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Biomedical subjects

N F Schrage

Publications and source records attributed to N F Schrage.

At least 19 recordsLinked to original sources

Emergency treatment of eye burns: which rinsing solution should we choose?

BACKGROUND: In the treatment of eye burns few data on the comparative application of rinsing solutions exist. We present experiments in vitro and ex vivo on the pH changes that can be achieved in alkali eye burns with currently distributed and propagated rinsing fluids like water, saline solution, Cederroth Eye Wash Solution (including borate buffer), Diphoterine, Ringers lactate solution and phosphate buffer. METHODS: Titration curves in beakers are compared with ex vivo experiments on isolated rabbit eyes. We exposed eyes to burns from filter paper soaked in 2 mol NaOH, continuously measuring the anterior chamber pH by means of a micro pH electrode placed near the endothelium. In each experiment--repeated five times--the corneal burn of 20 s in 2 mol NaOH was followed by a period of 15 min of rinsing under a defined flow of 66 ml/min. RESULTS: We found highly significant differences in intracameral pH related to different types of rinsing solutions. The return of the intracameral pH to normal was not achieved by any of the rinsing fluids, but the best results were noted for of Cederroth Eye Wash Solution (Cederroth Industrial Products, Upplands Väasby, Sweden) and the Diphoterine- and Previn solutions (Prevor, Cologne, Germany). Water played an intermediate role whereas saline and phosphate buffer were not efficient at lowering intracameral pH after alkali burns. CONCLUSION: In alkali burns we recommend efficient buffering solutions. The tested isotonic phosphate buffer (PBS) was not effective at buffering the intraocular pH. Water was found to be much less efficient than Previn, Diphoterine or Cederroth Eye Wash solution in balancing intraocular pH.

Animals↗

[Acute therapy for eye burns].

BACKGROUND: Eye rinsing is the major therapeutic measure with a decisive impact on prognosis after chemical or thermal eye irritation. Several different major targets are addressed by this measure. AIM OF THE STUDY: Up to now emphasis in research was placed mostly on the neutralisation of chemical products. Newer experimental results on the basis of biological experiments interpreted against the background of basic chemical reactions may enhance clinical treatment by introducing new mechanisms of intervention. MATERIALS AND METHODS: Experiments on the modification of osmolarity, buffering capacity and solubility products show new possibilities of therapy in eye rinsing after eye irritation. These mechanisms are demonstrated by means of key experiments. RESULTS: The official recommendation of rinsing a burnt eye with water seems to be insufficient against the background of actual experimental data. Measurements of pH after eye burns indicate no buffering effects for water, or aqueous saline solution. There was weak buffering for phosphate buffer in alkali burns and a high capacity for neutralisation for diphoterine in alkali and acid burns. Ionic contents and osmolarities of the rinsing solutions have a decisive influence on the ionic composition and osmolarity of the burnt cornea after rinsing. Cellular damage is enhanced in unaffected healthy cell cultures by hyposomolar rinsing. CONCLUSION: We recommend buffered solutions with high buffer capacities for initial eye rinsing. The advantage or disadvantage of the elevated concentration of ions in the buffered rinsing solutions determining osmolarity cannot be confirmed or refuted up to now. It seems to us to be certain that osmolarity is a decisive future factor in initial rinsing.

Acute Disease↗

Ascorbic acid reversibly inhibits proliferation of retinal pigment epithelial cells.

