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July2010 Vol.47 Issue:      3 (Supp.) Table of Contents
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Study of the Retinal Nerve Fiber Layer Thickness in Multiple Sclerosis by Using Optical Coherence Tomography

Azza A. Ghali1, Tarek R. Hussein2

 

Departments of Neuropsychiatry1, Ophthalmology2, Tanta University; Egypt

 



ABSTRACT

Background: Multiple sclerosis (MS) is being increasingly recognized as a complex neurodegenerative disorder of the brain and spinal cord Objective: to study the role of optical coherence tomography (OCT) in assessment of RNFL thickness as a structural biomarker for axonal loss in multiple sclerosis (MS). Methods: This study enrolled 15 patients (30 eyes) with remitting relapsing MS, 8 patients with secondary progressive MS, and 16 age and sex-matched healthy controls. Patients were divided into 2 subgroups: group I which included MS patients without optic neuritis (MS-N-ON). Group II included MS patients with history of optic neuritis (MS-ON).   All patients underwent neurologic assessment by Expanded Disability Status Scale (EDSS) and ophthalmic examination that included visual acuity, visual field examination, and OCT to measure retinal nerve fiber layer (RNFL) thickness. Results:  RNFL thickness measured by OCT for all MS patients was significantly reduced compared with the control (p =0.000). RNFL thickness was significantly reduced in MSON eyes compared to healthy controls and MS-N-ON eyes. Although MS ON eyes demonstrate the greatest reductions in RNFL thickness, MS|-N-ON eyes are also abnormal including fellow eyes of MS patients with a history of unilateral optic neuritis. Reduction of average RNFL also showed a correlation with disease duration and neurological disability in MS-N-ON and MS-ON unaffected eyes. Conclusion: The results support potential usefulness of OCT for MS patient monitoring and research applications. [Egypt J Neurol Psychiat Neurosurg. 2010; 47(3): 497-504]

 

Key Words: Retinal nerve fiber layer, Multiple sclerosis, Optical coherence tomography.

 

 

Correspondence to Azza Abbas Ghali, Department of Neuropsychiatry, Tanta University Hospital; Egypt

Tel.: +20127984473.  Email: azzaghali_4@hotmail.com

 





INTRODUCTION

 

Multiple  sclerosis  (MS)  is  being  increasingly recognized as a complex neurodegenerative disorder of the brain and spinal cord that involves autoimmune mechanisms that target both white  and gray matter elements1. Manifestations of MS are heterogeneous and include visual, motor, sensory, cognitive, functional, and emotional symptoms2.   Although MS has long been considered a primary demyelinating disease, axonal loss is of critical importance since this pathologic change appears to correlate with a patient's ultimate disability. Axonal loss is increasingly thought to occur early in the disease course and to be associated with, and predictive of neurologic deficits progressing to permanent disability2,3. Current techniques used to measure axonal loss in MS primarily nonconventional magnetic resonance imaging (MRI)-based sequences, have notable limitations of sufficient resolution to assess specific white matter tracts in the brain and spinal cord in a time-sensitive, cost-efficient protocol.2

The RNFL is of particular interest in MS, firstly, because optic neuritis (ON) is often the pivotal event in establishing the diagnosis4. Secondly, the retinal nerve fiber layer (RNFL) is composed of unmyelinated axons of retinal ganglion cells5,6. Measurements of the RNFL should, therefore, give relatively direct measures of the number of axons present without the confounding variable of tissue loss due to demyelination6. Moreover, it is estimated that nearly 20% of all patients with MS present initially with ON, and an additional 40% will have ON at some point in their disease course and. Preliminary studies have found a loss of RNFL thickness in ON, likely due to axons that are destroyed in the optic nerve.7

Unlike MRI measures of brain or optic nerve atrophy, OCT provides a unique opportunity to measure a structure within the central nervous system that consists of isolated axons (because axons within the RNFL are not myelinated)8,9. Optical coherence tomography is an imaging technology that uses light to create high-resolution, quantitative, real-time, cross-sectional images of biological tissues10. It has been used to image intraretinal layers, including the macular, peripapillary, and optic nerve head regions. The imaging technology of OCT has been compared to that of ultrasonography, but OCT utilizes light, not sound, to map tissue microstructure11. Axonal loss in the RNFL, as measured by OCT, has the potential to become a model to study axonal loss throughout the CNS in patients with MS2. The data  suggest  that  the  visual  system has  a  very high predilection for developing disease related disability  both  from  acute  episodes  of  AON and from the more constitutive elements of the disease process that contribute to an MS related chronic optic neuropathy, and that it could be used effectively to illustrate the histopathology of the disease process in MS12.

