When should intraocular lenses be implanted in patients with juvenile idiopathic arthritis-associated iridocyclitis?
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Age Factors↗
Biomedical subjects
Arnd Heiligenhaus
Publications and source records attributed to Arnd Heiligenhaus.
Pars plana vitrectomy with intravitreal triamcinolone: effect on uveitic cystoid macular oedema and treatment limitations.
OBJECTIVE: To investigate the effect of pars plana vitrectomy (PPV) in combination with intraoperative intravitreal triamcinolone acetonide injection on the course of cystoid macular oedema (CME) in patients with uveitis. METHODS: Patients with uveitis with CME (n = 19) not responding to systemic corticosteroids and/or immunosuppression combined with acetazolamide were retrospectively studied after PPV with additional intravitreal injection of 4 mg triamcinolone acetonide. Patients had chronic anterior uveitis (n = 4), intermediate uveitis (n = 9), posterior uveitis (n = 3) or panuveitis (n = 3). Visual acuity tests, tonometry, fluorescein angiographic appearance and postoperative complications were analysed. Mean follow-up was 14 months (SD 4.6). RESULTS: CME improved in 58% of the patients within the first 6 weeks postoperatively. After 12 months, CME was further improved in 44% and worsened in another 12%. Improvement of visual acuity was noted in 42% after 3 months and in 28% after 12 months. Cataract progressed in 85% of the phacic patients postoperatively. Increased intraocular pressure was detected in 27% at 2 weeks and in 11% at 12 months after surgery. CONCLUSION: Uveitic CME that is unresponsive to systemic immunosuppression and acetazolamide may improve after PPV with additional intravitreal triamcinolone application. The effect seems to be transient in many of the patients. Frequent complications were cataract formation and ocular hypertension.
Adolescent↗
Intraoperative intraocular triamcinolone injection prophylaxis for post-cataract surgery fibrin formation in uveitis associated with juvenile idiopathic arthritis.
PURPOSE: To assess the efficacy of a single intraoperative intraocular injection of triamcinolone acetonide during cataract surgery to prevent postoperative fibrin formation in patients with iridocyclitis associated with juvenile idiopathic arthritis. SETTING: Department of Ophthalmology, St. Franziskus Hospital, Muenster, Germany. METHODS: The charts of 22 patients (16 girls and 6 boys) with juvenile idiopathic arthritis and chronic iridocyclitis having lensectomy and anterior vitrectomy were retrospectively reviewed. In 12 patients (14 eyes), triamcinolone acetonide 4 mg was injected into the anterior chamber at the end of the surgery (triamcinolone group). Another 10 patients (13 eyes) received an intraoperative intravenous injection of methylprednisolone and postoperative oral prednisolone (systemic treatment group). No intraocular lenses were implanted. Postoperatively, prednisolone acetate 1% eyedrops were given. The main problems included intraocular inflammation, the need for additional systemic corticosteroids, and intraocular pressure (IOP) elevation. RESULTS: The mean patient age was 10.6 years +/- 3.1 (SD) in the triamcinolone group and 7.4 +/- 2.7 years in the systemic treatment group. The mean follow-up was 9.9 +/- 3.6 months and 10.9 +/- 1.2 months, respectively. All patients were taking systemic immunosuppression before surgery, and the medication was continued postoperatively. Fibrin formation was not seen after surgery in the triamcinolone group but occurred in 5 patients in the systemic treatment group (P = .02). Additional systemic corticosteroids were not required in the triamcinolone group. All patients had visual acuity improvement. No increase in IOP was noted after the triamcinolone acetate injections. CONCLUSIONS: Intraoperative intraocular injection of 4 mg of triamcinolone acetonide may be more effective than intraoperative intravenous methylprednisolone and additional postoperative short-term oral prednisolone in preventing postoperative fibrin formation after cataract surgery in patients with juvenile idiopathic arthritis and iridocyclitis.
Anterior Chamber↗
Prevalence of parvovirus B19-specific antibodies and of viral DNA in patients with endogenous uveitis.