PURPOSE: Proliferation control in adult retinal pigment epithelial (ARPE) cells is an essential factor in the clinical management of proliferative vitreoretinopathy (PVR). Factors which inhibit PVR and which are without toxic potential are therefore of interest in controlling proliferation. The aim of the present study was to gain insight into a possible function of high intraocular ascorbic acid levels as a physiological modulator of proliferation. METHODS: Adult retinal pigment epithelial cells were incubated in vitro with increasing concentrations of ascorbic acid (0.5-4 mmol, pH 7.4). Cell proliferation was assayed by the bromide-deoxy-uridine (BrdU) assay. The culture medium (CM) containing ascorbic acid was replaced with normal CM and the recovery of proliferation was measured after 24 hours. In order to be able to distinguish between proliferation inhibition, apoptosis, necrosis and recovery of proliferation, we performed TUNEL assays and fluorescence analysis cell-counter (FAC) analysis. RESULTS: Ascorbic acid significantly inhibits ARPE cell proliferation if it is present in concentrations above 2 mmol. Proliferation resumed in all ARPE cell cultures after pre-incubation with ascorbic acid, indicating that direct toxicity of ascorbic acid is a negligible factor. The time-point and extent of recovery in proliferation was dependent on the initial ascorbic acid concentration. Fluorescence-labelled cell counts on apoptosis markers (FAC) data showed some induction of apoptosis and necrosis after incubation with 4 mmol ascorbic acid. CONCLUSIONS: Ascorbic acid has a dose-dependent influence on the proliferation of vital ARPE cells. This possibly reflects the role of ascorbic acid at a physiological level within the vitreous cavity in preventing proliferative vitreoretinopathy (PVR). These findings may stimulate the development of new strategies in the clinical treatment of PVR.

Apoptosis↗

The Aachen-keratoprosthesis--a flexible KPro that permits intraocular pressure measurement.

PURPOSE: Postoperative glaucoma is one of the major complications observed in patients with keratoprostheses (KPro). The optical components of the majority of KPros are rigid and inflexible, which prevents indirect tonometry by common methods. This study confirms that the Aachen-KPro allows measurements of intraocular pressure (IOP) due to its flexible optical part with a modified Schiotz tonometer. METHODS: The Aachen-KPro was placed in a special chamber where pressure can be generated and monitored by a transducer. Measurements were taken by common ophthalmologic methods. The results were compared to the initial pressure values in the chamber. RESULTS: With the Goldmann tonometer, the Tono-Pen and the topography system (Technomed), no significant pressure changes could be observed. The results of the Schiotz tonometer were promising. It was slightly modified and standard curves with different weights could be obtained. CONCLUSIONS: With a modified Schiotz tonometer, it is possible to detect elevated IOPs. Modifying this common instrument is inexpensive and can be easily performed. This advantage of the Aachen-KPro permits early management of postoperative high tension glaucoma.

Cornea↗

Persistent indocyanine green (ICG) fluorescence 6 weeks after intraocular ICG administration for macular hole surgery.

BACKGROUND: Macular hole surgery including vitrectomy and peeling of epiretinal membranes and the internal limiting membrane (ILM) has become a standard procedure in retinal surgery. Poor visualization of epiretinal membranes and the ILM is an obstacle to successful surgery. Recently, indocyanine green (ICG) has been reported to be a helpful intraocular substance in identifying these membranes. METHODS: In a case of stage IV macular hole, epiretinal membranes and ILM were intraoperatively stained with three drops of 1:9 diluted ICG. After 1 min incubation the vitreous cavity was rinsed with Ringer's lactate solution, and the membranes were peeled. Autologous thrombocytes were applied to the macular hole, and the eye was endotamponaded with 20% SF6 gas. Six weeks postoperatively, visual acuity was measured and fundus photographs and autofluorescence images, as well as a multifocal ERG, were obtained. RESULTS: Intraoperatively, the ILM could be nicely visualized by ICG, which allowed immediate peeling. Six weeks after surgery, the visual acuity had improved from 0.1 to 0.7 and the macular hole was closed. Autofluorescence imaging at 795 nm revealed a strong signal. Multifocal ERG recording showed regular amplitudes. CONCLUSION: ICG as an intraocular tool for staining of the ILM is helpful in macular hole surgery. We did not observe any negative effect on retinal function; however, we were surprised to identify traces of ICG in retinal fluorescein angiography images 6 weeks postoperatively.

Basement Membrane↗

Phosphate buffer in alkali eye burns as an inducer of experimental corneal calcification.

