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Biomedical subjects

U Pleyer

Publications and source records attributed to U Pleyer.

At least 109 records · Page 6Linked to original sources

[Severe eye involvement in pemphigus vulgaris].

Pemphigus vulgaris (PV) is an immune-mediated vesiculobullous disease of the skin and mucous membranes. Generally, patients with PV present first with oral lesions, which may precede the cutaneous lesions, such as bullae and erosions, by several months. An ocular manifestation is unusual. The most common ophthalmologic involvement in pemphigus is conjunctivitis, but without progressive scarring such as occurs in ocular cictricial pemphigoid. Corneal involvement is very rare. CASE REPORT. We report on severe ocular involvement in a 56-year-old male Turkish patient with PV. Ophthalmologic findings included conjunctival cicatrization, corneal ulceration and corneal perforation, despite immunosuppressive therapy with azathioprine and corticosteroids. A penetrating keratoplasty was performed, but rapidly failed because of corneal vascularization. CONCLUSION. If a chronic bullous dermatosis leads to severe eye involvement, PV should be considered in the differential diagnosis besides ocular cicatricial pemphigoid. Pemphigus vulgaris can be differentiated on the basis of clinical findings and histopathological and immunohistological features. Generally, PV can be treated with steroids or with a combination of an immunosuppressant and steroids. However, the combination of prednisone and azathioprine could not prevent corneal perforation in our patient.

Conjunctiva↗

Neuroendocrine alterations in uveitis patients.

Experimental models of autoimmune uveitis are consistently associated with pinealitis. To investigate the interaction between the neuroendocrine and immune systems in humans with uveitis, we measured serum levels of the predominant pineal hormone melatonin (MEL), prolactin (PRL) and interleukin-2 (IL-2). A total of 100 patients with different forms of uveitis and 30 age-matched, healthy blood donors were evaluated retrospectively. The day-time MEL was reduced significantly (P < or = 0.01) in patients with iritis and iridocyclitis, and highly significantly (P < or = 0.001) in patients with intermediate uveitis, chorioretinitis and panuveitis. In 38% of patients day-time MEL levels in plasma were below the limit of detection. PRL was significantly reduced (P < 0.01) in patients with intermediate uveitis. IL-2 was reduced to about 50% of control values in all groups of patients. The results suggest a possible neuroendocrine-immune interaction in uveitis patients.

Adolescent↗

Ocular absorption of cyclosporine A from liposomes incorporated into collagen shields.

We investigated the ability of liposomes to deliver the immunosuppressive agent cyclosporine A (CsA) to the cornea, anterior sclera, aqueous humor, and vitreous in rabbit eyes. One drop (10 microliters) of liposome-encapsulated CsA (CsA-LIP) or olive oil drops containing an equivalent concentration of CsA (CsA-DR) were administered at 15-minute intervals within the first hour and then one hourly over a 6-hour period. In addition, collagen shields soaked for 30 minutes in the liposome preparation (CsA-LIP-CS) were tested in vitro and in vivo as a new drug delivery approach. CsA levels were measured by fluorescence-immunoassay after 1, 3, or 6 hours of drug administration. CsA levels in this study were highest in cornea and anterior sclera. In animals receiving either CsA-DR or CsA-LIP, CsA levels generally increased from 1 to 6 hours. In animals receiving a single application of CsA-CS-LIP, CsA levels peaked at 3 hours and declined at 6 hours in cornea and sclera. CsA-LIP and CsA-CS-LIP delivered significantly higher levels of CsA to the cornea and sclera at 1 and 3 hours than CsA-DR. In aqueous and vitreous humor, CsA levels increased from 1 to 6 hours in animals receiving either CsA-DR or CsA-LIP. On the other hand, animals receiving a single application of CsA-CS-LIP had lower levels of CsA at 6 hours than at the earlier time points. Animals receiving CsA-LIP or CsA-CS-LIP had significantly higher levels of CsA in aqueous and vitreous humor at 1, 3, and 6 hours than animals receiving CsA-DR.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

Collagen shields impregnated with gentamicin-dexamethasone as a potential drug delivery device.

