Biomedical subjects

U Schmidt-Erfurth

Publications and source records attributed to U Schmidt-Erfurth.

At least 55 records · Page 3Linked to original sources

PubMed1997

Photodynamic targeting of human retinoblastoma cells using covalent low-density lipoprotein conjugates.

Combination of photosensitizers with carrier molecules has been shown to enhance the efficiency of photodynamic therapy (PDT). Owing to an increased expression of their receptors on some malignant and proliferating cells, low-density lipoproteins (LDLs) are potential endogenous carriers. A photosensitizer, chlorin e6 (Ce6), was covalently bound to LDL via carbodiimide activation. The Ce6-LDL conjugate was evaluated on a fibroblast cell line with defined LDL receptor expression and a retinoblastoma cell line (Y79). Uptake of free Ce6 and Ce6 either covalently bound to or complexed with LDL was measured by spectrofluorimetry. Phototoxicity after irradiation at 660 nm was determined by a mitochondrial activity assay (MTT). Covalent binding to LDL significantly increased the uptake of Ce6 for both cell lines by a factor of 4-5. A Ce6: LDL binding ratio of 50:1 was optimal. A receptor-mediated uptake was demonstrated by saturability and competitive inhibition by free LDL. Binding also occurred at 2 degrees C and was attributed to non-specific associations. Irradiation with 10 J cm-2 of 660 nm light after treatment of cells with Ce6-LDL conjugate reduced the MTT activity by 80%, while free or mixed Ce6 induced a maximum of 10% reduction in the MTT activity following identical treatment conditions. These data suggest that targeting of LDL receptor-bearing cells using covalently bound carriers, such as LDL, might increase the efficiency and selectivity of PDT. Intraocular tumours such as retinoblastomas could be appropriate targets for such an approach owing to the ease of access of light sources and the need for non-invasive approaches in sensitive ocular sites.

Carrier Proteins↗

PubMed1997

Mitomycin-C in laser sclerostomy: benefit and complications.

BACKGROUND AND OBJECTIVE: The authors studied the effect of topical mitomycin-C administration on the maintenance of filter function and intraocular pressure (IOP) following laser sclerostomy. PATIENTS AND METHODS: Twenty-six patients with a presumed high risk of episcleral scarring were treated intraoperatively with topical mitomycin-C (0.5 mg/ml) for 3 to 5 minutes. Their IOPs were monitored for at least 2 years. The IOP data of these patients were compared with the results for 46 patients who underwent the identical procedure without antimetabolite. RESULTS: IOPs below 23 mm Hg were achieved in 70% of the mitomycin-C-treated patients. Compared with the non-mitomycin-C group, the rate and duration of early postoperative hypotony was significantly increased in the mitomycin-C-treated group. CONCLUSION: Mitomycin-C is useful for maintaining successful filter function in patients with unfavorable prognoses. However, severe and persistent hypotony may occur.

Administration, Topical↗

PubMed1996

Benzoporphyrin-lipoprotein-mediated photodestruction of intraocular tumors.

Benzoporphyrin derivative (BPD), a sensitizer currently in clinical trials, was evaluated for the treatment of experimental Greene melanoma implanted in the rabbit iris. To improve tumor targeting, BPD was complexed with low-density lipoprotein (LDL) representing an endogenous carrier system for BPD as previously described. Twelve tumors were irradiated at a sensitizer dose of 2 mg kg-1 body weight using a dye laser at 692 nm. Tumor responses were documented by photography, angiography and light and electron microscopy. All tumors treated with 80 J cm-2 regressed irreversibly. The principal mechanism of tumor necrosis was thrombosis following disruption of endothelial membranes. Ultrastructure data suggested tumor cell damage, although evidence for this being the result of direct PDT-mediated tumor cell death was less clear. These data suggest that BPD-LDL may be used to improve the selectivity of photodynamic tumor therapy possibly by the increased uptake of lipoprotein-delivered sensitizer to neovascular endothelial cells.

Animals↗

PubMed1996

[Cyclophotocoagulation with the diode laser in contact procedure with a new focussing tip].

