Glucocorticoid-induced osteoporosis: considerations in ophthalmology.
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Absorptiometry, Photon↗
Biomedical subjects
C Stephen Foster
Publications and source records attributed to C Stephen Foster.
Ocular cicatricial pemphigoid: pathogenesis, diagnosis and treatment.
Understanding of ocular cicatricial pemphigoid (OCP) has changed dramatically over the last three decades. Progress in basic science research in mucous membrane pemphigoid has been instrumental in outlining the key immune processes that participate in the autoimmune response. Immunomodulatory therapy has provided an avenue for preserving vision and preventing potentially fatal consequences of systemic pemphigoid. In this chapter we focus attention on the immunologic basis for disease and treatment strategies. We propose an algorithmic approach to diagnosis and management of OCP.
Autoimmune Diseases↗
Bilateral chronic anterior uveitis & neuro-ophthalmologic manifestations in a patient with Churg-Strauss syndrome: an unusual ocular presentation.
We describe a patient with Churg-Strauss syndrome (CSS) who developed bilateral chronic anterior uveitis and neuro-ophthalmologic manifestations 20 years after the onset of asthma and sinus disease. The patient was treated successfully with a combination of cyclophosphamide and prednisone, after other immunomodulatory strategies, aside from systemic prednisone, had failed.
Adult↗
Neurofibromatosis type 1 associated with central nervous system lymphoma.
PURPOSE: To report the occurrence of central nervous system (CNS) lymphoma in a patients with neurofibromatosis type 1 (NF1). DESIGN: Interventional case report. METHODS: A 47-year-old male with a parieto-occipital lobe lesion was referred for ocular evaluation. Skin, brain, and vitreous biopsies were performed. RESULTS: The discovery of Lisch nodules of the iris prompted a physical examination that revealed cutaneous stigmata of NF1. Biopsy of the CNS lesion revealed diffuse large B-cell lymphoma. Biopsy of papules on the back and abdomen were compatible with neurofibroma. No malignant cells were found in the vitreous specimen. A clinical diagnosis of NF1 was made. CONCLUSION: This is the first report of CNS lymphoma in a patient with NF1. Additional reports may shed more light on the possible association between the two conditions.
Antineoplastic Agents↗
Multiple sclerosis-associated uveitis.
BACKGROUND/AIMS: To describe the clinical characteristics and course of 16 patients with uveitis associated with multiple sclerosis (MS). METHODS: The records of 1254 patients with uveitis were reviewed. Sixteen of these patients had MS. The history, review of systems, ocular findings, and clinical test results of each of these 16 subjects were analyzed. The mean follow-up time was 38 months. RESULTS: Most patients with MS-associated uveitis were white females between 20 and 50 years of age. The diagnosis of MS preceded the onset of uveitis in 56%, followed it in 25%, and was made concurrently in 19% of the cases. In 94%, the uveitis was bilateral. Pars planitis was the most frequent form of uveitis in our study population (81%); concomitant anterior chamber inflammation was common and was granulomatous in nature 56% of the time. Forty-one percent of the eyes with MS-associated uveitis had 20/30 or better initial visual acuity. Among these treated patients, significant loss of visual acuity was uncommon. CONCLUSIONS: MS-associated uveitis should be suspected in white female patients with bilateral uveitis, especially if pars planitis is present. These patients often retain useful vision for many years if treated.
Adult↗
Elevated levels of interleukin 6 in the vitreous fluid of patients with pars planitis and posterior uveitis: the Massachusetts eye & ear experience and review of previous studies.
