[Glaucoma with unilateral reddening of the eye].
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Antihypertensive Agents↗
Biomedical subjects
K P Steuhl
Publications and source records attributed to K P Steuhl.
[Do antisense oligonucleotides improve viral immunopathology?].
BACKGROUND: Tumor necrosis factor (TNF)-alpha as a proinflammatory cytokine is of great importance during the development of herpes simplex virus-1 keratitis (HSK). In this study the local administration of antisense oligonucleotides (ASON) targeting TNF-alpha was examined for its usefulness in ameliorating this disease. METHODS: Uptake and efficacy of the oligonucleotides were studied in vitro by fluorescence microscopy and flow cytometry. Substance- and sequence-specific influences on the development of HSK were scrutinized in an animal model. RESULTS: Quick and stable uptake of FITC-labeled ASON by isolated spleen and lymph node cells was proved. The production of TNF-alpha by these cells after stimulation with HSV antigen or concanavalin A (ConA) was clearly downregulated after addition of ASON. In vivo, incidence and development of HSK were ameliorated after subepithelial corneal injection of ASON targeting TNF-alpha. When buffer and control oligonucleotides were given, no significant influence on the disease was found. CONCLUSION: The ASON effectively reduced TNF-alpha secretion in vitro and suppressed the development of experimental HSK in vivo.
Animals↗
[Chronic progressive cicatrizing conjunctival diseases: mucosal pemphigoid].
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Chronic Disease↗
[Amniotic membrane transplantation improves experimental herpetic keratitis. Modulation of matrix metalloproteinase-9].
PURPOSE: Transplantation of human amniotic membrane (AMT) accelerates the healing of experimental ulcerative herpetic keratitis. Here the expression and activity of matrix metalloproteinase (MMP)-9 was studied. METHODS: BALB/c mice were corneally infected with HSV-1. Whereas the infected corneas of mice in group 1 were covered with AM, tarsorrhaphies were performed in others (group 2). After 2 days, the appearance of corneal ulcers and stromal inflammation was judged clinically, and the corneal PMN infiltration was studied histologically. The expression of MMP-9 in the corneas was localized by immunohistochemistry and analyzed by Western-blot technique. The MMP-9 activity in the corneas was determined by zymography. RESULTS: On day 14, the ulcerating corneas had a dense PMN infiltration, the ulcers and the majority of PMNs were highly positive for MMP-9, and the active forms of MMP-9 were detected. Gelatinolytic activity was found in these corneas by zymography. Compared with the mice of group 2, ulceration, stromal inflammation and neovascularization markedly improved clinically and histologically within 2 days in mice of group 1. This was associated with a reduced expression of MMP-9 in corneal tissue and in PMNs. The gelatinolytic activity of MMP-9 was reduced after AMT. CONCLUSIONS: These observations suggest that improvement of herpetic corneal ulcers and reduced corneal neovascularization after AMT may result from a reduced expression and activity of MMP-9.
Adjuvants, Immunologic↗
[Amniotic membrane transplantation improves herpetic keratitis by local and not by systemic effects].
PURPOSE: The immune mediated HSV-1 stromal keratitis (HSK) rapidly improves after amniotic membrane transplantation (AMT). This study investigated whether AMT modulates the T cell response and whether the anti-inflammatory action of AMT is due to local or systemic effects. METHODS: Corneas of BALB/c mice were infected with 10(5) (PFU) of HSV-1. Animals with ulcerating keratitis on day 14 post-infection were divided into 4 groups: group 1 ( n=12): right eye AMT;group 2 ( n=12): right eye tarsorrhaphy; group 3 ( n=8): right eye tarsorrhaphy, left eye AMT;group 4 ( n=8): both eyes tarsorrhaphy. The mice were examined for clinical signs of HSV keratitis after 2 days. Corneal sections were studied histologically and the inflammatory cell infiltration was studied by immunohistochemical staining. DTH response and the HSV-specific 3H-thymidin-uptake were compared between the groups. RESULTS: Compared to group 2, ulceration and stromal inflammation was profoundly improved in group 1 ( p<0.01). The corneas in the AMT mice had fewer inflammatory cells, CD3+,CD4+ and CD8+ cells than the control mice ( p<0.01). There were no significant differences between groups 1 and 2 with respect to the delayed type hypersensitivity reaction (DTH response) and the HSV-specific 3H-thymidin uptake. AMT or tarsorrhaphy on the left eyes in groups 3 and 4 had no influence on the course of keratitis or the T cell response. CONCLUSIONS: Ulcerating herpetic keratitis markedly improves after AMT. Our observations indicate that this is caused predominantly by local and not by systemic AMT-related effects.
