Rituximab and bilateral HSV epithelial keratitis in a patient with mucous membrane pemphigoid.

BACKGROUND: B cell depleting therapy is widely used for lymphoproliferative diseases and immune-mediated disorders, including mucous membrane pemphigoid. The latter is an autoimmune blistering disease affecting predominantly the mucosae potentially associated with devastating complications. METHODS: A 71-year-old patient with severe mucous membrane pemphigoid involving ocular, oral pharyngeal and laryngeal involvement is described. To control the disease, the patient was given rituximab therapy in combination with oral corticosteroids. He subsequently experienced an epithelial herpes simplex virus keratitis in one eye and 3 months later in his fellow eye. Topical treatment with ganciclovir resulted in prompt recovery. RESULTS: For the first time, a correlation between rituximab and bilateral epithelial herpes simplex virus keratitis is described. CONCLUSIONS: Although rituximab is a promising biologic agent for the treatment of autoimmune diseases, it bears the risk of reactivation of viral infections, including the onset of herpes simplex virus keratitis.

Control of ocular disease in mucous membrane pemphigoid.

BACKGROUND: Mucous membrane pemphigoid is a rare immune-mediated disease. It is characterised by an abnormal binding of immunoglobulins to the basement membrane zone of mucous membranes and the skin. Conjunctival involvement in mucous membrane pemphigoid may lead to cicatrising conjunctivitis and eventually to corneal blindness. The factors that determine mild or progressive disease are not fully understood and need to be clarified. This study examines the features, progression and risk factors of patients with ocular involvement in mucous membrane pemphigoid. METHODS: 36 eyes of 18 patients with the diagnosis of ocular disease associated with MMP were identified. Fornix depth and keratopathy were repeatedly assessed using a standardised protocol to identify progression. MMP was diagnosed based on the characteristic clinical and laboratory features. Endpoints of the study were the incidence of progressive disease and the development of keratopathy with and without systemic immunomodulatory therapy. RESULTS: 12 eyes of 6 patients (33%) showed progressive conjunctival cicatrisation. Obvious progression was observed in 2 patients who had refused systemic treatment at an early stage. 10 eyes showed progression while on systemic treatment. In these patients, however, systemic treatment was started at an advanced stage of the ocular disease. None of the patients receiving systemic treatment developed persistent keratopathy. CONCLUSION: Systemic treatment with diaminodiphenyl sulfone and/or cyclophosphamide allows one to control the further progression of cicatrising conjunctivitis. It prevents keratopathy. To be efficient, however, treatment has to be started at an early stage of the ocular disease.

Contact lens-associated fusarium keratitis in Switzerland.

BACKGROUND: Fusarium has been an exceptionally rare cause of infectious keratitis. A recent outbreak of Fusarium keratitis in contact lens wearers in North America and Asia has been associated with the multipurpose disinfection solution ReNu with MoistureLoc (Bausch&Lomb). We report a series of Fusarium keratitis in Swiss contact lens wearers. PATIENTS AND METHODS: A multicentre retrospective case review of patients with corneal ulceration and a positive microbiological identification of Fusarium species was undertaken. RESULTS: Between September 2005 and August 2007, six cases of Fusarium keratitis were identified. Patients were 39 to 63 years of age. All patients were using disposable soft contact lenses for at least two years. Four patients used daily wear disposable lenses. Two patients were wearing 1-monthly disposable lenses and used ReNu with MoistureLoc solution. Due to multiresistant Fusarium, enucleation was required in two cases and an emergency keratoplasty was performed in three cases. An optical keratoplasty was undertaken in one case that developed corneal scarring. Final visual acuity in patients with preserved eyes ranged from light perception to 8 / 20. CONCLUSIONS: Exposure to ReNu with MoistureLoc is not the only risk factor for Fusarium keratitis. In addition to antifungal therapy, an early keratoplasty with excision of the infected tissue seems mandatory to improve prognosis.

Phosphate concentration in ophthalmic corticoid preparations.

