Search PubMed⌕ Search

Biomedical subjects

B Kirchhof

Publications and source records attributed to B Kirchhof.

At least 37 records · Page 2Linked to original sources
PubMed2001

Leukocyte-mediated endothelial cell injury and death in the diabetic retina.

Endothelial cell death is a hallmark of diabetic retinopathy. Its occurrence is required for the formation of acellular (devitalized) capillaries, lesions that produce irreversible retinal ischemia through their inability to support blood flow. The mechanisms underlying diabetic retinal endothelial cell injury and death remain largely unknown. The current study demonstrates that adherent leukocytes are temporally and spatially associated with retinal endothelial cell injury and death within 1 week of streptozotocin-induced experimental diabetes in rats. Moreover, the antibody-based neutralization of intercellular adhesion molecule-1 and CD18 is shown to prevent both leukocyte adhesion and retinal endothelial cell injury and death. These data highlight the central and causal role of adherent leukocytes in the pathogenesis of diabetic retinopathy. They also underscore the potential utility of anti-intercellular adhesion molecule1- and anti-CD18-based therapies in the treatment of diabetic retinopathy, a newly recognized inflammatory disease.

Animals↗
PubMed2001

Solitary peripapillary hemangioblastoma. A histopathological case report.

PURPOSE: Hemangioblastomas are highly vascularized tumors of not well-defined histological origin. They are the most frequent manifestation of the von-Hippel-Lindau (VHL) disease, but also occur as sporadic non-hereditary tumors. Much has been learned in the recent past about the genetic background, however, the cellular origin of the tumor is still not resolved. METHODS: We report a rare case of sporadic peripapillary hemangioblastoma in a 58-year-old patient. RESULTS: Histological examination demonstrated a highly vascularized tumor with intercapillary stromal cells. The tumor did not invade the adjacent tissues. Surrounding retinal areas showed cystic and gliotic changes. Immunohistochemistry was unable to prove neuroglial origin of the stromal cells. CONCLUSION: Histological findings show similarities to the findings in cerebral hemangioblastomas. The tumor location in this case together with the known response of glial cells to VHL, might indicate their involvement in the pathogenesis of hemangioblastoma.

Eye Enucleation↗
PubMed2001

Inhibition of inflammatory corneal angiogenesis by TNP-470.

PURPOSE: To determine the efficacy of the angiogenic inhibitor TNP-470 on inflammatory corneal neovascularization. Topical and systemic delivery of the drug were investigated in a murine model as well as inhibition of endothelial cell proliferation in vitro and in vivo. METHODS: The effect of TNP-470 on VEGF- and bFGF-stimulated bovine capillary endothelial (BCE) cell proliferation was evaluated in vitro. Corneal neovascularization was induced in vivo by mechanical debridement of the corneal and limbal epithelium with 0.15 M NaOH on C57BL6 mice. TNP-470 was administered systemically at 30 mg/kg body weight (BW) every other day or topically three times daily in a concentration of 5 ng/ml dissolved in methylcellulose. Vessel length was investigated on day 7. VEGF protein content in murine corneas was analyzed by ELISA on days 2, 4, and 7 of treatment. A modified bromouridine (BrdU) ELISA was used to quantify endothelial cell proliferation. RESULTS: TNP-470 exerted a dose-dependent inhibition of bFGF- and VEGF-induced endothelial cell proliferation in vitro. Both systemic and topical application of TNP-470 led to a significant reduction of inflammatory corneal neovascularization (P < 1 x 10(-5)). BrdU labeling showed that TNP-470 inhibited endothelial cell proliferation. VEGF protein levels were reduced by systemic TNP-470 treatment. CONCLUSIONS: These results suggest that TNP-470 reduces inflammatory corneal angiogenesis by directly inhibiting endothelial cell proliferation. Topical and systemic treatment with TNP-470 reduces VEGF levels that are responsible for vessel growth during the neovascularization process.

Administration, Topical↗
PubMed2001

In vivo retinal gene expression in early diabetes.

