The Evaluation of Corneal Innervation Using Corneal Confocal Microscopy
Authors:
I. Kovalová 1,2; M. Horáková 1,2; E. Vlčková 1,2; M. Michalec 3; J. Raputová 1,2; J. Bednařík 1,2
Authors place of work:
Neurologická klinika LF MU a FN Brno
1; CEITEC – Středoevropský technologický institut, MU, Brno
2; Oční klinika LF MU a FN Brno
3
Published in the journal:
Cesk Slov Neurol N 2017; 80/113(1): 49-57
Category:
Original Paper
doi:
https://doi.org/10.14735/amcsnn201749
Summary
Corneal confocal microscopy (CCM) is a novel noninvasive method enabling morphological evaluation of corneal structures including nerve fibers. These fibers are almost exclusively of A-delta and C type, i.e. small unmyelinated and poorly myelinated. CCM is thus used as a diagnostic tool for peripheral neuropathies and in particular small fiber neuropathy. The aim of this study was to introduce this method into clinical practice in the Czech Republic, to set-up appropriate normative data and to verify reproducibility of the method.
Material and methods:
A group of 71 healthy controls was examined using the CCM. The data were used to set normal values in three distinct age-related groups and compare these with CCM findings in a group of 54 patients with diabetic polyneuropathy (DPN). Fully-automated as well as expert manual analysis (by two evaluators) were used for quantification of nerve fiber densities, length and branches to verify reliability of the results.
Results:
CCM evaluation was easy, well-tolerated and time-efficient in the majority of patients/controls. Age-related normal values showed very good applicability in evaluated groups of healthy individuals and DPN patients. Compared to healthy controls, DPN patients showed highly significant changes of all the evaluated CCM parameters. Results by the two evaluators of the expert manual analysis showed very good reliability, while results from the automated analysis showed significantly lower values on the majority of the CCM parameters.
Conclusion:
The present study proved on a rather large cohort of healthy controls and a smaller sample of DPN patients that CCM is a easy to use, safe and reliable approach to evaluating corneal innervation. The data also highlighted the differences between automated analysis expert manual CCM analysis.
The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.
The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.
Key words:
confocal microscopy – cornea – small fiber neuropathy – diabetic neuropathies – reliability of results
Chinese summary - 摘要
激光共聚焦角膜神经支配的评价显微镜
作者:
摘要
角膜的共焦显微镜(角膜的共焦显微镜; CCM)可以实现角膜IU的无创形态学可视化检查。因为角膜神经纤维是薄或小的髓鞘 或没有髓鞘,所以CCM是一种SFN诊断方法,用于一般周围神经病变的检测。这样做的目的是为了引入临床检查的CCM神经系统的做法,在捷克共和国,设置适当的标准数据确定重复性测试。
患者和方法:
71名健康志愿者和54例糖尿病神经病患者(糖尿病神经病; DPN)进行了CCM检测。使用数据是
一套标准的三个不同年龄组。研究结果进行了自动评估和手动分析(由两个评价者独立地),以确定测试的可靠性。
结果:
CCM测试节省时间,运行稳定,并且绝大多数病人耐受性良好。年龄分层的标准数据显示
具有非常不错的人口实用性研究。与健康的CCM相比,DPN患者均已经表现出监测参数的显著变化。两名评估人员进行的手动分析也显示CCM具有很好的一致性,但监测参数的CCM值均显著下降。
结论:
本研究简单,安全和良好的证明通过角膜共焦显微镜测试角膜神经支配的可靠性,
一个包含健康对照和患者的DPN组的大样本研究表明,自动和手动评价的一致性。
关键词:
共聚焦显微镜 - 角膜 - 糖尿病神经病 - 结果的可靠性
Zdroje
1. Tavakoli M, Hossain P, Malik RA. Clinical applications of corneal confocal microscopy. Clin Ophthalmol 2008;2(2):435– 45.
2. Tavakoli M, Marshall A, Pitceathly R, et al. Corneal confocal microscopy: a novel means to detect nerve fibre damage in idiopathic small fibre neuropathy. Exp Neurol 2010;223(1):245– 50. doi: 10.1016/ j.expneurol.2009.08.033.