 

Aim of the Work

The aim of this work is to study the role of OCT in assessment of RNFL thickness as a structural biomarker for axonal loss in multiple sclerosis.

 

PATIENTS AND METHODS

 

Patients

The study included 23 patients (46 eyes) with clinically defined multiple sclerosis according to the revised McDonald criteria.13 Patients were recruited from inpatient and outpatient clinic in Departments of Neuropsychiatry and Ophthalmology; Tanta University Hospital. They were 21 females and 2 males, their age was ranged from 23 to 44 years (mean= 32.04±6.08). Fifteen patients had remitting relapsing MS (RRMS) and 8 had secondary progressive MS (SPMS) according to the Lublin and Reingold criteria14. Patients were divided into two subgroups: MS with optic neuritis (MS ON) 6 month after the last attack and MS without optic neuritis (MS N-ON). Most of our MS-ON had a single attack of unilateral ON and two have subsequent optic neuritis in both eyes.

Sixteen disease free controls were age (range 23-44 years, mean=34.9+6.3) and sex (14 females and 2 males) matched to the MS patients. They were recruited from staff and from among the family members of patients with no neurological disorders of any nature. Controls were required to have no history of ocular disease; visual acuity (VA) 6 9, normal visual field (VF) examination, and intra-ocular pressure (IOP) < 21 mm Hg. One randomly chosen eye from each control was included in the study.

Exclusion criteria: Patients experiencing an acute attack of ON that occurred less than 6 months prior to OCT examination were excluded from these analyses so that optic nerve edema would not potentially interfere with accurate measurement of RNFL thickness.   Patients with a visual acuity of 6/60 (Snellen scale) or less in both eyes were excluded also, because this would preclude some of the examinations. Patients with co-morbid ocular conditions not related to MS, including advanced glaucoma, and previous known history of retinal pathology (e.g., diabetic retinopathy) as ascertained by a detailed history and examination were excluded. None of the patients were on methylprednisolone treatment at the time of the OCT examination.

All patients were submitted to complete history taking including: duration and course of the disease as relapsing remitting (RRMS) or secondary progressive (SPMS). Presence of prior episodes of optic neuritis as reported by self report, physician report and confirmed by medical record review. Physical disability was assessed by The Expanded Disability Status Scale (EDSS) used in MS clinical trials. Magnetic Resonance Image (MRI) brain was done for all cases after triple dose gadolinium diethylene-triaminepentra acetic acid using (0.5-TESLA general electric sigma contour system). Positive MRI brain images were defined according to the revised McDonald criteria13.  All patients underwent complete ophthalmologic examination.  Evaluation of the optic nerve was performed by means of functional and structural assessments, and included visual acuity (Snellen decimal acuity), visual field examination, and OCT 

Standard automated perimetry (SAP): The visual field was assessed using a Humphrey Field Analyzer (Carl-Zeiss Meditec, Dublin, CA). A SITA Standard strategy, program 30-2, was used in order to decrease the duration of the examination. The outcome measures evaluated were mean deviation (MD, dB).

Optical coherence tomography (OCT): Nerve fiber layer imaging was done using the ZEISS Cirrus™ HD-OCT Model 4000 (Carl Zeiss, Meditec, Dublin, CA) which uses a super luminescent diode laser with a center wavelength of 840 nm. After pharmacologic dilation, three individual 200 x 200 cube optic disc scans were obtained with Cirrus OCT (software version 3.0.0.64). After the patient was seated and properly aligned, the iris was brought into view. The scanning laser ophthalmoscopic image was focused by adjusting for refractive error. Once the optic nerve head was centered on the live scanning laser ophthalmoscopic image using the internal fixation cross, centering (Z-offset) and enhancement (polarization) were optimized. A 6x6-mm square of data was captured. Peripapillary RNFL parameters evaluated were: average thickness (360°), temporal quadrant thickness  (316° to 45°), superior quadrant thickness (46° to 135°), nasal quadrant thickness (136° to 225°) and inferior quadrant thickness (226° to 315°).

