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 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 60  |  Issue : 2  |  Page : 162-165

Retinal nerve fibre layer changes in optic neuritis in Indian population


Department of Neuro Ophthalmology, Aravind Eye Hospital, Madurai, Tamil Nadu, India

Date of Submission17-Apr-2022
Date of Decision20-May-2022
Date of Acceptance20-May-2022
Date of Web Publication30-Jun-2022

Correspondence Address:
Kowsalya Akkayasamy
No. 1, Aravind Eye Hospital, Anna Nagar, Madurai, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/tjosr.tjosr_41_22

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  Abstract 


Context: Retinal nerve fibre layer (RNFL) loss associated with optic neuritis has been documented in western literature. However, only one study documents the same in Indian eyes. The RNFL thickness varies from in different populations, and several genetic and environmental factors may have an impact on RNFL changes. Aims: To evaluate retinal nerve fibre layer changes using spectral domain optical coherence tomography associated with optic neuritis in Indian population. Settings and Design: This was a cross-sectional observational study conducted at a tertiary eye care hospital in India, in the department of Neuro Ophthalmology. Methods and Material: This was a cross-sectional observational study which included 20 patients who were diagnosed to have optic neuritis, three months to one year prior. SDOCT was done to measure RNFL thickness and the same was compared with fellow unaffected eyes and normative database. Results: Average RNFL thickness of unilaterally affected eye (80.77 ± 25.59 μm), was significantly reduced when compared to the unaffected eye (97.92 ± 24.46 μm) (P = 0.031) and the normative data of device (98 ± 1.0 μm) (P = 0.031). Average RNFL thickness of bilaterally affected eyes was (67.71 ± 27.09 μm), and significantly reduced when compared with the normative data (98.43 ± 0.76μm) (P < 0.001). Conclusions: An overall significant reduction in the RNFL thickness was observed in the affected eyes when compared to the fellow unaffected eyes and the normative database. This reduction was most pronounced in the temporal quadrant indicating the affliction of the papillomacular bundle.

Keywords: Retinal nerve fibre layer loss, optic neuritis, optical coherence tomography


How to cite this article:
Ravikumar A, Muraleedharan M, Hariharasubramanian K, Chaudhary S, Akkayasamy K. Retinal nerve fibre layer changes in optic neuritis in Indian population. TNOA J Ophthalmic Sci Res 2022;60:162-5

How to cite this URL:
Ravikumar A, Muraleedharan M, Hariharasubramanian K, Chaudhary S, Akkayasamy K. Retinal nerve fibre layer changes in optic neuritis in Indian population. TNOA J Ophthalmic Sci Res [serial online] 2022 [cited 2022 Aug 10];60:162-5. Available from: https://www.tnoajosr.com/text.asp?2022/60/2/162/349523




  Introduction Top


Optic neuritis (ON) is an inflammatory disorder of the optic nerve, representing a common cause of acute optic nerve injury in both adults and children. Adult optic neuritis typically presents as sudden painful uniocular visual loss, with a female predominance. The clinical manifestations and consequent neurological sequelae in children differ considerably when compared to its adult counterpart. Although several aetiologies have been reported which include infectious, demyelinating, granulomatous, autoimmune and paraneoplastic disorders, Multiple sclerosis (MS) is one of the most frequent associations.[1]

Multiple sclerosis is an inflammatory and a neurodegenerative process.[2],[3] Retinal nerve fibre layer (RNFL) defects and optic disc atrophy are common clinical features resulting from the involvement of the afferent visual pathway.[4],[5],[6] Axons of the retinal ganglion cells (RGC) constitute the RNFL. The resulting degeneration of these axons from optic nerve inflammation in optic neuritis are responsible for the visible RNFL defects.[5],[6] Quantification of these deficits in vivo has now been made possible with the invent of optical coherence tomography (OCT). This indirectly measures the axonal injury in the afferent visual pathway in optic neuritis patients, which is presumed to occur early in the course of the disease.