We investigated the ability of collagen shields impregnated with gentamicin sulfate and dexamethasone to deliver medication into rabbit eyes. We compared the aqueous humor gentamicin and dexamethasone levels delivered by collagen shield and subconjunctival injection therapy at five time points over a ten-hour period, by using a fluorescence polarization immunoassay and high-pressure liquid chromatography. Our in vitro studies showed that impregnated collagen shields released most of the gentamicin within the first 30 minutes of elution, whereas dexamethasone was released gradually over a ten-hour period. The collagen shields impregnated with gentamicin and dexamethasone produced aqueous gentamicin levels that were significantly lower (P = .014) than those produced by subconjunctival injection therapy at 30 minutes and that were comparable to subconjunctival injection therapy at the other time points. Minimum inhibitory concentrations of gentamicin (approximately 4 micrograms) were observed in aqueous humor within 30 minutes in rabbits that received subconjunctival injections and at one hour in rabbits treated with impregnated collagen shields. The impregnated collagen shields produced aqueous dexamethasone levels that were significantly lower (P = .004) than those produced by subconjunctival injection therapy at one hour, significantly higher (P = .028) than subconjunctival injection therapy at six hours, and comparable to subconjunctival injection therapy at the other time points. Collagen shield delivery of gentamicin-dexamethasone may be comparable to subconjunctival injections and provide an alternative therapy after intraocular surgery.

Animals↗

Prolongation of corneal allograft survival with liposome-encapsulated cyclosporine in the rat eye.

PURPOSE: To study the effects of different formulations of topical cyclosporine (Cyclosporin A [CsA]) on corneal allograft rejection in a rat model. METHODS: Female Lewis rats received penetrating keratoplasties from female Wistar-Furth donors. A total of 78 allogeneic grafts were performed. An additional 15 syngeneic grafts (Lewis) were used as technical controls. Two CsA preparations with equivalent drug concentrations (2.1 mg/ml) were applied as drops: CsA encapsulated in large unilamellar liposomes (CsA-LIP) and CsA dissolved in olive oil (CsA-DR). Allogeneic grafts were randomly assigned to receive CsA-LIP or CsA-DR beginning on the day of surgery five times daily for 10 days. Animals without any treatment or receiving empty liposomes (EM-LIP) were used as treatment controls. Grafts were graded three times weekly and a rejection index was generated based on graft clarity, neovascularization, and vessel size. RESULTS: All syngeneic grafts remained clear over the observation period of 60 days. Rejected allogeneic grafts without any treatment and those receiving EM-LIP or CsA-DR showed a mean survival time (+/- standard deviation) of 14 +/- 4, 14 +/- 5, and 14 +/- 4 days, respectively. There was no significant difference in mean survival time between the grafts without any treatment and those in CsA-DR or EM-LIP treatment groups. The mean survival time of rejected grafts in animals receiving CsA-LIP was prolonged to 20 +/- 4 days. There was a significant difference in the mean survival time between the CsA-LIP treatment group and groups receiving CsA-DR, EM-LIP, or no treatment (P < or = 0.05). The Kaplan-Meier survival curve of the CsA-LIP treatment group was significantly different from the other experimental groups. The graft survival rate in the CsA-LIP group was 77%, whereas the rate was 37% in the non-treated group, 45% in the CsA-DR group, and 36% in the EM-LIP group. CONCLUSION: Encapsulation of CsA in liposomes might be a promising formulation for use in the prevention of corneal graft rejection.

Animals↗

Ocular absorption of topically applied FK506 from liposomal and oil formulations in the rabbit eye.