BACKGROUND: Parvovirus B19 causes erythema infectiosum (fifth disease) in children. The virus has been associated with several autoimmune diseases and has been found in synovium or serum from patients with long-standing arthritis or other rheumatic diseases. We investigated serum and aqueous fluid samples of patients with endogenous uveitis. METHODS: Sera of 70 consecutive uveitis patients were investigated for IgG against structural proteins VP1 and VP2 and non-structural protein NS1 by western blot technique. Viral DNA in serum was assessed by quantitative PCR. Simultaneous DNA analysis was also performed on aqueous fluid samples from 11 uveitis patients and 10 patients without uveitis during routine cataract extraction. RESULTS: In 15 (21.4%; healthy population: 16 of 10,000) of the 70 serum samples (mean age 42.69 years, range 9-82 years; 48 women, 22 men), viral DNA was detected. IgG directed against structural protein VP1 or VP2 was found in 60 patients (85.7%; healthy population: 80%) and IgG against non-structural protein NS1 in 33 patients (47.1%; healthy population: 22%). In none of the patients was IgM antibody as a serological marker for acute parvovirus infection found. Patients with posterior uveitis (n=11) had detectable serum DNA in 54.5% (p=0.021). This group displayed the highest rate of deterioration of visual acuity (>2 Snellen lines), at 72.7% (all patients: 58.6%; p=0.219). In 2 of the 11 aqueous fluid samples, viral DNA was detected. Antibodies against parvovirus B19 were found in both samples, whereas viral DNA was absent in the serum. In the control group of 10 healthy cataract patients, 3 had detectable DNA in the aqueous humor; 1 of these 3 also had detectable levels of viral DNA in serum. CONCLUSIONS: Prevalence of IgG antibodies against NS1 protein in serum samples and DNA in serum is increased in uveitis patients compared with the normal population, suggesting a persistent infection. The presence of DNA in aqueous humor samples shows, for the first time, persistence of parvovirus B19 in the eye in uveitis and also in healthy patients. The role of parvovirus DNA in the aqueous fluid and of IgG antibodies against NS1 in the pathogenesis of uveitis cannot be defined at present.
Adolescent↗
Immunomodulation by topical particle-mediated administration of cytokine plasmid DNA suppresses herpetic stromal keratitis without impairment of antiviral defense.
BACKGROUND: We investigated whether the course of herpetic stromal keratitis (HSK) in BALB/c mice could be altered by topical gene-gun-mediated administration of interleukin (IL)-4 or IL-10 plasmid DNA. METHODS: Corneas of BALB/c mice were transfected with plasmids expressing beta-galactosidase (beta-gal), IL-4, IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF), and pCR3.1 (control) 2 days before Herpes simplex virus-1 (HSV-1; KOS) infection. Development of keratitis and cell infiltration were studied. HSV-1 replication was monitored by plaque assay. Expression of cytokines was detected by enzyme-linked immunosorbent assay. HSV-specific proliferation in the regional lymph nodes and spleens was measured. HSV-1 neutralizing antibody titers and IgG2A/IgG1 ratios were determined. RESULTS: Expression of beta-gal was found in the treated corneas, but not in other tissues. IL-4 or IL-10 plasmid administration induced cytokine production in the corneas. After treatment with 300 psi, the severity of HSK was attenuated (each P<0.05), and the numbers of infiltrating inflammatory cells were lower than in the pCR3.1-treated controls (P<0.001). IL-6, but not IL-1alpha, expression in the cornea was reduced after treatment with IL-4 or IL-10 plasmid DNA. The HSV-1-specific DTH response, corneal Th1 cytokine profile, IgG/IgG2a/IgG1 ratio, neutralizing antibody titers, and virus clearance did not differ between the groups. CONCLUSIONS: Thus, topically administered IL-4 and IL-10 plasmid DNA can lead to a milder course of HSK without impeding viral clearance. The gene gun technique for corneal delivery of plasmid cytokine DNA may be useful for modulating local immune responses without affecting antiviral defense.
Administration, Topical↗
[Rehabilitation-psychological aspects of uveitis].