UNLABELLED: During contact cyclophotocoagulation (CPC) energy is transmitted through the conjunctiva and the sclera by direct contact of a plain fibre tip. Alteration and scarring of the conjunctiva and the outer parts of the sclera cannot always be avoided. We used a new fibre tip which defocuses the laser light on the conjunctiva and sclera and focuses the laser light on the ciliar body. The coupling and focusing medium between fibre and sclera is a small glass ball (3 mm diameter). METHODS: Up to now we have treated 52 human eyes of 35 patients affected by refractory glaucoma using a diode laser (Zeiss Visulas II) coupled with a 200-microns fibre and a 3-mm focusing ball tip. In all cases 20-40 spots were applied 1.5 mm posterior of the limbus, power varied between 1.5 and 2.2 W and exposure time was 1.5 s. RESULTS: In all cases the conjunctiva and the sclera was unaltered. The mean follow-up time was 224 days. The mean IOP values +/- SD before treatment and 6 days, 4 weeks and 1 year after treatment were 40.9 +/- 7.1, 19.3 +/- 7.9, 22.4 +/- 14.8 and 17.2 +/- 11.3 mmHg. No positive, linear correlation was found between number of spots and IOP drop after 6 days. There was considerable individual variance. The main complications were anterior fibrinous uveitis (10%), slight vitreous haemorrhage (2/52) and transitory hypotony (2/52). In one enucleated eye structural alterations to the pigmented and non-pigmented epithelial cells of the ciliary body were found histologically. CONCLUSIONS: Contact diode CPC can significantly reduce IOP, and the conjunctiva and sclera can be left totally unaltered by the focusing ball tip used in this study.

Aged↗

PubMed1996

[Follow-up of vitrectomy for central retinal detachment and optic disk pit].

BACKGROUND: The exact pathogenesis of central retinal detachment associated with optic disc pit is still unknown. Vitrectomy has proven to be the most effective therapy. PATIENTS AND METHODS: In two patients with macular detachment associated with optic disc pit, a pars-plana-vitrectomy with surgical posterior vitreous detachment and gastamponade was performed. We report on the interesting clinical course of these patients. RESULTS: After the gas bubble was absorbed, we observed a displacement of the subretinal fluid inferiorly in both patients. Schisislike changes persisted in the macular area. After several months the subretinal fluid resolved completely. CONCLUSION: The fluid displacement and the resolution-characteristics of the subretinal fluid after vitrectomy in cases of retinal detachment associated with optic disc pit are completely different from other rhegmatogenous retinal detachments. The gas bubble separates the central retinoschisis from the peripheral rhegmatogenous part. The reason for delayed resolution remains unclear. It may be due to tangential vitreous traction in the periphery.

Adult↗

PubMed1995

In vivo uptake of liposomal benzoporphyrin derivative and photothrombosis in experimental corneal neovascularization.

BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) has been used successfully to occlude neovascularizations experimentally. We evaluated the vasoocclusive potential of benzoporphyrin derivative (BPD), a new photosensitizer currently in clinical trials. Since liposomally formulated BPD strongly binds to endogenous low density lipoproteins (LDL) after i.v. injection, LDL act as carrier to deliver BPD preferentially to proliferating endothelial cells. STUDY DESIGN/MATERIALS AND METHODS: Corneal neovascularizations in rabbits were used as model. Time-dependent uptake and retention of liposomal BPD were measured in vivo by monitoring the laser-induced fluorescence (LIF). Photothrombosis was induced using a dye laser emitting at 692 nm. RESULTS: A maximal BPD concentration was measured at 60-90 minutes postinjection determining the optimal time interval for treatment. Exposures as low as 10 J/cm2 allowed complete and irreversible neovascular occlusion as documented angiographically. Histology revealed selective endothelial damage, adjacent corneal stroma, or iris vessels, remained intact. Identical results were obtained using BPD directly complexed with LDL suggesting use of a LDL-mediated pathway. CONCLUSION: We suggest BPD-PDT for a selective treatment of neovascular diseases.

Animals↗

PubMed1995

Development of a new Er: YAG laser conception for laser sclerostomy ab externo: experimental and first clinical results.