PURPOSE: To investigate the use of topically applied FK506, a new immunosuppressive compound, systemic and ocular absorption was determined in serum and various ocular tissues. METHODS: Two drops of 20 microliters FK506 were applied using oil dissolved (OD-FK506) or liposome-bound (LIP-FK506) drug. FK506 concentrations were measured at intervals of 30, 60, and 120 minutes by immunoassay. RESULTS: After application of OD-FK506, the highest concentrations of FK506 were found in the cornea and the conjunctiva (200-1200 ng/g) with substantial drug also present in anterior and posterior sclera. Relatively low concentrations were measured in the aqueous and vitreous humors (0.2-1.0 ng/g) of these animals. Using the same treatment regimen, LIP-FK506 was effective in delivering significantly higher drug concentrations (P < 0.05) to all ocular tissues and particularly aqueous humor (5-28 ng/g) and vitreous humor (12-22 ng/g) at all time points. During the observation period drug concentrations produced by LIP-FK506 remained well above the therapeutic range. FK506 levels were not detectable in serum (< 0.2 ng/ml) with either drug formulation. CONCLUSION: These findings indicate that liposomes may be a promising formulation for topical use of FK506 in ocular immune-mediated diseases.

Absorption↗

Use of collagen shields containing amphotericin B in the treatment of experimental Candida albicans-induced keratomycosis in rabbits.

We evaluated the effect of collagen shields presoaked with amphotericin B on the treatment of experimental Candida albicans-induced keratitis. Treatment results were compared to those of amphotericin B eyedrops instilled hourly. Forty-eight albino rabbits received intrastromal injections of 10(8) C. albicans organisms. Twenty-four hours later, eyes were treated for eight hours each day with hourly instillation of 0.15% amphotericin B drops, hourly instillation of saline drops, or application of a collagen shield presoaked in 0.5% amphotericin B for one hour. The rabbits were killed after one, three, or five days of treatment. Quantitation of fungi in the cornea was achieved by culturing homogenates and counting colony-forming units. Treatment with amphotericin B applied either as hourly instilled drops or absorbed in collagen shields significantly (P less than .05) reduced corneal fungal counts at all time points when compared to saline-treated control eyes. Rabbit eyes treated with amphotericin B-soaked collagen shields had significantly lower fungal counts compared with hourly instilled amphotericin B drops at Days 1 (P = .02) and 3 (P = .04), but not at Day 5. The collagen shields were as effective in reducing the number of colony-forming units as were amphotericin B drops at Day 5. These data suggest that collagen shields soaked in amphotericin B could be a useful and convenient treatment device in keratomycosis such as that caused by C. albicans.

Administration, Topical↗

[Clinical aspects, follow-up and results of cataract extraction in uveitis].

Over a 5-year period, a consecutive series of 52 eyes in 46 patients with uveitis underwent extracapsular cataract extraction. Twenty-eight of these cases received a posterior chamber intraocular lens (IOL). During an average follow-up of 25 months (range 7 to 58 months) 71% of eyes receiving an IOL achieved postoperatively a visual acuity of 0.5 or better; 54% of aphakic eyes reached this level. Persistent cystoid macular edema limited the visual improvement to 20/200 in 6 patients; none of the patients developed cystoid macular edema postoperatively on clinical observation. Intraocular hypertension occurred postoperatively in 12 eyes, but was limited to a 4-week postoperative period in 9 cases. YAG laser capsulotomy was performed in 2 eyes with opacification of the posterior lens capsule without any further complications. The results suggest that uveitis patients benefit from cataract extraction and in selected cases can tolerate IOL implantation without major complications.

Adolescent↗

The effect of systemic decomplementation with cobra venom factor on corneal complement levels in guinea pigs.