Until today little is known about the psychosomatic aspects of uveitis. The hypothesis that stressful life events are associated with the onset of diseases and that uveitis led to poor quality of life are discussed in the actual literature. Life events (Schedule of Recent Experiences), coping strategies (Coping Questionnaire; Essen Coping Questionnaire), psychological distress (Brief Symptom Inventory), and vision-specific quality of life (National Eye Institute Visual Functioning Questionnaire) of 51 patients with uveitis and 51 strict parallel controls were compared with another. The patients scored higher on the Schedule of Recent Experiences, lower regarding different coping strategies, and they demonstrated higher psychological distress (low effects), and they demonstrated lower disease-specific quality of life (high effect). In summary an unspecific stress hypothesis was supported; future directions of investigation were discussed.
Adaptation, Psychological↗
Uveitis in children.
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Arthritis, Juvenile↗
Transplantation of amniotic membrane in murine herpes stromal keratitis modulates matrix metalloproteinases in the cornea.
PURPOSE: To study matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) in the corneas from mice with ulcerative herpes stromal keratitis (HSK) treated with amniotic membrane transplantation (AMT). METHODS: The corneas from BALB/c mice were infected with HSV-1. Mice with ulcerative HSK on postinfection (PI) day 14 were used for the experiments. In one group of mice, the corneas were treated with transplantation of amniotic membrane (AMT) that was secured with a tarsorrhaphy, and a control group underwent tarsorrhaphy alone. After 2 days, the appearance of corneal ulcers and stromal inflammation was judged clinically. Corneal sections were studied by immunohistochemistry for the expression of MMP-2, -8, and -9 and TIMP-1 and -2. MMP activity in the corneas was investigated by zymography, and the expression of the enzymes was measured by the Western blot technique. RESULTS: At day 14 PI, the ulcers stained intensely positive for MMP-2, -8, and -9 and TIMP-1 and -2. Ulceration (P < 0.001), stromal inflammation (P < 0.01) and inflammatory cell infiltration (P < 0.001) markedly improved by day 2 after AMT. This was associated with reduced expression (P < 0.01) and activity of MMP-8, and -9 and increased localization of TIMP-1 (P < 0.01), whereas TIMP-2 was not affected. In contrast, high levels of expression of MMP-8 and -9 remained in the cornea after tarsorrhaphy, and the TIMP-1 expression was only slightly upregulated. CONCLUSIONS: Rapid improvement of HSV-1-induced ulcerative keratitis is noted after amniotic membrane transplantation. This may be caused by reduced expression and activity of MMP-8 and -9, increased expression of TIMP-1, and sustained expression of TIMP-2.
Amnion↗
Dry eye syndrome in thyroid-associated ophthalmopathy: lacrimal expression of TSH receptor suggests involvement of TSHR-specific autoantibodies.
PURPOSE: We evaluated the relationship between ocular surface damage, elevated lid aperture/impaired Bell's phenomenon and reduced tear production in thyroid-associated ophthalmopathy (TAO). Suspecting a possible role of autoantibodies specific for TSH receptor (TSHR), we further investigated TSHR expression in the healthy lacrimal gland (LG). METHODS: A total of 48 patients with active TAO and 26 controls were examined for basal tear secretion, Rose Bengal and fluorescein staining, impression cytology (IPC), break-up time (BUT), and blinking (lid width, lid closure, ocular surface, upward excursion). Healthy LGs were investigated immunohistochemically for expression of TSHR. RESULTS: Thyroid-associated ophthalmopathy patients showed significant ocular surface damage (Rose Bengal staining score: TAO: 2.0 [0-5] versus controls: 0 [0-0.4]; IPC score: TAO 3.0 [0-8] versus controls: 0 [0-1], and BUT: TAO: 3.0 seconds [0-9 seconds] versus controls: 19.5 seconds [13-35.4 seconds]), and significantly reduced tear secretion (TAO: 10 mm [3-20 mm] versus controls: 17 mm [10-27 mm]). Ocular surface damage correlated significantly with tear secretion (r = - 0.35) but not significantly with mechanical alterations (impaired upgaze [r = - 0.34] and ocular surface increase [r = 0.32]). We firstly demonstrate that lacrimal acinar cells physiologically express TSHR. CONCLUSIONS: As ocular surface damage in TAO significantly correlates with reduced tear production, LG impairment appears to be a major cause of ocular surface drying. Intriguingly, physiological expression of TSHR by LG suggests that, in thyroid disease, autoantibodies may bind to lacrimal TSHR and, perhaps via aberrant signal transduction, contribute to LG impairment and, hence, dry eye syndrome.
