Genomes and Genes
ocular motility disorders
Summary: Disorders that feature impairment of eye movements as a primary manifestation of disease. These conditions may be divided into infranuclear, nuclear, and supranuclear disorders. Diseases of the eye muscles or oculomotor cranial nerves (III, IV, and VI) are considered infranuclear. Nuclear disorders are caused by disease of the oculomotor, trochlear, or abducens nuclei in the BRAIN STEM. Supranuclear disorders are produced by dysfunction of higher order sensory and motor systems that control eye movements, including neural networks in the CEREBRAL CORTEX; BASAL GANGLIA; CEREBELLUM; and BRAIN STEM. Ocular torticollis refers to a head tilt that is caused by an ocular misalignment. Opsoclonus refers to rapid, conjugate oscillations of the eyes in multiple directions, which may occur as a parainfectious or paraneoplastic condition (e.g., OPSOCLONUS-MYOCLONUS SYNDROME). (Adams et al., Principles of Neurology, 6th ed, p240)
- Smyrnis N, Evdokimidis I, Mantas A, Kattoulas E, Stefanis N, Constantinidis T, et al. Smooth pursuit eye movements in 1,087 men: effects of schizotypy, anxiety, and depression. Exp Brain Res. 2007;179:397-408 pubmed
- . The convergence insufficiency treatment trial: design, methods, and baseline data. Ophthalmic Epidemiol. 2008;15:24-36 pubmed publisher..The baseline data reported herein define the clinical profile of those enrolled into the CITT. ..
- Rouse M, Borsting E, Mitchell G, Scheiman M, Cotter S, Cooper J, et al. Validity and reliability of the revised convergence insufficiency symptom survey in adults. Ophthalmic Physiol Opt. 2004;24:384-90 pubmed..The results of the study demonstrate that the CISS is a valid and reliable instrument that can be used clinically or as an outcome measure for research studies of adults with CI. ..
- Pinkhardt E, Kassubek J, Sussmuth S, Ludolph A, Becker W, Jurgens R. Comparison of smooth pursuit eye movement deficits in multiple system atrophy and Parkinson's disease. J Neurol. 2009;256:1438-46 pubmed publisher..The differences in pursuit tracking between PD and MSA were large enough to warrant their use as ancillary diagnostic criteria for the distinction between these disorders. ..
- Vedantham V, Jethani J, Agarwal A, Vijayalakshmi P. Retinitis pigmentosa associated with blepharophimosis, blue dot cataract and primary inferior oblique overaction: a new syndrome complex?. Indian J Ophthalmol. 2007;55:150-1 pubmed..Computerized search using Medline did not reveal any such previously reported association...
- Gooding D, Basso M. The tell-tale tasks: a review of saccadic research in psychiatric patient populations. Brain Cogn. 2008;68:371-90 pubmed publisher..g. cortical/basal ganglia circuits) that may be implicated in the underlying pathophysiology of several of these disorders. Future directions for research in this growing area are offered. ..
- Burgess H, Johnson S, Granato M. Unidirectional startle responses and disrupted left-right co-ordination of motor behaviors in robo3 mutant zebrafish. Genes Brain Behav. 2009;8:500-11 pubmed publisher..Moreover, we show that twitch twice mutants exhibit normal visual acuity but display defects in horizontal eye movements, suggesting a specific and critical role for twitch twice/robo3 in sensory-guided behavior. ..
- Mosimann U, Müri R, Burn D, Felblinger J, O Brien J, McKeith I. Saccadic eye movement changes in Parkinson's disease dementia and dementia with Lewy bodies. Brain. 2005;128:1267-76 pubmed..The similarities in saccade performance in PDD and DLB underline the overlap between these conditions and underscore differences from Alzheimer's disease and Parkinson's disease. ..
- Engle E. Oculomotility disorders arising from disruptions in brainstem motor neuron development. Arch Neurol. 2007;64:633-7 pubmed
- Scheiman M, Mitchell G, Cotter S, Cooper J, Kulp M, Rouse M, et al. A randomized clinical trial of treatments for convergence insufficiency in children. Arch Ophthalmol. 2005;123:14-24 pubmed..Neither pencil push-ups nor placebo vision therapy/orthoptics was effective in improving either symptoms or signs associated with convergence insufficiency. ..
- Rouse M, Borsting E, Deland P. Reliability of binocular vision measurements used in the classification of convergence insufficiency. Optom Vis Sci. 2002;79:254-64 pubmed..The large potential test-retest differences found could complicate clinical decision-making in regards to diagnosis and treatment. ..
