Glaucoma in patients with ocular cicatricial pemphigoid

This retrospective review of 111 patients with ocular cicatricial pemphigoid (CP) identifies 29 patients (26%) with glaucoma. Twenty-seven of these patients had a history of glaucoma for a mean of 11.3 years before the diagnosis of CP was made. Most had advanced glaucoma, with a long history of medication use, optic nerve damage, and visual field loss. Patients with CP and glaucoma were more likely to manifest continued high-grade conjunctival inflammation than those with CP alone despite treatment for CP (P less than 0.05). Possible mechanisms including genetic susceptibility to both diseases, drug-induced conjunctival cicatrization, and CP-induced alterations in aqueous outflow are discussed. Physicians who care for patients with CP should remain mindful of the possible coexistence or development of glaucoma in this group of patients. Patients with glaucoma and chronic conjunctivitis of uncertain etiology should be referred for evaluation by physicians experienced in the detection and management of CP.     

Conjunctival mucoepidermoid carcinoma in a patient with ocular cicatricial pemphigoid and a review of the literature

Invasive mucoepidermoid carcinoma of the conjunctiva of the left lower eyelid was diagnosed in an orbital exenteration specimen of a 57-year-old woman, after a biopsy of the same lesion was originally diagnosed as invasive squamous cell carcinoma. The woman was undergoing mitomycin C injections for ocular cicatricial pemphigoid, diagnosed in the same eye 2 years prior to identification of the neoplasm. The tumor invaded the cornea, sclera, lacrimal gland, regional small nerves, and lymphatics, but did not show intraocular involvement. The original biopsy specimen was reassessed with stains for mucin and found to be mucoepidermoid carcinoma of the conjunctiva. We reviewed 21 cases of mucoepidermoid carcinoma of the conjunctiva described to date in the English literature. We believe this number underestimates the true incidence of this condition, as it is frequently misdiagnosed both clinically and histopathologically. Evaluating suspected aggressive squamous cell carcinoma with special stains for mucin generally helps to identify mucoepidermoid carcinoma of the conjunctiva. More extensive surgical excision than that used for squamous cell carcinoma should be implemented in the management of mucoepidermoid carcinoma of the conjunctiva to prevent recurrence.     

Treatment of ocular cicatricial pemphigoid with sulfasalazine

PURPOSE: To assess the outcome of patients with ocular cicatricial pemphigoid (OCP) treated with sulfasalazine as an alternative to dapsone. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Nine patients with biopsy-proven OCP and previous dapsone-related adverse effects (hemolysis and gastrointestinal disturbances) treated with oral sulfasalazine. METHODS: Clinical data were abstracted from patients' medical records. MAIN OUTCOME MEASURES: Patients' symptoms, ocular inflammation, conjunctival scarring, complete blood cell count (including reticulocyte count). RESULTS: At the initiation of sulfasalazine therapy, ocular inflammation was controlled in all patients but one. Mean follow-up was 12 months (range, 2-35 months). Median oral sulfasalazine dosage was 3 g (range, 1-4 g). The disease remained controlled with sulfasalazine alone in four patients (45%). Two patients (22%) required adjunctive oral cyclophosphamide. Adverse effects necessitating drug withdrawal occurred in three patients (33%): hemolysis in two and gastrointestinal disturbances in one. CONCLUSIONS: Sulfasalazine may be useful in OCP patients with previous dapsone-related adverse effects.     

Cataract surgery in ocular cicatricial pemphigoid

The authors report the results of their experience with cataract surgery in 20 patients (26 eyes) with biopsy-proven cicatricial pemphigoid. All patients were on systemic immunosuppression at the time of surgery (dapsone, azathioprine, cyclophosphamide, or combinations) and were treated with perioperative oral corticosteroids. Patients were evaluated pre- and postoperatively for conjunctival inflammation, conjunctival cicatrization, degree of keratopathy, and disease stage. No patient progressed in disease stage. Vision improved an average of 3.5 Snellen lines (-3 to +8). Worse outcome was associated with chemotherapy intolerance or the presence of any preoperative conjunctival inflammation. Thirteen patients remained on immunosuppressives for the entire study. Corneal ulcers developed postoperatively in three patients in whom continued immunosuppression was not tolerated. Possible mechanisms for inflammatory exacerbation after surgery are discussed. Results indicate that after successful abolition of all conjunctival inflammation through chemotherapy, cataract surgery may be safely performed in patients with cicatricial pemphigoid.     

