We aimed to determine the ultrastructural changes of collagen fibrils and cells in the rabbit sclera after scleral crosslinking using riboflavin and blue light of different intensities. Scleral crosslinking is known to increase scleral stiffness and may inhibit the axial elongation of progressive myopic eyes.

Several scleral cross-linking (SXL) methods were suggested to increase the biomechanical stiffness of scleral tissue and therefore, to inhibit axial eye elongation in progressive myopia. In addition to scleral cross-linking and biomechanical effects caused by riboflavin and light irradiation such a treatment might induce tissue damage, dependent on the light intensity used. Therefore, we characterized the damage threshold and mechanical stiffening effect in rabbit eyes after application of riboflavin combined with various blue light intensities. Adult pigmented and albino rabbits were treated with riboflavin (0.5 %) and varying blue light (450 ± 50 nm) dosages from 18 to 780 J/cm(2) (15 to 650 mW/cm(2) for 20 min). Scleral, choroidal and retinal tissue alterations were detected by means of light microscopy, electron microscopy and immunohistochemistry. Biomechanical changes were measured by shear rheology. Blue light dosages of 480 J/cm(2) (400 mW/cm(2)) and beyond induced pathological changes in ocular tissues; the damage threshold was defined by the light intensities which induced cellular degeneration and/or massive collagen structure changes. At such high dosages, we observed alterations of the collagen structure in scleral tissue, as well as pigment aggregation, internal hemorrhages, and collapsed blood vessels. Additionally, photoreceptor degenerations associated with microglia activation and macroglia cell reactivity in the retina were detected. These pathological alterations were locally restricted to the treated areas. Pigmentation of rabbit eyes did not change the damage threshold after a treatment with riboflavin and blue light but seems to influence the vulnerability for blue light irradiations. Increased biomechanical stiffness of scleral tissue could be achieved with blue light intensities below the characterized damage threshold. We conclude that riboflavin and blue light application increased the biomechanical stiffness of scleral tissue at blue light energy levels below the damage threshold. Therefore, applied blue light intensities below the characterized damage threshold might define a therapeutic blue light tolerance range.

PURPOSE:To determine the visco-elastic properties of isolated rabbit scleral tissue and dose-dependent biomechanical and morphological changes after collagen cross-linking by riboflavin/blue light treatment.MATERIAL:Scleral patches from 87 adult albino rabbit eyes were examined by dynamic shear rheology. Scleral patches were treated by riboflavin and different intensities of blue light (450 nm), and the impact on the visco-elastic properties was determined by various rheological test regimes. The relative elastic modulus was calculated from non-treated and corresponding treated scleral patches, and treatments with different blue light intensities were compared.RESULTS:Shear rheology enables us to study the material properties of scleral tissue within physiological relevant parameters. Cross-linking treatment increased the viscous as well as the elastic modulus and changed the ratio of the elastic versus viscous proportion in scleral tissue. Constant riboflavin application combined with different blue light intensities from 12 mW/cm(2) up to 100 mW/cm(2) increased the relative elastic modulus of scleral tissue by factors up to 1.8. Further enhancement of the applied light intensity caused a decline of the relative elastic modulus. This might be due to destructive changes of the collagen bundle structure at larger light intensities, as observed by histological examination.CONCLUSION:Collagen cross-linking by riboflavin/blue light application increases the biomechanical stiffness of the sclera in a dose-dependent manner up to certain light intensities. Therefore, this treatment might be a suitable therapeutic approach to stabilize the biomechanical properties of scleral tissue in cases of pathological eye expansion.

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.

