Применение кросслинкинга роговицы у детей с кератоконусом. Обзор литературы
https://doi.org/10.21516/2072-0076-2025-18-4-164-168
Аннотация
Представлен анализ данных литературы о результатах применения кросслинкинга (CXL) роговицы для лечения кератоконуса (КК) у пациентов детского возраста. Сообщения о результатах CXL роговицы у детей с КК достаточно многочисленны, однако в основном исследования проведены в небольших когортных группах, имеют короткий период наблюдения, мнения об эффективности разных протоколов данной процедуры разноречивые. Результаты всех исследований свидетельствует о том, что CXL останавливает или замедляет прогрессирование КК у детей. Ввиду быстрого прогрессирования КК в детском возрасте некоторые авторы предлагают применение CXL роговицы даже при отсутствии документального подтверждения признаков прогрессии. Разработка наиболее оптимального протокола CXL роговицы с высокой эффективностью и безопасностью для детей различных возрастных групп остается важной проблемой, что требует продолжения исследований.
Об авторах
Г. Х. ЗайнутдиноваРоссия
Гузель Халитовна Зайнутдинова — д-р мед. наук, старший научный сотрудник отдела организации научных исследований и разработок
ул. Пушкина, д. 90, Уфа, 450008
Г. М. Казакбаева
Россия
Гюлли Мухаррамовна Казакбаева — канд. мед. наук, заведующая отделом офтальмологической и медицинской эпидемиологии
ул. Пушкина, д. 90, Уфа, 450008
А. В. Инсапова
Россия
Анастасия Валерьевна Инсапова — научный сотрудник, отдел офтальмологической и медицинской эпидемиологии
ул. Пушкина, д. 90, Уфа, 450008
Д. А. Тимербулатова
Россия
Диана Артуровна Тимербулатова — научный сотрудник, отдел офтальмологической и медицинской эпидемиологии
ул. Пушкина, д. 90, Уфа, 450008
Р. И. Багманов
Россия
Радмир Ильшатович Багманов — врач-офтальмолог 1-го микрохирургического отделения
ул. Пушкина, д. 90, Уфа, 450008
Список литературы
1. Vohra V, Tuteja S, Gurnani B, Chawla H. Collagen Cross linking for keratoconus. 2023 Jun 11. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan.
2. Prasher P, Sharma A, Sharma R, Vig VK., Nirankari VS. Paediatric cornea crosslinking current strategies: A review. Advances in Ophthalmology Practice and Research. 2023; 3,2: 55–62. doi: 10.1016/j.aopr.2022.11.002
3. Xu L, Wang YX, Guo Y, et al. Prevalence and associations of steep cornea/ keratoconus in greater Beijing. The Beijing Eye Study. PLoS One. 2012; 7(7): e39313. doi: 10.1371/journal.pone.0039313
4. Shehadeh MM, Diakonis VF, Jalil SA, et al. Prevalence of keratoconus among a palestinian tertiary student population. Open Ophthalmol J. 2015; (9): 172–6. doi: 10.2174/1874364101509010172
5. Godefrooij DA, de Wit GA, Uiterwaal CS, et al. Age-specific incidence and prevalence of keratoconus: a nationwide registration study. Am J Ophthalmol. 2017; 175: 169–2. doi: 10.1016/j.ajo.2016.12.015
6. Бикбов М.М., Бикбова Г.М. Эктазии роговицы. Москва: Изд-во «Офтальмология». 2011.
