Biomedical subjects

C Stephen Foster

Publications and source records attributed to C Stephen Foster.

At least 73 records · Page 4Linked to original sources

PubMed2003

Long-term progression, prognosis, and treatment of patients with recurrent ocular manifestations of Reiter's syndrome.

PURPOSE: To investigate the spectrum of ocular involvement, to examine the clinical outcome, and to analyze the influence of treatment in patients with chronic ocular manifestations of Reiter's syndrome (RS) referred to a tertiary care ocular immunology service. DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: Twenty-five patients with RS evaluated at the Ocular Immunology and Uveitis Service of the Massachusetts Eye and Ear Infirmary from 1981 through 2001. METHODS: Charts of patients were reviewed and data on age, gender, follow-up time, ocular symptoms, extraocular involvement, ocular complications, therapy, and visual acuities were recorded. MAIN OUTCOME MEASURES: Visual acuity, ocular complications, disease progression, clinical outcome, and systemic treatment. RESULTS: Twenty-five patients (20 male and 5 female) diagnosed with RS, with a mean age at presentation to our service of 37 years, were studied. The mean follow-up was 48.5 months. Eighty-five percent of patients tested were positive for human leukocyte antigen B27. Sixty-four percent of patients had a positive family history. All patients had oligoarthritis and enthesitis, most commonly affecting the back (56%), Achilles tendon (52%), and sacroiliac joint (24%). Eighty percent had a history of infection, most frequently urethritis (68%). Forty-four percent had a history of mucocutaneous lesions. All patients demonstrated ocular involvement at the time of diagnosis (68% with unilateral and 32% with bilateral disease), 84% had evidence of uveitis, 3% had scleritis, 2% had conjunctivitis, and 1% had pars planitis and iridocyclitis. During follow-up, the ocular complications included conjunctivitis (96%), anterior uveitis (92%), posterior uveitis (64%), keratitis (64%), cataract (56%), intermediate uveitis (40%), scleritis (28%), cystoid macular edema (28%), papillitis (16%), and glaucoma (16%). Systemic treatment for ocular inflammation was initiated in all patients. Ninety-six percent were treated with nonsteroidal anti-inflammatory agents. Eighty-eight percent were treated with corticosteroids, 64% requiring systemic prednisone. Immunosuppressive therapy was initiated in 52% of patients, with all receiving methotrexate. Seven patients required more than one immunosuppressive agent. The mean initial visual acuity was 20/25 in the right eye and 20/30 in the left eye. The mean final visual acuity was 20/25 in the right eye and 20/25 in the left eye. CONCLUSIONS: Reiter's syndrome may be associated with chronic recurrent ocular inflammation. Systemic therapy (including immunosuppressive treatment) typically is required to control the ocular inflammation and to prevent progressive visual loss.

Adolescent↗

PubMed2003

Neutrophil and eosinophil participation in atopic and vernal keratoconjunctivitis.

PURPOSE: A retrospective study was conducted at three centers to examine the participation of neutrophils and eosinophils in the inflammatory processes associated with atopic keratoconjunctivitis (AKC) and vernal keratoconjunctivitis (VKC). METHODS: Conjunctival specimens were obtained from four patients with AKC, six with VKC, and five normal subjects. Indirect immunofluorescent staining was used to localize neutrophil elastase (NE) and eosinophil granule major basic protein (MBP) in serial sections of all specimens. RESULTS: Specimens from both AKC and VKC patients revealed extracellular deposition of NE and MBP. Control specimens showed no or minimal extracellular NE, and no MBP. Statistical analysis demonstrated significantly greater extracellular MBP deposition in AKC specimens compared to controls (p = 0.009), and VKC specimens showed significantly greater staining for both extracellular MBP (p = 0.005) and NE (p = 0.006). CONCLUSIONS: These results suggest that neutrophils, in addition to eosinophils, play an active role in the pathogenesis of AKC and VKC as evidenced by the extracellular deposition of their specific granule proteins.

Adult↗

PubMed2003

Human mast cell subtypes in conjunctiva of patients with atopic keratoconjunctivitis, ocular cicatricial pemphigoid and Stevens-Johnson syndrome.

