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Biomedical subjects

U Pleyer

Publications and source records attributed to U Pleyer.

At least 37 records · Page 2Linked to original sources

[Differential diagnosis and therapy of graft rejection after keratoplasty].

Allograft rejection is the leading cause of corneal graft failure after perforating keratoplasty. Clinically, graft rejection may present as acute changes in corneal host tissue. All three corneal layers, epithelium, stroma and endothelium, can be affected separately or manifest combinations of rejection. Differentiation from other postoperative morphological changes following corneal transplantation can prove to be difficult, but is critical in treatment. This article is intended to provide a review on differential diagnoses and current therapeutic measures.

Diagnosis, Differential↗

[Ocular toxocariasis. Diagnostic and therapeutic options].

BACKGROUND: The diagnosis of ocular toxocariasis can be difficult and the aim of this study was to evaluate the benefit of ELISA testing of vitreous body fluid. PATIENTS AND METHODS: We present five consecutively treated patients with ocular symptoms of toxocariasis, three of these patients presenting with epiretinal membranes and subretinal granulomas were vitrectomized. Vitreous and body fluid and serum were tested for toxocara antibodies by ELISA. Moreover vitreous body fluid of 10 patients with epiretinal membranes of other origins were examined by the same ELISA. RESULTS: In all three operated patients toxocara antibodies were detected in the vitreous fluid but ELISA testing of serum samples was negative in two of the three patients. Visual acuity increased or remained stable in the operated patients. The ELISA test was negative in all vitreous fluid samples of the control group. CONCLUSIONS: ELISA testing of vitreous body fluid can prove the presence of toxocara infection when no systemic signs of infection are present and no antibodies are detectable in the serum. Well-timed vitrectomy is a suitable therapy for vitreo-retinal complications in ocular toxocariasis to improve prognosis and to confirm the diagnosis.

Adolescent↗

[Transcorneal-paracorneal penetration route for topical application of drugs to the eyt. Mycophenolate mofetil as a model substance].

PURPOSE: Topically applied drugs can penetrate transcorneally or paracorneally (transsclerally). There are only few studies to demonstrate the relationship of both penetration routes. The immuno-modulator mycophenolate mofetil (MMF), ester and pro-drug of mycophenolic acid (MPA), is a promising substance for such studies. MATERIAL AND METHODS: Rabbit eyes were treated with different preparations of MMF as a cyclodextrin complex (MM-CD) and as a suspension (MMF-SP) and MPA as a cyclodextrin complex (MPA-CD). The concentrations of both compounds were measured in the cornea, conjunctiva, aqueous humor, vitreous body and iris-ciliary body. RESULTS: Only MPA is detectable in the cornea after application of MMF-CD and MMF-SP. In the aqueous humor high concentrations of MPA are detectable after 60 min. In the iris-ciliary body both MMF and MPA can be found. CONCLUSION: The intraocularly detected mycophenolate mofetil represents the paracorneally penetrated fraction. After topical application of mycophenolate mofetil in suitable preparations high concentrations of the active substance can be achieved intraocularly. These favourable pharmacokinetic characteristics are promising for new therapeutic strategies in immune-mediated diseases of the anterior part of the eye.

Administration, Topical↗

[Current practice of immune prophylaxis and therapy in perforating keratoplasty. A survey of members of the Cornea Section of the German Ophthalmological Society].

PURPOSE: Different strategies are currently used for prophylaxis and therapy of immunological transplant reactions. The aim of the present study was to evaluate clinical practice in planning and treatment of perforating keratoplasty (KPL) in Germany. METHOD: A questionnaire was sent out to 148 members of the cornea section of the German Ophthalmological Society. The return consisted of 69 (47%) questionnaires representing 69% of institutions, 39% of responses returned from institutions performing <50 KPL/year, 15% from institutions operating >100 KPL and 4% from centres performing >300 KPL/year. RESULTS: Of the responders 13% currently never use HLA-matched grafts, 22% choose matched grafts in every risk KPL and 1.5% always use matched grafts. In normal risk situations 1.5% treat less than 2 weeks with topical steroids, 66% 3-12 months, 6.5% >1 year, 35% additionally treat with systemic steroids. Cyclosporine A (CsA) (92%) is besides steroids (80%) the most common systemic immunomodulatory agent in high risk situations, while methotrexate is used by only 9.5%. The duration of immunosuppressive therapy varies from <3 months (9%) up to >12 months (14%). The postoperative therapy after KPL in herpes includes topical (51%) and systemic aciclovir <3 (26%) and >3 weeks (67%) and additional systemic immunomodulatory agents (37%). The acute immune reaction is treated predominantly with steroids: topical (95%), subconjunctival (29%), intracameral (1.5%). Systemic steroids are given orally (48%) and intravenously (42%), 12% treat with topical CsA. CONCLUSIONS: Besides therapeutic options that are accepted as common practice (e.g. systemic CsA) clinical practice varies widely. This may reflect the lack of evidence-based clinical observations.

