New clinical pathways for keratoconus

Gore, Daniel M.; Shortt, Alex J.; Allan, Bruce

doi:10.1038/eye.2012.257

Cited by 66 publications

(45 citation statements)

References 76 publications

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“…[2][3][4] The corneal epithelium is removed in this protocol to facilitate riboflavin absorption and hence treatment efficacy. However, complications including infection, scarring, delayed healing, sterile inflammatory infiltration, tissue melting, and resultant vision loss have all been described in association with corneal epithelial removal in CXL.…”

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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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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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“…Gore et al in their review of contemporary studies determined the presence of one of the following parameters as a criterion for the disease progression: maximum K (Kmax) of >1D, a difference of >1D between maximum and minumum K values (KmaxKmin), corneal apex power of >1D, the mean K of >0.75D, an increase in MRSE by >0.5D or a decrease in the central corneal thickness by >2%. 30 This is the first study to show progression of keratoconus in adults in Turkey, where vernal keratoconjunctivitis and keratoconus are common.…”

Section: Discussionmentioning

confidence: 99%

Progression of Keratoconus in Turkish Adult Patients

Novruzlu¹,

Yüksel²,

Bi̇lgi̇han³

2016

Turkiye Klinikleri J Ophthalmol

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A AB BS S T TR RA AC CT T O Ob bj je ec ct ti iv ve e: : To evaluate progression of keratoconus in adult patients diagnosed as keratoconus and to compare it with the disease progression in pediatric patients reported in the literature. M Ma at te er ri ia al l a an nd d M Me et th ho od ds s: : Five hundred and forty-seven patients diagnosed as keratoconus were reviewed retrospectively and 143 eyes of 106 adult patients were included into the study. The patients were assigned into two groups: Group I was aged 18-24 years and Group II was aged over 24 years. Data about age, best corrected visual acuity (BCVA) with glasses, spherical equivalents (SE), corneal thickness, simulated mean kerotometry (SimK) and follow-up periods were collected. The patients having progression in keratoconus were recommended a treatment with corneal collagen cross-linking. R Re es su ul lt ts s: : The mean age of the patients was 21.34±1.75 years and 30.26±5.10 years in Group I and Group II respectively. The mean follow-up period was 11.96±7.24 months in Group I and 15.44±12.6 months in Group II. The rate of the progression was 25.6% and 23.1% in Group I and Group II respectively, though there was not a significant difference (p=0.549). The rate of the progression was 24.4% in the adults recently diagnosed as keratoconus at the end of a mean follow-up period of 12.74±10.60 months. C Co on nc cl lu us si io on n: : About one fourth of the adult patients required cross-linking therapy during a one-year follow-up and 75% of the adult patients with keratoconus did not have disease progression at the end of a one-year follow-up. Before adults recently diagnosed as keratoconus are advised to have cross-linking therapy, they should be given an anti-allergic treatment and followed for the disease progression.K Ke ey y W Wo or rd ds s: : Keratoconus; corneal surgery, laser Ö ÖZ ZE ET T A Am ma aç ç: : Keratokonus tanısı konulan erişkin hastalarda keratokonus progresyonunu değerlen-dirmek ve literatürde bildirilen çocuk hastalarla karşılaştırmak. G Ge er re eç ç v ve e Y Yö ön nt te em ml le er r: : Keratokonus tanısı alan 547 hasta retrospektif olarak incelendi, 106 hastanın 143 gözü çalışmaya dahil edildi. Çalışmada hastalar iki gruba ayrıldı. 1. grup 18-24 yaş, 2. grup 24 yaş üzeri olacak şekilde oluştu-ruldu. Hastaların dosyalarından, yaş, gözlükle en iyi görme keskinliği (EİDGK), sferik eşdeğer (SE), korneal kalınlık, ortalama simüle keratometri (SimK) ve takip süreleri not edildi. Keratokonusta progresyon görülen hastalara korneal çapraz bağlama tedavisi yapıldı. B Bu ul lg gu ul la ar r: : Hastaların ortalama yaşı, Grup 1 ve Grup 2'de sırasıyla 21,34±1,75 yıl ve 30,26±5,10 yıl idi. Grup 1'de takip süresi 11,96±7,24 ay, Grup 2'de 12,74±10,60 ay idi. Progresyon oranı, Grup 1 ve Grup 2'de sırasıyla %25,6 ve %23,1 idi (p=0,549). Erişkinlerde ortalama 12,74±10,60 ay sonunda progresyon oranı %24,4 idi. S So on nu uç ç: : Ortalama 1 yıl sonunda tüm erişkinlerin 1/4'ünde korneal çapraz-bağlama tedavisi ihtiyacı olmaktadır ve 3/4'ünde keratakonus ...

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“…[1][2][3][4] Riboflavin acts as a photosensitizer for the production of free radicals that drive the cross-linking process. 5 While riboflavin is hydrophilic with a molecular weight of 340 Daltons (Da), the corneal epithelium is lipophilic and has a reduced permeability to molecules larger than 180 Da.…”

Section: Methodsmentioning

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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New clinical pathways for keratoconus

Cited by 66 publications

References 76 publications

Transepithelial Riboflavin Absorption in an Ex Vivo Rabbit Corneal Model

Transepithelial Riboflavin Absorption in an Ex Vivo Rabbit Corneal Model

Progression of Keratoconus in Turkish Adult Patients

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

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