Melanoma-associated retinopathy.

Melanoma-associated retinopathy (MAR) is a rare paraneoplastic autoimmune manifestation of cutaneous malignant melanoma. Patients classically present with acute onset night blindness, positive visual phenomena and visual field defects, and typically have significantly reduced quality of life as a result. Early recognition of MAR is of prognostic significance as it can precede the diagnosis of primary or metastatic malignant melanoma, and early treatment can lower the risk of irreversible immunological damage to the retinal cells with improved visual outcomes. The focus of our review article is therefore to raise awareness of MAR and present the latest evidence relating to the investigation and management of this condition.

Detection of Papilloedema Study (DOPS): rates of false positive papilloedema in the community.

BACKGROUND: Overdiagnosis of papilloedema is common and carries significant potential for morbidity from over-investigation and over-treatment. We aimed to determine the community prevalence of false positive diagnosis of papilloedema (FPE) on fundus imaging. METHODS: We evaluated fundus images from a community cross-section of 198 12-14-year-olds from the Avon Longitudinal Study of Parents and Children (ALSPAC) longitudinal cohort study database and patient images from our hospital departmental database with and without papilloedema. We asked clinicians, in isolation, to rate the subjects as a forced choice task to "papilloedema" or "not papilloedema" based on the fundus images alone. Raters comprised (i) four neuro-ophthalmologists, (ii) four ophthalmologists, (iii) four neurologists and (iv) four emergency medicine physicians. RESULTS: The prevalence of FPE in the ALSPAC population, defined as images mistaken as papilloedema by χ% of raters (Pχ) varied from P100 = 0% to P50 = 21.3 ± 3.9%. In the hospital population, there was a lower rate of FPE, P50 = 7.1 ± 10.8%. Sensitivity for papilloedema detection approached 100%, though three raters incorrectly labelled the same patient with unilateral disc swelling as normal, all other cases were detected by all raters. CONCLUSIONS: Fundus photography assessment in isolation is highly sensitive but poorly specific for papilloedema detection. Using this method to screen the general population has significant potential for harm as overdiagnosis occurs, even in the hands of experienced clinicians.

Brachiocephalic vein stenosis in association with ipsilateral hyperdynamic brachio-basilic fistula causing ipsilateral facial swelling and contralateral papillodema and visual loss. A case report.

A 69-year-old hypertensive woman with a hyperdynamic, left brachio-basilic dialysis fistula presented with a long history of throbbing in her head, swelling of the left side of the face and two months of right visual loss with gross swelling of the right optic disc. Tight stenosis of left brachiocephalic vein was found to be causing retrograde flow into the left jugular vein which normalised after dilatation and stenting with resolution of the papillodema.

Idiopathic intracranial hypertension associated with iron deficiency anaemia: a lesson for management.

AIM: To document the causal association of iron deficiency anaemia (IDA) and intracranial hypertension (IH). METHODS: A consecutive case note review of patients with a clinical diagnosis of idiopathic intracranial hypertension (IIH) and anaemia presenting to a tertiary referral unit over a 2.5-year period. Demographics, aetiology and clinical details were recorded and analysed. RESULTS: Eight cases were identified from 77 new cases presenting with IIH. All 8 had documented microcytic anaemia with clinical evidence of raised intracranial pressure. There was no evidence of venous sinus thrombosis on MRI and MR venography in 7 subjects and on repeated CT venography in 1. On correction of anaemia alone, 7 cases resolved. One patient with severe progressive visual loss underwent ventriculoperitoneal shunt in addition to treatment of anaemia, with good outcome. The incidence of this association is 10.3%. CONCLUSION: These cases present an association between IDA and IH, in the absence of cerebral sinus thrombosis. As a clinically significant proportion of cases presenting with signs of IIH have IDA, we recommend all patients presenting with IIH have full blood counts and if they are found to be anaemic, they should be treated appropriately.

Elevated cerebrospinal fluid (CSF) leptin in idiopathic intracranial hypertension (IIH): evidence for hypothalamic leptin resistance?

OBJECTIVE: The aetiology of idiopathic intracranial hypertension (IIH) is not known, but its association with obesity is well-recognized. Recent studies have linked obesity with abnormalities in circulating inflammatory and adiposity related cytokines. The aim of this study was to characterize adipokine and inflammatory cytokine profiles in IIH. DESIGN: Paired serum and cerebrospinal fluid (CSF) specimens were collected from 26 patients with IIH and compared to 62 control subjects. Samples were analysed for leptin, resistin, adiponectin, insulin, IL-1beta, IL-6, IL-8 (CXCL8), TNFalpha, MCP-1 (CCL2), hepatocyte growth factor, nerve growth factor and PAI-1 using multiplex bead immunoassays. RESULTS: CSF leptin was significantly higher in patients with IIH (P = 0.001) compared to controls after correction for age, gender and body mass index (BMI). In the control population, BMI correlated with serum leptin (r = 0.34; P = 0.007) and CSF leptin (r = 0.51; P < 0.0001), but this was not the case for the IIH population. Profiles of other inflammatory cytokines and adipokines did not differ between IIH patients and controls once anthropometric factors had been accounted for. CONCLUSIONS: IIH was characterized by significantly elevated CSF leptin levels which did not correlate with BMI. We suggest that CSF leptin may be important in the pathophysiology of IIH and that obesity in IIH may occur as a result of hypothalamic leptin resistance.

