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Biomedical subjects

U Pleyer

Publications and source records attributed to U Pleyer.

At least 19 recordsLinked to original sources

Antibacterial protection of the ocular surface.

The outer surface of the eye is constantly exposed to a wide array of microorganisms. To protect the integrity or the ocular surface and to retain corneal transparency, a number of defense mechanisms have evolved. This article discusses the host mechanisms of the eyelids-, tears, cornea and conjunctiva. These host defense mechanisms are identified as either a native, nonspecific defense or a specifically acquired immunological defense requiring previous exposure to an antigen and the development of specific immunity. Nonspecific components that protect the eye include the eyelids, ocular surface epithelium, normal flora and tear proteins. Specifically acquired immunity in tears, cornea and conjunctiva involves the interaction of antigen-presenting cells, lymphocytes and humoral components of the immune system.

Animals

[Apparent wall shear rate and leukocyte-endothelium interaction in iris blood vessels in endotoxin-induced uveitis].

UNLABELLED: Inflammatory stimuli induce the expression of adhesion molecules on leukocytes and endothelial cells. The adhesive forces between leukocytes and the vascular endothelium are antagonized by the shear stress of the flowing blood. The aim of this study was to examine how differences in the apparent wall shear rate measured in iris venules with varying caliber affect leukocyte-endothelium interaction. METHODS: The microvasculature of the iris in Lewis rats (n = 6) was examined using intravital fluorescence microscopy [2]. Blood flow was visualized with FITC-HES and leukocytes were stained with rhodamine 6G. Venules (n = 110) ranging in diameter from 20-60 microns were analysed with regard to the following parameters: Flux of leukocytes, velocity of leukocytes in the center stream, number of rolling and adherent leukocytes. The apparent wall shear rate was calculated from the center stream velocity and the vessel diameter. Animals were examined 4 h after administration of endotoxin from S. typhimurium (500 mg/kg body wt i.p.), when leukocyte-endothelium interaction is strongly enhanced. RESULTS: The flux of leukocytes, the absolute number of rolling leukocytes and the velocity of leukocytes in the center stream was higher in larger than in smaller venules. The apparent wall shear rate decreased with increasing vessel diameter. Calculated values were 806 +/- 59 s-1 for vessels 20-30 microns in diameter and 483 +/- 34 s-1 for vessels of 50-60 microns (mean +/- SEM). The number of adherent leukocytes per mm2 endothelial surface and the rolling fraction did not show significant differences between vessels with varying caliber. CONCLUSION: Although the shear rate declined with increasing vessel diameter, we could not observe an increase in rolling and adherent leukocytes. The effects of vessel diameter on leukocyte adhesion to the vascular endothelium in postcapillary iris venules are minimal.

Animals

The immunology of bullous oculo-muco-cutaneous disorders.

In skin-blistering diseases, alteration of cellular adhesion results in a loss of cohesion of the epithelium of the skin and the mucous membranes. These disorders are often genetically determined and involve highly specific autoantibodies. A recent workshop discussed the immunology of these diseases.

Eye Diseases

[Autoimmune diseases of the peripheral cornea. Immunopathology, clinical aspects and therapy].

Noninfectious ulceration of the peripheral cornea remains a major diagnostic and therapeutic challenge. The pathogenesis in most of these disorders is unclear, however, on the basis of systemic connective tissue diseases, autoimmune mechanisms are most likely involved. The peripheral cornea has distinct morphological and immunological characteristics that predispose for inflammatory reactions. Major differences exist regarding humoral and cellular components of the immune system. In the peripheral cornea there is more high-molecular IgM and initial complement component C1 than in the central cornea and may predispose for immune complex formation. The close contact to the conjunctival vasculature provides the basis necessary to generate an immune response. Langerhans cells and macrophages as important antigen presenting and processing cells are present in higher number in the peripheral cornea. Autoimmune diseases that affect the peripheral cornea include collagen vascular diseases and Mooren's ulcer. Although this association is obvious in advanced rheumatoid arthritis more subtle forms of polyarteritis nodosa or systemic lupus erythematosus require careful medical evaluation and workup. Ocular manifestations may present as the initial clinical signs and require careful workup in these potentially lethal disorders.

