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Biomedical subjects

A Heiligenhaus

Publications and source records attributed to A Heiligenhaus.

At least 19 recordsLinked to original sources

Multifocal posterior uveitis in Crohn's disease.

PURPOSE: To report a case of rare posterior eye manifestation of Crohn's disease preceding recurrence of inflammatory bowel disease. METHODS: Case report with ophthalmoscopic findings, fluorescein/indocyanin green angiograms, automated perimetry and multifocal-ERG. RESULTS: The perimetry revealed absolute and relative scotomas corresponding to multifocal inflammatory lesions in the retina and choroid, reduced a/b amplitudes in multifocal-ERG and hypofluorescent dots in angiography. Under oral prednisolone visual defects, ophthalmoscopic and angiographic findings resolved, while a/b amplitudes remained mildly reduced. The ocular changes occurred without systemic hypertension and were followed by a new episode of intestinal symptoms. CONCLUSION: Multifocal inflammatory lesions in the retina and choroid in patients with Crohn's disease may occur and may precede a recurrent intestinal episode. Crohn's patients should be carefully followed up in collaboration with internal medicine specialists.

Adult↗

Comparison of two acrylic intraocular lenses with different haptic designs in patients with combined phacoemulsification and pars plana vitrectomy.

PURPOSE: The intra- and postoperative characteristics of two foldable single-piece intraocular lenses (IOL) with identical hydrophilic acrylic material, but different haptic designs (Akreos Adapt and Akreos Fit), were compared in combined phacoemulsification and pars plana vitrectomy (PPV). METHODS: This was a prospective, randomized study in patients with simultaneous cataract and vitreoretinal surgery. Group A (n=47 patients) included implantation of Akreos Fit IOL (two-point haptic) and group B (n=46 patients) implantation of Akreos Adapt IOL (four-point haptic). All intraoperative modifications of small-incision phacoemulsification and three-port PPV and IOL implantation and centration were documented. At 1 and 2 days and 6 months after surgery, best-corrected visual acuity (BCVA), slit-lamp appearance (including inflammation, IOL centration, capsulorhexis diameter, posterior capsule opacification (PCO), tonometry, and fundus findings were evaluated. RESULTS: The groups did not differ with respect to age, surgical indications and modifications, intraoperative IOL handling, and centration. At day 2, inflammation and capsulorhexis diameters were similar, but IOL decentration was slightly more frequent with Akreos-Fit IOLs. Six months after surgery, the rates of PCO, posterior synechiae, and BCVA were similar. Akreos-Fit had slightly smaller capsulorhexis diameters and slightly more capsular contraction and IOL decentration (P>0.05). CONCLUSIONS: Both of the Akreos IOL are feasible for combined phacoemulsification and PPV. Although similar in intraoperative handling, BCVA, and PCO, IOL centration was slightly better with Akreos-Adapt than with Akreos-Fit after combined surgery.

Aged↗

[Uveitis and the aging].

Uveitis can be found in all age groups, but the age of disease onset may provide important information on the etiology of the disease. New data on the epidemiology of uveitis disclose a higher incidence and prevalence in older patients then has previously been found. Masquerade syndromes which mimic uveitis may be found especially in younger and older patients. These have to be excluded from regular intraocular inflammation. Here, intraocular lymphoma plays a major role which is most often associated with severe clinical, diagnostic and therapeutic challenges. One of the major complications of uveitis is cataract formation. Keeping in mind the importance of pre- and postoperative treatment, even implantation of an intraocular lens in older patients with uveitis is currently a safe procedure.

Age Factors↗

Corneal calcification following intensified treatment with sodium hyaluronate artificial tears.

AIM: To report a potential adverse effect of intensified treatment with sodium hyaluronate artificial tears. METHODS: Five cases of deep calcium deposition in the cornea associated with ocular surface disease and frequent use of hyaluronic acid artificial tears are described. All patients used one formulation of phosphate buffered hyaluronate eye drops when rapid calcification developed. All eyes required corneal graft surgery for visual rehabilitation. Specimens at keratoplasty were available for light microscopy and investigation by dispersive x ray analysis. The phosphate concentration in the medication used for topical treatment was measured and compared to alternative hyaluronate preparations. RESULTS: Light microscopy showed dense mineralisation of the entire stroma. The crystalline deposits consisted of hydroxyapatite, Ca5(PO4)3OH. A 50-fold higher concentration of phosphate was measured in the sodium hyaluronate eye drops used for treatment (50.9 mmol/l) when compared with normal serum. The other hyaluronate formulations showed phosphate concentrations from <0.1 mmol/l to 10.9 mmol/l. CONCLUSIONS: The hyaluronate artificial tear formulation "Hylo-Comod" favours the formation of insoluble crystalline calcium phosphate deposits in presence of epithelial keratopathy. This is because of its high phosphate concentration and typically frequent instillation. Manufacturers and prescribers should be aware that topical preparations may contain considerable amounts of phosphate which may lead to sight threatening corneal complications.

