Hans Peter Iseli

Collagen crosslinking with ultraviolet-A and hypoosmolar riboflavin solution in thin corneas

&NA; Corneal collagen crosslinking (CXL) with riboflavin and ultraviolet‐A light is a method for treating progressive keratectasia. The currently accepted treatment parameters induce collagen crosslinking in the anterior 250 to 350 μm of corneal stroma. To protect the endothelium, CXL inclusion criteria require a minimum corneal thickness of 400 μm after removal of the epithelium. In advanced keratoconus, however, progressive corneal thinning often leads to a remaining stromal thickness of less than 400 μm. We have therefore modified the current treatment protocol by preoperatively swelling thin corneas to a stromal thickness of at least 400 μm using hypoosmolar riboflavin solution. This treatment protocol was performed in a case series of 20 patients, and no complications were observed. Preoperative swelling of the cornea safely broadens the spectrum of CXL indications to thin corneas that would otherwise not be eligible for treatment.

Ultraviolet A/riboflavin corneal cross-linking for infectious keratitis associated with corneal melts.

Purpose: To evaluate the efficacy of ultraviolet-corneal cross-linking (CXL) for treating infectious melting keratitis. Methods: Five patients with infectious keratitis associated with corneal melting were treated with CXL at the outpatient departments of the Institut für Refraktive und Ophthalmo-Chirurgie and the eye hospital at the University of Zurich. CXL was performed when the infection did not respond to systemic and topical antibiotic therapy. Follow-up after cross-linking ranged from 1 to 9 months. Results: In all cases, the progression of corneal melting was halted after CXL treatment. Emergency keratoplasty was not necessary in any of the 5 cases presented. Conclusions: CXL is a promising option for treating patients with therapy-refractory infectious keratitis to avoid emergency keratoplasty.

Scheimpflug imaging of corneas after collagen cross-linking.

Purpose: To compare geometrical shape factors of keratoconus corneas after cross-linking (CXL) by means of Scheimpflug imaging with those of untreated fellow eyes. Setting: Institut für Refraktive und Ophthalmo-Chirurgie, Zürich, Switzerland. Methods: Scheimpflug imaging of the anterior segments was performed with the Pentacam (Oculus, Wetzlar, Germany) in 21 patients with progressive keratectasia before and after CXL. Only 1 eye per patient was treated with corneal cross-linking using the riboflavin/UV-A approach, the fellow eye serving as control. The following corneal parameters and their postoperative evolution during 1 year after treatment have been evaluated: minimal curvature radius and its location, thickness at the thinnest point, location of the thinnest point, anterior and posterior elevation, conoid asphericity constants of the anterior and posterior surface, and 7 keratoconus indices. Statistical comparison was performed by means of the Wilcoxon test. Results: None of the treated eyes showed topographic progression in contrast to the untreated group where 8 eyes experienced significant progression. Minimal curvature radius increased significantly after 1 year compared with preoperative (6.14-6.21 mm), whereas in the untreated fellow eye, it significantly decreased (6.94-6.86 mm). Minimal corneal thickness was significantly reduced after treatment (P < 0.002 at 12 months). The cornea showed an evolution toward a more regular shape as indicated by a significant reduction in 4 of 7 keratoconus indices. No complications of CXL occurred in this small study group. Conclusions: After cross-linking, the corneal shape undergoes a process of regularization. This process is active during the first year after treatment and may continue. Longer follow-up is warranted to estimate the full amount of regression of the keratectasia after CXL.