Antigen-Presenting Cells

Traumatic wound dehiscence after penetrating keratoplasty.

BACKGROUND: Traumatic wound dehiscence after penetrating keratoplasty is probably underestimated. PATIENTS: From the files of the University Eye Hospital Tübingen (1981-1993), 15 patients with a traumatic wound dehiscence after penetrating keratoplasty were investigated. RESULTS: Latency between corneal grafting and wound rupture ranged from 1 month to 25 years (mean 6.2 years). Wound dehiscence was quite evenly distributed over the circle. Intraocular tissue was lost to a variable extent. Three eyes were primarily or secondarily enucleated. Seven eyes (47%) with an originally reduced but useful vision became blind or were removed. Most (67%) of the resutured grafts lost transparency. CONCLUSIONS: Traumatic wound dehiscence is a serious and not very rare complication after penetrating keratoplasty. Functional results are poor.

Adult

Impregnation of collagen corneal shields with liposomes: uptake and release of hydrophilic and lipophilic marker substances.

PURPOSE: Liposomes and collagen corneal shields (CCS) have been used as ophthalmic drug delivery devices. With regard to a possibly combined application, we studied the effects of surface charge and bilayer fluidity of liposomes on their uptake and release by CCS. METHODS: 12-hours-CCS were soaked in large unilamellar liposomes, which had been labelled with 4,5-carboxyfluorescein (CF) and N-(lissamine rhodamine B sulfonyl)-diacyl-phosphatidylethanolamine (PE-RhB) in the aqueous space and in the liposome bilayer, respectively. Released fluorophores were determined fluorometrically in the elution buffer at intervals from 1 to 240 min after immersion. RESULTS: The CF concentration in the CCS soaked in a CF solution was two to seven times higher than immersion in the liposome suspensions. Among those, the negatively charged, cholesterol-containing preparation led to the highest CF concentration in the CCS. The PE-RhB concentration was highest after soaking the CCS in neutral, cholesterol-free liposomes. All types of liposomes were found inside the CCS by freeze fracture electron microscopy. The release kinetics data indicate a first order release. More than 90% of CF was released by the CCS within the first 30 min. This was equal after soaking the CCS in the CF solution or in liposomes. With DOPC-liposomes, the maximal release was already attained after 10 min. In general, the differences in the release kinetics of both hydrophilic and lipophilic markers, obtained by the various liposome types were small. CONCLUSIONS: Our results indicate that surface charge and bilayer fluidity are of minor importance for the interaction with collagen corneal shields. However, since the release kinetics of a liposome-encapsulated hydrophilic or lipophilic substance are similar to the release of a non-encapsulated drug, the combination of liposomes with collagen shields may be useful mainly with respect to the encapsulation of drugs which do not penetrate the ocular surface as well as to prolong corneal contact time of the liposomes.

Biological Dressings

Therapy of Behçet's disease.

Behçet's disease (BD) is a multisystem vasculitis of unknown origin. In this retrospective study we analyzed the therapy of 32 patients seen between 1978 and 1993 at the Departments of Rheumatology, Ophthalmology, and Dermatology of the Tübingen University Clinic. The aim of this study was to evaluate the efficacy of different therapeutic strategies concerning different organ manifestations of the disease, especially eye disease. A total of 20 patients had cutaneous manifestations or arthritis. Whereas treatment with colchicine (Col), azathioprine (AZA), cyclosporine (CSA), or steroids (Ster) produced only partial remissions, a combination of CSA, AZA, and steroids led to complete remissions. Interferon-gamma (IFN-gamma) therapy led to remission rates of 60% (complete) and 20% (partial). In all, 22 patients had uveitis (posterior or panuveitis). Steroids were effective in only 50% of the patients and Col was partially effective in 66%. AZA induced a remission in 71% of cases and CSA was partial effective in 60%. The threshold combination of AZA, CSA, and Ster induced a complete remission in 66% of the patients. IFN-gamma was ineffective in 80%. IFN-alpha was used in one patient only and induced a complete remission. These results demonstrate that although our patient group is too small to allow significant conclusions to be drawn, in terms of the literature, for mucocutaneous disease and arthritis, IFNs might be the best therapy, whereas for uveitis as well as other more severe features of the disease, CSA or AZA + Ster should be used. If the latter are ineffective, the threefold combination (AZA, CSA, Ster) is probably the most effective alternative. The significance of IFN-alpha will be evaluated in further studies.

