Arthur Hammer - Academia.edu (original) (raw)
Papers by Arthur Hammer
BMJ open ophthalmology, May 1, 2022
Frontiers in Neurology
Purpose: We report two patients with toxic retinopathy from either ritonavir or didanosine and re... more Purpose: We report two patients with toxic retinopathy from either ritonavir or didanosine and reviewed the literature on the topics. We provide an overview of the retinal toxicity of these two antiretroviral drugs in human immunodeficiency virus-positive patients.Methods: First, we performed a retrospective study of the medical charts of two patients examined by us, one with ritonavir maculopathy and one with didanosine peripheral retinopathy. Secondly, we searched the world literature for similar cases through PubMed and Google Scholar, using the terms “HIV,” “AIDS,” “ritonavir,” “didanosine,” “maculopathy,” “retinopathy,” “visual loss,” and “toxicity” to retrieve the appropriate literature on the subject.Results: Patient 1: A 49-year-old woman complained of progressive central visual loss over the past 12 months. History disclosed ongoing ritonavir therapy for the past 11 years. Ritonavir maculopathy was diagnosed, and visual loss increased relentlessly despite cessation of treat...
Cette thèse décrit l'étude des molécules impliquées dans les photoréactions chimiques s... more Cette thèse décrit l'étude des molécules impliquées dans les photoréactions chimiques sous-jacentes au cross-linking du collagène cornéen (CXL), les limitations résultantes ainsi que l'effet du CXL dans le traitement de l'œdème de cornée. Le premier chapitre est une introduction générale à l'œil et son anatomie et décrit le principe du CXL et ses applications ainsi que son adaptation à l'ophtalmologie pour le traitement de certaine pathologie oculaires. Le deuxième chapitre se focalise sur les aspects physiques et les molécules liées au CXL, particulièrement en ce qui concerne l'effet de l'irradiance de la lumière UV, l'oxygène, les propriétés chimiques des différents composés de riboflavine tels que leur diffusion et concentration dans la cornée et leur potentiel électronégatif et d'ionisation. Le troisième chapitre décrit le développement d'un modèle murin pour l'analyse du CXL ce qui permettrait de futures recherches sur des souris génétiquement modifiées pour approfondir les connaissances actuelles quand aux molécules intrinsèques à la cornée impliquées dans les photoréactions chimiques du CXL. Le quatrième chapitre décrit le CXL comme potentiel traitement pour l'œdème de cornée, le principe sous-jacent et les limitations. Sont détaillés le prototype développé pour réaliser les expériences et dépasser ces limitations ainsi que les résultats obtenus
Investigative Ophthalmology & Visual Science, 2013
Investigative Ophthalmology & Visual Science, 2015
Investigative Ophthalmology & Visual Science, 2015
Investigative Ophthalmology & Visual Science, 2015
Investigative Ophthalmology & Visual Science, 2013
1 Corneal biomechanical properties at 1 different corneal collagen cross-linking 2 (CXL) Irradian... more 1 Corneal biomechanical properties at 1 different corneal collagen cross-linking 2 (CXL) Irradiances 3 4 Arthur Hammer , Olivier Richoz , Samuel Mosquera , David Tabibian , 5 Florence Hoogewoud 1, Farhad Hafezi 1,3 6 7 8 1 Dept. of Ophthalmology, Geneva University Hospitals, Geneva, Switzerland 9 2 Schwind eye-tech Solutions, Kleinostheim, Germany 10 3 Doheny Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, California 11 12 13 14 15 16 17 18 19 20 21 22 Disclosure: Arthur Hammer, None; Olivier Richoz, named co-inventor of PCT/CH 2012/000090 application; 23 Samuel Mosquera, None; David Tabibian, None; Florence Hoogewoud, None; Farhad Hafezi, named co24 inventor of PCT/CH 2012/000090 application 25 26 27 28 29 30 31 32 33 34 35 Corresponding author: Farhad Hafezi, MD PhD, Department of Ophthalmology, Geneva University Hospitals, Rue 36 Alcide-Jentzer 22, 1211 Geneva, Switzerland; farhad@hafezi.ch 37 38 39 IOVS Papers in Press. Published on March ...