BACKGROUND: Topical preparations, high in phosphate, may cause calcification when used on a damaged corneal surface. The knowledge of the phosphate concentration in medications helps to prevent corneal calcifications. Our study gives an overview of the amount of phosphate contained in ophthalmic corticoid preparations. METHODS: Samples of 38 commercially available corticoid preparations were tested. The quantification of phosphate was performed using the molybdate method on a Modular P autoanalyzer. RESULTS: 18 of 38 preparations (47%) had a phosphate concentration above physiological levels (>1.45 mmol/l). It varied greatly, and ranged from less than 0.1 mmol/l (18 preparations) to 62.6 mmol/l. The corticoids that were tested included betamethasone sodium phosphate (18.3-35.5 mmol/l), dexamethasone (0.1-17.6 mmol/l), dexamethasone sodium phosphate (<0.1-62.6 mmol/l), fluorometholone (<0.1-22.5 mmol/l), and prednisolone acetate (<0.1-0.5 mmol/l). CONCLUSIONS: The phosphate concentration in corticoid-phosphate formulations varies greatly, and is mainly determined by the chosen buffer. The prednisolone acetate preparations showed physiological phosphate concentrations. For a treatment on a damaged corneal surface, preparations with physiological phosphate concentrations should be used.

Phosphate concentrations in antiglaucoma medication.

BACKGROUND: Eye drops may contain phosphates as part of their buffer system. In the presence of epithelial keratopathy a high concentration of phosphate favours corneal calcification. To date European legislation does not require a quantitative declaration of the phosphates since buffers are regarded as additives. The knowledge of the phosphate concentration in medications helps to prevent corneal calcifications. Our study gives an overview on the amount of phosphate contained in antiglaucoma drops. METHODS: 21 samples of commercially available antiglaucoma drops were tested. The quantification of phosphate was performed using the molybdate method on a Modular P autoanalyzer. RESULTS: 10 of 21 (47 %) glaucoma drops had a phosphate concentration above physiological levels (> 1.45 mmol/L). A concentration higher than 100 mmol/L was found in four preparations that contained timolol. CONCLUSIONS: Many antiglaucoma drops contain unphysiological levels of phosphate, very high concentrations are found in some beta-blockers. These preparations have the potential to favour the formation of insoluble crystalline calcium phosphate deposits when used on a damaged corneal surface, and should therefore be avoided.

[Chronic (kerato-) conjunctivitis refractory to therapy in children]. / Therapierefraktäre chronische (Kerato-)Conjunctivitis bei Kindern.

BACKGROUND: Chronic conjunctivitis and keratoconjunctivitis account for a significant ocular morbidity. Early diagnosis and appropriate management are essential to avoid persisting structural damage and visual loss. In children, the correct diagnosis is frequently delayed because of the low individual experience with pediatric ocular inflammation, the uncommon clinical manifestations and the rarity of some conditions. This study aims to identify the problems associated with the diagnosis of chronic pediatric (kerato-)conjunctivitis. PATIENTS AND METHODS: 48 consecutive tertiary referrals (median age: 8.5 years) with chronic conjunctivitis or keratoconjunctivitis were studied. The ocular inflammation of all patients was denoted by their referring ophthalmologists as "chronic conjunctivitis refractory to therapy". The median time since disease onset was 23 months (range: 3 - 118). On average, 2.8 (range: 2 - 5) ophthalmologists were seen before the final diagnosis was made. A standardized protocol was used to classify and diagnose the ocular inflammation. Laboratory investigations were carried out to confirm the diagnosis in 20 out of 48 patients. RESULTS: In 33 out of 48 patients treatment failure was due to an inappropriate diagnosis. The most frequent diagnosis were Staphylococcus-associated inflammation (n = 21) and vernal keratoconjunctivitis (n = 12). Viral infection causing molluscum contagiosum was the most frequent condition that was missed (n = 7). Ligneous conjunctivitis (n = 2) was not recognised by the 9 ophthalmologists who were previously in charge of the treatment. Significant corneal involvement was found in 24 (50 %) patients. CONCLUSION: History taking and a thorough clinical examination of the entire ocular surface allow the correct diagnosis of and therapy for chronic surface inflammation in almost all pediatric patients. Subtle clinical changes have to be sought actively to avoid misdiagnosis. Such changes include lesions in the anterior lid margin, collarettes, follicules, papillae, and superficial punctate keratopathy.

Corneal calcification following intensified treatment with sodium hyaluronate artificial tears.

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

Phosphate concentration in artificial tears.