INTRODUCTION: Although the exact mechanisms that lead to uveitis are not entirely known, the role of cytokines in the pathogenesis of this disease has been shown to be important. Prior studies described the presence of an array of cytokines in the intraocular fluid of patients with uveitis. Review of these studies indicate that Interleukin-6 (IL-6) is present, and animal data suggest the important role of IL-6 in the regulation of ophthalmologic immune responses. PURPOSE: We investigated whether IL-6, TNF-alpha, IL-1 alpha, beta, IL-2 are present in the vitreous of patients with active intermediate and posterior uveitis. METHODS: Vitreous specimens were collected from 23 eyes of patients with active intermediate and posterior uveitis who underwent diagnostic or therapeutic vitrectomies. TNF-alpha, IL-1 alpha and beta, IL-2 and IL-6 were measured by enzyme-linked immunosorbent assay. Eight vitreous fluid samples from eye bank eyes were used as control. RESULTS: IL-6 was higher in the vitreous of patients with uveitis compared to control samples (p = 0.0119). No TNF-alpha, IL-2, IL1-alpha or beta was detected. The levels of IL-6 did not correlate with a specific clinical diagnosis, but patients with pars planitis and panuveitis had the highest levels (p = 0.58) CONCLUSIONS: IL-6 is elevated in the vitreous of patients with active intermediate and posterior uveitis.
Enzyme-Linked Immunosorbent Assay↗
Immunomodulatory medications in uveitis.
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Adjuvants, Immunologic↗
Ocular cicatricial pemphigoid review.
PURPOSE OF REVIEW: Ocular mucous membrane pemphigoid produces progressive cicatrizing conjunctivitis; this can result in scarring of the conjunctiva and cornea. RECENT FINDINGS: Increased expression of macrophage-colony-stimulating factor, collagen-binding heat shock protein 47, transforming growth factor-beta1, IL-4, IL-5, and macrophage migration inhibitory factor may enhance both conjunctival inflammation and conjunctival scarring. Recent developments on mucous membrane pemphigoid medical therapy include the efficacious effect of daclizumab, intravenous immunoglobulin therapy, and methotrexate. Subconjunctival mitomycin has proved not to be efficacious in controlling long-term, conjunctival inflammation and scarring. The Boston scleral lens enhances vision, reduces the disabling ocular pain and photophobia, and helps to heal persistent epithelial defects, reducing recurrence of defects. Recent developments on mucous membrane pemphigoid surgical therapy include keratolimbal allografts and amniotic membrane transplantation, with or without penetrating keratoplasty for ocular surface reconstruction in total stem cell deficiency. The prognosis is strongly influenced by preoperative conditions such as tear function and functional external ocular adnexae, and by postoperative conditions such as persistent inflammation, severe dry eye, or rejection of the keratolimbal allograft. Some authors find efficacious the use of amniotic membrane transplantation for reconstruction of the conjunctival fornices provided systemic immunosuppression is pre- and post-operatively used. SUMMARY: The use of daclizumab or intravenous immunoglobulin therapy, the better selection of candidates for surgical interventions, and the better pre- and post-operative management of keratolimbal allograft and amniotic membrane transplantation may improve visual rehabilitation in the patients with ocular mucous membrane pemphigoid.
Conjunctival Diseases↗
Ocular cicatricial pemphigoid, keratomycosis, and intravenous immunoglobulin therapy.
PURPOSE: To report the case of a patient developing fungal keratitis in the context of uncontrolled ocular cicatricial pemphigoid (OCP), which, despite intravenous immunoglobulin (IVIg) and other immunomodulatory therapy, progressed to end-stage pemphigoid, with corneal opacification, ankyloblepharon, and xerosis. Keratoprosthesis (KPro) restored functional vision for the patient. METHODS: A 39-year-old man presented with uncontrolled CP and corneal ulcer in the left eye. Conjunctival biopsy diagnosed OCP; corneal scraping and biopsy diagnosed the cause of the corneal ulcer. OCP was treated with systemic steroids, immunosuppressive drugs, and IVIg. Visual rehabilitation was accomplished with Ahmed valve and a type II Dohlman KPro. RESULTS: Immunohistology of the biopsied conjunctiva showed IgG at the epithelial basement membrane zone, confirming the clinical diagnosis of OCP. Microbiologic studies of the corneal biopsy specimen were negative for Acanthamoeba and herpes but positive for Aspergillus niger. The patient's keratomycosis resolved with topical antifungal therapy. Treatment with Dapsone, intravenous-pulse steroid, oral cyclophosphamide, and intravenous immunoglobulin (IVIg) failed to control the OCP, with resultant complete conjunctivization of the cornea. Keratoprosthesis improved the patient's visual acuity from hand movements to 20/20. CONCLUSIONS: Patients with uncontrolled OCP are at increased risk of corneal infection. The difficulty in diagnosing keratomycosis and the relatively rare occurrence of OCP explain the uniqueness of our reported case. OCP may progress to "end-stage" disease despite therapy. Keratoprosthesis can restore vision in selected otherwise seemingly hopeless cases.
