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Corneal Reinnervation after Recombinant Form of Nerve Growth Factor Treatment in Patients with Neurotrophic Keratitis

https://doi.org/10.18008/1816-5095-2024-4-786-792

Abstract

Purpose. To evaluate corneal reinnervation in patients with neurotrophic keratitis after treatment with a recombinant form of human nerve growth factor (cenegermin) using confocal microscopy.

Patients and methods. The results of 4 patients treatment with neurotrophic keratitis of various etiology were analyzed. All patients showed ineffectiveness of reparative and etiotropic therapy for 3 months, therefore, cenegermin was prescribed as pathogenetic treatment. Patients underwent standard and specialised diagnostics. In addition, confocal microscopy of the cornea was performed with subsequent analysis of the density of the subbasal nerve plexus, maximum, minimum and total lengths of the corneal nerves using the ImageJ program. The maximum follow-up period was 12 months.

Results. After 8 weeks of treatment, complete epithelialisation and an increase in corneal sensitivity were observed in all patients. Analysis of the confocal scans showed that the maximum density of the subbasal nerve plexus was observed after 8 weeks of treatment. With increasing follow-up, the density of the subbasal nerve plexus increased to a lesser extent and the length of the nerves increased to a greater extent.

Conclusion. Treatment with a recombinant form of human nerve growth factor for 8 weeks results in regeneration and significant increase of the subbasal nerve plexus density. With the increase of follow-up period corneal reinnervation continues due to elongation of nerve fibers.

About the Authors

M. R. Taevere
The S. Fyodorov Eye Microsurgery Federal State Institution
Russian Federation

Taevere Mariyam R., PhD, research officer, ophthalmologist

Beskudnikovskyi blvd, 59A, Moscow, 127486



D. Yu. Maychuk
The S. Fyodorov Eye Microsurgery Federal State Institution
Russian Federation

Maychuk Dmitry Yu., MD, head of Ophthalmology therapeutic department

Beskudnikovskyi blvd, 59A, Moscow, 127486



References

1. Roth M, Dierse S, Alder J, Holtmann C, Geerling G. Incidence, prevalence, and outcome of moderate to severe neurotrophic keratopathy in a German tertiary referral center from 2013 to 2017. Graefes Arch Clin Exp Ophthalmol. 2022;260(6):1961– 1973. doi: 10.1007/s00417-021-05535-z.

2. Kasparova EA, Marchenko NR. Neurotrophic Keratitis. Etiology, Pathogenesis, Clinical Manifestations. Review. Part 1. Ophthalmology in Russia. 2022;19(1):38–45 (In Russ.). doi: 10.18008/1816-5095-2022-1-38-45.

3. Puca A, Meglio M, Vari R, Tamburrini G, Tancredi A. Evaluation of fifth nerve dysfunction in 136 patients with middle and posterior cranial fossae tumors. Eur Neurol. 1995;35(1):33–37. doi: 10.1159/000117086.

4. Lockwood A, HopeRoss M, Chell P. Neurotrophic keratopathy and diabetes mellitus. Eye (Lond). 2006;20(7):837–839. doi: 10.1038/sj.eye.6702053.

5. Xie C, Liu B, Zhao X, He Q, Liu L, Wei R. Characteristics of the ocular surface in neurotrophic keratitis induced by trigeminal nerve injury following neurosurgery. Int Ophthalmol. 2023;43(4):1229–1240. doi: 10.1007/s10792-022-02521-0.

6. Maychuk DYu, Tarkhanova AA, Taevere MR, Shatskih AV, Sudakova SA. Subfamily of betaherpesviruses as a cause of epithelial and stromal keratitis. Russian Annals of Ophthalmology. 2024;140(1):25–31 (In Russ.). doi: 10.17116/oftalma202414001125.