 

Statistical Analysis

The data are reported as the mean±SD. The differences between MS patients, and control were evaluated with paired t-tests and Mann Whitney test. Comparing the results between RRMS, SPMS, and control; MS eyes with ON, MS eyes without ON and control was done by using One way ANOVA. Then Tukey test was applied to detect significant cell. Comparisons between non-parametric parameters as mean deviation of visual field were performed using the Kruskal–Wallis test. Correlation between OCT measures and disease duration, and overall disability (as measured by EDSS) were investigated with Spearman rank correlation. In order to test the sensitivity of OCT to detect RNFL affection in MS patients, ROC curve was done.

 

RESULTS

 

The clinical characteristics of the MS patients and control groups are shown in Table (1) and confirm appropriate matching in relation to age. Mean ages in the MS and control groups were 32.043±6.08 years and 34.9±6.28 years, respectively. Women represented about 91% of subjects in both groups (21 MS and 14 controls). The mean of disease duration was 4.7±3.2 years and EDSS score was 3.2±2.1.When both RRMS and SPMS patients were analyzed as a single group and compared with control values, there were significant reductions in RNFL thickness in all quadrants not only in those with a previous acute optic neuritis attack (MS-ON), but also in MS eyes with no history of optic neuritis (MS-NON). Mean deviation of visual field was significantly lower in MS patients than control subjects. On the other hand there was no significant difference between them regarding visual acuity (Table 1).

Comparing the results of OCT measures, visual acuity, and VF mean deviation in RRM, SPMS, and control was done using ANOVA and Kurskal tests (Table 3). The results were significant (p<0.001). Tukey’s test was then applied to detect the significant cell. Its results revealed that there was insignificant difference between RRMS and SPMS patients in all OCT measurements and MD of VF. On the other hand, the differences were significant between each group and the control group (Table 2).

When OCT measures were compared between MSON, MS-N-ON, and healthy control by ANOVA and Kurskal tests; the results were significant.  By Tukey test, RNFL thickness was significantly reduced in MSON eyes (68.13±12.6) compared to healthy controls and MS-N-ON eyes (80.8±13.2 and 93.44±6.22 respectively).  Quadrant analysis showed that, compared with MS N-ON, RNFL thickness in the MSON was significantly lower in superior (100.8±13.5 versus 84.44±17.65), inferior (106.1±15.3 versus 88.6±14.03), and temporal (56.4±10.97 versus 35.6±11.8) quadrants (Table 4). Although eyes with a history of acute optic neuritis (MS ON eyes) demonstrate the greatest reductions in RNFL thickness, MS non-ON eyes had significant reduction in RNFL thickness (including fellow eyes of MS patients with a history of unilateral optic neuritis) comparing with the control. We also examined the relation between average RNFL thickness and more global aspects of the disease in MS, including duration of disease and scores for overall neurological impairment by EDSS (Table 4). In MS ON patients, reduction of the RNFL in the UE correlated with disease duration (p = 0.004; r=-0.767), and disease disability (p=0.024; r=-0.644). Similarly, in MS N-ON there was a correlation between the average RNFL and disease duration (p=0.001; r=-0.748), and disease disability (p=0.05; r=-0.332) (Table 4). Interestingly, there was no correlation between RNFL in the AE of MS ON patients and disease duration (p=0.412; r=-0.282) and neurological disability (p=0.485; r=-0.188). Finally, In order to test the sensitivity of OCT to detect RNFL affection in MS patients, ROC curve was done (Table 5). The results revealed that sensitivity of OCT was 78.3 while the specificity was 97.3%. Moreover, the accuracy of this test was 0.895 (Figure 2).


 

 

Table 1. Characteristics of patients with multiple Sclerosis and disease free controls.

 

 

Patients

Control

T-test and Mann-Whitney Test

Mean±SD

Mean±SD

test value

P-value

Age

32.043±6.084

34.875±6.281

1.590

0.117

Duration

4.7±3.2

 

 

 

EDSS

3.2±2.1

 

 

 

OCT:

Average ( um )

Sup

Nasal

Inferior

Temporal

 

76.391±14.227

95.087±16.828

66.239±11.088

100.000±16.942

49.174±14.960

 

93.438±6.218

108.688±11.182

77.563±4.427

116.875±10.404

69.063±5.721

 

4.622

3.002

3.959

3.735

5.165

 

0.000*

0.004*

0.000*

0.000*

0.000*

VF MD(db)m

-5.172±5.536

-1.106±0.369

-5.285

0.000*

Visual acuity

0.652±0.174

0.700±0.183

0.937

0.352

EDSS expanded disability status scale, OCT optical coherence tomography, SD standard deviation, VF visual field

*Statistically significant at p<0.01

Table 2. Visual Function tests in Relapsing  remitting multiple sclerosis, Secondary progressive multiple sclerosis and disease-free controls.

