Evaluation of the retinal morphological and functional findings in optic neuritis related to multiple sclerosis

Katarina Katanić Pasovski; Nemanja Rančić; Viktor Pasovski; Marija Sajić; Mirko Resan; Evica Dinčić

doi:10.2298/VSP220525064K

Katarina Katanić Pasovski Military Medical Academy, Clinic for Ophthalmology, Belgrade, Serbia
Nemanja Rančić University of Defence, Faculty of Medicine of the Military Medical Academy, Belgrade, Serbia
Viktor Pasovski Military Medical Academy, Clinic for Neurology, Belgrade, Serbia
Marija Sajić UCL Queen Square Institute of Neurology, Department of Neuroinflammation, London, United Kingdom
Mirko Resan Military Medical Academy, Clinic for Ophthalmology, Belgrade, Serbia
Evica Dinčić Military Medical Academy, Clinic for Neurology, Belgrade, Serbia

DOI: https://doi.org/10.2298/VSP220525064K

Keywords: angiography, diagnosis, multiple sclerosis, optic neuritis, tomography, optical coherence

Abstract

Background/Aim. Unilateral optic neuritis (ON), and its pathological substrate, retrobulbar neuritis (RBN), is a common presentation of multiple sclerosis (MS). The aim of the study was to determine the diagnostic and prognostic value of structural and functional examination using novel ‘swept-source’ optical coherence tomography (SS-OCT) and OCT angiography (OCTA) techniques in patients with MS who experienced RBN. Methods. For examining retinal structural and functional changes in both the affected and nonaffected eye of patients with MS, novel techniques, OCT and OCTA, were used. The obtained results were compared with the results of the same examination on the left and right eye of the healthy controls. Results. Using OCT, significant differences in the structural integrity and thickness of retinal layers between the eye in which RBN had been detected and the contralateral, nonaffected eye were found (83.73 ± 18.36 vs. 98.67 ± 11.84; p = 0.013). On the other hand, the functional examination of the macular vascular plexus did not show significant differences between the affected and the nonaffected eye in these patients (41.86 ± 1.52 vs. 42.52 ± 1.40; p = 0.228). Interestingly, comparing the nonaffected eye of patients with RBN and healthy controls, a significant difference in the thickness of the retinal layers between the contralateral eye of the patient and both healthy eyes of healthy subjects was found. OCT examination showed particularly significant thinning of the macular ganglion cell-inner plexiform layer (mGCIPL) (61.07 ± 5.04 vs. 67.53 ± 4.57; p < 0.001). Conclusion. Overall, our research showed that OCT and OCTA offer an unprecedented opportunity for a safe, reliable, and repetitive assessment of structural and functional retinal changes as invaluable diagnostic and prognostic tools, paving the way for a better understanding of pathogenic mechanisms underlying inflammatory demyelinating and neurodegenerative diseases. In addition, mGCIPL may be a particularly sensitive and reliable biomarker of pathological changes in MS and perhaps in other neurodegenerative diseases.

References

1. Walton C, King R, Rechtman L, Kaye W, Leray E, Ann Marrie R, et al. Rising prevalence of multiple sclerosis worldwide: Insights from the Atlas of MS, third edition. Mult Scler 2020; 26(14): 1816‒21.

2. Compston A, Coles A. Multiple sclerosis. Lancet 2008; 372(9648): 1502‒17.

3. Costello F. The afferent visual pathway: designing a structural-functional paradigm of multiple sclerosis. ISRN Neurol 2013; 2013: 134858.

4. Sørensen TL, Frederiksen JL, Brønnum-Hansen H, Petersen HC. Optic neuritis as onset manifestation of multiple sclerosis: a nationwide, long-term survey. Neurology 1999; 53(3): 473‒8.

5. Shams PN, Plant GT. Optic neuritis: a review. Int MS J 2009; 16(3): 82‒9.

6. Optic Neuritis Study Group. The clinical profile of optic neuritis. Experience of the Optic Neuritis Treatment Trial. Arch Ophthalmol. 1991; 109(12): 1673‒8.

7. Dooley MC, Foroozan R. Optic neuritis. J Ophthalmic Vis Res 2010; 5(3): 182‒7.

8. Costello F. Inflammatory optic neuropathies. Continuum (Minneap Minn) 2014; 20(4 Neuro-ophthalmology): 816‒37.

9. Plant GT. Optic neuritis and multiple sclerosis. Curr Opin Neurol 2008; 21(1): 16‒21.

10. Palace J. Inflammation versus neurodegeneration: consequences for treatment. J Neurol Sci 2007; 259(1‒2): 46‒9.

11. Hauser SL, Oksenberg JR. The neurobiology of multiple sclerosis: genes, inflammation, and neurodegeneration. Neuron 2006; 52(1): 61‒76.

12. 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(2): 324‒32.

13. Filippi M, Preziosa P, Meani A, Ciccarelli O, Mesaros S, Rovira A, et al. Prediction of a multiple sclerosis diagnosis in patients with clinically isolated syndrome using the 2016 MAGNIMS and 2010 McDonald criteria: a retrospective study. Lancet Neurol 2018; 17(2): 133‒42.

14. Klistorner A, Arvind H, Nguyen T, Garrick R, Paine M, Graham S, et al. Multifocal VEP and OCT in optic neuritis: a topographical study of the structure-function relationship. Doc Ophthalmol 2009; 118(2): 129‒37.

15. Garcia-Martin E, Jarauta L, Pablo LE, Bambo MP, Ara JR, Martin J, et al. Changes in peripapillary choroidal thickness in patients with multiple sclerosis. Acta Ophthalmol 2019; 97(1): e77‒e83.

16. Spaide RF, Fujimoto JG, Waheed NK, Sadda SR, Staurenghi G. Optical coherence tomography angiography. Prog Retin Eye Res 2018; 64: 1‒55.