Klinische Monatsblätter für Augenheilkunde, 2019
Translational Vision Science & Technology, 2017
Purpose: We studied changes in gene transcription after corneal crosslinking (CXL) in the rabbit ... more Purpose: We studied changes in gene transcription after corneal crosslinking (CXL) in the rabbit cornea in vivo and identified potential molecular signaling pathways. Methods: A total of 15 corneas of eight male New-Zealand-White rabbits were deepithelialized and equally divided into five groups. Group 1 served as an untreated control. Groups 2 to 5 were soaked with 0.1% riboflavin for 20 minutes, which in Groups 3 to 5 was followed by UV-A irradiation at a fluence of 5.4 J/cm 2. Ultraviolet A (UVA) irradiation was delivered at 3 mW/cm 2 for 30 minutes (Group 3, standard CXL protocol), 9 mW/cm 2 for 10 minutes (Group 4, accelerated), and 18 mW/cm 2 for 5 minutes (Group 5, accelerated). At 1 week after treatment, corneal buttons were obtained; mRNA was extracted and subjected to cDNA sequencing (RNA-seq). Results: A total of 297 differentially transcribed genes were identified after CXL treatment. CXL downregulated extracellular matrix components (collagen types 1A1, 1A2, 6A2, 11A1, keratocan, fibromodulin) and upregulated glycan biosynthesis and proteoglycan glycosylation (GALNT 3, 7, and 8, B3GALT2). Also, CXL activated pathways related to protein crosslinking (transglutaminase 2 and 6). In 9.1% of the significantly different genes, CXL at 3 mW/cm 2 (Group 1) induced a more distinct change in gene transcription than the accelerated CXL protocols, which induced a lower biomechanical stiffening effect. Conclusions: Several target genes have been identified that might be related to the biomechanical stability and shape of the cornea. Stiffening-dependent differential gene transcription suggests the activation of mechano-sensitive pathways. Translational Relevance: A better understanding of the molecular mechanisms behind CXL will permit an optimization and individualization of the clinical treatment protocol.
Journal of Refractive Surgery, 2017
PURPOSE: To study whether repeated collagen cross-linking (CXL) performed in vivo in mice shows a... more PURPOSE: To study whether repeated collagen cross-linking (CXL) performed in vivo in mice shows an additive effect on mechanical corneal stiffness. METHODS: In this experimental study, epithelium-off CXL was performed in a total of 18 eyes from male C57BL/6 mice, with 0.27%-riboflavin solution applied for 20 minutes, followed by ultraviolet-A (UVA) irradiation (365 nm, 9mW/cm 2 ) for 2:50 minutes (fluence 1.53 J/cm 2 ). CXL was performed as either a single (1×CXL) or a repeated (2×CXL) treatment. Un-irradiated corneas served as controls. In the 2×CXL group, the procedure was performed on day 1 and day 4 to ensure complete reepithelialization between sessions. Biomechanical analysis was performed on day 7. Corneas were harvested with a small scleral ring and mounted on a customized two-dimensional flap holder. The biomechanical measurement consisted of three parts: (1) pre-conditioned during three cycles from 0.04 to 0.4 N, (2) stress relaxation during 120 seconds following 0.4 N for...
Translational Vision Science & Technology, 2017
Purpose: To morphologically, biochemically, and physiologically characterize corneal cross-linkin... more Purpose: To morphologically, biochemically, and physiologically characterize corneal cross-linking with riboflavin and UV-A light (CXL) in a newly established in vivo murine model. Methods: C57BL/6 wild-type mice (N ¼ 67) were treated with various CXL protocols, with modification of the following parameters: total energy (fluence) used, duration of UV-A irradiation, continuous versus pulsed irradiation, and CXL under hypoxic conditions (contact lens). Corneas were evaluated biomicroscopically, histologically, and using optical coherence tomography. Conformational collagen changes were evaluated via changes in the speed of enzymatic digestion. Results: A fluence of 5.4 J/cm 2 induced scar formation, while fluences of , 0.18 J/cm 2 induced neovascularization. Fluences between 1.62 and 2.7 J/cm 2 reduced epithelial thickness, but maintained a transparent cornea after 1 month. Pulsed UV irradiation inhibited neovascularization, but favored scar formation. Changes in the speed of enzymatic digestion suggest that CXL in mice, when compared to humans, requires less UV-A energy than the difference in corneal thickness between the species would suggest. Conclusions: We demonstrated the in vivo response of very strong and very weak CXL and identified the best suited range of UV fluence in murine corneas. The presented murine CXL model may be helpful in future research addressing cellular and molecular pathways associated to CXL treatment. Translational Relevance: Adverse tissue reactions following CXL treatment were observed, if the administered UV energy was out of the treatment window-raising concern about novel CXL treatment protocols that have not been previously validated in an experimental setting.