 

 

RRMS

SPMS

Controls

ANOVA and   Kruskal

Mean±SD

Mean±SD

Mean±SD

test value

P-value

OCT:

Average

75.067±15.501

78.875±11.517

93.438±6.218

11.137F

0.000

Sup

96.033±19.125

93.313±11.717

108.688±11.182

4.611 F

0.014

Nasal

64.233±11.539

70.000±9.395

77.563±4.427

10.063 F

0.000

Inferior

98.900±17.901

102.063±15.317

116.875±10.404

7.122 F

0.002

Temporal

48.767±16.326

49.938±12.455

69.063±5.721

13.173 F

0.000

VF MD(db)

-4.445 (14.67:18.32)

-3.615 (-15.34:2.89)

-0.945 (-1.98:-0.59)

28.533k

0.000

Visual acuity

0.657±0.165

0.644±0.193

0.700±0.183

0.460 F

0.634

OCT optical coherence tomography, RRMS relapsing remitting multiple sclerosis, SD standard deviation, SPMS secondary progressive multiple sclerosis, VF visual field

Tukey's test results:  -

·                  Control Vs Group RRMS <0.001*

·                  Control Vs Group SPMS <0.001* in all parameters except nasal quadrant

·                  Group RRMS Vs Group SPMS ˂0.05 in all parameters

 

 

 

 

Figure 1. OCT of a case of SPMS with no history of optic neuritis showing significant thinning

of all quadrants of both eyes together with significant reduction of the average thickness.

 

Table 3. Visual function tests in multiple sclerosis patients with optic neuritis, without optic neuritis, and control.

 

 

ON MS

NON MS

Control

ANOVA and T 

and Kruskal

Mean±SD

Mean±SD

Mean±SD

test value

P-value

Average

68.125±12.596

80.800±13.200

93.438±6.218

6.056F

0.005

Sup

84.438±17.652

100.767±13.503

108.688±11.182

6.305 F

0.004

Nasal

63.875±13.411

67.500±9.645

77.563±4.427

0.878 F

0.423

Inferior

88.625±14.033

106.067±15.299

116.875±10.404

7.678 F

0.001

Temporal

35.625±11.769

56.400±10.969

69.063±5.721

18.020 F

0.000

VF MD(db)

-8.8950 (-15.34:18.32)

-3.1100 (-12.43: 2.89)

-0.9450 (-1.98:-0.59)

36.02

0.00

Visual acuity

0.638±0.167

0.660±0.179

0.700±0.183

0.608 F

0.549

ON optic neuritis, MS multiple sclerosis, SD standard deviation, VF visual field

Tukey's test results:

·                  Control Vs MS ON ˂0.05*

·                  MSON Versus MS-NO  ˂0.05* in all parameters except nasal quadrant

·                  Control versus MS-N-ON  ˂0.05*  in all parameters

 

 

Table 4. Correlation between OCT parameters and disease duration and severity.

 

 

Correlations

Duration

EDSS

r

P-value

r

P-value

MS-N-ON

Average

-0.748

0.001

-0.332

0.050

Sup

-0.618

0.006

-0.356

0.147

Nasal

-0.711

0.001

-0.255

0.308

inferior

-0.643

0.004

-0.379

0.121

temporal

-0.765

0.000

-0.198

0.430

MSON

UE

Average

-0.767

0.004

-0.644

0.024

Sup

-0.619

0.032

-0.535

0.073

Nasal

-0.019

0.953

0.178

0.580

inferior

-0.777

0.003

-0.180

0.575

temporal

-0.623

0.030

-0.426

0.167

MSON

AE

Average

-0.282

0.412

-0.188

0.485

Sup

-0.426

0.167

-0.189

0.483

Nasal

-0.4638

0.148

-0.202

0.453

inferior

-0.379

0.121

-0.063

0.816

temporal

-0.137

0.557

-0.244

0.363

EDSS Expanded disability status Scale, MS-N-ON Multiple sclerosis without optic neuritis, MSON UE Multiple sclerosis with optic neuritis unaffected eyes, MSON AE Multiple sclerosis with optic neuritis affected eyes