Animals↗
Incidence and severity of herpetic stromal keratitis: impaired by the depletion of lymph node macrophages.
HSV-1 induced stromal keratitis (HSK) is an immune-mediated disease. The role of macrophages in this process is still unclear. In this study we investigated the influence of specific macrophage depletion from the spleen and the submandibular lymph nodes by dichloromethylene diphosphonate liposomes (Cl(2)MDP-LIP) on the course of HSV-1 keratitis. BALB/c mice were infected corneally with 10(5)PFU of HSV-1 (KOS). Groups of mice received Cl(2)MDP-LIP 7 and 2 days prior to infection. Cl(2)MDP-LIP were given by various routes: intravenously (i.v.) for macrophage depletion in the spleen; subcutaneously for macrophage depletion in the submandibular regional lymph node (s.c.); or both i.v. and s.c. The development of HSV-1 keratitis was evaluated clinically and histologically. A standard plaque assay from the infected eyes was used to measure virus clearance. Seventy-nine percent of the HSV-1-infected control mice (n = 14) developed severe stromal keratitis by day 14 p.i. The development of stromal keratitis was inhibited by Cl(2)MDP-LIP given s.c. (64%;n = 14;P < 0.05), i.v. and s.c. (50%;n = 14;P < 0.05), but not by i.v. treatment alone (77%;n = 13). After s.c., i.v. and s.c. Cl(2)MDP-LIP injection, histologically the corneal stroma had a decrease in inflammatory cell infiltration by day 14 p.i. compared to the control group, and the DTH response was reduced. The healing of epithelial HSV-1 keratitis and the virus clearance were not affected significantly. These results indicate an important function of macrophages in the course of HSV-1 keratitis. Virus replication in the eye does not appear to be affected by monocytes/macrophages of lymph nodes and spleen. In contrast, the immunopathological process of stromal HSV-keratitis that results in corneal destruction is profoundly accelerated by macrophages in the lymph nodes.
Animals↗
Antiphosphatidylserine antibodies are elevated in normal tension glaucoma.
The two main entities of open-angle glaucoma are primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG). Both diseases may be associated with autoimmune processes. Therefore, IgG and IgM antibodies to phospholipids (APL) and their subspecies cardiolipin (ACL), phosphatidylserine (APS) and beta2-glycoprotein (beta2GP) were determined in 43 NTG patients, 40 POAG patients and 40 healthy controls in a prospective study. The most prominent observation was the increase in APS concentrations in NTG patients (IgG 20.6 +/- 2.7 U/ml, IgM 24.4 +/- 3.4 U/ml) compared with POAG patients (IgG 8.8 +/- 1.2 U/ml, IgM 11.0 +/- 1.7), and controls (IgG 7.7 +/- 1.3 U/ml, IgM 12.8 +/- 1.5 U/ml). APS may be important due to their binding specificity to phosphatidylserine molecules which become accessible during apoptosis; this in turn may lead to local thrombosis.
Aged↗
[Normal tension glaucoma, sleep apnea syndrome and nasal continuous positive airway pressure therapy--case report with a review of literature].
BACKGROUND: In the pathogenesis of glaucoma, besides an elevated intraocular pressure (IOP), cardiovascular risk factors, such as arterial hypotension and hypertension, vasospasms, autoregulatory defects, atherosclerosis, and diabetes mellitus are of increasing importance, especially in normal tension glaucoma. Recently, there have been several reports of an additional risk factor: obstructive sleep apnea syndrome. METHODS: Literature review (Medline) and case report. RESULTS: The authors report on a 8 1/2 years follow-up of a 60-year-old patient with normal tension glaucoma. Despite successful pharmacological and surgical lowering of intraocular pressure a progressive glaucomatous damage with optic nerve atrophy and increasing visual field defects occurred. As a result of intensive investigations of possible cardiovascular risk factors, an obstructive sleep apnea syndrome was diagnosed. Since the beginning of therapy with nCPAP (nasal continuous positive airway pressure) more than 3 1/2 years ago, no further progression of glaucomatous optic nerve damage or visual field defects have been observed. CONCLUSIONS: In clinical practice, obstructive sleep apnea syndrome often is underdiagnosed. In patients suffering from glaucoma and obstructive sleep apnea syndrome, intraocular pressure lowering therapy may not be enough, whereas an additional nCPAP-therapy potentially could prevent the beginning/progression of glaucomatous optic nerve damage.