Adjuvants, Immunologic↗

[Immunomodulation in penetrating keratoplasty. Current status and perspectives].

The immune privileged nature of the cornea contributes to the favourable outcome in corneal grafts. However, preventive measures are necessary to reduce allograft rejection particular in "high-risk" cases. Although corticosteroids are still a major component of our immunopharmacological armentarium, they might be supplemented by other more specific immunomodulating agents. The spectrum includes agents such as azathioprin, methotrexate or more specific calcineurin inhibitors affecting T-cells (cyclosporin A, FK506) and highly selective monoclonal antibodies directed against T-cell subpopulations and other targets. In order to better evaluate the risks and benefit of these agents, the properties of established and forthcoming agents are presented. In addition, this review attempts to address some new concepts of tolerance induction following penetrating keratoplasty.

Adjuvants, Immunologic↗

Tumour necrosis factor alpha and interleukin 6 gene expression in keratocytes from patients with rheumatoid corneal ulcerations.

BACKGROUND/AIMS: Ultrastructural alterations in the stroma adjacent to corneal perforations have previously been reported in patients with longstanding rheumatoid arthritis. Since patients with rheumatoid arthritis often present upregulation of proinflammatory cytokines in serum and in synovial fluid, it was of interest to analyse the gene expression of these cytokines-for example, tumour necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6), in corneal samples from patients with corneal ulcerations and/or perforations associated with rheumatoid arthritis. METHODS: Corneal samples from seven patients with corneal ulcerations and/or perforations associated with rheumatoid arthritis were collected in 4% paraformaldehyde in "RNAse-free" conditions. Paraffin sections were fixed on silan coated slides and further analysed by systematic non-radioactive in situ hybridisation, using specific gene probes for TNF-alpha and IL-6 labelled with digoxigenin (DIG). Detection of hybrids was carried out by using a commercially available DIG detection system. RESULTS: Whereas an extended TNF-alpha gene expression could be clearly observed in the keratocytes surrounding the corneal ulcerations and/or perforations from five of the seven analysed patients, all seven patients presented clearly positive results for an extended IL-6 gene expression in the analysed tissue samples. CONCLUSIONS: Alterations in corneal cells surrounding ulcerations and/or perforations in patients with rheumatoid arthritis may occur with implication for inflammatory processes. Upregulation of the proinflammatory cytokines TNF-alpha and IL-6 may modify the production of metalloproteinases in the corresponding cells resulting in collagenolytic corneal damage.

Aged↗

[Antiviral therapy adjustment in corneal recipients using antibody testing in the aqueous humor].

INTRODUCTION: In corneal recipients with herpes infection, acyclovir given for 1 year postoperatively prevents viral reactivation and improves graft outcome. The indication for prophylactic antiviral therapy relies on the preoperative diagnosis of herpes. However, many patients present with corneal scars featuring sequelae of herpes without a proven history of herpes. Here we report the results of a prospective study of anti-herpes simplex virus (anti-HSV) and varicella zoster virus (VZV) antibody testing in the aqueous humor at the time of corneal transplantation to refine the indication of the antiviral treatment. MATERIAL AND METHODS: The study involved 33 keratitis corneal graft recipients, 21 of whom had documented herpes keratitis. A control group was made with 11 cataract patients. An anterior chamber puncture was performed just before surgery. The micro-ELISA test was done on both aqueous humor and serum, and local anti-HSV or VZV antibody synthesis was acknowledged if the ratio of antibody concentrations was above 4. RESULTS: Local antibody synthesis to HSV was detected in 22 cases, to VZV in 9 cases, to both HSV and VZV in 6 cases, and no synthesis in 8 cases. The sensitivity of the test was 65% in patients with a documented history of herpes (14 cases out of 21). Among non-herpetic patients, the test was positive in 9 patients, who thus benefited from postoperative antiviral therapy. No viral reactivation was encountered after a minimum follow-up of 1 year. CONCLUSIONS: Antibody testing in the aqueous humor at the time of keratoplasty is a convenient, inexpensive diagnostic tool in corneal recipients. It provides useful information before prescribing a long and expensive postoperative antiviral therapy.