PURPOSE: Investigate mast cell (MC(S)) subtypes in atopic keratoconjunctivitis (AKC), ocular cicatrical pemphigoid (OCP), and Stevens-Johnson Syndrome (SJS). METHODS: MC(S) subtypes were determined by immunohistochemistry of conjunctiva (obtained from 34 patients--9 AKC, 9 OCP, 9 SJS and 7 normal) using monoclonal antibodies directed against chymase (MC(C)) and tryptase (MC(T)). Double staining was used to distinguish MC(S) as positive for both chymase and tryptase (MC(TC)). RESULTS: The number of MC(S) was significantly increased in AKC, OCP and SJS patients, compared to normal subjects. MC( C) were especially high in AKC, and moderately high in OCP. MC(T ) and MC(TC) were similar in each disease group. CONCLUSIONS: While the AKC findings were not surprising, the result in OCP and SJS suggests that MC(S) play an underappreciated role in the inflammatory process of these disorders. Disparate proportions of MC(S) subtypes in these diseases may imply differential functions of MC(S) in these disorders.

Adult↗

PubMed2003

Diagnosis and treatment of juvenile idiopathic arthritis-associated uveitis.

PURPOSE OF REVIEW: This review surveys publications from peer-reviewed literature published since 2001on the matter of uveitis associated with juvenile idiopathic arthritis. RECENT FINDINGS: Uveitis associated with juvenile idiopathic arthritis (JIA) continues to blind substantial numbers of children every year, even in the most developed of societies. This is so because of delayed diagnosis (as a consequence of the silent, asymptomatic nature of ocular inflammation in some patients), and because of delayed referral by general ophthalmologists of children with JIA-associated uveitis to ocular immunologists prepared to move on to systemic immunomodulatory therapy in those instances where the child's uveitis is chronic or continues to recur with each attempt at tapering corticosteroid. The evidence for this is vast. SUMMARY: Progress in the matter of reducing the prevalence of blindness secondary to this disease will require the increasing willingness of the world's ophthalmologists to refer patients with JIA-associated uveitis much earlier in the course of his or her disease for consideration of immunomodulatory therapy, and will require legislation mandating visual acuity testing in children attending day care centers.

Adrenal Cortex Hormones↗

PubMed2003

The cell-layer- and cell-type-specific distribution of GalNAc-transferases in the ocular surface epithelia is altered during keratinization.

PURPOSE: It has been hypothesized that the biosynthesis of O-linked glycans on proteins, particularly on the highly O-glycosylated mucins, by the corneal and conjunctival epithelium is necessary for the protection and maintenance of a healthy ocular surface. The initial step in O-glycosylation is the enzymatic addition of N-acetyl galactosamine (GalNAc) to serine and threonine residues by a large family of polypeptide GalNAc-transferases (GalNAc-Ts). The purpose of this study was to determine the cellular distribution of GalNAc-Ts in the normal ocular surface epithelia and to compare their distribution with that in pathologically keratinized conjunctival epithelia. METHODS: Five conjunctival biopsy specimens and 5 corneas from normal individuals, and 14 conjunctival specimens from patients with ocular cicatricial pemphigoid (OCP) were used. Based on the histologic characteristics of their epithelia, OCP specimens were divided into two groups: less advanced, nonkeratinized (n = 6), and late-stage, keratinized (n = 8). Five monoclonal antibodies raised against the GalNAc-T1, -T2, -T3, -T4, and -T6 isoenzymes, were used for immunofluorescence microscopic localization according to standard protocols. RESULTS: Immunohistochemical studies revealed the presence of GalNAc-T2, -T3, and -T4 isoforms within the stratified epithelium of the cornea and the conjunctiva. The GalNAc-T4 isoenzyme was found in the apical cell layers, whereas GalNAc-T2 was found in the supranuclear region of the basal cell layers of both cornea and conjunctiva. GalNAc-T3 was distributed throughout the entire ocular surface epithelium, whereas GalNAc-T1 was found in scattered cells in conjunctiva only. Binding of antibody to GalNAc-T6 was restricted exclusively to conjunctival goblet cells. There were distinct alterations in expression patterns of GalNAc-T2, -T6, and -T1 in nonkeratinized OCP epithelia compared with normal epithelia. Both GalNAc-T2 and -T6 were expressed in the apical stratified epithelia, and T1 was detected in all cell layers in five of six biopsy specimens. By comparison with nonkeratinized OCP epithelia, a marked reduction in the binding of GalNAc-T antibody was observed in the late-stage keratinized conjunctival epithelia of patients with OCP. In all samples, apical GalNAc-T2 was absent, and GalNAc-T6 was entirely absent. Only one of eight samples was positive for GalNAc-T1. CONCLUSIONS: The presence of GalNAc-T isoenzymes in the human corneal and conjunctival epithelia is cell-layer and cell-type specific. The increased distribution of GalNAc-Ts observed in early stages of the keratinization process in patients with OCP suggests a compensatory attempt of the ocular surface epithelium to synthesize mucin-type O-glycans to maintain a wet-surface phenotype. This early increase in isoenzymes in nonkeratinized OCP epithelia is reduced as keratinization proceeds in the disease.

