Does access to a portable ophthalmoscope improve skill acquisition in direct ophthalmoscopy? A method comparison study in undergraduate medical education.

BACKGROUND: Direct ophthalmoscopy (DO) is an essential skill for medical graduates but there are multiple barriers to learning this. Medical students and junior doctors typically lack confidence in DO. Most students do not own an ophthalmoscope and learn via ward devices that vary in design and usability. The Arclight ophthalmoscope (AO) is an easy to use, low-cost and portable device that could help address device access. This study aimed to assess the impact of personal ownership of an AO on DO skill acquisition and competency amongst medical students in the clinical environment. METHODS: Method comparison study with 42 medical students randomised to either traditional device ophthalmoscope (TDO) control or AO intervention group during an 18-week medical placement. Three objective assessments of DO competency were performed at the beginning and end of the placement: vertical cup to disc ratio (VCDR) measurement, fundus photo multiple-choice questions (F-MCQ) and model slide examination (MSE). DO examinations performed during the placement were recorded via an electronic logbook. RESULTS: Students in both groups recorded a median number of six examinations each during an eighteen-week placement. There was no statistically significant difference between the groups in any of the objective assessment measures (VCDR p = 0.561, MCQ p = 0.872, Model p = 0.772). Both groups demonstrated a minor improvement in VCDR measurement but a negative performance change in F-MCQ and MSE assessments. CONCLUSIONS: Students do not practice ophthalmoscopy often, even with constant access to their own portable device. The lack of significant difference between the groups suggests that device access alone is not the major factor affecting frequency of DO performance and consequent skill acquisition. Improving student engagement with ophthalmoscopy will require a more wide-ranging approach.

Bilateral retinal vasculitis in a patient with systemic lupus erythematosus and its remission with rituximab therapy.

Severe retinal vasculitis is a rare, but potentially blinding, complication of patients with systemic lupus erythematosus (SLE). We describe here the first reported case of treating severe bilateral SLE-associated retinal vasculitis with the anti-CD20 monoclonal antibody rituximab, a drug which has established its role in rheumatoid arthritis and has shown promise in case series for the treatment of severe SLE that is unresponsive to other therapies. This case suggests that rituximab-induced B-cell depletion may provide an important new therapeutic option for refractory cases of this devastating ocular complication.

Serum cytokine profiles in Behçet's disease: is there a role for IL-15 in pathogenesis?

OBJECTIVES: Behçet's disease (BD) is a multisystem inflammatory disease characterised by recurrent orogenital ulceration, ocular inflammation and skin lesions whose aetiology is currently unknown. We hypothesized that levels of cytokines in the serum might provide either diagnostic or activity markers for the disease. METHODS: Levels of 10 cytokines were analysed in a multiplex bead analysis system as well as IL-15 by ELISA, in 79 serum samples from 52 patients with BD. The same cytokines were also measured in serum samples from 20 patients with recurrent aphthous stomatitis (RAS), as disease controls, and 15 healthy volunteers. The results were correlated with disease activity and current drug therapy. RESULTS: CXCL8 and TNF were the most abundant cytokines and were significantly raised compared to both patients with RAS and healthy controls. IL-15 was present in all samples and was significantly raised in both patients with BD and RAS compared to healthy controls. By comparison, cytokines associated with an adaptive immune response such as IFNgamma and IL-2 were found in few samples, while IL-4 and IL-10 were not detected in any sample. Levels of cytokines correlated with each other suggesting a response to the same stimulus, however, there was no association with either disease activity or treatment. CONCLUSION: Cytokines related to activity of the innate immune response were most prominent in this study and showed good correlation with each other. In particular, it was shown that IL-15 was raised in BD. However, there was no pattern of cytokine expression relating to disease activity or treatment.

Ocular manifestations of systemic lupus erythematosus.

