Immunological investigations in the evaluation of patients with cicatrising conjunctivitis.
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Biomedical subjects
Publications and source records attributed to W Bernauer.
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BACKGROUND: Recurrent corneal erosions can occur as a sequel of trauma, of dystrophies or spontaneously. Therapeutic options include topical lubricating and desiccating agents, therapeutic contact lenses, anterior stromal puncture and, most recently, phototherapeutic keratectomy. At present there are no studies available assessing the value of these different therapeutic options. METHODS: Fifteen eyes of 12 patients underwent therapeutic excimer photoablation after failure of other forms of treatment (lubricating agents in all cases, therapeutic contact lenses in 8, anterior stromal puncture in 2). Ablation depth was 5 microns, except in patients with stromal dystrophy or myopia (6 eyes), who had a deeper ablation. RESULTS: After a first photokeratectomy 9 eyes remained asymptomatic (mean follow-up 12.8 months), 2 eyes had persistent symptoms and 4 had recurrent corneal erosions after 1-24 months. The chance of success after one treatment was 60% after 12 months as calculated by the Kaplan-Meier method. CONCLUSIONS: The method of photoablation as applied in this study has a similar chance of success to other surgical methods such as anterior surgical stromal puncture. Patients included in this study, however, were highly selected and were refractory to other forms of treatment.
BACKGROUND: Acanthamoeba keratitis is an uncommon condition which is usually associated with contact lens wear. The use of home made saline and poor hygiene are important risk factors. Early diagnosis is crucial since these cases respond well to medical therapy. The purpose of this paper is to describe and demonstrate early clinical signs. METHOD: Between September 1992 and October 1994, 70 cases of acanthamoeba keratitis, one of them bilateral, were prospectively monitored at Moorfields Eye Hospital in London. A database of all patients was set up and the clinical findings, diagnostic methods, therapeutic interventions and the outcome were recorded. RESULTS: 66 patients (96%) were contact lens wearers, 64 of them (97%) wore soft lenses. The mean interval between first symptoms and correct diagnosis was 42%. The most frequent initial diagnoses were "unclear keratoconjunctivitis" and "herpetic keratitis". Early corneal findings included punctate keratopathy (n = 14; 20%), pseudodendrites (n = 4; 6%), epithelial infiltrates (n = 17; 24%), diffuse or focal sub-epithelial infiltrates (n = 36; 51%) and radial keratoneuritis (n = 5; 7%). Ring infiltrates (n = 13; 18%) and corneal ulceration (n = 13) were late signs. CONCLUSION: When the above corneal findings are observed, particularly in contact lens wearers, the diagnosis of acanthamoeba keratitis should be considered. The diagnosis of "herpetic keratitis" in association with contact lens wear should be encountered with scepticism.
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.
In isolated perfused rat hearts with coronary occlusion and reperfusion, the effect of adenosine antagonists on the release of adenosine and its degradation products inosine, hypoxanthine, xanthine and uric acid was investigated. An antagonist with high selectivity for the A1 receptor, 8-phenyltheophylline, was applied and compared with the relatively unspecific antagonist theophylline, used in its water-soluble form aminophylline. Depending on the duration of coronary occlusion, more or less severe tachyarrhythmias occurred during the myocardial ischemia, and particularly during the subsequent coronary reperfusion. Large amounts of the nucleosides and oxypurines were released after reopening the coronary artery. The release was particularly, high in hearts with ventricular fibrillation. Both adenosine antagonists increased the release in a highly significant way. The findings let assume that adenosine has perhaps a modulating effect on its own release, which can be blocked by adenosine antagonists.