In modern cataract surgery, the precision by which the target refraction is achieved still remains unsatisfactory in many cases. Potential reasons include interindividual differences in wound healing, a postoperative shift of the anatomical position of the lens or previous refractive laser surgery. A system that allows for postoperative adjustment of target refraction would be highly beneficial. The light-adjustable lens (LAL, Calhoun Vision, Inc., Pasadena, CA) potentially represents such a system where refractive power is adjusted postoperatively using photosensitive silicone molecules and irradiation with ultraviolet (UV) light.1Sandstedt C.A. Chang S.H. Grubbs R.H. Schwartz D.M. Light-adjustable lens: customizing correction for multifocality and higher-order aberrations.Trans Am Ophthalmol Soc. 2006; 104: 29-39PubMed Google Scholar, 2Schwartz D.M. Light-adjustable lens.Trans Am Ophthalmol Soc. 2003; 101: 417-436PubMed Google Scholar, 3Schwartz D.M. Sandstedt C.A. Chang S.H. et al.Light-adjustable lens: development of in vitro nomograms.Trans Am Ophthalmol Soc. 2004; 102 (discussion 72–4): 67-72PubMed Google Scholar Based on the principle of photochemistry and diffusion and using a well-defined spatial and temporal UV irradiance profile, the LAL is modified to add or subtract spherical power. Ultraviolet radiation is applied at clearly defined postoperative times. Between these time points and during the first 2 postoperative weeks, it is mandatory for the patient to protect the eye from any unscheduled UV exposure by using UV protection glasses.4Chayet A. Sandstedt C. Chang S. et al.Correction of myopia after cataract surgery with a light-adjustable lens.Ophthalmology. 2009; 116: 1432-1435Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar, 5Chayet A. Sandstedt C.A. Chang S.H. et al.Correction of residual hyperopia after cataract surgery using the light adjustable intraocular lens technology.Am J Ophthalmol. 2009; 147: 392-397.e1Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar The proof of principle of the method was given recently in 2 pilot studies for the correction of myopia and hyperopia.4Chayet A. Sandstedt C. Chang S. et al.Correction of myopia after cataract surgery with a light-adjustable lens.Ophthalmology. 2009; 116: 1432-1435Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar, 5Chayet A. Sandstedt C.A. Chang S.H. et al.Correction of residual hyperopia after cataract surgery using the light adjustable intraocular lens technology.Am J Ophthalmol. 2009; 147: 392-397.e1Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar We here report on the implantation of a +10.0 diopter (D) LAL in the left eye of a 57-year-old female patient with bilateral cataract that we performed in April 2009. Preoperatively, manifest refraction was −9.75 −1.25 × 175 and best spectacle-corrected visual acuity (BSCVA) was 20/25. Bilateral slit lamp examination and examination of the central and peripheral retina showed no pathological findings except for the cataract. Surgery was uneventful and the postoperative examinations at 1 day and 1 week after surgery showed regular findings. At day 14 after surgery, the point in time when the first UV irradiation is performed following the manufacturer's protocol, the patient reported decreased vision and halos in the operated eye. Refraction was −1.25 −0.5 × 115 and BSCVA was 20/40. We performed the UV irradiation as planned. One week later, refraction was sphere (sph) −3.25 and BSCVA had decreased to 20/125. We noted a distinct paracentral elevation in the lens in slit lamp examination (Fig 1 A-B, available at http://aaojournal.org). Upon questioning, the patient admitted that she had not used the UV protecting glasses at several occasions during the postoperative period and had exposed herself to sunlight for several hours. We explanted the LAL and implanted a conventional intraocular lens (+10.0 D Acrysof Natural, Alcon Laboratories Inc, Fort Worth, TX) (Fig 1 C-D, available at http://aaojournal.org). At 1 week after the lens exchange, refraction was sph −0.5 and BSCVA was 20/25. This report demonstrates that postoperative compliance might be of extraordinary importance in patients receiving LALs and that the sensitivity by which the lens reacts to unplanned UV exposure might be extraordinarily high. Correction of Myopia after Cataract Surgery with a Light-Adjustable LensOphthalmologyVol. 116Issue 8PreviewTo determine whether residual myopia could be corrected postoperatively using the light-adjustable lens (LAL) technology in patients undergoing cataract surgery and LAL implantation. Full-Text PDF

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.

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 mu m of corneal stroma. To protect the endothelium, CXL inclusion criteria require a minimum corneal thickness of 400 mu m after removal of the epithelium. In advanced keratoconus, however, progressive corneal thinning often leads to a remaining stromal thickness of less than 400 pm. We have therefore modified the current treatment protocol by preoperatively swelling thin corneas to a stromal thickness of at least 400 mu m 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.

PURPOSE: To evaluate the efficacy of blue-light scleral cross-linking as well as its safety in preventing retinal damage beneath the treated sclera.METHODS: Six rabbits were unilaterally treated with topical riboflavin (0.5%) and blue light (465 nm) on the equatorial sclera using a light emitting diode source with an exposure area of 9 mm in diameter. Four weeks after the treatment, the animals were euthanized and the exposed sclera and contralateral eye sclera excised for comparative testing of biomechanical rigidity and histologic retinal cellular damage. Extensiometry was performed to evaluate the stress-strain curve of treated versus untreated sclera, and light microscopy of the treated sclera and underlying retina were also comparatively evaluated.RESULTS: Blue-light scleral cross-linking showed a three-fold increased stiffening in all tested animals in the stress-strain curve. Histological investigation revealed no retinal damage in any of the treated eyes.CONCLUSIONS: Scleral cross-linking with riboflavin and blue light (465 nm) has a stiffening effect on the sclera without histological tissue damage to the retina.