Aged↗

Transscleral diode laser cyclophotocoagulation as primary surgical treatment for secondary glaucoma in juvenile idiopathic arthritis: high failure rate after short term follow up.

AIM: To evaluate the success rates of transscleral diode cyclophotocoagulation (TD-CPC) for secondary glaucoma in patients with juvenile idiopathic arthritis (JIA) as primary surgical treatment. METHODS: Retrospective chart review of 12 paediatric patients with JIA associated uveitis and secondary open angle glaucoma. RESULTS: 21 eyes of the 12 patients had chronic anterior uveitis, 21 eyes had secondary open angle glaucoma, and 19 eyes were treated 41 times with TD-CPC. Patients underwent a mean of 2.15 treatment sessions per eye. Pretreatment intraocular pressure (IOP) was 30.2 (5.5) mm Hg before the first treatment, 30.5 (5.7) mm Hg before the second treatment, and 28.7 (6.3) mm Hg before the third treatment. Reduction of IOP 6 weeks after treatment was highest after the second and third treatments with 9.4 (8.8) and 8.7 (5.8) mm Hg, respectively and 5.2 (10.7) mm Hg after the first treatment. Qualified success (IOP </=21 mm Hg with glaucoma medication) was achieved at the end of follow up in six of 19 eyes (32%, follow up time 10.1 (9.3) months). CONCLUSION: TD-CPC as a primary surgical treatment in JIA patients, is often unsatisfactory in eyes with uveitic glaucoma.

Antihypertensive Agents↗

[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↗

[Vision-threatening complications in childhood uveitis].

PURPOSE: We analyzed the epidemiologic data and vision-threatening complications in different forms of childhood uveitis. METHODS: This retrospective study included 187 consecutive patients with onset of uveitis before the age of 16 years classified as anterior (AU), intermediate (IU), posterior (PU), and panuveitis (PanU). We analyzed the epidemiologic data as well as visual acuity, uveitic complications and the conservative and surgical therapy. RESULTS: Associated disease was observed in 85 of 187 patients. The most common complications in AU patients were cataract, posterior synechiae, band keratopathy and CME. IU was accompanied by dense vitreous opacities, cataract and CME. Macular scars were the most frequent cause for visual loss in PU. PanU was complicated by dense vitreous opacities, cataract, retinal detachment, CME and phthisis bulbi. CONCLUSIONS: Childhood uveitis is frequently associated with systemic immune-mediated diseases. The diverse uveitis types have different but typical complications.

Adolescent↗

[Uveitis in childhood sarcoidosis].

BACKGROUND: Sarcoidosis is a rare cause of uveitis in childhood. Differentiation from other rheumatic diseases may be difficult. We report on five children with uveitis in childhood sarcoidosis and review the previous literature. RESULTS: Children were aged between seven month and 13 years at the time of diagnosis of uveitis. Four of the five patients had panuveitis, the fifth one had intermediate uveitis. In addition, three children had systemic disease with skin, joint and central nervous system involvement. The two children younger than 5 years showed the clinical triad of eye, joint and skin disease. Uveitic complications included corneal band keratopathy, cataract, posterior synechiae, macular scars and choroidal neovascularisation. Vision-limiting complications were found in six of nine eyes at the first visit. CONCLUSION: In childhood sarcoidosis two clinical courses can be differentiated. Younger children aged up to five years express a clinical triad of arthritis, skin lesions and uveitis. In the older group of patients, the clinical course is more similar to that of adults. Rapid diagnosis and quiescence of disease are of particular importance to improve the long-term visual prognosis.

Adolescent↗

[Diagnostic and therapeutic recommendations for mucous membrane pemphigoid of the eye].

Mucous membrane pemphigoid (MMP) is often accompanied with a chronic cicatrizing conjunctivitis that may eventually lead to loss of vision. The study is intended to investigate the current scientific knowledge on the diagnosis of and therapy for MMP involving the eye. Previous studies published before December 2004 have been systematically reviewed for their level of evidence. Consequently, recommendations for patient management are provided.

Chronic Disease↗

[Epidemiology of uveitis in juvenile idiopathic arthritis from a national paediatric rheumatologic and ophthalmologic database].

