Neurotrophic Keratopathy
Özet
Bu bölüm, trigeminal sinir innervasyonunun bozulmasına bağlı olarak gelişen nadir ancak görmeyi tehdit edebilen bir kornea hastalığı olan nörotrofik keratopatiyi kapsamlı biçimde ele almaktadır. İlk olarak hastalığın etiyolojisi ve patofizyolojisi açıklanarak korneal sinirlerin epitel bütünlüğünün korunması, gözyaşı sekresyonunun düzenlenmesi ve korneal iyileşme süreçlerindeki kritik rolü tartışılmaktadır. Ardından nörotrofik keratopatinin klinik bulguları ve hastalığın evreleri ayrıntılı biçimde incelenmekte, tanı sürecinde korneal duyarlılık ölçümü, biyomikroskobik muayene ve konfokal mikroskopi gibi yöntemlerin önemi vurgulanmaktadır. Bölümde ayrıca hastalığın yönetimi evreye dayalı bir yaklaşımla ele alınarak oküler yüzeyin korunmasına yönelik destekleyici tedaviler, biyolojik tedaviler ve cerrahi seçenekler değerlendirilmektedir. Özellikle rekombinant insan sinir büyüme faktörü (rh-NGF) tedavisi ve korneal nörotizasyon gibi güncel tedavi yaklaşımlarının korneal sinir fonksiyonunun yeniden sağlanmasındaki potansiyel rolü ele alınmaktadır. Son olarak nörotrofik keratopatinin prognozu ve gelecekteki araştırma alanları tartışılarak erken tanı ve uygun tedavi stratejilerinin korneal bütünlüğün korunması ve görme kaybının önlenmesindeki önemi vurgulanmaktadır.
This chapter provides a comprehensive academic overview of neurotrophic keratopathy, a rare but potentially vision-threatening corneal disorder resulting from impairment of trigeminal nerve innervation. The chapter first outlines the etiology and pathophysiological mechanisms underlying the disease, emphasizing the critical role of corneal nerves in maintaining epithelial integrity, regulating tear secretion, and supporting corneal wound healing. The clinical manifestations and staging of neurotrophic keratopathy are subsequently discussed, highlighting the importance of recognizing progressive corneal damage despite reduced or absent corneal sensation. Diagnostic approaches are reviewed, with particular emphasis on slit-lamp biomicroscopy, corneal sensitivity assessment, and in vivo confocal microscopy. Management strategies are presented within a staged therapeutic framework, including supportive ocular surface protection, biologic therapies, and surgical interventions. Recent therapeutic advances, such as recombinant human nerve growth factor (rh-NGF) and corneal neurotization, are discussed for their potential to restore corneal innervation and enhance epithelial regeneration. The chapter concludes by addressing prognosis and emerging research directions, emphasizing that early diagnosis and timely intervention are essential for preserving corneal integrity and preventing vision loss.
Referanslar
Gurnani B, Feroze KB, Patel BC. Neurotrophic Keratitis. [Updated 2025 Mar 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK431106/
Semeraro F, Forbice E, Romano V, et al. Neurotrophic keratitis. Ophthalmologica. 2014;231(4):191-7.
Dana R, Farid M, Gupta PK, et al. Expert consensus on the identification, diagnosis, and treatment of neurotrophic keratopathy. BMC Ophthalmol. 2021 Sep 8;21(1):327. doi: 10.1186/s12886-021-02092-1. PMID: 34493256; PMCID: PMC8425140.
Dua HS, Said DG, Messmer EM, et al. Neurotrophic keratopathy. Prog Retin Eye Res. 2018;66:107–131. doi: 10.1016/j.preteyeres.2018.04.003.
Labetoulle M, Baudouin C, Calonge M, et al. Role of corneal nerves in ocular surface homeostasis and disease. Acta Ophthalmol. 2019;97(2):137–145. doi: 10.1111/aos.13844.
NaPier E, Camacho M, McDevitt TF, et al. Neurotrophic keratopathy: current challenges and future prospects. Ann Med. 2022 Dec;54(1):666-673. doi: 10.1080/07853890.2022.2045035. PMID: 35243932; PMCID: PMC8903790.