Ocular manifestations of lupus are fairly common, may be the presenting feature of the disease and can be sight-threatening. Almost any part of the eye and visual pathway can be affected by inflammatory or thrombotic processes. Ocular pain and visual impairment require urgent assessment by an ophthalmologist. Infection should be excluded. Optic neuritis and ischaemic optic neuropathy may be difficult to distinguish. Scleritis and severe retinopathy require systemic immunosuppression but episcleritis, anterior uveitis and dry eyes can usually be managed with local eye drops. Vaso-occlusive disease, particularly in the presence of antiphospholipid antibodies, requires treatment with anticoagulation and proliferative retinopathy is treated with laser therapy. Hydroxychloroquine rarely causes ocular toxicity at doses under 6.5 mg/kg/day. When this has occurred, it has been associated with more than 5 years of drug exposure.

Corticosteroids, 11beta-hydroxysteroid dehydrogenase isozymes and the rabbit choroid plexus.

The epithelial cells of the choroid plexus (CP) are responsible for cerebrospinal fluid (CSF) secretion into the ventricles of the brain. The balance between CSF production and drainage, in part, facilitates a normal intracranial pressure. The secretion of Na(+) and anions by the CP creates an osmotic gradient driving water into the ventricles. This is opposite to classical Na(+) transporting tissues, such as the kidney, where Na(+) and water reabsorption is mediated by 11beta-hydroxysteroid dehydrogenase type 2 that protects the mineralocorticoid receptor by abrogating active cortisol to inactive cortisone. In the human ocular ciliary epithelium, Na(+) and water secretion is dependent on a novel mediator of ciliary epithelial Na(+) transport, 11beta-HSD type 1 (11beta-HSD1), that generates intraocular cortisol. In a mechanism analogous to that of the embryologically related ocular ciliary epithelium, we propose that autocrine regulation of intracranial cortisol is dependent on 11beta-HSD1 expression in the CP epithelial cells. By conducting immunolocalisation studies on brains from New Zealand White Albino rabbits, we defined the expression of 11beta-HSD1 in the secretory CP epithelial cells. Enzyme assays performed on intact rabbit CP whole tissue explants confirmed predominant 11beta-HSD1 activity, generating cortisol that was inhibited by glycyrrhetinic acid (an 11beta-HSD inhibitor). Using the real time-polymerase chain reaction, rabbit CP tissue was found to express levels of 11beta-HSD1, glucocorticoid receptor alpha and serum and glucocorticoid-regulated kinase 1 mRNA comparable to that expressed in rabbit ocular ciliary body, thereby highlighting the similarity between these two tissues. Furthermore, an enzyme-linked immunosorbent assay of rabbit CSF revealed a median cortisol concentration of 1.7 nmol/l (range 1.4-4.3 nmol/l, n = 9). Our data have identified a functional 11beta-HSD1 within the CP, mediating intracranial cortisol bioavailability. Expression of 11beta-HSD1 may be fundamental in the regulation of CSF secretion and the local generation of cortisol may represent a pathophysiological mechanism underlying cortisol-dependent neuroendocrine diseases.

Unregistered visual impairment: is registration a failing system?

BACKGROUND/AIMS: To assess the current level of under-registration of blindness and partial sight among patients attending a large teaching hospital, and to determine any risk factors for under-registration. METHODS: Medical records of all patients attending general ophthalmology outpatient clinics over a 3 month period were included in a retrospective analysis of registration rates; questionnaire survey assessing the level of knowledge of registration practices among 35 ophthalmologists working in the West Midlands. RESULTS: 146/2161 (7%) patients were eligible for blind or partial sight registration, or were in possession of a completed BD8 form. Of these 146 patients, 65 (45%) were unregistered with 18 fulfilling the criteria for blind and 47 for partially sight. In addition, 32/81 (40%) registered patients appeared to have been inappropriately registered. Partially sighted patients were more likely to be unregistered than blind patients (OR 2.31, 95% CI 1.15 to 4.63, p = 0187), and patients from ethnic minorities were more than three times more likely to be unregistered than white patients (OR 3.23, 95% CI 1.56 to 6.65, p = 0.0015). A patient with a treatable condition was more likely to be unregistered than a patient with an untreatable condition (OR 4.87, 95% CI 2.10 to 11.33, p = 0.0002). The overall level of knowledge of registration practices among doctors was found to be low and there was no indication of increasing knowledge with increasing experience. CONCLUSIONS: There has been little improvement in registration rates of visually impaired patients over the past decade. Ophthalmologists lack the necessary knowledge to cater for visually impaired patients' needs.

