  254.9200  29.6759  242.6704  267.1696 
Nasal sector  <1.5  50  250.9000  37.4864  240.2465  261.5535 
  1.5-3.5  48  248.0208  29.0088  239.5976  256.4441 
  >3.5  26  247.4000  32.7363  233.8871  260.9129 
Temporal sector  <1.5  50  245.3600  19.6839  239.7659  250.9541 
  1.5-3.5  48  238.8125  21.2869  232.6314  244.9936 
  >3.5  26  236.3200  28.2956  224.6401  247.9999 

Macular thickness: retinal thickness in the central 1000-μm diameter area. Superior, inferior, nasal, and temporal sectors: thickness in the 3000-μm-diameter area. Comparison of RNFL mean thickness and thickness in each sector. Values are expressed in microns. 95% confidence intervals for means±SD.

EDSS, expanded disability status scale.

When comparing quantitative values of macular thickness in the sectors of the 3000-μm-diameter area between patients without optic neuritis and those with a history of optic neuritis (between 3 and 6 months, or more than 6 months) (Table 10), differences were found to be statistically significant in the superior, temporal, and inferior sectors (P<.01).

Table 10.

Retinal thickness in the central 1000- and 3000-μm-diameter areas in patients with and without optic neuritis.

Retinal thickness  History of ON  Eyes  Mean  SD 
Macular thickness  ON>6 months  20  214.5000  20.9982 
  ON between 3 and 6 months  16  212.2500  19.2854 
  No history of ON  88  219.6552  21.2235 
Superior sector  ON>6 months  20  247.1429  23.2215 
  ON between 3 and 6 months  16  250.6250  15.3244 
  No history of ON  88  266.9080  18.2161 
Inferior sector  ON>6 months  20  245.2143  26.8415 
  ON between 3 and 6 months  16  250.6250  14.2722 
  No history of ON  88  263.7126  20.4813 
Nasal sector  ON>6 months  20  239.4286  29.9313 
  ON between 3 and 6 months  16  247.5000  22.6967 
  No history of ON  88  252.3103  34.6219 
Temporal sector  ON>6 months  20  228.6071  25.4490 
  ON between 3 and 6 months  16  230.7500  12.8480 
  No history of ON  88  245.8851  20.2791 

Macular thickness: thickness in the central 1000-μm-diameter area. Superior, inferior, nasal, and temporal sectors: thickness in the 3000-μm-diameter area. Comparison of RNFL mean thickness and thickness in each sector. Values are expressed in microns. Mean±SD.

ON, optic neuritis.

Discussion

Our study analysed RNFL thickness using time-domain optical coherence tomography. RNFL thickness measurements obtained with this tool are strongly correlated with the values obtained with spectral-domain optical coherence tomography; however, the results from these 2 techniques are not interchangeable.16

Our results show a statistically significant decrease in mean RNFL thickness in patients with MS compared to controls. These differences were also statistically significant in the temporal and inferior sectors. However, if we exclude the patients with a history of optic neuritis, differences were significant only in the temporal sector. Pueyo et al.3 and Bock et al.11 described a decrease in thickness in the temporal sector exclusively.

Gundogan et al.17 compared a series of patients with MS with no visual symptoms and a control group without MS, and found a statistically significant reduction in thickness in the temporal sector.

According to Costello et al.,18 the temporal sector is more sensitive to retinal axonal damage in patients with MS. In this study, decreases in mean thickness manifested 2 months after the episode of optic neuritis, whereas decreases in thickness in the superior and inferior sectors manifested after 3 or 4 months. Decreases in RNFL thickness during progression of MS were independent of immunomodulatory therapy.10

In our sample, 85.4% of the patients (53/62) had relapsing-remitting MS and 14.6% (9/62) had secondary-progressive MS. These percentages are similar to those reported by Fisher et al.2 (80% vs 20%) and Iester et al.19 (78.2% vs 21.8%) in their studies of RNFL thickness in patients with MS.

We found differences in mean thickness and thickness in each sector between the patients with secondary-progressive and relapsing-remitting MS both before and after excluding the patients with a history of optic neuritis. Although these differences were not statistically significant, our findings suggest that RNFL thickness is lower in patients with secondary-progressive MS than in those with relapsing-remitting MS.

Oberwahrenbrock et al.20 and Albrecht et al.13 reported differences in RNFL thickness between these 2 clinical forms of MS. Pulicken et al.,21 however, found no statistically significant differences in thickness between these 2 groups.

Henderson et al.22 analysed the differences in RNFL thickness in patients with MS. According to this study, the patients with secondary-progressive MS and no history of optic neuritis showed a significant decrease in thickness compared to controls.

The discrepancies between these results and our own may be due to the heterogeneity of the series, the differences in the number of patients included in each subgroup, and the lack of a model for estimating thickness according to age, sex, and disease duration.

Mean RNFL thickness in patients with MS decreases with disease severity. These decreases are statistically significant in the superior, inferior, and temporal sectors.

In the study by Fisher et al.,2 thickness decreased as EDSS scores increased, which suggests a direct relationship between the degree of optic nerve axonal loss and the level of neurological impairment.

The comparative analysis of RNFL thickness between the eyes with and without optic neuritis showed significant differences in terms of mean thickness and thickness in all the peripapillary sectors. García-Martín et al.23 found more pronounced axonal loss in the eyes with a history of optic neuritis. Optic neuritis episodes in patients with MS cause axonal degeneration during the acute phase. After 6 months, however, RNFL atrophy is associated with MS progression regardless of the history of optic neuritis.

Regarding macular thickness in 1000- and 3000-μm-diameter areas, we found no significant differences between EDSS levels. However, we did find significant differences in macular thickness in the temporal, superior, and inferior sectors of the 3000-μm-diameter area between the patients with a history of optic neuritis and those without. The patients with a history of optic neuritis had greater thickness in those sectors than the patients without optic neuritis.

In our study, we measured thickness in the central 1000-μm-diameter area since it has a higher ratio of bipolar cells to ganglion cells, which led us to hypothesise that there may be a connection between RNFL thickness and retinal thickness. However, the differences between groups were not statistically significant.

Burkholder et al.24 studied RNFL thickness and macular volume in a series of patients with MS and no history of optic neuritis and found statistically significant differences in both parameters between patients with MS and controls.

In summary, mean RNFL thickness decreases as EDSS scores increase. Patients with a history of optic neuritis usually show a more marked axonal loss; this decrease in thickness has been shown to depend on the time elapsed from the last episode of optic neuritis. In contrast, we found no connection between macular thickness within the central 1000- and 3000-μm-diameter areas and EDSS scores.

Conflicts of interest

The authors have no conflicts of interest to declare.

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Please cite this article as: Soler García A, Padilla Parrado F, Figueroa-Ortiz LC, González Gómez A, García-Ben A, García-Ben E, et al. Análisis del grosor macular y de capa de fibras nerviosas en pacientes con escle rosis múltiple en relación con su nivel de gravedad y antecedentes previos de neuritis óptica. Neurología. 2016;31:379–388.

Copyright © 2014. Sociedad Española de Neurología
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