Current eye research, Jan 14, 2016
To investigate the composition and concentration of individual riboflavin compounds in the cornea... more To investigate the composition and concentration of individual riboflavin compounds in the corneal stroma in vivo after soaking with various commercially available riboflavin formulations. Experiments were performed in 26 rabbit corneas in vivo: 24 corneas were soaked with riboflavin formulations for 30 minutes or with 0.9% NaCl for control (n = 2). After treatment, corneas were excised and prepared for ultra-high-pressure liquid chromatography (UHPLC) analysis. Additionally, computational chemical analysis of riboflavin compounds and keratan sulfate were performed. The amount of riboflavin and riboflavin phosphate isomers in cornea decreased by a factor of 10 to 100, when compared to the amount in riboflavin formulations. In particular, we found an inverse relationship in the ratio of riboflavin to riboflavin phosphate isomer concentration between formulations and cornea. The electronegativity and ionization potential of riboflavin and phosphate isomers are different. The inverse r...
Journal of refractive surgery (Thorofare, N.J. : 1995), 2015
To compare the currently available ultraviolet-A (UV-A) corneal cross-linking (CXL) treatment pro... more To compare the currently available ultraviolet-A (UV-A) corneal cross-linking (CXL) treatment protocols for thin corneas with respect to oxygen, UV fluence, and osmotic pressure. Freshly enucleated murine (n = 16) and porcine (n = 16) eyes were used. The dependency on oxygen and the amount of UV absorption were evaluated using different CXL protocols, including standard CXL, contact lens-assisted CXL (caCXL), and CXL after corneal swelling. The CXL protocol was adapted from the treatment parameters of the human cornea to fit the thickness of murine and porcine corneas. Immediately after CXL, the corneas were subjected to biomechanical testing, including preconditioning, stress relaxation at 0.6 MPa, and stress-strain extensiometry. A two-element Prony series was fitted to the relaxation curves for viscoelastic characterization. Standard CXL was most efficient; prior corneal swelling reduced the long-term modulus by 6% and caCXL by 15% to 20%. Oxygen reduction decreased the long-term...
Investigative Opthalmology & Visual Science, 2015
PURPOSE. To establish corneal cross-linking (CXL) with riboflavin and UV-A in in the mouse cornea... more PURPOSE. To establish corneal cross-linking (CXL) with riboflavin and UV-A in in the mouse cornea in vivo and to develop tools to measure the biomechanical changes observed. METHODS. A total of 55 male C57BL/6 wild-type mice (aged 5 weeks) were divided into 14 groups. Standard CXL parameters were adapted to the anatomy of the mouse cornea, and riboflavin concentration (0.1%-0.5%) and fluence series (0.09-5.4 J/cm 2) were performed on the assumption of the endothelial damage thresholds. Untreated and riboflavin only corneas were used as controls. Animals were killed at 30 minutes and at 1 month after CXL. Corneas were harvested. Two-dimensional (2D) biomechanical testing was performed using a customized corneal holder in a commercially available stress-strain extensometer/indenter. Both elastic and viscoelastic analyses were performed. Statistical inference was performed using t-tests and specific mathematical models fitted to the experimental stress-strain and stressrelaxation data. Adjusted P values by the method of Benjamini and Hochberg are reported. RESULTS. For all CXL treatment groups, stress-relaxation showed significant differences (P < 0.0001) after 120 seconds of constant strain application, with cross-linked corneas maintaining a higher stress (441 6 40 kPa) when compared with controls (337 6 39 kPa). Stress-strain analysis confirmed these findings but was less sensitive to CXL-induced changes: at 0.5% of strain, cross-linked corneas remained at higher stress (778 6 111 kPa) when compared with controls (659 6 121 kPa). CONCLUSIONS. Cross-linking was induced in the mouse cornea in vivo, and its biomechanical effect successfully measured. This could create opportunities to study molecular pathways of CXL in transgenic mice.