Adult↗
Expression of fibronectin isoforms bearing the alternatively spliced EIIIA, EIIIB, and V segments in corneal alkali burn and keratectomy wound models in the rat.
PURPOSE: To better understand the healing process in the wounded cornea, fibronectin (FN) isoforms bearing the alternatively spliced EIIIA, EIIIB, and V segments (EIIIA+, EIIIB+, and V+ FNs) were evaluated in alkali burn and keratectomy wound models in the rat. METHODS: Alkali burn or keratectomy wounds (both 2 mm) were created, and corneas were harvested at various time points and analyzed by indirect immunofluorescence using antibodies specific for the EIIIA, EIIIB, and V segments as well as for the total pool of FN (total FN). RESULTS: There was minimal staining for any variety of FN in the epithelium or basement membrane zone (BMZ) in normal cornea, but each antibody produced granular staining in the stroma. Bright staining for V+ and total FNs was evident at the denuded stromal surface 1 day following keratectomy. In contrast, staining for EIIIA+ and EIIIB+ FNs was negligible at 24 hours but appeared on the wound surface under the migrating unstained epithelium by the second day. BMZ staining for FN then gradually subsided, such that there was little or no staining by 6 weeks. In contrast, alkali burn wounds exhibited very little BMZ staining throughout the time course. Although there was preferential staining of the anterior aspect of Descemet membrane by anti-EIIIA and anti-EIIIB antibodies under normal conditions, the staining intensity of the anterior and posterior aspects became similar following corneal wounding. CONCLUSION: Deposition of EIIIA+ and EIIIB+ FNs in the BMZ of the keratectomy wound occurs more slowly than deposition of V+ and total FNs. EIIIA+ FN is expressed in a distribution that overlaps with that previously described for the alpha 9 integrin subunit following corneal debridement, suggesting that EIIIA-alpha 9 interactions could occur during corneal wound healing. In contrast, the relative lack of FN deposition in alkali burn wounds suggests that proteolytic degradation of FN may occur; and this, along with impairment of new FN synthesis because of cellular damage, could play a role in the high prevalence of recurrent epithelial erosions in alkali-wounded corneas.
Alternative Splicing↗
Role of macrophage migration inhibitory factor in conjunctival pathology in ocular cicatricial pemphigoid.