PURPOSE: Studies have demonstrated a causal role for specific molecules in the pathogenesis of diabetic retinopathy. Among the implicated mediators are growth factors such as vascular endothelial growth factor (VEGF) as well as adhesion molecules and proliferation- and apoptosis-related genes. However, a coordinated large-scale investigation of gene expression in the diabetic retina has not yet been reported. Here the retinal gene expression profile of diabetic and nondiabetic animals using cDNA microarrays were analyzed and compared. METHODS: Long-Evans rats were made diabetic with streptozotocin. Retinal gene expression was analyzed over 3 weeks using high-density nylon filter-based cDNA arrays. Genes were sorted into clusters according to their temporal expression profiles. They were also grouped according to their potential pathophysiological significance. The in vivo gene expression profiles of selected genes were verified via RNase protection assay. RESULTS: The rat GeneFilter contains a total of 5147 genes, of which 1691 are known genes and 3456 are expressed sequence tags (ESTs). On day 3, the expression of 27 known genes was increased by more than twofold. On days 7 and 21, the corresponding numbers were 60 and 12, respectively. A transient upregulation (>2-fold) in expression was seen in 627 of 5147 total genes. A subset of 926 genes exhibited a modest (<2-fold) decrease in expression. No genes showed a greater than twofold decrease in expression. Overall, the identity of the genes that were upregulated suggests that the response of the retina to the diabetic challenge contains an inflammatory component. Moreover, most regulatory activity occurs during the first week of diabetes. CONCLUSIONS: The development of a rational therapy for diabetic retinopathy will be assisted by detailed knowledge regarding the molecular pathophysiology of the disease. Here, an expression profile of an underlying retinal inflammatory process in early diabetes was extracted. Beyond providing insight into the general nature of the response to a pathogenic challenge, gene expression profiling may also allow the efficient identification of potential drug targets and markers for monitoring the course of disease.

Animals↗
PubMed2000

Treatment of corneal neovascularization with dietary isoflavonoids and flavonoids.

The purpose of this study was to investigate the use of dietary isoflavonoids and flavonoids for the treatment of ocular neovascularization. Corneal blood vessels were induced by intrastromal implantation of pellets containing bFGF. Isoflavonoids and flavonoids (Genistein, Fisetin and Luteolin) were dissolved in a microemulsion to increase bioavailability and applied topically in concentrations between 0.5 and 1 ng ml(-1). Corneal neovascularization was quantified under the microscope. In comparison to control eyes, all three substances significantly inhibited corneal neovascularization (P < or = 0.05). Fisetin had the strongest effect followed by Genistein and Luteolin. No significant topical side effects were observed. We concluded that the isoflavonoid Genistein and two structurally related flavonoids are potent inhibitors of corneal angiogenesis in vivo. The wide distribution of the flavonoids in the plant kingdom together with the presented results suggests that flavonoids may contribute to the preventive effect of a plant-based diet on neovascular disease of the eye.

Administration, Topical↗
PubMed2000

Iris pigment epithelial cell translocation in exudative age-related macular degeneration. A pilot study in patients.

BACKGROUND: This prospective, non-controlled pilot study investigates the practicability of IPE translocation and functional outcome in ARMD patients. Removal of submacular choroidal neovascularization (CNV) in age-related macular degeneration (ARMD) is usually associated with RPE damage and poor visual prognosis. Homologous RPE transplants fail to preserve macular function, possibly due to immune rejection. Instead of homologous RPE, we suggest translocating autologous iris pigment epithelium (IPE), building on earlier evidence from animal and in vitro investigations that IPE can substitute RPE functions in the experimental animal. Immunological cell rejection is avoided. METHODS: Four eyes with well-defined and eight eyes with ill-defined subfoveal CNV were submitted to operation and followed up for a minimum of 6 months. IPE cells were harvested from a peripheral iridectomy. A vitrectomy was performed. Submacular membranes were removed, and isolated IPE cells were injected into the subretinal space. Examinations included ETDRS visual acuity, fluorescein angiography, and SLO microperimetry. RESULTS: All patients underwent successful surgical removal of CNV and subretinal IPE injection. Compared to preoperative visual acuity (20/400-20/100) no significant change was observed after 6 months (20/320-16/80). A change of more than two ETDRS chart lines was defined as significant. One eye with preoperative ill-defined CNV developed a recurrence, leading to reduced visual acuity. In all patients, postoperative fluorescence angiography revealed early hyperfluorescence (window defect) in the surgically denuded area. Central fixation was demonstrated in 50% of eyes. CONCLUSIONS: Preliminary data suggests that IPE translocation in submacular surgery for ARMD can preserve but not improve preoperative visual acuity over 6 months. Functional results are promising compared to submacular membrane extraction alone and RPE transplantation. Continued research on improvement of IPE translocation seems justified.

