Quantitative analysis of corneal stromal riboflavin concentration without epithelial removal

Rubinfeld, Roy S.; Stulting, R. Doyle; Gum, G G; Talamo, Jonathan H.

doi:10.1016/j.jcrs.2018.01.010

Cited by 22 publications

(26 citation statements)

References 10 publications

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“…The failure rate of the standard epi-off CXL is known to be as high as 7.6%, especially in more advanced cases of ectasia. 12 In the current case, novel treatment with CK followed by non-invasive TE-CXL with a proprietary transepithelial riboflavin formulation and system 9 successfully treated advanced ectasia and stabilized the patient's vision without complications such as DLK.…”

Section: Discussionmentioning

confidence: 83%

“…Two, TE-CXL can successfully treat ongoing postsurgical ectasia after epi-off CXL. We also suggest that effective TE-CXL 8 may, by avoiding surgical removal or disruption of the corneal epithelium, reduce the risk of DLK, infection, scarring and extended recovery that can occur as a result of epi-off CXL 6 , 9 in this situation.…”

Section: Discussionmentioning

confidence: 93%

“…In brief, 4 CK spots were placed over the steep infero-central area to flatten the corneal apex as described previously 6 , 7 . Under topical anesthesia, a novel, proprietary, TE-CXL system was utilized for 20 minutes and adequate stromal loading was confirmed by slit-lamp evaluation 9 , 10 . The eye was exposed to ultraviolet light (365 nm) at 4 mW/cm 2 cycled off and on with a proprietary duty cycle for 20 minutes (CXL Ophthalmics, Encinitas, CA).…”

Section: Case Reportmentioning

confidence: 99%

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Diffuse lamellar keratitis after epi-off corneal crosslinking: An under-recognized complication?

Mannschreck

Rubinfeld

Soiberman

et al. 2019

American Journal of Ophthalmology Case Reports

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PurposeTo report diffuse lamellar keratitis (DLK) occurring in an eye that underwent epithelium-off (epi-off) corneal cross-linking (CXL) as a treatment for post-surgical ectasia and the successful treatment of progressive ectasia with a novel epi-on CXL and conductive keratoplasty (CK) treatment.ObservationsA 42-year-old man presented with corneal ectasia in his right eye 3 years after laser in situ keratomileusis (LASIK) surgery. He underwent epi-off corneal CXL using the Dresden protocol. Grade II DLK was diagnosed within days of CXL. Despite successful treatment of DLK, best-corrected visual acuity in the right eye deteriorated over the next 4 months due to progression of ectasia and remained worse than the patient's pre-operative baseline 1 year after epi-off CXL. Because of apparent disease progression, despite his CXL treatment, the patient underwent a novel, transepithelial CXL (TE-CXL) treatment combined with conductive keratoplasty (CK). This treatment improved his vision and stabilized his ectasia without subsequent DLK. Approximately 3 years after CK and TE-CXL, his eye remains stable with 4 Snellen lines of improved vision and no progression of ectasia.Conclusion and importanceEpithelium-off CXL is used increasingly to treat post-LASIK ectasia. First, in this case, DLK occurred after epi-off CXL. We suggest careful scrutiny of such cases as DLK is difficult to identify after epi-off CXL. Second, the epi-off CXL was unsuccessful in stopping the post-LASIK ectasia. Transepithelial CXL successfully treated the ongoing ectasia after resolution of the DLK with no subsequent re-occurrence of DLK. We suggest that TE-CXL may provide a successful initial treatment for post-LASIK ectasia that also minimizes the epithelial disruption that can lead to DLK.

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 93%

Section: Case Reportmentioning

confidence: 99%

See 1 more Smart Citation

Diffuse lamellar keratitis after epi-off corneal crosslinking: An under-recognized complication?