Die Vernetzung der Hornhaut (CXL) ist die bisher einzige Behandlung, die eine progressive Keratekasie zum Stillstand bringen kann. Daneben bewirkt das Crosslinking des Stromas jedoch auch eine vermehrte Resistenz gegenüber deren Abbau durch Kollagenasen und eine Änderung im Quellverhalten der Hornhaut. Diese beiden Nebeneffekte des CXL könne in der Augenheilkunde ebenfalls zum Nutzen des Patienten eingesetzt werden.

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.

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 patient's 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.

Fragestellung: Bisher standen nur die Versorgung mit formstabilen Kontaktlinsen und die Keratoplastik (tief lamellierend oder perforierend) als Therapieoptionen bei der Keratektasie nach LASIK zur Verfügung. Seit neuestem wird auch die korneale Quervenetzung (X-linking) eingesetzt. Methoden: Bei 7 Fällen von Keratektasie nach LASIK wurde mit der Standardquervernetzung (Riboflavin und UVA) behandelt und bis zu 3 Jahren nachkontrolliert. Die Progression war in jedem Fall durch corneale Topographien dokumentiert. Ergebnisse: In allen 7 Fällen wurde die Progression aufgehalten, in 5 dieser Fälle fand eine zum Teil hochsignifikante Reduktion der Keratektasie statt. Bei einem Auge kam es zur Endothelschädigung, da die Hornhaut unter der Ektasiespitze zu dünn war (<400µm). Schlussfolgerung: Korneales X-linking stellt eine weitere Therapieoption bei iatrogener Keratektasie dar, die sogar eine Regression ermöglicht. Auf die minimale Hornhautdicke muss geachtet werden.

Fragestellung: Bei kontaktlinsen-intoleranten Keratokonuspatienten ermöglicht die Brille oft nur einen ungenügenden Visus. Liegt eine forme fruste der Keratektasie vor könnte eine optische Homogenisierung der Hornhaut wieder zu einem annehmbaren Brillenvisus verhelfen. Methoden: Bei 13 Augen mit gesicherter Forme-fruste-Keratektasie wurde eine topographie- oder wellenfront-geführte Oberflächenablation durchgeführt und mehr als 1 Jahr nachkontrolliert. Die Hornhaut war an der dünnsten Stelle mindestens 450µm dick. Ergebnisse: Statistisch signifikant reduziert waren sphärisches Aequivalent, Zylinder, Schwiegerlings Keratoconusparameter Z3 und Geisterbilder. Bei keinem Auge stellte sich im Beobachtungszeitraum bis zu 4 Jahren eine Progression ein. Der Brillenvisus nahm hochsignifikant bei allen Patienten zu. Schlussfolgerung: Die optische Homogenisierung der Keratokonushornhaut mittels individualisierter Oberflächenablation ist eine therapeutisch wertvolle Option um den Brillenvisus zu verbessern. Im Allgemeinen ist allerdings nicht Emmetropie anzustreben.

PURPOSE:To compare the correlation between corneal and total wavefront aberrations in normal phakic and pseudophakic eyes after implantation of foldable monofocal intraocular lenses (IOLs). SETTING:University Hospital, Eye Clinic, Zurich, Switzerland. METHODS:Wavefront aberrations and corneal topography of 29 eyes that had cataract surgery with implantation of hydrophobic monofocal foldable IOL (AcrySof, Alcon Labs) were measured at least 2 months postoperatively and compared with wavefront measurements performed in 33 normal young phakic eyes. The total wavefront aberrations were measured by means of a Tscherning wavefront sensor at a wavelength of 660 nm (Allegro Wave Analyzer, WaveLight Laser Technology). The corneal aberrations were derived from corneal topography measurements ascertained with a Placido-based topography system (Keratograph 70600, Oculus). The correlations between corneal and total wavefront aberrations were calculated for all Zernike coefficients from 2nd up to 6th order. RESULTS:There was a significant correlation between corneal and total wavefront aberrations in astigmatism C3 and C5 as well as for all 3rd-order Zernike coefficient in both groups (except C8 in the pseudophakic group). The correlation between corneal and total astigmatism (C3 and C5) was higher in the pseudophakic than in the phakic eyes. In contrast, the correlation for the coma-like aberrations was weaker in the pseudophakic eyes (R>0.18) than in the group of phakic eyes (R>0.58). In both groups, there was no significant correlation between spherical aberration C12 of the cornea and the C12 of the total eye. CONCLUSION:After cataract surgery with an IOL implantation, both vertical and horizontal coma, as well as spherical aberration, were of higher value than in normal eyes. The compensation effect for corneal aberrations of the natural lens is absent in the IOL and explains these findings. The corneal aberrations in pseudophakic eyes reflect better the optical quality of the total eye than the phakic eyes. Nevertheless, the missing correlation in some specific aberrations, such as C8 and C10, shows the inability of corneal topography to provide suitable information on the optical quality of the total eye after cataract surgery. Thus, both corneal and total wavefront measurements are relevant for the assessment of outcomes after cataract surgery.