Immunosuppressive therapy in ocular cicatricial pemphigoid

To evaluate the efficacy of systemic immunosuppressive drugs, including corticosteroids, in the long-term treatment of ocular cicatricial pemphigoid, we conducted a prospective clinical trial in 57 patients (34 women and 23 men ranging in age from 46 to 94 years). Each patient was assigned to one of five groups. Group 1 (26 patients) served as the control group (four patients in this group who showed progression were later switched to treatment groups). Group 2 (eight patients) received combination therapy with cyclophosphamide and prednisone; Group 3 (13 patients) received cyclophosphamide alone: Group 4 (nine patients) received azathioprine; and Group 5 (five patients) received prednisone alone. We found that untreated ocular cicatricial pemphigoid has a variable course and does not necessarily progress. Further, the disease may be asymmetric in severity and progression; progression is more likely in advanced stages than in the earlier stages. Although immunosuppressive therapy inhibited conjunctival shrinking in all four treatment groups, some eyes in each group progressed despite treatment. Serious complications included hemorrhagic cystitis, dermatitis, anorexia and weight loss, gastrointestinal bleeding, and leukopenia.     

Penetrating keratoplasty in ocular cicatricial pemphigoid

PURPOSE: Ocular cicatricial pemphigoid (OCP) is a chronic progressive disease characterised by exacerbations of immunologically driven conjunctival inflammation. In the advanced stages of the disease, severe xerosis with mechanical factors may contribute to the development of blinding keratopathy. The authors report two cases of penetrating keratoplasty (PK) in patients with OCP and discuss the modalities of the surgical procedure for this particular disease. METHODS: Two patients with stage III OCP according to Foster's classification, underwent PK. Initial and final visual acuity, indications of PK, surgical procedure, postoperative therapy, and complications were recorded. RESULTS: For the first patient, after 3 months of follow-up, the graft is still clear, with a remarkable improvement in vision (3/10). For the second patient, however, graft rejection developed 15 days after the operation, complicated later by endophthalmitis, which was controlled with an antibiotic. DISCUSSION: The progression of ocular pemphigoid involves the filling of the conjunctival fornices, formation of symblepharon with lagophthalmos, and dry eye, from which blinding keratopathy can originate. A corticosteroid-based or immunosuppressant treatment blocks the progression of the fibrosis but does not get rid of palpebrale or corneal anomalies, making surgery necessary. This surgery generally gives disappointing results and should be planned when the disease is perfectly under control, during a lull in the disease so as to avoid reactivation of the fibrosis process. Reconstruction of the conjunctival fornices should also precede any corneal transplantation. CONCLUSION: These results indicate that PK may be performed to restore of sight in patients with advanced OCP after controlling the primary immunological process and aggressive treatment of the mechanical factors damaging the ocular surface.     

Treatment of ocular cicatricial pemphigoid with sulfasalazine]

PURPOSE: To report on three patients with biopsy-proven ocular cicatricial pemphigoid successfully treated with sulphasalazine. METHODS: Three case reports. RESULTS: A 71-year-old man, treated with dapsone for ocular cicatricial pemphigoid stopped his treatment because of an allergy to this drug. Oral sulphasalazine, 2.5 grams daily was successfully used as an alternative treatment (3 month follow-up). Two patients, aged 71 and 84 year old, were treated with dapsone for ocular cicatricial pemphigoid. Both patients stopped their treatment because of drug induced hemolytic anemia. They then received oral sulphasalazine, 4 grams daily. The disease was successfully controlled. In the first patient, sulphasalazine was discontinued after 13 months; and in the second patient no relapse was seen after a 16 month follow-up period. No adverse side effect of sulphasalazine occurred. CONCLUSION: Sulphasalazine, that has already been proven to be effective for Crohn's disease, also can be used in ocular cicatricial pemphigoid. However, further studies including a larger series of patients along with a longer follow-up are necessary to confirm the efficacy of sulphasalazine in this disease.     