7. Bonini S, Rama P, Olzi D, Lambiase A. Neurotrophic keratitis. Eye (Lond). 2003;17(8):989–995.

8. Müller LJ, Marfurt CF, Kruse F, Tervo TM. Corneal nerves: structure, contents and function. Exp Eye Res. 2003;76(5):521–542. doi: 10.1016/s0014-4835(03)00050-2.

9. Shimizu T, Izumi K, Fujita S, Koja T, Sorimachi M, Ohba N, Fukuda T. Capsaicin induced corneal lesions in mice and the effects of chemical sympathectomy. J Pharmacol Exp Ther 1987;243:690–695.

10. Reid TW, Murphy CJ, Iwahashi CK, Foster BA, Mannis MJ. Stimulation of epithelial cell growth by the neuropeptide substance P. J Cell Biochem 1993;52:476–485. doi: 10.1002/jcb.240520411.

11. Versura P, Giannaccare G, Pellegrini M, Sebastiani S, Campos EC. Neurotrophic keratitis: current challenges and future prospects. Eye Brain. 2018;10:37–45. doi: 10.2147/EB.S117261.

12. AlAqaba MA, Anis FS, Mohammed I, Dua HS. Nerve terminals at the human corneoscleral limbus. Br J Ophthalmol. 2018;102(4):556–561. doi: 10.1136/bjophthalmol2017311146.

13. LeviMontalcini R. The nerve growth factor 35 years later. Science 1987;237:1154– 1162.

14. Linhares ACB, Martinelli AC, Ghem MRD, Dias PB, Wasilewski D. Amniotic membrane transplantation for neurotrophic corneal ulcers. Arq Bras Oftalmol. 2024 Mar 4;87(2):e20220341. doi: 10.5935/0004-2749.2023-2022-0341.

15. Kasparova EA, Kasparov AA, Sobkova OI, Kasparova EA, Rozinova VN. A method of treating purulent corneal ulcer in the eyes with neuroparalytical keratitis and lagophthalmos. Vestnik oftal’mologii. 2019;135(5 Pt. 2):220–225 (In Russ.). doi: 10.17116/oftalma2019135052220.

16. Giannaccare G, Coco G, Rossi C, Borselli M, Lucisano A, Vaccaro S, Verdiglione M, Scorcia V. Combined Use of Therapeutic HyperCL Soft Contact Lens and Insulin Eye Drops for the Treatment of Recalcitrant Neurotrophic Keratopathy. Cornea. 2024;43(1):120–124. doi: 10.1097/ICO.0000000000003361.

17. Grusha YO, Novikov ML, Danilov SS, Fettser EI, Karapetyan AS. Neurotization of the cornea as pathogenically targeted method of treating neurotrophic keratitis in patients with facial paralysis. Russian Annals of Ophthalmology. 2020;136(5):52– 57 (In Russ.). doi: 10.17116/oftalma202013605152.

18. Catapano J, Fung SSM, Halliday W, Jobst C, Cheyne D, Ho ES, Zuker RM, Borschel GH, Ali A. Treatment of neurotrophic keratopathy with minimally invasive corneal neurotisation: longterm clinical outcomes and evidence of corneal reinnervation. Br J Ophthalmol. 2019;103(12):1724–1731. doi: 10.1136/bjophthalmol-2018-313042.

19. Saini M, KaliaA, JainAK, Gaba S, MalhotraC, GuptaA, Soni T, SainiK, Gupta PC, Singh M. Clinical outcomes of corneal neurotization using sural nerve graft in neurotrophic keratopathy. PLoS One. 2023;18(11):e0294756. doi: 10.1371/journal.pone.0294756.

20. Fogagnolo P, Giannaccare G, Bolognesi F, Digiuni M, Tranchina L, Rossetti L, Dipinto A, Allevi F, Lozza A, Rabbiosi D, Mariani S, Pellegrini M, Cazzola FE, Bagaglia S, Mazzotta C, Gabriele G, Gennaro P, Badiali G, Marchetti C, Campos EC, Biglioli F. Direct Versus Indirect Corneal Neurotization for the Treatment of Neurotrophic Keratopathy: A Multicenter Prospective Comparative Study. Am J Ophthalmol. 2020;220:203–214. doi: 10.1016/j.ajo.2020.07.003.

