James Acheson

Retinal nerve fiber layer thickness in vigabatrin-exposed patients.

Vigabatrin‐associated visual field loss (VAVFL) occurs in 25 to 50% of exposed patients and is routinely monitored using perimetry, which has inherent limitations. Using optical coherence tomography (OCT), retinal nerve fiber layer (RNFL) thinning has been described in a small number of vigabatrin‐exposed patients. We explored the relationship between RNFL thickness and visual field size, to determine whether OCT is a suitable tool to use in patients exposed to vigabatrin.

A pharmacogenetic exploration of vigabatrin-induced visual field constriction

INTRODUCTION Use of the antiepileptic drug (AED) vigabatrin is severely limited by irreversible visual field constriction, an adverse reaction to the drug reported in approximately 40% of patients. Given the evidence suggesting an idiosyncratic drug response, we set out to detect genetic variation of strong, clinically relevant effect that might guide clinicians in the safe, controlled prescribing of this otherwise usefuldrug. METHODS Patients with a history of at least 1-year exposure to vigabatrin were enrolled at two independent referral centers. Using Goldmann perimetry, visual fields and the extent of constriction were calculated for each patient. We examined the correlation between the extent of vigabatrin induced visual field constriction and genetic variation across six candidate genes (SLC6A1, SLC6A13, SCL6A11, ABAT, GABRR1 and GABRR2). We availed of HapMap data and used a tagging SNP technique in an effort to efficiently capture all common variation within these genes. We attempted to replicate any positive associations before drawing conclusions from our results. RESULTS The degree of visual field constriction correlated with three SNPs and one haplotype in a cohort of 73 patients. However we were unable to replicate these findings in a second independent cohort consisting of 58 patients, suggesting the initial results were possibly false positives, or variants of weak effect. CONCLUSION Common variants of strong, clinically relevant effect do not appear to reside in the candidate genes studied here. This does not rule out the presence of genetic variants of weak effect in these genes, nor of variants of strong effect in other genes.

Evolution of visual field loss over ten years in individuals taking vigabatrin.

PURPOSE Vigabatrin-associated visual field loss (VAVFL) occurs in around 45% of exposed people. It is generally accepted that, once established, VAVFL is stable and does not progress with continued VGB use. Most studies have, however, only followed people for short periods. We assessed the evolution of VAVFL over a ten-year period of continued VGB use. METHODS From a group of 201 vigabatrin-exposed individuals with epilepsy, fourteen individuals were identified who were currently taking vigabatrin. All individuals had at least ten years exposure to vigabatrin. Individuals underwent several visual field examinations using Goldmann perimetry between Test 1 (first recorded examination) and Test 2 (most recent examination). All visual field results were analysed and quantified retrospectively by one investigator. RESULTS 174 visual fields from the fourteen participants were available. The average follow-up period was 128 months. The prevalence of VAVFL increased from 64% at Test 1 to 93% at Test 2. The visual field size was significantly smaller at Test 2 compared to Test 1. All subjects showed a trend for decreasing visual field size with increasing cumulative vigabatrin exposure, when all fields for an individual were taken into account. There was a high degree of variability in visual field size between successive test sessions. CONCLUSIONS VAVFL progresses with continued vigabatrin exposure over a ten-year period. Progression may be slow and difficult to detect because of the high degree of variability in visual field size between successive test sessions. New techniques are needed to monitor the effects of vigabatrin retinotoxicity in people who continue vigabatrin therapy.

Patterns of Peripapillary Retinal Nerve Fiber Layer Thinning in Vigabatrin-Exposed Individuals