Glaucoma↗
Bilateral conjunctival lesions in Melkersson-Rosenthal syndrome.
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Anti-Inflammatory Agents, Non-Steroidal↗
Improvement of HSV-1 necrotizing keratitis with amniotic membrane transplantation.
PURPOSE: Stromal herpes simplex virus keratitis (HSK) is an immune-mediated disease. Previous studies have indicated that T cells, neutrophils, and macrophages contribute to the tissue damage in HSK. It has been shown that human amniotic membrane promotes epithelial wound healing and has diverse anti-inflammatory effects. In this study, the effect of amniotic membrane transplantation (AMT) on corneal wound healing and on inflammation in mice with necrotizing HSK was examined. METHODS: BALB/c mice were corneally infected with 10(5) plaque-forming units (PFU) of HSV-1 (KOS strain). In 16 mice that exhibited severe ulcerating HSK, the cornea was covered with a preserved human amniotic membrane as a patch. Corneas in 16 infected mice remained uncovered and served as a control. On days 2 and 7 after surgery, the amniotic membrane was removed (eight mice in each group), the HSV-1-infected cornea was evaluated clinically, and the eye was enucleated. Tissue sections were analyzed histologically for epithelialization and cellular infiltration and immunohistochemically with anti-CD3 mAb to T cells, anti-CD11b mAb to both macrophages and neutrophils, or anti-F4/80 mAb to macrophages. RESULTS: Profound regression of corneal inflammation and rapid closure of epithelial defects were observed clinically within 2 days in the amniotic membrane-covered eyes, whereas HSV-1 keratitis and ulceration progressed in all mice in the control group (P < 0.001). Histologically, corneal edema and inflammatory infiltration, and immunohistochemically the number of CD3(+), CD11b(+), and F4/80(+) cells in the cornea were markedly decreased at 2 and 7 days after amniotic membrane application, compared with the uncovered control corneas (P < 0.001). CONCLUSIONS: AMT promotes rapid epithelialization and reduces stromal inflammation and ulceration in HSV-1 keratitis. AMT in mice with HSV necrotizing stromal keratitis appears to be a useful model for investigating the effect and the action mechanism of human amniotic membrane.
Amnion↗
Scanning laser polarimetry, retinal nerve fiber layer photography, and perimetry in the diagnosis of glaucomatous nerve fiber defects.
BACKGROUND: Retinal nerve fiber layer defects are part of early glaucomatous damage. In the present study, we compared the ability of retinal nerve fiber layer photography (NFP) and scanning laser polarimetry (SLP) to detect nerve fiber layer defects in glaucoma patients. METHODS: Besides ophthalmological standard examinations, we performed NFP (Zeiss Ikon fundus camera 30 degrees, green filter), SLP (GDx, 1.0.14 and 2.0.09, LDT) and automated perimetry (Oculus, Twinfield, 30 degrees) in 150 glaucoma patients [74 with primary open-angle glaucoma (POAG) and 76 with normal-tension glaucoma (NTG)]. The perimetric results were evaluated according to a modified Aulhorn classification. NFP and SLP were graded according to Quigley. RESULTS: In POAG, 42% of NFP and 5% of SLP were not evaluable. In NTG, 24% of NFP and 4% of SLP were not evaluable. In POAG, NFP and SLP revealed a direct agreement in 54.5%, and in NTG, 55%; there was a small difference of one stage in 39.5% (POAG) and 41% (NTG). In POAG, NFP/SLP showed agreement with perimetric results in 35%/30% of cases and differences of one stage in 56%/58%. In NTG, NFP/SLP agreed with perimetry in 52%/48% of cases and differed by only one stage in 32%/39%. Larger deviations were found in less than 13% of the cases. CONCLUSIONS: NFP and SLP mostly showed good agreement or little deviation as to grading of nerve fiber layer damage. In clinical use, SLP has advantages over NFP because a higher rate of good-quality images can be obtained and pupils do not have to be dilated. Additionally, SLP measurements provide quantitative data and a large normative data base exists.
