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.

Subjective visual perceptions during vitreoretinal surgery under local anaesthesia.

PURPOSE: To evaluate the visual experiences of patients during vitreoretinal surgery under local anaesthesia (LA). METHODS: Prospective questionnaire survey of 80 patients within 30 min of completion of vitreoretinal surgery under LA. Preoperative visual acuity, surgical procedure and its duration, efficacy of the local block, as well as intraoperative perceptions of flashes, colours, movements, and seeing instruments were documented. RESULTS: A sub-Tenon's block was performed in 62/80 (77.5%) and a peribulbar block in the remainder. Overall, 72 (90%) of patients perceived light at some stage during their surgery. Of these, 51 (70.83%) observed movements, 45 (62.5%) saw colours, 38 (52.77%) saw instruments, and 24 (33.33%) saw flashes. The commonest observations were colourful swirls, black pipes, and the colour red. Most patients found these experiences pleasant or bearable; two found them frightening, and four would like to have been warned preoperatively about them. Preoperative visual acuity, diagnosis, gender of the patient, degree of akinesia, and the duration of surgery did not associate with visual perceptions. Logistic regression analysis showed that younger people were more likely to experience flashing lights (P=0.03) and to see instruments (P=0.04), patients having a sub-Tenon's block to perceive light (P=0.005), and those who did not receive awake sedation were more likely to see instruments (P=0.04). CONCLUSIONS: Visual experiences are common during vitreoretinal surgery undertaken under LA. Where appropriate, patients should be forewarned about these experiences and reassured that they are not normally frightening.

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.

CTLA-4 polymorphisms are not associated with ocular inflammatory disease.

Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) is regarded with other molecules such as HLA, PTPN22 and CARD15 as genetic master switches of autoimmunity. Single nucleotide polymorphisms (SNPs) in the genes encoding these molecules have been associated with autoimmune conditions. We analysed the SNPs -318C/T and 49A/G in CTLA-4 in patients with Behcet's disease (BD), patients with intermediate uveitis and appropriate controls. Blood was collected from 236 patients with BD from the UK and the Middle East (ME), all fulfilling the International Study Group criteria for the diagnosis of BD, and 143 patients with idiopathic intermediate uveitis were recruited from the Medical Eye Unit at St Thomas' Hospital. Samples from healthy individuals from each geographical centre were used as controls. DNA was prepared by standard methods, and SNPs -318 and 49 in CTLA-4 were detected by a polymerase chain reaction-sequence specific primers (PCR-SSP) assay using primer mixes. The results showed that there was no association with either polymorphism in patients with BD from the UK or the ME. Similarly, there was no association in patients with intermediate uveitis. Moreover, there was no association with SNP in CTLA-4 and disease manifestations in BD or outcome in patients with intermediate uveitis. Both BD and intermediate uveitis have HLA associations, but there is no difference in distribution of CTLA-4 polymorphisms that are associated with other autoimmune diseases. The lack of association with polymorphisms in CTLA-4 and other master controlling genes of autoimmunity suggests that mechanisms that mediate such a description for BD and intermediate uveitis have still to be elucidated.

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.

Adalimumab for sight-threatening uveitis in Behçet's disease.

AIMS: To describe the clinical outcome of three patients with Behçet's disease maintained on infliximab who were switched to adalimumab therapy. METHODS: Case note review. Main outcome measure was recurrence of uveitis. RESULTS: All patients remained free of recurrence with stable visual acuities. CONCLUSIONS: Adalimumab appears to maintain disease remission in Behçet's disease.

Penetrating ocular injuries in the home.

BACKGROUND: We studied the prevalence and aetiology of penetrating ocular injuries, in particular ones that were sustained whilst undertaking Do It Yourself (DIY) or gardening in the domestic environment. We also examined the extent of eye safety promotion in DIY stores and garden centres and on their websites. METHODS: We conducted a case note review of patients who underwent surgery for penetrating ocular trauma between January 2000 and June 2004. Eight DIY stores and garden centres and 10 websites were visited and evaluated using standardized questions. RESULTS: Of the 85 patients identified, 35 (41.2%) patients had injuries that occurred in the home with 10 patients having visual acuities of <6/60 at final follow up. Accidents from DIY or gardening were the cause in 17 of 33 (51.5%) patients, with a failure to wear eye protection in all cases. Overall, DIY stores and garden centres were poor at promoting eye safety both in their stores and on their websites. CONCLUSION: The home is a frequent place for severe penetrating ocular injury, with highly popular pastimes such as DIY and gardening as common causes. As many of these injuries are preventable, additional safety information is essential to educate the public on the potential dangers of these pastimes.

Infliximab: a novel treatment for sight-threatening thyroid associated ophthalmopathy.

We describe a patient with sight threatening thyroid associated ophthalmopathy (TAO) who was successfully treated with infliximab, an anti-tumour necrosis factor (TNF)-a antibody.