Association of HLA-DR4 with ocular cicatricial pemphigoid

HLA typing for A, B, and C locus antigens was performed on 70 patients with ocular cicatricial pemphigoid (OCP) and on 1849 controls. Additionally, typing for DR and DQ antigens and for the complement proteins (C2, factor B, C4A, and C4B) was performed on 63 patients and on the same control population. A significantly higher incidence of the following antigens was found in the OCP patients when compared to the control population: DR4 (43% in patients compared to 18% in controls, p = 0.0001); DR5 (41% compared to 16%, p = 0.0001); DQw3 (57% compared to 31%, p = 0.0010); A2 (60% compared to 28%, p = 0.0001); B8 (24% compared to 13%, p = 0.0086); B35 (19% compared to 9%, p = 0.0097); and B49 (7% compared to 2%, p = 0.0052). The complement types SC01, SC30, SC32, SC41, and SC42 were also significantly increased in patients compared to controls. No significant differences were found based on ethnic background, involvement of multiple mucous membranes, history of glaucoma, or deposition of specific immunoreactants in conjunctival biopsy samples. These findings may provide further insights into the pathogenesis of OCP and may help to localize a susceptibility gene for this autoimmune disease.     

眼部Wegener肉芽肿12例临床分析

目的:研究韦格纳肉芽肿病(wegener granulomatosis,WG)的眼部表现、实验室检查、病理及影像学特点,提高眼科医师对本病的认识。方法:分析44例WG病例,入选其中有眼部表现的12例患者,回顾性研究其眼部临床表现、实验室指标、病理结果以及影像学特点。结果:发病平均年龄39岁。从发病到确诊的平均时间为11mo。眼部的任何一个部位都可能受累,包括眼球、附属器及视路。其中眼前节及眼眶最常累及。83%患者AN-CA结果阳性。病理表现有实质组织坏死、肉芽肿、多核巨细胞、微脓肿和血管炎等。CT、MRI是目前辅助诊断WG的有效方法。结论:WG是一种致死性疾病,早期诊断和治疗至关重要,对于以眼科首诊和仅有眼部表现的可疑病例,眼科医生要注意鉴别。     

HLA antigens in ocular cicatricial pemphigoid.

HLA antigen frequencies were studied in 20 patients with ocular cicatricial pemphigoid and 245 normal persons. HLA-B12 demonstrated an increased frequency of 45% in patients with ocular cicatricial pemphigoid which was statistically significant when compared to a frequency of 19.6% in the general population (P less than 0.02). In patients with ocular cicatricial pemphigoid the prevalance of HLA-A3 was increased to 35% when compared to 22.9% in the general population, but this was not statistically significant. The frequency of finding either HLA-A3 or B12 in patients with ocular cicatricial pemphigoid was increased to 75% in comparison with 38.8% in the general population (P less than 0.005). The present study suggests that HLA-B12 and possibly HLA-A3 are genetic markers for ocular cicatricial pemphigoid.     

Surgical treatment with dacryocystitis and retinal detachment in a patient with Wegener granulomatosis

BACKGROUND: We report surgical treatment of a patient with dacryocystitis and retinal detachment (RD), which are rare ophthalmic involvements of Wegener granulomatosis (WG). CASE: The patient was a 26-year-old man with WG. He was diagnosed as having WG 4 years ago and he has been treated by maintenance doses of predonisolone and cyclophosphamide. Rheumatoid factor and serum antinuclear antibody were negative. Cytoplasmic pattern-antineutrophil cytoplasmic antibody (C-ANCA) and renal function were normal. He was found to have nasolacrimal duct obstruction and lattice degeneration bilaterally, retinal tear with RD in the left eye and tear without RD in the right eye. No sign of vasculitis was found in fluorescein angiography. Bilateral dacryocystorhinostomy was performed without any sign of postoperative necrosis of the wound. After the surgery, epiphora and eye discharge disappeared and lacrimal passage has been maintained without obstruction. The pathological findings of his nasal mucosa and lacrimal sac showed chronic inflammation and no typical changes of WG. There was no abnormal change in the conjunctiva and sclera after an uncomplicated scleral buckling surgery. CONCLUSION: We conclude that operations such as dacryocystorhinostomy and scleral buckling surgery may be performed successfully when WG is controlled within the normal limits of C-ANCA.     

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.     

Progression of disease in ocular cicatricial pemphigoid.