7. Халимов А.Р., Суркова В.К., Казакбаева Г.М. Строение и функции роговицы. Обзор литературы Точка зрения. Восток — Запад. 2022; 1: 45–50. https://east-west-journal.ru/index.php/east-west/article/view/32
8. Tur VM, MacGregor C, Jayaswal R, et al. A review of keratoconus: Diagnosis, pathophysiology, and genetics. Surv Ophthalmol. 2017; 62 (6): 770–83. doi: 10.1016/j.survophthal.2017.06.009
9. Wisse RP, Kuiper JJ, Gans R, et al. Cytokine expression in keratoconus and its corneal microenvironment: a systematic review. Ocul Surf. 2015; 13 (4): 272–83. doi: 10.1016/j.jtos.2015.04.006
10. Singh RBr, Koh S, Sharma N, et al. Keratoconus. Nat Rev Dis Primers. 2024; 10 (1): 81. doi: 10.1038/s41572-024-00565-3
11. Chatzis N, Hafezi F. Progression of keratoconus and efficacy of corneal collagen cross-linking in children and adolescents. J Refract Surg. 2012; 28 (11): 753–8. doi: 10.3928/1081597X-20121011-01
12. McAnena L, Doyle F, O’Keefe M. Cross-linking in children with keratoconus: a systematic review and meta-analysis. Acta Ophthalmol. 2017; 95 (3): 229–39. doi: 10.1111/aos.13224
13. Polido J, Araújo ME, Dos XS, Alexander JG, et al. Pediatric Crosslinking: Current Protocols and Approach. Ophthalmol. Ther. 2022; 11: 983–99. doi: 10.1007/s40123-022-00508-9
14. Chang CY, Hersh PS. Corneal collagen cross-linking. Eye Contact Lens. 2014; 40 (6): 345–52. doi: 10.1097/ICL.0000000000000094
15. Léoni-Mesplié S, Mortemousque B, Touboul D, et al. Scalability and severity of keratoconus in children. Am J Ophthalmol. 2012; 154: 6–62.e1. doi: 10.1016/j.ajo.2012.01.025
16. Ahuja P, Dadachanji Z, Shetty R, et al. Relevance of IgE, allergy and eye rubbing in the pathogenesis and management of Keratoconus. Indian J Ophthalmol. 2020; 68: 2067–74. doi: 10.4103/ijo.IJO_1191_19
17. Galvis V, Tello A, Carreño NI, Berrospi RD, Niño CA. Risk factors for keratoconus: Atopy and eye rubbing. Cornea. 2017; 36: e1. doi: 10.1097/ICO.0000000000001052
18. Peyman A, Namgar M, Feizi A, Ganjalikhani M. Interleukin-6 and tumor necrosis factor-α levels in tear film of Keratoconus patients. Journal of Research in Medical Sciences. 2021; 26 (1): 75. doi: 10.4103/jrms.jrms_35_21
19. Balasubramanian SA, Mohan S, Pye DC, Willcox MD. Proteases, proteolysis and inflammatory molecules in the tears of people with keratoconus. Acta Ophthalmol. 2012; 90: e303–9. doi: 10.1111/j.1755-3768.2011.02369.x
20. Macsai M, Maguen E, Nucci P. Keratoconus and Turners syndrome. Cornea.1997; 16 (5): 534–6.
21. Ren S, Yang K, Xu L, et al. Machine learning analysis with the comprehensive index of corneal tomographic and biomechanical parameters in detecting pediatric subclinical keratoconus. Front Bioeng Biotechnol. 2023; 11: 1273500. doi: 10.3389/fbioe.2023.1273500
22. Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol. 2003; 135: 620–7. doi:10.1016/s0002-9394(02)02220-1
23. Wollensak G, Iomdina E. Long-term biomechanical properties of rabbit cornea after photodynamic collagen crosslinking. Acta Ophthalmol. 2009 Feb; 87 (1): 48–51. doi: 10.1111/j.1755-3768.2008.01190.x
24. O’Brart DPS, Chan E, Samaras K, et al. A randomised, prospective study to investigate the efficacy of riboflavin/ultraviolet A (370 nm) corneal collagen cross-linkage to halt the progression of keratoconus. Br J Ophthalmol. 2011; 95: 1519–24. doi:10.1136/bjo.2010.196493