Acyclovir↗

Corticosteroids in ophthalmology.

Corticosteroids are, even 50 years after introduction in ophthalmology, the best, and often only choice of treatment for acute inflammatory eye disorders. Their broad spectrum of actions may not only explain the greater potency compared with other anti-inflammatory agents but also be responsible for multiple serious side effects. For future developments, several directions may be chosen including development of safer drugs with high therapeutic index and application of long-term drug-release systems.

Adrenal Cortex Hormones↗

[Macrophage depletion inhibits leukocyte recruitment in experimental melanin-induced uveitis (EMIU)].

BACKGROUND: To study the role of macrophages in experimental melanin-induced uveitis (EMIU), we used the method of intravital microscopy to analyse changes in leukocyte adhesion to iris venules of live rats with EMIU after pretreatment with liposomal clodronate. MATERIALS AND METHODS: EMIU was induced in Lewis rats (n = 48) by intraperitoneal immunisation with bovine crude melanosomes emulsified in complete Freund's adjuvant (CFA) and pertussis toxin (PTX). Control animals received CFA and PTX only (n = 12) or no injection (n = 6). Animals were treated with liposomal clodronate (DMDP-lip) or empty liposomes on days -2, +1, 4, 6 and 8. Using IVM, postcapillary iris venules of rats were examined to quantify leukocyte rolling and firm adhesion to the vascular endothelium. RESULTS: Depletion of macrophages caused a decreased percentage of rolling leukocytes on day 8 (2 +/- 1.1% vs 15.2 +/- 1.6%, DMDP-lip vs EMIU, mean +/- SEM, ANOVA, p < 0.05) and day 10 (2.6 +/- 0.3% vs 14.2 +/- 1.6%). A significant decline in the number of firmly adherent leukocytes was detected on days 8 and 10 (88 +/- 13/mm2 vs 175 +/- 18/mm2 and 129 +/- 13/mm2 vs 372 +/- 31/mm2, DMDP-lip vs EMIU). Treatment with empty liposomes showed no changes in leukocyte firm adhesion. CONCLUSIONS: Elimination of macrophages prevents the induction of EMIU. In autoimmune-mediated uveitis, macrophages play a crucial role in the initiation of leukocyte-endothelium interaction.

Animals↗

[Ocular toxoplasmosis antibodies in aqueous humor and serum].

BACKGROUND: The diagnosis of ocular toxoplasmosis is mainly based on ophthalmological examination but might be difficult to establish in some cases. The purpose of our study was to evaluate the value of aqueous humor and serum analysis in ocular toxoplasmosis. PATIENTS AND METHODS: We analyzed the avidity of toxoplasma-specific IgG in aqueous humor and serum samples from 50 patients with toxoplasmic retinochoroiditis, with 25 patients with uveitis posterior or panuveitis serving as controls. RESULTS: Specific intraocular antibody synthesis could be confirmed in 49 patients (98%). In two patients (8%) of the control group, antibody synthesis was detected (false positive). Forty-nine patients with diagnoses of ocular toxoplasmosis were positive for serum anti-T. gondii IgG, but only three patients had increased IgM levels. CONCLUSIONS: Analysis of local antibody production is a reliable method for confirming or excluding a suspected clinical diagnosis of toxoplasma retinochoroiditis. The determination of toxoplasma antibodies in the patients' serum is of limited value.