Versura P, Giannaccare G, Pellegrini M, et al. Neurotrophic keratitis: current challenges and future prospects. Eye Brain. 2018 Jun 28;10:37-45. doi: 10.2147/EB.S117261. PMID: 29988739; PMCID: PMC6029608.
Sacchetti M, Lambiase A. Diagnosis and management of neurotrophic keratitis. Clin Ophthalmol. 2014;8:571-579.
Vera-Duarte GR, Jimenez-Collado D, Kahuam-López N, Ramirez-Miranda A, Graue-Hernandez EO, Navas A, Rosenblatt MI. Neurotrophic keratopathy: General features and new therapies. Surv Ophthalmol. 2024 Sep-Oct;69(5):789-804. doi: 10.1016/j.survophthal.2024.04.004. Epub 2024 Apr 26. PMID: 38679146.
Ruiz-Lozano, R.E. ∙ Hernandez-Camarena, J.C. ∙ Loya-Garcia, D. et al.The molecular basis of neurotrophic keratopathy: Diagnostic and therapeutic implications. A review. Ocul Surf. 2021 Jan; 19:224-24.
Semeraro, F. ∙ Forbice, E. ∙ Romano, V. Neurotrophic keratitis. Ophthalmol J Int Ophtalmol Int J Ophthalmol Z Augenheilkd. 2014; 231:191-197. doi:10.1159/000354380.
Chikama, T. ichiro ∙ Wakuta, M. ∙ Liu, Y. Deviated mechanism of wound healing in diabetic corneasCornea. 2007 Oct; 26:S75-S81.
Mastropasqua, L. ∙ Massaro-Giordano, G. ∙ Nubile, M. Understanding the pathogenesis of neurotrophic keratitis: The role of corneal nerves. J Cell Physiol. 2017 Apr; 232:717-724.
Müller, L.J. ∙ Marfurt, C.F. ∙ Kruse, F. Corneal nerves: structure, contents and function. Exp Eye Res. 2003 May; 76:521-542.
Sacchetti, M. ∙ Lambiase, A. Neurotrophic factors and corneal nerve regeneration cited 2022 Nov 27]; Neural Regen Res [Internet]. 2017 Aug; 12:1220-1224.
Pérez-Bartolomé, F. ∙ Mingo Botín, D. ∙ de Dompablo, E. Post-herpes neurotrophic keratopathy: Aetiopathogenesis, clinical signs and current therapies. Arch Soc Esp Oftalmol. 2019 Apr; 94:171-183.
Bonini, S. ∙ Rama, P. ∙ Olzi, D. Neurotrophic keratitis. Eye Lond Engl. 2003 Nov; 17:989-995.
Saad, S. ∙ Abdelmassih, Y. ∙ Saad, R. Neurotrophic keratitis: Frequency, etiologies, clinical management and outcomes. Ocul Surf. 2020 Apr; 18:231-236.
A. Mackie Neuroparalytic Keratitis 1995 452 454.
Stanca, T.H. ∙ Tabacaru, B. ∙ Celea, C. Correlations between confocal microscopy and histological aspects of normal cornea. Rom J Ophthalmol. 2015; 59:19-23.
Dua, H.S. ∙ Otri, A.M. ∙ Said, D.G. The “up-down” sign of acute ocular surface drug toxicity. Br J Ophthalmol. 2012 Nov; 96:1439-1440.
Grey, F. ∙ Carley, F. ∙ Biswas, S. Scleral contact lens management of bilateral exposure and neurotrophic keratopathy. Contact Lens Anterior Eye J Br Contact Lens Assoc. 2012 Dec; 35:288-291.
Liu, D. ∙ Sadhan, Y. Surgical punctal occlusion: a prospective study. Br J Ophthalmol. 2002 Sep; 86:1031-1034.
Giannaccare, G. ∙ Versura, P. ∙ Buzzi, M. Blood derived eye drops for the treatment of cornea and ocular surface diseases. Transfus Apher Sci J World Apher Assoc J Eur Soc Haemapheresis. 2017 Aug; 56:595-604.
