[Opacification of a hydrophilic intraocular lens 4 years after cataract surgery. A biomaterial analysis]. / Eintrübung einer hydrophilen Intraokularlinse 4 Jahre nach Kataraktoperation. Eine Biomaterialanalyse.

Calcification of hydrophilic intraocular lenses (IOL) is a rare complication. We report about the uneventful replacement of an opacified hydrophilic IOL. The patient presented 4 years after uneventful cataract surgery with a reduction of visual acuity due to calcification of the IOL. Macroscopically, the optic and the haptics were opacified. Light and scanning electron microscopy revealed granular deposits on the external surface of the IOL and numerous fine granular deposits within the optic of the IOL which were distributed in a line parallel to the surface of the IOL.

Serum levels of adiponectin are associated with diabetic retinopathy and with adiponectin gene mutations in Caucasian patients with diabetes mellitus type 2.

INTRODUCTION: Even diabetic patients with excellent glycemic control can develop diabetic complications very early. Possibly, not only the degree of glycemic control, but other factors as well are responsible for the development of diabetic microangiopathy. Since adiponectin represents an adipocyte-specific secretory protein modulating endothelial cell functions, it was the aim of the present study to investigate the role of adiponectin serum levels as well as adiponectin gene polymorphisms in the development of diabetic retinopathy. METHODS: A population based cohort of caucasian patients (n=523) with type 2 diabetes mellitus was recruited from an epidemiological field survey. Serum adiponectin levels were determined by ELISA. Genotypes of the Tyr111His and the Gly15Gly polymorphism were determined by PCR-based RFLP analysis. Diabetic retinopathy was graded by fundus photography. RESULTS: The data demonstrate, that a) the Tyr111His (T-->C) polymorphism influences adiponectin serum levels, b) adiponectin serum levels do correlate with the prevalence of diabetic retinopathy, and c) patients heterozygous for the +45 T-->G (Gly15Gly) polymorphism show a lower prevalence of diabetic retinopathy. Furthermore, we could generate the proof of principle that adiponectin is detectable in the fluid of the human vitreous body. SUMMARY: Adiponectin gene polymorphisms influence adiponectin serum levels and elevated adiponectin serum levels are associated with diabetic retinopathy in patients with diabetes mellitus type 2. Therefore, endothelial cell modulating adiponectin should be further investigated as a candidate gene in the development and progression of retinopathy associated with type 2 diabetes mellitus.

Trabecular meshwork bypass tube shunt: initial case series.

AIMS: This study describes a prospective consecutive case series of the initial six eyes of five patients undergoing implantation of the trabecular bypass tube shunt. METHODS: A prospective consecutive case series. The initial six eyes of five patients with uncontrolled open angle glaucoma who had never previously undergone ocular surgery. Implantation of the trabecular bypass tube shunt measuring 150 micro m outer diameter and 50 micro m inner diameter was performed with the distal end placed in Schlemm's canal and the proximal end in the anterior chamber. The main outcome measures were visual acuity, intraocular pressure, glaucoma medication use. RESULTS: The tube was successfully implanted in five of six eyes. In four eyes longer term follow up of 5-9 months showed no loss of visual acuity with decreased intraocular pressure from preoperative levels (mean 23.4-16.5 mm Hg) and reduced requirement of glaucoma medications (mean 3-0.5). In a subset of two eyes, there was no measured increase in aqueous flare or reduction of endothelial cell count. In one eye the tube was explanted because of presumed misplacement by excessive bleeding during surgery. Two eyes showed a diffuse bleb. CONCLUSIONS: This study reports the initial experience with a novel approach to surgical glaucoma therapy. This very small tube allows a direct communication to be established between the anterior chamber and Schlemm's canal, effecting a trabecular bypass. In this small number of eyes this procedure reduced intraocular pressure and the need for glaucoma medications without appreciable side effects.

New substances for intraocular tamponades: perfluorocarbon liquids, hydrofluorocarbon liquids and hydrofluorocarbon-oligomers in vitreoretinal surgery.