Mannschreck

Rubinfeld

Soiberman

et al. 2019

American Journal of Ophthalmology Case Reports

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“…In contrast to other methods of measuring stromal riboflavin concentration such as fluorescence imaging, slit-lamp examination, or high-performance liquid chromatography (HPLC), this method was able to provide a real-time measurement without relying on fluorescence measurements taken within the corneal stromal and produced comparative measurements to other techniques. 27,36,38,39 Mastropasqua et al 27 reported using iontophoresis and additives to achieve stromal riboflavin concentrations that were 21% and 44%, respectively, compared to the standard Dresden protocol using HPLC. Additionally, Cui et al 36 reported a peak stromal concentration of 50% standard measured via two-photon fluorescence after transepithelial BAK treatment.…”

Section: Measuring Stromal Rf Concentrationmentioning

confidence: 99%

Enhanced Transepithelial Riboflavin Delivery Using Femtosecond Laser-Machined Epithelial Microchannels

Bradford

Mikula

Xie

et al. 2020

Trans. Vis. Sci. Tech.

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This study describes a femtosecond laser (FS) approach to machine corneal epithelial microchannels for enhancing riboflavin (Rf) penetration into the cornea prior to corneal crosslinking (CXL). Methods: Using a 1030-nm FS laser with 5-to 10-μJ pulse energy, the corneal epithelium of slaughterhouse rabbit eyes was machined to create 2-μm-diameter by 25-μmlong microchannels at a density of 100 or 400 channels/mm 2. Rf penetration through the microchannels was then determined by applying 1% Rf in phosphate-buffered saline for 30 minutes followed by removal of the cornea and extraction from the central stromal button. Stromal Rf concentrations were then compared to those obtained using standard epithelial debridement or 0.01% benzalkonium chloride (BAK) to disrupt the epithelial barrier. Results: Microchannels formed using a 5-μJ/pulse at a density of 400 channels/mm 2 achieved a stromal Rf concentration that was 50% of that achieved by removal of the corneal epithelium and imbibing with 1% Rf. Stromal Rf levels were also equal to that of debrided corneas soaked with 0.5% Rf, threefold higher than those soaked with 0.1% Rf, and twofold higher than corneas soaked in BAK without epithelial debridement. Organ culture of treated corneas showed a normal corneal epithelium following FS machining while BAK-treated corneas showed extensive epithelial and stromal damage at 24 hours posttreatment. Conclusions: FS corneal epithelial machining can be used to enhance penetration of Rf into the stroma for corneal CXL. Translational Relevance: The creation of epithelial microchannels allows for stromal Rf concentrations high enough to perform true transepithelial crosslinking.

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“…The intact nature of the epithelium has been confirmed on slitlamp examination by an independent laboratory. 6 Next, in each subject a sponge-like loading device (CXL Ophthalmics), shaped to conform to the cornea's curvature (including steep, cone-shaped corneas) and maximize contact with the cornea was saturated with the riboflavin solution and placed over the entire cornea.…”

Section: Epithelium-on Corneal Cross-linking For Progressive Keratocomentioning

confidence: 99%

Epithelium-on Corneal Cross-linking for Progressive Keratoconus: Two-year Outcomes

Cummings¹,

Shaw²,

Kelly³

2018

International Journal of Keratoconus and Ectatic Corneal Diseases

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Corneal cross-linking (CXL) has been established as a successful treatment tool for the treatment of progressive keratoconus in terms of slowing or halting progressive corneal steepening and thinning and even on some occasions, reversing the steepening. To date the Dresden epithelium-off protocol is regarded as the gold standard and the epithelium-on (epi-on) approaches have met with less success. Both doctors and patients would welcome an epi-on CXL procedure that provided good outcomes as the morbidity with epi-on CXL is so much less and the safety is enhanced. Patient comfort is greater with the epi-on techniques when compared to epi-off. This study looked at 82 eyes that had documented progression of keratoconus and then underwent epi-on CXL using the CXLO system. The results show that corneal steepening can be halted and even reversed over a 2-year follow-up period with no complications noted. Over the 24 months post treatment on average there was a decrease in all keratometry values, BAD and ISV when compared to before treatment with IHD being marginally increased.Further studies over a longer follow-up period are required but recent publications using the same approach are validating the findings seen in this study.

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Quantitative analysis of corneal stromal riboflavin concentration without epithelial removal

Cited by 22 publications

References 10 publications

Diffuse lamellar keratitis after epi-off corneal crosslinking: An under-recognized complication?

Diffuse lamellar keratitis after epi-off corneal crosslinking: An under-recognized complication?

Enhanced Transepithelial Riboflavin Delivery Using Femtosecond Laser-Machined Epithelial Microchannels

Epithelium-on Corneal Cross-linking for Progressive Keratoconus: Two-year Outcomes

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