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Biomedical subjects

G F Kieselbach

Publications and source records attributed to G F Kieselbach.

16 recordsLinked to original sources

Intravitreal acetylsalicylic acid in silicone oil: pharmacokinetics and evaluation of its safety by ERG and histology.

BACKGROUND: A new method of intravitreal drug delivery of acetylsalicyclic acid (AS) in silicone oil was investigated for safety and for its pharmacokinetics in the posterior pole of the eye. METHODS: The AS was mixed in silicone oil to a concentration of 1.67 mg/ml. After vitrectomy, 15 NZW rabbits received an intravitreal injection of AS/silicone oil suspension. Clinical examination, pre- and postoperative electroretinography (ERG) and histology were performed. The pharmacokinetics of the distribution of salicylic acid was determined by HPLC analysis at 6 h, 24 h and 5 days in optic nerve, retina, choroid, vitreous, and blood. RESULTS: Clinical examination and histology revealed no adverse effects or signs of toxicity. The ERGs showed no significant difference between the pre- and postoperative results. The salicylic acid concentrations demonstrated peak values in the residual vitreous (640.0 micrograms/ml), choroid (446.0 ng/mg) and retina (281.3 ng/mg) at 6 h. At 24 h, the salicylic acid concentration decreased to 20.9 micrograms/ml in the residual vitreous and to 38.5 ng/mg in the retina. At 5 days the retinal level was still 48.1 ng/mg. CONCLUSIONS: AS delivery by intravitreal administration of loaded silicone oil is a safe method and results in high concentrations of salicylic acid in the posterior segment of the eye while maintaining low blood levels.

Animals↗

Slow release of acetylsalicylic acid by intravitreal silicone oil.

PURPOSE: To assess in vitro the potential of silicone oil as a delivery system for acetylsalicylic acid (ASA) and to evaluate in vivo the pharmacokinetic distribution of salicylic acid (SA) in the eye. METHODS: In an experimental model ASA/silicone oil suspension mixed to a concentration of 1.67 mg/mL was investigated for release rate of ASA and SA. In vivo vitrectomy and intravitreal injection of two different ASA/silicone oil suspensions, both mixed to a concentration of 1.67 mg/mL, was performed on two groups, A and B, of New Zealand white rabbits. Salicylic acid concentrations in ocular tissues, aqueous, vitreous, and blood plasma were evaluated at 6 hours, 24 hours, and 5 days using high performance liquid chromatography. RESULTS: Salicylic acid was detected in all tissues. The highest levels were obtained in the vitreous: 745.4 microg/mL (A) and 640.0 microg/mL (B) at 6 hours. The retina followed with 332.9 ng/mg (A) and 281.3 ng/mg (B) at 6 hours and 31.6 ng/mg (A) and 48.1 ng/mg (B) at day 5. The maximum blood plasma levels were 5.2 microg/mL. CONCLUSION: Silicone oil is an efficacious delivery system of ASA in vitro and in vivo. Higher concentrations of SA were found in all ocular tissues and fluids when compared to intravenous administration of maximum doses.

Animals↗

Elevated levels of calcitonin gene-related peptide in aqueous humor of patients with proliferative vitreoretinopathy.

PURPOSE: To detect the levels of the sensory peptide calcitonin gene-related peptide in aqueous humor of patients with proliferative vitreoretinopathy and to compare them with those of uninflamed eyes (cataract and uncomplicated rhegmatogenous retinal detachment). MATERIALS AND METHODS: Using a highly specific and sensitive radioimmunoassay the concentration of calcitonin gene-related peptide was detected in fresh samples of aqueous humor obtained via paracentesis. Furthermore, calcitonin gene-related peptide-like immunoreactivities were characterized by high-pressure liquid chromatography. RESULTS: The mean level of calcitonin gene-related peptide was 6.11 fmol/ml in cataract controls and 14.77 fmol/ml in uncomplicated rhegmatogenous retinal detachment. In the cataract group, 9 of 18 cases were below the detection limit and in the retinal detachment group, 5 of 16. In proliferative vitreoretinopathy, the peptide averaged 76.92 fmol/ml and none of the samples was below the detection limit. High-pressure liquid chromatography revealed one major peak corresponding to synthetic calcitonin gene-related peptide. CONCLUSION: In recent studies, we found elevated levels of the sensory peptide substance P in aqueous humor of patients with proliferative vitreoretinopathy. This fact and the present result, the elevation of calcitonin gene-related peptide in aqueous humor of eyes with proliferative vitreoretinopathy, clearly point to an involvement of sensory peptides in the pathobiology of the disease. The source of the elevation is not clear, but we hypothesize that it originates from a neurogenic mechanism, i.e. an acceleration of the peptides by their enhanced release from the iris/ciliary body complex subsequent to sensitization of sensory neurons, thus representing a very interesting epiphenomenon of proliferative vitreoretinopathy. Our results constitute novel aspects in the pathophysiological concept of proliferative vitreoretinopathy and extend the knowledge about the pathobiology of the disease process.