Virus-directed, enzyme prodrug therapy with nitroimidazole reductase: a phase I and pharmacokinetic study of its prodrug, CB1954.

CB1954 [5-(aziridin-1-yl)-2,4-dinitrobenzamide] is converted by the bacterial enzyme nitroimidazole reductase (NTR) into a potent cytotoxic bifunctional alkylating agent, which can be delivered to tumors in adenoviral vectors as virus-directed, enzyme prodrug therapy. This report summarizes a Phase I and pharmacokinetic study of the prodrug, CB1954. Thirty patients, ages 23-78 years (median 62 years), with predominantly gastrointestinal malignancies were treated. CB1954 was administered by i.v. injection every 3 weeks or i.p. followed by 3-weekly i.v. injections, toward a maximum of six cycles. The dose was escalated from 3 to 37.5 mg/m2. No significant toxicity was seen until 24 mg/m2 (recommended i.v. dose). Dose-limiting toxicities (DLT) were diarrhea and hepatic toxicity, seen at 37.5 mg/m2. DLT has not been observed at the current i.p. dose of 24 mg/m2. There was no alopecia, marrow suppression, or nephrotoxicity. Clearance data suggest hepatic metabolism, and <5% of CB1954 was renally excreted. There was a nonlinear relationship between i.v. dose and area under the curve (AUC). At the recommended i.v. dose of 24 mg/m2, the AUC was 5.8 microM/h. Intraperitoneal administration (24 mg/m2) achieved an AUC of 387 microM/h, giving a considerable regional advantage. In vitro, the AUC required to achieve the IC50 for CB1954, in NTR-expressing cancer cells, ranges from 10-50 microM/h. Thus, CB1954 is well tolerated at a dose of 24 mg/m2, and sufficient serum/peritoneal levels are achieved for an enzyme-prodrug approach to be feasible. We are now conducting a Phase I trial combining adenovirus-mediated NTR and i.v. CB1954 (24 mg/m2) in patients with primary and secondary liver tumors.

Local connected fractal dimensions and lacunarity analyses of 60 degrees fluorescein angiograms.

PURPOSE: The retinal vascular tree exhibits fractal characteristics. These findings relate to the mechanisms involved in the vascularization process and to the objective morphologic characterization of retinal vessels using fractal analysis. Although normal retinas show uniform patterns of blood vessels, in pathologic retinas with central vein or artery occlusions, the patterns are irregular. Because the generalized box fractal dimension fails to differentiate successfully between normal and abnormal retinal vessels in 60 degrees fluorescein angiograms, the authors have further investigated this problem using the local connected fractal dimension (alpha). METHODS: The authors studied 24 digitized 60 degrees fluorescein angiograms of patients with normal retinas and 5 angiograms of patients with central retinal vein or artery occlusion. The pointwise method estimated the local complexity of the angiogram within a finite window centered on those pixels that belong to the retinal vessels. Color-coded dimensional images of the angiograms were constructed by plotting the pixels forming the object with a color that corresponded to specific values of alpha +/- delta alpha. RESULTS: The color-coded representation allowed recognition of areas with increased or decreased local angiogram complexity. The alpha distributions showed differences between normal and pathologic retinas, which overcomes problems encountered when using the methods of calculating the generalized fractal dimensions. A multivariate linear discriminant function using parameters from the alpha distribution and a further fractal parameter--lacunarity--reclassified 23 of the 24 normal and 4 of the 5 pathologic angiograms in their original groups (total: 92.1% correct). CONCLUSIONS: This methodology may be used for automatic detection and objective characterization of local retinal vessel abnormalities.