 

 

 

 

 

Figure 2. ROC curve between patient and Control as regard Average RNFL thickness

 

 

Table 5. Sensitivity of OCT (Optical coherence tomography) to detect RNFL (retinal nerve fiber layer) affection in MS patients

 

Cutoff

Sensitivity

Specificity

PPV

NPV

Accuracy

<=87 *      

78.3

93.7

97.3   

60.0

0.895

NPV negative predictive value, PPV positive predictive value

 


DISCUSSION

 

MS is an immune-mediated demyelinating and neurodegenerative disease of the central nervous system. The evidence that axonal damage occurs in MS, and its relationship with permanent disability, has been described previously15. Some recent models support the presence of two connected mechanisms, inflammation and neurodegeneration, taking place in MS16. The retina is a good model for the study of neurodegeneration since it lacks myelin, meaning that changes in the RNFL thickness will be due only to axonal damage. RNFL thickness was assessed by OCT which is non-invasive and noncontact technique provides precise measurements of RNFL thickness17. The aim of this work is to study the role of OCT in assessment of RNFL thickness as a structural biomarker for axonal loss in multiple sclerosis

The effect of age on RNFL thickness has been described in histological studies18 and has recently been demonstrated by means of OCT19. To avoid this source of bias, we selected a control group that was age-matched with the MS patients. Data from 46 eyes of 23 patients with MS (sixteen eyes with ON, 6 months prior and 30 eyes without ON) are reported.

RNFL thickness in eyes of MS patients was significantly reduced compared with the control in all quadrants. These data are supported by previous studies6,17,20,21,22 There was significant reduction in RNFL thickness in both RRMS and SPMS when compared with the control. This data are similar to that reported by Pulicken et al.23. On the other hand there was no significant difference in average RNFL between RRMS and SPMS which is different from data reported by Pulicken et al.23, who found that RNFL thickness is significantly reduced in the progressive forms than RRMS. This difference can be explained by that in our study, most cases of ON present in RRMS group.

The average RNFL thickness was significantly reduced in MSON eyes compared to healthy controls and MS-N-ON eyes. The results were highly significant in every parameter provided by OCT. Our results of RNFL reduction in MS ON patients are in agreement with the findings of previously published data21-26, which showed significant RNFL thinning in this population compared with the control group. Costello et al.24 found thinning of the RNFL thickness measured by OCT in 74% of patients with optic neuritis.

As the visual acuity often recovers well, it is not a good clinical measure to monitor visual dysfunction in MS9, so, we use mean deviation of visual field examination as an index for visual dysfunction in this study as  axonal loss in ON is associated with reduced visual function. This reduced visual function appears as significant reduction in the mean deviation of visual field in patients with optic neuritis when compared with those without optic neuritis. Previous research has shown a correlation between optic nerve atrophy and visual field (VF) mean deviation (MD) in MS patients with a prior episode of optic neuritis25,26

Although eyes with a history of acute optic neuritis (MS ON eyes) demonstrate the greatest reductions in RNFL thickness, MS non-ON eyes are also abnormal (including fellow eyes of MS patients with a history of unilateral optic neuritis), supporting the occurrence of chronic axon damage in MS eyes distinct from episodes of acute optic neuritis. This could be explained by two possible mechanisms. The first one is that there could be a microscopic subclinical process of ongoing inflammatory demyelination and axonal damage which causes chronic demyelination leading to secondary axonal thinning or loss. The other explanation is that the primary pathophysiologic process in MS could be one of neuronal cell death leading to the secondary changes and death of axons6,23.

Average RNFL also showed a correlation with disease duration and neurological disability, two clinical parameters consistently linked with progressive axonal loss2. Axonal damage occurring in MS is responsible for permanent disability17. Fisher et al.26 described a correlation between RNFL thickness and duration of the disease or functional impairment measured by EDSS. These results are in agreement with the findings obtained in this study. In this study, there is significant negative correlation between average RNFL thickness and disease duration and disability in the fellow eyes of MS-ON patients and eyes of MS-N-ON while this correlation is absent in eyes affected by ON.

The thickness of the RNFL around the optic disc is not uniform. Relative thickness of the superior and inferior poles of the disc reflects a greater density of fibers originating from the temporal retina which course around the macula. Because the temporal quadrant of the optic disc is relatively thinner than other quadrants12, the higher significant reduction between MS patients and control; RRMS, SPMS, and control; MS-ON and MS-N-ON appears in this quadrant. The specificity of OCT points to its importance in clinical application to exclude cases without MS. While being highly sensitive, OCT is useful in diagnosing MS.