17. Zhang Q, Zheng F, Motulsky EH, Gregori G, Chu Z, Chen CL, et al. A Novel Strategy for Quantifying Choriocapillaris Flow Voids Using Swept-Source OCT Angiography. Invest Ophthalmol Vis Sci 2018; 59(1): 203‒11.

18. Fjeldstad AS, McDaniel J, Witman MA, Ives SJ, Zhao J, Rose JW, et al. Vascular function and multiple sclerosis. J Neurol 2011; 258(11): 2036‒42.

19. Feucht N, Maier M, Lepennetier G, Pettenkofer M, Wetzlmair C, Daltrozzo T, et al. Optical coherence tomography angiography indicates associations of the retinal vascular network and disease activity in multiple sclerosis. Mult Scler 2019; 25(2): 224‒34.

20. Marrie RA, Rudick R, Horwitz R, Cutter G, Tyry T, Campagnolo D, et al. Vascular comorbidity is associated with more rapid disability progression in multiple sclerosis. Neurology 2010; 74(13): 1041‒7.

21. Keményová P, Siarnik P, Sutovský S, Blaho A, Turcáni P, Kollár B. Impairment of endothelial function in patients with multiple sclerosis. Neuro Endocrinol Lett 2015; 36(1): 67‒71.

22. Hirata M, Tsujikawa A, Matsumoto A, Hangai M, Ooto S, Yamashiro K, et al. Macular choroidal thickness and volume in normal subjects measured by swept-source optical coherence tomography. Invest Ophthalmol Vis Sci 2011; 52(8): 4971‒8.

23. Copete S, Flores-Moreno I, Montero JA, Duker JS, Ruiz-Moreno JM. Direct comparison of spectral-domain and swept-source OCT in the measurement of choroidal thickness in normal eyes. Br J Ophthalmol 2014; 98(3): 334‒8.

24. Sriram P, Wang C, Yiannikas C, Garrick R, Barnett M, Parratt J, et al. Relationship between optical coherence tomography and electrophysiology of the visual pathway in non-optic neuritis eyes of multiple sclerosis patients. PLoS One 2014; 9(8): e102546.

25. saidha A, Balcer LJ, Calabresi PA, Costello F, Frohman TC, Frohman EM, et al. Retinal layer segmentation in multiple sclerosis: a systematic review and meta-analysis. Lancet Neurol 2017; 16(10): 797‒812.

26. Saidha S, Syc SB, Durbin MK, Eckstein C, Oakley JD, Meyer SA, et al. Visual dysfunction in multiple sclerosis correlates better with optical coherence tomography derived estimates of macular ganglion cell layer thickness than peripapillary retinal nerve fiber layer thickness. Mult Scler 2011; 17(12): 1449‒63.

27. Saidha S, Sotirchos ES, Oh J, Syc SB, Seigo MA, Shiee N, et al. Relationships between retinal axonal and neuronal measures and global central nervous system pathology in multiple sclerosis. JAMA Neurol 2013; 70(1): 34‒43.

28. Janáky M, Jánossy Á, Horváth G, Benedek G, Braunitzer G. VEP and PERG in patients with multiple sclerosis, with and without a history of optic neuritis. Doc Ophthalmol 2017; 134(3): 185‒93.

29. Garcia-Martin E, Pueyo V, Pinilla I, Ara JR, Martin J, Fernandez J. Fourier-domain OCT in multiple sclerosis patients: reproducibility and ability to detect retinal nerve fiber layer atrophy. Invest Ophthalmol Vis Sci 2011; 52(7): 4124‒31.

30. 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(11): 2520‒7.

31. Xu SC, Kardon RH, Leavitt JA, Flanagan EP, Pittock SJ, Chen JJ. Optical coherence tomography is highly sensitive in detecting prior optic neuritis. Neurology 2019; 92(6): e527‒35.

32. Yau GS, Lee JW, Lau PP, Tam VT, Wong WW, Yuen CY. Longitudinal Changes in Retinal Nerve Fibre Layer Thickness after an Isolated Unilateral Retrobulbar Optic Neuritis: 1-Year Results. Neuroophthalmology 2015; 39(1): 22‒5.

33. Behbehani R, Al-Moosa A, Sriraman D, Alroughani R. Ganglion cell analysis in acute optic neuritis. Mult Scler Relat Disord 2016; 5: 66‒9.

34. Syc SB, Saidha S, Newsome SD, Ratchford JN, Levy M, Ford E, et al. Optical coherence tomography segmentation reveals ganglion cell layer pathology after optic neuritis. Brain 2012; 135(Pt 2): 521‒33.

35. Yoon SP, Grewal DS, Thompson AC, Polascik BW, Dunn C, Burke JR, et al. Retinal Microvascular and Neurodegenerative Changes in Alzheimer's Disease and Mild Cognitive Impairment Compared with Control Participants. Ophthalmol Retina 2019; 3(6): 489‒99.

36. Lanzillo R, Cennamo G, Criscuolo C, Carotenuto A, Velotti N, Sparnelli F, et al. Optical coherence tomography angiography retinal vascular network assessment in multiple sclerosis. Mult Scler 2018; 24(13): 1706‒14.

37. Murphy OC, Kwakyi O, Iftikhar M, Zafar S, Lambe J, Pellegrini N, et al. Alterations in the retinal vasculature occur in multiple sclerosis and exhibit novel correlations with disability and visual function measures. Mult Scler 2020; 26(7): 815‒28.

38. Yilmaz H, Ersoy A, Icel E. Assessments of vessel density and foveal avascular zone metrics in multiple sclerosis: an optical coherence tomography angiography study. Eye (Lond) 2020; 34(4): 771‒8.