Evaluation of Epithelial Integrity with Various Transepithelial Corneal Cross-Linking Protocols for Treatment of Keratoconus

Taneri, Suphi; Oehler, Saskia; Lytle, Grace; Dick, H. Burkhard

doi:10.1155/2014/614380

Cited by 23 publications

(27 citation statements)

References 9 publications

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“…Enhanced UV absorption with free radical generation within the epithelium could result in ''arc eye''-type epithelial toxicity. Epithelial defects are commonly observed on day 1 after transepithelial CXL using currently available protocols, 21 and punctate epitheliopathy is evident in all cases (O' Brart D, oral communication, 2015).…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…The barrier function of the intact epithelium also limit the key components of effective cross linking like optimal homogenous riboflavin saturation and incident UVA light penetration 13-15. ParaCel (avedro), is a dextran-free, hypoosmolar new transepithelial riboflavin formulation that contains epithelial permeability enhancers like BAC, EDTA to facilitate penetration through intact epithelium.…”

Section: Discussionmentioning

confidence: 99%

Transepithelial corneal crosslinking in treatment of progressive keratoconus: 12 months’ clinical results

Akbar¹,

Intisar-Ul-Haq²,

Ishaq³

et al. 2017

Pak J Med Sci

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Objective:The purpose of this study was to evaluate the safety and efficacy of transepithelial corneal collagen cross linking (TE-CXL) with modified riboflavin and accelerated UVA irradiance in thin corneas with pachymetry less than 400 microns at thinnest point, untreatable by epithelium off corneal collagen cross linking (CXL) in adult Pakistani population with progressive keratoconus.Methods:This quasi experimental study included twenty six eyes of 26 patients with progressive keratoconus who underwent accelerated transepithelial CXL in Armed forced institute of ophthalmology with 12 months follow up. Modified riboflavin, ParaCel ((riboflavin 0.25%, Benzalkonium chloride, EDTA, Trometamol, hydroxypropyl methylcellulose) and vibeX Xtra (riboflavin 0.25%) (Avedro, USA)) were applied to cornea in two stages. Uncorrected and Corrected Distant Visual Acuities (UDVA, CDVA), spherical equivalent (SE), astigmatism, pachymetry at thinnest point (Pachy thin), apex keratometry (Kmax), simulated and steep keratometry (Sim K, steep K) were measured at baseline and at 3, 6 and 12 months post operatively. The cornea was then exposed to accelerated UVA irradiance of 9mW/cm2 for 10 min (total dose 30 mW/cm2).Results:The mean age of the patient was 24.54±5.16 years. UDVA, CDVA, SE, astigmatism significantly improved at all postoperative test points (p=0.000, 0.004, 0.000, 0.004 respectively). Kmax and pachy thin were significantly reduced over baseline at 1 year (p=0.000, 0.004 respectively). Topographic indices Sim K and steep K did not show significant changes. No intra or post-operative complications were reported.Conclusion:Transepithelial accelerated CXL with modified riboflavin is a safe and effective procedure which halt disease progression in thin corneas with progressive keratoconus.

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“…It may also result in an ''arc-eye'' type of reaction, particularly where riboflavin preparations including BAC are used, accounting for the epithelial defects seen in up to twothirds of patients after transepithelial CXL using MedioCross TE. 35 The ideal transepithelial protocol would load the stroma with riboflavin while leaving the epithelium relatively clear. To this end, in this study we rinsed the surface of the globe after iontophoresis in a bid to wash out some of the riboflavin from within the epithelium.…”

Section: Discussionmentioning

confidence: 99%

A Comparison of Different Corneal Iontophoresis Protocols for Promoting Transepithelial Riboflavin Penetration

Gore

O’Brart

French

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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Citation: Gore DM, O'Brart DP, French P, Dunsby C, Allan BD. A comparison of different corneal iontophoresis protocols for promoting transepithelial riboflavin penetration. Invest Ophthalmol Vis Sci. 2015;56:7908-7914. DOI:10.1167/iovs.15-17569 PURPOSE. To measure corneal riboflavin penetration using different transepithelial iontophoresis protocols. METHODS.Freshly enucleated rabbit eyes were divided into nine treatment groups of 4 eyes. One group, in which 0.1% wt/vol riboflavin was applied for 30 minutes without iontophoresis after corneal epithelial debridement, acted as a control. The remaining groups were treated with an intact epithelium using different riboflavin formulations and varying iontophoresis current, soak, and rinse times. After riboflavin application, eyes were snap frozen in liquid nitrogen. Corneal cross sections 35 lm thick were then imaged immediately by two-photon fluorescence microscopy, using image processing software to quantify stromal riboflavin concentration at different corneal depths.RESULTS. In the epithelium-on iontophoresis treatment groups, greater stromal riboflavin penetration was achieved with higher-concentration riboflavin solutions, greater iontophoresis dosage, and longer solution contact times. A protocol utilizing 0.25% wt/vol riboflavin with benzalkonium chloride (BAC) 0.01% and two cycles of applied current and subsequent soaking (1 mA 5 minutes, soak 5 minutes; 0.5 mA 5 minutes, soak 5 minutes) achieved similar stromal riboflavin penetration to epithelium-off controls. The best-performing non-BACcontaining protocol produced stromal riboflavin penetration approximately 60% that of epithelium-off controls. Riboflavin solutions containing saline resulted in minimal stromal penetration. Riboflavin loading within the epithelium was equivalent to or higher than that in the subjacent stroma, despite rinsing the ocular surface with balanced salt solution.CONCLUSIONS. Modified iontophoresis protocols can significantly improve transepithelial riboflavin penetration in experimental corneal collagen cross-linking.

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Evaluation of Epithelial Integrity with Various Transepithelial Corneal Cross-Linking Protocols for Treatment of Keratoconus

Cited by 23 publications

References 9 publications

Transepithelial Riboflavin Absorption in an Ex Vivo Rabbit Corneal Model

Transepithelial Riboflavin Absorption in an Ex Vivo Rabbit Corneal Model

Transepithelial corneal crosslinking in treatment of progressive keratoconus: 12 months’ clinical results

A Comparison of Different Corneal Iontophoresis Protocols for Promoting Transepithelial Riboflavin Penetration

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