- Bosley T, Salih M, Jen J, Lin D, Oystreck D, Abu Amero K, et al. Neurologic features of horizontal gaze palsy and progressive scoliosis with mutations in ROBO3. Neurology. 2005;64:1196-203 pubmed..The syndrome also includes a distinctive brainstem malformation and defective crossing of some brainstem neuronal pathways. ..
- Aziz S, Cleary M, Stewart H, Weir C. Are orthoptic exercises an effective treatment for convergence and fusion deficiencies?. Strabismus. 2006;14:183-9 pubmed..Their role in esophoria is unclear and needs further study. ..
- Straube A. Therapeutic considerations for eye movement disorders. Dev Ophthalmol. 2007;40:175-92 pubmed..Finally, anticonvulsants like carbamazepine are the drugs of choice for disorders involving a nerve-blood vessel contact that induces symptoms of vestibular paroxysmia or superior oblique myokymia. ..
- Scheiman M, Cotter S, Rouse M, Mitchell G, Kulp M, Cooper J, et al. Randomised clinical trial of the effectiveness of base-in prism reading glasses versus placebo reading glasses for symptomatic convergence insufficiency in children. Br J Ophthalmol. 2005;89:1318-23 pubmed
- Utsch B, Sayer J, Attanasio M, Pereira R, Eccles M, Hennies H, et al. Identification of the first AHI1 gene mutations in nephronophthisis-associated Joubert syndrome. Pediatr Nephrol. 2006;21:32-5 pubmed..One patient had the association of JBTS and NPHP with chronic renal failure. This is the first report of AHI1 mutations causing JBTS associated with NPHP, confirming the clinical and genetic heterogeneity of NPHP...
- Brancati F, Barrano G, Silhavy J, Marsh S, Travaglini L, Bielas S, et al. CEP290 mutations are frequently identified in the oculo-renal form of Joubert syndrome-related disorders. Am J Hum Genet. 2007;81:104-13 pubmed..One patient with mutation displayed complete situs inversus, confirming the clinical and genetic overlap between JSRDs and other ciliopathies. ..
- Fluss J, Blaser S, Chitayat D, Akoury H, Glanc P, Skidmore M, et al. Molar tooth sign in fetal brain magnetic resonance imaging leading to the prenatal diagnosis of Joubert syndrome and related disorders. J Child Neurol. 2006;21:320-4 pubmed..We report a case of Joubert syndrome diagnosed prenatally using fetal MRI. We also discuss the etiology of Joubert syndrome in view of the recent genetic advances and murine models of cerebellar dysgenesis. ..
- Sturm V, Leiba H, Menke M, Valente E, Poretti A, Landau K, et al. Ophthalmological findings in Joubert syndrome. Eye (Lond). 2010;24:222-5 pubmed publisher..It has been associated with ocular and oculomotor abnormalities. The aim of our study was to extend the ophthalmic knowledge in JS and to add new findings...
- Smyrnis N, Kattoulas E, Stefanis N, Avramopoulos D, Stefanis C, Evdokimidis I. Schizophrenia-related neuregulin-1 single-nucleotide polymorphisms lead to deficient smooth eye pursuit in a large sample of young men. Schizophr Bull. 2011;37:822-31 pubmed publisher..NRG1 genotype variations were related to smooth eye pursuit variations both at the SNP level and at the haplotype level adding to the validation of this gene as a candidate gene for the disorder. ..
- Le Ber I, Moreira M, Rivaud Pechoux S, Chamayou C, Ochsner F, Kuntzer T, et al. Cerebellar ataxia with oculomotor apraxia type 1: clinical and genetic studies. Brain. 2003;126:2761-72 pubmed..The frequency of chorea at onset suggests that this diagnosis should also be considered in children with chorea who do not carry the IT15 mutation responsible for Huntington's disease. ..
- Zamponi N, Rossi B, Messori A, Polonara G, Regnicolo L, Cardinali C. Joubert syndrome with associated corpus callosum agenesis. Eur J Paediatr Neurol. 2002;6:63-6 pubmed..Nevertheless, the hypothesis of a developmental abnormality of midline structures extended to the supratentorial compartment is rather attractive. ..