Revue médicale suisse, Jan 4, 2014
Keratoconus is a disease of the cornea that usually begins during puberty and progressively weake... more Keratoconus is a disease of the cornea that usually begins during puberty and progressively weakens its biomechanical structure. Keratoconic eyes show a conic shape and progressive thinning, both leading to irregular astigmatism and reduced vision that cannot be corrected by glasses. In early cases, special contact lens can partly compensate for the visual loss while they do not stop disease progression. Until recently, the only treatment option was a corneal transplant. In 1999, a technique called corneal collagen cross-linking (CXL) was used in human corneas suffering from keratoconus for the first time. CXL uses a process called photopolymerization to halt the progression of keratoconus with an efficacy of more than 95%. Today our challenge is to screen and identify patients early enough to offer a treatment on time before irreversible vision loss develops.
Investigative ophthalmology & visual science, Jan 22, 2014
When treating peripheral ectatic disease-like pellucid marginal degeneration (PMD), corneal cross... more When treating peripheral ectatic disease-like pellucid marginal degeneration (PMD), corneal cross-linking with UV-A and riboflavin (CXL) must be applied eccentrically to the periphery of the lower cornea, partly irradiating the corneal limbus. Here, we investigated the effect of standard and double-standard fluence corneal cross-linking with riboflavin and UV-A (CXL) on cornea and corneal limbus in the rabbit eye in vivo. Epithelium-off CXL was performed in male New Zealand White rabbits with two irradiation diameters (7 mm central cornea, 13 mm cornea and limbus), using standard fluence (5.4 J/cm(2)) and double-standard fluence (10.8 J/cm(2)) settings. Controls were subjected to epithelial removal and riboflavin instillation, but were not irradiated with UV-A. Following CXL, animals were examined daily until complete closure of the epithelium, and at 7, 14, 21, and 28 days. Animals were killed and a corneoscleral button was excised and processed for light microscopy and immunohisto...
BMJ open ophthalmology, May 1, 2022
Frontiers in Neurology
Purpose: We report two patients with toxic retinopathy from either ritonavir or didanosine and re... more Purpose: We report two patients with toxic retinopathy from either ritonavir or didanosine and reviewed the literature on the topics. We provide an overview of the retinal toxicity of these two antiretroviral drugs in human immunodeficiency virus-positive patients.Methods: First, we performed a retrospective study of the medical charts of two patients examined by us, one with ritonavir maculopathy and one with didanosine peripheral retinopathy. Secondly, we searched the world literature for similar cases through PubMed and Google Scholar, using the terms “HIV,” “AIDS,” “ritonavir,” “didanosine,” “maculopathy,” “retinopathy,” “visual loss,” and “toxicity” to retrieve the appropriate literature on the subject.Results: Patient 1: A 49-year-old woman complained of progressive central visual loss over the past 12 months. History disclosed ongoing ritonavir therapy for the past 11 years. Ritonavir maculopathy was diagnosed, and visual loss increased relentlessly despite cessation of treat...