BACKGROUND: Irrigating solutions and eye drops may contain phosphates as part of their buffer system. In the presence of epithelial keratopathy, a high concentration of phosphate favours corneal calcification. Knowledge of the phosphate concentration in artificial tear products helps to prevent this sight-threatening complication. This study gives an overview on the amount of phosphate contained in artificial tears. METHODS: Fifty-nine samples of commercially available artificial tear preparations were tested. The quantification of phosphate was performed using the molybdate method on a Modular P autoanalyzer. RESULTS: Twenty-six of 59 (44%) artificial tear products had a phosphate concentration above physiological levels (>1.45 mmol/l). A phosphate concentration above 25 mmol/l was found in nine products (15%), a concentration higher than 50 mmol/l in three (5%). CONCLUSIONS: Many artificial tear formulations contain unphysiological levels of phosphate, but very high concentrations are found only in a few products. These preparations have the potential to favour the formation of insoluble crystalline calcium phosphate deposits when used on a damaged corneal surface, and should therefore be used cautiously.

The corynebacterial flora of the normal human conjunctiva is lipophilic.

Corynebacterial isolates, obtained by selective and non-selective media from conjunctival swabs, were speciated by using two recently developed systems. All 25 strains from 92 individuals, as well as 12 strains from a previous similar study, belonged to lipophilic species. The significance of this unusual finding is discussed.

Compound-heterozygous mutations in the plasminogen gene predispose to the development of ligneous conjunctivitis.

Homozygous type I plasminogen deficiency has been identified as a cause of ligneous conjunctivitis. In this study, 5 additional patients with ligneous conjunctivitis are examined. Three unrelated patients (1 boy, 1 elderly woman, and 1 man) had plasminogen antigen levels of less than 0.4, less than 0.4, and 2.4 mg/dL, respectively, but had plasminogen functional residual activity of 17%, 18%, and 17%, respectively. These subjects were compound-heterozygotes for different missense mutations in the plasminogen gene: Lys19 --> Glu/Arg513 --> His, Lys19 --> Glu/Arg216 --> His, and Lys19 --> Glu/Leu128 --> Pro, respectively. The other 2 patients, a 14-year-old boy and his 19-year-old sister, who both presented with a severe course of the disease, exhibited plasminogen antigen and functional activity levels below the detection limit (<0.4 mg/dL and <5%, respectively). These subjects were compound-heterozygotes for a deletion mutation (del Lys212) and a splice site mutation in intron Q (Ex17 + 1del-g) in the plasminogen gene. These findings show that certain compound-heterozygous mutations in the plasminogen gene may be associated with ligneous conjunctivitis. Our findings also suggest that the severity of clinical symptoms of ligneous conjunctivitis and its associated complications may depend on the amount of plasminogen functional residual activity.

Headache and bilateral visual loss in a young hypothyroid Indian man.

We describe the exceptional association of Vogt-Koyanagi-Harada syndrome (VKHS) and hypothyroidism in a 29-year-old man of Indian heritage. VKHS is a rare uveomeningoencephalitic syndrome with probably autoimmune pathogenesis. Nontraumatic uveitis, aseptic meningoencephalitis, vitiligo, alopecia and poliosis are the leading clinical features of VKHS. The reported patient presented with bilateral visual loss and progressive frontal headache. VKHS was diagnosed due to characteristic ophthalmological findings and the diagnosis of aseptic meningitis. Due to the autoimmune pathogenesis, VKHS may be rarely associated with other autoimmune disorders. Association of VKHS with autoimmune thyroid disease has been described in the literature in three patients. In the reported case hypothyroidism due to chronic autommune thyroiditis was diagnosed in association with VKHS. Routinely determination of thyroid function in patients with VKHS is recommended.

[Bilateral cystoid macular edema after successful treatment of AIDS-associated cytomegalovirus retinitis]. / Bilaterales zystoides Makulaödem nach erfolgreich therapierter AIDS-assoziierter CMV-Retinitis.