Azathioprine

[Cogan I syndrome. Audio-vestibular, ophthalmologic findings and therapy in 6 patients].

We report clinical experiences with six patients treated at the University of Tübingen between 1982 and 1994 for symptoms of typical and atypical ocular manifestations of Cogan's syndrome. All cases had systemic symptoms in addition to involvement of the cochleovestibular system. Otologic symptoms were the initial presentation in four cases. Vestibular dysfunction often preceded hearing loss. Five patients had keratitis and also demonstrated signs of ocular inflammation diagnosed as scleritis or episcleritis. In two patients these ocular symptoms were the first signs of Cogan's syndrome, recurred periodically and did not respond to corticosteroids. Three patients were diagnosed early, allowing corticosteroid treatment to begin early with stabilization of hearing. Total bilateral deafness could not be prevented in the remaining patients. The importance of being aware of auditory-vestibular dysfunction occurring in patients with ocular inflammation and the role of early immunotherapy in preventing deafness has to be emphasized.

Adolescent

Sudden increase in intraocular pressure as an initial manifestation of myelodysplastic syndrome.

PURPOSE/METHODS: We studied a rare initial manifestation of myelodysplastic syndrome in an 82-year-old woman who had acute secondary glaucoma in the right eye and mature cataracts in both eyes. RESULTS/CONCLUSION: Therapy with glaucoma control medications and cataract extraction in the right eye resulted in expulsive hemorrhage and subsequent enucleation of the right eye. After cataract extraction, examination of the left eye disclosed a central serous retinal detachment and hemorrhage. Histopathologic analysis of the right eye demonstrated myelocytic and lymphocytic infiltration.

Aged

Analysis of interactions between the corneal epithelium and liposomes: qualitative and quantitative fluorescence studies of a corneal epithelial cell line.

Transcorneal drug transport is normally limited by the intrinsic permeation characteristics of the corneal epithelium. However, liposomes, i.e., phospholipid vesicles composed of phospholipid membranes, have recently attracted attention as carriers of topically applied agents. The present study therefore describes a qualitative and quantitative laboratory investigation of interactions between corneal epithelial cells and liposomes. The lipid bilayers and interior spaces of liposomes were labelled with different fluorophores. Fluorescence microscopy revealed a rapid uptake of rhodamine B-labelled liposome bilayer components by the epithelial cell membrane and the cytoplasm. Simultaneously, intracellular uptake of aqueous liposome content was indicated by uniform fluorescence of the cytoplasm due to carboxyfluorescein (CF). The fluorimetric experiments showed that the uptake of liposomes by SIRC cells depended on liposome concentrations and the time of exposure of the cells to the liposomes, and that saturation effect characteristics were present. Cell fluorescence dropped by approximately 45% when the incubation temperature of the cells was reduced from 37 degrees C to 4 degrees C. Both this phenomenon and a significant reduction in liposome uptake (p < 0.05 and p < 0.01) after incubation with the metabolic inhibitors 2-deoxyglucose and sodium azide indicated active, energy-dependent processes. Phagocytosis in cell-liposome interactions was directly shown by a significant reduction in cell fluorescence (p < 0.05) after application of the actin inhibitor cytochalasin B. The results presented here give concrete data on interactions between liposomes and superficial cells of the eye in vitro.