Adult↗
Amniotic membrane transplantation for acute chemical or thermal burns.
PURPOSE: To determine whether preserved human amniotic membrane (AM) can be used to treat ocular burns in the acute stage. DESIGN: Prospective, noncomparative, interventional case series. PARTICIPANTS: Thirteen eyes from 11 patients with acute burns, 10 eyes with chemical burns and 3 with thermal burns of grades II-III (7 eyes) and grade IV (6 eyes), treated at 7 different facilities. METHODS: Patients received amniotic membrane transplantation (AMT) within 2 weeks after the injury. MAIN OUTCOME MEASURES: Integrity of ocular surface epithelium and visual acuity during 9 months of follow-up. RESULTS: Ten patients were male and one patient was female; most were young (38.2 +/- 10.6 years). For a follow-up of 8.8 + 4.7 months, 11 of 13 eyes (84.63%) showed epithelialization within 2 to 5 weeks (23.7 +/- 9.8 days), and final visual acuity improved > or = 6 lines (6 eyes), 4 to 5 lines (2 eyes), and 1 to 3 lines (2 eyes); only one eye experienced a symblepharon. Eyes with burns of grade II to III showed more visual improvement (7.3 +/- 3 lines) than those with burns of grade IV (2.3 +/- 3.0 lines; P < 0.05, unpaired t test). In the group with grade II or III burns, none had limbal stem cell deficiency. All eyes in the group with grade IV burns did experience limbal stem cell deficiency. CONCLUSIONS: Amniotic membrane transplantation is effective in promoting re-epithelialization and reducing inflammation, thus preventing scarring sequelae in the late stage. In mild to moderate burns, AMT alone rapidly restores both corneal and conjunctival surfaces. In severe burns, however, it restores the conjunctival ocular surface without debilitating symblepharon and reduces limbal stromal inflammation, but does not prevent limbal stem cell deficiency, which requires further limbal stem cell transplantation. These results underscore the importance of immediate intervention in the acute stage of eyes with severely damaged ocular surface. Further prospective randomized studies including a control group are required to determine the effectiveness of AMT in acute chemical and thermal burns of the eye.
Acids↗
[Apoptosis in human non-necrotizing stromal herpes simplex keratitis].
BACKGROUND: Herpes simplex virus (HSV-1) stromal keratitis is an immune-mediated disease. Recently, it has been shown that infection of cells with HSV-1 induces apoptosis. In this study we investigated the presence of apoptotic cell death in keratectomy specimens from patients with HSV-1 stromal keratitis. PATIENTS AND METHODS: Keratectomy specimens from six patients with HSV-1 non-necrotizing stromal keratitis were chosen and compared to healthy corneas. Paraffin sections were analyzed histologically and cryosections were studied by the immunoperoxidase technique for the presence of HSV-1, Fas and FasLigand (FasL) antigens. Apoptosis was assessed by TUNEL assay (TdT-mediated dUTP nick-end labeling). RESULTS: In healthy corneas, Fas was detected in the epithelium, keratocytes and endothelium; FasL was present in the epithelium and endothelium; TUNEL-positive cells were only found in the superficial epithelial cells. In contrast, inflammatory cells and scars were found in all HSV-diseased corneas; HSV-1 antigen was detected in only one specimen. Cells within inflammatory infiltrations and epithelium were apoptotic. Fas was detected in all corneal cell layers and inflammatory cells. FasL was restricted to areas of inflammation. CONCLUSIONS: The data suggest that apoptosis plays a role in the pathogenesis of HSV keratitis. The Fas-FasL system appears to be involved in the induction of apoptosis. Apoptosis could be involved in the depletion of inflammatory cells in the cornea and may limit the extension of viral replication to the eye.
Antigens, Viral, Tumor↗
Macrophage-depletion influences the course of murine HSV-1 keratitis.