The erbium:YAG laser is a preferable energy source for laser sclerostomy ab externo due to the high absorption of its radiation (2940-nm wavelength) in the aqueous parts of scleral tissue. It has thus far been a disadvantage that laser energy has to be transmitted from the laser source to the application site via very susceptible special optical fibers (ZrF). As a consequence of technical improvements, the laser source could be integrated into the application probe. Therefore, only a robust quartz fiber was necessary for contact application. A fiber diameter of 400 microns was chosen according to the experience gained in previous studies. A total of 24 eyes with chronical open-angle glaucoma were treated. A fistula end-point detection unit was developed for safe indication of a full-thickness perforation of the sclera. With a fiber diameter of 400 microns, a postoperative success rate of about 54% was achieved at 6 months follow-up. The automated full-thickness perforation detection prevented the application of additional, surplus laser pulses in the anterior chamber. The postoperative success rate could be improved over that achieved in previous studies. The new device/conception offers more technical reliability and is a further step toward minimally invasive fistulating laser surgery of open-angle glaucoma.

Erbium↗

PubMed1995

[Progress in laser sclerotomy ab externo] Enlarging the sclerostomy channel and local mitomycin administration].

In a previous study we presented our first results after sclerostomy using a pulsed erbium/holmium: YAG laser. At a fiber diameter of 300 microns a success rate of 20-30% was found after a 1-year follow-up. This study concentrates on the improvement of the parameters for filter survival. METHODS. The fiber diameter and thus the size of the fistula increased to 400 microns. Patients who had undergone fibrosis for a previous fistula were treated intraoperatively with topical mitomycin administration. RESULTS. After a follow-up of 6 months, filter function in the 300 microns group was maintained in 26% of the treated eyes (n = 23), while 400 microns fistulas were successful in 48% (n = 26). In the mitomycin-treated group (n = 6), sclerostomy achieved an IOP regulation in four patients. Postoperative hypotony was more frequent, but did not exceed 2 weeks. CONCLUSION. An increase in fistula diameter improves the long-term results of laser sclerostomy. Mitomycin is useful in maintaining filter function in patients with an unfavorable prognosis.

Antibiotics, Antineoplastic↗

PubMed1995

Laser sclerostomy ab externo using two different infrared lasers: a clinical comparison.

This study was designed to compare the clinical results of an ab externo approach to laser sclerostomy using two different laser sources under identical conditions. A pulsed (200 microseconds) erbium-YAG laser (lambda = 2940 nm) and a pulsed (200 microseconds) holmium:YAG laser (lambda = 2120 nm) were used. The energy of each laser was transmitted via a fiber (300 microns in diameter) and applied near the limbus, with the fiber tip remaining in steady contact with the sclera. According to the higher tissue absorption coefficient, a shorter penetration depth and, therefore, fewer complications were expected for the Er:YAG laser. A total of 26 patients with advanced open-angle glaucoma were treated and followed for up to 6 months. In all cases a functioning fistula with a prominent filtering bleb and a marked reduction in the intraocular pressure (from up to 35 mm Hg to < 10 mm Hg) could be achieved primarily. The total energy required was about 4 times lower for erbium:YAG laser was compared with holmium:YAG laser sclerostomies. No complication occurred intraoperatively. Postoperatively, reversible adherence of the iris to the internal ostium was more frequently observed in Ho:YAG laser sclerostomies (60%) and small hyphemas were more often seen in Er:YAG laser sclerostomies (30%). After 6 months of follow-up, about 40% of the fistula remained patent in both groups. In principle, both lasers are suited to serve as energy sources for the described approach. Under the conditions of the present study, different levels of thermal effects did not cause any significant difference in the clinical success rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Vitreoretinal surgery in advanced Coat's disease.

