The Egyptian Journal of Neurology, Psychiatry and Neurosurgery

ORIGINAL ARTICLE
Year
: 2016  |  Volume : 53  |  Issue : 4  |  Page : 200--205

Visual dysfunction and neurological disability in multiple sclerosis patients in correlation with the retinal nerve fiber layer and the ganglion cell layer using optical coherence tomography


Said A Gomaa1, Mohamed B Badawy1, Amr M Elfatatry2, Amr A Elhennawy3,  
1 Department of Ophthalmology, Faculty of Medicine, University of Alexandria, Alexandria, Egypt
2 Department of Neuropsychiatry, Faculty of Medicine, University of Alexandria, Alexandria, Egypt
3 Department of Ophthalmology, General Ophthalmology Hospital, Alexandria, Egypt

Correspondence Address:
Amr A Elhennawy
28 Omar Elmokhtar Street, Alhamd Building, 8th Floor, Alexandria
Egypt

Abstract

Aim The aim of this study was to measure retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) complex thickness with Cirrus optical coherence tomography (OCT) in Egyptian multiple sclerosis (MS) patients, and to correlate the OCT findings with the visual functions and neurological conditions. Patients and methods This study design was a cross-sectional one. A total of 40 eyes of 22 MS patients diagnosed according to the McDonald criteria were included in this study. Exclusion criteria were as follows: optic neuritis less than 6 months ago; best-corrected visual acuity (BCVA) less than 0.5; intraocular pressure more than 21 mmHg; cup-to-disc ratio more than 0.5; myopia more than 5 D; and eyes with other ocular or central nervous system diseases. All patients were subjected to the following: full history taking; complete ophthalmic examination, including visual functions (BCVA, color vision, and contrast sensitivity), intraocular pressure, and anterior and posterior segment examination; ophthalmic investigations using the Cirrus OCT (peripapillary RNFL thickness and macular GCL complex thickness); and complete neurological examination containing Expanded Disability Status Scale (EDSS). Results There were statistically significant negative correlations (which is mostly still thickened or biased with BCVA selection) between BCVA and the GCL complex of the superior areas among the studied patients. There were statistically significant negative correlations between color total errors and the GCL complex of the inferior temporal areas among the studied patients. No statistically significant correlations between contrast or EDSS and the GCL complex of any area were found among the studied patients. Conclusion GCL complex thickness is correlated better compared with RNFL thickness in MS patients with their visual functions (mainly color vision with the inferior temporal area of the GCL complex), and visual function is better correlated with them than with neurological disability measured using EDSS.



How to cite this article:
Gomaa SA, Badawy MB, Elfatatry AM, Elhennawy AA. Visual dysfunction and neurological disability in multiple sclerosis patients in correlation with the retinal nerve fiber layer and the ganglion cell layer using optical coherence tomography.Egypt J Neurol Psychiatry Neurosurg 2016;53:200-205


How to cite this URL:
Gomaa SA, Badawy MB, Elfatatry AM, Elhennawy AA. Visual dysfunction and neurological disability in multiple sclerosis patients in correlation with the retinal nerve fiber layer and the ganglion cell layer using optical coherence tomography. Egypt J Neurol Psychiatry Neurosurg [serial online] 2016 [cited 2017 Aug 16 ];53:200-205
Available from: http://www.ejnpn.eg.net/text.asp?2016/53/4/200/202376


Full Text

 Introduction



Multiple sclerosis (MS) is a chronic demyelinating and neurodegenerative disease of the central nervous system [1].

The exact etiology of MS is unknown [2].

Axonal loss may ultimately determine neurologic disability [3],[4].

A person with MS can have almost any neurological symptom or sign [5].

MS affects many aspects of vision and ocular health, from afferent to efferent pathways [6],[7],[8],[9].

There is a correlation between retinal nerve fiber layer (RNFL) thickness and visual function, both cross-sectionally [10],[11],[12] and longitudinally over time [13],[14]. Ganglion cell layer (GCL)+inner plexiform layer (IPL) thinning was significantly associated with reduced visual function and vision-specific quality of life [15],[16],[17].

Optical coherence tomography (OCT) is a noninvasive imaging technology that provides high-resolution cross-sectional images of tissue microstructures in vivo [18].