PURPOSE: Herpes simplex virus type 1 infection of the cornea induces an immune-mediated disease termed "herpes stromal keratitis" (HSK) that is a major cause of blindness. In this study we investigated the influence of macrophage depletion by Cl(2) MDP encapsulated in liposomes (Cl(2) MDP-LIP) on the course of HSV-1 keratitis. METHODS: The corneas of BALB/c mice were infected with 10(5) PFU of HSV-1 (KOS strain). Mice groups received sub-conjunctival PBS or Cl( 2) MDP-LIP injections 7 and 2 days prior to infection. The eyes were studied clinically, histologically and immunohistochemically with F4/80 antibody at various time points after treatment. Clearance of the virus from the HSV-infected eyes was measured with a standard plaque assay. RESULTS: After subconjunctival Cl(2) MDP-LIP treatment, the HSV-1-induced epithelial keratitis was more severe (P < 0.05). The virus titers were significantly higher after macrophage depletion (day 7, P < 0.005). Stromal keratitis developed in 78.6% of HSV-1 infected PBS treated control mice ( n = 14) by day 14 after infection. By subconjunctival Cl(2) MDP-LIP treatment (n = 14) the incidence of stromal keratitis was reduced to 42.9%, and the keratitis was less severe (P < 0.05). CONCLUSIONS: The data demonstrate an influence of macrophages on the course of HSV-1 keratitis in mice. Macrophage depletion influence the viral replication in the cornea and the immune-mediated process of HSK.
Animals↗
CD4+ T-cell type 1 and type 2 cytokines in the HSV-1 infected cornea.
PURPOSE: It has been previously shown that CD4+ T-lymphocytes are critical mediators in HSV-1 stromal keratitis (HSK). CD4+ T cell subpopulations (type 1, type 2) can be defined by their capabilities of producing different sets of cytokines. This study was performed to determine the role of type 1 and type 2 cytokines in murine HSK. METHODS: BALB/c mice (n = 20) were inoculated with 10(5) PFU of HSV-1 (KOS strain) and were followed clinically. At various time points post-infection (p.i.), the conjunctival and corneal tissues were analyzed histologically (n = 2 each time point), and immunohistochemically (n = 5 each time point) for the presence of interleukin-1alpha (IL-1alpha), type 1 cytokines (IL-2, interferon-gamma) and a type 2 cytokine (IL-4). The expression of cytokine mRNA was tested in eye samples by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Stromal keratitis clinically progressed after day 9. In 15% of the mice, disease regressed until day 14 p.i. Polymorphonuclear neutrophils, lymphocytes and other mononuclear cells infiltrated the conjunctiva by day 2 and rapidly expanded to the central cornea between days 7 and 14. IL-1alpha, IFN-gamma and IL-2 mRNA were found in the eyes at days 1 and 2 p.i. IL-1alpha protein was detected in the conjunctiva, limbus and corneal epithelium at day 2. The IL-1alpha staining intensities increased with disease progression. This was paralleled by IL-2 and IFN-gamma staining intensities. In contrast, IL-4 mRNA and protein were detected at days 7 through 14 after HSV-1 infection; compared to IL-2 and IFN-gamma, IL-4 staining intensities were lower. CONCLUSIONS: The findings suggest that the lymphocytic infiltrate during the development of HSV-1 keratitis is predominantly composed of type 1 cells expressing IL-2 and IFN-gamma. Type 2 cytokines participate in the late stage of inflammation and might be useful to improve the course of the disease.
Animals↗
Treatment of HSV-1 stromal keratitis with topical cyclosporin A: a pilot study.
