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Raiskup F.,Carl Gustav Carus University Hospital | Pinelli R.,Instituto Laser Microchirurgia Oculare | Spoerl E.,Carl Gustav Carus University Hospital
Current Eye Research | Year: 2012

Purpose: To investigate the influence of osmolarity on the transepithelial permeability of riboflavin solutions in a cross-linking procedure. Methods: Several riboflavin 0.1% solutions that contained different NaCl and benzalkonium chloride (BAC) concentrations were applied to 36 rabbit eyes for 30min. To serve as a control, the epithelium was removed in group A (standard protocol). The groups then received the following solutions: (A) riboflavin 0.1% in NaCl 0.9% solution; (B) riboflavin 0.1% in NaCl 0.44% solution with BAC 0.02%; (C) riboflavin 0.1% in NaCl 0.44% solution with BAC 0.01%; (D) riboflavin 0.1% in NaCl 0.44% solution without BAC; (E) riboflavin 0.1% in NaCl 0.9% solution with BAC 0.02%; and (F) riboflavin 0.1% in NaCl 0.9% solution without BAC. Six eyes in each group were treated. The absorption coefficients of the corneas were measured to characterize the riboflavin penetration into the cornea. Results: There is a large difference in the transepithelial riboflavin penetration of riboflavin 0.1% + BAC 0.02% solutions that contain different NaCl concentrations (NaCl 0.9% versus NaCl 0.44%). The absorption coefficients differed by more than a factor of two (P=0.004). No statistically significant difference was found between riboflavin 0.1% in NaCl 0.44% solution containing BAC 0.02% and BAC 0.01%. Compared to the standard protocol, these solutions resulted in an absorption coefficient of 37% (BAC 0.02%) and 33% (BAC 0.01%) of the standard epithelium-off procedure. Conclusion: The transepithelial riboflavin solution should contain no dextran, but it should include 0.01% BAC and 0.44% NaCl to promote the permeability of riboflavin through the epithelium, resulting in a sufficient concentration of riboflavin in the corneal stroma. © 2012 Informa Healthcare USA, Inc.

Lunze K.,RWTH Aachen | Singh T.,State University of New York at Buffalo | Walter M.,RWTH Aachen | Brendel M.D.,Mellitus | And 2 more authors.
Biomedical Signal Processing and Control | Year: 2013

A method for optimal continuous insulin therapy for diabetes patients has been sought since the early 1970s. Although technical and medical advances have been made, a fully automated artificial pancreas to replace the functions of the natural organ is still a research aim. This review compares recent control algorithms for type 1 diabetic patients which automatically connect continuous glucose monitoring and insulin injection, without patient intervention. Black-box model and gray-box model based control strategies are described and their performances are evaluated, with a focus on their feasibility of implementation in a real-life situation. In conclusion, a satisfactory control strategy has not yet been proposed, mainly because most control algorithms rely on continuous blood glucose measurement which is not yet available. Modeling the effect of glucose ingestion as an external disturbance on the time evolution of blood glucose concentration, is now the norm for the control community. In contrast, the effects of physical activity on the metabolic system is not yet fully understood and remain an open issue. Moreover, clinical studies on evaluation of control performance are scarce. Therefore, research on blood glucose control needs to concentrate on advanced patient modeling, control optimization and control performance evaluation under realistic patient-oriented conditions. © 2012 Elsevier Ltd. All rights reserved.

Podlesek D.,Carl Gustav Carus University Hospital | Geiger K.,Carl Gustav Carus Institute | Hendry D.J.,Highlands Health Center | Schackert G.,Carl Gustav Carus University Hospital | Krex D.,Carl Gustav Carus University Hospital
Journal of Neuro-Oncology | Year: 2011

