Iontophoretic Transepithelial Corneal Cross-linking to Halt Keratoconus in Pediatric Cases

Buzzonetti, Luca; Petrocelli, Gianni; Valente, Paola; Iarossi, Giancarlo; Ardia, Roberta; Petroni, Sergio

doi:10.1097/ico.0000000000000410

Cited by 64 publications

(34 citation statements)

References 23 publications

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“…Plus, they confirmed that this Epi-ON protocol resulted in keratoconus evolution after 24 months of follow-up, adding a note of caution to its application in pediatric patients that often suffer from more aggressive forms of the disease 32 . Indeed, as for other transepithelial protocols, iontophoresis does not seem to ensure an improvement in topographic indices in pediatric patients 33 . This absence of efficacy can be explained by limited riboflavin and UVA penetration with the epithelium in situ 11,[34][35][36] .…”

Section: Discussionmentioning

confidence: 99%

Three Different Protocols of Corneal Collagen Crosslinking in Keratoconus: Conventional, Accelerated and Iontophoresis

Bouheraoua

Jouve

Borderie

et al. 2015

JoVE

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Keratoconus is a bilateral and progressive corneal ectasia. In order to slow down its progression, corneal collagen cross-linking (CXL) has recently been introduced as an efficient treatment option. In biological and chemical sciences, crosslinking refers to new chemical bonds formed between reactive molecules. Hence, the aim of corneal collagen CXL is to synthetically increase the formation of crosslinks between collagen fibrils in the corneal stroma. Despite the fact that the efficiency of the conventional CXL (C-CXL) protocol has already been shown in several clinical studies, it might benefit from improvements in duration of the procedure and removal of corneal epithelium. Hence, in order to provide a coherent evaluation of two new and optimized CXL protocols, we studied keratoconus patients who had undergone one of the three CXL treatments: iontophoresis (I-CXL), accelerated CXL (A-CXL), and conventional CXL (C-CXL). A-CXL is a 6 time faster CXL procedure using a ten time higher UVA irradiance but still including an epithelium removal. Iontophoresis is a transepithelial non-invasive technique in which a small electric current is applied to improve riboflavin penetration throughout the cornea. Using anterior segment optical coherence tomography (AS OCT) and in vivo confocal microscopy (IVCM), we conclude that regarding the depth of treatment penetration, conventional CXL protocol remains the standard for treating progressive keratoconus. Accelerated CXL seems to be a quick, effective and safe alternative to treat thin corneas. The use of iontophoresis is still being investigated and should be considered with greater caution. Video LinkThe video component of this article can be found at

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Section: Discussionmentioning

confidence: 99%

Three Different Protocols of Corneal Collagen Crosslinking in Keratoconus: Conventional, Accelerated and Iontophoresis

Bouheraoua

Jouve

Borderie

et al. 2015

JoVE

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“…For iontophoresis, up to 15-month followup data have been published, with reported cessation of disease progression and improvements in keratometric and visual parameters. [7][8][9] The longer-term relative efficacy of all these transepithelial techniques compared to epithelium-off CXL remains unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Another method involves iontophoresis, in which negatively charged riboflavin is driven through the epithelium down an electrical gradient. [7][8][9] Previous studies to quantify riboflavin penetration through an intact epithelium have used high-performance liquid chromatography (HPLC) [10][11][12] and fluorescence microscopy. [13][14][15][16][17] High-performance liquid chromatography, in which the sample is dissolved in a solvent for analysis, can accurately quantify the concentration of riboflavin in a whole block of tissue, but is unable to provide information about the concentration at different depths within the corneal stroma (unless lamella sections are prepared and separately dissolved).…”