3. Tavakoli M, Quattrini C, Abbott C, et al. Corneal confocal microscopy: a novel noninvasive test to diagnose and stratify the severity of human diabetic neuropathy. Diabetes Care 2010;33(8):1792– 7. doi: 10.2337/ dc10-0253.
4. Ferrari G, Gemignani F, Macaluso C. Chemotherapy--associated peripheral sensory neuropathy assessed using in vivo corneal confocal microscopy. Arch Neurol 2010;67(3):364– 5. doi: 10.1001/ archneurol.2010.17.
5. Papanas N, Ziegler D. Corneal confocal microscopy: a new technique for early detection of diabetic neuropathy. Curr Diab Rep 2013;13(4):488– 99. doi: 10.1007/ s11892-013-0390-z.
6. Guthoff RF, Zhivov A, Stachs O. In vivo confocal microscopy, an inner vision of the cornea – a major review. Clin Exp Ophthalmol 2009;37(1):100– 17. doi: 10.1111/ j.1442-9071.2009.02016.x.
7. Müller LJ, Pels L, Vrensen GF. Ultrastructural organization of human corneal nerves. Invest Ophthalmol Vis Sci 1996;37(4):476– 88.
8. Pawley JB, Masters BR. Handbook of biological confocal microscopy. Optical Engineering 1996;35(9):2765– 6.
9. Papanas N, Ziegler D. Corneal confocal microscopy: recent progress in the evaluation of diabetic neuropathy. J Diabetes Investig 2015;6(4):381– 9. doi: 10.1111/ jdi.12335.
10. Chen X, Graham J, Dabbah MA, et al. Small nerve fiber quantification in the diagnosis of diabetic sensorimotor polyneuropathy: comparing corneal confocal microscopy with intraepidermal nerve fiber density. Diabetes Care 2015;38(6):1138– 44. doi: 10.2337/ dc14-2422.
11. Petropoulos IN, Alam U, Fadavi H, et al. Rapid automated diagnosis of diabetic peripheral neuropathy with in vivo corneal confocal microscopy. Invest Ophthalmol Vis Sci 2014;55(4):2071– 8. doi: 10.1167/ iovs.13-13787.
12. Lacomis D. Small-fiber neuropathy. Muscle Nerve 2002;26(2):173– 88.
13. Buršová Š, Vlčková E, Hnojčíková M, et al. Vyšetření hustoty intraepidermálních nervových vláken z kožní biopsie – normativní data. Cesk Slov Neurol N 2012;75/ 108(4):455– 9.
14. Vlckova-Moravcova E, Bednarik J, Dusek L, et al. Diagnostic validity of epidermal nerve fiber densities in painful sensory neuropathies. Muscle Nerve 2008;37(1):50– 60.
15. Pritchard N, Edwards K, Dehghani C, et al. Longitudinal assessment of neuropathy in type 1 diabetes using novel ophthalmic markers (LANDMark): study design and baseline characteristics. Diabetes Res Clin Pract 2014;104(2):248– 56. doi: 10.1016/ j.diabres.2014.02.011.
16. Lovblom LE, Halpern EM, Wu T, et al. In vivo corneal confocal microscopy and prediction of future-incident neuropathy in type 1 diabetes: a preliminary longitudinal analysis. Can J Diabetes 2015;39(5):390– 7. doi: 10.1016/ j.jcjd.2015.02.006.
17. Tavakoli M, Marshall A, Thompson L, et al. Corneal confocal microscopy: a novel noninvasive means to diagnose neuropathy in patients with Fabry disease. Muscle Nerve 2009;40(6):976– 84. doi: 10.1002/ mus.21383.
18. Tavakoli M, Marshall A, Banka S, et al. Corneal confocal microscopy detects small-fiber neuropathy in Charcot-Marie-Tooth disease type 1A patients. Muscle Nerve 2012;46(5):698– 704. doi: 10.1002/ mus.23377.
