RESUMO
PURPOSE: Corneal cross-linking (CXL) requires an adequate corneal riboflavin impregnation, which is clinically assessed by verification of a riboflavin "flare" in the anterior chamber. We set out to replace this subjective assessment with an objective measurement method and evaluated fluorophotometry as an apparatus-based technique for riboflavin detection in the anterior chamber. METHODS: In an artificial anterior chamber model using human corneas and a modified Fluorotron fluorophotometer, we determined the detection limits of riboflavin concentrations across native corneas by comparison measurements of the same concentrations in glass cuvettes. Subsequently, standard CXL procedures with corneal application of riboflavin were simulated and the proportions of riboflavin entering the anterior chamber were measured fluorophotometrically. RESULTS: The measurement results of the riboflavin dilution series in the artificial anterior chamber showed a very high concordance with the results obtained in a glass cuvette (Pitman test P = 0.329). In the CXL simulation, the mean riboflavin concentration measured in the anterior chamber increased within 15 minutes from 5 (±1) to 903 (±204) ng/mL and stood at 1089 (±56) ng/mL after 30 minutes. CONCLUSIONS: Fluorophotometry is able to measure riboflavin in an artificial anterior chamber across human corneas over a wide range of concentrations and it reliably detects the increasing riboflavin signal in simulated CXL procedures. TRANSLATIONAL RELEVANCE: The replacement of the subjective riboflavin detection by a technically straightforward, objective detection method might increase patient safety and treatment efficiency in CXL.
RESUMO
Introducción y objetivos Investigamos si la autoadministración de riboflavina por parte de los pacientes podría ser una opción viable para el cross-linking corneal (CXL), teniendo en cuenta los importantes recursos necesarios para la impregnación de la córnea. Analizamos si administrar la riboflavina en el fórnix inferior (lugar de autoadministración) resulta en concentraciones de riboflavina no menores a cuando se aplica directamente en la córnea (zona de aplicación por personal médico). Pacientes y métodos Realizamos un estudio prospectivo para evaluar las concentraciones de riboflavina en seis puntos de tiempo (basal, cinco, 15, 30, 45 y 60 minutos) en 18 voluntarios para cada uno de los dos lugares de aplicación: córnea y fórnix. Las concentraciones de riboflavina (Peschke® TE 0,25%; Peschke Trade GmbH, Huenenberg, Suiza) en la cámara anterior fueron medidas por fluorofotometría (FluorotronTM Master FM-2; OcuMetrics Inc., Mountain View, CA, EE. UU.). Resultados En los dos lugares de aplicación, córnea y fórnix, se observó una autofluorescencia de 16,7 ng/mL (desviación estándar [DE] 5,5) y 14,6 ng/mL (DE 4,6) al inicio de la serie de mediciones (p = 0,221). Después de 30 minutos, las concentraciones de fluorescencia en la cámara anterior habían aumentado a 55,1 ng/mL (DE 25,5) y a 46,1 ng/mL (DE 25,1) (p = 0,293) sin un incremento relevante adicional a los 60 minutos. Conclusiones Este estudio encontró que la aplicación de gotas de riboflavina en el fórnix inferior no fue menor a la aplicación directa en la córnea, según las mediciones fluorométricas de las concentraciones de riboflavina en la cámara anterior. Sugiere que la autoadministración es viable en términos de impregnación corneal de riboflavina (AU)
Introduction and objectives We investigated whether riboflavin self-administration by patients could be a feasible option for corneal cross-linking, given the considerable resources required to impregnate the cornea with riboflavin. We analysed whether administering riboflavin in the inferior fornix (the site of self-administration) results in non-inferior riboflavin concentrations as when applied directly on the cornea (the site of administration by medical personnel). Patients and methods We conducted a prospective study to evaluate riboflavin concentrations at six time-points (baseline, 5, 15, 30, 45 and 60min) in 18 healthy volunteers for each of two application sites: cornea and fornix. Anterior chamber riboflavin (Peschke® TE 0.25%) concentrations were measured by fluorophotometry (Fluorotron Master FM-2). Results For the two application sites cornea and fornix, participants did not differ in terms of age and sex. At baseline, the autofluorescence in the anterior chamber was 16.7ng/ml (SD 5.5) and 14.6ng/ml (SD 4.6) (p=0.221). After 30min, anterior chamber fluorescein concentrations had risen to 55.1ng/ml (SD 25.5) and 46.1ng/ml (SD 25.1) (p=0.293) without a further relevant increase by 60min. Conclusions This study found that applying riboflavin drops in the inferior fornix was non-inferior to applying it directly to the cornea, based on fluorophotometric measurements of anterior chamber riboflavin concentrations. This suggests that self-application of riboflavin is feasible in terms of corneal riboflavin impregnation (AU)