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confidence: 99%

Transepithelial Riboflavin Absorption in an Ex Vivo Rabbit Corneal Model

Gore

O’Brart

French

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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Citation: Gore DM, O'Brart D, French P, Dunsby C, Allan BD. Transepithelial riboflavin absorption in an ex vivo rabbit corneal model. Invest Ophthalmol Vis Sci. 2015;56:5006-5011. DOI:10.1167/iovs.15-16903 PURPOSE. To measure depth-specific riboflavin concentrations in corneal stroma using twophoton fluorescence microscopy and compare commercially available transepithelial corneal collagen cross-linking (CXL) protocols. METHODS.Transepithelial CXL riboflavin preparations-MedioCross TE, Ribocross TE, Paracel plus VibeX Xtra, and iontophoresis with Ricrolinþ-were applied to the corneal surface of fresh postmortem rabbit eyes in accordance with manufacturers' recommendations for clinical use. Riboflavin 0.1% (VibeX Rapid) was applied after corneal epithelial debridement as a positive control. After riboflavin application, eyes were snap frozen in liquid nitrogen. Corneal cross sections 35-lm thick were cut on a cryostat, mounted on a slide, and imaged by two-photon fluorescence microscopy. Mean (SD) concentrations were calculated from five globes tested for each protocol.RESULTS. Peak riboflavin concentration of 0.09% (60.01) was observed within the most superficial stroma (stromal depth 0-10 lm) in positive controls (epithelium-off). At the same depth, peak stromal riboflavin concentrations for MedioCross TE, Ricrolinþ, Paracel/Xtra, and Ribocross TE were 0.054% (60.01), 0.031% (0.003), 0.021% (60.001), and 0.015% (60.004), respectively. At a depth of 300 lm (within the demarcation zone commonly seen after corneal cross-linking), the stromal concentration in epithelium-off positive controls was 0.075% (60.006), while at the same depth MedioCross TE and Ricrolinþ achieved 0.018% (60.006) and 0.016% (0.002), respectively. None of the remaining transepithelial protocols achieved concentrations above 0.005% at this same 300-lm depth. Overall, MedioCross TE was the best-performing transepithelial formulation.CONCLUSIONS. Corneal epithelium is a significant barrier to riboflavin absorption into the stroma. Existing commercial transepithelial CXL protocols achieve relatively low riboflavin concentrations in the anterior corneal stroma when compared to gold standard epithelium-off absorption. Reduced stromal riboflavin concentration may compromise the efficacy of riboflavin/ultraviolet corneal CXL.

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“…Исход лечения характеризовался существенным улучшением функци-ональных показателей, основанных на специфичных морфологических изменениях в роговице [78]. Хорошие результаты продемонстрировала трансэпителиальная техника CXL, выполненная у подростков от 10 до 18 лет с помощью ионофореза в ускоренном режиме облучения (5 мин, 10 мВт/см 2 ) [79].…”

Section: возможности клинического применения уф-кросслинкингаunclassified

Ultraviolet Corneal Crosslinking

Бикбов¹,

Khalimov²,

Usubov³

2016

Annals RAMS

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Во всем мире ежегодно отмечается значительный рост заболеваний роговицы, сопровождающихся деструктив-ными изменениями коллагена в ее составе, что связывают с ухудшением экологии, интенсификацией глазной хи-рургии, травмами глаза, а также с увеличившимся числом офтальмоинфекций [1]. В Российской Федерации на больных с заболеваниями роговицы приходится до 18% общего числа слепых и слабовидящих [2].В основе кератоэктазий, в частности кератоконуса, лежит прогрессирующая деградация коллагеновой струк-туры роговицы и, соответственно, снижение ее прочност-но-механических свойств, приводящие к помутнению, нередко рубцеванию и значительному снижению остроты зрения. Как правило, это билатеральный патологический процесс, чаще наблюдаемый у лиц молодого трудоспо-собного возраста. Качественные и количественные из-менения состава коллагена органа зрения, отрицательно сказываясь на его структуре, проявляются в различных сочетаниях симптоматики болезни.Этиология кератоконуса считается многофакторной и наряду с вышеуказанными причинами включает также наследственную, эндокринную, аллергическую, имму-нологическую и другие теории, среди которых наиболее признанной у специалистов считается генетическая ги-потеза [3]. Несомненно, в пользу этого свидетельствуют семейные случаи заболевания, а также их сочетание с некоторыми наследственными синдромами. Так, по дан-ным мультицентрового проспективного исследования CLERK (США), генетические формы кератоконуса были выявлены в 13,5% случаев [4].В последнее десятилетие так называемый инжини-ринг тканей, базирующийся на процессах фотополи-меризации, стали использовать для лечения широкого спектра заболеваний. В частности, с целью укрепления роговой оболочки глаза при хронических дегенеративных процессах успешно применяется ультрафиолетовый (УФ) кросслинкинг роговицы (UV Corneal Crosslinking, CXL), основанный на ее облучении при длине волны 370 нм с использованием светочувствительного рибофлавина [5].Кросслинкинг (перекрестное связывание, или сши-вание) способствует стабилизации биомеханических свойств роговицы за счет увеличения количества свя-зей между фибриллами стромального коллагена, кера-тоцитами и белками межклеточной адгезии посредством рибофлавин-УФ-индуцируемых фотохимических реак-ций [5−8]

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Iontophoretic Transepithelial Corneal Cross-linking to Halt Keratoconus in Pediatric Cases

Abstract: Transepithelial collagen cross-linking by iontophoresis, unlike other transepithelial techniques, seems to halt pediatric keratoconus progression over 15 months. However, we did not record significant improvement in higher-order aberrations and topographic indices.

Cited by 64 publications

References 23 publications

Three Different Protocols of Corneal Collagen Crosslinking in Keratoconus: Conventional, Accelerated and Iontophoresis

Three Different Protocols of Corneal Collagen Crosslinking in Keratoconus: Conventional, Accelerated and Iontophoresis

Transepithelial Riboflavin Absorption in an Ex Vivo Rabbit Corneal Model

Ultraviolet Corneal Crosslinking

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