25. Wittig-Silva C, Chan E, Islam FMA, et al. A randomized, controlled trial of corneal collagen cross-linking in progressive keratoconus. Ophthalmology. 2014; 121: 812–21. doi: 10.1016/j.ophtha.2013.10.028
26. Galvis V, Tello A, Ortiz AI, Escaf LC. Patient selection for corneal collagen cross-linking: an updated review. Clin Ophthalmol. 2017; 11: 657–68. doi: 10.2147/OPTH.S101386
27. Суркова В.К., Халимов А.Р., Казакбаева Г.М. Кератэктазии и современные методы их лечения. Точка зрения. Восток — Запад. 2022; 2: 84–8. https://east-west-journal.ru/index.php/east-west/article/view/116
28. Hersh P, Greenstein S, Fry K. Corneal collagen crosslinking for keratoconus and corneal ectasia: One-year results. Journal of Cataract and Refractive Surgery. 2011; 37 (1): 149–60. doi: 10.1016/j.jcrs.2010.07.030
29. Gomes JA, Tan D, Rapuano CJ, et al. Group of Panelists for the Global Delphi Panel of Keratoconus and Ectatic Diseases. Global consensus on keratoconus and ectatic diseases. Cornea. 2015; 34 (4): 359–69. doi: 10.1097/ICO.0000000000000408
30. Hafezi F. Limitation of collagen crosslinking with hypo-osmolar riboflavin solution: failure in extremely thin corneas. Cornea. 2011; 30 (8): 917–9. doi: 10.1097/ICO.0b013e31820143d1
31. Koç M, Uzel M, Koban Y, et al. Accelerated corneal crosslinking with hypoosmolar riboflavin solution in keratoconus thin corneas: short-term results. Cornea. 2016; 35 (3): 350–4. doi: 10.1097/ICO.000000000000000701
32. Zamora KV, Males JJ. Polymicrobial keratitis after a collagen cross-linking procedure with postoperative use of a contact lens: a case report. Cornea. 2009; 28 (4): 474–6. doi: 10.1097/ICO.0b013e31818d381a
33. Sharma N, Maharana P, Singh G, Tritiya JS. Pseudomonas keratitis after collagen crosslinking for keratoconus: case report and review of literature. J Cataract Refract Surg. 2010; 36 (3): 517–20. doi: 10.1016/j.jcrs.2009.08.041
34. Al-Qarni A, AlHarbi M. Herpetic keratitis after corneal collagen cross-linking with riboflavin and ultraviolet-a for keratoconus. East Afr J Ophthalmol. 2015; 22 (3): 389–92. doi: 10.4103/0974-9233.159777
35. Yuksel N, Bilgihan K, Hondur AM. Herpetic keratitis after corneal collagen cross-linking with riboflavin and ultraviolet-A for progressive keratoconus. Int Ophthalmol. 2011; 31 (6): 513–5. doi: 10.1007/s10792-011-9489-x
36. Ferrari G, Iuliano L, Viganò M, Rama P. Impending corneal perforation after collagen cross-linking for herpetic keratitis. J Cataract Refract Surg. 2013; 39 (4): 638–41. doi: 10.1016/j.jcrs.2013.02.006
37. Sitaula S, Singh SK, Gurung A. Bilateral viral keratitis following corneal collagen crosslinking for progressive keratoconus. J Ophthalmic Inflamm Infect. 2019; 9 (1): 16. doi: 10.1186/s12348-019-0185-8
38. Wang L, Deng Y, Ma K, et al. Herpetic keratitis following corneal crosslinking for keratoconus: A case series. Infect Drug Resist. 2022; 15: 6555–62. doi: 10.2147/IDR.S389920
39. Steinwender G, Pertl L, El-Shabrawi Y, et al. Complications from corneal cross-linking for keratoconus in pediatric patients. J Refract Surg. 2016; 32 (1): 68–9. doi: 10.3928/1081597X-20151210-03
40. Maharana PK, Sahay P, Sujeeth M, et al. Microbial keratitis after accelerated corneal collagen cross-linking in keratoconus. Cornea. 2018; 37 (2): 162–7. doi: 10.1097/ICO.0000000000001439