Analysis of aqueous humor immunoglobulin G in uveitis by enzyme-linked immunosorbent assay, isoelectric focusing, and immunoblotting.

Immunoglobulin G (IgG) in aqueous humor from patients with various uveitis syndromes was analyzed using a number of immunologic techniques. Sixty-five percent of patients with Fuchs' heterochromic cyclitis (FHC), 70% of patients with other forms of uveitis, and 44% of controls showed local synthesis of IgG, as demonstrated by an elevated IgG:albumin relative concentration ratio. Using an enzyme-linked immunosorbent assay to measure the concentration of IgG subclasses 1-4, a relative excess of IgG1 was found in the aqueous compared with the serum in FHC. Isoelectric focusing and immunoblotting studies revealed oligoclonal IgG bands in the aqueous of 13 of 23 (57%) patients with FHC, most being of the IgG1 subclass. Oligoclonal bands were not found in 18 patients with other types of uveitis or 13 patients undergoing surgery for senile cataract. These findings indicate intraocular production of IgG of restricted specificity in FHC, providing further evidence for local immune dysfunction in this condition. As yet the antigenic stimulus for this oligoclonal B-cell response has not been identified.

Analysis of interleukin-6 in endotoxin-induced uveitis.

The mechanisms underlying the induction of intraocular inflammation in the rat model of endotoxin-induced uveitis (EIU) and the subsequent development of tolerance after repeated endotoxin injections are poorly understood. Interleukin-6 (IL-6) was measured in the aqueous humor and serum of Lewis rats after single and repeated injections of endotoxin into the footpad. After a single injection, a rise in serum and aqueous-humor levels of IL-6 was seen after 2 and 16 hr, respectively. The highest aqueous-humor level of IL-6 was seen 20 hr postinjection and was tenfold that seen in the serum sample taken at the same time, suggesting intraocular synthesis of this cytokine. Four hours later the most active uveitis and the highest total aqueous-humor protein level were observed. Repeated injection of endotoxin still resulted in a moderate but significant systemic release of IL-6 but no detectable IL-6 in the aqueous humor and the absence of uveitis. Intravitreal injection of endotoxin-free human recombinant IL-6 (10-10(5) U) in rats resulted in uveitis, resembling the ocular response to endotoxin. There appeared to be a prozone effect regarding the total aqueous-humor protein concentration. The largest amount of aqueous-humor protein was seen in the eyes injected with 10(2) U of IL-6, but increasing concentrations of intravitreal IL-6 showed a corresponding decrease in protein levels. In the fellow saline-injected eyes, a clear consensual response was observed with regard to the extravasation of protein, although the uveitic grade in these eyes was low or zero. Repeated intravitreal injection of IL-6 resulted in ocular unresponsiveness in nine of 11 rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Expression and putative role of 11 beta-hydroxysteroid dehydrogenase isozymes within the human eye.