Aged↗
PubMed2000

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↗
PubMed2000

Silicone oil removal from a silicone intraocular lens with perfluorohexyloctane.

Silicone oil can be easily dissolved in vivo from silicone intraocular lenses by perfluorohexyloctane. Using specular microscopy, we examined the corneal endothelium in a patient with silicone lens implantation immediately after cataract surgery and 5 weeks postoperatively. There were no signs of acute or chronic toxicity to the endothelium.

Cataract Extraction↗
PubMed2000

Aachen-Keratoprosthesis as temporary implant. Case report on first clinical application.

BACKGROUND: The Aachen-Keratoprosthesis was designed to serve as a permanent keratoprosthesis, modeling natural corneal physical properties as closely as possible. Prior to permanent application in patients, keratoprostheses are commonly tested in animal models to assess biochemical and biomechanical compatibility. However, immune and inflammatory responses acquired through animal experimentation are difficult to extrapolate in order to develop a predictable and generalized outcome in humans. Therefore, this preliminary report includes results following a temporary implantation of the Aachen-Keratoprosthesis in a patient during vitreoretinal surgery to assess the long-term prospect of application as a permanent artificial cornea. PATIENT AND METHODS: A 43 year old man presented with a ruptured right eye resulting in an opaque cornea and retinal detachment. A soft silicone rubber keratoprosthesis, the Aachen-Keratoprosthesis, was temporarily implanted. Subretinal membranes were removed and the total retinal detachment was reattached. Liquid perfluorocarbon and silicone oil were used. The temporary keratoprosthesis was replaced by a 7 mm corneal graft after completion of surgery. RESULTS: The Aachen-Keratoprosthesis was securely positioned into the trephined hole. It allowed complete visualisation of vitreous, retina and thus controlled manipulations in the vitreous cavity up to the extreme periphery. Leakage across the trephination-prosthesis interface was minimal. CONCLUSION: We report the first temporary application of an innovative keratoprosthesis. Its flexibility and good optical qualities allow visualisation and control of intraoperative procedures. This temporary pilot study of the Aachen KPro encourages further investigation of the Aachen KPro as a permanent replacement for a diseased cornea.

Adult↗
PubMed2000

New approaches in the management of choroidal neovascular membrane in age-related macular degeneration.

Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly population. The prevalence is reported to be 1.2-1.4% in several population-based epidemiological studies. Currently 25-30 million people worldwide are blind due to AMD. With the aging world population it is bound to increase significantly, and could become a significant public health problem in next two decades, with serious socio-economic implications. Several strategies are today available to treat the wet form of AMD, which is responsible for significant visual loss. These were until recently confined to laser photocoagulation, and subretinal surgery, but today two other modalities, namely, radiation and photodynamic therapy, are available. These treatment modalities however, are aimed at preservation of vision only, and not at reversing the process of the disease. Further research on antiangiogenic drugs and gene therapy could significantly help AMD patients.

Blindness↗
PubMed1999

Macular translocation for surgical management of subfoveal choroidal neovascularizations in patients with AMD: first results.