The association of visual disturbances and rheumatic disease has been known for centuries. This review provides a synopsis of the ocular conditions that are associated with inflammatory rheumatic disease. The major ophthalmic manifestations of the rheumatic diseases include keratoconjunctivitis sicca, ulcerative keratitis, scleritis, uveitis, retinal vascular disease, and neuro-ophthalmic lesions. Each of these ocular conditions is most characteristically associated with a few, but not all, of the rheumatic disorders. Scleritis, for example, is most often seen with rheumatoid arthritis or with vasculitis. Acute anterior uveitis is most often seen with the seronegative spondylarthropathies. Retinal vascular and neuro-ophthalmic lesions are seen with disorders having either a vaso-occlusive component, such as systemic lupus erythematosus, or with one of the vasculitides. Important considerations for a successful collaboration between ophthalmologists and physicians/rheumatologists are discussed.
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In isolated perfused rat hearts the left coronary artery was occluded for 5 min, with subsequent reperfusion for 20 min. During the reperfusion severe tachyarrhythmias were observed, with ventricular fibrillation occurring in all hearts. Simultaneously, large amounts of adenosine and its degradation products inosine, hypoxanthine, xanthine and uric acid were released into the coronary perfusate. The antiarrhythmics quinidine, lidocaine and gallopamil significantly decreased the release. The effect of quinidine and lidocaine was linked with the antifibrillatory action of these drugs. Also the interruption of fibrillation immediately after its appearance by potassium chloride decreased the release of adenosine and its metabolites in a highly significant way. The effect of gallopamil on the release was independent of an antifibrillatory action. The findings indicate that different kinds of antiarrhythmic drugs can affect the release of nucleosides and oxypurines in hearts with ischaemia and reperfusion.
BACKGROUND: Sterile corneal ulceration is a rare complication of rheumatoid arthritis and may lead to corneal perforation. Surgical management for visual restoration frequently is unsuccessful. The authors analyze the factors that may determine the failure of corneal surgery in perforations associated with rheumatoid arthritis. METHOD: The management of 29 patients with rheumatoid arthritis with corneal perforations requiring surgical intervention was reviewed. The corneal lesions were classified either as necrotizing keratitis (n = 20) or as ulcers secondary to surface disease (n = 12), depending on the most evident primary pathology. The outcome of different methods for primary repair (i.e., application of tissue adhesive, lamellar graft, or penetrating keratoplasty) and graft survival in penetrating keratoplasties were analyzed. RESULTS: Fifty-seven corneal procedures were performed in 32 eyes. Primary repair was successful (i.e., no further corneal surgery within 6 months was required) in five eyes (25%) with necrotizing keratitis and in eight eyes (67%) with perforations secondary to surface disease. The application of tissue adhesive, when planned as long-term treatment, was unsuccessful in all five eyes. Immunosuppression significantly improved the survival of first penetrating grafts (42% graft survival after 1 year versus 11% without immunosuppression, P = 0.02). Of 25 graft failures, 20 (80%) were caused by recurrent melts up to 6 months after penetrating keratoplasty. Ocular surface infection was responsible for failure in six of ten grafts after that time. CONCLUSION: Complications of corneal surgery in rheumatoid corneal perforations are frequent. The type of surgical procedure, the predominant pathogenic mechanism, and the perioperative immune status influence the outcome. The control of corneal melting and the prevention of surface infection are critical for graft survival.
BACKGROUND: Scleritis can be a destructive disease frequently associated with autoimmune disorders. It is believed that primary vasculitis plays an important role in its pathogenesis, but little is known about the cellular effector mechanisms. The purpose of this study was to analyze the inflammatory cellular infiltrate in scleritis. PATIENTS AND METHODS: Two enucleated eyes were studied. In one patient, enucleation was done after perforation occurred in anterior necrotizing scleritis and, in the other, after the misdiagnosis of posterior scleritis as an intraocular tumor. Morphological criteria and immunohistochemical methods were used to characterize the inflammatory cellular infiltrate. RESULTS: The cells infiltrating the scleral fibers in the enucleated eyes consisted predominantly of T cells in both cases; many of the T cells were CD4-positive. Clusters of B cells were found in perivascular areas. In circumscribed areas neutrophils, macrophages, and plasma cells were part of the scleral infiltrate. Signs of a granulomatous process with activated macrophages (epitheloid and giant cells) were present in necrotizing scleritis. Expression of major histocompatibility class II molecules (MHC II) was found on lymphocytes and rarely on macrophages. Signs of primary vasculitis were not found in any of the specimens. CONCLUSION: The cellular infiltrate in scleritis shows, at least at certain stages, features compatible with a T-cell mediated (autoimmune) disorder, which has major therapeutic implications.