Massive subretinal exudates as well as vitreal traction often induce complicated retinal detachments in patients with advanced Coats' disease. If left untreated, most patients experience secondary glaucoma by rubeosis and phthisis bulbi in addition to irreversible visual loss. We report on the surgical procedures used and results obtained in three patients aged between 21 and 28 years with combined exudative and traction-induced detachment. In all cases, extensive but unsuccessful retinal coagulation had been performed. The surgical intervention was done by application of an encircling buckle followed by vitrectomy and removal of preretinal membranes and subretinal lipid exudates via retinectomies. Particular attention was paid to the intensive endodiathermy of retinal teleangiectasies during surgery. Surgery was concluded by siliconeoil tamponade. Postoperatively, progressive resorption of remaining exudates and teleangiectatic vessels could be observed. All patients demonstrated stable functional and anatomic results at the last follow-up examination performed at 13 months to 6 years after surgery. A stabilization of the anatomic and functional situation can be achieved even in advanced cases of Coats'-induced traction retinal detachment by vitreoretinal surgery.

Adult↗

PubMed1994

Vascular targeting in photodynamic occlusion of subretinal vessels.

PURPOSE: To evaluate the potential of photodynamic therapy (PDT) using benzoporphyrin derivative (BPD) for occlusion of subretinal neovascular membranes, the authors studied efficiency and collateral damage of PDT-induced photothrombosis in the rabbit choriocapillary layer. METHOD: Benzoporphyrin derivative, a new photosensitizer, currently in clinical trials for tumor therapy, was used. Low-density lipoprotein served as a carrier to enhance selective targeting of vascular endothelial cells. RESULTS: Complete choriocapillary occlusion was achieved at a BPD dose of 2 mg/kg and a radiant exposure as low as 10 J/cm2. When PDT was performed 3 hours after BPD application, damage to the neural retina was minimal. Only inner photoreceptor segments showed mitochondrial swelling probably secondary to choroidal ischemia. Bruch's membrane remained intact. Retinal pigment epithelium was invariably damaged as seen with other photosensitizers. CONCLUSION: Compared with photocoagulation BPD-PDT allows endothelial-bound intraluminal photothrombosis, sparing important structures such as neural retina and Bruch's membrane. It may thus provide a more selective treatment of juxtafoveal and subfoveal neovascular membranes.

Animals↗

PubMed1994

Photodynamic therapy of experimental choroidal melanoma using lipoprotein-delivered benzoporphyrin.

BACKGROUND: Benzoporphyrin derivative monoacid (BPD) is a new photosensitizer currently undergoing clinical trial for cutaneous malignancies. Compared with the clinically most frequently used sensitizer, Photofrin, BPD may offer higher tumor phototoxicity, better tissue penetration, and absence of significant skin sensitization. Low-density lipoprotein (LDL) carriers heighten efficiency and selectivity of BPD because neovascular and tumor cells express an increased number of LDL receptors. Hence, in addition to the vaso-occlusive effects similar to most other photosensitizers, LDL-BPD also has been shown to cause direct tumor cell damage. METHODS: Benzoporphyrin derivative monoacid was complexed with human LDL and used in photodynamic treatment of choroidal melanomas experimentally induced in eight albino rabbits. Five rabbits served as controls. Three hours after intravenous injection of 2 mg/kg body weight of LDL-BPD, eight tumors were irradiated at 692 nm and 100 J/cm2 via an argon-pumped dye laser coupled into a slit lamp. RESULTS: Angiography and histologic findings showed immediate photothrombosis after disintegration of endothelial membranes. After complete necrosis of tumor cells within 24 hours, a small fibrotic scar slowly developed. No tumor regrowth was noted up to 6 weeks when animals were killed. CONCLUSION: These data suggest that photodynamic treatment with LDL-BPD may be a promising modality for multiple clinical applications, including tumors and neovascularizations II.

Animals↗

PubMed1994

[Selective occlusion of subretinal neovascularization with photodynamic therapy].