Adult↗
[Expression of matrix metalloproteinases in experimental herpes simplex virus keratitis].
OBJECTIVE: To determine the distribution and activities of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) during the course of experimental herpes simplex virus type-1 (HSV-1) keratitis. METHODS: Keratitis was induced in BALB/c mice by inoculating the cornea with 10(5) plaque-forming units (pfu) of HSV-1 (KOS strain). Corneas were harvested at days 0, 2, 7, 14 and 28 post-infection. Expression of MMP-2, MMP-9, MMP-8, TIMP-1 and TIMP-2 were detected by immunohistochemistry and Western blot. The enzymatic activities were analyzed by Zymography. RESULTS: At day 2 post-infection, MMP-2 and MMP-9 expression were increased in the epithelium as compared to the uninfected control eyes, and were detected in the superficial stroma and in inflammatory cells beneath the epithelium. Similar staining patterns were detected for TIMP-1 and TIMP-2. MMP-2 and MMP-9 epithelial staining persisted until day 28 post-infection. Necrotizing keratitis with corneal ulceration was present on days 14 and 28 post-infection. This correlated with increased expression of MMP-2 and MMP-9 within the stroma and in infiltrating inflammatory cells. MMP-2, MMP-9, TIMP-1 and TIMP-2 staining were particularly intense in the proximity of the ulcers. The neutrophils, which were abundant at the site of ulceration, were stained positive with MMP-8. Both gelatinolytic activities and caseinolytic activities were upregulated after HSV-1 corneal infection. CONCLUSIONS: Our data suggest that MMPs produced by resident corneal cells and by inflammatory cells possibly promote epithelial keratitis and ulcerative process after corneal HSV-1 infection. The interaction of MMPs and TIMPs may regulate the course of necrotizing HSV keratitis.
Animals↗
Evaluation of vitrectomy specimens and chorioretinal biopsies in the diagnosis of primary intraocular lymphoma in patients with Masquerade syndrome.
PURPOSE: To correlate the histopathological diagnoses established by diagnostic vitrectomy and chorioretinal biopsy in patients with clinically suspected primary intraocular lymphoma (PIOL) or chronic idiopathic uveitis, and the clinical follow-up data. METHODS: Eighty-four consecutive pars plana vitrectomy (PPV) specimens, three chorioretinal biopsies and two enucleated eyes taken from 80 patients were evaluated. All PPV specimens were unfixed; these were centrifuged, the "cytospins" being stained conventionally (May-Grünwald-Giemsa) and using immunocytology (CD79a, CD3, CD68, immunoglobulin (Ig) light chains). An extended immunohistochemical panel, as well as polymerase chain reaction (PCR) for rearrangements of the Ig heavy chain gene (IgH-PCR), were used to investigate the chorioretinal biopsies and the enucleated eyes. Diagnoses, made on the basis of morphology and immunophenotype, included "reactive cellular infiltrate", "malignant lymphoma", "suspicious of neoplastic disease", and "insufficient for diagnosis". The corresponding clinical data were collected and compared with the diagnosis. RESULTS: The 80 patients consisted of 46 women and 34 men. The patients' age range varied from 21 to 100 years (mean age 62 years). Sixty-two (74%) of the 84 vitrectomy specimens were diagnosed as "reactive cellular infiltrate", 12 (14%) as definite "malignant lymphoma", 5 (6%) as "suspicious of neoplastic disease" and 5 (6%) specimens were considered "insufficient for diagnosis". An additional chorioretinal biopsy enabled an unequivocal diagnosis of PIOL to be reached in 3 patients. All PIOL were diffuse large cell B-cell lymphoma (DLBCL), with the immunophenotype CD79+, CD20+, BCL-2+, BCL-6+, MUM1+ and monotypical expression for IgM+. A monoclonal IgH-PCR amplification product was obtained in four vitrectomy specimens, two chorioretinal biopsies and one of the enucleated eyes. Comparison of the diagnoses with long-term follow-up clinical data resulted in concordance in 77 (96%) cases and discrepancies ("false-negative" diagnoses) in 3 patients (4%). The patients diagnosed with lymphoma were treated with either radiotherapy, chemotherapy or both. At final follow-up (mean 35 months), 5 patients (6%) had developed cerebral lymphomatous manifestation, and 7 (9%) had succumbed to their disease. CONCLUSION: The diagnosis of PIOL is often extremely difficult, requiring sufficient rapidly transported good-quality material, and experienced interpretation. Although cytological examination of vitreal aspirates remains the gold standard in diagnosis, examination of chorioretinal biopsies increase the reliability of diagnosing or excluding a PIOL that involves the retina or choroid. Most PIOL are DLBCL with an immunophenotype suggesting a cellular origin from germinal centre cells.