Animals

[Cogan I syndrome: too often detected too late? A contribution to early diagnosis of Cogan I syndrome].

BACKGROUND: Cogan's syndrome is an uncommon disease characterized by ocular inflammation, vestibuloauditory dysfunction and symptoms of systemic disease. The etiology is unknown, however there is evidence for an autoimmune pathogenesis. The "typical" Cogan's syndrome presents as bilateral interstitial keratitis and progressing vestibuloauditory dysfunction. The presence of other inflammatory manifestations in addition of keratitis has been termed as "atypical" Cogan's syndrome. PATIENTS: We report on six patients presenting with typical as well as atypical ocular manifestations between 1982 and 1994. Typically, the illness was accompanied by systemic symptoms. Each patient had audiovestibular involvement, that was the initial presentation in 4 cases. Vestibular dysfunction often preceded hearing loss. Five of our patients not only presented with keratitis but also demonstrated signs of ocular inflammation diagnosed as scleritis or episcleritis. In two patients these ocular symptoms were the first signs of Cogan's syndrome, recurred periodically and did not respond to corticosteroids. RESULTS: In 3 patients that were diagnosed early and treatment with corticosteroids was initiated early, hearing could be stabilized, in the remaining patients total bilateral deafness could not be prevented. CONCLUSION: The importance of being aware that vestibuloauditory dysfunction may occur in patients with ocular inflammation, and the fact that early immunotherapy may prevent the risk of deafness, has to be emphasized.

Adolescent

Behçet's disease: epidemiology and eye manifestations in German and Mediterranian patients.

Behçet's disease (BD) is a systemic disease of unknown etiology, characterized by multiple organ involvement. Although its incidence is high in the Mediterranean countries and in Japan, BD is not often found in German patients. We therefore compared the epidemiological and clinical involvement of BD in 39 patients of German and of Mediterranean origin. The first manifestation was oral aphthosis in 72% of patients, followed by eye involvement (62%), skin lesions (25%), and arthritic problems (23%). Eventually, all our patients developed oral aphthosis. Whereas Germans had eye involvement in only 55% of cases (Mediterraneans, 71%), they came up with venous thrombosis or thrombophlebitis more often (64%) as compared with Mediterraneans (29%). The first ocular symptom was anterior uveitis in 87.5% of patients; the visual prognosis was poor due to occlusive retinopathy. Among 22 eyes of 12 patients, 16 had a visual acuity of 0.1 or less after 5 years of disease. We found a similar association with human leukocyte antigen B5 (HLA-B5) in the German patients (66.7%) and in the Mediterranean group (54.4%). There was no significantly higher HLA-B5 association with the uveitis or arthritis type. These results demonstrate a few differences between the two ethnic groups but illustrate that in Germans the disease also has a poor prognosis.

Adolescent

[Keratoplasty à chaud].

Between 1980 and 1992 we performed 128 keratoplasties à chaud on 69 (54%) eyes with progressive bacterial and on 59 (46%) eyes with progressive herpetic keratitis. In 44 of the eyes the corneas were spontaneously perforated, and in 28 (22%) a descemetocele was present. Only grafts that had been followed for at least 1 year (3.2 +/- 2.4 years) were analyzed. During this time 88 (95%) of the severely threatened eyes were preserved. In the operated eyes visual acuity improved in 20 (54%) in the bacterial and in 36 (69%) in the herpetic group. The main complications were immunological allograft rejection, cataract progression and recurrence of herpes. Allograft rejection occurred in 29 (71%) of the bacterial grafts and remained irreversible in 18 (44%) cases. 30 (63%) eyes in the group with herpetic corneal lesions developed graft rejection, 19 (37%) of these rejections were irreversible. Cataract occurred in the postoperative course in 25 (61%) of the bacterial eyes and in 23 (44%) of the herpetic ones. Recurrence of herpes presented a specific problem in this group and appeared in 12 (23%) of the grafts during a follow-up of 1 month to 12 years (3.8 +/- 2.4 years). Our results demonstrate that keratoplasty à chaud is a valuable form of managing urgent pathological processes of the cornea and shortening the course of the disease. This procedure also allows satisfactory primary functional results in many cases, however, secondary re-keratoplasty and cataract surgery are necessary to achieve functional rehabilitation.