Conventional photocoagulation of subretinal membranes induces a non-selective thermal necrosis of retinal and choroidal layers with extensive collateral damage. Hence, this modality is of limited value for the treatment of lesions close to or underneath the fovea. Photodynamic therapy uses systemic administration of a primarily non-toxic photosensitizer with localized light activation of the dye by subthermal light intensities. It provides intraluminal vascular occlusion by means of localized endothelial damage. Enhanced selectivity for neovascularization is achieved by the use of carrier molecules with increased receptor density on proliferating endothelial cells, e.g. low-density lipoproteins (LDL). Benzoporphyrin derivative (BPD), currently in phase I clinical trials, was complexed with LDL. BPD-LDL was used for photodynamic occlusion of the choriocapillary layer in the rabbit model. Subretinal photothrombosis and collateral damage to neural retina, retinal pigment epithelium, Bruch's membrane and large choroidal vessels were documented by ophthalmoscopy, angiography and light and electron microscopic histology. Homogenous vascular occlusion without retinal destruction was induced with light doses as low as 10 J/cm2. Selective neovascular occlusion by photodynamic therapy may allow occlusion of subretinal membranes while preserving retinal integrity and visual function.

Animals↗

PubMed1994

[Photodynamic therapy of experimental, intraocular tumors with benzoporphyrin-lipoprotein].

Photodynamic therapy (PDT) with its potential for precise localization and absence of severe side effects such as radiation retinopathy may be particularly appropriate for the treatment of intraocular tumors. Benzoporphyrin (BPD), a potent photosensitizer currently in clinical trial, absorbs light at 692 nm, thus allowing sufficient tissue penetration due to minor light absorption in melanin and hemoglobin. The efficiency and selectivity of BPD are significantly pronounced through preassociation with low-density lipoprotein (LDL), since proliferating cells exhibit an increased metabolism of lipoproteins. As an experimental model Greene's melanomas were implanted either into the iris or choroid of albino rabbits. Irradiation at a radiation energy of 80 for iris and 100 J/cm2 for choroidal tumors 3 h after the i.v. injection of BPD-LDL (2 mg/kg) was administered via a laser arrangement with argon-pumped dye-laser, using the slit-lamp. Angiographies and LM/EM histologies were done immediately, and 1, 3, and 14-21 days post-exposure. All 16 treated tumors demonstrated complete regression with a remaining avascular, fibrotic scar. Immediate vascular occlusion within the tumor was seen angiographically, suggesting a direct vascular mechanism. Histologically, two primary mechanisms could be detected: destruction of neovascular endothelial cells and intracellular tumor cell damage. These results indicate that PDT using BPD-LDL complexes may provide an efficient and selective modality for the management of intraocular neoplasms. The availability of new and potent photosensitizers may also lead to broader clinical applications.

Animals↗

PubMed1994

[Clinical heterogeneity of non-Hodgkin's lymphoma of the eye with extraocular manifestations].

Primary, ocular Non-Hodgkin lymphoma is a multicentric disease. The prognosis is mostly determined by involvement of the central nervous system and/or visceral organs. Since ocular symptoms often precede accompanying manifestations and since the eye is easily accessible to diagnostic measures, the ophthalmological diagnosis is essential for early detection and treatment of this complex disease, which has a poor prognosis. To illustrate the extraordinary heterogeneity of the clinical symptoms, four case reports have been selected which demonstrate various ocular symptoms and extraocular localizations. The ophthalmological variability ranges from typical uveitis to retinitis and vasculitis with varying symptoms during the progression of the disease. Completely different extraocular features were induced by long-standing, local infiltrates within basal ganglia, a diffuse infiltration of the brain leading to an acute increase in intracranial pressure, a peripheral tumour within the spinal channel or massive infiltrates of liver, lung and kidneys. Lack of pathognomonic features, high clinical variability and the limited value of imaging techniques and histopathological measures often lead to serious delays in diagnosis.

Aged↗

PubMedDate not supplied

Mechanisms of action of photodynamic therapy with verteporfin for the treatment of age-related macular degeneration.

Age-related macular degeneration, especially the neovascular form of the disease, is the leading cause of blindness in elderly people in developed countries. Thermal photocoagulation is still the preferred treatment for choroidal neovascularization that does not involve the fovea, but it is suitable for only a small number of patients and it can lead to immediate loss of visual acuity. Photodynamic therapy with use of photochemical light activation of verteporfin as a photosensitizer (verteporfin therapy) has been shown to be effective in treating vascularized tumors, and its potential to treat other conditions involving neovascularization has also been suggested. Preclinical and clinical studies have indicated that verteporfin therapy can be used to treat choroidal neovascularization secondary to age-related macular degeneration effectively and safely. Selective occlusion of choroidal neovasculature by this therapy causes minimal damage to the neurosensory retina and, therefore, does not induce loss of visual acuity. This benefit allows verteporfin therapy to be used in the large proportion of patients who are not eligible for treatment by laser photocoagulation. The mechanistic aspects of the mode of action of light-activated verteporfin are described in this review.