Aged↗

PubMed2003

Strong associations between specific HLA-DQ and HLA-DR alleles and the tubulointerstitial nephritis and uveitis syndrome.

PURPOSE: To identify genetic markers for the tubulointerstitial nephritis and uveitis (TINU) syndrome by using human leukocyte antigen (HLA) genotyping. METHODS: Eighteen patients who had TINU syndrome were evaluated at three institutions. Typing of class I and II genes was performed by using DNA-based techniques. RESULTS: Significant associations were found with HLA-B14 (6/18 patients, 33.3%; control subjects, 5.5%; P = 0.0003; relative risk [RR] = 8.5), HLA-DQA1*01 (17/18 patients, 94.4%; control subjects, 46.6%, P = 0.0001; RR = 19.5), HLA-DQA1*0101 (14/18 patients, 77.8%; control subjects 22.2%; P < 0.0001; RR = 12.2), HLA-DQB1*05 (14/18 patients, 77.8%; control subjects 17.7%; P < 0.0001; RR = 16.3), HLA-DQB1*0501 (13/18 patients, 72.2%; control subjects 12.9%; P < 0.0001; RR = 17.6), HLA-DRB1*01 (14/18 patients, 77.8%; control subjects, 12.1%; P < 0.0001; RR = 25.5), and HLA-DRB1*0102 (13/18 patients, 72.2%; control subjects, 1.6%; P < 0.0001, RR = 167.1). The HLA haplotype most frequently identified in the study patients was HLA-DQA1*01/DQB1*05/DRB1*01 (13/18 patients, 72.2%). CONCLUSIONS: TINU syndrome is strongly associated with HLA-DQA1*01, HLA-DQB1*05, and HLA-DRB1*01. The association with HLA-DRB1*0102 is one of the highest reported for any disease. Because these genes are in linkage disequilibrium, the role of the individual alleles is difficult to assess. Based on the results of the present study and on previously reported HLA associations in patients with TINU syndrome, the alphabeta dimer encoded by HLA-DQA1*01/DQB1*05 may be particularly important in conferring risk for development of this disease.

Adolescent↗

PubMed2003

Role of collagen-binding heat shock protein 47 and transforming growth factor-beta1 in conjunctival scarring in ocular cicatricial pemphigoid.

PURPOSE: Submucosal fibrosis due to excessive accumulation of collagens is an important histologic feature in the pathogenesis of ocular cicatricial pemphigoid (OCP). Heat shock protein 47 (HSP47), a collagen-binding protein, plays an important role in the biosynthesis of procollagens. In the present study, we examined the role of HSP47 in conjunctival scarring in patients with OCP. METHODS: Biopsy specimens of the conjunctiva of 15 patients with OCP and 5 normal subjects were studied for the expression of HSP47, transforming growth factor (TGF)-beta1, type I collagen, and type III collagen. The role of TGF-beta1 on the induction of HSP47 and type I collagen by conjunctival fibroblasts was studied by immunostaining, Western blot analysis, and quantitative real-time PCR. RESULTS: Compared with the control, increased accumulations of type I and type III collagens were detected by immunohistochemistry in fibrotic conjunctiva of patients with OCP. Weak and sparse expression of HSP47 was detected in the epithelial cells and stromal fibroblasts in control conjunctival tissues. In contrast to the control, the expression of HSP47 was markedly increased in the stromal fibroblasts in conjunctival tissues obtained from patients with OCP, as detected by immunohistochemistry. By quantitative real-time PCR, compared with control conjunctival tissues, a 3.4-fold increase in the expression of HSP47 was noted in the conjunctival tissues obtained from patients with OCP. Similar to conjunctival tissues, fibroblasts isolated from conjunctiva of patients with OCP exhibited 4.8-fold increase in the expression of HSP47, compared with control fibroblasts. When conjunctival fibroblasts were treated with various concentration of TGF-beta1, upregulation in the expression of HSP47 and type I collagen was detected. CONCLUSIONS: This study demonstrated increased expression of HSP47 and TGF-beta1 by conjunctival fibroblasts in biopsy specimens obtained from patients with OCP. TGF-beta1 induced the expression of HSP47 and type I collagen by conjunctival fibroblasts. Increased levels of TGF-beta1 and HSP47 may regulate increased synthesis, assembly, and production of collagens and thereby could significantly contribute to the process of conjunctival scarring in patients with OCP.