19. Kass-Iliyya L, Javed S, Gosal D, et al. Small fiber neuropathy in Parkinson‘s disease: a clinical, pathological and corneal confocal microscopy study. Parkinsonism Relat Disord 2015;21(12):1454– 60. doi: 10.1016/ j.parkreldis.2015.10.019.
20. Tavakoli M, Ferdousi M, Petropoulos IN, et al. Normative values for corneal nerve morphology assessed using corneal confocal microscopy: a multinational normative data set. Diabetes Care 2015;38(5):838– 43. doi: 10.2337/ dc14-2311.
21. Kallinikos P, Berhanu M, O‘Donnell C, et al. Corneal nerve tortuosity in diabetic patients with neuropathy. Invest Ophthalmol Vis Sci 2004;45(2):418– 22.
22. Dabbah MA, Graham J, Petropoulos I, et al. Dual-model automatic detection of nerve-fibres in corneal confocal microscopy images. Med Image Comput Comput Assist Interv 2010;13(1):300– 7.
23. Dabbah MA, Graham J, Petropoulos IN, et al. Automatic analysis of diabetic peripheral neuropathy using multi-scale quantitative morphology of nerve fibres in corneal confocal microscopy imaging. Med Image Anal 2011;15(5):738– 47. doi: 10.1016/ j.media.2011.05.016.
24. Nitoda E, Kallinikos P, Pallikaris A, et al. Correlation of diabetic retinopathy and corneal neuropathy using confocal microscopy. Curr Eye Res 2012;37(10):898– 906. doi: 10.3109/ 02713683.2012.683507.
25. Ziegler D, Papanas N, Zhivov A, et al. Early detection of nerve fiber loss by corneal confocal microscopy and skin biopsy in recently diagnosed type 2 diabetes. Diabetes 2014;63(7):2454– 63. doi: 10.2337/ db13-1819.
26. Ahmed A, Bril V, Orszag A, et al. Detection of diabetic sensorimotor polyneuropathy by corneal confocal microscopy in type 1 diabetes: a concurrent validity study. Diabetes Care 2012;35(4):821– 8. doi: 10.2337/ dc11-1396.
27. Halpern EM, Lovblom LE, Orlov S, et al. The impact of common variation in the definition of diabetic sensorimotor polyneuropathy on the validity of corneal in vivo confocal microscopy in patients with type 1 diabetes: a brief report. J Diabetes Complicat 2012;27(3):240– 2. doi: 10.1016/ j.jdiacomp.2012.10.011.
28. Asghar O, Petropoulos IN, Alam U, et al. Corneal confocal microscopy detects neuropathy in subjects with impaired glucose tolerance. Diabetes Care 2014;37(9):2643– 6. doi: 10.2337/ dc14-0279.
29. Ostrovski I, Lovblom LE, Farooqi MA, et al. Reproducibility of in vivo corneal confocal microscopy using an automated analysis program for detection of diabetic sensorimotor polyneuropathy. PLoS One 2015;10(11):e0142309. doi: 10.1371/ journal.pone.0142309.
30. Pacaud D, Romanchuk KG, Tavakoli M, et al. The reliability and reproducibility of corneal confocal microscopy in children. Invest Ophthalmol Vis Sci 2015;56(9):5636– 40. doi: 10.1167/ iovs.15-16995.
31. Hertz P, Bril V, Orszag A, et al. Reproducibility of in vivo corneal confocal microscopy as a novel screening test for early diabetic sensorimotor polyneuropathy. Diabet Med 2011;28(10):1253– 60. doi: 10.1111/ j.1464-5491.2011.03299.x.
32. Petropoulos IN, Manzoor T, Morgan P, et al. Repeatability of in vivo corneal confocal microscopy to quantify corneal nerve morphology. Cornea 2013;32(5):e83– 9. doi: 10.1097/ ICO.0b013e3182749419.
Štítky
Paediatric neurology Neurosurgery NeurologyČlánok vyšiel v časopise
Czech and Slovak Neurology and Neurosurgery
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