The authors examined the effect of systemic administration of cobra venom factor (CVF) on hemolytic complement levels in guinea pig sera and corneas. Guinea pigs received repeated intraperitoneal injections of CVF. Sera and corneas were obtained before and 1, 2, 5, 8, 10, 12, 16, and 20 d after the initial injection of CVF. Total hemolytic complement activity was measured by lysis of sheep erythrocytes sensitized with rabbit antibodies. There was a significant decrease in serum complement levels at days 1, 2, 5, 8, and 10 after the initial injection of CVF. After this, complement levels rose to levels that exceeded preinjection values. Complement levels in corneas also declined after CVF injections with a significant decrease at days 2, 5, 8, and 10 and a return to normal thereafter. Corneal complement depletion and restoration lagged behind serum. Moreover, the rate of complement depletion and restoration was greater for serum than cornea. Light microscopic examination of representative corneas at each time did not show local tissue changes during decomplementation. This is first study (to the authors' knowledge) to document corneal complement depletion by systemic administration of CVF. Low-to-absent corneal complement levels were present 2 d after the initial injection of CVF and persisted for 6 d. This model could be used to study the influence of complement on traumatic and immunologic injuries to the cornea.

Animals↗

Immune response to Staphylococcus epidermidis-induced endophthalmitis in a rabbit model.

Although Staphylococcus epidermidis is the most common cause of postoperative pseudophakic endophthalmitis, little is known about the immune response to S. epidermidis-induced endophthalmitis. Using a rabbit model, the immune response to an intravitreal injection of 7000 S. epidermidis (group 1) or 30,000 S. epidermidis (group 2) organisms was investigated. Clinical evaluations showed that rabbits in group 2 had a more severe inflammatory reaction in the conjunctiva, cornea, iris, and vitreous than those in group 1. The inflammatory reaction in group 1 largely resolved by day 30; group 2 continued to show a severe inflammatory response. Histopathologic findings correlated with clinical findings, with rabbits in group 2 showing a more severe inflammatory reaction in both the anterior and posterior segments of the globe. Positive vitreous cultures for S. epidermidis were present in rabbits in group 1 on days 3, 7, 10, 14, and 21 but not thereafter. However, group 2 had higher vitreous colony counts at days 3, 7, and 14 and negative vitreous cultures thereafter. Neither group showed delayed hypersensitivity to S. epidermidis antigens (evaluated by skin tests). Serum immunoglobulin (Ig) G antibody levels to phenol-inactivated S. epidermidis and glycerol teichoic acid (GTA) increased progressively, reached a peak at days 10-14, and then declined in both groups. Serum IgA antibody levels to these antigens were not detected. Group 2 had a more prolonged IgG antibody response in vitreous and aqueous than group 1. Tear fluid showed the weakest IgG and IgA antibody response to S. epidermidis and GTA. S. epidermidis-induced endophthalmitis was associated with a humoral but not a delayed hypersensitivity response to this organism.

Animals↗

Elevated prolactin levels in human aqueous humor of patients with anterior uveitis.

Evidence is accumulating that prolactin (PRL) may play a physiological role in the regulation of humoral and cell-mediated immune responses. On the basis of these observations, we measured levels in the serum and aqueous humor of 28 patients with cataract or anterior uveitis with concomitant cataract. Intraocular concentrations were measured in a range from 0.1 to 3.4 ng/ml. Whereas serum PRL levels failed to show significant differences between the two groups (P = 0.39), intraocular concentrations were significantly higher in uveitis patients (P less than 0.001). The level in aqueous humor did not reflect the serum concentration in either group. To the best of our knowledge, this is the first study measuring PRL concentrations in human aqueous humor.

Adolescent↗

Device drug delivery to the eye. Collagen shields, iontophoresis, and pumps.

External devices have been used to enhance drug delivery. This article reviews the role of collagen shields, iontophoresis, and pumps used to deliver ophthalmic medications. Collagen shields have been used to deliver drugs and promote corneal epithelial healing. Presoaked collagen shields deliver many drugs to the eye as well as or better than traditional methods such as frequent topical therapy or subconjunctival injection. The efficacy of drug delivery by collagen shields was demonstrated in animal models of graft rejection and bacterial keratitis. Iontophoresis uses an electrical current to carry an ionized drug across tissue. Transcorneal iontophoresis delivers high concentrations of a drug to the anterior segment of the eye. Transscleral iontophoresis bypasses the lens-iris diaphragm and produces adequate vitreous levels. Pumps deliver fluid to the eye for extended periods of time via a tube with its distal opening in the conjunctival sac, corneal stroma, anterior chamber, or vitreous cavity. Clinical acceptance of the collagen shield for drug delivery to the anterior segment is better than iontophoresis or pumps, probably because the collagen shield is simpler and more convenient to use.