Corneal calcification is a common problem in severe inflammation, chronic glaucoma, renal disorders and other diseases with disturbed calcium and phosphorus metabolism. The pathogenesis of corneal calcifications in ocular diseases is not yet completely understood. We present a model of an induced corneal calcification by local treatment. In a double-masked experiment 16 rabbits underwent eye burn of one cornea followed by immediate rinsing (160 ml) with isotonic phosphate buffer (n=8) or saline solution (n=8) three time a day for 16 days. Tissues were excised, shock frozen and cut into 10 microm slices, freeze dried and coated with evaporated carbon. In the phosphate buffer group an early onset of corneal opacification occurred resulting in completely white corneas after 16 days, combined with corneoscleral ulceration. The other group showed similar corneal erosion and a little corneal ulceration, but no opacifications. The opacifications of the phosphate buffer group could be identified as calcifications by direct measurements of calcium and phosphate (by energy dispersive X-ray analysis on corneal samples). In conclusion, inappropriate application of phosphate leads to uncontrolled calcifications of the cornea after severe burns to the eye. This reflects clinically observed calcifications after eye burns and possibly the adverse side effects of phosphate buffered eye drops being applied in ophthalmology.

Alkalies↗

Effects of ascorbic acid on retinal pigment epithelial cells.

PURPOSE: Evaluation of effects of ascorbic acid on cell characteristics of dedifferentiated porcine retinal pigment epithelial (pRPE) cells. METHODS: pRPE cells were incubated in vitro with increasing concentrations of ascorbic acid (0.25-1.5 mMol). Cell proliferation was assayed by measuring the incorporation of 5-bromo-2'-deoxy-uridine (BrdU) into cellular DNA. Migration and contraction properties were studied on a cell permissive porous membrane and collagen gels, respectively. Phenotypic changes in response to ascorbic acid and its derivative ascorbic acid 2-phophate were evaluated by microscopy and indirect immunofluorescence. RESULTS: Ascorbic acid significantly inhibits cell proliferation, migration, and contraction in concentrations of 1 mMol or more. Under the influence of at least 1 mMol ascorbic acid dedifferentiated pRPE cells exhibited a pigmented status within 24 hours. Addition of 500 U/ml catalase prevented the antiproliferative effect of ascorbic acid and the formation of pigment. Concentrations of 0.5 mMol ascorbic acid as well as 1 mMol ascorbic acid 2-phosphate promoted differentiation of cell phenotype. Furthermore, ascorbic acid 2-phosphate supported the formation of in vivo-like epithelial structures. CONCLUSIONS: Ascorbic acid has an influence on vital cell characteristics such as proliferation, migration, contraction and differentiation of pRPE cells. As dedifferentiation of these cells is an integral part in the development of proliferative vitreoretinopathy (PVR), ascorbic acid should be taken into consideration as a supplement in the clinical management of this disease.

Animals↗

Aachen keratoprosthesis as temporary implant for combined vitreoretinal surgery and keratoplasty: report on 10 clinical applications.

UNLABELLED: A new keratoprosthesis was used during pars plana vitrectomy in order to test the optical quality, watertightness, short-term biocompatibility and handling of the new device. The implantability was also tested, given that this keratoprosthesis might in future be left in place for several months. This Aachen keratoprosthesis (Aachen-KPro) is developed to be used as permanent implant to restore vision in corneal blind patients. PATIENT AND METHODS: The Aachen-KPro was used during pars plana vitrectomy in 10 patients with opaque corneas. In four cases, trauma precipitated the ocular disease. Eye burn was the cause of corneal and retinal disorders in another four cases. One patient had a history of congenital glaucoma with myopia, and one of uveitis with corneal dystrophy. After trephination of 6.5 mm in diameter, the Aachen-KPro, composed of soft silicone rubber, was temporarily placed in the trephination hole. After completion of the vitrectomy, the Aachen-KPro was replaced by a 7 mm corneal graft. RESULTS: Intraoperative use of the Aachen-KPro allowed uncomplicated intraoperative handling, smooth adaptation to the corneal rim in the trephination hole, and an undistorted view of the central and peripheral retina. Leakage, even during scleral depression, could be avoided by individual suturing of the scleral rim. After a follow-up period of 1-10 months, the retina was still attached in all cases. The corneal graft was clear after surgery in four eyes, and edema was found in three cases. Amnion or conjunctiva was placed over three patients' transplants. CONCLUSION: We report the first temporary implantations of a new keratoprosthesis in 10 patients. Its flexibility and good optical qualities allowed control of intraoperative procedures. The outcome and prognosis of the vitreoretinal surgery and keratoplasty were related to the primary diagnosis. The Aachen-KPro has shown advantages, especially in eyes where the anterior eye segment is severely damaged by eye burn or previous surgical interventions. In the future, prolonged use of the Aa-chen-KPro is planned for selected eyes.