Adult↗
Matrix metalloproteinases (MMP-2 and 9) and tissue inhibitors of matrix metalloproteinases (TIMP-1 and 2) during the course of experimental necrotizing herpetic keratitis.
To determine the distribution and activities of metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) during the course of experimental herpes simplex virus (HSV) type-1 keratitis, BALB/c mice were corneally infected with 10(5) plaque-forming units (PFU) of HSV-1 (KOS strain) and then observed for the clinical signs of keratitis. Corneas were harvested at days 0, 2, 7 and 14 post-infection (p.i.). MMP-2, MMP-9, MMP-8, TIMP-1 and TIMP-2 were detected by immunohistochemistry and the Western blot technique. The enzymatic activities were analyzed by zymography. Epithelial HSV keratitis was present at day 2 after corneal infection and healed by day 5 p.i. While the expression and activity of MMP-2, MMP-8 and MMP-9 increased in the corneas at day 2 p.i., it was reduced at day 7 p.i. TIMP-1 and -2 were expressed in the corneas before and seven days after infection. Necrotizing stromal keratitis with corneal ulceration and dense polymorphonuclear leukocyte (PMN) infiltration was present at day 14 p.i. This correlated with increased expression of MMP-2, MMP-8 and MMP-9 in the corneas. MMP-8, MMP-9 and MMP-2 staining was particularly intense in the proximity of the ulcers and in areas of PMN infiltration. At day 14 p.i., MMP-2, -8 and -9 activities were upregulated, and TIMP-2 was expressed. These data suggest that MMPs produced by resident corneal cells and PMNs may possibly play a role in early epithelial keratitis and in the ulcerative process in the late phase after corneal HSV-1 infection. The ratio of MMPs to TIMPs may be important for the course of necrotizing HSV keratitis. TIMPs might participate in the repair process.
Animals↗
Combined phacoemulsification and pars plana vitrectomy: clear corneal versus scleral incisions: prospective randomized multicenter study.
PURPOSE: To compare the complications and outcomes of implantation of a foldable intraocular lens (IOL) through a clear corneal incision and implantation of a poly(methyl methacrylate) (PMMA) IOL through a scleral incision in combined phacoemulsification and pars plana vitrectomy. SETTING: Departments of Ophthalmology, St. Franziskus Hospital, Muenster, Eye Hospital, Muelheim, and University of Essen, Essen, Germany. METHODS: This prospective randomized study included 62 eyes having implantation of a PMMA IOL (811B, Pharmacia) through a scleral incision and 61 eyes having implantation of a polyacrylic (AcrySof, Alcon) IOL through a clear corneal incision. The preoperative visual acuity, underlying retinal disease, and vitreoretinal surgical maneuvers did not differ between groups. The surgical methods and intraoperative complications were noted. Examinations 2 days and 3 months after surgery included visual acuity, refractive error, keratometry, slitlamp evaluation, tonometry, and ophthalmoscopy. RESULTS: Intraoperatively, both incisions were stable and no serious complications occurred. Two days after surgery, the incidence and quantity of cells and fibrin in the anterior chamber were lower in the clear corneal incision group than in the scleral incision group (P<.05). Corneal endothelial dysfunction was more common in the clear corneal group than in the scleral group (P<.05). Three months after surgery, the astigmatic changes did not differ significantly between groups and the incidence of posterior capsule opacification (PCO) was lower in the clear corneal group (P<.05). Postoperative visual acuity improved significantly in 63% of eyes and 61% of eyes in the scleral group and clear corneal group, respectively. Visual acuity was limited by macular pathology. CONCLUSIONS: Both clear corneal and scleral incisions were safe in combined phacoemulsification and vitrectomy. Eyes with smaller clear corneal incisions and foldable IOLs had less postoperative inflammation and PCO.