Imanishi, J. ∙ Kamiyama, K. ∙ Iguchi, I. Growth factors: importance in wound healing and maintenance of transparency of the cornea. Prog Retin Eye Res. 2000 Jan; 19:113-129.
Trosan, P. ∙ Svobodova, E. ∙ Chudickova, M. The key role of insulin-like growth factor I in limbal stem cell differentiation and the corneal wound-healing process. Stem Cells Dev. 2012 Dec 10; 21:3341-3350.
Fernandes, M. ∙ Sridhar, M.S. ∙ Sangwan, V.S. Amniotic membrane transplantation for ocular surface reconstruction. Cornea. 2005 Aug; 24:643-653.
Rajak S., Rajak J., Selva D. Performing a tarsorrhaphy. Community Eye Health [Internet]. 2015 [cited 2023 Apr 9];28(89):10–1. Available from: 〈https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4579993/〉.
Koaik, M. ∙ Baig, K. Corneal neurotization. Curr Opin Ophthalmol. 2019 Jul; 30:292-298.
Epitropoulos, A.T. ∙ Weiss, J.L. Topical human recombinant nerve growth factor for stage 1 Neurotrophic Keratitis: Retrospective case series of cenegermin treatment. Am J Ophthalmol Case Rep. 2022 Sep; 27, 101649.
Referanslar
Gurnani B, Feroze KB, Patel BC. Neurotrophic Keratitis. [Updated 2025 Mar 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK431106/
Semeraro F, Forbice E, Romano V, et al. Neurotrophic keratitis. Ophthalmologica. 2014;231(4):191-7.
Dana R, Farid M, Gupta PK, et al. Expert consensus on the identification, diagnosis, and treatment of neurotrophic keratopathy. BMC Ophthalmol. 2021 Sep 8;21(1):327. doi: 10.1186/s12886-021-02092-1. PMID: 34493256; PMCID: PMC8425140.
Dua HS, Said DG, Messmer EM, et al. Neurotrophic keratopathy. Prog Retin Eye Res. 2018;66:107–131. doi: 10.1016/j.preteyeres.2018.04.003.
Labetoulle M, Baudouin C, Calonge M, et al. Role of corneal nerves in ocular surface homeostasis and disease. Acta Ophthalmol. 2019;97(2):137–145. doi: 10.1111/aos.13844.
NaPier E, Camacho M, McDevitt TF, et al. Neurotrophic keratopathy: current challenges and future prospects. Ann Med. 2022 Dec;54(1):666-673. doi: 10.1080/07853890.2022.2045035. PMID: 35243932; PMCID: PMC8903790.
Versura P, Giannaccare G, Pellegrini M, et al. Neurotrophic keratitis: current challenges and future prospects. Eye Brain. 2018 Jun 28;10:37-45. doi: 10.2147/EB.S117261. PMID: 29988739; PMCID: PMC6029608.
Sacchetti M, Lambiase A. Diagnosis and management of neurotrophic keratitis. Clin Ophthalmol. 2014;8:571-579.
Vera-Duarte GR, Jimenez-Collado D, Kahuam-López N, Ramirez-Miranda A, Graue-Hernandez EO, Navas A, Rosenblatt MI. Neurotrophic keratopathy: General features and new therapies. Surv Ophthalmol. 2024 Sep-Oct;69(5):789-804. doi: 10.1016/j.survophthal.2024.04.004. Epub 2024 Apr 26. PMID: 38679146.
Ruiz-Lozano, R.E. ∙ Hernandez-Camarena, J.C. ∙ Loya-Garcia, D. et al.The molecular basis of neurotrophic keratopathy: Diagnostic and therapeutic implications. A review. Ocul Surf. 2021 Jan; 19:224-24.
Semeraro, F. ∙ Forbice, E. ∙ Romano, V. Neurotrophic keratitis. Ophthalmol J Int Ophtalmol Int J Ophthalmol Z Augenheilkd. 2014; 231:191-197. doi:10.1159/000354380.