Our data strongly support the role of assessment of RNFL thickness using OCT provides a unique opportunity to measure a central nervous system structure that consists of axons without myelin. Other important characteristics that make RNFL thickness an appealing candidate biomarker for MS include (1) accessibility of the retina for imaging (reliable and feasible in many patients even without  pupillary dilation), (2) ability to acquire and analyze images quickly and easily (˂ 5 minutes per eye), (3) markedly reduced expense compared with MRI techniques that examine brain and optic nerve morphology, and (4) capacity to correlate structure (RNFL thickness) with its corresponding functional disability in MS directly. By detecting subclinical axon loss with OCT, it may prove to be a useful complementary measure to MRI for the evaluation of MS patients, particularly for assessing neurodegeneration. In this capacity, OCT could conceivably be used for patient monitoring and for evaluating the neuroprotective and reparative drugs that need to emerge among the next generation of MS therapies. Our results provide the rationale and scientific support for further studies to assess and validate OCT-derived measures versus conventional, non-conventional, and regional brain and optic nerve MRI measures for these applications.

 

[Disclosure: Authors report no conflict of interest]

 

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الملخص العربى

 

ان مرض التصلب المتناثر أصبح ينظر اليه بشكل متزايد على أنه مرض ضمورى بالجهاز العصبى ناتج عن خلل بالجهاز المناعى للمرضى مما أدى إلى التهاب وضمور بالمخ والحبل الشوكى. وقد وجد أن الضمور الذى يلحق بالمحاور العصبية هو أساس العجز الذى يصيب المرضى لذا كان من الضرورى البحث عن طريقة تشخيصية لتشخيص هذا الضمور ومتابعة انتشاره كمؤشر لتقدم المرض. وقد وضع هذا البحث لقياس سمك طبقة المحاور العصبية الموجودة فى شبكية العين  بواسطة جهاز الأشعة المقطعية الضوئية المتراصة ودراسة إمكانية اعتبار هذا الجهاز كمؤشر طبى فى تشخيص المرض ومتابعة تطوره. وقد اختيرت طبقة الأعصاب الموجودة بشبكية العين لهذا الغرض نظرا لعدة عوامل: منها أن الأعصاب بشبكية العين مؤلفة فقط من محاور عصبية بدون ميلين كما أن إصابة عصب العين بمرض التصلب المتناثر من الأعراض الشائعة لهذا المرض. وقد شملت الدراسة 23 مريضا مصابين بمرض التصلب المتناثر خمسة عشر منهم المرض لديهم من النوع التردد وثمانية المرض لديهم من النوع المتقدم الثانوى. هذا بالإضافة إلى 16 شخص من الأصحاء كعينة ضابطة. وقد قسم المرضى إلى مجموعتين: الأولى المرضى الذين سبق تعرضهم لالتهاب حاد بعصب العين ستة شهور قبل إجراء البحث والمجموعة الثانية وتشمل المرضى الذين لم يسبق لهم التعرض لهذا الالتهاب من قبل. وقد تم إجراء فحص جميع المرضى إكلينيكيا من أجل تحديد مدة وشدة المرض التصلب المتناثر كما تم فحص المرضى لمعرفة مدى تأثر العصب البصرى بالمرض و ذلك عن طريق تحديد قوة الإبصار وعمل مجال إبصار وأخيرا تم فحص المرضى بواسطة جهاز الأشعة المقطعية الضوئية المتراصة. وقد أظهرت نتائج البحث وجود انخفاض ذو دلالة إحصائية فى سمك طبقة المحاور العصبية بشبكية العين لدى مرضى التصلب المتناثر عنها فى العينة الضابطة. وقد كان هذا الانخفاض واضحا لدى النوعين من المرضى سواء النوع المتردد أو النوع المتقدم الثانوى عند مقارنة كل من النوعين بالعينة الضابطة, وكان هذا الانخفاض واضحا فى المجموعة الأولى عند مقارنتها بالعينة الضابطة أو بالمجموعة الثانية. كما اثبت البحث دور جهاز الأشعة المقطعية الضوئية المتراصة فى تشخيص مرض التصلب المتناثر ومتابعة تقدمه.

 



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