BACKGROUND: Cystoid macular edema (CME) in AIDS patients with inactive cytomegalovirus (CMV) retinitis is an uncommon but potentially sight-threatening complication. The pathogenesis of CME in these patients is unclear. This study tries to identify possible risk factors by analyzing the charts of five patients. METHODS: Ten eyes of 5 patients that finally developed CME were followed for an average of 18 months. The initial retinal lesions, their response to antiviral treatment, the development of CME, and the patients' immune status were prospectively monitored. RESULTS: CMV retinitis was diagnosed at a median CD4+ count of 3 cells/mm3 (range 0-11). All eyes responded to the initial systemic anti-viral treatment. At the onset of CME, CMV retinitis was controlled by antiviral maintenance therapy in all patients [ganciclovir (n = 2), cidofovir (n = 2), foscarnet (n = 1)]. The median time between diagnosis of CMV retinitis and onset of CME was 11.5 months (range 5-24). Development of CME was associated with significant visual loss: acuity ranged from 0.05 to 0.7 when CME was first noticed, compared to 0.8-1.25 at diagnosis of CMV retinitis. Duration of inflammation, size or zone of retinal necrosis did not favor the development of CME, neither did the antiviral therapy. A weak correlation of CME development and immune status (expressed as increase of CD4+ cells) was found. Due to systemic corticosteroids CME resolved. CONCLUSIONS: CME is a new visual threat to AIDS-patients with CMV retinitis whose immune status improved under the latest combined antiretroviral therapy. Therapy with oral corticosteroids may positively influence this condition.

Corynebacterium macginleyi has to date been isolated exclusively from conjunctival swabs.

Fifteen strains of Corynebacterium macginleyi were exclusively isolated from conjunctival swabs of patients with either conjunctivitis or corneal ulcers. Up to now, only three C. macginleyi strains had been described in the literature. The characteristics of the 15 patients from whom C. macginleyi was isolated are outlined, characteristics useful for the identification of C. macginleyi are described, and the antimicrobial susceptibility pattern of the species is provided. C. macginleyi is uniformly susceptible to penicillins, quinolones, and aminoglycosides. Although considered to be of rather low pathogenicity C. macginleyi seems to have the potential to cause superinfections in selected patients with ocular surface problems.

Successful management of Aspergillus scleritis by medical and surgical treatment.

BACKGROUND: Inflammatory scleral disease is frequently associated with autoimmune disorders and only occasionally caused directly by an infective agent. Fungal infections primarily involving the sclera are rare, and the outcome is generally poor. Here we report three patients with post-operative Aspergillus scleritis who were successfully managed by medical therapy and surgical intervention. PATIENTS: Scleral infection with Aspergillus sp. was diagnosed 6 and 5 months after cataract extraction in a 76-year-old diabetic and an 82-year-old woman respectively, and in a 54-year-old man 3 months after trabeculectomy. Swabs and/or scrapings had not been conclusive and the diagnosis of Aspergillus infection was established in all cases only after scleral biopsy. RESULTS: The infection was eliminated in all cases. This was achieved in one eye by treatment with systemic and topical amphotericin B. The two patients with fungal scleritis after cataract extraction required in addition to the medical therapy (oral itraconazole, topical econazole and amphotericin B) scleral excisions and patch grafts to control infection. CONCLUSION: Fungal scleritis may remain undiagnosed for months. A scleral biopsy may be necessary to establish this diagnosis. Prolonged systemic antifungal therapy alone may not eradicate fungal infection. Surgical excision improves the outcome of fungal scleritis.

[Clinical evaluation of impression cytology in diagnosis of superficial viral infections]. / Klinische Evaluation der Impressionszytologie zur Diagnostik viraler Oberflächeninfektionen.

BACKGROUND: Impression cytology is a non invasive technique for the diagnosis of external eye disease. As infected epithelial cells are losing their adhesion to neighbouring cells they are an ideal target for impression cytology. Despite its diagnostic potential impression cytology has not yet become a routine diagnostic tool because of technical inconvenience in use of conventional membranes. The aim of this study was to evaluate a practicable technique of impression cytology for the rapid diagnosis of superficial viral eye disease. MATERIAL AND METHODS: 52 patients with suspected viral conjunctivitis or keratitis underwent impression cytology with a Biopore membrane device. After air fixation immunologic detection tests using either peroxidase antiperoxidase or fluorescent techniques were performed directly on the membrane. RESULTS AND CONCLUSIONS: 21 of 38 patients with suspected Herpes-simplex-virus (HSV), 3 of 4 patients with suspected Varicella-Zoster-virus (VZV) and 2 of 10 patients with suspected Adenovirus infection had a positive result on the impression cytology membrane. These results were confirmed by virus cultures or polymerase chain reactions (PCR) a few days later. No patient with a negative impression cytology had a positive culture result. Using impression cytology and an immunodetection test results became available within 1 to 4 hours. CONCLUSIONS: Impression cytology combined with immunologic detection tests is a rapid, sensitive and practicable diagnostic test for superficial viral eye diseases.