Purpose: To evaluate the efficacy of customized surface ablation in cases of forme fruste keratoconus.Design: Prospective noncomparative case series.Participants: Eleven eyes of 8 contact lens-intolerant patients with forme fruste keratoconus treated at the Institute of Refractive and Ophthalmic Surgery and the University Eye Clinic Zurich.Intervention: Topography-guided customized surface ablation by means of a scanning spot excimer laser.Main Outcome Measures: Visual acuity, refraction, quality of vision (ghosting), corneal topography including the Zernike parameter Z3.Results: Statistically significant reduction of manifest refractive error, corneal irregularity, and ghosting. The spherical equivalent was reduced by -2.8 +/- 0.62 diopters (D) (P = 0.0007), the cylinder by 1.34 +/- 0.18 D (P = 0.015), Z3 was reduced by 41% (P < 0.001), and all patients had less ghosting compared to their preoperative status. No eye lost >= 1 lines in best spectacle-corrected visual acuity; however, 7 of 11 eyes gained >= 1 line.Conclusion: Topography-guided surface ablation is a promising option to rehabilitate vision in contact lens-intolerant patients with forme fruste keratoconus.

BACKGROUND:Repeat operations after refractive surgery have increased in frequency during the past 10 years. The spectrum of the indications for repeat LASIK may have changed.METHODS:All cases of repeat operations after refractive surgery performed between May 1, 2004 and April 30, 2005 at the Institute of Refractive and Ophthalmic Surgery (IROC) were retrospectively investigated regarding indication for repeat surgery and visual and refractive results. The 1-month results were used to estimate the refractive and visual success rate.RESULTS:Of the 76 reoperations, 69 were performed as re-lifts, 3 eyes had new lamellae cut, and 3 cases needed keratoplasties. The reoperations took place 7.5 +/- 13 months after the primary operation (range 0.5 to 60 months). The most frequent indication was residual astigmatism of 0.5 D and more. Visual loss of more than 1 decimal line did not occur and unaided visual acuity increased from 0.64 to 1.05. No complications were reported, however, 3 eyes needed additional enhancement.CONCLUSIONS:Reoperations after LASIK performed as re-lifts appear to be effective and reasonably safe when using the technique described and respecting a residual stromal thickness of 280 microns.

Background: Repeat operations after refractive surgery have increased in frequency during the past 10 years. The spectrum of the indications for repeat LASIK may have changed. Methods: All cases of repeat operations after refractive surgery performed between May 1, 2004 and April 30, 2005 at the Institute of Refractive and Ophthalmic Surgery (IROC) were retrospectively investigated regarding indication for repeat surgery and visual and refractive results. The 1-month results were used to estimate the refractive and visual success rate. Results: Of the 76 reoperations, 69 were performed as re-lifts, 3 eyes had new lamellae cut, and 3 cases needed keratoplasties. The reoperations took place 7.5 +/- 13 months after the primary operation (range 0.5 to 60 months). The most frequent indication was residual astigmatism of 0.5 D and more. Visual loss of more than 1 decimal line did not occur and unaided visual acuity increased from 0.64 to 1.05. No complications were reported, however, 3 eyes needed additional enhancement. Conclusions: Reoperations after LASIK performed as re-lifts appear to be effective and reasonably safe when using the technique described and respecting a residual stromal thickness of 280 microns.

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 I 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: Delta Q(15) = 0.25 in Q-factor customized versus Delta Q(15) = 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.