Animals↗

PubMedDate not supplied

Correlation of blood-glucose control with oxidative metabolites in plasma and vitreous body of diabetic patients.

PURPOSE: In diabetes hyperglycemia and other mechanisms lead to the production of oxidative metabolites that can enhance the production of growth factors, leading to increased proliferative activity. Strict blood-glucose control reduces the progression of retinopathy better than standard control. This study investigated patients with diabetic retinopathy for evidence of oxidative metabolites in plasma and the vitreous body, correlating these values with blood-glucose control. METHODS: The study comprised 136 patients suffering from proliferative diabetic retinopathy. They were grouped according to their mean glycosylated hemoglobin value for the last 9-12 months. Patients with values < or = 10% (mean 8.7%; n=64) were considered strict glucose control patients, those with values > 10% (mean 12.8%; n=72) were considered standard glucose control patients. Lipid peroxides were determined in blood plasma and the vitreous body by two methods (thiobarbituric acid reactive substances and malondialdehyde-like substances). If present, retinal traction with fibrovascular proliferations (>2 disk areas) was quantified and served as an indicator of proliferative activity. RESULTS: Patients with strict blood-glucose control had significantly (p < 0.01) lower lipid peroxide values in plasma and the vitreous body than standard glucose control patients. These latter had significantly (p<0.01) higher rate of fibrovascular proliferation (50%) than strict glucose control patients (9. 7%). DISCUSSION: Strict blood-glucose control leads to reduced oxidative tissue damage both systemically and locally in the eye, and reduced proliferative activity. Oxidative metabolites can stimulate proliferation by increasing the amounts of different growth factors an cytokines such as vascular endothelial growth factor. Thus, it can be speculated that in hyperglycemia the relative increase of oxidative metabolites contributes both to damage of retinal vessels and to more pronounced proliferative activity in diabetic retinopathy.

Blood Glucose↗

PubMedDate not supplied

Anecortave acetate for the treatment of subfoveal choroidal neovascularization secondary to age-related macular degeneration.

PURPOSE: Anecortave acetate is a novel angiostatic cortisene being evaluated clinically for treatment of exudative age-related macular degeneration (ARMD). A randomized, placebo-controlled, efficacy and safety dose duration study of anecortave acetate for depot suspension (3 mg, 15 mg, 30 mg) in this patient population was completed in June 2003. As part of this trial, 128 patients with subfoveal choroidal neovascularization (CNV) secondary to ARMD were enrolled and treated for up to 2 years by 18 clinical sites in the United States and European Union. METHODS: Study patients were evaluated clinically with detailed ophthalmic examinations, general physical examinations, assessments of best-corrected logMAR visual acuity, and angiographic evaluations. The Digital Angiography Reading Center (New York City, NY) assessed lesion eligibility while the clinical investigators assessed overall patient eligibility prior to treatment. As part of this study, study medication was delivered as a posterior juxtascleral depot using a specially designed curved cannula at 6-month intervals if in the masked investigator's opinion the patient's lesion could benefit from additional treatment. RESULTS: The 2-year efficacy results of this placebo-controlled study demonstrated that RETAANE 15 mg (anecortave acetate for depot suspension) was statistically superior to placebo for stabilization of vision (<3 logMAR line change from baseline) and for inhibition of neovascular lesion growth. There were no serious treatment-related safety issues associated with either the study medication or the procedure for administration. CONCLUSIONS: Anecortave acetate 15 mg for depot suspension is clinically efficacious compared to placebo for treatment of subfoveal exudative ARMD lesions when administered at 6-month intervals as a posterior juxtascleral depot.

Angiogenesis Inhibitors↗