Q-factor customized ablation profile for the correction of myopic astigmatism

PURPOSE: To compare the results of the Q‐factor customized aspheric ablation profile with the wavefront‐guided customized ablation pattern for the correction of myopic astigmatism. SETTING: Institute for Refractive and Ophthalmic Surgery, Zurich, Switzerland. METHODS: Thirty‐five patients were enrolled in a controlled study in which the nondominant eye was treated with the Q‐factor customized profile (custom‐Q study group) and the dominant eye was treated with wavefront‐guided customized ablation (control group). Preoperative and 1‐month postoperative high‐contrast visual acuity, low‐contrast visual acuity, and glare visual acuity, as well as aberrometry and asphericity of the cornea, were compared between the 2 groups. All eyes received laser in situ keratomileusis surgery, and the laser treatment was accomplished with the Wavelight Eye‐Q 400 Hz excimer laser. RESULTS: For corrections up to −9 diopters (D) of myopia, there were no statistically significant differences between the 2 groups regarding any visual or optical parameter except coma‐like aberrations (3rd Zernike order), where the wavefront‐guided group was significantly better 1 month after surgery (P = .002). For corrections up to −5 D (spherical equivalent), the Q‐factor optimized treated eyes had a significantly smaller shift toward oblate cornea: ΔQ15 = 0.25 in Q‐factor customized versus ΔQ15 = 0.38 in wavefront‐guided treatment (P = .04). CONCLUSIONS: Regarding safety and refractive efficacy, custom‐Q ablation profiles were clinically equivalent to wavefront‐guided profiles in corrections of myopia up to –9 D and astigmatism up to 2.5 D. Corneal asphericity was less impaired by the custom‐Q treatment up to −5 D of myopia.

Pregnancy-related exacerbation of iatrogenic keratectasia despite corneal collagen crosslinking.

Iatrogenic keratectasia after laser in situ keratomileusis (LASIK) represents a serious complication of refractive laser surgery. We describe a woman who developed bilateral iatrogenic keratectasia during her first pregnancy 26 months after LASIK. Corneal collagen crosslinking (CCL) with riboflavin and ultraviolet-A was performed in March 2005 (right eye) and April 2005 (left eye). This treatment stopped the progression and even caused the keratometric steepness to regress over a postoperative follow-up of 22 months, as demonstrated by preoperative and postoperative corneal topographies and maximum K-readings. During the patients second pregnancy, the keratectasia exacerbated. To our knowledge, this is the first case showing exacerbation of keratectasia despite CCL and, as the exacerbation occurred only during pregnancy, suggesting that hormonal changes might affect corneal biomechanical stability.

Why study rod cell death in retinal degenerations and how

Age-related macular degeneration (AMD) is a main causes of severe visual impairment in the elderly in industrialized countries. The pathogenesis of this complex diseases is largely unknown, even though clinical characteristics and histopathology are well described. Because several aging changes are identical to those observed in AMD, there appears to exist an unknown switch mechanism from normal ageing to disease. Recent anatomical studies using elegant innovative techniques reveal that there is a 30% rod loss in normal ageing, which is increased in early AMD. Those and other observations by Curcio and co-workers indicate that early rod loss is an important denominator of AMD (Curcio CA. Eye 2001; 15:376). As in retinitis pigmentosa (RP), rods appear to die by apoptosis. Thus it seems mandatory to study the regulation of rod cell death in animal models to unravel possible mechanisms of rod loss in AMD. Our laboratory investigates signal transduction pathways and gene regulation of rod death in our model of light-induced apoptosis. The transcription factor AP1 is essential, whereas other classical pro- and antiapoptotic genes appear to be less important in our model system. Caspase-1 gene expression is distinctly upregulated after light exposure and there are several factors which completely protect against light-induced cell death, such as the anesthetic halothane, dexamethasone and the absence of bleachable rhodopsin during light exposure. A fast rhodopsin regeneration rate increased damage susceptibility. Our data indicate that rhodopsin is essential for the initiation of light-induced rod loss. Following photon absorption, there may be the generation of photochemically active molecules wich then induce the apoptotic death cascade.

Laboratory measurement of the absorption coefficient of riboflavin for ultraviolet light (365 nm).

PURPOSE Corneal cross-linking (CXL) is an increasingly used treatment technique for stabilizing the cornea in keratoconus. Cross-linking (polymerization) between collagen fibrils is induced by riboflavin (vitamin B2) and ultraviolet light (365 nm). Although reported to reach a constant value at higher riboflavin concentrations, the Lambert-Beer law predicts a linear increase in the absorption coefficient. This work was carried out to determine absorption behavior at different riboflavin concentrations and to further investigate the purported plateau absorption coefficient value of riboflavin and to identify possible bleaching effects. METHODS The Lambert-Beer law was used to calculate the absorption coefficient at various riboflavin concentrations. The following investigated concentrations of riboflavin solutions were prepared using a mixture of 0.5% riboflavin and 20% Dextran T500 dissolved in 0.9% sodium chloride solution: 0%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.08%, 0.1%, 0.2%, 0.3%, 0.4%, and 0.5%, and were investigated with and without aperture plate implementation. An additional test series measured the transmitted power at selected riboflavin concentrations over time. RESULTS In diluted solutions, a linear correlation exists between the absorption coefficient and riboflavin concentration. The absorption coefficient reaches a plateau, but this occurs at a higher riboflavin concentration (0.1%) than previously reported (just above 0.04%). Transmitted light power increases over time, indicating a bleaching effect of riboflavin. CONCLUSIONS The riboflavin concentration can be effectively varied as a treatment parameter in a considerably broader range than previously thought.