Chikama, T. ichiro ∙ Wakuta, M. ∙ Liu, Y. Deviated mechanism of wound healing in diabetic corneasCornea. 2007 Oct; 26:S75-S81.
Mastropasqua, L. ∙ Massaro-Giordano, G. ∙ Nubile, M. Understanding the pathogenesis of neurotrophic keratitis: The role of corneal nerves. J Cell Physiol. 2017 Apr; 232:717-724.
Müller, L.J. ∙ Marfurt, C.F. ∙ Kruse, F. Corneal nerves: structure, contents and function. Exp Eye Res. 2003 May; 76:521-542.
Sacchetti, M. ∙ Lambiase, A. Neurotrophic factors and corneal nerve regeneration cited 2022 Nov 27]; Neural Regen Res [Internet]. 2017 Aug; 12:1220-1224.
Pérez-Bartolomé, F. ∙ Mingo Botín, D. ∙ de Dompablo, E. Post-herpes neurotrophic keratopathy: Aetiopathogenesis, clinical signs and current therapies. Arch Soc Esp Oftalmol. 2019 Apr; 94:171-183.
Bonini, S. ∙ Rama, P. ∙ Olzi, D. Neurotrophic keratitis. Eye Lond Engl. 2003 Nov; 17:989-995.
Saad, S. ∙ Abdelmassih, Y. ∙ Saad, R. Neurotrophic keratitis: Frequency, etiologies, clinical management and outcomes. Ocul Surf. 2020 Apr; 18:231-236.
A. Mackie Neuroparalytic Keratitis 1995 452 454.
Stanca, T.H. ∙ Tabacaru, B. ∙ Celea, C. Correlations between confocal microscopy and histological aspects of normal cornea. Rom J Ophthalmol. 2015; 59:19-23.
Dua, H.S. ∙ Otri, A.M. ∙ Said, D.G. The “up-down” sign of acute ocular surface drug toxicity. Br J Ophthalmol. 2012 Nov; 96:1439-1440.
Grey, F. ∙ Carley, F. ∙ Biswas, S. Scleral contact lens management of bilateral exposure and neurotrophic keratopathy. Contact Lens Anterior Eye J Br Contact Lens Assoc. 2012 Dec; 35:288-291.
Liu, D. ∙ Sadhan, Y. Surgical punctal occlusion: a prospective study. Br J Ophthalmol. 2002 Sep; 86:1031-1034.
Giannaccare, G. ∙ Versura, P. ∙ Buzzi, M. Blood derived eye drops for the treatment of cornea and ocular surface diseases. Transfus Apher Sci J World Apher Assoc J Eur Soc Haemapheresis. 2017 Aug; 56:595-604.
Imanishi, J. ∙ Kamiyama, K. ∙ Iguchi, I. Growth factors: importance in wound healing and maintenance of transparency of the cornea. Prog Retin Eye Res. 2000 Jan; 19:113-129.
Trosan, P. ∙ Svobodova, E. ∙ Chudickova, M. The key role of insulin-like growth factor I in limbal stem cell differentiation and the corneal wound-healing process. Stem Cells Dev. 2012 Dec 10; 21:3341-3350.
Fernandes, M. ∙ Sridhar, M.S. ∙ Sangwan, V.S. Amniotic membrane transplantation for ocular surface reconstruction. Cornea. 2005 Aug; 24:643-653.
Rajak S., Rajak J., Selva D. Performing a tarsorrhaphy. Community Eye Health [Internet]. 2015 [cited 2023 Apr 9];28(89):10–1. Available from: 〈https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4579993/〉.
Koaik, M. ∙ Baig, K. Corneal neurotization. Curr Opin Ophthalmol. 2019 Jul; 30:292-298.
Epitropoulos, A.T. ∙ Weiss, J.L. Topical human recombinant nerve growth factor for stage 1 Neurotrophic Keratitis: Retrospective case series of cenegermin treatment. Am J Ophthalmol Case Rep. 2022 Sep; 27, 101649.