41. Arora R, Simalandhi P, Goyal JL, Gupta D. Results of corneal collagen cross-linking in pediatric patients. J Refract Surg. 2012; 11: 759–62. doi: 10.3928/1081597X-20121011-02
42. Padmanabhan P, Reddi SR, Rajagopal R, et al. Corneal collagen cross-linking for keratoconus in pediatric patients — long term results. Cornea. 2017; 36 (2): 138–3. doi: 10.1097/ICO.0000000000001102
43. Zotta PG, Diakonis VF, Kymionis GD, et al. Long-term outcomes of corneal cross-linking for keratoconus in pediatricpatients. J AAPOS. 2017; 21 (5): 397–401. doi: 10.1016/j.jaapos.2017.07.205
44. Mazzotta C, Traversi C, Baiocchi S, et al. Corneal collagen crosslinking with riboflavin and ultraviolet a light for pediatric keratoconus: ten-year results. Cornea. 2018; 37 (5): 560–6. doi: 10.1097/ICO.0000000000001505
45. Chatzis N, Hafezi F. Progression of keratoconus and efficacy of pediatric [corrected] corneal collagen cross-linking in children and adolescents. J Refract Surg. 2012; 28 (11): 753–8. doi: 10.3928/1081597X-20121011-01
46. Vinciguerra P, Albé E, Frueh BE, et al. Two-year results of corneal crosslinking in patients younger than 18 years with documented progressive keratoconus. Am J Ophthalmol. 2012;154:520–6. doi: 10.1016/j.ajo.2012.03.020.
47. Godefrooij DA, Soeters N, Imhof SM, et al. Corneal crosslinking in childhood keratoconus: long-term results. Cornea. 2016; 35: 954–8. doi: 10.1097/ICO.00000000000000819
48. Бикбов М.М., Зайнутдинова Г.Х., Усубов Э.Л., Лукьянова Е.Э., Оганисян К.Х. Результаты лечения кератоэктазий методом кросслинкинга роговицы у детей и подростков. Офтальмохирургия. 2015; (3): 43–6.
49. Padmanabhan P, Reddi SR, Rajagopal R, et al. Corneal collagen cross-linking for keratoconus in pediatric patients-long-term results. Cornea. 2017; 36 (2): 138–3. doi: 10.1097/ICO.0000000000001102
50. Chowdhury K, Dore C, Burr JM, et al. A randomised, controlled, observermasked trial of corneal cross-linking for progressive keratoconus in children: the KERALINK protocol. BMJ Open. 2019 Sep 12; 9 (9): e028761. doi: 10.1136/bmjopen-2018-028761
51. Larkin DFP, Chowdhury K, Burr JM, et al. KERALINK Trial Study Group. Effect of corneal cross-linking versus standard care on keratoconus progression in young patients: The KERALINK randomized controlled trial. Ophthalmology. 2021; 128 (11): 1516–6. doi: 10.1016/j.ophtha.2021.04.019
52. Nicula CA, Rednik AM, Bulboacă AE, et al. Comparative results between “Epi-Off” conventional and accelerated corneal collagen crosslinking for progressive keratoconus in pediatric patients. Therapeut Clin Risk Manag. 2019; 15: 1483–90. doi: 10.2147/TCRM.S224533
53. Nath S, Shen C, Koziarz A, et al. Transepithelial versus epithelium-off corneal collagen cross-linking for corneal ectasia: a systematic review and meta-analysis. Ophthalmology. 2021; 128 (8): 1150–60. doi: 10.1016/j.ophtha.2020.12.023
54. Бикбов М.М., Бикбова Г.М., Суркова В.К., Зайнуллина Н.Б. Клинические результаты лечения кератоконуса методом трансэпителиального кросслинкинга роговичного коллагена. Офтальмология. 2016; 13 (1): 4–9. https://doi.org/10.18008/1816-5095-2016-1-4-9
55. Singh T, Taneja M, Murthy S, et al. Evaluation of safety and efficacy of different protocols of collagen cross linking for keratoconus. Rom J Ophthalmol. 2020 Apr-Jun; 64 (2): 158–67. PMID: 32685782.