Fra-1 substitutes for c-Fos in AP-1-mediated signal transduction in retinal apoptosis.

Lack of the AP‐1 member c‐Fos protects photoreceptors against light‐induced apoptosis, a model for retinal degeneration. In mice, light damage increases the activity of the transcription factor AP‐1, while pharmacological suppression of AP‐1 prevents apoptosis, suggesting the involvement of pro‐apoptotic AP‐1 target genes. Recently, however, it was shown that photoreceptors expressing Fra‐1 in place of c‐Fos (FosFosl1/Fosl1) are apoptosis competent despite the lack of transactivation domains in Fra‐1. Here, we show that morphological features of light‐induced apoptosis were indistinguishable in FosFosl1/Fosl1 and wild‐type mice. Furthermore, light exposure comparably increased AP‐1 activity in both genotypes. Opposite to wild‐type mice, Fra‐1, but not c‐Fos, was detectable in AP‐1 complexes of FosFosl1/Fosl1 mice. Importantly, AP‐1 responsiveness for glucocorticoid receptor‐mediated inhibition was preserved in FosFosl1/Fosl1 mice. Thus, Fra‐1 takes over for c‐Fos in pro‐ and anti‐apoptotic signal transduction. As Fra‐1 lacks transactivation domains, AP‐1 may not induce, but rather suppress genes in retinal light damage.

Clinical photoablation with a 500-Hz scanning spot excimer laser.

PURPOSE The aim of this study was to use a 500-Hz scanning spot laser (Concept500, WaveLight Laser Technologie AG, Erlangen, Germany) to investigate potential side effects that might be associated with the use of a high repetition rate laser platform. METHODS Seven eyes were treated using a 500-Hz scanning spot laser for laser in situ keratomileusis (LASIK). The local frequency of the ablation was kept below 40 Hz to avoid local heating of corneal tissue. With the exception of the high repetition rate (500 Hz), all other laser parameters such as fluence, algorithm, ablation profile, and spot diameter were identical to a standard WaveLight Allegretto laser system. Patients were examined at 1 month and 1 year after initial treatment. Preoperative and postoperative examination included manifest sphere and cylinder, uncorrected and best spectacle-corrected visual acuity (BSCVA). RESULTS All eyes were treated for myopia or myopic astigmatism. Five eyes received spherocylindrical and two eyes spherical ablation only. No adverse events correlated with the use of a high repetition rate laser system were observed during surgery or at any point during follow-up. All eyes maintained or had improved BSCVA at 12 months after treatment when compared to preoperative values. CONCLUSION The use of an excimer laser with a maximal repetition rate of 500 Hz and a local repetition rate of less than 40 Hz was free of any specific side effect that might be associated with the use of such a high repetition rate.

Continuous expression of the homeobox gene Pax6 in the ageing human retina.

PurposeIn the past few years, the essential role of the homeobox gene Pax6for eye development has been demonstrated unambiguously in a variety of species including humans. In humans, Pax6mutations lead to a variety of ocular malformations of the anterior and posterior segment. However, little is known about PAX6 expression in the adult human retina. We have therefore investigated PAX6 levels and localization in the human retina at various ages.MethodsAdult human eyes of various ages (17–79 years) were obtained from the Zurich Eye Bank. PAX6 expression levels and patterns were analysed by Western blot analysis of total retinal protein and by immunohistochemistry on paraffin sections, respectively.ResultsPAX6 expression in the retina was detected up to 79 years of donor age and was predominantly localized to the ganglion cell layer and the inner part of the inner nuclear layer.ConclusionsPAX6 remains distinctly expressed throughout the lifespan of the human retina suggesting a role for PAX6 in the retina after completion of eye morphogenesis.