Blotting, Western↗

PubMed2003

Role of connective tissue growth factor in the pathogenesis of conjunctival scarring in ocular cicatricial pemphigoid.

PURPOSE: Conjunctival fibrosis due to excessive accumulation of collagens is an important histologic feature in ocular cicatricial pemphigoid (OCP). Studies have suggested a role of transforming growth factor (TGF)-beta1 in conjunctival fibrosis in patients with OCP. Connective tissue growth factor (CTGF) is an important downstream mediator of TGF-beta1-induced collagen synthesis. CTGF usually acts synergistically with TGF-beta1 during the process of fibrosis in various organs. Hence, studying the mechanism by which CTGF influences TGF-beta1-induced synthesis of collagen in conjunctiva of patients with OCP would provide insight into the mechanism of conjunctival fibrosis in patients with OCP. METHODS: Biopsy specimens from conjunctiva of 10 patients with OCP and 5 normal subjects, were studied, with immunohistochemistry and real-time PCR, for the expression of CTGF and interstitial type I collagen. Using fibroblasts cultured from conjunctival biopsies we determined the effects of TGF-beta1 on the induction of CTGF and type I collagen by immunostaining, and quantitative real-time PCR. The effects of blocking the bioactivity of TGF-beta1 on the expression of CTGF and type I collagen were determined in TGF-beta1-stimulated fibroblasts, before and after treatment with type II receptor neutralizing antibody. RESULTS: An increased stromal accumulation of interstitial type I collagen with an increased expression of CTGF was observed in biopsy sections of patients with OCP, compared with the control. By quantitative real-time PCR, a 3.2-fold increase in the expression of CTGF was detected in conjunctival tissues obtained from patients with OCP, compared with control conjunctiva. Fibroblasts isolated from conjunctiva of patients with OCP expressed 4.4-fold more CTGF, compared with control conjunctival fibroblasts, by real-time PCR. When these cultured fibroblasts were immunostained, an increased expression of CTGF was detected in fibroblasts isolated from patients with OCP, compared with control. Furthermore, when conjunctival fibroblasts were treated with TGF-beta1, an approximately ninefold increase in the expression of CTGF and an approximately threefold increase in the expression of type I collagen were detected by real-time PCR, compared with unstimulated fibroblasts. Finally, when antibody to TGF-beta type II receptor was added before TGF-beta1 treatment of these fibroblasts, the expression of type I collagen and CTGF was significantly reduced. CONCLUSIONS: In the present study, an increased expression of CTGF was recorded in conjunctiva of patients with OCP. TGF-beta1 can induce production of CTGF and type I collagen by fibroblasts obtained from conjunctiva in OCP. This induction of CTGF by TGF-beta1 can be blocked by antibody to TGF-beta type II receptors. The findings lead to the conclusion that CTGF is one of the molecules involved in the pathogenesis of conjunctival fibrosis in patients with OCP.

Cells, Cultured↗

PubMed2003

Effects of IL-4 on conjunctival fibroblasts: possible role in ocular cicatricial pemphigoid.