PURPOSE: The human eye is an important target tissue for steroid hormones, and glucocorticoids have been implicated in the pathogenesis of ocular disease, including glaucoma. In peripheral tissues, corticosteroid hormone action is regulated at a prereceptor level through the activity of the 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) isozymes: an oxo-reductase (11 beta-HSD1) that activates cortisol (F) from cortisone (E) and a dehydrogenase (11 beta-HSD2) that inactivates F to E. The purpose of this study was to analyze the expression and putative role of 11 beta-HSD within the human eye. METHODS: Immunohistochemical and reverse transcription-polymerase chain reaction (RT-PCR) studies were performed on sections of human ocular tissues, surgical trabecular meshwork (TM) specimens and a ciliary nonpigmented epithelial (NPE) cell-line. Free F and E concentrations in aqueous humor were determined by gas chromatography-mass spectrometry (GC/MS). IOP was measured in eight male volunteers before and after oral ingestion of carbenoxolone (CBX), a known inhibitor of 11 beta-HSD. RESULTS: 11 beta-HSD1 was expressed in the basal cells of the corneal epithelium and the NPE. 11 beta-HSD2 was restricted to the corneal endothelium. RT-PCR revealed mRNA for only the glucocorticoid receptor (GR) in the TM specimens, whereas GR, mineralocorticoid receptor and 11 beta-HSD1 mRNAs were all present in the NPE cell line. The demonstration of free F in excess of E (F/E 14:1) in the aqueous humor suggested predominant 11 beta-HSD1 activity. Compared with baseline (14.7 +/- 1.06 mm Hg, mean +/- SD), the IOP decreased significantly on both the third and seventh days of CBX ingestion (12.48 +/- 1.11 mm Hg, P < 0.0001 and 11.78 +/- 1.50 mm Hg, P < 0.0001, respectively). CONCLUSIONS: These results suggest that the 11 beta-HSD1 isozyme may modulate steroid-regulated sodium transport across the NPE, thereby influencing IOP.

Aqueous humor interleukin-6 levels in uveitis.

The level of Interleukin-6 (IL-6) in the aqueous humor of 24 patients with 2 types of uveitis was measured with a specific bioassay using the murine hybridoma cell line B9. Sixteen patients had Fuchs' heterochromic cyclitis (FHC) and 8 had toxoplasma uveitis (TU). Sixty-three percent of each of the FHC and TU groups had raised levels of IL-6 in their aqueous (mean: 543 and 19,228 units/ml respectively). Thirteen control aqueous samples, obtained at surgery for senile cataract, showed IL-6 levels of less than 10 units/ml. Serum obtained at the same time as each aqueous humor sample also showed IL-6 levels of less than 10 units/ml, indicating that the raised levels of IL-6 found in the aqueous of uveitis patients did not result from serum leakage, but from local production. This is the first report on intraocular IL-6 levels, and indicates that IL-6 may play a role as an inflammatory mediator in uveitis.

Behçet's syndrome: a multidisciplinary approach to clinical care.

Behçet's syndrome is a multisystem disorder characterized by recurrent orogenital ulceration and an occlusive vasculitis. Histologically, there is a combination of a perivascular lymphocytic infiltration with endothelial cell damage coupled with a pro-thrombotic tendency. We present a multidisciplinary approach to the management of Behçet's syndrome, and compare our findings with other published studies. Over a nine-year period, 50 patients with Behçet's syndrome were followed in a multidisciplinary combined clinic. Patients were assessed by an ophthalmologist, a rheumatologist and a specialist in oral medicine. Data on disease activity and damage were collected using a standardized proforma for each specialty. Mean age of onset was 30 years; 56% were male. Recurrent oral ulceration was the commonest manifestation and the presenting feature in 76%. The commonest second systems involved were genital mucosae and eyes. We found a larger proportion of patients with ophthalmic (80%) and central nervous system (14%) manifestations compared with many other studies. There was an association between central nervous system and thrombotic events (p<0.001). Our multidisciplinary approach allowed us to keep each system involved in Behçet's syndrome under careful review. The development of recurrent sight-threatening eye disease was unpredictable and occurred despite aggressive immunosuppression.

Inhibition of 11beta-hydroxysteroid dehydrogenase type 1 lowers intraocular pressure in patients with ocular hypertension.