Aetiology and outcomes of adult superior oblique palsies: a modern series.

PURPOSE: To establish the contemporary aetiology of adult superior oblique palsy (SOP). MATERIALS AND METHODS: A retrospective consecutive case series of 150 persons diagnosed with SOP between 1 January 1999 and 31 May 2005 at a neuro-ophthalmology centre in the West Midlands, the United Kingdom. Interrogating two different hospital databases identified all cases. A case note review was performed on all participants to determine demographics and aetiology based on diagnostic criteria, neuroimaging used, and outcome. RESULTS: We identified 133 unilateral isolated, 7 unilateral associated with other cranial nerve involvement, and 10 bilateral cases of SOP. Eighty-six were acquired, 51 congenital, and 13 undetermined. Of the unilateral isolated cases, 38.3% were considered to be congenital, 29.3% followed trauma, 23.3% were presumed to be vasculopathic in origin, and no cause could be established in 7.5%. All presumed microvascular-associated palsies resolved within 6 months of presentation. Unilateral SOPs associated with other cranial nerve palsies were commonly caused by trauma (71.4%), followed by tumour and undetermined causes (both 14.3%). Trauma was the most frequent cause of bilateral SOP (50%), followed by tumours and undetermined causes (both 20%), with congenital causes being uncommon (10%). CONCLUSION: We present a contemporary aetiological spectrum for adult SOP, with the lowest incidence of undetermined cases published in the medical literature. Neuroimaging did not change the management for the vast majority of cases and should be prompted by atypical presentations.

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.

Dominant optic atrophy. Refining the clinical diagnostic criteria in light of genetic linkage studies.

OBJECTIVE: To describe the clinical findings and refine the clinical diagnostic criteria for dominant optic atrophy based on eight British families in which the diagnosis was confirmed by linkage analysis. DESIGN AND PARTICIPANTS: Case series; 92 subjects in 8 pedigrees had both eyes examined. INTERVENTION: Family members received a domiciliary examination based on best-corrected visual acuity, color vision using Ishihara and Hardy Richter Rand (HRR) plates, confrontation field testing using a red target, and optic disc evaluation using a direct ophthalmoscope. Genomic DNA was extracted from leukocytes or buccal mucosal cells and genotyped using 12 fluorescently labeled microsatellite markers from the region 3q27-q29. MAIN OUTCOME MEASURES: Subjects were classified clinically as definitely or possibly affected on the basis of the domiciliary examination before genetic analysis, and these results were compared with the haplotype analysis. RESULTS: Clinically, 43 subjects were identified as definitely affected, 4 as possibly affected, and 45 as unaffected. Visual acuity in affected subjects ranged from 6/6 to count fingers and declined with age. On genetic analysis, a haplotype was identified in each family, which was found in all definitely affected members but not in those regarded as unaffected. The four possibly affected individuals also bore the haplotype that segregated with the disease. CONCLUSIONS: Simple clinical tests are highly efficacious in diagnosing dominant optic atrophy. Contrary to accepted criteria, symptoms begin before the age of 10 years in only 58% of affected individuals. Visual acuity in affected subjects is highly variable. A mild degree of temporal or diffuse pallor of the optic disc and minimal color vision defects, in the context of a family with dominant optic atrophy, are highly suggestive of an individual being affected, even if the visual acuity is normal. This widens the generally accepted diagnostic criteria for this disease.

Dominant optic atrophy, Kjer type. Linkage analysis and clinical features in a large British pedigree.

OBJECTIVES: To perform DNA linkage studies in an extensive 5-generation British pedigree with dominant optic atrophy and to validate the efficacy of domiciliary screening for affected members. METHODS: Family members received a domiciliary examination based on corrected visual acuity, color vision, visual field defects, and optic disc appearance; DNA linkage analysis was performed using 7 microsatellite markers on 3q27-qter. RESULTS: Based on the results of the ophthalmic examination, 15 members could be classified as definitely affected, 1 probably affected, and 25 unaffected. Two-point linkage analysis gave significant maximum lod scores at theta [corrected] = 0.00, with the markers D3S3669, D3S3590, and D3S3642. A haplotype segregating with the disease was identified in affected individuals, including the probably affected subject. Informative meioses defined the disease interval between markers D3S1601 and D3S1265. CONCLUSIONS: Domiciliary screening was effective in identifying all 16 affected members of a British family with dominant optic atrophy. The typical clinical features were present. The location of the OPA1 gene in this new British family seems to be in the 3q27-28 region and is the same as that reported in Danish, Cuban, and French families, suggesting no genetic heterogeneity in this disorder.

