Professor Irene Gottlob
Professor of Ophthalmology
Department of Neuroscience, Psychology & Behaviour, University of Leicester
Tel: 0116 252 3268
Address: Cardiovascular Sciences, University of Leicester, Robert Kilpatrick Clinical Sciences Building, Level 5, Leicester Royal Infirmary, Leicester, LE2 7LX
For general enquiries, please email the secretary Mrs Sam Kerr or phone 0116 252 3152.
I lead the Leicester Ophthalmology group and my main areas of research are the regulation of eye movements and their disorders, in particular nystagmus. Current areas of active research include understanding the genetics of neuro-ophthalmic diseases, improving diagnosis and treatment of nystagmus, amblyopia and other neuro-ophthalmic diseases . Professor Gottlob is the author of more than 150 peer reviewed research papers and book chapters. She is section editor of the British Journal of Ophthalmology and on the editorial board of other scientific journals. Professor Gottlob is an enthusiastic teacher of clinical and research students and trainees. She greatly enjoys teaching and has been named academic role model for students and trainees by the BMA.
Thomas MG, Crosier M, Lindsay S, Kumar A, Thomas S, Araki M, Talbot CJ, McLean RJ, Surendran M, Taylor K, Leroy BP, Moore AT, Hunter DG, Hertle RW, Tarpey P, Langmann A, Lindner S, Brandner M, Gottlob I. The clinical and molecular genetic features of idiopathic infantile periodic alternating nystagmus. Brain. 2011 Mar;134(Pt 3):892-902
Betts-Henderson J, Bartesaghi S, Crosier M, Lindsay S, Chen HL, Salomoni P, Gottlob I, Nicotera P. The nystagmus-associated FRMD7 gene regulates neuronal outgrowth and development. Hum Mol Genet. 2010 Jan 15;19(2):342-51.
Knapp CM, Gottlob I, McLean RJ, Rajabally YA, Abbott RJ, Rafelt S, Proudlock FA. Vertical optokinetic nystagmus in Parkinson's disease. Mov. Disord. 2009;24:1533-8.
Sarvananthan N, Surendran M, Roberts EO, Jain S, Shah N, Proudlock FA, Thompson JR, McLean RJ, Degg C, Woodruff G, Gottlob I. The prevalence of nystagmus: The Leicestershire nystagmus survey. Invest. Ophthalmol. Vis. Sci. 2009.
Thomas S, Proudlock FA, Sarvananthan N, Roberts EO, Awan M, McLean RJ, Surendran M, Kumar AS, Farooq SJ, Degg C, Gale RP, Reinecke RD, Woodruff G, Langmann A, Lindner S, Jain S, Tarpey P, Raymond FL, Gottlob I. Phenotypical characteristics of idiopathic infantile nystagmus with and without mutations in FRMD7. Brain. 2008;131:1259-67.
Farooq SJ, Gottlob I, Benskin S, Proudlock FA. The effect of aging on torsional optokinetic nystagmus. Invest. Ophthalmol. Vis. Sci. 2008; 49:589-93.
Knapp CM, Gottlob I, McLean RJ, Proudlock FA. Horizontal and vertical look and stare optokinetic nystagmus symmetry in healthy adult volunteers. Invest. Ophthalmol. Vis. Sci. 2008; Feb;49(2):581-8;(3.3766).
Pieh C, Simonsz-Toth B, Gottlob I. Nystagmus characteristics in congenital stationary night blindness (CSNB). Br. J. Ophthalmol. 2008;Feb:92(2):236-40.
McLean RJ, Proudlock FA, Thomas S, Degg C, Gottlob I. 'Congenital nystagmus: randomized, controlled, double-masked trial of memantine/gabapentin.' Ann. Neurol. 2007 Feb;61(2):130-8.
Tarpey P, Thomas S, Sarvananthan N, Mallya U, Lisgo S, Talbot CJ, Roberts EO, Awan M, Surendran M, McLean RJ, Reinecke RD, Langmann A, Lindner S, Koch M, Jain S, Woodruff G, Gale RP, Degg C, Droutsas K, Asproudis I, Zubcov AA, Pieh C, Veal CD, Machado RD, Backhouse OC, Baumber L, Constantinescu CS, Brodsky MC, Hunter DG, Hertle RW, Read RJM, Edkins S, O'Meara S, Parker A, Stevens C, Teague J, Wooster R, Futreal PA, Trembath RC, Stratton MR, Raymond FL, Gottlob I. 'Mutations in FRMD7, a newly identified member of the FERM family, cause X-linked idiopathic congenital nystagmus'. Nat. Genet. 2006 Nov;38(11):1242-4.
Proudlock FA, Khanna A, Gottlob I. Filling-in along horizontal and vertical meridian. Invest. Ophthalmol. Vis. Sci. 2006; 47:453-60.
Sabri K, Knapp CM, Thompson JR, Gottlob I. The VF-14 and psychological impact of amblyopia and strabismus. Invest Ophtalmol Vis Sci 2006; 47; 4386-92.
Infantile nystagmus (IN) is a to and fro oscillation of the eyes which is estimated to have a prevalence of 2.4 per 1000. It has a direct impact upon visual function through constant motion of images on the retina as well as often being associated with retinal deficits.