Adolescent↗

A comparison of two different formulations of diclofenac sodium 0.1% in the treatment of inflammation following cataract-intraocular lens surgery.

OBJECTIVE: To compare the efficacy, tolerability and local tolerance of diclofenac sodium 0.1% containing hydroxypropylgamma cyclodextrin preserved with benzalkonium chloride 0.005% (Voltaren Ophtha CD), with that of diclofenac sodium 0.1% preserved with thiomersal 0.004% (Voltaren Ophtha) in the treatment of inflammation after cataract-intraocular lens surgery. DESIGN AND SETTING: Randomised 2:1, double-masked, parallel-group study in six centres in Germany. STUDY PARTICIPANTS: 299 patients scheduled to undergo phacoemulsification with posterior chamber intraocular lens implantation. INTERVENTIONS: Study medications were instilled four times in the 30 minutes before surgery and four times daily from the first postoperative day. MAIN OUTCOME MEASURES: The key efficacy variable was the reduction in anterior chamber flare (photons/millisecond) from day 1 to day 6 to 8. Patients underwent comprehensive ocular examinations, including laser flaremetry (KOWA), preoperatively and postoperatively at days 1, 6 to 8 and 24 to 32. RESULTS: 268 patients (Voltaren Ophtha CD 177, Voltaren Ophtha 91) completed the day 6 to 8 visit without any protocol violations. Reduction in the degree of intraocular inflammation with Voltaren Ophtha CD was equivalent to that achieved with Voltaren Ophtha at the day 6 to 8 [95% confidence interval (CI) -3.07 to +0.54] and day 24 to 32 (95% CI -1.44 to +1.40) visits. Although there was no significant (p = 0.464) difference between the two study groups in patients' global assessment of local tolerance at day 24 to 32, ocular discomfort was significantly (p = 0.023) less with Voltaren Ophtha CD compared with Voltaren Ophtha. CONCLUSIONS: Voltaren Ophtha CD was as effective and well tolerated but had less ocular discomfort compared with Voltaren Ophtha in the treatment of ocular inflammation after phacoemulsification with intraocular lens implantation. This new formulation of diclofenac sodium 0.1% may be used as an alternative to the existing formulations of ophthalmic diclofenac sodium 0.1%.

Adult↗

Efficiency and toxicity of liposome-mediated gene transfer to corneal endothelial cells.

Gene transfer to corneal endothelial cells could be an important advance to modulate functions of these critical cells and is a field of current investigations. The development of gene transfer methods is a prerequisite for gene therapy to realize its full potential. We attempted to investigate and optimize the efficacy and safety of cationic liposome mediated gene transfer into corneal endothelial cells using different lipid formulations. Mono- and polycationic lipids and the neutral helper lipid dioleolphosphotidyl-ethanolamine (DOPE) were used for preparation of cationic liposomes. Six liposomal formulations containing DAC/DOPE 30/70 (DAC 30), DOSGA/DOPE 30/70 (DOSGA 30), DOSGA 100, DMRIE/DOPE 50/50 (DMRIE 50) and SP/DOPE 20/80 (SP 20) were complexed with the pUT 651-plasmid, encoding the E. coli beta-galactosidase gene. Subconfluent primary and passaged bovine corneal endothelial cells (BCEC) were transfected with different amounts of liposomes and DNA or uncomplexed free DNA as control. Quantitative expression of beta-galactosidase was measured using a colorimetric assay. In order to assess the effects on cell viability and growth, a modified acidic phosphatase assay was employed. Differences were detected using these various liposome preparations. Transfection experiments demonstrated the highest gene expression using SP 20> DMRIE 50 ranging at approximately 3 mU per beta-gal per well. Low expression of beta-galactosidase was achieved using DAC 30, DOSGA 30 and DOSGA 100. No beta-galactosidase expression was found in control dishes. There was no difference seen following transfection of primary or subsequent passages of BCEC. As indicated by the acid phosphatase assay, no significant toxicity was detected for the most efficient lipids used. Of the preparations studied, SP 20 appeared as the optimal vehicle for plasmid-mediated transfection of BCEC. The ability to deliver genes to BCEC via liposomes could be valuable, since the use of other vectors for transfection may be limited by undesired effects.

Animals↗