Faculty Bibliography

BACKGROUND:Since the late 1990s corneal crosslinking (CXL) has been proposed as a new treatment option which can stop progression of keratoconus with promising results in adults. OBJECTIVE:Keratoconus presents a higher rate and faster progression in paediatric patients and for this reason prompt and effective treatment is essential. Due to its success in adult keratoconus patients, CXL has been recently applied to children in order to stop or slow progression of keratoconus in paediatric patients. CONCLUSIONS:This article will present an update of the literature on the topic of CXL in this age group.

PURPOSE:The Argus II Retinal Prosthesis System (Second Sight Medical Products, Inc, Sylmar, CA) was developed to restore some vision to patients blind as a result of retinitis pigmentosa (RP) or outer retinal degeneration. A clinical trial was initiated in 2006 to study the long-term safety and efficacy of the Argus II System in patients with bare or no light perception resulting from end-stage RP. DESIGN:Prospective, multicenter, single-arm clinical trial. Within-patient controls included the nonimplanted fellow eye and patients' native residual vision compared with their vision with the Argus II. PARTICIPANTS:Thirty participants in 10 centers in the United States and Europe. METHODS:The worse-seeing eye of blind patients was implanted with the Argus II. Patients wore glasses mounted with a small camera and a video processor that converted images into stimulation patterns sent to the electrode array on the retina. MAIN OUTCOME MEASURES:The primary outcome measures were safety (the number, seriousness, and relatedness of adverse events) and visual function, as measured by 3 computer-based, objective tests. Secondary measures included functional vision performance on objectively scored real-world tasks. RESULTS:Twenty-four of 30 patients remained implanted with functioning Argus II Systems at 5 years after implantation. Only 1 additional serious adverse event was experienced after the 3-year time point. Patients performed significantly better with the Argus II on than off on all visual function tests and functional vision tasks. CONCLUSIONS:The 5-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind as a result of RP. The Argus II is the first and only retinal implant to have market approval in the European Economic Area, the United States, and Canada.

PURPOSE:To investigate the composition and concentration of individual riboflavin compounds in the corneal stroma in vivo after soaking with various commercially available riboflavin formulations. METHODS: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. RESULTS: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. CONCLUSIONS:The inverse relationship observed might be explained by a stronger electronegativity of the phosphate isomers, leading to a stronger repulsion by corneal proteoglycans. Indicating the individual concentration of riboflavin compounds in formulations is more representative than the total riboflavin concentration. Riboflavin formulations and CXL protocols might be improved considering the differences in diffusion and ionization potentials of the different riboflavin compounds.

OBJECTIVE:CXL penetration depth is an important variable influencing clinical treatment effect and safety. The purposes of this study were to determine the penetration depth of CXL in rabbit and equine corneas in epithelium-on and epithelium-off procedures and to assess an ex vivo fluorescent biomarker staining assay for objective assessment of CXL penetration depth. PROCEDURES/METHODS:CXL treatment was performed according to a standardized protocol on 21 and 17 rabbit eyes and on 12 and 10 equine eyes with and without debridement, respectively. Control corneas were treated similarly, but not exposed to CXL. Hemicorneas were stained with either phalloidin and DAPI to visualize intracellular F-actin and nuclei, or with hematoxylin and eosin. Loss of actin staining was measured and compared between groups. RESULTS:Epithelium-off CXL caused a median actin cytoskeleton loss with a demarcation at 274 μm in rabbits and 173 μm in horses. In non-CXL-treated controls, we observed a median actin cytoskeleton loss with a demarcation at 134 μm in rabbits and 149 μm in horses. No effect was detected in the epithelium-on procedure. CONCLUSIONS:CXL penetration depth, as determined by a novel ex vivo fluorescent assay, shows clear differences between species. A distinct effect was observed following epithelium-off CXL treatment in the anterior stroma of rabbits, but no different effect was observed in horses in comparison with nontreated controls. Different protocols need to be established to effectively treat equine patients with infectious corneal disease.

PURPOSE/OBJECTIVE:To assess the efficacy of a modified high concentration riboflavin solution containing benzalkonium chloride 0.01% for transepithelial corneal cross-linking (CXL). METHODS:In this prospective, interventional multicenter cohort study, 26 eyes of 26 patients with documented progressive keratoconus who underwent transepithelial CXL were included. Follow-up at 6 and 12 months postoperatively included slit-lamp examination, uncorrected and corrected distance visual acuity (logMAR), maximum keratometry (Kmax), and corneal pachymetry (corneal thinnest point) as determined by Scheimpflug imaging. Statistical analysis was performed using repeated measures analysis of variance and the Friedman test for parametric and non-parametric data, respectively. P values less than .05 were considered significant. RESULTS:Kmax did not change significantly at postoperative months 6 and 12. Changes in corneal thinnest point did not change postoperatively over 12 months. Uncorrected and corrected distance visual acuity did not change postoperatively. Progression (defined by an increase in Kmax greater than 1.00 diopter occurred in 46% of eyes at 12 months. Corneal epithelial defects were observed in 46% of the patients and marked punctate corneal epitheliopathy/loose epithelium in 23% of the patients in the immediate postoperative period. No corneal infection, sterile infiltrates, or haze were observed. CONCLUSIONS:Transepithelial CXL with an enhanced riboflavin solution did not effectively halt progression of keratoconus. Significant epithelium damage was evident in the immediate postoperative period. [J Refract Surg. 2016;32(6):372-377.].

PURPOSE/OBJECTIVE:To compare the stromal demarcation line depth in pulsed versus continuous corneal cross-linking (CXL) for keratoconus. METHODS:Seventy eyes underwent epithelium-off cross-linking, with 0.1% riboflavin applied during 10 minutes prior to ultraviolet irradiation at 30 mW/cm2. Thirty-six eyes received pulsed irradiation (1 second on, 1 second off) for 8 minutes and 34 eyes underwent continuous irradiation for 4 minutes. Total fluence was 7.2 J/cm2 for both groups. Patients were evaluated at 3 months after the procedure. RESULTS:A significantly deeper stromal demarcation line was observed in the pulsed group compared to the continuous group (201.11 ± 27.76 vs. 159.88 ± 20.86 µm; P < .001). CONCLUSIONS:The pulsed corneal cross-linking protocol induced a significantly deeper stromal demarcation line when compared to the 4 minutes of highly accelerated continuous CXL protocol. Neither CXL protocol induced a shallower demarcation line comparable to less accelerated CXL protocols previously reported.