Adolescent↗

Retinal thickness analysis in subjects with different refractive conditions.

PURPOSE: The aim of the present study is to evaluate a measure of retinal thinning at the posterior pole in eyes with increasing axial myopia. METHODS: 129 eyes of 79 healthy persons with different refractive conditions were examined using a commercially available prototype of retinal thickness analyzer. RESULTS: Increasing myopia has been found to be accompanied by bulbus elongation, and calculation of the values obtained with the instrument revealed a significant decrease in retinal thickness at the posterior pole in eyes with increasing axial myopia, i.e. 4.8 microm/spherical equivalent in the foveolar region and 6.6 microm/spherical equivalent in the other areas of the posterior pole. CONCLUSION: Our data show retinal thinning at the posterior pole in myopic eyes based for the very first time on in vivo measurements. Furthermore, our findings might influence measurement data for other purposes, if the degree of myopia is not taken into account.

Adolescent↗

[Diabetes: can severe vision disorders be prevented?].

No matter how well known the causes of diabetic microangiopathy are, the growth factors responsible for the development of diabetic retinopathy are still not fully investigated; however, promising new concepts are presently in the experimental stage. Now known for decades, laser coagulation of the ocular fundus represents the only current method to stabilize a diabetic retinopathy or to treat an already existing diabetic macular edema. The results of almost all studies prove that besides an optimal management of metabolism timely begin of laser coagulation is of high priority. In addition to consistent therapy, continual follow-up of the patients is of importance, because recurrences can follow successful laser coagulation.

Diabetic Retinopathy↗

Influence of serum lipid fractions on the course of diabetic macular edema after photocoagulation.

The influence of serum lipid fractions [triglyceride, cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol] on the visual outcome after central laser photocoagulation of 39 patients (65 eyes) with clinically significant macular edema was investigated in a prospective study. Referring to normal Austrian serum lipid levels, the patients were classified into a normal and a pathological group for each of the 4 lipids. Concerning triglycerides and HDL cholesterol, the normal group (triglyceride < 2.29 mmol/l, HDL cholesterol > 1.3 mmol/l) showed a statistically significantly better visual outcome than the pathological group. Also, patients with normal total cholesterol and LDL cholesterol values tended to achieve better results after treatment. We therefore conclude that serum lipid fractions may influence not only the success of laser treatment but also the course of diabetic macular edema.

Adult↗

Fibroblast growth-promoting activity in proliferative vitreoretinopathy: antagonism by acetylsalicylic acid.

Proliferative vitreoretinopathy is a severe reactive process which leads to the formation of cellular membranes on the surface of the retina and in the vitreous. We determined the fibroblast growth-promoting activity of intraocular fluid from patients suffering from proliferative vitreoretinopathy, retinal detachment or cataract and further evaluated the effect of acetylsalicylic acid on growth-stimulated fibroblasts. The results demonstrated a significant enhancement of growth-promoting activity of intraocular fluid in proliferative vitreoretinopathy as compared to that of control samples. We showed that the augmented growth-promoting activity of intraocular fluid in proliferative vitreoretinopathy was significantly antagonized by inhibition of cyclooxygenase with acetylsalicylic acid (ID50 approximately 5 microM). In contrast, no significant effect was seen in corresponding control experiments. The findings suggest that metabolites of the cyclooxygenase pathway are involved in the regulation of enhanced intraocular fluid-induced fibroblast proliferation in proliferative vitreoretinopathy and that acetylsalicylic acid might be useful as an antiproliferative agent in intraocular fibrogenesis.

Adult↗

Electrophysiological changes in juvenile diabetics without retinopathy.

Several components of the electroretinogram were studied in 31 juvenile diabetics and 15 age-matched normal controls. The diabetic group consisted of 18 patients without retinopathy and 13 with mild background retinopathy. Oscillatory potentials were measured at low-stimulation energies. Significantly reduced amplitudes and component-specific delayed peak implicit times were found in both diabetic groups compared with the data from the controls. Similar results were obtained in the photopic and scotopic electroretinogram. From these findings, we suggest that retinal dysfunction is already present in juvenile diabetics without photographic evidence of retinopathy after a mean duration of diabetes of 7 years.

