Ciliary tissue transplantation in the rabbit.

Irreversible damage of the ciliary body can be responsible for prolonged ocular hypotony and phthisis bulbi, which, currently, cannot be treated. The aim of this study was to achieve survival of morphologically normal ciliary tissue (CT) transplants in the anterior chamber of a rabbit's eye. Outbred female New Zealand albino rabbits received CT allografts, which were placed on to the surface of the host iris. We evaluated the influence of ciclosporin (CsA), VEGF and donor perfusion on graft survival. Operated eyes were assessed clinically and histologically, and revascularization of the grafts was determined by fluorescein angiography. All grafts became dark and ischemic during the first five to seven days after transplantation. Reperfusion of the grafted tissue was complete at approximately ten days after transplantation. In untreated animals, transplants became infiltrated by inflammatory cells, which led to destruction of the tissue. This was prevented by systemic use of CsA. Transplants treated with VEGF prior to transplantation had fewer ischemic areas but epithelial cell survival was not improved. Whole body donor perfusion prior to preparation of the grafts resulted in less inflammation and, histologically, in a better quantity and quality of the epithelial cells in the CT transplants. Ciliary tissue can be successfully transplanted but the ciliary epithelium suffers from ischemia and in untreated animals the whole transplant is rejected in the classical fashion. If the donor is perfused and the host immunosuppressed, histologically normal ciliary epithelium can be preserved together with rapid revascularization, minimal inflammation and good survival of the transplant, although fibrosis continued to occur during the two months after transplantation.

Smoking delays the response to treatment in episcleritis and scleritis.

PURPOSE: To evaluate the influence of smoking on comorbidity, treatment, visual and general outcome in patients with scleritis. METHODS: The smoking habits of 103 patients with a diagnosis of episcleritis or scleritis were evaluated. These patients were treated by one ruling protocol at the Leiden University Medical Center between 1997 and 2000. Medical records of each patient were evaluated in detail. Data on possible factors concerning smoking were collected by postal questionnaire. RESULTS: Of all 103 patients diagnosed with either episcleritis or scleritis, 41 (39.8%) were smoking during treatment of the scleral inflammation. In total, 19 patients (18.4%) had a smoking history while 43 (41.7%) patients have never smoked. The response to any of the given medications could be delayed by at least 4 weeks in many smoking patients (odds ratio (OR) 5.4 [95% confidence interval 1.9-15.5]), particularly those with posterior scleritis. Smoking patients above the age of 48 years were even more likely to respond belatedly to any given therapy (OR 6.6 [2.1-20.7]). However, having a smoking history did not delay the response. Furthermore, smoking did not worsen the visual prognosis and was not associated with additional recurrences or ocular complications after successful treatment. CONCLUSIONS: Although scleritis patients who smoked during treatment eventually responded, there was frequently over a month's delay before the medication became effective when compared to nonsmokers. This was irrespective of the type of disease or given therapy. As a consequence, smokers required more intensive therapy than those who did not smoke.

Orbital myositis in scleritis.

AIMS: To investigate the association between scleritis and myositis. METHODS: Retrospective, non-comparative case series. Records and ultrasonograms were examined of 132 patients, with a diagnosis of episcleritis or scleritis, who attended the ophthalmology department at Leiden University Medical Center between 1997 and 2000. 103 were eligible for comprehensive examination. Medical records were evaluated. Ultrasonography was performed in all patients diagnosed with episcleritis or scleritis. Clinical features, precipitating factors, systemic associations, ocular complications, treatment, and outcome of each patient were assessed. RESULTS: Of the 103 patients, 27 (26.2%) had episcleritis and 76 (73.8%) had scleritis. Myositis was found to be present in 11 patients. It was present in 14.5% of all patients with scleritis and 30.5% of those in whom the posterior sclera was affected. The presence of the associated myositis did not worsen the visual prognosis and the presence of myositis was not associated with other systemic diseases. There were no cases of unilateral scleritis with bilateral orbital myositis. During an attack ocular complications were more common in patients with scleritis and myositis (64%) than in patients with scleritis alone (30.4%), indicating a more diffuse and potentially dangerous inflammation. There was no evidence that the inflammatory changes in the orbit had spread to involve the sclera, so it is assumed that the muscle changes are an extension of a generalised response to intense inflammation of the episclera and sclera. CONCLUSION: This study found a frequent association between myositis and scleritis. Prognosis for vision was not affected by coexistence of myositis.