Adult↗

Eye burns: an emergency and continuing problem.

Adequate treatment of eye burns is an essential task of rescue teams. Clinical and occupational medicine studies have shown that efficient emergency treatment can prevent severe eye damage, but therapy is frequently delayed or inadequate. When initial therapy has been delayed or missed, several treatment strategies, including surgery, are available that may improve the outcome of an injury with poor visual prognosis. Discussed in this review are common accident mechanisms, causative agents and biophysical/pathogenetic aspects of eye burns, together with emergency and long-term treatment strategies including surgical procedures, and factors influencing outcome.

Antidotes↗

Microbiopsy in healthy rabbit corneas. A long-term study.

PURPOSE: Corneal biopsies are important in diagnosing multiple corneal diseases. They were previously performed by way of keratectomy, a method that causes corneal opacity and topographic changes due to scarring. Microbiopsy is a new way to perform corneal biopsies. Before microbiopsy may be performed on human corneas, the safety of this procedure has to be proved concerning clinical development, histological changes and topographic changes after multiple biopsies. METHODS: The healthy right cornea of 24 rabbits was punctured. 12 microtrephinations in 4 different symmetric patterns were performed. The clinical development of the bioptic sites as well as the topographic changes were observed over 5 months. After enucleation, serial sections of the corneas were analysed histologically. RESULTS: Out of 294 performed biopsies, 291 samples could be collected. 4 perforations occurred. The initial epithelial defect closed within 3 days. A pale stromal scar remained. The histological analysis of these scars showed a facette underlined by a dense hypocellular fibrous layer and a typical star-shaped figure consisting of a loose hypercellular stromal tissue. Only dioptric power of corneas with circle-pattern showed a statistically significant decrease. CONCLUSION: Micropuncture is a safe and efficient bioptic procedure. Even 12 micropunctures do not lead to significant changes of dioptric power in most patterns. Further studies are necessary to evaluate the reproducibility of refractive changes by circle patterns and corrections of astigmatisms.

Animals↗

A new way of removing silicone oil from the surface of silicone intraocular lenses.

PURPOSE: This study was performed to ascertain the efficacy of Perfluorhexyl-octan, C14F13H17 (F6H8), in dissolving silicone oil from the surface of silicone intraocular lenses. So far F6H8 is the only solvent of silicone oil that is tolerated by intraocular tissues. MATERIALS AND METHODS: Intraocular silicone lenses (Domilens) were examined after application of small droplets of silicone oil of two different viscosities (AdatoSIL-OL 1000 and 5000) followed by rinsing with F6H8. To allow distinction between silicone oil and F6H8 the silicone oil was stained. Microscopic examination was carried out under video control. RESULTS: One hundred microliters of AdatoSIL-OL 1000 could be easily removed with about 800 microl of F6H8; 50 microl of AdatoSIL-OL 5000 also disappeared after 800 microl of F6H8. A larger drop of the latter oil could not be removed even after application of 2 ml of F6H8. CONCLUSION: Silicone oil 1000 can be easily dissolved by F6H8, whereas silicone oil 5000 is more difficult to remove because of its higher viscosity.

Equipment Contamination↗

The "Aachen" keratoprosthesis: a new approach towards successful keratoprosthesis-surgery.

