[Collagen cross-linking with riboflavin and UVA light in keratoconus. Results from Dresden]. / Kollagenvernetzung mit Riboflavin und UVA-Licht bei Keratokonus. Dresdner Ergebnisse.

PURPOSE: The aim of this long-term retrospective study was to prove a long-term halting effect of riboflavin and UVA-induced collagen cross-linking in progressive keratoconus. METHODS: Since 1998, within an ethics-committee-approved study (EK 310 499), patients with progressive keratoconus and a minimal corneal thickness of 400 microm have received cross-linking treatment. An increase of the maximum K-value by > or =1 D within the previous year, a patient's statement of deteriorating visual acuity, or the need for a new contact lens fitting more than once in 2 years was considered progression. The maximum follow-up time was 7.5 years. At the first examination and all follow-up examinations, refraction, best corrected visual acuity, corneal topography, and ultrasound pachymetry were recorded. RESULTS: The analysis included 153 eyes of 111 patients, with a minimal follow-up of 12 months. Keratectasia significantly decreased in the 1st year by 2.29 D, in the 2nd year by 3.27 D, and in the 3rd year by 4.34 D. Visual acuity improved significantly in at least one line or remained stable (i.e., no line loss) in the 1st year in 48.9% and 23.8%, respectively; in the 2nd year in 50.7% and 29.6%, respectively; and in the 3rd year in 60.6% and 36.4%, respectively. We saw no severe side effects. Three patients showed continuous progression of keratoconus and received cross-linking treatment again. Despite the small number of patients with a follow-up longer than 3 years, therefore limiting the statistical assertions, our results indicate long-term stabilization or improvement after collagen cross-linking. CONCLUSION: With regard to the size of our cohort and the follow-up time, no comparable data have been published in the literature. The results of this study indicate that collagen cross-linking appears to be an effective therapeutic option for progressing keratoconus. Besides the clinical benefit, there are enormous economic and psychosocial benefits. Cross-linking is an outpatient, minimally invasive, cost-effective treatment involving minimal effort for the persons concerned.

[Biomechanical condition of the cornea as a new indicator for pathological and structural changes]. / Biomechanische Zustand der Hornhaut als neuer Indikator für pathologische und strukturelle Veränderungen.

AIM: Several methods permit the measurement of geometric parameters of the cornea, but until now biomechanical conditions of the cornea have been ignored (e.g. in refractive corneal surgery). Besides the geometric condition, biomechanical properties of the cornea have been shown to influence applanation measurement of intra-ocular pressure (IOP) and epidemiological studies have identified corneal thickness as an independent risk factor for the development and progression of glaucoma. The aim of this investigation was to characterize the biomechanical properties of the cornea using the ocular response analyzer (ORA). METHODS: The ocular response analyzer (ORA) is a new method available for non-contact measurement of the biomechanical properties of the cornea. We evaluated the reproducibility of measurements, the difference between static and dynamic factors and the impact of independent factors (e.g. IOP, age, CCT, swelling of the cornea) on 2,500 measurements of corneal hysteresis (CH) and corneal resistance factor (CRF). RESULTS: In a large sample size we observed changes in CH and CRF after refractive surgery procedures (LASIK, UV-A cross-linking, keratoplasty) and in other corneal disorders (keratoconus, corneal dystrophies). CONCLUSIONS: CRF and CH changes may reflect structural changes of the cornea. Thus, the ORA provides valuable information for a better understanding and characterization of the biomechanical condition of the cornea, especially with regard to diseases such as keratoconus and glaucoma.

[Biophysical principles of collagen cross-linking]. / Biophysikalische Grundlagen der Kollagenvernetzung.

BACKGROUND: The reduced mechanical stability of the cornea in keratoconus or in keratectasia after Lasik may be increased by photooxidative cross-linking of corneal collagen. The biophysical principles are compiled for the safe and effective application of this new treatment method. METHODS: The setting of the therapy parameters should be elucidated from the absorption behaviour of the cornea. The safety of the method for the endothelium cells and the lens will be discussed. The induced cross-links are shown to be the result of changes in the physico-chemical properties of the cornea. RESULTS: To reach a high absorption of the irradiation energy in the cornea, riboflavin of a concentration of 0.1% and UV light of a wavelength of 370 nm, corresponding to the relative maximum of absorption of riboflavin, were used. An irradiance of 3 mW/cm(2) and an irradiation time of 30 min lead to an increase of the mechanical stiffness. The endothelium cells will be protected due to the high absorption within the cornea, that means the damaging threshold of the endothelium cells will not be reached in a 400 microm thick stroma. As evidence for cross-links we can consider the increase of the biomechanical stiffness, the increased resistance against enzymatic degradation, a higher shrinkage temperature, a lower swelling rate and an increased diameter of collagen fibres. CONCLUSIONS: The therapy parameters were tested experimentally and have been proven clinically in the corneal collagen cross-linking. These parameters should be respected to reach a safe cross-linking effect without damage of the adjacent tissues.