PURPOSE To explore the relationship of peripapillary retinal nerve fiber layer (ppRNFL) thinning in individuals exposed to the antiepileptic drug vigabatrin with respect to 2 separate variables: cumulative vigabatrin exposure and severity of vigabatrin-associated visual field loss (VAVFL). DESIGN Cross-sectional observational study. PARTICIPANTS Subjects were older than 18 years, 129 with vigabatrin-treated epilepsy (vigabatrin-exposed group) and 87 individuals with epilepsy never treated with vigabatrin (nonexposed group). METHODS All subjects underwent ppRNFL imaging using spectral-domain optical coherence tomography. Eighty-four vigabatrin-exposed individuals underwent Goldmann kinetic perimetry. The visual field examined from the right eye was categorized as normal (n = 47), mildly abnormal (n = 18), or moderately to severely abnormal (n = 19). In 91 vigabatrin-exposed individuals, the cumulative vigabatrin exposure could be ascertained: 41 subjects received 1000 g or less, 23 subjects received more than 1000 g but equal to or less than 2500 g, 16 subjects received more than 2500 g but equal to or less than 5000 g or less, and 11 subjects received more than 5000 g. MAIN OUTCOME MEASURES Differences in ppRNFL thickness across the twelve 30° sectors: (1) among all nonexposed individuals and all vigabatrin-exposed individuals, (2) between each vigabatrin-exposed group, according to cumulative vigabatrin exposure, and the nonexposed group, (3) among different vigabatrin-exposed subjects grouped according to cumulative vigabatrin exposure, and (4) among vigabatrin-exposed subjects grouped according to severity of VAVFL. RESULTS The ppRNFL was significantly thinner in vigabatrin-exposed compared with nonexposed individuals in most 30° sectors (P<0.004). The temporal, temporal superior, and temporal inferior 30° sectors, as well as the nasal 30° sector, were not affected. There was a trend for increasing ppRNFL thinning with increasing cumulative vigabatrin exposure. The nasal-superior 30° sector was significantly thinner in group 1 (≤1000 g) compared with nonexposed individuals (P<0.05) and in vigabatrin-exposed individuals with normal visual fields compared with nonexposed individuals (P<0.05). CONCLUSIONS After vigabatrin exposure in individuals receiving cumulative doses of 1000 g or less or in the presence of normal visual fields, ppRNFL thinning in the nasal superior 30° sector may occur. With higher cumulative doses of vigabatrin exposure, additional ppRNFL thinning was observed. The temporal aspects of the ppRNFL are spared, even in individuals with large cumulative vigabatrin exposures and moderate or severe VAVFL.

New algorithm for assessing patient suitability for macular translocation surgery

Purpose:  We propose a case selection algorithm to assess suitability for macular translocation for subfoveal neovascular membrane (CNV) secondary to age‐related macular degeneration. The algorithm is based on preoperative assessment of residual foveal function, as assessed by a slit‐lamp fixation task and duration of visual loss, in patients with poor acuity. We validate our slit‐lamp fixation task against an objective analysis (Nidek MP‐1 Microperimetry) and proceed to examine surgical outcomes as selected by the algorithm.

Familial Bell's Palsy in Females: A Phenotype with a Predilection for Eyelids and Lacrimal Gland

The authors report a family with familial Bells palsy affecting seven individuals, six of whom are females. This is a distinct subtype of Bells palsy with a predilection for juvenile females, previously reported only very rarely. In conjunction with a review of the literature, this case suggests that this phenotype carries with it a greater risk of serious complications affecting the eyelids and lacrimal gland. These carry significant functional and cosmetic implications owing to aberrant regeneration of the seventh, sixth and possibly third cranial nerves, chronicity and relapses. Clinical features include synkinesis of the eyelids with the orbicularis oris causing synkinetic ptosis, recurrent paralytic ectropion, paralysis of facial muscles of expression with dry eye, hyperlacrimation (crocodile tears), and transient strabismus. Clinically, the decision to offer surgery in place of conservative treatment should consider the natural history of chronicity and relapses often seen with this subtype of familial Bells palsy. Botulinum toxin injections are especially versatile in managing the complications associated with this phenotype.

Vigabatrin associated visual field constriction

Peripheral visual field defects in patients taking vigabatrin seem to arise in a proportion of patients. Typically a concentric narrowing of the field is seen with preservation of central acuity and colour vision. Case definition remains poorly defined and prevalence figures ranging from as low as 0.14% to as high as 39% have appeared.1 2 The high figures reported by Lawden et al , this issue, pp 716–722,3 reflect a definition which includes any bilateral field defect that could not be explained in terms of other retinal or neurological pathology regardless of severity of symptomaticity. This clearly highlights the problem but leaves more work to be done. Visual field …

Retinal nerve fibre layer thinning is associated with drug resistance in epilepsy