Rosette-forming glioneuronal tumor of the fourth ventricle (RGNT) is a rare condition, which previously has been described predominantly in middle-aged patients. There is limited experience with this kind of tumor in the elderly. Clinical, neuroimaging, and histological features of an example in a 70-year-old male who presented initially with vertigo are detailed and compared with published cases. Neuroimaging studies demonstrated a 4-cm cystic lesion in posterior fossa containing a 1-cm contrast-enhancing nodule on its lateral margin. The lesion was confined to the fourth ventricle and initially thought to be a hemangioblastoma until angiography clarified the minimal tumor vascularization. Gross total resection was achieved. Pathological examination showed a rosette-forming low grade tumor with a cell proliferation rate of 2% being consistent with RGNT. The postoperative course was uneventful and clinical symptoms resolved completely. There was no tumor recurrence after 2 years follow-up. We confirm that the rare and only recently characterized tumor entity of RGNT can also be found in elderly patients; furthermore, it can be associated with a benign course. The main differential diagnosis of RGNT resulting from CNS-imaging modalities in elderly patients are pilocytic astrocytoma and hemangioblastoma of the posterior fossa, which after metastasis are the most common primary adult intra-axial posterior fossa tumors. Therefore, a subtle preoperative radiological diagnosis is warranted and surgery should be performed by experienced hands to avoid neurological deterioration. © 2010 Springer Science+Business Media, LLC.

Rein S.,Carl Gustav Carus University Hospital | Fabian T.,Carl Gustav Carus University Hospital | Zwipp H.,Carl Gustav Carus University Hospital
Foot and Ankle International | Year: 2010

Background: The aim of this study was to examine the influence of age, body mass index (BMI) and leg dominance on the PRT, balance control and foot position sense. Materials and Methods: The proprioception of the ankle was investigated in 210 participants. All participants completed a questionnaire. The PRT was measured on a tilting platform. The position sense test was performed. Balance control was assessed with the Biodex Stability System (BSS), measuring the overall stability index (OSI) at the stable level 8 and the unstable level 2. Correlation analyses were performed between these data and age, BMI and leg dominance, using the Spearman-Rho coefficient with a two-sided significance level of p < 0.05. Results: Significant increases of the PRT and OSI in correlation to increased age and BMI were noted for both legs (p < 0.05). No positive correlation to age, BMI or leg dominance could be demonstrated for the foot position sense test. The PRT of the right leg was always significantly faster than that of the left leg, irrespective of leg dominance (p < 0.05). Surprisingly, individuals with a dominant right leg achieved better OSI scores in left single leg stance at the unstable level 2 (p < 0.05). Conclusion: The PRT and the postural stability correlate with age and BMI, whereas the position sense test of the ankle does not. Furthermore, the PRT in right legs is always faster. This should be noted when functional ankle stability is evaluated in patients. Copyright © 2010 by the American Orthopaedic Foot & Ankle Society.

Krishnan K.G.,Goethe University Frankfurt | Schackert G.,Carl Gustav Carus University Hospital | Seifert V.,Goethe University Frankfurt
Neurosurgery | Year: 2010

Background: The functions of the human face are not only of esthetic significance but also extend into metaphoric nuances of psychology. The loss of function of one or both facial nerves has a remarkable impact on patients' lives. Objective: To retrospectively analyze the functional outcomes of microneurovascular facial reanimation using masseteric innervation. Methods: Seventeen patients with irreparable facial paralysis resulting from benign lesions involving the facial nuclei (n = 14) or Möbius syndrome (n = 3) were treated with free muscle flaps for oral commissural reanimation using ipsilateral masseteric innervation and using temporalis muscle transfer for eyelid reanimation. Results were analyzed by the absolute commissural excursion and commissural excursion index and by a patient self-evaluation score. Presence of synkinesis was documented. Follow-up ranged from 8 to 48 months (mean, 26.4 months). Results: Normalization of the commissural excursion index was observed in 8 of 17 patients (47%), an improvement was seen in 7 of 17 (41%), and failure was observed in 2 of 17 (12%). The individual dynamics of absolute commissural excursion and commissural excursion index changes are presented. A natural smiling response was observed in 10 of 17 patients (59%) but not in the remaining 7 (41%). This response reflected the patient's ability to relay the natural emotion of smiling through the masseteric nerve. Patients' self-evaluation scores were a level higher than objective indices. CONCLUSIONS: Innervation of free muscle flaps with the masseteric nerve for oral commissure reanimation might play an important role in patients with lesions of the facial nuclei (as in Möbius syndrome). Synkinesis persists for long periods after surgery. However, most of the patients learned to express their emotions by overcoming this phenomenon. Despite hypercorrection or inadequate correction, patients evaluated themselves favorably. © 2010 by the Congress of Neurological Surgeons.