Cette thèse décrit l'étude des molécules impliquées dans les photoréactions chimiques s... more Cette thèse décrit l'étude des molécules impliquées dans les photoréactions chimiques sous-jacentes au cross-linking du collagène cornéen (CXL), les limitations résultantes ainsi que l'effet du CXL dans le traitement de l'œdème de cornée. Le premier chapitre est une introduction générale à l'œil et son anatomie et décrit le principe du CXL et ses applications ainsi que son adaptation à l'ophtalmologie pour le traitement de certaine pathologie oculaires. Le deuxième chapitre se focalise sur les aspects physiques et les molécules liées au CXL, particulièrement en ce qui concerne l'effet de l'irradiance de la lumière UV, l'oxygène, les propriétés chimiques des différents composés de riboflavine tels que leur diffusion et concentration dans la cornée et leur potentiel électronégatif et d'ionisation. Le troisième chapitre décrit le développement d'un modèle murin pour l'analyse du CXL ce qui permettrait de futures recherches sur des souris génétiquement modifiées pour approfondir les connaissances actuelles quand aux molécules intrinsèques à la cornée impliquées dans les photoréactions chimiques du CXL. Le quatrième chapitre décrit le CXL comme potentiel traitement pour l'œdème de cornée, le principe sous-jacent et les limitations. Sont détaillés le prototype développé pour réaliser les expériences et dépasser ces limitations ainsi que les résultats obtenus
Investigative Ophthalmology & Visual Science, 2013
Investigative Ophthalmology & Visual Science, 2015
Investigative Ophthalmology & Visual Science, 2015
Investigative Ophthalmology & Visual Science, 2015
Investigative Ophthalmology & Visual Science, 2013
1 Corneal biomechanical properties at 1 different corneal collagen cross-linking 2 (CXL) Irradian... more 1 Corneal biomechanical properties at 1 different corneal collagen cross-linking 2 (CXL) Irradiances 3 4 Arthur Hammer , Olivier Richoz , Samuel Mosquera , David Tabibian , 5 Florence Hoogewoud 1, Farhad Hafezi 1,3 6 7 8 1 Dept. of Ophthalmology, Geneva University Hospitals, Geneva, Switzerland 9 2 Schwind eye-tech Solutions, Kleinostheim, Germany 10 3 Doheny Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, California 11 12 13 14 15 16 17 18 19 20 21 22 Disclosure: Arthur Hammer, None; Olivier Richoz, named co-inventor of PCT/CH 2012/000090 application; 23 Samuel Mosquera, None; David Tabibian, None; Florence Hoogewoud, None; Farhad Hafezi, named co24 inventor of PCT/CH 2012/000090 application 25 26 27 28 29 30 31 32 33 34 35 Corresponding author: Farhad Hafezi, MD PhD, Department of Ophthalmology, Geneva University Hospitals, Rue 36 Alcide-Jentzer 22, 1211 Geneva, Switzerland; farhad@hafezi.ch 37 38 39 IOVS Papers in Press. Published on March ...
Klinische Monatsblätter für Augenheilkunde, 2019
Translational Vision Science & Technology, 2017
Purpose: We studied changes in gene transcription after corneal crosslinking (CXL) in the rabbit ... more Purpose: We studied changes in gene transcription after corneal crosslinking (CXL) in the rabbit cornea in vivo and identified potential molecular signaling pathways. Methods: A total of 15 corneas of eight male New-Zealand-White rabbits were deepithelialized and equally divided into five groups. Group 1 served as an untreated control. Groups 2 to 5 were soaked with 0.1% riboflavin for 20 minutes, which in Groups 3 to 5 was followed by UV-A irradiation at a fluence of 5.4 J/cm 2. Ultraviolet A (UVA) irradiation was delivered at 3 mW/cm 2 for 30 minutes (Group 3, standard CXL protocol), 9 mW/cm 2 for 10 minutes (Group 4, accelerated), and 18 mW/cm 2 for 5 minutes (Group 5, accelerated). At 1 week after treatment, corneal buttons were obtained; mRNA was extracted and subjected to cDNA sequencing (RNA-seq). Results: A total of 297 differentially transcribed genes were identified after CXL treatment. CXL downregulated extracellular matrix components (collagen types 1A1, 1A2, 6A2, 11A1, keratocan, fibromodulin) and upregulated glycan biosynthesis and proteoglycan glycosylation (GALNT 3, 7, and 8, B3GALT2). Also, CXL activated pathways related to protein crosslinking (transglutaminase 2 and 6). In 9.1% of the significantly different genes, CXL at 3 mW/cm 2 (Group 1) induced a more distinct change in gene transcription than the accelerated CXL protocols, which induced a lower biomechanical stiffening effect. Conclusions: Several target genes have been identified that might be related to the biomechanical stability and shape of the cornea. Stiffening-dependent differential gene transcription suggests the activation of mechano-sensitive pathways. Translational Relevance: A better understanding of the molecular mechanisms behind CXL will permit an optimization and individualization of the clinical treatment protocol.