Pneumocystis carinii infection of the conjunctiva in a patient with acquired immune deficiency syndrome.

BACKGROUND: Ocular disease, especially the development of choroidal lesions, is a known extrapulmonary manifestation of Pneumocystis carinii infection in the acquired immune deficiency syndrome (AIDS). To our knowledge, conjunctival involvement due to P. carinii has not been described previously. METHODS: The authors describe a 33-year-old homosexual male with AIDS in whom a large placoid, white lesion developed involving the tarsal conjunctiva of the right upper lid. Conjunctival malignancy was suspected and biopsies and swabs were taken. At this time, the patient had been receiving monthly aerosolized pentamidine prophylaxis for 18 months, and there was neither a history of pneumonia nor any clinical signs of disseminated infection due to P. carinii. RESULTS: Histopathologic examination results of the conjunctival biopsy specimen showed a necrotic, frothy tissue surrounded by activated fibroblasts. Within this material, Gomori methenamine silver stains showed numerous round and cup-like cysts of P. carinii, confirming the diagnosis that had already been obtained by an indirect fluorescent-antibody stain of a conjunctival smear specimen. CONCLUSIONS: The presence of white placoid conjunctival lesions in a patient with AIDS may indicate an infection due to P. carinii. Conjunctival disease due to P. carinii widens the spectrum of AIDS-associated ophthalmic pneumocystosis.

Diagnosis of MALT lymphoma by conjunctival biopsy: a case report.

BACKGROUND: Most extranodular lymphatic tissue is found in the intestinal mucosa. Together with similarly structured lymphatic tissue at other locations it has been named mucosa-associated lymphatic tissue (MALT). Malignant transformation of such tissue to lymphoma is well known. Although MALT lymphoma has been described in tissue physiologically void of MALT, lymphoma manifestation in the conjunctiva is rare. METHODS: We report a case of a 47-year-old woman who was referred to our clinic for symptomatic treatment and evaluation of severe symptoms of dry eyes. She was thought to suffer from Sjögren's syndrome because of xerophthalmia and xerostomia, as well as massive bilateral swelling of the parotid gland. Ophthalmological examination revealed marked hyperplasia of the conjunctiva, of which a biopsy was taken. RESULTS: Histological and immunohistochemical examination of the conjunctival biopsy, together with analysis of gene rearrangement by Southern blot, led to the diagnosis of low-grade B-cell lymphoma of the MALT. CONCLUSION: The differential diagnosis of keratoconjunctivitis sicca presenting with conjunctival swelling of unknown origin should include lymphoma, especially since Sjögren's syndrome may be associated with malignant disorders of the lymphatic system. A biopsy of suspicious conjunctival changes can clarify a multisystem disease by providing a tissue diagnosis.

Concerning the effect of the K+ channel blocking agent glibenclamide on ischaemic and reperfusion arrhythmias.

Reports on effects of ATP-dependent K+ channel modulating drugs on ischaemia-induced cardiac arrhythmias have been scarce and contradictory. The channel blocking agent glibenclamide (glyburide) has been considered as an antiarrhythmic candidate, because it antagonizes the ischaemic K+ efflux and the shortening of the refractory period. In the present investigation its effects were tested, therefore, in rat hearts with coronary occlusion and reperfusion. In untreated hearts, tachyarrhythmias occurred during the reperfusion, and less pronounced during the coronary occlusion itself. Large amounts of adenosine and its degradation products were released during the coronary reperfusion, particularly from hearts which developed ventricular fibrillation. Glibenclamide (0.1 and 1.0 micromol/l perfusion fluid) neither antagonized the ischaemic nor the reperfusion arrhythmias. Ischaemic arrhythmias were even intensified. Also in control hearts without coronary occlusion, pro-arrhythmic effects of glibenclamide were observed. Furthermore, the coronary flow was considerably decreased by the drug, and the release of adenosine and its metabolites was significantly increased. Sodium nitroprusside antagonized the glibenclamide-induced decrease in the coronary flow, but did not prevent the arrhythmias. The Ca2+ channel blocking agent gallopamil increased the coronary flow, decreased the adenosine release, and antagonized the arrhythmias in hearts with and without glibenclamide. In conclusion, the present findings do not favour the idea of an antiarrhythmic effect of glibenclamide. Rather, some propensity to the occurrence of arrhythmias can be produced by the drug.