OCT is a non-invasive, quick, economical and easy to use optical imaging modality. Based on the principle of optical interference, it uses near infrared light to generate high resolution and reproducible images of the retina.[7] Western literature has documented RNFL changes using OCT associated with optic neuritis. However, only one study evaluates the changes in Indian population.[8]

In this study, we evaluate the RNFL thickness in Indian eyes affected with optic neuritis using spectral domain OCT (SDOCT) and compare it with fellow unaffected eye, as well as the normative database.


  Subjects and Methods Top


This was a cross-sectional observational study to evaluate the retinal nerve layer thickness (RNFLT) in optic neuritis using Spectral Domain Optical Coherence Tomography (SDOCT-Heidelberg Engineering software version 5.4.6). The RNFLT measured in the affected eye in unilateral cases, was compared with the same in the fellow unaffected eye and the normative database of the SDOCT. In bilaterally affected eyes, the RNFLT was compared only with the normative data. Visual acuity was measured using Snellen's chart, color vision using Ishihara chart, visual fields using Bjerrum's screen and contrast sensitivity using Pelli-Robson chart. A thorough torch light and dilated slit lamp examination was done, where fundus was evaluated using a 90-dioptre lens.

Clinically diagnosed cases of unilateral and bilateral optic neuritis, below the age of 60 years, having the disease onset three months to one year prior, were included in the study. Patients with recurrent optic neuritis, impaired visual fixation, confounding factors which are likely to cause defective vision in the clinically affected eye, medial opacities, diabetic retinopathy, autoimmune disorders and those with paraneoplastic syndromes were excluded from the study. This study was conducted in the Neuro Ophthalmology Department of a tertiary eye care hospital, from January 2013 to May 2014, after approval from Institutional Ethics Committee.

Statistical analysis used

Descriptive statistics were presented with frequency and percentage for categorical parameters. Mean and standard deviations (SD) were used for continuous parametric data. Normality of the data was checked by using Shapiro-Wilk test and Box-Whisker plot. Student t-test/Mann–Whitney U test was used to find out the significant difference between affected and unaffected eye also find out the difference between affected eye and normal data. P value < 0.05 considered as statistical significance. All analysis was carried out by using STATA 14.0 (Texas, USA).


  Results Top


During the study period, all cases that fulfilled the inclusion and exclusion criteria were chosen for the study, yielding a sample size of 20. A post-hoc power analysis was performed to ensure that the study's power was adequate. The average RNFL thickness for the bilateral cases (one of the objectives) in the affected (67.71) and the normal eyes (98.43) were used for the power analysis, which resulted in a power of 88%.

Overall, optic neuritis was found to be more common in females (60%) and to have a unilateral presentation (65%). [Table 1] represents the presenting BCVA and shows that visual loss varied from mild to profound without any predominance. Defective colour vision (92.6%), decreased contrast sensitivity (92.6%), relative afferent pupillary defect (94.6%), disc changes (83.8%), abnormal visual fields (86.5%) were present in majority of patients. Most common visual field defect encountered was a centrocecal scotoma.
Table 1: Presenting BCVA

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RNFL thickness was measured in six quadrants – superotemporal, temporal, inferotemporal, inferonasal, nasal and superonasal – using SD-OCT. The thickness in each quadrant of the involved eye was compared with thickness in the same quadrant of the unaffected eye of the same individual and with the normative data. In bilateral cases, RNFL thickness was only compared with the normative data.

[Table 2] and [Table 3] summarise the RNFL thickness in each quadrant along with an overall average, and its comparison with the unaffected eye and the normative data respectively.
Table 2: Quadrant wise RNFL thickness comparison between affected eye and unaffected eye

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Table 3: Quadrant wise comparison of RNFL thickness between affected eye and the normative data

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Average RNFL thickness was found to be significantly reduced in unilaterally affected cases (80.77 μm) when compared to the other unaffected eye (97.92 μm) (P < 0.05) and normative data (98 μm) (P < 0.05) as well as in bilateral cases (67.71 μm) when compared to the normative data (98.43 μm) (P < 0.001).