[Transcorneal and transscleral iontophoresis of the dexamethasone phosphate into the rabbit eye]. / Transkorneá1na a transsklerálna ionoforéza dexametazón fosfátu do oka králika.

PURPOSE: To evaluate the efficiency of the dexamethasone phosphate penetration into the rabbit eye after transcorneal and transscleral iontophoresis using a drug loaded hydrogel assembled on a portable iontophoretic Mini Ion device. METHODS: lontophoresis of dexamethasone phosphate was studied in healthy rabbits using drug-loaded disposable HEMA hydrogel sponges and portable iontophoretic device. Corneal iontophoretic administration was performed with electric current of 1 mAmp for 1, 2, and 4 min. In the control group, the dexamethasone was applied in drops into the conjunctival sac. Transconjunctival and transscleral iontophoresis were performed in the pars plana area, through the conjunctiva or directly on the sclera. Dexamethasone concentrations were assayed using HPLC method. To study the anatomical changes after iontophoresis application, histological examinations of corneas excised 5 minutes and 8 hours after the procedure were performed. RESULTS: Dexamethasone levels in the rabbits' corneas after a single transcorneal iontophoresis were up to 38 times higher compared to those obtained after topical eye drops instillation. High drug concentrations were obtained in the retina and sclera 4 hours after transscleral iontophoresis as well. There were no statistically significant differences in the drug concentration after transscleral and tranconjunctival iontophoresis. Histological examination of the corneas after the iontophoresis showed only discrete reversible changes of the epithelium and the stroma. CONCLUSION: A short, low-current, non-invasive iontophoretic treatment using the dexamethasone-loaded hydrogels has a potential clinical value in increasing the drug's penetration into the anterior and posterior segment of the eye.

[Functional examination of retinal vessels in patients with central retinal vein occlusion]. / Funkcní vysetrení retinálních cév u pacientu s okluzí centrální sítnicové zíly.

Retina vessel analyzer (RVA) provides the functional examination of retinal vessels based on the analysis of the extent (size) of their dilation and constriction. The RVA measures continuously on-line the diameter of retinal arteries and veins after different kind of stimulation. Beyond dynamic vessel analysis, another possibility of the RVA's utilization is a static vessel assessment, measuring the arterial and venous diameter ratio (A/V ratio), which provides the information about the rate of arterial vasoconstriction. The aim of the presented study was to investigate static and dynamic retinal vessel changes in patients with central retinal vein occlusion (Group 1). The second investigated group consists of patients with arterial hypertension; as a control group, healthy persons without any vascular disease were examined. Altogether 40 eyes were examined. Statistically significant differences of A/V ratio were observed in the static vessel analysis in all three investigated groups. The dynamic analysis showed statistically significant differences in arterial dilatation and constriction between all investigated groups as well. The presented results confirm that the degree of retinal vessels endothelial dysfunction is one of the determinating ethiopathological factors of central retinal vein occlusion.

[Delivery of gentamicin to the rabbit eye using hydrogel and iontophoresis]. / Transport gentamycínu z hydrogélu do oka králika pomocou ionoforézy.

The aim of this study was to evaluate the use of solid hydrogel as a probe for the drug delivery to the rabbit eye upon application of low current iontophoresis. Hydroxyethyl methacrylate (HEMA), cross-linked with ethylenglycol dimethacrylate (EGDMA) were prepared to form solid hydrogels. The concentrations of gentamicin sulfate in different segments of rabbit eye after transconjunctival and transscleral iontophoresis were also studied. For iontophoresis we used a portable Mini Ion device (designed at Hebrew University of Jerusalem) and applied a current from 0 mA to 1.5 mA for pre-set period from 30 to 120 seconds and after application the concentrations of gentamicin in cornea were assayed. The rabbits in control group were treated with fortified gentamicin eye-drops (concentration 1.4 %). The highest concentration of gentamicin sulfate was reached after iontophoresis with current intensity of 1.5 mA applied for 60 s. High gentamicin concentration were found in the retina and in the sclera four hours after transscleral iontophoresis, the lowest concentration was obtained in vitreous. The delivery of gentamicin to the eye via iontophoresis with solid HEMA/EGDMA hydrogels seems to be promising method achieving high concentrations of the drug in the eye tissue.