ophthalmologyОфтальмологияOphthalmology in Russia1816-50952500-0845Ophthalmology10.18008/1816-5095-2014-3-13-19ophthalmology-183Research ArticleОБЗОРЫREVIEWSМетод перекрестного связывания коллагена роговицы при кератоконусе. Обзор литературыCorneal collagen crosslinking for keratoconus. A reviewБикбовМ. М.BikbovM. M.СурковаВ. К.SurkovaV. K.ufaeyenauka@mail.ruГосударственное бюджетное учреждение «Уфимский НИИ глазных болезней Академии наук Республики Башкортостан»РоссияUfa Eye Research Institute of Academy of Sciences of the Republic of BashkortostanRussian Federation2014111020141131319Copyright © Бикбов М.М., Суркова В.К., 20142014Бикбов М.М., Суркова В.К.Bikbov M.M., Surkova V.K.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.ophthalmojournal.com/opht/article/view/183

В офтальмологии нашел применение фотохимический кросслинкинг коллагеновых волокон, биохимический эффект которого обусловлен высвобождением синглетного кислорода, способствующего анаэробному типу фотохимической реакции. Кератоконус — один из самых распространенных видов эктазии роговицы, частота которого варьирует от 1:250 до 1:250000 населения. В настоящее время возрастает число ятрогенных кератэктазий после эксимерлазерной коррекции аметропий вследствие нарушения биомеханики роговицы. Патоморфологические и биохимические особенности роговицы при кератэктазии включают истончение всех ее слоев, появление контакта стромы с эпителием в местах разрыва боуменовой оболочки, фрагментацию хроматина в ядрах кератоцитов, явления фагоцитоза, разрушение коллагеновых фибрилл, нарушение тинкториальных свойств и параллельного расположения коллагеновых волокон, сбой ферментативных систем и апоптоз кератоцитов. При кератэктазиях происходит нарушение ферментативных процессов в кератоцитах, приводящее к нарушению процесса коллагенообразования. Степень упаковки коллагеновых волокон обусловлена активностью ряда ферментов экстрацеллюлярного матрикса стромы, связывающих аминогруппы и альдегидгруппы аминокислот коллагеновых волокон между собой. На поздних стадиях возникают морфологическиеизменения десцеметовой мембраны (разрыв, отслойка). Дистрофия эндотелия проявляется в нарушении правильной гексогональной формы кератоцитов и апоптозе. Отсутствие аналогов в отечественной офтальмологии побудило исследователей Уфимского НИИ глазных болезней к разработке устройства для проведения процедуры перекрестного связывания коллагена роговицы. Определены параметры УФО (длина волны, длительность воздействия, мощность) для получения желаемого эффекта, изучены особенности некоторых фотосенсибилизаторов в процессе процедуры. Разработаны и внедрены в клиническую практику устройства для ультрафиолетового облучения роговицы глаза «УФалинк и фотосенсибилизатора «Декстралинк». Из-за опасности повреждения эндотелия применение способа противопоказано при тяжелых стадиях кератоконуса, когда толщина роговицы составляет менее 400 мкм. Основные эффекты кросслинкинга роговичного коллагена следующие: увеличение модуля Юнга (показателя упругости) в среднем на 328,9 %, повышение устойчивости к температуре на 5ºС, увеличение диаметра коллагенового волокна в передних отделах стромы на 12,2 %, в задних — на 4,6 %. Продемонстрирована антимикробная эффективность кросслинкинга в лечении буллезной кератопатии легкой степени тяжести. При средней и тяжелой степени кросслинкинг обеспечивает купирование болевого синдрома, снижение отека роговицы и увеличение остроты зрения непосредственно после процедуры. Описано обострение герпетического кератита после процедуры. Среди осложнений имеют место инфицирование, эффект halo, повреждение задних структур глаза. Невысокий рефракционный эффект роговичного кросслинкинга может быть усилен его сочетанием с имплантацией интрастромальных сегментов или колец.

Photochemical crosslinking is widely applied in ophthalmology. Its biochemical effect is due to the release of singlet oxygen that promotes anaerobic photochemical reaction. Keratoconus is one of the most common corneal ectasia affecting 1 in 250 to 250 000 persons. Currently, the rate of iatrogenic ectasia following eximer laser refractive surgery increases due to biomechanical weakening of the cornea. Morphologically and biochemically, ectasia is characterized by corneal layers thinning, contact between the stroma and epithelium resulting from Bowman’s membrane rupture, chromatin fragmentation in keratocyte nuclei, phagocytosis, abnormal staining and arrangement of collagen fibers, enzyme system disorders, and keratocyte apoptosis. In corneal ectasia, altered enzymatic processes result in the synthesis of abnormal collagen. Collagen packing is determined by the activity of various extracellular matrix enzymes which bind amines and aldehydes of collagen fiber amino acids. In the late stage, morphological changes of Descemet’s membrane (i.e., rupture and detachment) develop. Abnormal hexagonal-shaped keratocytes and their apoptosis are the signs of endothelial dystrophy. The lack of analogs in domestic ophthalmology encouraged the scientists of Ufa Eye Research Institute to develop a device for corneal collagen crosslinking. The parameters of ultraviolet (i.e., wavelength, exposure time, power) to achieve the desired effect were identified. The specifics of some photosensitizers in the course of the procedure were studied. UFalink, a device for UV irradiation of cornea, and photosensitizer Dextralink were developed and adopted. Due to the high risk of endothelial damage, this treatment is contraindicated in severe keratoconus (CCT less than 400 microns). Major effects of corneal collagen crosslinking are the following: Young’s modulus (modulus of elasticity) increase by 328.9 % (on average), temperature tolerance increase by 5°C, and collagen fiber diameter increase by 12.2 % (anterior stroma) and 4.6 % (posterior stroma). In mild bullous keratopathy, corneal crosslinking provides antimicrobial effect. In moderate and severe keratopathy, crosslinking reduces pain and corneal edema and improves visual acuity immediately after the procedure. A case of HSV keratitis exacerbation was described. Amongst the complications, infection, halos, and posterior segment damage should be mentioned. Poor refractive results can be improved by the implantation of intrastromal corneal ring segments.

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The authors declare that there are no conflicts of interest present.