Superotemporal and temporal quadrants showed significant reduction in RNFL thickness in both unilateral and bilateral cases when compared to both, the unaffected eye and the normative data.

Nasal and inferonasal quadrants showed RNFL loss, but it was significantly reduced only when compared with the thickness in the other unaffected eye and not with the normative data.

In inferotemporal quadrant, the reduction was significant when compared with the normative data. Similarly, in superonasal quadrant, RNFL loss was significant only when compared with the normative data but only for bilaterally affected eyes.


  Discussion Top


Our study population's demographic profile matches that of prior studies published in the literature. In accordance with the typical presentation of optic neuritis, there was a female predilection and predominant unilateral involvement.[1]

In our study, average RNFL thickness was found to be significantly reduced in unilaterally affected cases when compared to the other unaffected eye and normative data as well as in bilateral cases when compared to the normative data. The average RNFL thickness was much less in bilaterally affected eyes (67.71 ± 27.09 μm) when compared to the unilaterally affected eyes (80.77 ± 25.59 μm). Superotemporal and temporal quadrants showed most consistent results. Significant RNFL loss was observed when compared to both, unaffected eyes, and the normative database. In Caucasian populations as well, it has been observed that the RNFL loss is more prominent in the temporal quadrant.[9],[10] RNFL loss in other quadrants achieved significance only when compared either with the fellow unaffected eye, or the normative database.

Saxena et al.[8] evaluated RNFL thickness in cases of ON and MS in Indian population. They observed RNFL thinning in all four quadrants for both, ON and MS cases. On comparing the RNFL thinning between the two groups, more thinning was observed in ON cases when compared to MS, although statistically significant difference was found. In both the groups, maximum thinning was observed in temporal quadrant which indicated involvement of papillomacular bundle.

In our study, the earliest point of detection of RNFL changes using SDOCT from disease onset could not be evaluated. Costello et al.[11] observed that significant regional RNFL thinning occurred as early as two months after ON. This was observed in the temporal quadrant, implying that temporal RNFL may be more susceptible to the early impacts of axonal degeneration than other locations. Significant overall, quadrant and sector RNFL thinning developed in the affected at three or more months after ON and stabilised at six months. This could probably represent a window period where optic nerve function can be restored using regenerative strategies. Nasal quadrant showed less consistent comparisons over time.

Optic neuritis is a predominant feature of myelin oligodendrocyte glycoprotein (MOG) antibody disease (MOG-AD) and neuromyelitis optica (NMO). The serological markers for these entities are MOG antibody (MOG-ab) and Aquaporin 4 antibody (AQP4 ab).[12],[13] A systematic review done by Peng et al.[14] has compared the RNFL thickness in MOG-ab positive, AQP4-ab positive, seronegative and MS-like patients. They found that RNFL loss more severe in MOG-ab associated ON than those with seronegative optic neuritis. However, no significant difference between MOG-ab and AQP4-ab affected eyes was found. Comparison between MOG-ab positive and MS-like patients showed inconsistent results.

There have been several studies evaluating the correlation between the RNFL thickness and the visual and neurological function in ON patients.[15],[16],[17],[18],[19],[20],[21],[22] Saxena et al.[8] concluded significant correlation of average RNFL thinning and quadrantic thinning with visual function parameters. Of these, strongest correlation of RNFL loss in ON patients was seen with visual fields. Fisher et al.[16] observed RNFL thickness was reduced significantly among eyes of MS patients (92 μm) versus controls (105 μm) (P < 0.001) and particularly was reduced in multiple sclerosis optic neuritis eyes (85 μm) (P < 0.001). Lower visual function scores were associated with reduced average overall RNFL thickness in MS eyes; for every 1-line decrease in low-contrast letter acuity or contrast sensitivity score, the mean RNFL thickness decreased by 4 μm. Parisi et al.[10] demonstrated a correlation between pattern electroretinogram (pERG) changes and RNFL thickness in MS patients affected by a prior episode of optic neuritis, but a relationship couldn't be established between VEP changes and RNFL thickness. Reduction in the RNFL thickness also correlates with measures of optic nerve and brain atrophy on magnetic resonance imaging (MRI).[19],[21]

