<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">ophthalmology</journal-id><journal-title-group><journal-title xml:lang="ru">Офтальмология</journal-title><trans-title-group xml:lang="en"><trans-title>Ophthalmology in Russia</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1816-5095</issn><issn pub-type="epub">2500-0845</issn><publisher><publisher-name>Ophthalmology</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.18008/1816-5095-2024-4-786-792</article-id><article-id custom-type="elpub" pub-id-type="custom">ophthalmology-2504</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>КЛИНИЧЕСКИЙ СЛУЧАЙ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>CASE REPORT</subject></subj-group></article-categories><title-group><article-title>Реиннервация роговицы после лечения рекомбинантной формой фактора роста нервов у пациентов с нейротрофическим кератитом</article-title><trans-title-group xml:lang="en"><trans-title>Corneal Reinnervation after Recombinant Form of Nerve Growth Factor Treatment in Patients with Neurotrophic Keratitis</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-1013-6924</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Таевере</surname><given-names>М. Р.</given-names></name><name name-style="western" xml:lang="en"><surname>Taevere</surname><given-names>M. R.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Таевере Мариям Рамазановна, кандидат медицинских наук, научный сотрудник, врач-офтальмолог</p><p>Бескудниковский бульвар, 59а, Москва, 127486</p></bio><bio xml:lang="en"><p>Taevere Mariyam R., PhD, research officer, ophthalmologist</p><p>Beskudnikovskyi blvd, 59A, Moscow, 127486</p></bio><email xlink:type="simple">taeveremr@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-1674-4656</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Майчук</surname><given-names>Д. Ю.</given-names></name><name name-style="western" xml:lang="en"><surname>Maychuk</surname><given-names>D. Yu.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Майчук Дмитрий Юрьевич, доктор медицинских наук, заведующий отделом терапевтической офтальмологии</p><p>Бескудниковский бульвар, 59а, Москва, 127486</p></bio><bio xml:lang="en"><p>Maychuk Dmitry Yu., MD, head of Ophthalmology therapeutic department</p><p>Beskudnikovskyi blvd, 59A, Moscow, 127486</p></bio><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГАУ НМИЦ «МНТК “Микрохирургия глаза” им. академика С.Н. Федорова» Министерства здравоохранения Российской Федерации</institution><country>Россия</country></aff><aff xml:lang="en"><institution>The S. Fyodorov Eye Microsurgery Federal State Institution</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2024</year></pub-date><pub-date pub-type="epub"><day>24</day><month>12</month><year>2024</year></pub-date><volume>21</volume><issue>4</issue><fpage>786</fpage><lpage>792</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Таевере М.Р., Майчук Д.Ю., 2024</copyright-statement><copyright-year>2024</copyright-year><copyright-holder xml:lang="ru">Таевере М.Р., Майчук Д.Ю.</copyright-holder><copyright-holder xml:lang="en">Taevere M.R., Maychuk D.Y.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.ophthalmojournal.com/opht/article/view/2504">https://www.ophthalmojournal.com/opht/article/view/2504</self-uri><abstract><sec><title>Цель исследования</title><p>Цель исследования: провести оценку реиннервации роговицы у пациентов с нейротрофическим кератитом после лечения рекомбинантной формой фактора роста нервов человека (ценегермин) с помощью конфокальной микроскопии.</p></sec><sec><title>Пациенты и методы</title><p>Пациенты и методы. Проведен анализ результатов лечения 4 пациентов с нейротрофическим кератитом различной этиологии. У всех пациентов репаративная и этиотропная терапия на протяжении 3 месяцев оказалась неэффективной, в связи с этим в качестве патогенетического лечения был назначен препарат ценегермин. Пациентам проводилась стандартная и специализированная диагностика, включающая конфокальную микроскопию роговицы с последующим анализом плотности суббазального нервного сплетения, максимальной, минимальной и суммарной длины нервов роговицы при помощи программы ImageJ. Максимальный срок наблюдения составил 12 месяцев.