Objective Retinal nerve fibre layer (RNFL) thickness is related to the axonal anterior visual pathway and is considered a marker of overall white matter ‘integrity’. We hypothesised that RNFL changes would occur in people with epilepsy, independently of vigabatrin exposure, and be related to clinical characteristics of epilepsy. Methods Three hundred people with epilepsy attending specialist clinics and 90 healthy controls were included in this cross-sectional cohort study. RNFL imaging was performed using spectral-domain optical coherence tomography (OCT). Drug resistance was defined as failure of adequate trials of two antiepileptic drugs to achieve sustained seizure freedom. Results The average RNFL thickness and the thickness of each of the 90° quadrants were significantly thinner in people with epilepsy than healthy controls (p<0.001, t test). In a multivariate logistic regression model, drug resistance was the only significant predictor of abnormal RNFL thinning (OR=2.09, 95% CI 1.09 to 4.01, p=0.03). Duration of epilepsy (coefficient −0.16, p=0.004) and presence of intellectual disability (coefficient −4.0, p=0.044) also showed a significant relationship with RNFL thinning in a multivariate linear regression model. Conclusions Our results suggest that people with epilepsy with no previous exposure to vigabatrin have a significantly thinner RNFL than healthy participants. Drug resistance emerged as a significant independent predictor of RNFL borderline attenuation or abnormal thinning in a logistic regression model. As this is easily assessed by OCT, RNFL thickness might be used to better understand the mechanisms underlying drug resistance, and possibly severity. Longitudinal studies are needed to confirm our findings.

The cost-effectiveness of different strategies to evaluate optic disk drusen in children.

To the Editor: Leon and colleagues reported on the costeffectiveness of performing ultrasonography prior to neuroimaging in patients with optic disk drusen (ODD), with an overall reduction in the number of other investigations undertaken.However, it is important to bear inmind that drusen and raised intracranial pressure can coexist and that a diagnosis of drusen does not preclude the need for investigations for papilledema. ODD have a prevalence of 0.3% to 2.4%, with bilateral occurrence in 75% of cases. Drusen have been observed in children 3.6 to 19.5 years of age, with a mean age of 12.1 years at first detection. Although detection of ODD with ultrasound B-scan is well established, the detection of true papilledema is also possible, by measuring optic nerve sheath diameter, with a sensitivity of 90% to detect papilledema and a specificity of 79% to detect pseudopapilledema in adult patients. To determine the prevalence of ODD and true papilledema in children referred for apparent optic nerve head swelling we retrospectively reviewed the medical records of children #16 years of age presenting to Moorfields Eye Hospital NHS Foundation Trust, London, over a 2-year period (2008-2009) with optic disk swelling and in whom ODD had been demonstrated on ultrasonography (performed by a single experienced ultrasonographer [MR]). In 22 of 39 children an isolated diagnosis of ODD was established, based on clinical examination and, where indicated, ancillary tests, including neuroimaging (CT or MRI) in 3 patients and visual electrophysiology testing in one. However, 17 patients had other conditions in addition to ODD. Importantly, 4 patients (10%) had true papilledema, 3 had papilledema secondary to idiopathic intracranial hypertension, and one due to an intracerebral tumor. The remaining 13 patients had other ocular conditions unrelated to intracranial pressure, such as high hypermetropia and anisometropic amblyopia. Although 21 of 39 patients (53.8%) had only ultrasonography as a diagnostic test, the clinical course and duration of follow-up supported the diagnosis and confirmed other pathology was not present. Our findings support and supplement those of Leon and colleagues. In addition, we found the prevalence of coexisting ODD and raised intracranial pressure in children to be 10%. It is important to use ultrasonography not only to detect drusen but also to measure optic nerve sheath diameter. B-mode imaging can be used to image the anterior half of the optic nerve. However, the lateral resolution on all B-scan systems is poor compared to the axial resolution. Therefore, to accurately measure optic nerve diameter requires a deviation of gaze to present the optic nerve more perpendicularly to the incoming ultrasonic pulses.

An old friend revisited: chloramphenicol optic neuropathy

With increasing antibiotic resistance, oral chloramphenicol may be utilized more frequently; below we highlight the risk of toxic optic neuropathy.