Linkage studies in dominant optic atrophy, Kjer type: possible evidence for heterogeneity.

Dominant optic atrophy, Kjer type, is an autosomal dominant disorder causing progressive loss of visual acuity and colour vision from early childhood. The gene (OPA1) has variable expressivity, a penetrance of 0.98, and the locus has been localised to 3q28-29. We have genotyped nine British families with the disease using 12 polymorphic microsatellite markers from this region. Linkage and haplotype analysis shows the OPA1 gene to be located in a 2.3 cM interval between markers D3S1601 and D3S2748. One family showed no evidence of linkage with the chromosome 3 markers, suggesting for the first time that locus heterogeneity for this disease may exist, although exclusion for linkage is based on unaffected subjects. In addition, analysis of recombinants has enabled us to order the 12 markers along chromosome 3.

The retina.

Prominent amongst last year's diverse papers on the retina were a study of the clinical manifestations of dominant cerebellar ataxia with pigmentary macular dystrophy, a review of the pathogenesis of carcinoma associated retinopathy, the Ischaemic Optic Neuropathy Decompression Trial, and a review of congenital optic disc anomalies. Ocular complications of several neurosurgical procedures were also reported during this period.

Comparison of pars plana vitrectomy and scleral buckling for uncomplicated rhegmatogenous retinal detachment.

Retinal detachment surgery can now achieve a final reattachment rate in over 90% of cases. The operation of choice in most cases is that of external scleral buckling with or without drainage of subretinal fluid. However, in a minority of cases these techniques are difficult to apply either when the breaks are unseen due to media opacities or when the breaks are complex, eg, posterior, large, or multiple breaks at different distances from the ora. Improvements in the technique of pars plana vitrectomy for retinal detachment now offers us an alternative method for treating these difficult cases. Pars plana vitrectomy for retinal detachments with unseen or complex breaks has a final attachment rate of over 90%, is technically easier to perform than conventional surgery, and avoids the refractive and ocular motility problems associated with complicated buckles. For these reasons and despite the high risk of nuclear sclerosis in phakic eyes, a pars plana vitrectomy may be the preferred option in selected cases of primary retinal detachment.

A survey of corneal graft practice in the United Kingdom.

A questionnaire designed to survey current corneal graft practice was sent to 498 consultant ophthalmologists in the United Kingdom. Three hundred and twenty-nine completed questionnaires (66%) were returned. Seventy per cent of these were from consultants who perform corneal grafts, of whom 36% had a specialist interest in corneal surgery. The survey found that most consultants preferred to perform corneal grafts on an inpatient basis with the patient under general anaesthesia. Agreement (> 80%) was also found in the following areas: use of a hand-held trephine, concurrent cataract surgery (if indicated), post-operative immunosuppression, and refraction to assess post-operative astigmatism. There was less agreement on the choice of donor material, use of tissue matching, donor-trephine size disparity, suture technique, relative timing of trabeculectomy surgery (if required), the management of intraocular lenses during surgery for pseudophakic bullous keratopathy, timing of discharge after surgery, use of prophylactic acyclovir, management of astigmatism, routine removal of all corneal sutures, and discharge of uncomplicated cases from routine follow-up.

Flash and pattern visual evoked potentials in the diagnosis and monitoring of dysthyroid optic neuropathy.

Flash and pattern visual evoked potentials were recorded in 8 patients (13 eyes) with dysthyroid optic neuropathy (DON), diagnosed using the American Thyroid Association classification. All were treated with systemic steroids, but 4 patients (6 eyes) also required orbital decompression. Flash VEP (P2) and pattern VEP (P100) were recorded prior to and 2 weeks after commencing steroid treatment or decompression. Fifteen patients with Graves orbitopathy but without DON, and 20 healthy subjects, acted as controls. Before treatment visual acuity was reduced in 10 eyes and visual fields were abnormal in 5, but the VEP was abnormal in all 13, with the group mean amplitude of P2 and P100 significantly less than controls, and the group mean P100 latency significantly greater than controls. After treatment with high-dose steroids or surgical decompression there were significant improvements in the group mean amplitude of P2 and P100, and significant reductions in P2 and P100 latency; however, individually, improvements in amplitude were more significant than improvements in latency. We conclude that the VEP to flash and pattern stimuli provides a useful diagnostic and monitoring tool in patients with DON, combining objectivity with quantitative analysis.

Dissociated eye movements in craniosynostosis: a hypothesis revived.

A characteristic pattern of dissociated eye movements was observed in a large proportion of our patients with a variety of craniosynostosis syndromes. These anomalies simulate overaction of the inferior oblique and underaction of the superior oblique muscles which, however, cannot fully explain the abnormalities. In a number of cases, excyclorotation of the muscle cone was observed, with the upper pole of the eye tilted away from the midline. It is postulated that such excyclorotation of the eyes will lead to dissociated eye movements which can be explained on physiological grounds according to Hering's law. This paper presents a review of our patients and evidence to support this hypothesis.