Adolescent

[Amphotericin B--bioavailability in the cornea. Studies with local administration of liposome incorporated amphotericin B].

Amphotericin B remains an important antifungal agent in the treatment of ocular mycosis. Since topical ocular application is limited because of ocular irritation and poor penetration, we studied the pharmacokinetics of amphotericin B encapsulated in unilamellar liposomes (AmBisome). One drop (20 microliters) of AmBisome or an equivalent concentration of amphotericin B was applied to rabbit eyes. Drug concentrations were measured 15, 60, 120 and 240 min following administration of the agents by HPLC in cornea and aqueous humor. The effect of intact (group A) and debrided corneal epithelium (group B) was also studied. Corneal amphotericin B levels were significantly higher (P < 0.01) after 15 min in animals receiving amphotericin B as compared to AmBisome in group A. At later time points no differences in the corneal drug levels were found, and the drug levels following AmBisome application were remarkably stable. Epithelial removal resulted in increased corneal drug levels following application of both amphotericin B preparations. Significantly higher drug levels were observed after free amphotericin B treatment at 15-60 min (P < 0.01). Drug levels in the aqueous humor did not differ between the two amphotericin B preparations and remained below therapeutically effective concentrations. These results suggest that topically delivered AmBisome provides stable corneal drug levels, but has the potential benefit of lowered ocular toxicity.

Amphotericin B

In vivo study of leukocyte-endothelium interaction in endotoxin-induced uveitis.

PURPOSE: To analyze leukocyte-endothelium interaction in iris venules of living rats and to quantify changes of leukocyte dynamics in endotoxin-induced uveitis (EIU). METHODS: Lewis rats received an intraperitoneal injection of 100 micrograms of lipopolysaccharide (LPS; Salmonella typhimurium). Using intravital fluorescence microscopy, the iris vessels were examined, 2, 4, 6, 10, 14, 24, and 72 hours after LPS injection. A setup for intravital fluorescence microscopy of iris venules in the rat is described. Images are recorded with a video camera and stored on S-VHS videotape for off-line analysis. For contrast enhancement, erythrocytes and plasma were stained with fluorescein isothiocyanate (FITC) and FITC-hydroxyethylstarch, respectively. Rhodamine 6G was used for intravital staining of leukocytes. Resolution and magnification (x850) of the system facilitates observation of individual cells in the bloodstream in real time. Leukocytes were either flowing in the center stream, rolling along the endothelium, or firmly adherent. Image analysis provided data on microvascular leukocyte flux and leukocyte velocity. RESULTS: The percentage of leukocytes rolling on postcapillary venular endothelium increased significantly (P < 0.05) 4 hours after endotoxin administration, as did the number of firmly adherent cells. Leukocyte-endothelium interaction reached its maximum 6 to 10 hours before an increase of inflammatory cells in the aqueous humor. The response to endotoxin was reversible, subsiding to near-normal values after 72 hours. CONCLUSIONS: Intravital fluorescence microscopy provides data on microvascular parameters, including the number of rolling and sticking leukocytes on vascular endothelium. Inflammation of the anterior uvea was characterized with regard to leukocyte recruitment from blood to the vessel wall.

Animals

Ophthalmomyiasis externa due to the sheep botfly Oestrus ovis (Diptera: Oestridae) in southwest Germany.