Posterior scleritis: clinical features, systemic associations, and outcome in a large series of patients.

OBJECTIVE: To document the clinical features, systemic associations, and visual outcome in a large number of patients with posterior scleritis. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: There were 137 patient records showing patients with a diagnosis of posterior scleritis who were attending or had attended the scleritis clinic at Moorfields Eye Hospital between 1974 and 1996. Ninety-nine records were suitable for detailed analysis. METHODS: The medical records and B-mode ultrasound examinations were reviewed. MAIN OUTCOME MEASURES: The clinical features, systemic associations, treatment, and outcome of each patient were determined. RESULTS: Posterior scleritis occurred at all ages. The mean age at onset was 49.3 years. Posterior scleritis began before age 40 in 30% of patients and was twice as common in women as in men. The B-mode ultrasound examination showed diffuse and nodular changes in the posterior sclera. Necrotizing posterior scleritis was not identified. Twenty-nine percent of patients had an associated systemic disease that included systemic vasculidites, autoimmune diseases, and lymphoma. Such patients more commonly had nodular changes on B-mode ultrasound examination. Early treatment controlled posterior scleral inflammation and limited visual loss. Thirty-one percent of patients lost two or more lines of vision. Statistical analysis revealed that patients older than age 50 had an increased risk of having an associated systemic disease and were more likely to experience visual loss. Patients with associated systemic disease required more aggressive immunosuppressive therapy and more frequently had accompanying anterior scleritis. There was no association between unilateral, bilateral, or recurrent disease and the presence of systemic disease or visual loss from posterior scleritis. CONCLUSIONS: The B-mode ultrasound examination reveals that posterior scleritis occurs far more often than previously thought and can lead to rapid and permanent visual loss. All patients with posterior scleritis must be assumed to be at risk of visual loss. Forty percent of patients had no anterior scleral inflammation, and 9% had no detectable physical signs. All patients need to be investigated for an associated systemic disease and all require early treatment to minimize loss of vision.

Latanoprost in the treatment of glaucoma and ocular hypertension.

Latanoprost (Xalatan) is a prostaglandin F(2alpha) analog prodrug which is activated when hydrolyzed in the cornea and plasma. Latanoprost reduces the intraocular pressure (IOP) by increasing uveoscleral outflow. Other locally applied medications reduce IOP either by increasing the outflow of fluid through the trabecular drainage system or by reducing the production of fluid in the eye. Latanoprost, which is used topically in the eye at the low dose of 0.005% once daily, has been shown in phase III studies carried out in Scandinavia, the U.K. and the U.S. to be capable of lowering the IOP in patients with open-angle glaucoma and ocular hypertension by 35%. This low IOP is maintained over at least a 2-year period. Latanaprost is as effective, or possible slightly more effective than timolol in its pressure reducing effects. Additional pressure reduction can be achieved by adding latanoprost to existing glaucoma medications. Because latanoprost is rapidly metabolized outside the eye, systemic side effects do not occur. Increased iris pigmentation occurs in at least 10% of hazel (but not blue or dark-eyed patients). So far no ocular problem has occurred because of the increased production of pigment which is not released from the iris. Isolated cases of cystoid macular edema have occurred, so that anyone complaining of reduction of vision while using the drug should be fully investigated.

The management of corneal perforations associated with rheumatoid arthritis. An analysis of 32 eyes.

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.

