Neurotrophic Keratitis. Etiology, Pathogenesis, Clinical Manifestations. Review. Part 1
https://doi.org/10.18008/1816-5095-2022-1-38-45
Abstract
Neurotrophic keratitis (also called neurotrophic keratopathy) (NTK) is a degenerative disease of the cornea, accompanied with neurogenic inflammation. It caused by a sensitive innervation loss of the trigeminal nerve and characterized by reduced sensitivity of the cornea and a retardation of its healing process. NTC-causing damage to the trigeminal nerve can occur at different levels-from the nucleus to the terminals located in the cornea, and can be caused by ocular and systemic diseases both. The most common causes include herpetic keratitis, diabetes, chemical burns and iatrogenic injuries during ophthalmic operations, intracranial neoplasms, disorders of cerebral circulation and neurosurgical interventions. Corneal changes include epitheliopathy (grade I), persistent erosion (grade II), ulcer and its complications (grade III). The determining diagnostic sign of NTK is a decrease or loss of corneal sensitivity. The morphological characteristics of the corneal nerves can be studied using confocal microscopy.
About the Authors
E. A. Kasparova
Research Institute of Eye Diseases
Russian Federation
Russian Federation
Kasparova Evgeniya A., PhD, Leading Research Officer of the optical media of the eye pathology department
Rossolimo str., 11A, B, Moscow, 119021
N. R. Marchenko
Research Institute of Eye Diseases
Russian Federation
Russian Federation
Marchenko Nikolay R., PhD, Research Officer of the optical media of the eye pathology department
Rossolimo str., 11A, B, Moscow, 119021
References
1. Dua H.S., Said D.G., Messmer E.M., Rolando M., Benitez-Del-Castillo J.M., Hossain P.N., Shortt A.J., Geerling G., Nubile M., Figueiredo F.C., Rauz S., Mastropasqua L., Rama P., Baudouin C. Neurotrophic keratopathy. Prog. Retin. Eye Res. 2018 Sep;66:107–131. DOI: 10.1016/j.preteyeres.2018.04.003
2. Muller L.J., Marfurt C.F., Kruse F., Tervo T.M. Corneal nerves: structure, contents and function. Exp Eye Res. 2003;76(5):521–542.
3. Sigelman S., Friedenwald J.S. Mitotic and wound healing activities of the corneal epithelium: effect of sensory denervation. Arch Ophthalmol. 1954;52:46–57.
4. Simone S. De ricerche sul contenuto in acqua totale ed in azoto totale della cornea di coniglio in condizione di cheratite neuroparalitica sperimentale. Arch Ottalmol. 1958;62:151.
5. Mackie I.A. Neuroparalytic keratitis. In: Fraunfelder F., Roy F.H., Meyer S.M., editors. Current Ocular Therapy. Philadelphia, PA, USA: WB Saunders; 1995.
6. Sacchetti M., Lambiase A., Diagnosis and management of neurotrophic keratitis. Clin. Ophthalmol. 2014;8:571–579. DOI: 10.2147/OPTH.S45921
7. Labetoulle M., Auquier P., Conrad H., Crochard A., Daniloski M., Bouee S., El Hasnaoui A., Colin J. Incidence of herpes simplex virus keratitis in France. Ophthalmology. 2005;112:888–895.
8. Dworkin R.H., Johnson R.W., Breuer J., Gnann J.W., Levin M.J., Backonja M., Betts R.F., Gershon A.A., Haanpaa M.L., McKendrick M.W., Nurmikko T.J., Oaklander A.L., Oxman M.N., Pavan-Langston D., Petersen K.L., Rowbotham M.C., Schmader K.E., Stacey B.R., Tyring S.K., van Wijck A.J., Wallace M.S., Wassilew S.W., Whitley R.J. Recommendations for the management of herpes zoster. Clin. Infect. Dis. 2007;44 (Suppl. 1):S1–S26.
9. Bhatti M.T., Patel R. Neuro-ophthalmic considerations in trigeminal neuralgia and its surgical treatment. Curr. Opin. Ophthalmol. 2005;16:334–340.
10. Azuma M., Yabuta C., Fraunfelder F.W., Shearer T.R. Dry Eye in LASIK Patients, BMC Res Notes. 2014;7:420. DOI: 10.1186/1756-0500-7-420
11. Versura P., Giannaccare G., Pellegrini M., Sebastiani S., Campos E.C. Neurotrophic keratitis: current challenges and future prospects. Eye Brain. 2018;10:37–45. DOI: 10.2147/EB.S117261
12. Hamrah P., Cruzat A., Dastjerdi M.H., Zheng L., Shahatit B.M., Bayhan H.A., Dana R. Pavan-Langston Corneal sensation and subbasal nerve alterations in patients with herpes simplex keratitis: an in vivo confocal microscopy study. Ophthalmology. 2010;117(10):1930–1936. DOI: 10.1016/j.ophtha.2010.07.010
13. Lee B.H., McLaren J.W., Erie J.C., Hodge D.O., Bourne W.M. Reinnervation in the cornea after LASIK. Invest Ophthalmol Vis Sci. 2002;43(12):3660–3664.