BACKGROUND: Intraocular pressure (IOP) is maintained by a balance between aqueous humour (AH) production (dependent on sodium transport across a ciliary epithelial bi-layer) and drainage (predominantly through the trabecular meshwork). In peripheral epithelial tissues, sodium and water transport is regulated by corticosteroids and the 11beta-hydroxysteroid dehydrogenase (11beta-HSD) isozymes (11beta-HSD1 activating cortisol from cortisone, 11beta-HSD2 inactivating cortisol to cortisone). AIM: To analyse expression of 11beta-HSD in the human eye and investigate its putative role in AH formation. DESIGN: Multipart prospective study, including a randomized controlled clinical trial. METHODS: The expression of 11beta-HSD1 in normal human anterior segments was evaluated by in situ hybridization (ISH). RT-PCR for 11beta-HSDs, glucocorticoid and mineralocorticoid receptors (GR, MR) was performed on human ciliary body tissue. AH cortisol and cortisone concentrations were measured by radioimmunoassay on specimens taken from patients with primary open-angle glaucoma (POAG) and age-matched controls. Randomized, placebo-controlled studies of healthy volunteers and patients with ocular hypertension (OHT, raised IOP but no optic neuropathy) assessed the effect of oral carbenoxolone (CBX, an inhibitor of 11beta-HSD) on IOP. RESULTS: ISH defined expression of 11beta-HSD1 in the ciliary epithelium, while RT-PCR analysis of ciliary body tissue confirmed expression of 11beta-HSD1, with additional GR and MR, but not 11beta-HSD2 expression. In both POAG patients and controls, AH concentrations of cortisol exceeded those of cortisone. The CBX-treated healthy volunteers who demonstrated the largest change in urinary cortisol metabolites, indicative of 11beta-HSD1 inhibition, had the greatest fall in IOP. Patients with OHT showed an overall reduction of IOP by 10% following CBX administration, compared to baseline (p<0.0001). DISCUSSION: CBX lowers IOP in patients with ocular hypertension. Our data suggest that this is mediated through inhibition of 11beta-HSD1 in the ciliary epithelium. Selective and topical inhibitors of 11beta-HSD1 could provide a novel treatment for patients with glaucoma.

Long-term follow-up of trabeculectomy without antimetabolites in patients with uveitis.

PURPOSE: To determine the long-term success rate after trabeculectomy without antimetabolites in patients with uveitis. METHODS: Review of data from all patients with uveitis who underwent trabeculectomy for uncontrolled intraocular pressure secondary to intraocular inflammation between May 1990 and December 1994. Results were compared with those from a group of patients with primary open-angle glaucoma matched for sex and surgeon. RESULTS: The uveitis group consisted of 32 eyes (20 patients). Maximum control of intraocular inflammation was achieved for a minimum of 2 months before surgery. Mean (+/-SD) age was 40.0 +/- 12.5 years (range, 14 to 67 years), with a median (+/-SE) follow-up of 53.0 +/- 1.8 months (range, 33 to 84 months). The primary open-angle glaucoma group consisted of 33 eyes (23 patients), with a mean age of 62.0 +/- 13.7 years (range, 26 to 81 years) and a median follow-up of 63.0 +/- 12.0 months (range, 34 to 299 months). The overall 5-year success rate (intraocular pressure < or =21 mm Hg with or without topical medication) for the uveitis group was 78% compared with 82% for the primary open-angle glaucoma group (P = .7). The absolute 5-year success rate (intraocular pressure < or =21 mm Hg with no medication) for the uveitis group was 53% compared with 67% for the primary open-angle glaucoma group (P = .87). CONCLUSIONS: In the absence of other risk factors, such as Afro-Caribbean race and previous intraocular surgery, and with adequate preoperative control of inflammation, trabeculectomy without antimetabolites may be considered the primary surgical procedure for increased intraocular pressure in patients with uveitis.

Labial adenocarcinoma after treatment with cyclosporin a in a patient with panuveitis.

PURPOSE: To report a case of labial basal cell adenocarcinoma in a patient with uveitis on treatment with cyclosporin A. METHOD: Case report. A 73-year-old woman with panuveitis and retinal vasculitis presented with a lump on her lip after 52 months of treatment with cyclosporin A. RESULT: Excision biopsy showed a labial adenocarcinoma. CONCLUSION: Malignancy can occur after long-term cyclosporin A treatment for uveitis.

Immunohistochemical analysis of iris biopsy specimens from patients with Fuchs' heterochromic cyclitis.