IN also has a profound effect on psychosocial aspects of life such as self-esteem and confidence. More than a decade of collaborative research has resulted in the Leicester group being at the forefront of nystagmus research pioneering investigations from many different aspects the disease.
In 2006 we discovered the first gene causing idiopathic IN (the FRMD7 gene) in collaboration with the University of Cambridge and the Sanger Institute (Tarpey et al., 2006). The causes of IN are currently unknown. The discovery of the gene has opened up avenues for identifying the mechanisms behind IN.
Since then we have shown that FRMD7 expression is spatially and temporally regulated in the retina and gaze stabilization centres and that FRMD7 expression promotes neurite outgrowth during development of the ocular motor neural network (Betts-Henderson et al., 2010). Recent work in collaboration with the genetics department in the University of Leicester has shown that the FRMD7 protein interacts with Calcium Calmodulin Dependant Kinase (CASK) a protein which links the plasma membrane to the actin cytoskeleton in developing neurons (Watkins et al., 2013). As a result of this work the Leicester group has developed a genetic test for FRMD7 mutations which is now used clinically by the NHS. This can help patients in excluding other diseases earlier reducing the amount of diagnostic tests needed to diagnose the type of IN.
We have used high-resolution optical coherence tomography (OCT), a technique which provides near microscopic resolution of retinal tissue in vivo, and eye movement recordings to improve the diagnosis of IN. Over recent years we have been at the forefront of using these technologies in IN where we have been able to use then to fully characterise the retinal and ocular motor abnormalities in diseases such as:
• FRMD7 associated IN (Thomas et al., 2008; Kumar et al., 2011)
• Achromaptosia (Thomas et al., 2012, 2013)
• Albinism (Mohammad et al., 2011)
• PAX6 mutations (Thomas et al., 2014)
Further work is ongoing on the characterisation of visual pathway abnormalities in these disease and other conditions associated with IN. These developments have changed the specificity and ease with which we can diagnose IN. We have also developed a grading scheme to quantify foveal hypoplasia clinically based on our findings (Thomas et al., 2011).
In 2011, the Leicester group was the first UK centre to acquire hand-held OCT, for research and clinical use in infants and young children. The group has since been used hand-held OCT to develop improved strategies of diagnosing in this age group (Lee et al., 2013).
This work is important for providing early diagnosis as well as improving the prognosis of the degree of visual deficit later in life to parents. We are also using hand-held OCT to investigate normal retinal development and disrupted development of the retina caused by premature birth
Infantile nystagmus has long been considered an untreatable condition with limited options for pharmacological or surgical intervention. Treatment options are now emerging with the Leicester group pioneering many of these new treatments.
The success of two medications, memantine and gabapentin, for treating acquired nystagmus led the Leicester group to complete the first randomised controlled trial into pharmacological treatment for IN (McLean et al., 2007). This work has continued in the form of a large crossover trial for the same two medications, which is nearing completion.
We have also collaborated with MERZ Pharma to test a new medication, Neramexane. Other forms of treatment that have been evaluated by the group include comparing contact lens wear in IN, evaluating of the effects of the surgical procedure of “tenotomising” eye muscles for IN, and investigating the effect of biofeedback for improving nystagmus. These studies have informed clinicians about the value of different options and provide possibilities of treatment for patients with nystagmus that were not previously possible.
The Leicester group is currently developing ways to evaluate the impact of interventions on patient centred outcome measures such as quality of life and measures of functional vision such as reading performance.
The Leicester Ophthalmology Group has now become the foremost centre for the diagnosis and treatment of nystagmus in the UK and sees over 600 patients with nystagmus per year. The majority of patients are referred from outside the service area, including patients being referred to internationally from Europe and even further afield.
Exploring reasons for poor outcomes for amblyopia treatment
We have developed electronic monitors in collaboration with the Medical Physics department in Leicester to measure adherence to patching treatment in amblyopia. We found that adherence is variable and often poor (Awan et al., 2005) which explains the prolonged treatment times and poor outcomes we have observed (Awan et al., 2010).
More recently we have developed electronic monitors to measure glasses wearing for the first time. We find that adherence is variable and outcomes of treatment are suboptimal.
Improving adherence and optimising treatment
We used feedback from parents and children to develop an educational/motivational intervention pack to improve amblyopia treatment (Pradeep et al., 2014). The pack contains a story book for children with illustrations of treatment of an amblyopic boy where the eyes are represented as two characters “Ra Ra” and “La La” speaking to each other. The pack also contains information booklets for parents, children, teachers, family and friends about amblyopia, its treatment and common misconceptions as well as other motivational elements such as an “amblyopia passport” and reward stickers for the children.
We are also looking at the effect of using electronic monitors to feedback to the parents and children how well they are doing. We are currently running a large clinical trial into the role of glasses wearing in amblyopia (funded by Action Medical Research). It is a multicentre study involving centres in Austria, Germany, Switzerland as well as around the UK.
Effect on reading
We have investigated the effect of amblyopia on reading using eye movement recordings and find that there are often subclinical deficits present for example when reading with both eyes open or the non-amblyopic eye open (Kanonidou et al., 2010, 2014).