BACKGROUND: At present no satisfying treatment for subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) is available. Visual results after successful surgical removal of subfoveal CNV are disappointing. This has been explained by a primary dysfunction of the retinal pigment epithelium (RPE) in the macular region and the surgical trauma to the RPE in patients with AMD. Therefore, Machemer and Steinhorst developed a technique for macular translocation after surgical removal of subfoveal CNV. We report our first experiences with this technique in patients with subfoveal CNV secondary to AMD. METHODS: Seven patients aged between 71 and 83 years with subfoveal CNV were included in the study. Visual acuity of the fellow eyes was below 20/400. All patients underwent pars plana vitrectomy. Retinal detachment was produced by subretinal infusion of balanced salt solution and a 360 degrees retinotomy at the base of the vitreous was performed. After removal of the CNV, retinal rotation and reattachment, the retina bordering the retinotomy was coagulated with endolaser photocoagulation. Silicone oil was used as temporary tamponade. RESULTS: In all patients the subfoveal CNV was removed and the macula was translocated by a 15 degrees-45 degrees rotation onto functional RPE. The mean duration of follow-up was 11 +/- 3 months. Initial visual acuity ranged from 20/80 to hand movements. Final visual acuity was 20/100 to 20/400. Initially all patients complained of tilted vision. During follow-up the rotation of the image regressed and was well tolerated by all patients. Complications included the development of retinal detachment in three patients after silicone oil removal, development of a macula pucker, and a significant increase of lens opacity in the phakic eyes. CONCLUSION: In our series rapid improvement of visual function was observed in one patient only, even if the macula appeared ophthalmoscopically and angiographically normal. Vitreoretinal complications occurred frequently during follow-up.

Aged↗
PubMed1999

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↗
PubMed1999

Effect of thalidomide and structurally related compounds on corneal angiogenesis is comparable to their teratological potency.

Neovascular diseases are the leading causes of blindness in humans. Although several promising compounds have been isolated, pharmacological treatment remains difficult. Thalidomide has inhibitory effects on angiogenesis in the corneal micropocket assay. However, the results vary considerably depending on the administration route and animal model. The aim of this study, therefore, was to investigate thalidomide and two of its derivatives, supidimide and EM12, in the rabbit corneal micropocket assay. Using both basic fibroblast growth factor and vascular endothelial growth factor for initiation of the neovascular response, we were able to show a significant inhibition of neovascularisation with all three substances. EM12, the most teratogenic derivative analysed, was demonstrated to be the most potent inhibitor of angiogenesis in this model. Thalidomide and supidimide did not show systemic side effects in the applied dosage. An equal dosage of EM12, however, resulted in significant weight loss of the animals, but did not increase angiogenic activity compared with lower doses. Together with earlier findings, these data support a strong correlation between the antiangiogenic potential and the teratogenic activity of thalidomide and structurally related compounds.

Administration, Oral↗
PubMed1999

Corneal biopsy in keratitis performed with the microtrephine.

BACKGROUND: The aetiology of most cases of keratitis remains unclear because the causative agents respond to broad-spectrum antibiotics. Problems occur when they become resistant to local therapies. Further diagnostic measures such as corneal scrapings or biopsies are then necessary. In order to ensure early and gentle biopsy followed by effective diagnosis within 24 h, corneal biopsy specimens were obtained with a microtrephine. PATIENTS AND METHODS: Microbiopsies were obtained from 28 patients suffering from corneal infiltrates or ulcerative keratitis. Different stainings were used to identify the pathogens. Photographs of the clinical healing process were taken immediately after biopsy and during the follow-up. RESULTS: One hundred and ten microbiopsies were performed. One hundred and eighteen specimens could be obtained. No perforation occurred. In 5 of 10 cases in which herpetic keratitis was predicted, herpes DNA could be confirmed. The other five cases were found to be caused by other microbes. In 15 of 18 cases, the bacterial pathogen could be confirmed by Gram's stain diagnosis after microtrephination. Corneal smear was positive in only 7 of these cases. In 2 of 6 cases, predicted to be caused by fungi, lactophenol-blue staining of the microbiopsies showed positive results. Corneal smear was positive in only 1 of these 2 fungal cases. No intraoperative or postoperative complications occurred. No worsening of the disease as a result of treatment could be observed. CONCLUSIONS: The confirmation of microbial cause of keratitis is more effective using microbiopsy than with corneal smears. As a result of the effective treatment after biopsy diagnosis, the majority of cases of keratitis healed. Local therapy seems to have been optimised due to the unroofing of infection during biopsy as well. Therefore microbiopsy in combination with laboratory diagnosis may prove to be a very useful diagnostic and possibly therapeutic method in the clinical routine.

Animals↗
PubMed1999

Topical application of methotrexate for inhibition of corneal angiogenesis.