The average RNFL thickness (97.92 ± 24.46 μm) in unaffected eye was relatively less, when compared to that of healthy or control population in other studies. Indian eyes tend to have a thinner RNFL as compared to the East Asians and Hispanics though it is thicker than the Caucasian eyes.[23],[24] However this evidence doesn't rule out subclinical RNFL loss in the fellow unaffected eye.

MS has been as accepted as an inflammatory and neurodegenerative process, where the axonal loss can be secondary to optic neuritis, denoting the inflammatory process, as well as subclinical due neurodegeneration. Studies have demonstrated subclinical RNFL loss in MS patients without optic neuritis.[3] This supports the use of RNFL thickness as a biomarker in such patients.

There have been several studies documenting RNFL changes using OCT associated with optic neuritis in western literature.[10],[15],[16],[17],[18],[19],[20],[21] However, to the best of our knowledge only one study evaluates the changes in Indian population.[8] Our study attempts to add to the existing literature and supports the role of OCT as a structural biomarker of optic nerve integrity and the use of RNFL thickness measurement to quantify axonal damage patients presenting with ON.

SDOCT and other retinal imaging modalities, may facilitate visualization of the disease process in optic neuritis and may be helpful in detecting and monitoring the process of neuroprotection in response to therapeutic agents.

A few limitations were identified in our study. Serological tests such as MOG-ab and AQP4-ab were not done. This did not allow for evaluation of RNFL thickness specific to these sub-entities and their comparison. Correlation between RNFL thickness and other visual function parameters was not done. Establishing a strong correlation between the same could have further strengthened the role of RNFL thickness.


  Conclusions Top


An overall significant reduction in the RNFL thickness was observed in the affected eyes when compared to the fellow unaffected eyes and the normative database. This reduction was most pronounced in the temporal quadrant indicating the affliction of the papillomacular bundle. OCT can be used a structural biomarker of optic nerve integrity and RNFL thickness measurement may be able to quantify axonal damage in the visual system in Indian eyes in a way that is comparable to that seen in Caucasian patients and predict visual prognosis.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Bennett JL. Optic neuritis. Continuum 2019;25:1236-64.  Back to cited text no. 1
    
2.
Serbecic N, Beutelspacher SC, Geitzenauer W, Kircher K, Lassmann H, Reitner A, et al. RNFL thickness in MS-associated acute optic neuritis using SD-OCT: Critical interpretation and limitations. Acta Ophthalmologica 2011;89:e451-60.  Back to cited text no. 2
    
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Barkhof F, Filippi M. MRI—the perfect surrogate marker for multiple sclerosis? Nat Rev Neurol 2009;5:182-3.  Back to cited text no. 3
    
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Elbøl P, Work K. Retinal nerve fiber layer in multiple sclerosis. Acta Ophthalmologica 2009;68:481-6.  Back to cited text no. 4
    
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Kerrison JB, Flynn T, Green WR. Retinal pathologic changes in multiple sclerosis. Retina 1994;14:445-51.  Back to cited text no. 5
    
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Frisén L. Insidious atrophy of retinal nerve fibers in multiple sclerosis: Funduscopic identification in patients with and without visual complaints. Arch Ophthalmol 1974;92:91-7.  Back to cited text no. 6
    