BACKGROUND: In stromal keratitis induced by herpes simplex virus (HSV) the host's immune response contributes to corneal scarring and neovascularization. The purpose of this study was to analyze the efficacy of topically applied cyclosporin A (CsA) in patients with HSV keratitis. METHODS: The authors performed a prospective pilot study in patients with HSV stromal keratitis (n = 18). Eyes were treated with CsA eyedrops and acyclovir ointment. The drugs were tapered off gradually. Visual acuity, slit-lamp appearance, intraocular pressure and corneal sensitivity were evaluated monthly (follow-up 5.2+/-0.28 months, mean +/- SEM. RESULTS: Keratitis resolved with CsA treatment in 10 of 14 patients with non-necrotizing keratitis and in 2 of 4 with necrotizing keratitis. As CsA was used topically, the corticosteroids could be withdrawn in all patients with non-necrotizing keratitis and in 1 of 3 with necrotizing keratitis. Under CsA therapy, persistent or progressive inflammation was noted in 6 of the 18 patients. These 6 patients with keratitis improved only with combined CsA/corticosteroids. Corneal ulcers healed in 4 patients with topical CsA, and corneal neovascularization improved in a further 8. Except for toxic epitheliopathy, no further CsA complications were noted. CONCLUSIONS: The findings in this pilot study suggest that HSV stromal keratitis can be treated successfully with CsA eyedrops, especially in non-necrotizing disease. CsA may be particularly helpful in the presence of steroid glaucoma, herpetic corneal ulcers, and to taper off topical corticosteroids. Additional use of acyclovir may aid in suppressing the recurrence of epithelial HSV keratitis. A randomized study should be performed to evaluate the role of topical CsA in more detail.
Acyclovir↗
[Laser scanning topography and polarimetry with implantation of intraocular lenses before and after cataract surgery].
BACKGROUND: In the last years, scanning laser measurements were established in glaucoma diagnostics. Techniques of special interest are scanning laser topometry (SLT) for exact measurements of the optic disc and its cup and scanning laser polarimetry (SLP) for precise assessment of the retinal nerve fiber layer thickness. As glaucoma patients often suffer from a cataract, too, and a trabeculectomy additionally favors the advance of lens opacities, in the follow up of glaucoma patients cataract surgery is often necessary. PATIENTS AND METHODS: The influence of cataract surgery in phacotechnique with intraocular lens implantation (31 PMMA-IOLs, Pharmacia/Upjohn, model 811 B, and 25 HEMA/MMA-IOLs, Technomed, Memory Lens) on SLT and SLP was evaluated before and 3 to 4 weeks after cataract surgery in 56 eyes of otherwise healthy patients. Lens opacities were classified according to LOCS III. For SLT, we applied a TopSS, and for SLP a Nerve Fiber Analyzer II and a GDx (LDT, USA). RESULTS: Our results show that SLT and SLP are mostly performable at lens opacities with visual acuity reductions down to 0.16. In SLT, we usually found no big differences in the assessed parameters before and after cataract surgeries with IOL implantation. Standard deviations between three single measurements were mostly smaller postop. In SLP, nerve fiber layer patterns were very similar before and after cataract surgeries with IOL implantation whereas total nerve fiber layer thickness values postoperatively were slightly higher. CONCLUSIONS: Our results indicate that cataract surgeries with IOL-implantation have only mild influence on SLT and SLP. These findings seem to be of clinical interest especially in the follow up of glaucoma patients.
Aged↗
Effect of dacarbazine (DTIC) on cultures from malignant melanoma of the choroid: an immunohistochemical and electron microscopic study.
INTRODUCTION: Dacarbazine (DTIC) is a very effective chemotherapeutic agent used in the treatment of cutaneous melanoma; it also could have a potential therapeutic value as an antimetastatic agent in the treatment of choroidal melanoma. OBJECTIVE: To study the HMB-45 and S100 protein expression in choroidal melanoma cultures with and without DTIC, and compare the immunohistochemical and electron microscopic changes in both groups. METHODS: Five- and seven-day cultures of choroidal melanoma (n = 21) were cultivated in diffusion chambers. The cultures were divided in two groups: I group (control group)--the cells were grown in 199-medium; II group--the cells were in 199-medium supplemented with 0.03 mg/ml of DTIC. Immunohistochemical studies were performed with paraffin-embedded material of the cultures by the avidin-biotin-alkaline phosphatase technique. Araldit-embedded material was studied by electron microscopy. RESULTS: The expression of HMB-45 and S100 protein in the cultures with DTIC ranged from slightly positive to negative. The tumor cells were severely damaged. Electron microscopy in this group showed presence only of cellular fragments. In the DTIC-free group the HMB-45 and S100 expressions were strongly positive. There were no electron microscopic evidence of cellular death. CONCLUSION: DTIC suppresses the growth of choroidal melanoma in vitro. These results indicate that further studies are warranted to elucidate the effect of DTIC in vivo.
Antigens, Neoplasm↗