We present a case of ophthalmomyiasis externa in a 54-year-old man in southwest Germany (Baden-Württemberg). After the patient had been attacked by a fly, he complained of a foreign-body sensation and itching in his right eye and developed purulent conjunctivitis. Slit-lamp examination revealed the presence of translucent, rapidly moving insect larvae in the conjunctival sac and on the corneal surface. Following removal of all larvae and instillation of gentamicin, the symptoms completely resolved within 2 days. Two of the nine larvae removed were examined by light microscopy and taxonomically classified as first-instar larvae of the sheep botfly Oestrus ovis L. 1758. Although this fly is the most common causative agent of external ophthalmomyiasis in the world, infestations in central Europe have only rarely been reported. Besides the case report and a detailed description of the larvae, an overview of the literature on European cases of ophthalmomyiasis externa caused by Oestrus ovis is given.

Animals

Effect of topically applied anti-CD4 monoclonal antibodies on orthotopic corneal allografts in a rat model.

PURPOSE: Monoclonal antibodies (mAb) have generated interest as therapeutic agents. Limited data are available on the treatment of corneal graft rejection. The purpose of this study was to assess the use of topically applied mAb on experimental corneal grafts. METHODS: W 3/25, an IgG 1 mouse antirat mAb that recognizes a CD4+ cell subset, was used to treat Lewis recipient rats that received orthotopic corneal grafts of Wistar-Furth donors. Recipients were randomly assigned to receive topically applied drops of liposome-incorporated anti-CD4 mAb (LIP-anti-CD4 mAb), an equivalent amount of free anti-CD4 mAb, an isotype-matched control mAb encapsulated in liposomes (LIP-control mAb), or empty liposomes (emp-LIP) 5 times daily for 10 days. To investigate the immunologic effect of mAb treatment, flow cytometry of the targeted cells and cytotoxic activity of lymphocytes were analyzed. RESULTS: Application of LIP-anti-CD4 mAb was effective in reducing the rejection rate (P < .05) and in prolonging the mean survival time of corneal grafts that underwent rejection (P < .05). In contrast, no significant effect on graft outcome was observed after the application of control agents. Flow cytometry analysis did not reveal systemic depletion of the targeted lymphocyte subset in any anti-CD4 mAb treated animals. Rejected grafts elicited a cellular cytotoxic immune response in a cell-mediated lymphocytotoxic assay independent of the treatment given. CONCLUSION: The results suggest that treatment with topically applied LIP-anti-CD4 mAb prolongs graft survival in orthotopic corneal grafts in a rat model. The beneficial effect of LIP-anti-CD4 mAb, probably due to enhanced intraocular delivery, was achieved by using relatively low doses of mAb.

Administration, Topical

[Erythema exsudativum multiforme major].

UNLABELLED: Erythema exudativum multiforme major (EEMM), also know as Stevens-Johnson syndrome, may cause severe conjunctival and corneal alterations. The etiology remains unknown. The aim of are study was to evaluate the clinical course, therapy and prognosis of ocular involvement. PATIENTS AND METHODS: In a retrospective study, we evaluated ten patients with EEMM who were treated between 1986 and 1994 at the University Eye Clinic Tübingen. RESULTS: The age of the four female and six male patients varied between 5 and 70 years. Drugs as a possible precipitating factor were found in all cases (acetylsalicylicacid, sulfonamide, erythromycin, cotrimoxazole, Valproinicacid, paracetamol). Eight patients experienced an infection at the same time. Clinically, we were able to differentiate two groups regarding severity of the disease. Seven patients were characterized by ocular alterations that only involved the conjunctiva, leading to conjunctival scars. In those cases local treatment with antibiotics and corticosteroids was effective. In the second group severe ocular damage occurred, with symblephara, keratinization and consecutive perforating keratoplasty. Secondary infections became evident in a total of six cases from the two groups. SUMMARY: Drugs as a possible precipitating factor could be identified in all cases. In eight of ten patients previous infection was known. This agrees with literatures reports of viral infections (e.g. herpes simplex) as cofactors causing EEMM, especially for the aggressive form, remains unresolved. The danger of possible superinfection should always be taken into consideration.

Adolescent