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.

Ocular findings in patients with solid tumours treated with the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib ('Iressa', ZD1839) in Phase I and II clinical trials.

PURPOSE: To describe the strategy used for large-scale ophthalmological monitoring in the clinical development of the novel anticancer agent gefitinib ('Iressa', ZD1839), an epidermal growth factor receptor tyrosine kinase inhibitor, which had demonstrated ocular effects in preclinical animal models. METHODS: In this extensive clinical trial programme, patients in Phase I and II trials underwent frequent and intensive ophthalmological monitoring at baseline and during the trials. Data were reviewed by an external independent Ophthalmology Advisory Board. RESULTS: Ophthalmological data for 221 patients in Phase I trials of gefitinib and 425 patients in Phase II trials revealed no evidence of any consistent or drug-related ophthalmological toxicity. Interestingly, the baseline data revealed that, in an asymptomatic population, transient ophthalmological events are identified during monitoring. CONCLUSIONS: This study reports the methodology and normative data in an ophthalmological screening programme that should prove useful for future studies.

The first cut is the deepest: basic surgical training in ophthalmology.

PURPOSE: To examine the basic surgical training received by Senior House Officers (SHOs) in ophthalmology and the influence on training of sociodemographic and organisational factors. METHODS: Cross-sectional survey of SHOs in recognised UK surgical training posts asking about laboratory training and facilities, surgical experience, demographic details, with the opportunity to add comments. RESULTS: A total of 314/466 (67%) questionnaires were returned. In all, 67% had attended a basic surgical course, 40% had access to wet labs and 39% had spent time in a wet lab in the previous 6 months. The mean number of part phakoemulsification (phako) procedures performed per week was 0.79; the mean number of full phakos performed per week was 0.74. The number of part phakos performed was negatively correlated, and the number of full phakos completed was positively correlated, with length of time as an SHO. Respondents who had larger operating lists performed more full phakos per week (P<0.001). Compared to men, women were less likely to have access to a wet lab (P=0.013), had completed fewer full phakos per week (P=0.003), and were less likely to have completed 50 full phakos (P=0003). SHOs' comments revealed concerns about their limited 'hands on' experience. CONCLUSIONS: There are significant shortcomings in the basic surgical training SHOs receive, particularly in relation to wet lab experience and opportunities to perform full intraocular procedures. SHOs themselves perceive their training as inadequate. Women are disadvantaged in both laboratory and patient-based training, but minority ethnic groups and those who qualified overseas are not.

Degree, duration, and causes of visual loss in uveitis.

BACKGROUND/AIMS: Uveitis is a major cause of visual morbidity in the working age group. The authors investigated the duration, degree, and causes of visual loss in uveitis patients with the aim of better defining the visual morbidity and identifying potential risk factors. METHODS: A retrospective, non-interventional, observational survey of 315 consecutive patients attending a tertiary referral uveitis service. RESULTS: The mean duration of follow up was 36.7 months. Reduced vision (< or =6/18) was found in 220/315 (69.95%) of the patients with a subset of 120 patients having vision < or =6/60. Unilateral visual loss occurred in 109 (49.54%), while 111 (50.45%) had bilateral loss. The mean duration of visual loss was 21 months. Of the 148 patients with pan-uveitis, 125 (84.45%) had reduced vision, with 66 (53%) having vision < or =6/60. Main causes of visual loss were cystoid macular oedema (CMO) (59/220, 26.8%), cataract (39/220, 17.7%), and combination of CMO and cataract (44/220, 20%). The following were predictive of a poorer visual prognosis: pan-uveitis (p = 0.0005), bilateral inflammation (p = 0.0005), increasing duration of reduced vision (p = 0.0005), an Indian or Pakistani ethnic background (p = 0.004), and increasing patient age (p = 0.02). CONCLUSION: Prolonged visual loss occurred in two thirds of uveitis patients, with 70 (22%) patients meeting the criteria for legal blindness at some point in their follow up. Older patients with bilateral inflammation and an increasing duration of reduced vision are at the greatest risk of severe visual loss (< or =6/60). CMO and cataract were responsible for visual loss in 64.5% of patients.

Uveitis: a potentially blinding disease.

Uveitis (intraocular inflammation) is a potentially blinding group of, probably autoimmune, conditions predominantly occurring in the working age group. Although the aetiology is unknown in most cases, many patients have an associated underlying systemic disease. Central vision loss, in the form of cystoid macular oedema, is the commonest type of visual impairment. Although historical incidence and prevalence data exists, little is known about the degree of vision loss experienced, and the social and financial consequences of having temporary or permanent visual impairment in this age group. The literature is also full of uncontrolled studies and case reports of different modalities of drug therapy for uveitis. This article attempts to raise the awareness of uveitis as an important sight-threatening group of conditions by highlighting the paucity of evidence-based data on epidemiological, quality of life, socioeconomic, and therapeutic aspects.