Absorption↗

[Intraocular availability of liposome encapsulated monoclonal antibodies in the rabbit model. Results of a pilot study].

The results of local application of monoclonal antibodies (mAb) in rabbit eyes are presented. To improve intraocular access of the high-molecular-weight protein it was entrapped in large (0.2 microns) unilamellar, negatively charged liposomes. Concentrations of the free or encapsulated drug were measured by ELISA in different eye compartments following repetitive drop administration or single subconjunctival injection. Although mAb became measurable in specimens of conjunctiva and cornea, it was not detectable (less than 0.5 ng/ml) in aqueous humor, lens or the vitreous body. In contrast, concentrations of the liposome-encapsulated drug were measurable as little as 30 min after topical application in the aqueous humor.

Animals↗

[Bromocriptine in therapy of chronic recurrent anterior uveitis].

In animal studies, bromocriptine (Pravidel) has demonstrated immunosuppression because of inhibition of prolactin. After publication of positive results in the treatment of uveitis in a few case reports and in an uncontrolled study we conducted a double-blind placebo-controlled study in 13 patients with chronic recurrent anterior uveitis who had experienced three or more recurrences during the previous year. Therapy was started gradually during the symptom-free interval and continued for 1 year with 2.5 mg twice daily. Two recurrences or relevant side effects led to discontinuation of the therapy. In the bromocriptine group, 2 of 7 patients had no recurrences during the study period. Two patients had to stop because of two recurrences but, in contrast to earlier recurrences, they responded to local corticosteriod treatment within a few days. The remaining 3 patients (1 with one recurrence, 2 without) had to stop because of the side effects (arterial hypotension, arthritic complaints). In 5 of 6 patients in the placebo group treatment was stopped because of recurrences and in 1 patients because she believed she was experiencing a side effect from bromocriptine (breast atrophy). In summary, bromocriptine seems to have a prophylactic effect on anterior uveitis. Side effects were frequent but mild compared to other immunosuppressives. In case of arterial hypotension, additional therapy could make this drug more tolerable.

Adolescent↗

[Drug-induced exudative erythema multiforme major with a chronic progressive course and bilateral blindness. Clinical and immunohistologic follow-up].

A 24-year-old male patient who had been received Fansidar developed exudative erythema multiforme major with massive involvement of the skin, mucous membranes, and both eyes. The chronic inflammation led to proliferation of the conjunctiva, with keratinization of the ocular surface and corneal vascularization. The final result was comparable to cicatricial pemphigoid, with blindness of both eyes. In histological sections, massive lympho-plasma-cellular infiltration with circumscribed perivasculitis was seen. The lymphocyte transformation test was still positive 18 months after onset of the disease. Class II antigens were evident in some of the conjunctival biopsies.

Adult↗

[Isolated infiltration of the vitreous body as a sign of blast crisis in chronic myeloid leukemia].

A 29-year-old man with chronic myeloid leukemia and two successfully treated blast crises exhibited ocular symptoms. Eighteen months after the diagnosis of leukemia he presented with unilateral hyperplastic iris stroma, anterior chamber inflammation and vitreous infiltration. Uveitis was diagnosed tentatively, and local therapy was begun with corticosteroids. Because the findings remained unchanged an invasive diagnostic evaluation followed. Although iris biopsy revealed only unspecific mononuclear cell infiltration (mainly T-lymphocytes), selectively aspirated vitreous material contained myeloid cells of different stages of maturation and blast cells. Peripheral blood, liquor and bone marrow showed no signs of acceleration or transition of the primary disease. Thus, an extramedullary blast crises with isolated vitreous infiltration was diagnosed.

Adult↗