14. Semeraro F., Forbice E., Romano V. Neurotrophic keratitis. Ophthalmologica. 2014;231(4):191–197. DOI: 10.1159/000354380
15. Kasparova Evg.A., Kasparov A.A., Sobkova O.I., Kasparova El.A., Rozinova V.N. A method of treating purulent corneal ulcers that have developed in the eyes with neurotrophic keratitis and lagophthalmos. Annals of Ophthalmology = Vestnik oftal’mologii 2019;135(5) p. 2:220–225 (In Russ.). DOI: 10.17116/oftalma2019135052220
16. Tavakoli M., Marshall A., Pitceathly R. Corneal confocal microscopy: a novel means to detect nerve fibre damage in idiopathic small fibre neuropathy. Exp Neurol. 2010;223(1):245–250. DOI: 10.1016/j.expneurol.2009.08.033
17. Avetisov S.E., Chernenkova N.A., Curnina Z.V., Ahmedzhanova L.T., Fokina A.S., Strokov I.A. The possibilities of early diagnosis of diabetic polyneuropathy based on the study of corneal nerve fibers. Annals of Ophthalmology = Vestnik oftal’mologii 2020;136(5):155–162 (In Russ.). DOI: 10.17116/oftalma2020136052155
18. Banerjee P.J., Chandra A., Sullivan P.M., Charteris D.G. Neurotrophic corneal ulceration after retinal detachment surgery with retinectomy and endolaser: a case series. JAMA Ophthalmol. 2014;132(6):750–752. DOI: 10.1001/jamaophthalmol.2014.280
19. Qi H., Chuang E.Y., Yoon K.C., de Paiva C.S., Shine H.D., Jones D.B., Pflugfelder S.C., Li D.Q. Patterned expression of neurotrophic factors and receptors in human limbal and corneal regions. Mol. Vis. 2007;13:1934–1941.
20. Levi-Montalcini R. The nerve growth factor 35 years later. Science. 1987;237(4819):1154–1162.
21. Bonini S., Aloe L., Bonini S., Rama P., Lamagna A., Lambiase A. Nerve growth factor (NGF): an important molecule for trophism and healing of the ocular surface. Adv Exp Med Biol. 2002;506(Pt A):531–537. DOI: 10.1007/978-1-4615-0717-8_75
22. Lambiase A., Manni L., Bonini S., Rama P., Micera A., Aloe L. Nerve growth factor promotes corneal healing: structural, biochemical, and molecular analyses of rat and human corneas. Invest Ophthalmol Vis Sci. 2000;41(5):1063–1069.
23. Heigle T.J., Pflugfelder S.C. Aqueous tear production in patients with neurotrophic keratitis. Cornea. 1996;15(2):135–138.
24. Sacchetti M., Lambiase A. Neurotrophic factors and corneal nerve regeneration. Neural Regen Res. 2017;12(8):1220–1224. DOI: 10.4103/1673-5374.213534
25. Hosoi J., Murphy G.F., Egan C.L., Lerner E.A., Grabbe S., Asahina A., Granstein R.D. Regulation of Langerhans cell function by nerves containing calcitonin generelated peptide. Nature. 1993;363:159–163.
26. Belmonte C., Acosta M.C., Gallar J. Neural basis of sensation in intact and injured corneas. Exp. Eye Res. 2004;78:513–525. DOI: 10.1016/j.exer.2003.09.023
27. Baudouin C., Aragona P., Messmer E.M., Tomlinson A., Calonge M., Boboridis K.G., Akova Y.A., Geerling G., Labetoulle M., Rolando M. Role of hyperosmolarity in the pathogenesis and management of dry eye disease: proceedings of the OCEAN group meeting. Ocul. Surf. 2013;11:246–258. DOI: 10.1016/j.jtos.2013.07.003
28. Fini M.E., Cook J.R., Mohan R. Proteolytic mechanisms in corneal ulceration and repair. Arch. Dermatol. Res. 1998;290 (Suppl. l):S12–S23.