PURPOSE: Macrophage migration inhibitory factor (MIF) is a pleiotropic, proinflammatory cytokine that mediates various immunoinflammatory processes. Ocular cicatricial pemphigoid (OCP) is an autoimmune disease in which affected conjunctivae show features of an immunoinflammatory disease. In this study, the role of MIF in the pathogenesis of OCP was examined. METHODS: The expression of MIF in conjunctival tissues of patients with OCP (n = 10) and normal subjects (n = 5) was studied by quantitative real-time PCR and immunohistochemistry. The production of MIF by conjunctival fibroblasts of normal control subjects and patients with OCP was determined, by using quantitative real-time PCR and enzyme-linked immunosorbent assay (ELISA). In addition, the effects of interleukin (IL)-1, tumor necrosis factor (TNF)-alpha, and transforming growth factor (TGF)-beta1 on the induction of MIF by conjunctival fibroblasts were studied by quantitative real-time PCR. To determine the relationship between conjunctival expression of MIF and accumulation of macrophages, in patients with OCP, a correlation study was performed. RESULTS: An increased conjunctival expression of MIF was detected in patients with OCP, both at the mRNA (by real-time PCR) and protein level (by immunohistochemistry), compared with normal control patients. The expression of MIF was detected in the epithelial cells and occasionally in the stromal cells in control conjunctival tissues, by immunohistochemistry. In contrast, a statistically significant increase (P < 0.0001) in the expression of MIF was detected in the stromal cells of conjunctival tissues obtained from patients with OCP (control: 4.89 +/- 0.5; OCP: 19.82 +/- 1.34). By quantitative real-time PCR, compared with control conjunctiva, an increase in the expression of MIF was detected in the conjunctiva obtained from patients with OCP. A similar increase in the expression of MIF was also detected in conjunctival fibroblasts of patients with OCP, compared with control fibroblasts, by quantitative real-time PCR. A significantly increased (P < 0.001) level of MIF was also detected in supernatant collected from conjunctival fibroblasts of patients with OCP (186 +/- 5.4), compared with supernatant collected from control fibroblasts (9.3 +/- 7.6). Moreover, IL-1, TNF-alpha, and TGF-beta1, known factors involved in the pathogenesis of OCP, were found to induce the expression of MIF by conjunctival fibroblasts. A statistically significant correlation (P < 0.0001, r(2) = 0.4465) was observed between the expression of MIF and accumulation of CD68-positive macrophages in conjunctiva of patients with OCP. CONCLUSIONS: This study demonstrated an increased conjunctival expression of MIF in patients with OCP. MIF may be actively involved in the pathogenesis of OCP, possibly regulating the inflammatory events of the disease process.
Conjunctiva↗
Treatment of ocular inflammation in children.
Ocular inflammation in children is of substantial epidemiologic importance, particularly since uveitis in children produces more vision loss than it does in adults. This is partially because there is a higher rate of posterior uveitis in childhood uveitis than in the adult population. Treatment of ocular inflammation in children, ranging from conjunctivitis to keratitis to scleritis to uveitis, depends, of course, on whether or not the problem is microbial, traumatic, malignant, or autoimmune. Most of the cases that are vision threatening are autoimmune, and corticosteroids represent the mainstay of short-term therapy. However, abundant evidence exists which shows that all too often imprudent, prolonged use of corticosteroids is employed with resultant iatrogenic damage, including cataract, glaucoma, and secondary infection.A new paradigm for treating ocular inflammation (uveitis in particular) is espoused in this article. It is based on a limited tolerance to corticosteroid use and a more proactive approach to corticosteroid-sparing immunomodulatory therapy in an effort to induce a durable remission off all corticosteroids.
Anti-Inflammatory Agents, Non-Steroidal↗
Outcomes of early and late immunomodulatory treatment in patients with HLA-B27-associated chronic uveitis.
PURPOSE: To evaluate the outcomes of early versus late immunomodulatory treatment (IMT) in patients with HLA-B27-associated chronic uveitis. METHODS: Seventy-two patients (114 eyes) with HLA-B27-associated chronic uveitis received IMT at the Ocular Immunology & Uveitis Service of the Massachusetts Eye and Ear Infirmary and were evaluated retrospectively. Main outcome measures were visual acuity, control of inflammation, number of flare-ups and steroid-sparing effect. RESULTS: The median time between diagnosis and start of IMT was 3.05 years. Accordingly, patients were divided into two groups: group A comprised those in whom initiation of IMT was within the first 3 years (36 patients), and in group B initiation of IMT was more than 3 years from the initial diagnosis (36 patients). Control of inflammation was achieved in 29 patients (80.5%) of the early-treated group and in 33 patients (91.6%) of the late-treated group. A steroid-sparing effect was achieved for 13 (81.25%) of the 16 and for 11 (73.33%) of the 15 patients who were on systemic steroid in the early- and late-treated groups respectively. The mean follow-up for the early-treated group was 2.14 years and for the late-treated group, 3.46 years. CONCLUSIONS: Immunomodulatory therapy is an effective treatment for severe HLA-B27 uveitis that fails to respond to conventional steroid treatment, regardless of the timing of its initiation. However, introduction of IMT within 3 years of the disease onset prevents the adverse effects of steroids (cataract, glaucoma) and reduces the likelihood of repeated recurrences of the uveitis.