Adolescent↗

[Treatment of diffuse diabetic macular edema].

Treatment of diabetic macular edema was discussed in the first report of the Early Treatment Diabetic Research Study in 1985. Since then, patients treated at Innsbruck University Eye Clinic have been given grid-pattern argon laser therapy. Between February 1986 and April 1987, 106 eyes of 82 patients with diffuse diabetic macular edema underwent argon blue-green coagulation at the center of the fundus, excluding the foveal avascular zone. Four weeks after laser treatment, visual acuity was improved in 76 eyes, unchanged in 36, and had deteriorated in two patients. Thirty-eight eyes were retreated one to three times for reduction of visual acuity.

Adult↗

[Treatment of atopic keratoconjunctivitis in childhood].

In recent years atopic keratoconjunctivitis has been diagnosed increasingly frequently in children and adolescents. At Innsbruck University Eye Clinic all the children suffering from this condition have so far been satisfactorily treated with therapeutic contact lenses and locally applied antibiotics and steroids.

Adolescent↗

[Double-blind study with cyclosporin A eyedrops in healthy probands].

Cyclosporin-A eye drops initiate an immunosuppression after corneal transplantation in rabbits as well as in humans, as experimental and clinical studies showed. A tolerance study with 12 volunteers (healthy and without any ophthalmological disease) was designed as a randomized double-blind study. Apart from two objectively slight intolerance reactions there were no side-effects. The use of these drops after corneal transplantation is discussed.

Adult↗

[Immunosuppression with cyclosporin A in high-risk keratoplasties].

It is generally accepted that corneal grafts in hypervascular and sclerosed host corneas have little chance of success. At the end of a three-month postoperative immunosuppression period using the new immunosuppressant Cyclosporin A, full incorporation of transplants was achieved in 10 out of 11 high-risk patients. Patients were observed over a period of between 3 and 15 months, the median being 9 months.

Corneal Diseases↗

Autoradiographic analysis of binding sites for 125I-Bolton-Hunter-substance P in the human eye.

Substance P is known to exert potent effects in peripheral tissues, and is thought to be important for ocular function. The mechanism of action of substance P in the human eye is not known. As a basis for biochemical characterization specific binding of 125I-Bolton-Hunter-substance P was demonstrated in the human eye using autoradiographic methods. Biochemical characterization on slide-mounted tissue preparations showed that binding was saturable with a KD of 0.27 +/- 0.1 nmol/l. Specific binding occurred at comparable autoradiographic densities to both human retina and choroid. Substance P and its carboxyterminal fragment, substance P(3-11), were shown to be highly potent in binding competition experiments against 125I-Bolton-Hunter-substance P. Similar concentrations of substance P(1-9), neurokinin A and neurokinin B failed to significantly alter specific binding of 125I-Bolton-Hunter-substance P. The results indicate expression of high affinity substance P binding sites in human retina and choroid.

Autoradiography↗

Elevated levels of substance P in intraocular fluid in proliferative vitreoretinopathy.

Proliferative vitreoretinopathy is the most common reason for failure in retinal reattachment surgery. Since both substance P (SP) and SP receptors were found to be present in the human eye, and as pharmacological studies suggest an importance of SP for ocular functions, we investigated intraocular fluids for the presence of SP in eyes elected for cataract surgery, retinal detachment surgery and retina surgery for severe proliferative vitreoretinopathy (PVR) as well as in eyes with proliferative diabetic retinopathy (PDR). High performance liquid chromatography and radioimmunoassay (RIA) for SP immunoreactivities were performed. The SP mean concentration in intraocular fluid (IOF) of patients for cataract surgery (CS) was 2.2 fmol/ml, for retinal detachment (RD) was 2.7 fmol/ml and for PDR was 1.9 fmol/ml; significantly higher levels (mean concentration of 26.9 fmol/ml) were measured in eyes with PVR. HPLC analysis revealed two immunoreactive peaks coeluting with synthetic SP and SP-sulfoxide, indicating that RIA values represent authentic SP. We conclude that SP may play an important role in PVR. Since SP antagonists are known to inhibit a variety of SP effects in the eye, there might be a useful tool to reveal the importance of SP in this disease and, in this instance, a new possible treatment.

Adult↗