BACKGROUND: Tumor necrosis and cell death are common features of retinoblastoma. In non-malignant retinal cells after ischemia, as well as in many non-retinal tumors, cell death occurs in at least two ways. We investigated whether similar patterns of cell death could be demonstrated in retinoblastoma cells. METHODS: Nine globes with retinoblastoma from eight patients were studied. Paraffin sections stained with HE or the Feulgen method were examined by light microscopy. Several samples from each tumor were selected for electron microscopic study. RESULTS: Ultrastructurally, two main types of cell death were identified. Type I was characterized by progressive lysis of the cytoplasm and karyoplasm. Nuclear chromatin either dissolved or was transformed into compact clumps becoming extracellular dense bodies. Phagocytosis of cell remnants by neighboring tumor cells, or occasional macrophages, was common. Type II was characterized by progressive condensation and shrinkage of the cytoplasm and nucleus. Type II was subdivided in two forms distinguished mainly by characteristic patchy vs crescentic chromatin condensation. Small parts of condensed cytoplasm were engulfed by neighboring tumor cells. Compact cell remnants then underwent either phagocytosis by neighboring retinoblastoma cells or progressive intercellular disaggregation. CONCLUSION: Retinoblastoma cells may undergo at least two types of cell death. Type I fits the definition of necrosis, while both forms of type II exhibited several features consistent with apoptosis. The types of cell death observed in retinoblastoma exhibited similarities to patterns observed in ischemic retina, as well as in other malignant tumors. Type II cell death (apoptosis) may play a role in limiting tumor growth.
BACKGROUND: Chronic progressive conjunctival cicatrisation is poorly understood, and therapy of this condition remains difficult. This study assessed the value of immunohistochemical investigations in the evaluation of patients who present with chronic cicatrising conjunctivitis similar to cicatricial pemphigoid (CP). METHODS: Bulbar conjunctival biopsies from 36 patients with acute (n = 5), subacute (n = 13) and chronic (n = 18) ocular disease were studied. The biopsy was retaken in 7 patients to evaluate the present immunological findings in comparison with a biopsy more then 5 years ago. All the specimens were investigated for the presence of immunoglobulins and complement at the epithelial basement membrane, and the phenotype of the inflammatory cellular infiltrate was analysed. Twenty-nine patients were evaluated for the presence of circulating IgG-anti-basement membrane zone antibodies. RESULTS: CP was confirmed by immunoglobulins and/or complement deposition at the epithelial basement membrane in 11 patients (31%). IgA was found to be the most frequent deposit. Eleven CP patients, mainly those with active or "burnt-out" disease, showed absence of immunoglobulins and/or complement at the conjunctival basement membrane. In 14 of 36 patients, conjunctival cicatrisation was subsequently felt to be caused by conditions other than CP. The cellular phenotype in the subepithelial conjunctiva was unspecific, but in CP the disease activity was reflected by the number of neutrophils and macrophages. Circulating IgG antibodies were found in none of the patients' serum. CONCLUSION: Immunoglobulin and/or complement deposition at the epithelial basement membrane confirms the diagnosis of mucous membrane pemphigoid. Their absence, however, does not rule it out and is a frequent feature in very active conjunctival disease or after immunosuppressive treatment. The analysis of the cellular phenotype in mucous membrane pemphigoid may be useful in the assessment of disease activity but does not help in determining the underlying disease process causing the cicatrising conjunctivitis.
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.