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Aumann S, Donner S, Fischer J, Müller F. Optical coherence tomography (OCT): Principle and technical realization. In: Bille JF, editor. High Resolution Imaging in Microscopy and Ophthalmology. Cham: Springer International Publishing; 2019. p. 59-85. Available from: http://link.springer.com/10.1007/978-3-030-16638-0_3. [Last accessed on 2022 Apr 15].  Back to cited text no. 7
    
8.
Saxena R, Bandyopadhyay G, Singh D, Singh S, Sharma P, Menon V. Evaluation of changes in retinal nerve fiber layer thickness and visual functions in cases of optic neuritis and multiple sclerosis. Indian J Ophthalmol 2013;61:562-6.  Back to cited text no. 8
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Bock M, Brandt AU, Dörr J, Kraft H, Weinges-Evers N, Gaede G, et al. Patterns of retinal nerve fiber layer loss in multiple sclerosis patients with or without optic neuritis and glaucoma patients. Clin Neurol Neurosurg 2010;112:647-52.  Back to cited text no. 9
    
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Parisi V, Manni G, Spadaro M, Colacino G, Restuccia R, Marchi S, et al. Correlation between morphological and functional retinal impairment in multiple sclerosis patients. Invest Ophthalmol Vis Sci 1999;40:2520-7.  Back to cited text no. 10
    
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Costello F, Hodge W, Pan Y, Eggenberger E, Coupland S, Kardon R. Tracking retinal nerve fiber layer loss after optic neuritis: A prospective study using optical coherence tomography. Mult Scler 2008;14:893-905.  Back to cited text no. 11
    
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Wynford-Thomas R, Jacob A, Tomassini V. Neurological update: MOG antibody disease. J Neurol 2019;266:1280-6.  Back to cited text no. 12
    
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Carnero Contentti E, Correale J. Neuromyelitis optica spectrum disorders: from pathophysiology to therapeutic strategies. J Neuroinflammation 2021;18:208.  Back to cited text no. 13
    
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Peng A, Kinoshita M, Lai W, Tan A, Qiu X, Zhang L, et al. Retinal nerve fiber layer thickness in optic neuritis with MOG antibodies: A systematic review and meta-analysis. J Neuroimmunol 2018;325:69-73.  Back to cited text no. 14
    
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Trip SA, Schlottmann PG, Jones SJ, Altmann DR, Garway-Heath DF, Thompson AJ, et al. Retinal nerve fiber layer axonal loss and visual dysfunction in optic neuritis. Ann Neurol 2005;58:383-91.  Back to cited text no. 15
    
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Fisher JB, Jacobs DA, Markowitz CE, Galetta SL, Volpe NJ, Nano-Schiavi ML, et al. Relation of visual function to retinal nerve fiber layer thickness in multiple sclerosis. Ophthalmology 2006;113:324-32.  Back to cited text no. 16
    
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Noval S, Contreras I, Rebolleda G, Muñoz-Negrete FJ. Optical coherence tomography versus automated perimetry for follow-up of optic neuritis. Acta Ophthalmologica Scandinavica 2006;84:790-4.  Back to cited text no. 17
    
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Costello 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;59:963-9.  Back to cited text no. 18
    
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Sepulcre J, Fernandez MM, Salinas-Alaman A, Garcia- Layana A, Bejarano B, Villoslada P. Diagnostic accuracy of retinal abnormalities in predicting disease activity in MS. Neurology 2007;68:1488-94.  Back to cited text no. 20
    
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Trip SA, Schlottmann PG, Jones SJ, Li WY, Garway-Heath DF, Thompson AJ, et al. Optic nerve magnetization transfer imaging and measures of axonal loss and demyelination in optic neuritis. Mult Scler 2007;13:875-9.  Back to cited text no. 22
    
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Kanamori A, Escano MF, Eno A, Nakamura M, Maeda H, Seya R, et al. Evaluation of the effect of aging on retinal nerve fiber layer thickness measured by optical coherence tomography. Ophthalmologica 2003;217:273-8.  Back to cited text no. 23
    
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  [Table 1], [Table 2], [Table 3]



 

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