</p></sec><sec><title>Результаты</title><p>Результаты. Через 8 недель терапии у всех пациентов наблюдались полная эпителизация и повышение чувствительности роговицы. При анализе конфокальных сканограмм определено, что максимальное повышение плотности суббазального нервного сплетения наблюдалось на 8-й неделе терапии. При дальнейшем наблюдении плотность суббазального нервного сплетения увеличивалась в меньшей степени, а длина нервов — в большей.</p></sec><sec><title>Заключение</title><p>Заключение. Лечение рекомбинантной формой фактора роста нервов человека способствует восстановлению и значительному увеличению плотности суббазального нервного сплетения. При дальнейшем наблюдении после окончания терапии реиннервация роговицы продолжалась за счет удлинения нервных волокон.</p></sec></abstract><trans-abstract xml:lang="en"><sec><title>Purpose</title><p>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.</p></sec><sec><title>Patients and methods</title><p>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.</p></sec><sec><title>Results</title><p>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.</p></sec><sec><title>Conclusion</title><p>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.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>нейротрофический кератит</kwd><kwd>конфокальная микроскопия роговицы</kwd><kwd>суббазальное нервное сплетение</kwd><kwd>фактор роста нервов</kwd><kwd>ценегермин</kwd></kwd-group><kwd-group xml:lang="en"><kwd>neurotrophic keratitis</kwd><kwd>corneal confocal microscopy</kwd><kwd>subbasal nerve plexus</kwd><kwd>nerve growth factor</kwd><kwd>cenegermin</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Каспарова ЕА, Марченко НР. Нейротрофический кератит. Этиология, патогенез, клинические проявления. Обзор литературы. Часть 1. Офтальмология. 2022;19(1):38–45. doi: 10.18008/1816-5095-2022-1-38-45.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Lockwood A, HopeRoss M, Chell P. Neurotrophic keratopathy and diabetes mellitus. Eye (Lond). 2006;20(7):837–839. doi: 10.1038/sj.eye.6702053.</mixed-citation><mixed-citation xml:lang="en">Lockwood A, HopeRoss M, Chell P. Neurotrophic keratopathy and diabetes mellitus. Eye (Lond). 2006;20(7):837–839. doi: 10.1038/sj.eye.6702053.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Майчук ДЮ, Тарханова АА, Таевере МР, Шацких АВ, Судакова СА. Подсемейство бетагерпесвирусов как причина эпителиальных и стромальных кератитов. Вестник офтальмологии. 2024;140(1):25–31. doi: 10.17116/oftalma202414001125.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Bonini S, Rama P, Olzi D, Lambiase A. Neurotrophic keratitis. Eye (Lond). 2003;17(8):989–995.</mixed-citation><mixed-citation xml:lang="en">Bonini S, Rama P, Olzi D, Lambiase A. Neurotrophic keratitis. Eye (Lond). 2003;17(8):989–995.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">LeviMontalcini R. The nerve growth factor 35 years later. Science 1987;237:1154– 1162.</mixed-citation><mixed-citation xml:lang="en">LeviMontalcini R. The nerve growth factor 35 years later. Science 1987;237:1154– 1162.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Каспарова ЕвгА, Каспаров АА, Собкова ОИ, Каспарова ЕлА, Розинова ВН. Способ лечения гнойной язвы роговицы, развившейся на глазах с нейротрофическим кератитом и лагофтальмом. Вестник офтальмологии. 2019;135(5 ч. 2):220–225. doi: 10.17116/oftalma2019135052220.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Груша ЯО, Новиков МЛ, Данилов СС, Фетцер ЕИ, Карапетян АС. Невротизация роговицы как патогенетически направленный метод лечения нейротрофического кератита у пациентов с лицевым параличом. Вестник офтальмологии. 2020;136(5):52–57. doi: 10.17116/oftalma202013605152.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