Adult↗
Expression profiles of collagens, HSP47, TGF-beta1, MMPs and TIMPs in epidermolysis bullosa acquisita.
Epidermolysis bullosa acquisita (EBA) is a chronic, uncommon, sub-epidermal blistering disease involving the skin and mucous membranes that heals with scar formation and milia. Collagens, matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are important components that play an essential role(s) in matrix remodeling during scar formation. However, the possible involvement of these components in EBA-induced scarring is not yet known. In the present study, we examined the expression profile of collagens, collagen-binding heat shock protein 47 (HSP47), MMPs and their inhibitory enzymes, TIMPs, in matrix remodeling during conjunctival scarring. The involvement of TGF-beta1, a fibrogenic factor, was also studied. Compared to the controls, an increased expression of type I collagen, type III collagen and HSP47 was detected in conjunctival biopsy sections of patient with EBA using immunohistochemistry. Similar increase in the expression of type I collagen, type III collagen and HSP47 was noted in conjunctival fibroblasts obtained from the patient with EBA. Up-regulation in the expression of MMP-1 and MMP-14 was also noted in conjunctival fibroblasts isolated from the patient with EBA, while no significant changes in the expression of MMP-3, MMP-8, MMP-9 and MMP-13 were seen. As for TIMPs, conjunctival fibroblasts isolated from the patient with EBA, grown in vitro, exhibited increased expression of TIMP-1, TIMP-2 and TIMP-3, when compared with fibroblasts grown from control conjunctival tissues, although the expression level varies with different molecules of the same family. Additionally, compared to the control conjunctival fibroblasts, an increased expression of TGF-beta1 was detected in fibroblasts isolated from the conjunctival tissues of patient with EBA. This study suggests that there is up-regulation in the production of collagens (type I and III), collagen-binding protein (HSP47), matrix degrading collagenases (MMP-1 and 14), and their inhibitory enzymes (TIMP-1, 2 and 3) during the process of conjunctival matrix remodeling in the patient with EBA. The presented data is preliminary and could serve as a basis for further studies to enhance our understanding about the molecular mechanisms of conjunctival scarring in patients with EBA.
Collagen↗
Efficacy of etanercept in preventing relapse of uveitis controlled by methotrexate.
OBJECTIVE: To evaluate the efficacy of etanercept vs placebo in preventing relapses of uveitis in patients taking methotrexate with control of uveitis and whose methotrexate dosage was being tapered. METHODS: Patients with chronic or recurrent noninfectious uveitis with inflammation controlled by low-dose methotrexate were randomized to either the drug or placebo group in a double-masked manner, given a methotrexate taper schedule, and followed for 24 weeks. The main outcome measures were control of inflammation, visual acuity, and adverse reactions. Data were analyzed both as an attempt-to-treat analysis and an analysis only of those patients who completed the study. RESULTS: A total of 20 patients were randomized to the drug and placebo groups. Relapse of uveitis occurred in 3 of 10 patients in the treatment group and 5 of 10 patients in the control group. Two patients in the treatment group withdrew prematurely from the study due to adverse effects. There was no significant difference between the treatment and placebo groups with regard to the rate of relapse and the final visual acuity. No patient suffered from any irreversible, long-term morbidity or mortality. CONCLUSION: Etanercept has no significant efficacy over placebo in preventing relapses of uveitis in patients being tapered from methotrexate.
Anti-Inflammatory Agents, Non-Steroidal↗
Treatment of ocular inflammatory disorders with daclizumab.