Aged↗
[Indication and effect of immunosuppression in patients with scleritis].
PURPOSE: The value of immunosuppressive drugs for the therapy of scleritis patients is unclear. The authors investigated the indications and effects of immunosuppression in a group of patients with scleral inflammation. METHOD: Retrospective study of patients treated for scleritis (n = 87) or episcleritis (n = 18). The demographic factors, clinical symptoms, visual outcome, course of inflammation, ocular complications resulting from inflammation, topical and systemic antiinflammatory medication, and associated systemic diseases were analysed. RESULTS: Only one patient with episcleritis, but 37 with scleritis presented with ocular complications (P = 0.003). The vision was impaired in 15 patients with scleritis, but not in episcleritis patients (P = 0.022). In the group of patients with episcleritis, only those with frequent relapses required more than topical antiinflammatory drugs, especially systemic non-steroidals. In contrast, systemic therapy was indicated in all of the scleritis patients. Ocular complications were found more often in patients with necrotising (n = 7/10) or posterior scleritis (n = 10/11) than in those with diffuse (9/39) or nodular (11/27) scleritis. Compared with the other patients, associated systemic autoimmune diseases were more common in patients with necrotising scleritis (P = 0.03). The need for immunosuppression was associated with vision-threatening complications (glaucoma, uveitis, peripheral ulcerative keratitis) (P < 0.01), systemic autoimmune disease, and necrotising and posterior form of scleritis (P < 0.01). Quiescence of scleritis was obtained in 59 of the scleritis patients, and improvement of inflammation was achieved in further 21. In 26 patients, scleritis did not improve with systemic steroid or non-steroidal treatment, but with immunosuppression. CONCLUSIONS: Scleritis is often associated with life-threatening systemic diseases and vision-threatening ocular complications. In patients with severe scleritis, especially with the posterior and necrotising form, improvement can often be achieved with immunosuppression.
Adult↗
[Juvenile idiopathic arthritis and uveitis: screening and anti-inflammatory therapy].
This article provides an overview of the rheumatic diseases in childhood, their pathogenesis, epidemiology, diagnosis and clinical course. EULAR, ACR and the current ILAR-classification are compared. The antiinflammatory medical treatment is described. The characteristics of uveitis in the various forms of arthritis are reviewed. The prognostic factors for uveitis manifestation, the clinical course, complications, the prognostic factors for visual loss, and the diverse antiinflammatory medical regimens are evaluated. The suggestions of the "uveitis in childhood study group" concerning screening and treatment of uveitis in patients with juvenile idiopathic arthritis are provided, and a nation-wide documentation of these patients is described.
Anti-Inflammatory Agents, Non-Steroidal↗
Topical treatment with antisense oligonucleotides targeting tumor necrosis factor-alpha in herpetic stromal keratitis.
PURPOSE: Tumor necrosis factor (TNF)-alpha is a pleiotropic factor that is critical for the development of inflammation. The authors investigated whether topical application of TNF-alpha-antagonizing molecules, antisense oligonucleotides (ASON), might be an effective way of modifying the course of immune-mediated herpetic stromal keratitis (HSK). METHODS: ASON targeting TNF-alpha mRNA were examined for their efficiency in interfering with the production of this cytokine in vitro. In vivo uptake was determined by FITC-labeled ASON. HSV-1 corneally infected mice were injected three times with ASON. Mice from the control groups received unrelated control oligonucleotides (CON) or buffer. The clinical course of HSK, the delayed-type hypersensitivity (DTH) reaction, the uptake of [(3)H]thymidine from cells derived from the spleen, virus-neutralizing antibody titers in the serum, and viral replication in the infected eyes were determined. The eyes were examined histologically. The corneal TNF-alpha content was measured by ELISA. RESULTS: The TNF-alpha ASON reduced the lymphocytic cytokine expression in vitro. In vivo, the FITC-labeled molecules were detected in the cornea even after 10 days. In the TNF-alpha ASON mice the incidence of HSK decreased, and the severity of the disease was diminished. The corneal content of TNF-alpha was reduced, and the number of inflammatory cells was decreased. The other investigated parameters were not significantly altered by TNF-alpha ASON treatment. CONCLUSIONS: The data suggest that TNF-alpha ASON diminishes the release of TNF-alpha from cultured lymphocytes and from lymphocytes in the HSV-1-infected cornea. This topical treatment mitigates the course of HSK, whereas the systemic antiviral effector functions were not impaired.