PURPOSE: Increased stromal accumulation of macrophages and submucosal fibrosis due to excessive accumulation of collagens are central histologic features in ocular cicatricial pemphigoid (OCP). Interleukin (IL)-4 plays an important role in both the inflammatory and fibrotic events in several human and experimental diseases. In the present study, the possible role of IL-4 in the pathogenesis of OCP was investigated. METHODS: Biopsy specimens from the conjunctivae of 10 patients with OCP and 5 normal subjects were studied for the expression of IL-4 by immunohistochemistry. The expression level of IL-4 was also examined in conjunctival fibroblasts of normal control subjects and patients with OCP. The effects of IL-4 in the induction of inflammatory and fibrogenic molecules was studied in IL-4-treated conjunctival fibroblasts, and the expression levels of macrophage colony-stimulating factor (m-CSF), heat shock protein (HSP)-47 and type I collagen was determined by quantitative real-time PCR. The level of IL-4 was also measured by enzyme-linked immunosorbent assay (ELISA) in serum samples obtained from patients with OCP during active stage and remission and were compared with the levels in control sera. RESULTS: Compared with the weak expression of IL-4 in the normal conjunctival sections, an increased expression of IL-4 was noted in conjunctival sections of patients with OCP. A similar increase in the expression of IL-4 was also detected in fibroblasts isolated from conjunctiva of patients with OCP, compared with control fibroblasts. Real-time PCR and ELISA detected a significantly increased level of m-CSF, at both the mRNA and protein levels in IL-4-stimulated cells. Similarly, IL-4 treatment resulted in the induction of type I collagen and collagen-binding HSP47 by conjunctival fibroblasts, as detected by real-time PCR. However, no apparent changes in the levels of IL-4 were detected by ELISA in serum samples of patients with OCP and control subjects. CONCLUSIONS: Increased conjunctival expression of IL-4 may play an important role in the regulation of local accumulation of macrophages (by inducing m-CSF), and matrix accumulation (by inducing HSP47 and collagen) during conjunctival scarring in patients with OCP. IL-4, therefore, may augment or enhance both conjunctival inflammatory and subsequent fibrotic responses in patients with OCP.

Collagen Type I↗

PubMed2003

High-dose methotrexate for intraocular lymphoma.

PURPOSE: Intraocular lymphoma (IOL) frequently coexists with primary central nervous system lymphoma(PCNSL). We sought to determine the efficacy of high-dose methotrexate (MTX) alone in patients with IOL. We also sought to determine whether micromolar levels of MTX could be achieved in the aqueous and vitreous humor of the eye after i.v. administration of the drug. EXPERIMENTAL DESIGN: Nine patients with concurrent PCNSL and IOL or isolated IOL were treated with MTX alone. All patients were treated with i.v. 8 g/m(2) MTX. MTX concentrations in serum, aqueous humor, and vitreous humor were obtained in seven of nine patients with IOL and in one additional patient with PCNSL but no evidence of IOL. RESULTS: Micromolar concentrations of MTX were present in both ocular chambers 4 h after completion of the infusion in eight of eight patients. Levels of MTX were lower in the vitreous humor compared with the aqueous humor in five of six patients in whom both chambers were assayed. Initial response of IOL to MTX was demonstrated by seven of nine patients (six complete responses and one partial response), whereas two patients had persistent IOL despite achievement of micromolar concentrations of MTX. In the patients with concurrent PCNSL and IOL, seven of seven had complete responses in the brain after treatment with MTX. Three of seven patients with initial response of IOL experienced relapse in the eye requiring orbital radiation, and four of nine patients had sustained response of IOL to MTX. CONCLUSIONS: A subset of patients with IOL may experience sustained remission when treated with high-dose i.v. MTX alone. Although micromolar MTX concentrations are present in the eye 4 h after infusion, the lower concentration achieved in vitreous humor may contribute to persistence of IOL.

Adult↗

PubMed2002

Sectorial keratitis and uveitis: differential diagnosis.

PURPOSE: The purpose of this study was to examine the importance of considering the differential diagnosis for patients with sectorial keratitis and uveitis by case summary and literature review. METHODS: A retrospective review of patients with sectorial keratitis and uveitis seen at the Ocular Immunology and Uveitis Service of the Massachusetts Eye and Ear Infirmary and a summary of the diagnoses of cases with similar ocular findings that have been reported in the literature. RESULTS: Data on six patients with sectorial keratitis and uveitis were reviewed. Four patients were female and two were male, ages 21-50 years. All were eventually diagnosed with herpes simplex viral stromal sectorial keratitis. The corneal infiltrates were most common in the superior corneal quadrants, located in the posterior corneal layers. Anterior non-granulomatous uveitis was present in all cases. One case had bilateral ocular involvement. Five of the six patients responded to topical steroids and antiviral treatment. Immunomodulation with methotrexate, cyclosporine, and systemic prednisone was required in one patient. Glaucoma was a complication in six of the seven eyes. Five patients developed corneal scarring, localized in the anterior and mid-stroma. CONCLUSION: The differential diagnosis of sectorial keratitis and uveitis is limited. The entities included in the differential are diverse; some of them threaten not only vision but also life. It is important for the ophthalmologist to be familiar with these entities, in order to pursue pertinent diagnostic investigations and arrive at an accurate diagnosis and institute appropriate management.