Prevention of immune-mediated corneal graft destruction with the anti-lymphocyte monoclonal antibody, CAMPATH-1H.

We report a patient with peripheral rheumatoid corneal melting who developed a corneal perforation in one eye requiring tectonic keratoplasty. Nine consecutive corneal grafts were rapidly destroyed despite systemic immunosuppression with corticosteroid, cyclophosphamide, azathioprine and cyclosporin A. A rejection episode was observed in one graft before it melted and allograft rejection may have contributed to the destruction of other grafts. Corneal graft survival was ultimately achieved by systemic immunosuppression with the anti-lymphocyte monoclonal antibody, CAMPATH-1H. A single episode of rejection developed in the early post-operative period which was easily reversed by topical corticosteroid. Corneal melting has not recurred and the graft has now remained intact and clear for 24 months. Anti-lymphocyte monoclonal antibodies may therefore provide effective immunosuppression in the treatment of refractory ocular disorders.

Collagenase (MMP-1) and TIMP-1 in destructive corneal disease associated with rheumatoid arthritis.

The aim of the study was to immunolocalise interstitial collagenase (MMP-1) and the tissue inhibitor of metalloproteinases (TIMP-1) in ulcerating corneas from patients with rheumatoid arthritis, to determine whether changes in expression are associated with destructive corneal disease. Collagenase was expressed by stromal cells in 8 of 8 ulcerating corneas but was not seen in normal tissue (n = 3). TIMP-1 was abundant throughout the normal stroma, but was much reduced or absent from diseased corneas. Collagenase staining was frequently more intense near the epithelial surface and associated with a cellular infiltrate consisting of activated antigen-presenting cells (HLA-DR+), many of which were macrophages (CD68+) and derived from the epithelium or limbus (S100+). Interstitial collagenase produced by infiltrating macrophages and/or stimulated corneal fibrocytes is probably a major mediator of collagen degradation in rheumatoid corneal ulceration. In addition, reduced levels of TIMP-1 expression are consistent with collagenase activity and tissue destruction. Epithelial-stromal cell interactions and the production of local inflammatory mediators are of major importance in the pathogenesis of corneal destruction, although the precise nature of the antigenic stimulation and/or cellular interactions remains to be elucidated.

A randomised, double-blind, parallel group study to compare subcutaneous interferon alpha-2a plus podophyllin with placebo plus podophyllin in the treatment of primary condylomata acuminata.

OBJECTIVES: The primary objective was to determine if six weeks treatment with subcutaneous interferon alpha-2a (IFN) and podophyllin 25% W/V administered twice per week, preceded by IFN alpha-2a three times weekly for one week showed a greater complete response rate in patients with primary condylomata acuminata when assessed at week 10 than treatment with podophyllin and placebo injections in the same schedule. The secondary objective was to compare recurrence rates in complete responders at six months in the two treatment groups. DESIGN: Randomised, double-blind parallel group study. SETTING: Multicentre study in six genitourinary clinics within the U.K. PATIENTS: One hundred and twenty-four patients with primary anogenital warts. MAIN OUTCOME MEASURES: Complete response rate at week 10, and recurrence rate at week 26 in complete responders. RESULTS: At week 10 analysis of the efficacy population showed complete response in 36% (15/42 patients) of IFN-treated group and 26% (11/43 patients) in the placebo group (no significant difference). Analysis of the safety population at week 26 showed persistence of the complete response in 57% (8/14 patients) of the IFN-treated group and 80% (12/15 patients) of the placebo group (no significant difference). Adverse effects were more common in IFN-treated patients, involved particularly application site reaction and malaise but were generally mild. CONCLUSIONS: At the dose and with the regime described treatment with IFN alpha-2a in combination with podophyllin is no more effective in the treatment of primary anogenital warts than podophyllin alone and is associated with more adverse events.

Large corneal transplants in corneal destructive disease.