Journal of Refractive Surgery, 2017
PURPOSE: To study whether repeated collagen cross-linking (CXL) performed in vivo in mice shows a... more PURPOSE: To study whether repeated collagen cross-linking (CXL) performed in vivo in mice shows an additive effect on mechanical corneal stiffness. METHODS: In this experimental study, epithelium-off CXL was performed in a total of 18 eyes from male C57BL/6 mice, with 0.27%-riboflavin solution applied for 20 minutes, followed by ultraviolet-A (UVA) irradiation (365 nm, 9mW/cm 2 ) for 2:50 minutes (fluence 1.53 J/cm 2 ). CXL was performed as either a single (1×CXL) or a repeated (2×CXL) treatment. Un-irradiated corneas served as controls. In the 2×CXL group, the procedure was performed on day 1 and day 4 to ensure complete reepithelialization between sessions. Biomechanical analysis was performed on day 7. Corneas were harvested with a small scleral ring and mounted on a customized two-dimensional flap holder. The biomechanical measurement consisted of three parts: (1) pre-conditioned during three cycles from 0.04 to 0.4 N, (2) stress relaxation during 120 seconds following 0.4 N for...
Translational Vision Science & Technology, 2017
Purpose: To morphologically, biochemically, and physiologically characterize corneal cross-linkin... more Purpose: To morphologically, biochemically, and physiologically characterize corneal cross-linking with riboflavin and UV-A light (CXL) in a newly established in vivo murine model. Methods: C57BL/6 wild-type mice (N ¼ 67) were treated with various CXL protocols, with modification of the following parameters: total energy (fluence) used, duration of UV-A irradiation, continuous versus pulsed irradiation, and CXL under hypoxic conditions (contact lens). Corneas were evaluated biomicroscopically, histologically, and using optical coherence tomography. Conformational collagen changes were evaluated via changes in the speed of enzymatic digestion. Results: A fluence of 5.4 J/cm 2 induced scar formation, while fluences of , 0.18 J/cm 2 induced neovascularization. Fluences between 1.62 and 2.7 J/cm 2 reduced epithelial thickness, but maintained a transparent cornea after 1 month. Pulsed UV irradiation inhibited neovascularization, but favored scar formation. Changes in the speed of enzymatic digestion suggest that CXL in mice, when compared to humans, requires less UV-A energy than the difference in corneal thickness between the species would suggest. Conclusions: We demonstrated the in vivo response of very strong and very weak CXL and identified the best suited range of UV fluence in murine corneas. The presented murine CXL model may be helpful in future research addressing cellular and molecular pathways associated to CXL treatment. Translational Relevance: Adverse tissue reactions following CXL treatment were observed, if the administered UV energy was out of the treatment window-raising concern about novel CXL treatment protocols that have not been previously validated in an experimental setting.
Current eye research, Jan 14, 2016
To investigate the composition and concentration of individual riboflavin compounds in the cornea... more To investigate the composition and concentration of individual riboflavin compounds in the corneal stroma in vivo after soaking with various commercially available riboflavin formulations. Experiments were performed in 26 rabbit corneas in vivo: 24 corneas were soaked with riboflavin formulations for 30 minutes or with 0.9% NaCl for control (n = 2). After treatment, corneas were excised and prepared for ultra-high-pressure liquid chromatography (UHPLC) analysis. Additionally, computational chemical analysis of riboflavin compounds and keratan sulfate were performed. The amount of riboflavin and riboflavin phosphate isomers in cornea decreased by a factor of 10 to 100, when compared to the amount in riboflavin formulations. In particular, we found an inverse relationship in the ratio of riboflavin to riboflavin phosphate isomer concentration between formulations and cornea. The electronegativity and ionization potential of riboflavin and phosphate isomers are different. The inverse r...
Journal of refractive surgery (Thorofare, N.J. : 1995), 2015
To compare the currently available ultraviolet-A (UV-A) corneal cross-linking (CXL) treatment pro... more To compare the currently available ultraviolet-A (UV-A) corneal cross-linking (CXL) treatment protocols for thin corneas with respect to oxygen, UV fluence, and osmotic pressure. Freshly enucleated murine (n = 16) and porcine (n = 16) eyes were used. The dependency on oxygen and the amount of UV absorption were evaluated using different CXL protocols, including standard CXL, contact lens-assisted CXL (caCXL), and CXL after corneal swelling. The CXL protocol was adapted from the treatment parameters of the human cornea to fit the thickness of murine and porcine corneas. Immediately after CXL, the corneas were subjected to biomechanical testing, including preconditioning, stress relaxation at 0.6 MPa, and stress-strain extensiometry. A two-element Prony series was fitted to the relaxation curves for viscoelastic characterization. Standard CXL was most efficient; prior corneal swelling reduced the long-term modulus by 6% and caCXL by 15% to 20%. Oxygen reduction decreased the long-term...