Spoerl E.,Carl Gustav Carus University Hospital | Hoyer A.,Carl Gustav Carus University Hospital | Pillunat L.E.,Carl Gustav Carus University Hospital | Raiskup F.,Carl Gustav Carus University Hospital
Open Ophthalmology Journal | Year: 2011

Purpose: To compile the safety aspects of the corneal collagen cross-linking (CXL) by means of the riboflavin/UVA (370 nm) approach. Materials and Methodology: Analysis of the current treatment protocol with respect to safety during CXL. Results: The currently used UVA dose density of 5.4 J/cm 2 and the corresponding irradiance of 3 mW/cm 2 are below the known damage thresholds of UVA for the corneal endothelium, lens, and retina. Regarding the photochemical damages due to the free radicals the damage threshold for endothelial cells is 0.35 mW/cm 2. In a 400μm thick corneal stroma saturated with riboflavin, the irradiance at the endothelial level is about 0.18 mW/cm 2, which is a factor of 2 smaller than the damage threshold. Conclusion: As long as the corneal stroma treated has a minimal thickness of 400 microns (as recommended), neither corneal endothelium nor deeper structures such as lens and retina will suffer any damages. The light source should provide a homogenous irradiance avoiding hot spots. © Spoerl et al.

Spoerl E.,Carl Gustav Carus University Hospital | Terai N.,Carl Gustav Carus University Hospital | Scholz F.,Carl Gustav Carus University Hospital | Raiskup F.,Carl Gustav Carus University Hospital | Pillunat L.E.,Carl Gustav Carus University Hospital
Journal of Refractive Surgery | Year: 2011

PURPOSE: To investigate biomechanical changes after corneal cross-linking (CXL) with riboflavin/ultraviolet-A (UVA) in keratoconus using the recently developed Ocular Response Analyzer (ORA, Reichert Technologies) software. METHODS: Through use of the new ORA software (version 2.04), 37 new parameters derived from the best measurement signal with the highest wavescore of 4 measurements from 50 eyes of 46 patients with keratoconus were obtained before and 1 year after CXL. The parameters of 96 eyes from 96 age-matched, healthy individuals with a spherical equivalent refraction <3.00 diopters served as controls. RESULTS: Corneal hysteresis (CH) and corneal resistance factor (CRF) before CXL were 7.38±1.42 mmHg and 6.16±1.42 mmHg, respectively, compared to 7.37±1.26 mmHg (P=.971) and 6.16±1.50 mmHg after CXL (P=.997), respectively. Based on these 37 new parameters, the area under peak 2 (p2area) showed a statistically significant increase from 1262.3±623.1 before CXL to 1704.3±732.3 1 year after CXL (35%; P=.001). The related value for the p2area of the healthy control group was 3374.9±1099.9. A significant negative correlation was observed between the p2area and the difference in CH-CRF values (r=-0.29, P=.001). CONCLUSIONS: The area under peak 2 appears to be a more sensitive parameter to detect biomechanical changes after CXL than CH or CRF alone. After CXL, keratoconic corneas display altered biomechanical properties, which remain different to those observed in healthy corneas. Copyright © SLACK Incorporated.

Raiskup F.,Carl Gustav Carus University Hospital | Spoerl E.,Carl Gustav Carus University Hospital
Ocular Surface | Year: 2013

Changes in the biomechanical properties of the human cornea play an important role in the pathogenesis of corneal ectatic diseases. Biomechanical investigation shows significant differences between human ectatic corneas and normal corneas, including decreased stiffness and reduction of collagen crosslinks in the ectatic cornea. Induction of crosslinks is a well-established procedure in polymer chemistry to increase the elastic modulus of materials. Crosslinking (CXL) in connective tissue can occur during aging and as a side effect of diabetes mellitus. CXL has been used medically to increase stability and reduce the biodegradation of collagen-based biomaterials for bioprostheses. CXL of the cornea using riboflavin and UVA light with a wavelength of 370 nm and a dosage of 5.4 J/cm2 is a new approach that increases the mechanical and biochemical stability of stromal tissue. This technique combines the principles of CXL (chemical and nonenzymatic) and the biochemical mechanisms of photo-oxidative CXL with riboflavin as a photosensitizer. In this review, the enrichment of riboflavin in the stroma by standard (epi-off) and transepithelial (epi-on) CXL is discussed. The theoretical and experimental measurements of the absorption of UV light explain the stronger CXL effect in the anterior stroma and its importance for the prevention of damage to the endothelial cells. UV devices are described. Changes of the physical properties after CXL, as well as the cellular changes, are discussed. From these basic investigations, treatment parameters for effective and safe CXL are identified. © 2013 Elsevier Inc.