UNLABELLED: Perfluorocarbon liquids (PFCLs) and heavy fluorocarbon liquids (HFCLs) are being increasingly used as soft tools during vitreoretinal surgery. However, since long-term intraocular tolerance is still unsatisfactory, at present complete removal at the end of surgery is recommended. With the aim to improve long-term intraocular compatibility and to enlarge the spectrum of clinical applications, modified HFCLs have been developed. HFCL-oligomers with a higher viscosity represent the latest perspective. All three groups of fluorocarbon liquids will be compared with respect to their physical and chemical properties, experimental and clinical results, and prospects for clinical applications. Common features of PFCLs, HFCLs and HFCL-oligomers are biological inertness, specific gravity higher than water, immiscibility with water or blood, and a high gas binding capacity. In PFCLs such as decalin, octane, or phenanthrene. All carbon atoms of the carbon backbone are completely fluorinated. In experimental and clinical use, emulsification, vascular changes and structural alterations of the retina have been described. By only partial replacement of hydrogen atoms by fluorine, the specific gravity of HFCLs is reduced, whereas lipophilic properties increase. Thus HFCLs are potential solvents for intraocular silicone oil remnants. However. after long-term application, side-effects are similar to those observed with PFCLs. Substances of this group, such as F6H6, F6H8, 044, and 062 are used intraoperatively and are currently being investigated for clinical long-term application. With the aim to avoid emulsification and to improve intraocular tolerance, we have developed HFCL-oligomers consisting of 2-4 HFCL molecules with increased viscosity. The oligomers were tolerated well in rabbit eyes for up to 4 months. In contrast to PFCLs or monomers, they did not emulsify nor show vascular alterations. ERGs returned to normal after removal of the oligomer from the eye. Histology of the retina showed mild alterations. CONCLUSION: according to physical properties, experimental intraocular compatibility and stability against emulsification, HFCL-oligomers are promising candidates for improved long-term tamponade of the lower retina. At present, indications for an application in human eyes have to be determined in clinical trials.

Ocular toxicity study of trypan blue injected into the vitreous cavity of rabbit eyes.

BACKGROUND: To evaluate the ocular toxicity of trypan blue (TB) injected into the vitreous cavity of rabbit eyes. TB is a dye that could be useful for staining epiretinal membranes during vitrectomy surgery. METHODS: Ten New Zealand White (NZW) rabbits underwent gas-compression vitrectomy. Rabbits were divided into three groups to receive injections of 0.1 ml basic salt solution, 0.1 ml of a 0.06% TB solution or 0.1 ml of a 0.2% TB solution. Ocular toxicity was assessed by slit-lamp biomicroscopy, ophthalmoscopy, electroretinography and histology. RESULTS: Transient posterior capsule opacification was noted in all animals. No significant reductions in a-wave or b-wave amplitudes were found in any of the animals. Light and electron microscopic examination of the inferior retina in the 0.2% TB-treated eyes showed damaged photoreceptors and marked disorganization. Immunohistochemical staining for rhodopsin was strongly reduced in those sections and staining for proliferation with Ki-67 was positive. No histological abnormalities were found in the upper retina of the 0.2% TB-treated eyes or in any part of the retina of the 0.06% TB-treated or control eyes. No histological abnormalities were found in any of the anterior chamber angle specimens. CONCLUSIONS: Although no signs of toxicity were found after the prolonged presence of TB at a concentration of 0.06% in the vitreous cavity of rabbit eyes, marked damage occurred in the lower retina of 0.2% TB-treated eyes. The short-term presence of TB at a concentration of 0.06% in the vitreous cavity is harmless to the rabbit eye but a higher concentration of TB could be unsafe.

Combined use of partially fluorinated alkanes, perfluorocarbon liquids and silicone oil: an experimental study.