Using immunohistochemical techniques, we analyzed iris biopsy specimens from eight patients with Fuchs' heterochromic cyclitis, seven patients with various other types of uveitis, and eight glaucoma patients without uveitis. No specific abnormalities related to Fuchs' heterochromic cyclitis could be detected. Four of the patients with Fuchs' heterochromic cyclitis and four of the patients with uveitis showed evidence of an inflammatory cell infiltrate, which was a mixture of interleukin-2 receptor-negative T helper and suppressor cells, B lymphocytes, and plasma cells. Only an occasional T lymphocyte could be seen in two of the patients without uveitis. The class II antigen HLA-DR was expressed on iris stromal cells in every patient in the Fuchs' heterochromic cyclitis group and uveitis group and in six of the patients in the nonuveitis group. In six of the Fuchs' heterochromic cyclitis patients, including two without immunohistochemical evidence of inflammatory cell infiltrate, histologic abnormalities were present on hematoxylin and eosin sections.

Fuchs' heterochromic uveitis and sarcoidosis.

AIMS/BACKGROUND: The aetiology of Fuchs' heterochromic uveitis (FHU) is unknown although it can occur in combination with a number of different ocular conditions. Five patients with FHU who show an association with sarcoidosis were studied. METHODS: Four patients with clinical signs compatible with FHU who had elevated serum angiotensin converting enzyme levels (sACE), and a fifth case with a normal sACE and a positive Kveim test were described. RESULTS: All five cases had iris nodules, two later developed mutton fat keratic precipitates, and one had peripheral retinal periphlebitis. Of the four cases with elevated sACE, one had respiratory function test abnormalities and an abnormal chest x ray compatible with pulmonary sarcoidosis. Another had a chorioretinal scar and developed intermediate uveitis 2 years after presentation. CONCLUSIONS: In all of these cases a diagnosis of FHU may represent a specific secondary ocular response to sarcoidosis rather than a primary idiopathic uveitis syndrome. Although FHU remains a clinical diagnosis, routine uveitis investigations should still be performed in this group of patients.

Pathogenesis of Mooren's ulcer: some new concepts.

Mooren's ulcer is a chronic, painful corneal ulceration of unknown aetiology. Recent histological and immunological studies suggest an autoimmune basis. It is now becoming clear that the immune system plays an intricate role in maintaining homoeostasis in health and disease. Regulation of the immune response appears to involve a subset of peripheral blood T lymphocytes known as suppressor cells. A qualitative or quantitative deficiency of suppressor cells may therefore be responsible for chronic inflammation, autoimmune disease, and immunodeficiency states. To explain the reported immunological aberrations the number of suppressor T cells in addition to other immunological parameters were studied in a patient with bilateral Mooren's ulcers. A deficiency of suppressor T cells was found in the peripheral blood. This deficit in the immunoregulatory mechanism explains some of the immunological abnormalities reported in previous studies. Furthermore this study provides additional evidence for an autoimmune aetiology. In the light of these findings the possibility of a new line of treatment has been raised.

Status of hepatitis B virus in the aetiology of uveitis in Great Britain.

Viruses have been demonstrated or suspected as the causative agents of various types of uveitis. Hepatitis B virus (HBV), apart from causing hepatitis, has also been implicated in the pathogenesis of systemic vasculitis, for example in glomerulonephritis and polyarteritis nodosa. It is therefore possible to postulate that a similar vasculitic process might occur in the eye leading to intraocular inflammation. A recent report from Switzerland suggests that HBV may be implicated in the aetiology of uveitis, as hepatitis B surface antigen (HBsAg) was found in the serum of 13% of cases of uveitis. Since the status of HBV in the aetiology of uveitis in Great Britain has not been investigated, we have examined serum from 200 cases of uveitis of various clinical types for the presence of circulating HBsAg. Only 4 cases (2%) were found to be HBsAg positive. This study failed, therefore, to confirm HBV as an important cause of uveitis in this country, but one cannot exclude the possibility that it may play a pathogenetic role in a small proportion of such cases.