PURPOSE: Methotrexate (MTX) is a folic acid antagonist used in chemotherapy regimens. Additional therapeutic applications have been suggested based on effect as an immuno-modulating drug in systemic rheumatoid disease and associated uveitis. Since chronic inflammatory disease is often associated with a neovascular response, we investigated the use of MTX for treatment of corneal angiogenesis. METHODS: Neovascularizations were induced by fibroblast growth factor in a corneal pocket model. Vessels were examined biomicroscopically. MTX was applied topically to rabbit corneas in a concentration of 0.2 mg/day. MTX level was measured in aqueous humor and plasma. RESULTS: On day 9 the vascularized area was 12.0+/-6.9 mm(2) in control eyes and significantly smaller, 2. 2+/-1.86 mm(2), in treated eyes. Treated animals showed no local side effects such as epithelial defects. Although therapeutic levels were measured in the aqueous humor, MTX could not be detected in the serum of treated animals. CONCLUSION: The antiangiogenic mechanism of MTX might be due to inhibition of both macrophage invasion during early angiogenesis and endothelial cell proliferation. The high levels in the aqueous humor indicate a possible application of topical MTX for inflammations of the anterior segment of the eye.

Animals↗
PubMed1999

Perfluorohexyloctane as a long-term vitreous tamponade in the experimental animal. Experimental perfluorohexyloctane substitution.

BACKGROUND: Perfluorocarbon liquids are established tools for intraoperative hydrokinetic retinal manipulation. Because of their high specific gravity, however, they may well cause mechanical damage to the retina when applied as a long-term vitreous substitute. Perfluorohexyloctane, a semi-fluorinated liquid fluorocarbon of low specific gravity (1.35 g/cm3), was developed as a long-term vitreous substitute. The current study was performed to investigate intraocular tolerance to perfluorohexyloctane as a long-term vitreous substitute in the experimental animal. METHODS: 34 vitrectomised eyes of pigmented rabbits underwent intravitreal injection of 1.0-1.2 ml perfluorohexyloctane or balanced salt solution. In 5 eyes the anterior chamber was filled. During the follow-up period of 3 months, the eyes were examined by slit lamp biomicroscopy, by fluorescein angiography and by electroretinography. The eyes were then enucleated and processed for light- and electron microscopy. RESULTS: Perfluorohexyloctane depicted dispersion beginning between the first and third week. Over a period of 9 weeks no toxic effect on retina, lens and cornea was noticed. At 14 weeks ERG showed a slight decrease in amplitude and early morphological changes in the retina. CONCLUSION: Our findings suggest that perfluorohexyloctane is tolerated in the rabbit eye for 9 weeks. Since avascular rabbit retina is more susceptible to mechanical and toxic damage than vascularized primate retina, we suggest proceeding from here, and investigating tolerance and quality of tamponade of perfluorohexyl octane in man for up to 9 weeks.

Animals↗
PubMed1999

[Radiation therapy of occult choroidal neovascularisation (CNV) in age-related macular degeneration (AMD)].

BACKGROUND: Occult choroidal neovascularisation secondary to age-related macular degeneration cause severe visual loss due to exsudation, hemorrhage and fibrovascular scarring. So far, no efficient treatment of this condition could be established. Recently, some publications described an improved prognosis after low-dose radiation therapy of the neovascular membranes. PATIENTS AND METHODS: Patients with occult choroidal neovascularisation as defined by the Macular Photocoagulation Study were inclosed in our study. Irradiation with Photons (10 to 12 MeV) in fractions of 5 x 2 Gy were administered. At three-month follow-up intervals visual acuity a complete ophthalmological examination including visual acuity, fluorescein- and ICG-angiography as well as fundus photography was performed. RESULTS: In our study 64 patients (74 +/- 7 years) with occult CNV secondary to AMD were included. Follow-up was between 3 and 39 months (14.5 +/- 10). Compared to studies who investigated the natural history of this disease, the visual acuity measured in our study did not differ significantly from the natural course. CONCLUSIONS: Our results do not support the general use of radiation therapy in patients with occult choroidal neovascularisation secondary to AMD. However, the controlled multicenter studies might provide a better basis for a general recommendations.

Aged↗