BACKGROUND: Partially fluorinated alkanes (FALKs) are a new class of substances which can be used in vitreoretinal surgery as an intraoperative tool and as a long-term tamponade. The aim of this in vitro study was (1) to investigate the solubility of FALKs in silicone oil during direct exchange, (2) to study their combined use and solubility in PFCLs, (3) to evaluate their lipophilic properties and (4) to investigate the possibility of preparing "heavy silicone oil". METHODS: (1) Four different FALKs (F6H6, F6H8, O44 and O62) were directly exchanged with silicone oil (5,000 mPas). The dissolved amount of fluorocarbons in the removed silicone oil was determined by gas chromatography and by gravimetry. Furthermore, the diffusion phenomena during the exchange process were studied. (2) The behaviour of FALKs in PFCLs was investigated and the solubility of the resulting mixtures in silicone oil was measured. (3) The solubility of FALKs and PFCLs in native olive oil was analysed. (4) Different FALKs were added to silicone oil and measurements of the resulting specific gravity and the viscosity were performed. RESULTS: (1) FALKs dissolved in silicone oil up to the following values: F6H6=45 m%, F6H8=54 m%, 044=100 m%, O62=18 m%. (2) FALKs dissolved in PFCL, thereby changing the physicochemical properties of PFCL depending on the type of FALK and ratio used. (3) The lipophilic properties of FALKs and PFCLs could be characterized by their dissolution in native olive oil (F6H8=23.4 m%, 044=16.7 m%, F6H6=12.3 m%, 062=5.3 m%, PFD=1.1 m%, PFO=0.6 m%). (4) It was possible to prepare "heavy silicone oil" e.g. by adding 30 vol% F6H8, resulting in a specific gravity of 1.08 g/ml, or by adding 80 vol% 044, resulting in a specific gravity of 1.25 g/ml, but decreasing the viscosity of the mixtures dramatically. CONCLUSION: (1) If FALKs are used as an intraoperative tool, a direct exchange with silicone oil should be avoided owing to their capacity to dissolve in silicone oil, resulting in a mixture with unpredictable properties. (2) A combined use with PFCLs and silicone oil is possible, if the right ratio is chosen. (3) The solubility of FALKs in native olive oil may be an indicator for their tissue penetration and may render feasible their use as a long-term tamponade. (3) "Heavy silicone oil" preparation using FALKs is possible, but the mixture needs further evaluation in terms of emulsification, mobilization of oligosiloxanes, tissue penetration and long-term stability.

[Subretinal microphotodiode array as replacement for degenerated photoreceptors?]. / Subretinales Mikrophotodioden-Array als Ersatz für degenerierte Photorezeptoren?

A survey is given on the status of developments, concerning a subretinal electronic microphotodiode array that aims at replacing degenerated photoreceptors. Various prototypes have been developed, tested, and implanted in various experimental animals up to 18 months. The fact that electrical responses were recorded from the visual cortex of pigs after electrical stimulation by subretinal electrodes and the fact that responses are also recorded in-vitro in degenerated rat retinae, shows the feasibility of this approach. However, there are a number of open questions concerning the biocompatibility, the long-time stability, and the type of transmitted image to be solved before application in patients can be considered.

[Implant in Schlemm's canal. A new method for regulating intraocular pressure in patients with primary open-angle glaucoma?]. / Implantat in den Schlemm-Kanal. Eine neue Methode, den intraokularen Druck bei Patienten mit primärem Offenwinkelglaukom zu regulieren?

BACKGROUND: A surgical technique was developed using a Schlemm's canal implant to bypass the obstruction of outflow of the juxtacanalicular trabecular meshwork in patients with primary open-angle glaucoma. The implant device should also bridge healing processes after trabeculotomy and laser techniques. PATIENTS AND METHODS: An 8- to 15-mm-long silicone tube was implanted in each of two human autopsy eyes connecting the anterior chamber directly with Schlemm's canal. Serial sectioning was performed at two sections of 1-mm length. RESULTS: Implantation of the tube was technically uneventful. Histological examination showed no evidence of mechanical disruption of the endothelial lining of the inner wall of Schlemm's canal. CONCLUSION: These preliminary results demonstrate the possibility of shunting aqueous directly into Schlemm's canal using a silicone tube. A clinical study in a selected group of patients is planned.

Studies on the feasibility of a subretinal visual prosthesis: data from Yucatan micropig and rabbit.