PURPOSE: To evaluate the efficacy and safety of daclizumab therapy for patients with various ophthalmologic inflammatory disorders (all having previously failed standard treatment methods). DESIGN: Retrospective, nonrandomized case series. PARTICIPANTS: Fourteen patients. METHODS: Fourteen patients were treated with daclizumab after previously failing standard treatment methods. MAIN OUTCOME MEASURES: Inflammation and visual acuity. RESULTS: Twelve of 27 (44%) eyes and 5 of 14 (36%) patients had improvement in visual acuity; 9 of 27 (33%) eyes and 5 of 14 (36%) patients had no change in visual acuity; and 6 of 27 (22%) eyes and 4 of 14 (27%) patients had continued visual loss. Based on degree of inflammation, 16 of 27 eyes (59%) had improvement, 3 of 27 (11%) eyes had no change, and 8 of 27 (30%) eyes worsened. CONCLUSIONS: Daclizumab is safe and, at least in some patients, appears to be an effective medication in the treatment of ocular inflammatory disorders.
Adolescent↗
Multifocal nodular episcleritis and scleritis with undiagnosed Hodgkin's lymphoma.
PURPOSE: To report the case of a patient with undiagnosed Hodgkin's lymphoma who presented with coexistent unilateral nodular episcleritis and scleritis. DESIGN: Interventional case report and literature review METHODS: Review of clinical history, laboratory findings, histology of episcleral and cervical lymph node biopsies, and follow-up. RESULTS: A 20-year-old female presented with a 5-month history of redness and pain in her left eye, with associated symptoms of dyspnea, malaise, and fever. The patient was found to have multifocal nodular episcleritis and scleritis that was not responsive to topical steroids or systemic nonsteroidal anti-inflammatory treatment. Laboratory tests subsequently revealed evidence of systemic inflammation, and radiologic studies showed extensive mediastinal and cervical adenopathy. A cervical lymph node biopsy showed Reed-Sternberg cells and a chronic lymphocytic infiltrate consistent with nodular sclerosing Hodgkin's lymphoma. Histopathologic analysis of an episcleral nodule revealed a necrotizing granuloma with vasculitis. Systemic chemotherapy was instituted for the Hodgkin's disease; this therapy abolished the nodular scleritis. CONCLUSIONS: This case raises the possibility of concurrent undiagnosed systemic vasculitis with only an ocular manifestation with Hodgkin's lymphoma, either as a coincidence or as a paraneoplastic syndrome. Moreover, it emphasizes the important role of tissue biopsy in establishing diagnosis and directing treatment.
Adult↗
Mycophenolate mofetil as an immunomodulatory agent in the treatment of chronic ocular inflammatory disorders.
PURPOSE: To evaluate the outcomes of patients with chronic ocular inflammatory disease treated with mycophenolate mofetil as an immunosuppressive and steroid-sparing agent. DESIGN: Retrospective noncomparative interventional case series. PARTICIPANTS: All patients with ocular inflammatory disease treated with mycophenolate mofetil at a single institution between 1998 and 2001. METHODS: Charts of patients seen on the Ocular Immunology and Uveitis Service at the Massachusetts Eye and Ear Infirmary were reviewed. Patients with chronic ocular inflammatory disease were included in the study. MAIN OUTCOME MEASURES: Control of inflammation, steroid-sparing effect, visual acuity, and adverse reactions were measured. RESULTS: A total of 54 patients were evaluated. Control of ocular inflammation with mycophenolate mofetil as monotherapy was achieved in 35 patients (65%) and in 67 eyes (62%), and a steroid-sparing effect was achieved in 29 (54%) patients. Visual acuity was maintained or improved in 51 patients (94%) and in 97 eyes (90%). Side effects requiring discontinuation of medication occurred in 10 patients (18%). There was neither long-term morbidity nor mortality due to mycophenolate mofetil. CONCLUSIONS: Mycophenolate mofetil is effective in the treatment of patients with steroid-dependent or -resistant chronic ocular inflammatory disorders that fail to respond to conventional steroid treatment. It is a safe and effective steroid-sparing immunomodulatory agent and can be considered an important addition to our armamentarium in the care of patients with ocular inflammatory disease.
Adolescent↗