Acyclovir↗

PubMed2002

Electroretinograms as an indicator of disease activity in birdshot retinochoroidopathy.

PURPOSE: To determine whether electroretinogram results can help predict the success in tapering of immunosuppressive medication in patients with birdshot retinochoroidopathy. METHODS: Fifteen patients with birdshot retinochoroidopathy who had at least three serial electroretinograms (ERG) during the course of their disease were included in the study. Charts of patients seen at the Immunology and Uveitis Service at the Massachusetts Eye and Ear Infirmary, Boston, Massachusetts were retrospectively reviewed. Seven parameters of the ERGs were examined: dim scotopic amplitude, bright scotopic amplitude, bright scotopic implicit time, single-flash photopic amplitude, single-flash photopic implicit time, 30 Hz flicker amplitudes, and 30 Hz flicker implicit times. For each parameter the patients were divided into two groups, those with normal and those with abnormal responses at the time their immunosuppressive medication taper was initiated. The percentage of patients in each group who were able to successfully taper their immunosuppressive medication was calculated. A successful taper of medication was defined as no recurrence of disease signs or symptoms for at least 1 year after the medication was terminated. RESULTS: Abnormalities in the bright scotopic response amplitudes and 30 Hz flicker implicit times were associated with recurrence of inflammation as immunosuppressive therapy was tapered. CONCLUSION: ERG can serve as a useful adjunct in helping determine when to initiate tapering of immunosuppressive therapy in patients with birdshot retinochoroidopathy.

Adult↗

PubMed2002

Biology of interleukin-5 in ocular cicatricial pemphigoid.

BACKGROUND: Ocular cicatricial pemphigoid (OCP) is an autoimmune disease characterized by the presence of autoantibodies, T-cell dysregulation, and abnormal serum levels of cytokines such as interleukin-6, interleukin-1, and tumor necrosis factor-alpha. The purpose of the present study was to investigate levels of interleukin-5 (IL-5) in the sera, eosinophil counts in the peripheral blood, and eosinophil and mast cell counts in the inflamed conjunctivae of patients with active OCP. METHODS: Seven patients diagnosed in the active phase of OCP presenting with chronic cicatrizing conjunctivitis were studied. The serum levels of IL-5 were compared to a group of seven age-, race-, and sex-matched normal human subjects. Eosinophil and mast cell counts in the patients' conjunctivae were compared to those in normal conjunctivae harvested during cataract surgery from seven normal individuals. In addition, eosinophil counts in peripheral blood of patients with active OCP were compared to those in normal individuals. RESULTS: The mean serum level of IL-5 in patients with active OCP was higher (67.23 pg/ml, range 46.33-98.26 pg/ml) than that in normal individuals (12.18 pg/ml, range 7.66-18.86). The difference was statistically significant ( P<0.001). On light microscopy the biopsied conjunctivae stained with hematoxylin and eosin revealed statistically significant differences ( P<0.001) in the mean numbers of eosinophils in the substantia propria between the patients with active OCP (6.8 cells/cm(2), range 4.8-8.2 cells/cm(2)) and normal controls (0.91 cells/cm(2), range 0.4-1.8 cells/cm(2)). The average number of mast cells found in the substantia propria of the biopsied conjunctivae was statistically significantly higher in patients with OCP (13.79 cells/cm(2), range 6.6-19.4) than in normal individuals (4.34 cells/cm(2), range 3.2-7.8; P<0.01). The average number of eosinophils in the peripheral blood of patients with active OCP (6.6x10(7)/l, range 2.9 - 9.3x10(7)/l) was statistically significantly higher ( P<0.01) than in normal controls (2.09x10(7)/l, range 0 - 4.5x10(7)/l). CONCLUSIONS: The results suggest that IL-5 may play an important role in the pathogenesis of OCP.

Aged↗

PubMed2002

The first international consensus on mucous membrane pemphigoid: definition, diagnostic criteria, pathogenic factors, medical treatment, and prognostic indicators.