21. Hamrah P, Yavuz Saricay L, Ozmen MC. Cutting Edge: Topical Recombinant Nerve Growth Factor for the Treatment of Neurotrophic KeratopathyBiologicals as a Novel Therapy for Neurotrophic Keratopathy. Cornea. 2022;41(6):673–679. doi: 10.1016/j.ajo.2020.07.003.

22. Bu JB, GerickeA, PfeifferN, WasielicaPoslednik J. Neurotrophic keratopathy: Clinical presentation and effects of cenegermin. Am J Ophthalmol Case Rep. 2022;26:101488. doi: 10.1016/j.ajoc.2022.101488.

23. Epitropoulos AT, Weiss JL. Topical human recombinant nerve growth factor for stage 1 Neurotrophic Keratitis: Retrospective case series of cenegermin treatment. Am J Ophthalmol Case Rep. 2022;27:101649. doi: 10.1016/j.ajoc.2022.101649.

24. Hao M, Cheng Y, Wu J, Cheng Y, Wang J. Clinical observation of recombinant human nerve growth factor in the treatment of neurotrophic keratitis. Int J Ophthalmol. 2023;16(1):60–66. doi: 10.18240/ijo.2023.01.09.

25. BalbuenaPareja A, Bogen CS, Cox SM, Hamrah P. Effect ofrecombinant human nerve growth factor treatment on corneal nerve regeneration in patients with neurotrophic keratopathy. Front Neurosci. 2023 30;17:1210179. doi: 10.3389/fnins.2023.1210179.

26. Hamrah P, MassaroGiordano M, Schanzlin D, Holland E, Berdy G, Goisis G, Pasedis G, Mantelli F. Phase IV Multicenter, Prospective, OpenLabel Clinical Trial of Cenegermin (rhNGF) for Stage 1 Neurotrophic Keratopathy (DEFENDO). Ophthalmol Ther. 2024;13(2):553–570. doi: 10.1007/s40123-023-00866-y.

27. Inferrera L, Aragona E, Wylęgała A, Valastro A, Latino G, Postorino EI, Gargano R, OrzechowskaWylęgała B, Wylęgała E, Roszkowska AM. The Role of HiTech Devices in Assessment of Corneal Healing in Patients with Neurotrophic Keratopathy. J Clin Med. 2022;11(6):1602. doi: 10.3390/jcm11061602.

28. BalbuenaParejaA, BogenCS, Cox SM, HamrahP. Effect ofrecombinant human nerve growth factor treatment on corneal nerve regeneration in patients with neurotrophic keratopathy. Front Neurosci. 2023;17:1210179. doi: 10.3389/fnins.2023.1210179.

29. Niruthisard D, Fung SSM. Recombinant Human Nerve Growth Factor for Pediatric Neurotrophic Keratopathy. Eye Contact Lens. 2022;48(7):303–305. doi: 10.1097/ICL.0000000000000912.

30. Pedrotti E, Bonacci E, Chierego C, De Gregorio A, Cozzini T, Brighenti T, Caldarella G, Pastore G, Fasolo A, Marchini G. Eight months followup of corneal nerves and sensitivity after treatment with cenegermin for neurotrophic keratopathy. Orphanet J Rare Dis. 2022;17(1):63. doi: 10.1186/s13023-022-02237-5.


Review

For citations:


Taevere M.R., Maychuk D.Yu. Corneal Reinnervation after Recombinant Form of Nerve Growth Factor Treatment in Patients with Neurotrophic Keratitis. Ophthalmology in Russia. 2024;21(4):786-792. (In Russ.) https://doi.org/10.18008/1816-5095-2024-4-786-792

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ISSN 1816-5095 (Print)
ISSN 2500-0845 (Online)