BACKGROUND: Ocular cicatricial pemphigoid (OCP) is a sight threatening autoimmune disease that can lead to severe conjunctival cicatrisation and keratopathy. It has a variable course and little is known about the factors that determine disease progression. This study analysed the factors that have prognostic significance regarding disease outcome, progression, and keratopathy. METHODS: Sixty six patients with OCP were monitored prospectively at Moorfields Eye Hospital. The influence of ocular features, the systemic disease, and the management were analysed to identify factors that influence the outcomes and disease progression. RESULTS: The mean age at presentation was 67 years; 56% were men. The binocular visual acuities were 6/24 or worse in 25%. Extensive cicatrisation at presentation was common but correlated only weakly with the visual prognosis. Systemic manifestations included lesions of the mouth in 44%, pharynx in 30%, oesophagus in 27%, nose/sinus in 18%, and skin in 17%. There was no association between the ocular and systemic manifestations. Persistent corneal epithelial defects and limbitis occurred in 18% and 32%, respectively, and both were associated with a worse visual prognosis. Systemic immunosuppression was ultimately prescribed in 74%, mainly in patients with advanced stages of conjunctival cicatrisation. Of patients with more than 24 months follow up, progression of cicatrisation occurred in 35% of eyes (16/46) all but one of which were associated with episodes of conjunctival inflammation. CONCLUSIONS: Persistent epithelial defects, limbal inflammation, and ongoing conjunctival inflammation are important factors that lead to keratopathy and visual handicap. These require aggressive management, often with systemic immunosuppressive treatment. Close follow up is required in cases with extensive cicatrisation.     

Cryotherapy for trichiasis in ocular cicatricial pemphigoid.

Trichiasis is a common and potentially sight threatening complication of ocular cicatricial pemphigoid and is usually secondary to cicatricial entropion. This study aimed to assess the success and complications of eyelid cryotherapy for trichiasis in a group of patients with long term follow up. The case records of all patients with ocular cicatricial pemphigoid that attended the external disease clinic at Moorfields Eye Hospital from 1980 to 1992 were reviewed. Each eyelid was divided into three horizontal zones. Cryotherapy was delivered with an Amoilette cryoprobe for approximately 30 seconds. Failure of the cryotherapy was defined as a regrowth of the eyelashes within the treated zone that either required epilation for symptom control or caused keratopathy. Ninety two lid zones were treated, involving 25 lids of 12 patients. The cumulative chance of success decreased rapidly to 40% over the first year. Thereafter, the chance of success declined slowly to 34% at 4 years. Complications included lid notching (n = 2), tarsal atrophy (n = 1), altered lid contour (n = 1), and temporarily raised intraocular pressure (n = 1). All patients had quiescent disease at the time of the cryotherapy and no patients showed increased conjunctival disease activity after treatment. Six patients were taking systemic immunosuppression medication. When ocular cicatricial pemphigoid is quiescent, lid cryotherapy has an acceptable complication rate. The major reason for recurrence of the trichiasis was attributed to inadequate follicle freezing.     

Blood group related antigens in ocular cicatricial pemphigoid

AIM: To study the MUC5AC and the blood group related antigen expression in ocular cicatricial pemphigoid (OCP) according to the distribution of Lewis and secretor phenotypes in OCP patients compared to normal subjects. METHODS: Immunostaining was performed on conjunctival biopsy specimens from 22 consecutive patients suffering from OCP, using monoclonal antibodies (Mabs) directed against the peptidic core MUC5AC mucin (anti-M1/MUC5AC Mabs) and against the saccharide moieties (anti-blood group related antigens). These latter included anti-Le(a), anti-Le(b), anti-sialyl Le(a), and H type 2 Mabs, which immunoreact with Lewis positive and non-secretor (Le(a)), Lewis positive and secretor (Le(b)), Lewis positive (sialyl Le(a)), and secretor (H type 2) phenotypes respectively. Serological tests were also performed to confirm the phenotype of each patient. The immunohistopathological patterns and the distribution of Lewis and secretor phenotypes were compared with the results of a previous study in normal individuals. RESULTS: (1) In OCP patients compared to the normal population, anti-M1 immunoreactivity of goblet cells was unchanged, whereas anti-Le(a), anti-Le(b), and anti-sialyl Le(a) immunoreactivities of epithelial and/or goblet cells were markedly decreased. (2) 41% of OCP patients had a non-secretor phenotype, which is statistically significantly more than the estimated incidence of the same phenotype in the French population (20%) (p approximately 0.04). CONCLUSIONS: Mucins in OCP patients showed a decreased expression of blood group related antigens whereas the MUC5AC peptidic core detected by anti-M1 Mab remained unchanged. These results also seem to indicate that OCP may be associated with a non-secretor phenotype.