BACKGROUND: To estimate the feasibility of the subretinal concept of a visual prosthesis, animal models and prototypes, each representing a certain aspect of the final prosthesis, were utilised to test for requirements for such a medical device: (1) the ability to elicit--by electrical stimulation--event-related central activity in the central visual system, and (2) the long-term biocompatibility and biostability of the implant within the subretinal space. METHODS: (1) In rabbit and Yucatan minipig, cortical evoked potentials were recorded with chronically implanted epidural electrodes during stimulation with light flashes as well as during electrical stimulation in the subretinal space. Voltage pulses ranging from -3 V to +3 V were applied via an acutely implanted electrode array on a wired prototype. (2) For biocompatibility studies a silicon-based micro-photodiode array (MPDA) was used that closely resembled the design and composition of the final prosthesis. Fourteen months after implantation, angiography was performed and the histological findings of the retina in the immediate vicinity of the implant were evaluated. RESULTS: (1) In both rabbit and minipig, subretinal electrical stimulation resulted in evoked cortical potentials that were comparable to visual evoked potentials. The lowest threshold levels for the subretinal stimulation were 0.6 V for rabbits and 2 V for minipigs. (2) Long-term stability of an implanted MPDA and its biocompatibility were proven for a postoperative period of 14 months. CONCLUSIONS: Data from animal experiments with certain prototypes of the final prosthesis suggest the feasibility of the concept of a subretinal visual prosthesis: Both requirements were met: (1) the functioning of the subretinal stimulation and (2) the biocompatibility of the MPDA implant.

Epinephrine, but not dexamethasone, induces apoptosis in retinal pigment epithelium cells in vitro: possible implications on the pathogenesis of central serous chorioretinopathy.

BACKGROUND: The pathogenesis of central serous chorioretinopathy is poorly understood. It is believed to be due to dysfunction of the retinal pigment epithelium and/or choroid and has been associated with elevated levels of epinephrine and administration of corticosteroids. Epinephrine and corticosteroids have previously been shown to induce apoptosis (programmed cell death) in various types of cells. The objective of this study was to investigate whether these agents can induce apoptosis in cultured retinal pigment epithelium cells. This may help elucidate the pathogenesis of central serous chorioretinopathy. METHODS: Third-passage porcine retinal pigment epithelium cells were grown to confluence and incubated for 1-7 days in culture medium containing epinephrine (10(2)-10(9) pg/ml) or a corticosteroid, dexamethasone (4-4x10(4) ng/ml). The cultures were evaluated for apoptosis by phase-contrast microscopy and in situ terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. RESULTS: Epinephrine (7x10(7)-10(9) pg/ml) induced apoptosis in a dose- and time-dependent manner. Exposure to lower concentrations of epinephrine (10(2)-6x10(7) pg/ml) and all tested levels of dexamethasone did not result in apoptosis. CONCLUSION: Retinal pigment epithelium cells may undergo apoptosis following exposure to elevated levels of epinephrine. These findings suggest a possible pathophysiologic mechanism for the development of central serous chorioretinopathy.

Polar application of test substances in an organotypic environment and under continuous medium flow: a new tissue-based test concept for a broad range of applications in pharmacotoxicology.

We have established a new test concept for in vitro pharmacological trials. Our model employs tissue explants to test compounds for toxicity which arises with the metabolic interactions among different cell types. Microsurgical preparation of tissue explants avoids the destruction of the organ-specific tissue architecture. Explants were mounted in tissue carriers to improve nutrition and handling of the sample. To allow for the omission of serum supplementation of the culture medium, explants were cultured under continuous medium flow. Test substances are applied considering the polar architecture of most tissues in vivo, for example, covering the apical aspect of epithelia. In principal, all tissues obtained from any species, including man, can be used in this system. A trial application was performed with vitreous body substitutes, substances used in ophthalmology. One compound had passed cell culture tests, but caused massive blood vessel deterioration in vivo. Using our test system based on the developing renal vessel system, we could confirm, within 24 hours, severe vessel damage which resembles the injury suffered by the rabbit retina. We demonstrate that an improved tissue culture assay is a suitable tool for the detection of toxicity that remained unidentified in cell culture tests.