PATIENTS AND METHODS: Forty nine keratoplasties were performed in 18 eyes of 17 patients with severe corneal destructive disease. RESULTS: One eye became phthisical and 5 others lost useful visual acuity but retained a satisfactory cosmetic result. No eyes were enucleated. Recurrence of the host disease in the graft was the largest cause of visual failure. Primary allograft rejection was rare in spite of the large size of the grafts and their proximity to the limbus and new vessels. CONCLUSION: For these grafts to succeed it is essential to bring the underlying systemic disease under control by intensive systemic immunosuppressive therapy before, during and for many months after surgery. It was found that those with Mooren's ulcer had the worst prognosis for the retention of vision.

Cells perpetuating the inflammatory response in scleritis.

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 analyse the inflammatory cellular infiltrate in scleritis. Six episcleral biopsies and two enucleated eyes were studied. The episcleral biopsies were taken from patients with nodular scleritis. In one patient enucleation was done after perforation in anterior necrotising scleritis and, in the other after misdiagnosis of posterior scleritis as intraocular tumour. Morphological criteria and immunohistochemical methods were used to characterise the inflammatory cellular infiltrate. The inflammatory cells infiltrating the episcleral tissue were mainly T lymphocytes and macrophages. There was a predominance of CD4 positive cells, but only few lymphocytes were activated (expressed IL-2 receptor). The cells infiltrating the scleral fibres in the enucleated eyes consisted in both cases predominantly of T cells. 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 (epithelioid and giant cells) were present in necrotising 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. The cellular infiltrate in scleritis shows, at least at certain stages, features compatible with a T cell mediated (autoimmune) disorder, which may have major therapeutic implications.

Cancer rehabilitation: an overview.

Cancer rehabilitation is a practical attempt to maximize independence and dignity and to reduce the extent to which cancer interferes with an individual's physical, psychosocial, and economic functioning. The rehabilitation process should begin at the time of diagnosis or definitive medical intervention and should continue until the individual is able to maintain the desirable level of independence.

The optimal functioning plan. A key element in cancer rehabilitation.

Individuals with cancer should be assisted to achieve optimal levels of functioning before, during, and after cancer treatment. However, to reach optimal functioning a well-defined plan of action is required. This article presents an Optimal Functioning Plan (OFP) aimed at attaining the best possible outcomes for all individuals treated for cancer. The OFP centers on physical functioning, nutritional adequacy, a practical level of independence in activities of daily living, self-care competence, a realistic optimistic outlook, and effective management of side effects. The OFP is a key element of cancer rehabilitation. It represents a way of packaging cancer care in a health-oriented framework.

Exudative retinal detachment and posterior scleritis associated with massive scleral thickening and calcification treated by scleral decompression.

A 66-year-old man presented with massive bilateral scleral thickening and calcification associated with a unilateral exudative retinal detachment which did not respond to systemic anti-inflammatory agents including steroids and cyclophosphamide but improved with scleral resection. This patient shows the features of both posterior scleritis and the uveal effusion syndrome, providing further evidence for the role of a thickened sclera and interference with the trans-scleral flow of fluid in the formation of such an exudative retinal detachment.

Diagnosis and management of systemic Wegener's granulomatosis presenting with anterior ocular inflammatory disease.

The ocular and systemic features of 10 patients whose Wegener's granulomatosis presented with corneoscleral inflammatory disease are described. Marginal corneal infiltrates were seen in all patients with anterior scleritis and were a valuable sign of disease activity. Nine out of 10 patients had symptoms of systemic vasculitis on presentation; seven had renal impairment; three had chest x-ray abnormalities. Autoantibodies against neutrophil cytoplasmic determinants (ANCA) were present in all cases. In seven patients the scleritis responded well to pulsed immunosuppressive therapy followed by long term oral steroids and cyclophosphamide. Oral steroid therapy alone failed to control severe disease. Corneoscleral disease was not a cause of visual loss. It is important to realise that inflammatory corneoscleral disease may be the presenting feature of a severe systemic vasculitis.