56. Маркова Е.Ю., Авакянц Г.В., Кечин Е.В. Кератоконус у детей. Современные возможности лечения. Офтальмология. 2021; 18 (4): 840–4. doi: 10.18008/1816-5095-2021-4-840-844
57. Eissa SA, Yassin A. Prospective, randomized contralateral eye study of accelerated and conventional corneal cross-linking in pediatric keratoconus. Int Ophthalmol. 2019; 39 (5): 971–9. doi: 10.1007/s10792-018-0898-y
58. Oliverio GW, Vagge A, Gargano R, Aragona P, Roszkowska AM. Clinical results of accelerated iontophoresis-assisted epithelium-on corneal cross-linking for progressive keratoconus in children. J Pediatr Ophthalmol Strabismus. 2024; 61 (1): 44–50. doi: 10.3928/01913913-20230421-01
59. Buzzonetti L, Petrocelli G, Valente P, et al. Iontophoretic transepithelial collagen cross-linking versus epithelium-off collagen cross-linking in pediatric patients: 3-year follow-up. Cornea. 2019; 38 (7): 859–63. doi: 10.1097/ICO.0000000000001965
60. Henriquez MA, Rodríguez AM, Izquierdo LJr. Accelerated epi-on versus standard epi-off corneal collagen cross-linking for progressive keratoconus in pediatric patients. Cornea. 2017; 36 (12): 1503–8. doi: 10.1097/ICO.0000000000001366
61. Iqbal M, Elmassry A, Saad H, et al. Standard cross-linking protocol versus accelerated and transepithelial cross-linking protocols for treatment of paediatric keratoconus: A 2-year comparative study. Acta Ophthalmol. 2020; 98: e352–e362. doi: 10.1111/aos.14275
62. Henriquez MA, Hernandez-Sahagun G, Camargo J, Izquierdo JrL. Accelerated epi-on versus standard epi-off corneal collagen cross-linking for progressive keratoconus in pediatric patients: Five years of follow-up. Cornea. 2020; 39 (12): 1493–8. doi: 10.1097/ICO.0000000000002463
63. Sarac O, Caglayan M, Uysal BS, Uzel AGT, Tanriverdi B, Cagil N. Accelerated versus standard corneal collagen cross-linking in pediatric keratoconus patients: 24 months follow-up results. Cont Lens Anterior Eye. 2018; 41 (5): 442–7. doi: 10.1016/j.clae.2018.06.001
64. Saleh S, Koo EB, Lambert SR, Manche EE. Outcomes after corneal crosslinking for keratoconus in children and young adults. Cornea. 2022; 41 (4): 408–16. doi: 10.1097/ICO.0000000000002730
65. Kobashi H, Hieda O, Itoi M, et al. The Keratoconus Study Group of Japan. Corneal cross-linking for paediatric keratoconus: A systematic review and meta-analysis. J Clin Med. 2021; 10 (12): 2626. doi: 10.3390/jcm10122626
66. Cehelyk EK, Syed ZA. Long-term outcomes of corneal crosslinking. Current Opinion in Ophthalmology. 2024; 35 (4): 315–21. doi: 10.1097/ICU.0000000000001054
Рецензия
Для цитирования:
Зайнутдинова Г.Х., Казакбаева Г.М., Инсапова А.В., Тимербулатова Д.А., Багманов Р.И. Применение кросслинкинга роговицы у детей с кератоконусом. Обзор литературы. Российский офтальмологический журнал. 2025;18(4):164-168. https://doi.org/10.21516/2072-0076-2025-18-4-164-168
For citation:
Zainutdinova G.Kh., Kazakbaeva G.M., Insapova A.V., Timerbulatova D.A., Bagmanov R.I. Сorneal crosslinking in children with keratoconus. Literature review. Russian Ophthalmological Journal. 2025;18(4):164-168. (In Russ.) https://doi.org/10.21516/2072-0076-2025-18-4-164-168


