 Patients and methods



Forty eyes of 22 MS patients [18 oculus utro (OU) (bilaterally) and four oculus dexter (OD) (right)] from outpatient clinics of the Department of Neurology diagnosed according to the McDonald criteria were included in this study. The procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation and with the principals of Helsinki Declaration. Informed consent was obtained from all participants, and ethical committee permission from our institution was obtained before starting our work. Exclusion criteria were as follows: episode of optic neuritis (ON) less than 6 months ago; best-corrected visual acuity (BCVA) less than 0.5 decimal; intraocular pressure (IOP) more than 21 mmHg; cup-to-disc ratio more than 0.5; myopia more than 5 D; and eyes with other ocular diseases and other central nervous system diseases.

All patients were subjected to the following: full history taking; complete ophthalmic examination, including visual functions [BCVA using Tumbling E Eye Chart, color vision using Roth 28-Hue Test, and total error score calculated according to Erb et al. [19] and contrast sensitivity using The Snellen contrast Chart]; IOP; and anterior and posterior segment examination), ophthalmic investigations using the OCT for each studied eye, three optic disc cubes 200×200 scans, and three macular cubes 512×128 were taken with the Cirrus HD-OCT (software version 6.0.0.599; Carl Zeiss Meditec Inc., California, USA) ([Figure 1] and [Figure 2]) on the same session by the same operator.{Figure 1}{Figure 2}

Pupils were dilated to at least 7 mm. Artificial tears were instilled in participants suffering from dry eye. Macular scans were taken before optic disc cube scans. Between the two procedures, participants were allowed to rest for few seconds, and they were allowed to lean backward between each scan.

Uncooperative participants with frequent blinking or poor fixation were excluded from the study. In addition, scans with signal strength less than 5, interscan signal strength differences more than 3, malpositioned scans, or scans showing any pathological condition not detected with clinical examination were excluded from the study, and complete neurological examination containing Expanded Disability Status Scale (EDSS) was carried out.

Statistical analysis

Data were analyzed using IBM SPSS software package, version 20.0, IBM Inc., Chicago, IL, USA.

 Results



The study included 40 eyes of 22 patients (18 OU and four OD). There were 17 female and five male patients. Their ages ranged between 23 and 50 years, with a mean age of 36.45±7.84 years. As regards ON, there were nine patients who did not have ON and 13 patients with ON [six patients OD, six patients oculus sinister (left), and one OU]. MS duration in the studied patients ranged between 1.2 and 15 years with a mean duration of 6.57±4.4 years. The frequency of MS in the last year in the studied patients ranged between 0 and 5 attacks with a mean frequency of 1.27±1.35. Last attack of MS in the studied patients ranged between 2 and 28 months with a mean of 9.05±7.49. As regards BCVA it ranged between decimal 0.50 and 2 with a mean of 0.95±0.29, whereas the IOP ranged between 8 and 18 mmHg with a mean pressure of 11.08±2.31 and cup–disc ratio ranged between 0.10 and 0.40 with a mean ratio of 0.25±0.10. Refractive error ranged in the sphere refraction of the studied patients between −2 and +3.25 with a mean of −0.16±0.96, whereas the cylinder refraction ranged between −4.5 and 0 with a mean of −0.58±0.84. The range of contrast sensitivity of the studied patients was between 80 and 100% with a mean of 88±8.53. The range of the color total error in the studied patients was between 108 and 660 with a mean of 292.2±127.48. As regards the EDSS, the range of the scale in the studied patients was between 0 and 6 with a mean of 2.57±1.83.

As regards the GCL complex, the average ranged between 46.0 and 86.0 with a mean of 68.55±9.36. As regards the RNFL, the range of the thickness in average in the studied patients was between 57.0 and 103.0 with a mean thickness of 78.50±12.95.

The correlations between the RNFL and different studied parameters among the studied patients is presented in [Table 1]and the correlation of the GCL complex with different studied parameters is presented in [Table 2].{Table 1}{Table 2}

 Discussion



However, dyschromatopsia is well documented in MS patients, even in those without a history of acute ON [20],[21]. In the present study there were statistically significant negative correlations between color total errors and the GCL complex of inferior temporal areas only among the studied patients. Martínez-Lapiscina et al. [20] stated that impaired color vision in non-ON eyes was detected in 21 of 108 patients at baseline; they said that these patients had thinner RNFL.

Although Walter et al. [15] stated that peripapillary RNFL and macular GCL+IPL were significantly correlated with visual acuity (P≤0.001), 2.5% low-contrast letter acuity (P<0.001), and 1.25% low-contrast letter acuity (P≤0.001), all these correlations were not significant in our study; a part of it may be due to their usage of low-contrast charts unlike us.