BACKGROUND: None of the keratoprostheses available today is absolutely successful in the long term, neither the problems of extrusion, retroprosthetic membrane formation and intraocular pressure rise are yet solved. A new type of keratoprosthesis is required which can show improved ingrowth characteristics and allow intraocular pressure measurements. In order to possibly meet the above mentioned requirements we developed a flexible silicone keratoprosthesis with scleral fixation and chemical surface modification. METHODS: The one-piece keratoprosthesis is made of silicone rubber. Its optical zone has a diameter of 11 mm and is 0.3 mm thick. The surface-modified haptic consists of a scleral rim and eight branches for scleral fixation. A ridge at the back of the keratoprosthesis fitting into the trephination hole shall avoid leakage and retroprosthetic membrane formation. Optical and mechanical qualities are characterised by tensile tests, spectrophotometry and topography. RESULTS: A method for keratoprosthesis-production was established. The optical quality of the device was improved by submicron lathing of the mould. Spectrophotometry showed high visible and ultraviolet light transmission of the silicone. Mechanical tests with silicone samples revealed high tensile strength and elongation at break. The mechanical properties were not impaired by surface modification. CONCLUSIONS: The production of a flexible silicone keratoprosthesis with high optical and mechanical properties was established. Its use both for the treatment of permanently opacified corneas and as temporary keratoprosthesis seems to be possible.

Biomechanical Phenomena↗

Functionally adapted surfaces on a silicone keratoprosthesis.

BACKGROUND: Silicone intraocular lenses as well as silicone sponges and encircling bands on the bulbar surface are widely used and are well tolerated. The aim of this project is a new one-piece silicone keratoprosthesis with enhanced cell adhesion in the haptic region to optimize the keratoprosthesis stability. These investigations show how enhanced profileration of conjunctival fibroblasts and, therefore, improved tissue compatibility can be achieved by hydrophilizing and by protein immobilisation on a hydrophobic silicone surface. This allows a combination of desired chemical and mechanical properties of the silicone bulk material with surfaces of improved tissue compatibility. METHODS: Silicone foils with surface modifications of different kinds were tested. Experiments were done using cell cultures with murine fibroblasts L-929 and human conjuctival fibroblasts. Cytotoxicity assays were carried out with cells grown on the material in direct contact, as well as in indirect contact, with extracts (EN 30993-5). Viability stains by means of fluoresceindiacetate and ethidiumbromide together with morphology analyses by hemalaun-staining were performed. RESULTS: For the unmodified and modified foils themselves and their extracts any negative influence on cell cultures of murine and human cells could be excluded. There was a gradual improvement of cell morphology, spreading and proliferation dependent on the degree of surface modification. Covalently immobilised fibronectin showed the best results in contrast to adsorptive binding. CONCLUSIONS: Silicone surfaces can be modified chemically with bioactive proteins. These modifications are cell compatible and do not result in toxic reactions. The degree and type of silicone hydrophilization results in improved development of cell morphology, spreading and proliferation. Even better results are obtained after covalent binding of bioactive proteins like fibronectin. Improved biocompatibility with enhanced cellular overgrowth has been demonstrated in vitro for the modified silicone of the haptic region. We believe that this type of modification will help in reducing extrusion problems observed with former keratoprostheses.

Animals↗

Changes in mineral composition of rabbit corneas after alkali burn.

BACKGROUND: Mineral balance is essential for maintaining corneal transparency. In preliminary investigations, we found alterations of mineral concentrations in the human cornea after chemical burns. In this prospective study the mineral content of the rabbit cornea was quantified after experimental alkali burns. METHODS: Thirty-two eyes of rabbits were burnt for 30 s with 1 M NaOH. A short period of saline rinsing followed, but no further therapy was given. The eyes of 20 healthy rabbits served as a control. We measured the water content by weighing the cornea before and after drying. The mineral content of the cornea was determined in different stromal layers using energy-dispersive X-ray analysis in the scanning electron microscope. Groups of eight rabbits were examined on days 0, 1, 4 and 8 after the experimental burns. RESULTS: After alkali burns the mineral composition of the corneal stroma changed considerably. Sodium was present in high concentrations immediately after burning, up to 708 mmol/kg dry weight, and returned to normal on day eight. Chlorine increased significantly throughout the whole period. Sulphur concentrations stayed almost normal, showing only a minute loss of ground substance after alkali burn. A considerable and increasing edema could be concluded from the water content. CONCLUSIONS: Alkali burns resulted in a dramatic change of the corneal mineral content. Therapeutic intervention with appropriate solutions is required to restore and maintain the normal mineral composition of the denuded corneal stroma.