Investigative Opthalmology & Visual Science, 2015
PURPOSE. To establish corneal cross-linking (CXL) with riboflavin and UV-A in in the mouse cornea... more PURPOSE. To establish corneal cross-linking (CXL) with riboflavin and UV-A in in the mouse cornea in vivo and to develop tools to measure the biomechanical changes observed. METHODS. A total of 55 male C57BL/6 wild-type mice (aged 5 weeks) were divided into 14 groups. Standard CXL parameters were adapted to the anatomy of the mouse cornea, and riboflavin concentration (0.1%-0.5%) and fluence series (0.09-5.4 J/cm 2) were performed on the assumption of the endothelial damage thresholds. Untreated and riboflavin only corneas were used as controls. Animals were killed at 30 minutes and at 1 month after CXL. Corneas were harvested. Two-dimensional (2D) biomechanical testing was performed using a customized corneal holder in a commercially available stress-strain extensometer/indenter. Both elastic and viscoelastic analyses were performed. Statistical inference was performed using t-tests and specific mathematical models fitted to the experimental stress-strain and stressrelaxation data. Adjusted P values by the method of Benjamini and Hochberg are reported. RESULTS. For all CXL treatment groups, stress-relaxation showed significant differences (P < 0.0001) after 120 seconds of constant strain application, with cross-linked corneas maintaining a higher stress (441 6 40 kPa) when compared with controls (337 6 39 kPa). Stress-strain analysis confirmed these findings but was less sensitive to CXL-induced changes: at 0.5% of strain, cross-linked corneas remained at higher stress (778 6 111 kPa) when compared with controls (659 6 121 kPa). CONCLUSIONS. Cross-linking was induced in the mouse cornea in vivo, and its biomechanical effect successfully measured. This could create opportunities to study molecular pathways of CXL in transgenic mice.
Revue médicale suisse, Jan 4, 2014
Keratoconus is a disease of the cornea that usually begins during puberty and progressively weake... more Keratoconus is a disease of the cornea that usually begins during puberty and progressively weakens its biomechanical structure. Keratoconic eyes show a conic shape and progressive thinning, both leading to irregular astigmatism and reduced vision that cannot be corrected by glasses. In early cases, special contact lens can partly compensate for the visual loss while they do not stop disease progression. Until recently, the only treatment option was a corneal transplant. In 1999, a technique called corneal collagen cross-linking (CXL) was used in human corneas suffering from keratoconus for the first time. CXL uses a process called photopolymerization to halt the progression of keratoconus with an efficacy of more than 95%. Today our challenge is to screen and identify patients early enough to offer a treatment on time before irreversible vision loss develops.
Investigative ophthalmology & visual science, Jan 22, 2014
When treating peripheral ectatic disease-like pellucid marginal degeneration (PMD), corneal cross... more When treating peripheral ectatic disease-like pellucid marginal degeneration (PMD), corneal cross-linking with UV-A and riboflavin (CXL) must be applied eccentrically to the periphery of the lower cornea, partly irradiating the corneal limbus. Here, we investigated the effect of standard and double-standard fluence corneal cross-linking with riboflavin and UV-A (CXL) on cornea and corneal limbus in the rabbit eye in vivo. Epithelium-off CXL was performed in male New Zealand White rabbits with two irradiation diameters (7 mm central cornea, 13 mm cornea and limbus), using standard fluence (5.4 J/cm(2)) and double-standard fluence (10.8 J/cm(2)) settings. Controls were subjected to epithelial removal and riboflavin instillation, but were not irradiated with UV-A. Following CXL, animals were examined daily until complete closure of the epithelium, and at 7, 14, 21, and 28 days. Animals were killed and a corneoscleral button was excised and processed for light microscopy and immunohisto...