Villoslada et al. [23] stated that we found that MS patients have impairments in high-contrast visual acuity and low-contrast visual acuity (P<0.001) but that they suffer from even more profound abnormalities in color discrimination (P<0.0001), but there was a correlation between color vision and spectral domain OCT measures of RNFL thickness.

As regards the GCL complex, our correlation is in agreement with that by Lampert et al. [11]; they found moderate significant correlations between color vision and the ganglion cell complex (ρ=0.353, P<0.001).

One of the most important findings from OCT in studies of patients with MS (both with and without a history of acute ON) is the correlation between RNFL thickness and visual function, both cross-sectionally [10],[11],[12] and longitudinally over time [13],[14].

In 2006, Costello et al. [11] reported that the majority of patients with MS who have ON (about 75%) will sustain 10–40 µm of RNFL loss within a period of ∼3–6 months, and hence one of our exclusion criteria was history of ON less than 6 months.

In 2005, Fisher et al. [10] found that lower visual function scores were associated with reduced average overall RNFL thickness in MS eyes; for every one-line decrease in low-contrast letter acuity or contrast sensitivity score, the mean RNFL thickness decreased by 4 µm.

The first longitudinal study to investigate the relationship between RNFL thickness and visual loss was carried out by Talman et al. [14]. The authors concluded that progressive RNFL thinning occurs as a function of time in some patients with MS, even in the absence of ON.

Sakai et al. [25] demonstrated that GCL+IPL thinning is most significantly correlated with both visual function and vision-specific quality of life in MS.

Earlier studies of total macular volume using time domain OCT suggested that retinal ganglion cell neuronal loss occurs in MS eyes and that this correlates with visual function [26].

Davies et al. [27] stated that reduced GCL volumes were not associated with worse high-contrast visual acuity (P=0.14), but did predict visual loss with low-contrast acuity (P=0.003).

In contrast to our study results, EDSS was correlated with retinal thinning and more with GCL complex thinning in the study by Tátrai et al. [28]. The results of Malik et al. [22] are in agreement with our study with regard to EDSS; they stated that all quadrants of the GCL and the IPL in both eyes were significantly decreased in MS patients (P<0.005). The mean OD RNFL was significantly reduced in MS versus healthy controls (P<0.05); no layer showed consistent associations with EDSS or Functional System scores.

 Conclusion



GCL complex thickness is correlated better than RNFL thickness in MS patients with their visual functions; color vision is more sensitive compared with contrast sensitivity and BCVA in MS patients in correlation with retinal structures. In MS patients, visual function is better correlated with retinal structures compared with neurological disability measured with EDSS.