Raiskup F.,Carl Gustav Carus University Hospital | Spoerl E.,Carl Gustav Carus University Hospital
Ocular Surface | Year: 2013

Changes in the biomechanical properties of the human cornea play an important role in the pathogenesis of corneal ectatic diseases. A variety of conditions in primary acquired (keratoconus and pellucid marginal degeneration) or secondary induced (iatrogenic keratectasia after excimer refractive laser surgery) corneal ectatic disorders lead to reduced biomechanical resistance. Corneal collagen crosslinking (CXL) has emerged as a promising technique to slow or even to stop the progression of these corneal ectatic pathologies. In this procedure, riboflavin (vitamin B2) is administered in conjunction with ultraviolet A light (UVA, 365 nm). This interaction causes the formation of reactive oxygen species, leading to the formation of additional covalent bonds between collagen molecules, with consequent biomechanical stiffening of the cornea. Although this method is not yet accepted as an evidence-based medicine modality for the treatment of corneal primary or secondary ectasias, the results of prospective, randomized studies of CXL used in the treatment of these pathologic entities show significant changes in the properties of corneal tissue. This procedure is currently the only etiopathogenetic approach in ectatic eyes that can delay or stop the process of cornea destabilization, reducing the necessity for keratoplasty. Despite promising results, CXL is associated with issues that include long-term safety and duration of the stabilizing effect. Combination of CXL with vision-improving procedures, such as topography-guided custom ablation and implantation of intracorneal ring segments of phakic intraocular lenses, may expand the indications for this procedure. © 2013 Elsevier Inc.

Raiskup F.,Carl Gustav Carus University Hospital | Spoerl E.,Carl Gustav Carus University Hospital
American Journal of Ophthalmology | Year: 2011

Purpose: To evaluate the 1-year results of keratoconic eyes with thin corneas that were treated by a hypo-osmolar riboflavin solution and ultraviolet A collagen cross-linking (CXL). Design: Retrospective, nonrandomized study. Methods: setting: Department of Ophthalmology, Carl Gustav Carus University Hospital, Dresden, Germany. study population: Thirty-two eyes of 29 patients with progressive keratoconus and a corneal thickness of less than 400 μm (without the epithelium). intervention: Application of a hypo-osmolar riboflavin solution to the cornea after its de-epithelization followed by ultraviolet A collagen cross-linking. main outcome measures: Thirty-two eyes with a follow-up within 1 year were evaluated before and after the procedure. Examinations comprised an evaluation of visual acuity, corneal topography, slit-lamp microscopy, and corneal thickness measurements. Results: Before surgery, the mean corneal thickness (with the epithelium) was 382.3 ± 41.9 μm, and after the removal of epithelium, the thickness of the cornea was reduced to 337.0 ± 51.9 μm. After the application of the hypo-osmolar riboflavin solution, this value increased to 451.8 ± 46.7 μm. Before surgery, the mean K-value of the apex of the keratoconus was 65.6 ± 11.2 diopters, and 1 year after treatment, this value remained unchanged at 64.9 ± 11.0 diopters (P = .839). Mean best-corrected visual acuity at the time of the treatment was 0.63 ± 0.37 logarithm of the minimal angle of resolution, and 1 year after the treatment, this value was not statistically different (0.59 ± 0.42 logarithm of the minimal angle of resolution; P = .662). At the last follow-up examination, which was 1 year after the procedure, all corneas were transparent, without any scarring lesions in the stroma. Conclusions: The results of our study, using hypo-osmolar riboflavin solution in a cross-linking procedure of thin corneas, show a stability of keratoconus one year after cross-linking. Application of the hypo-osmolar riboflavin solution preserved cross-linked corneas from developing stromal scars. © 2011 Elsevier Inc.

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