29. Mohammed I., Said D.G., Dua H.S. Human antimicrobial peptides in ocular surface defense. Prog. Retin. Eye Res. 2017;61:1–22. DOI: 10.1016/j.preteyeres.2017.03.004
30. Pflugfelder S.C., Farley W., Luo L., Chen L.Z., de Paiva C.S., Olmos L.C., Li D.Q., Fini M.E. Matrix metalloproteinase-9 knockout confers resistance to corneal epithelial barrier disruption in experimental dry eye. Am. J. Pathol. 2005;166:61–71. DOI: 10.1016/S0002-9440(10)62232-8
31. Chotikavanich S., de Paiva C.S., de Li Q., Chen J.J., Bian F., Farley W.J., Pflugfelder S.C. Production and activity of matrix metalloproteinase-9 on the ocularsurface increase in dysfunctional tear syndrome. Invest. Ophthalmol. Vis. Sci. 2009;50:3203–3209. DOI: 10.1167/iovs.08-2476
32. Hamrah P., Cruzat A., Dastjerdi M.H., Prüss H., Zheng L., Shahatit B.M., Bayhan H.A., Dana R., Pavan-Langston D. Unilateral herpes zoster ophthalmicus results inbilateral corneal nerve alteration: an in vivo confocal microscopy study. Ophthalmology 2013;20:40–47. DOI: 10.1016/j.ophtha.2012.07.036
33. Cavalcanti B.M., Cruzat A., Sahin A., Pavan-Langston D., Samayoa E., Hamrah P. In vivo confocal microscopy detects bilateral changes of corneal immune cellsand nerves in unilateral herpes zoster ophthalmicus. Ocul. Surf. 2018;16:101–111. DOI: 10.1016/j.jtos.2017.09.004
34. Yamaguchi T., Turhan A., Harris D.L., Hu K., von Andrian H.P.U., Hamrah P. Bilateral nerve alterations in a unilateral experimental neurotrophic keratopathy model: a lateral conjunctival approach for trigeminal axotomy. PLoS One 2013;14:е70908. DOI: 10.1371/journal.pone.0070908
35. Yamaguchi T., Hamrah P., Shimazaki J. Bilateral alterations in corneal nerves,dendritic cells, and tear cytokine levels in ocular surface disease. Cornea 2016;35(Suppl.1):S65–S70. DOI: 10.1097/ICO.0000000000000989
36. Bonini S., Rama P., Olzi D., Lambiase A. Neurotrophic keratitis. Eye (Lond) 2003;17:989–995.
37. Alio J.L., Pastor S., Ruiz-Colecha J., Rodriguez A., Artola A. Treatment of ocular surface syndrome after LASIK with autologous platelet-rich plasma. J Refract Surg. 2007;23(6):617–619.
38. Ambrósio R. Jr, Tervo T., Wilson S.E. LASIK-associated dry eye and neurotrophic epitheliopathy: pathophysiology and strategies for prevention and treatment. J Refract Surg. 2008;24(4):396–407. DOI: 10.3928/1081597X-20080401-14
39. Bentivoglio A.R., Bressman S.B., Cassetta E., Carretta D., Tonali P., Albanese A. Analysis of blink rate patterns in normal subjects. Mov Disord. 1997;12(6):1028– 1034. DOI: 10.1002/mds.870120629
40. Al-Aqaba M.A., Otri A.M., Fares U., Miri A., Dua H.S. Organization of the regenerated nerves in human corneal grafts. Am J Ophthalmol. 2012;153(1):29–37.e4. DOI: 10.1016/j.ajo.2011.06.006
41. Zabel R., Mintsioulis G. Hyperplastic precorneal membranes. Extending the Spectrum of Neurotrophic Keratitis. Cornea. 1989;8(4):247–250.
42. Cavanagh H.D., Colley A.M., Pihlaja D,J. Persistent corneal epithelial defects, Int Ophthalmol Clin 1979;19(2):197–206.
43. Radzihovskiy B.L., Luchik V.I. Corneal sensitivity and its diagnostic significance in the pathology of the eye and the body. Kiev: Zdorov’e. 1974:11–21 (In Russ.).
44. Golebiowski B., Papas E., Stapleton F. Assessing the sensory function of the ocular surface: implications of use of a non-contact air jet aesthesiometer versus the Cochet-Bonnet aesthesiometer. Exp Eye Res. 2011;92(5):408–413. DOI: 10.1016/j.exer.2011.02.016
45. Belmonte C., Acosta M.C., Schmelz M., Gallar J. Measurement of corneal sensitivity to mechanical and chemical stimulation with a CO2 esthesiometer. Invest Ophthalmol Vis Sci. 1999;40(2):513–519.
46. Tesón M., Calonge M., Fernández I., Stern M.E., González-García M.J. Characterization by Belmonte’s gas esthesiometer of mechanical, chemical, and thermal corneal sensitivity thresholds in a normal population. Invest Ophthalmol Vis Sci. 2012;53(6):3154–3160. DOI: 10.1167/iovs.11-9304
47. Dhillon V.K., Elalfy M.S., Al-Aqaba M., Gupta A., Basu S., Dua H.S. Corneal hypoesthesia with normal sub-basal nerve density following surgery for trigeminal neuralgia. Acta Ophthalmol. 2016;94(1):e6–10. DOI: 10.1111/aos.12697
Review
For citations:
Kasparova E.A., Marchenko N.R. Neurotrophic Keratitis. Etiology, Pathogenesis, Clinical Manifestations. Review. Part 1. Ophthalmology in Russia. 2022;19(1):38-45. (In Russ.) https://doi.org/10.18008/1816-5095-2022-1-38-45
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