To evaluate the electrooculogram (EOG) in a large series of patients with Best disease and autosomal recessive bestrophinopathy.
A retrospective review of consecutive cases at Moorfields Eye Hospital, London, United Kingdom. Patients with Best disease or autosomal recessive bestrophinopathy who, after electrophysiologic testing, had a normal or atypical EOG light rise were identified. Main outcome measure was EOG amplitude, clinical phenotype and genotype.
One hundred thirteen patients were identified with likely disease-causing sequence variants in BEST1 (99 Best disease and 14 autosomal recessive bestrophinopathy). Electrooculograms had been performed in 75 patients. Twenty patients (27%) had no detectable light rise (Arden ratio of 100%) and 49 (65%) had Arden ratios of between 100% to 165%. Six patients (8%) were found to have an EOG light rise of >165%. No cases demonstrated significant interocular asymmetry in EOG amplitude.
The current work provides significant clinical evidence that the EOG phenotype in Best disease and autosomal recessive bestrophinopathy is more variable than currently appreciated. As a normal EOG may occur in the presence of a classical fundus appearance, the consequences of BEST1 mutation may be independently expressed, possibly mediated through differential effects on intracellular calcium homeostasis.
The bestrophinopathies are a group of inherited eye disorders that arise from either dominant or recessive mutations in the BEST1 gene. Electrooculography is invaluable in the diagnosis of Best disease and autosomal recessive bestrophinopathy, as a reduced Arden ratio is a highly penetrant feature of disease. We demonstrate that electrooculogram phenotype in Best disease and autosomal recessive bestrophinopathy is more variable than currently appreciated.
*University College London Institute of Ophthalmology, University College London, London, United Kingdom;
†Medical Retina Service, Moorfields Eye Hospital, London, United Kingdom;
‡Department of Ophthalmology, Leeds Institute of Molecular Medicine, St James' University Hospital, Leeds, United Kingdom; and
§Ophthalmology Department, University of California San Francisco Medical School, San Francisco, California.
Reprint requests: Kamron N. Khan, PhD, FRCOphth, Department of Genetics, Institute of Ophthalmology, University College London, 11–43 Bath St, London EC1V 9EL, UK; e-mail: email@example.com
M. Michaelides is supported by an FFB Career Development Award. This research has been funded/supported by the National Institute for Health Research Rare Diseases Translational Research Collaboration (NIHR RD-TRC).
National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital National Health Service Foundation Trust and UCL Institute of Ophthalmology (UK; K.N.K., A.R.W., A.T.M., and M.M.), Fight For Sight (UK; A.R.W., M.M., and O.A.M.), Moorfields Eye Hospital Special Trustees (UK; M.M.), the Foundation Fighting Blindness (FFB, USA; A.R.W., A.T.M., and M.M.), Retinitis Pigmentosa Fighting Blindness (UK; A.R.W., A.T.M., and M.M.), and the Wellcome Trust (099173/Z/12/Z; A.R.W., M.M.). The remaining authors have no conflicting interests to disclose.
The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health.