Recommendations

Multicenter studies on larger scales of MS patients should be conducted to cover most areas of Egypt to give more accurate data about Egyptian MS patients. Low-contrast visual acuity if available will be more accurate in such correlations. BCVA must not be selected in such correlations and visual field and electrophysiological studies should be included.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Fox RJ, Miller DH, Phillips JT, Hutchinson M, Havrdova E, Kita M et al. CONFIRM Study Investigators Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N Engl J Med 2012; 367:1087–1097.
2Oksenberg JR, Hauser SL. Genetics of multiple sclerosis. Neurol Clin 2005; 23:61–75.
3Ferguson B, Matyszak MK, Esiri MM, Perry VH. Axonal damage in acute multiple sclerosis lesions. Brain 1997; 120:393–399.
4Van Waesberghe JH, Kamphorst W, de Groot CJ, van Walderveen MA, Castelijns JA, Ravid R. Axonal loss in multiple sclerosis lesions: magnetic resonance imaging insights into substrates of disability. Ann Neurol 1999; 46:747–754.
5Dyment DA, Cader MZ, Willer CJ, Risch N, Sadovnick AD, Ebers GC. A multigenerational family with multiple sclerosis. Brain 2002; 125:1474–1482.
6Chen L, Gordon LK. Ocular manifestations of multiple sclerosis. Curr Opin Ophthalmol 2005; 16:315–320.
7Graves J, Balcer LJ. Eye disorders in patients with multiple sclerosis: natural history and management. Clin Ophthalmol 2010; 4:1409–1422.
8Allegri P, Rissotto R, Herbort CP, Murialdo U. CNS diseases and uveitis. J Ophthalmic Vis Res 2011; 6:284–308.
9Steinlin MI, Blaser SI, MacGregor DL, Buncic JR. Eye problems in children with multiple sclerosis. Pediatr Neurol 1995; 12:207–212.
10Fisher JB, Jacobs DA, Markowitz CE, Galetta SL, Volpe NJ, Nano-Schiavi ML et al. Relation of visual function to retinal nerve fiber thickness in multiple sclerosis. Opththalmology 2006; 113:324–332.
11Costello F, Coupland S, Hodge W, Lorello GR, Koroluk J, Pan YI et al. Quantifying axonal loss after optic neuritis with optical coherence tomography. Ann Neurol 2006; 59:963–969.
12Henderson APD, Trip SA, Schottman PG, Altmann DR, Garway-Heath DF, Plant GT et al. An investigation of the retinal nerve fibre layer in progressive multiple sclerosis using optical coherence tomography. Brain 2008; 131:277–287.
13Henderson APD, Altmann DR, Trip SA, Kallis C, Jones SJ, Schlottmann PG et al. A serial study of retinal changes following optic neuritis with sample size estimates for acute neuroprotection trials. Brain 2010; 133:2592–2602.
14Talman LS, Bisker ER, Sackel DJ, Long DA, Galetta KM, Ratchford JN et al. Longitudinal study of vision and retinal nerve fiber layer thickness in multiple sclerosis. Ann Neurol 2010; 67:749–760.
15Walter SD, Ishikawa H, Galetta KM, Sakai RE, Feller DJ, Henderson SB et al. Ganglion cell loss in relation to visual disability in multiple sclerosis. Ophthalmology 2012; 119:1250–1257.
16Ishikawa H, Stein DM, Wollstein G, Beaton S, Fujimoto JG, Schuman JS. Macular segmentation with optical coherence tomography. Invest Ophthalmol Vis Sci 2005; 46:2012–2017.
17Tan O, Chopra V, Lu AT, Schuman JS, Ishikawa H, Wollstein G et al. Detection of macular ganglion cell loss in glaucoma by Fourier-domain optical coherence tomography. Ophthalmology 2009; 116:2305–2314.
18Huang D, Swanson EA, Lin CP. Optical coherence tomography. Science 1991; 254:1178–1181.
19Erb C, Adler M, Stübiger N, Wohlrab M, Thiel HJ. Evaluationof the desaturated Roth 28-hue colour test-preliminary results. In: Cavonius CR, editor. Colour-vision deficiencies XIII Documenta Ophthalmologica Proceedings Series 59. Dordrecht, the Netherlands: Kluwer; 1997:323–329.
20Martínez-Lapiscina EH, Ortiz-Pérez S, Fraga-Pumar E, Martínez-Heras E, Gabilondo I, Llufriu S et al. Colour vision impairment is associated with disease severity in multiple sclerosis. Mult Scler 2014; 20:1207–1216.
21Moura AL, Teixeira RA, Oiwa NN, Costa MF, Feitosa-Santana C, Callegaro D et al. Chromatic discrimination losses in multiple sclerosis patients with and without optic neuritis using the Cambridge Colour Test. Vis Neurosci 2008; 25:463–468.
22Malik MT, Healy B, Glanz B, Weiner H, Chitnis T. In vivo assessment of retinal neuronal layers in multiple sclerosis patients. Neurology 2014; 82(Suppl):2.
23Villoslada P, Cuneo A, Gelfand J, Hauser SL, Green A. Color vision is strongly associated with retinal thinning in multiple sclerosis. Mult Scler 2012; 18:991–999.
24Lampert EJ, Andorra M, Torres-Torres R, Ortiz-Pérez S, Llufriu S, Sepúlveda M et al. Color vision impairment in multiple sclerosis points to retinal ganglion cell damage. J Neurol 2015; 262:2491–2497.
25Sakai RE, Feller DJ, Galetta KM, Galetta SL, Balcer LJ. Vision in multiple sclerosis: the story, structure-function correlations, and models for neuroprotection. J Neuroophthalmol 2011; 31:362–373.
26Burkholder BM, Osborne B, Loguidice MJ, Bisker ER, Frohman TC, Conger A et al. Macular volume determined by optical coherence tomography as a measure of neuronal loss in multiple sclerosis. Arch Neurol 2009; 66:1366–1372.
27Davies EC, Galetta KM, Sackel DJ, Talman LS, Frohman EM, Calabresi PA et al. Retinal ganglion cell layer volumetric assessment by spectral-domain optical coherence tomography in multiple sclerosis: application of a high-precision manual estimation technique. J Neuroophthalmol 2011; 31:260–264.
28Tátrai E, Simó M, Iljicsov A, Németh J, Debuc DC, Somfai GM. In vivo evaluation of retinal neurodegeneration in patients with multiple sclerosis. PLoS One 2012; 7:e30922.