OBJECTIVE: We aimed to develop consensus-based recommendations for streamlining medical communication among various health care professionals, to improve accuracy of diagnosis and treatment, and to facilitate future investigations for mucous membrane pemphigoid. PARTICIPANTS: Because of the highly specific nature of this group of diseases, the 26 invited participants included either international scholars in the field of mucous membrane pemphigoid or experts in cutaneous pharmacology representing the 3 medical disciplines ophthalmology, oral medicine, and dermatology. EVIDENCE: The first author (L.S.C.) conducted a literature search. Based on the information obtained, international experts who had contributed to the literature in the clinical care, diagnosis, and laboratory investigation for mucous membrane pemphigoid were invited to participate in a consensus meeting aimed at developing a consensus statement. CONSENSUS PROCESS: A consensus meeting was convened and conducted on May 10, 1999, in Chicago, Ill, to discuss the relevant issues. The first author drafted the statement based on the consensus developed at the meeting and the participants' written comments. The draft was submitted to all participants for 3 separate rounds of review, and disagreements were reconciled based on literature evidence. The third and final statement incorporated all relevant evidence obtained in the literature search and the consensus developed by the participants. The final statement was approved and endorsed by all 26 participants. CONCLUSIONS: Specific consensus-based recommendations were made regarding the definition, diagnostic criteria, pathogenic factors, medical treatment, and prognostic indicators for mucous membrane pemphigoid. A system of standard reporting for these patients was proposed to facilitate a uniform data collection.

Humans↗

PubMed2002

Ocular characteristics and disease associations in scleritis-associated peripheral keratopathy.

OBJECTIVES: To evaluate ocular characteristics and systemic disease associations in patients with scleritis-associated peripheral keratopathy and its different patterns, and to assess any ocular or systemic prognostic significance of the presence of the types of peripheral keratopathy in patients with scleritis. DESIGN: Review of 125 patients with scleritis alone and 47 patients with scleritis-associated peripheral keratopathy; review of patients with scleritis and the different patterns of peripheral keratopathy: peripheral corneal thinning, stromal keratitis, and peripheral ulcerative keratitis (PUK); review of ocular and systemic outcomes comparisons between patients with scleritis with and without peripheral keratopathy. RESULTS: Patients with peripheral keratopathy had more necrotizing scleritis (57%, P<.001), decrease in vision (81%, P<.001), anterior uveitis (62%, P<.002), impending corneal perforation (62%, P<.001), and potentially lethal specific-disease association (87%, P<.001) than did patients with scleritis alone. Patients with PUK had the worst ocular and systemic outcomes. Of the 24 patients with PUK, 16 (67%) had necrotizing scleritis (P =.02), virtually all had a potentially lethal systemic disease (P =.02), and all had impending corneal perforation (P<.001). CONCLUSION: The detection of peripheral keratopathy, and especially PUK, in a patient with scleritis indicates a poor ocular and systemic prognosis.

Adolescent↗

PubMed2002

Chronic postoperative endophthalmitis due to pseudomonas oryzihabitans.

PURPOSE: To report a case of chronic postoperative endophthalmitis caused by the gram-negative bacterium Pseudomonas oryzihabitans. DESIGN: Interventional case report. METHODS: A 77-year-old man was referred to our service for nonpainful uveitis in the right eye accompanied by increased intraocular pressure of 2 years' duration with onset 4 months after uncomplicated extracapsular cataract extraction and posterior chamber intraocular lens implantation. The uveitis partially responded to topical corticosteroid therapy but was recurrent with tapering of steroids. An anterior chamber tap and vitreous biopsies sent for cultures were negative. Owing to the persistence of inflammation despite intraocular vancomycin injection, the lens implant and capsule were removed and culture of the latter revealed the bacterium P. oryzihabitans. RESULTS: There was no recurrence of inflammation after removal of the lens implant and capsule. CONCLUSIONS: Unlike other gram-negative organisms, which are associated with poor outcomes, P. oryzihabitans may masquerade as chronic uveitis because of its low virulence.

Aged↗

PubMed2002

The effect of treatment and its related side effects in patients with severe ocular cicatricial pemphigoid.