Animals↗

Development of a surface modified silicone-keratoprosthesis with scleral fixation.

BACKGROUND: Many attempts have been made to create artificial corneas. The keratoprostheses currently available do not allow measurements of the intraocular pressure (IOP) and restrict the visual field. The main problem is extrusion due to an insufficient connection between implant and surrounding tissue. It is our aim to create a flexible keratoprosthesis with a wide field optic allowing measurements of the IOP. Surface modification will improve cell adhesion and therefore stability between implant and tissue. METHODS: The keratoprosthesis is made of silicone rubber. The optical zone is 11 mm in diameter with a thickness of 0.3 mm. The surface modified haptic consists of a scleral rim and 8 branches for scleral fixation. Optical and mechanical qualities were tested by tensile tests, spectrophotometry and topography. RESULTS: A method to produce one-piece silicone keratoprostheses was established. Submicron lathing of the mould led to an excellent optical quality. Spectrophotometry showed high degree of visible and ultraviolet light transmission of the silicone. Mechanical tests revealed high tensile strength and elongation at break which were not impaired by surface modification. CONCLUSION: The production of a flexible silicone keratoprosthesis with high optical and mechanical properties was accomplished, with possible use as both permanent and temporary keratoprosthesis.

Corneal Diseases↗

The corneal stroma: an inhomogeneous structure.

PURPOSE: This study was conducted to determine the elemental composition of the human cornea. Special attention was paid to corneal stroma inhomogeneity. METHODS: Seventy human corneas were examined by means of energy-dispersive X-ray analysis. Epithelium, subepithelium, middle stroma, sub-Descemet layer, Descemet's membrane and endothelium were subjected to repeated measurements. RESULTS: In the cellular layers the phosphorus concentrations were high [0.35 mol/kg dry weight (dw) in the epithelium and 0.403 mol/kg dw in the endothelium]. Similar concentrations were found for sulphur (0.38 mol/kg dw in the epithelium). Stromal layers showed high contents of sulphur: 0.26 mol/kg dw. The phosphorus concentration was found to be higher in the subepithelium than in the middle stroma. Sulphur concentrations were highest in Descemet's membrane, followed by the subepithelium and the middle stroma. DISCUSSION: Nucleic acids and energy-containing phosphates explain the high levels of phosphorus in the cellular layers. The high sulphur concentrations may be related to the phosphoadenosinphosphosulfate and protein turnover in the epithelium. We interpret the inhomogeneous distribution of phosphorus in the stroma as a function of the density of keratocytes. An evaluation of all known sulphur-containing biochemical components of the stroma (0.217 mol sulphur/kg dw) corresponds to our measurements. In contrast to former results we find the corneal stroma to be an inhomogeneous structure.

Aged↗

[Temperature changes of the cornea by applying an eye bandage].

BACKGROUND: The corneal temperature is not often measured, but it may be useful to evaluate the temperature-changing effect of the application of eye bandages. The reason for applying an eye bandage is to calm an inflamed eye and to provide mechanical protection. Everyone knows that some patients have more complaints after an eye bandage has been applied. This phenomenon might be caused by the inflamed eye being warmed up by bandage application. MATERIALS AND METHODS: In 40 apparently healthy subjects 24 +/- 1.93 years of age we examined the temperature changes caused by two different types of eye bandage. The measurements were done with a Jeol infrared camera. Twenty probands received a monocular bandage consisting of a perforated plastic cap and another 20 subjects a monocular mull bandage with a perforated plastic cap. RESULTS: The mean corneal apex temperature was 32.05 +/- 0.74 degrees C. Both bandages caused the corneal temperature to go up considerably. The perforated plastic cap increased the mean apex temperature by 0.58 +/- 0.48 degree K and the combined mull bandage by 1.15 +/- 0.57 degrees K (P < 0.05). CONCLUSIONS: Application of an eye bandage increases the corneal temperature significantly. This is known to change enzyme activities and to cause prostaglandin liberation and pain. A change in the bacterial spectrum may result. Cooling as a universal principle in antiphlogistic therapy might be a supplementary therapy in treating sterile, but inflamed eyes.

Adult↗