BACKGROUND: Uveitis is a frequent and potentially vision-threatening manifestation of juvenile idiopathic arthritis (JIA). There are only a few population-based studies providing data on the frequency and severity of uveitis. METHODS: Documentation of patients with JIA was collected in a national database. An analysis of the paediatric rheumatologic and ophthalmologic data collected from all patients that were included in 2002 was performed. RESULTS: Uveitis was documented in 12 % of a total of 3271 JIA patients: extended oligoarthritis (25 %), persistent oligoarthritis (16 %), seronegative polyarthritis (4 %), seropositive polyarthritis (2 %), psoriatic arthritis (10 %), enthesitis-related arthritis (ERA) (7 %), systemic arthritis (1 %), other arthritis forms (11 %). Ophthalmologic data were available from 115 uveitis patients (28 %). Mean age at onset of uveitis was 5.2 (SD 3.2) years. JIA patients with uveitis were significantly younger at onset of arthritis (3.8 vs. 7.0 years), and were more often girls (74 vs. 63 %) or ANA-positive (86 vs. 42 %) than the patients without uveitis. Uveitis complications were present in 45 % at initial presentation of uveitis. After a mean duration of 5.6 years, complications were noted in 56 %, and included band keratopathy (29 %), posterior synechiae (27 %), cataract (26 %), glaucoma (8 %), and macula oedema (6 %). Final visual acuity was less than 20/50 in 31 % and less than 20/200 in 12 % of eyes. In patients with uveitis, immunosuppressive or immunomodulatory drugs were used significantly more often than in patients without uveitis (75 % vs. 43 %). CONCLUSIONS: The nationwide data documents the spectrum of uveitis in patients with JIA, the complications and the therapy for uveitis. The high rate of uveitis complications at the time of diagnosis points out the need for early ophthalmologic screening and therapy, and for a close collaboration between ophthalmologist and paediatric rheumatologist.

Adolescent↗

Improvement of herpetic stromal keratitis with fumaric acid derivate is associated with systemic induction of T helper 2 cytokines.

Fumaric acid derivates have been shown to stimulate T helper-2-cytokines (interleukin (IL)-4, -5) without affecting the T-helper-1-cytokine (IL-2, interferon (IFN)-gamma)-response. Herein, the influence of systemic treatment with the fumaric acid derivate dimethylfumarate (DMF) on the secretion of T helper-cytokines and the development of HSV-1 stromal keratitis (HSK) was studied in mice. The corneas from BALB/c mice were infected with 10(5) PFU of HSV-1 (KOS strain). While one group of mice was treated intraperitoneally with PBS, another group of mice received DMF at 15 mg/kg of body weight. Expression of IL-2, -4, -10 and IFN-gamma was analysed in HSV-1 activated lymphocytes by ELISA. The severity of epithelial and stromal herpetic keratitis was investigated clinically. Corneas were studied for the inflammatory cell infiltration, and the CD3-, CD4- and CD8-positive cells were analysed by immunohistochemistry. The IL-2, -4, 10 and IFN-gamma content was measured in the corneas. Virus replication in the eyes was analysed by a plaque-assay. The DTH-response, the HSV-specific T cell proliferation and the serum neutralizing antibody-titres were investigated. DMF increased IL-4 and IL-10, but not IL-2 and IFN-gamma, secretion in activated lymphocytes from the spleen. Incidence and severity of stromal HSV-1 keratitis was reduced in the DMF group (P < 0.01). In the corneas from DMF-treated mice, the numbers of CD3+ and CD4+ cells were decreased and IL-4 was increased. Severity of epithelial disease and the virus-clearance from the eyes did not differ between the PBS and DMF group of mice. DTH, HSV-specific T cell proliferation and the neutralizing antibody-titres were not impaired. DMF increased the T helper-2-cytokine secretion in activated lymphocytes. After corneal HSV-1 infection, corneas from DMF treated mice had increased IL-4 content. This is associated with an improvement of herpetic stromal keratitis and reduced corneal T cell infiltration. DMF did not impair the systemic antiviral response.

Animals↗

Interferon as a treatment for uveitis associated with multiple sclerosis.

AIM: In addition to optic neuritis (ON), multiple sclerosis (MS) may also involve the eye with a typically bilateral intermediate uveitis. The aim of this pilot study was to evaluate the efficacy of type I interferons (IFN) for the treatment of MS associated uveitis. METHODS: In this non-randomised, retrospective observational case series 13 patients (eight female, five male) with proved MS and associated uveitis from five uveitis centres who were treated with interferon beta1a were included. Visual acuity (VA), cell count in the aqueous humour and vitreous, as well as the presence of cystoid macula oedema (CMO) were observed. RESULTS: All except one patient had a bilateral form of intermediate uveitis (total of 24 eyes). Seven patients had documented CMO before IFN treatment (n = 13 eyes). Median duration of treatment was 24.6 months (range 7.9-78.7). VA improved in 17 eyes (comparing VA before therapy and at last follow up); while 10 eyes (36%) improved >or=3 Snellen lines. Aqueous cell count improved by 1.2 (SD 1.1) grades in all eyes. Vitreous cell count improved by 1.7 (1.4) in all eyes. Only two patients still had minimal CMO on last follow up angiographically. CMO resolved after or during IFN treatment in nine eyes. CONCLUSIONS: IFN has been shown to have beneficial effects in patients with MS and/or ON. As shown in the models of experimental allergic encephalomyelitis (EAE) and uveitis, the neurological and ophthalmological manifestations seem to share similar pathogenic mechanisms. Treatment of MS associated uveitis with IFN appears to have beneficial effects on VA, intraocular inflammation activity, and the presence of CMO.