Administration, Topical↗
Conjunctival macrophage-mediated influence of the local and systemic immune response after corneal herpes simplex virus-1 infection.
Recently it has been shown that selective subconjunctival macrophage depletion reduced the incidence and severity of stromal herpes simplex virus (HSV) keratitis in mice. In this study, we examined the effect of conjunctival macrophage depletion on the corneal and systemic T-cell-mediated immune response. BALB/c mice were treated with subconjunctival injections of dichloromethylene diphosphonate (Cl2MDP)-liposomes (Cl2MDP-LIP) or phosphate-buffered saline (PBS) 7 and 2 days before corneal infection with 105 plaque-forming units (PFU) of HSV-1 (KOS strain). Interferon (IFN)-gamma, interleukin (IL)-2, and IL-4 production in the cornea was analysed by enzyme-linked immunosorbent assay (ELISA), and cytokine mRNA levels (IFN-gamma, IL-4) were measured by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Cell culture supernatants from submandibular lymph nodes were analysed by ELISA for expression of IFN-gamma, IL-2, and IL-4 and by bioassay for IL-6. The HSV-1-specific proliferative response of lymphocytes from regional lymph nodes and the delayed-type hypersensitivity (DTH) response were tested after corneal infection. Virus-neutralizing antibody titres and HSV-1-specific immunoglobulin G (IgG)2a/IgG1-ratios were measured. Cytokine mRNA expression (IFN-gamma, IL-4) and secretion (IFN-gamma, IL-2, IL-4) in the corneas were decreased after HSV-1 corneal infection in the macrophage-depleted mice. The secretion of IFN-gamma and IL-2 was decreased in the regional lymph nodes from Cl2MDP-LIP-treated animals (P<0.05). Furthermore, Cl2MDP-LIP-treated mice had decreased HSV-1 specific proliferative responses (P<0.05) and DTH response after corneal HSV-1 infection (P<0.05). The virus-neutralizing serum-antibody levels (P<0.05) increased while the HSV-1 specific IgG2a/IgG1-ratio was unaffected after macrophage depletion. Macrophage depletion did not induce a shift between the T helper 1 (Th1) and Th2 response in this HSK model. The data suggest that conjunctival macrophage functions are enhancing the T-cell-mediated immune response after corneal infection. This effect is at least in part responsible for the impaired course of herpetic keratitis after macrophage depletion.
Animals↗
[Tubulointerstitial nephritis and uveitis (TINU syndrome) - comorbidity and complications in four patients].
BACKGROUND: TINU syndrome probably is a frequently overlooked disease where uveitis occurs in association with acute tubulointerstitial nephritis. Diagnostic criteria have been published recently. PATIENTS AND METHODS: In this retrospective case series the charts of four consecutive patients with TINU syndrome (follow-up 36, 23, 17, and 12 months, respectively) were analysed, including comorbidity and complications, and the literature was reviewed. RESULTS: Two patients were treated with methotrexate or ciclosporin A and mycophenolate mofetil. In one patient autoimmune thyroiditis was known. During the follow-up, symptoms indicative of rheumatoid arthritis were observed. Because of her uveitis she required methotrexate therapy. Three patients were obese (mean BMI 32.2 kg/m (2)). Ocular complications were posterior synechiae (two patients) and papillary and macular oedema (three patients). One patient developed cerebrospinal hypertension under ciclosporin A treatment which resolved after discontinuation of therapy. CONCLUSIONS: Patients with definite TINU syndrome frequently suffer from other diseases and associated immune phenomena. The course of the disease can vary considerably. Complications do occur, despite overall good prognosis. Regional and systemic steroids may be sufficient; frequently steroid sparing immunosuppressives are necessary at least temporarily. Patients with this multiorgan disease do need to be followed by a paediatrician or a medical specialist.
Adolescent↗