PURPOSE: To determine the clinical outcome of patients with ocular-cicatricial pemphigoid (OCP) and the influence of systemic treatment on clinical progression. DESIGN: Noncomparative interventional case series. PARTICIPANTS: Sixty-one patients with biopsy-proven OCP. METHODS: Patients with documented disease progression treated with chemotherapy and/or corticosteroids were followed between 1985 and 2000. The parameters evaluated were ocular stage at presentation, visual acuity, ocular complications, disease progression, control of ocular inflammation, and presence of extraocular involvement. Systemic treatment and related side effects were analyzed. MAIN OUTCOME MEASURES: Visual acuity, ocular complications, extraocular involvement, disease progression, clinical outcome, systemic treatment, and related side effects. RESULTS: Sixty-one patients (32 female; 29 male) with a mean age of 67 years were studied. Extraocular involvement was present in 50% of patients. Sixty percent of eyes were initially seen with stage III (advanced cicatrizing) disease at first evaluation. Seven percent of involved eyes at first visit and 21% at the end of follow-up were legally blind. The most common ocular complications encountered were dry eye, corneal abnormalities, and glaucoma. Dapsone was the most commonly used drug (51 patients), followed by methotrexate (24 patients), azathioprine (23 patients), and cyclophosphamide (15 patients); prednisone, always given as adjunctive treatment, was used in 17 patients. Control of ocular inflammation (total or partial) was achieved in 90% of patients, but 46% of them needed continuation of systemic treatment to avoid disease recurrences, and 10% progressed despite different drugs used. Two agents were required in 32% of cases to control disease activity. The most common treatment-related side effects were hematologic complications (n = 34) followed by gastrointestinal (n = 17), cardiovascular (n = 15), and urinary complications (n = 11). Dapsone was responsible for the greatest number of side effects (n = 43); methotrexate caused the least trouble (n = 6). Corticosteroid-related complications (n = 34) were mostly cardiovascular and endocrinologic. CONCLUSIONS: Ocular-cicatricial pemphigoid is an autoimmune disease that, untreated, progresses to conjunctival scarring and blindness; systemic immunosuppression is required to control it. Long-term systemic treatment and more than one drug are frequently necessary to avoid recurrences, exposing elderly patients to a higher risk of drug toxicity. The most frequently encountered treatment-related side effects were anemia, leukopenia, liver toxicity, and hypertension.

Adult↗

PubMed2002

Efficacy and safety of chlorambucil in intractable noninfectious uveitis: the Massachusetts Eye and Ear Infirmary experience.

PURPOSE: To report our experience with the use of chlorambucil for otherwise treatment-resistant uveitis and to assess its safety and efficacy. DESIGN: Noncomparative interventional case series. PARTICIPANTS: Twenty-eight patients with intractable noninfectious uveitis. METHODS: We reviewed the records of 28 patients (56 eyes) with chronic noninfectious uveitis who were treated with chlorambucil from 1987 to 2000. Diagnoses included Adamantiades-Behçet's disease (ABD) (7 patients), juvenile rheumatoid arthritis (JRA)-associated uveitis (10 patients), pars planitis (2 patients), sympathetic ophthalmia (1 patient), idiopathic uveitis (6 patients), Crohn's disease (1 patient), and HLA-B27-associated uveitis (1 patient). All patients were refractory to other immunomodulatory therapy and systemic steroids. The median duration of treatment with chlorambucil was 12 months (range, 4-50 months), whereas the median daily dosage was 8 mg (range, 4-22 mg). Patients were followed for a median follow-up period of 46 months (range, 4-166 months) after chlorambucil treatment was begun and continued to be followed for relapse after cessation of therapy. MAIN OUTCOME MEASURES: Visual outcome, response to treatment, treatment-related side effects, drug dosage, previous and final treatment, discontinuation of systemic corticosteroids. RESULTS: Chlorambucil was discontinued in seven patients because of side effects: two females had temporary amenorrhea develop, two patients had unacceptable gastrointestinal intolerance, one patient had infection, and 2 patients had progressive leukopenia. Nineteen patients (68%) showed positive clinical response to the treatment, four (14%) initially responded then relapsed after discontinuation of the drug, three patients with ABD had improvement of ocular disease but worsening of systemic symptoms, and two had persistent inflammation. Visual acuity was improved in 24 eyes (43%), stable in 22 (39%), and worsened in 10 eyes (18%). Systemic prednisone was successfully discontinued in 19 of the 28 patients (68%), and 14 patients were free of inflammation at the end of follow-up without any systemic medication. CONCLUSIONS: Chlorambucil can be a safe and effective alternative for preserving vision in patients with otherwise treatment resistant uveitis.

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