Adult↗

Influence of dimethylfumarate on experimental HSV-1 necrotizing keratitis.

BACKGROUND: This study was performed to investigate the influence of fumaric acid esters on the course of herpes stromal keratitis (HSK). METHODS: The corneas of BALB/c mice were inoculated with 105 plaque-forming units of herpes simplex virus 1 (HSV-1, KOS strain). Groups of mice were treated intraperitoneally with phosphate buffered saline (PBS) (control mice), or with dimethylfumarate (DMF) at 15 mg/kg of body weight dissolved in PBS daily for 28 days pre-infection and for 14 days post-infection. The course of HSV-1 keratitis was studied clinically. Corneal sections were examined for inflammatory cell infiltration. The numbers of CD3, GR-1, CD11b and F4/80-expressing cells infiltrating the corneas were analyzed by immunohistochemistry. RESULTS: On day 14 after HSV infection, 72% of the mice in the control group had severe HSK. The development of HSK was reduced by DMF treatment in the DMF group (22%) (P=0.004). The total number of inflammatory cells and infiltration of polymorphonuclear-neutrophils (PMNs) were reduced in the corneas of DMF-treated mice. Compared to the PBS-treated mice, numbers of CD3, CD11b, GR-1 and F4/80-positive cells were reduced in the DMF group of mice. CONCLUSIONS: The course of experimental herpes stromal keratitis can be improved with systemic fumaric acid ester treatment. The improvement of keratitis correlates with a reduced corneal infiltration of T cells and mononuclear cells.

Animals↗

[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↗

Soluble HLA class I and HLA-DR plasma levels in patients with anterior uveitis.

Anterior uveitis (AU) is an autoimmune disease frequently associated with HLA-B27 antigen. Because of the immune regulatory properties of soluble human leukocyte antigen (sHLA) molecules, we quantified sHLA class I (sHLA-I) and sHLA-DR plasma levels in HLA-typed AU patients (n = 60). Randomly selected healthy individuals (n = 128) and HLA-B27 antigen-positive individuals (n = 24) with HLA phenotype frequencies similar to the HLA-B27 antigen-positive AU patients served as control panels. As expected, HLA-B27 phenotype was significantly increased in AU patients (n = 60), compared to healthy controls. Mean sHLA-I levels in AU patients were slightly higher than in randomly selected healthy controls. Regarding AU subgroups, elevated sHLA-I levels were only found in HLA-B27 antigen-negative patients. Compared to controls, sHLA-DR levels were significantly increased in AU patients and the subgroups of HLA-B27 antigen-negative and -positive patients but not Fuchs' heterochromic cyclitis (FHC). AU patients negative for HLA-B27 antigen with a chronic course had higher sHLA-DR levels than those with an acute course. The presence of associated systemic diseases in AU patients was related to elevated sHLA-DR levels. Secretion of sHLA-DR in blood differs among the various forms of AU. Systemic immune activation was present in AU but not in FHC.

HLA-DR Antigens↗

[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↗

Management of acute ulcerative and necrotising herpes simplex and zoster keratitis with amniotic membrane transplantation.

AIM: To report promoted healing of acute ulcerative and necrotising herpetic keratitis after amniotic membrane transplantation (AMT). METHODS: Retrospective, non-comparative case series of seven patients with acute ulcerative and necrotising herpetic stromal keratitis. Single or multilayer AMT with epithelial side facing up was performed. The main outcome measures were wound healing of the corneal ulcers and decrease of stromal inflammation. RESULTS: The mean follow up was 10.7 (SEM 1.4) months (range 5-15 months). AMT was performed once in five cases, and twice in further two. Improvement of stromal inflammation was noted within 16.4 (2.5) days (range 7-28 days). Epithelial defects healed within a mean of 17 (2.7) days (range 7-28 days). Vision improved in all but two patients. No serious side effects occurred during the follow up. CONCLUSIONS: Although performed in an uncontrolled and non-randomised series of patients, these findings indicate that the AMT shows promise in selected cases for the restoration of ocular surface integrity, reduction of stromal inflammation, and improvement of vision in acute ulcerative and necrotising herpetic keratitis.

Acute Disease↗