- Weiss A, Doherty D, Parisi M, Shaw D, Glass I, Phillips J. Eye movement abnormalities in Joubert syndrome. Invest Ophthalmol Vis Sci. 2009;50:4669-77 pubmed publisher..3 or less and phase was indeterminate in four subjects. The abnormalities in gaze-holding and eye movements are consistent with the distributed abnormalities of midline cerebellum and brain stem regions associated with Joubert syndrome. ..
- Chan W, Traboulsi E, Arthur B, Friedman N, Andrews C, Engle E. Horizontal gaze palsy with progressive scoliosis can result from compound heterozygous mutations in ROBO3. J Med Genet. 2006;43:e11 pubmed..More comprehensive examinations of parents and siblings of HGPPS patients are required to determine if the incidence of scoliosis in individuals harbouring heterozygous ROBO3 mutations is greater than in the general population. ..
- Gorden N, Arts H, Parisi M, Coene K, Letteboer S, van Beersum S, et al. CC2D2A is mutated in Joubert syndrome and interacts with the ciliopathy-associated basal body protein CEP290. Am J Hum Genet. 2008;83:559-71 pubmed publisher..These observations extend the genetic spectrum of JSRD and provide a model system for studying extragenic modifiers in JSRD and other ciliopathies. ..
- Shaikh A, Miura K, Optican L, Ramat S, Leigh R, Zee D. A new familial disease of saccadic oscillations and limb tremor provides clues to mechanisms of common tremor disorders. Brain. 2007;130:3020-31 pubmed
- Scheiman M, Cooper J, Mitchell G, de L, Cotter S, Borsting E, et al. A survey of treatment modalities for convergence insufficiency. Optom Vis Sci. 2002;79:151-7 pubmed..This survey suggests that most eyecare practitioners prescribe PPT as the initial treatment for CI. ..
- Hwang J, Lim H. Acquired simulated brown syndrome following surgical repair of medial orbital wall fracture. Korean J Ophthalmol. 2005;19:80-3 pubmed..Postoperatively, the patient was asymptomatic in all diagnostic gaze positions...
- Hood A, Amador S, Cain A, Briand K, Al Refai A, Schiess M, et al. Levodopa slows prosaccades and improves antisaccades: an eye movement study in Parkinson's disease. J Neurol Neurosurg Psychiatry. 2007;78:565-70 pubmed..These findings suggest levodopa improves function of the voluntary frontostriatal system, which is deficient in PD. ..
- Schultz K, Lee A. Diagnostic yield of the evaluation of isolated third nerve palsy in adults. Can J Ophthalmol. 2007;42:110-5 pubmed..8%; diagnostic yield in cases concordant with published neuroimaging recommendations was 100%. The degree of external and internal dysfunction can direct the type of neuroimaging performed in TNP. ..
- Adler P. Efficacy of treatment for convergence insufficiency using vision therapy. Ophthalmic Physiol Opt. 2002;22:565-71 pubmed..The study also evaluates the associated symptoms before and after therapy...
- Gutowski N, Bosley T, Engle E. 110th ENMC International Workshop: the congenital cranial dysinnervation disorders (CCDDs). Naarden, The Netherlands, 25-27 October, 2002. Neuromuscul Disord. 2003;13:573-8 pubmed
- Glasauer S, Hoshi M, Büttner U. Smooth pursuit in patients with downbeat nystagmus. Ann N Y Acad Sci. 2005;1039:532-5 pubmed
- Gradstein L, Danek A, Grafman J, Fitzgibbon E. Eye movements in chorea-acanthocytosis. Invest Ophthalmol Vis Sci. 2005;46:1979-87 pubmed..Patients with this progressive, intractable disease have pronounced ocular motor abnormalities. Eye movement recordings could assist in diagnosing ChAc, monitoring its progression and possible treatment evaluation. ..
- Montagnese S, Gordon H, Jackson C, Smith J, Tognella P, Jethwa N, et al. Disruption of smooth pursuit eye movements in cirrhosis: relationship to hepatic encephalopathy and its treatment. Hepatology. 2005;42:772-81 pubmed..Treatment status confounds the classification of neuropsychiatric status and should be taken into account when categorizing these patients. ..
- Amoiridis G, Tzagournissakis M, Christodoulou P, Karampekios S, Latsoudis H, Panou T, et al. Patients with horizontal gaze palsy and progressive scoliosis due to ROBO3 E319K mutation have both uncrossed and crossed central nervous system pathways and perform normally on neuropsychological testing. J Neurol Neurosurg Psychiatry. 2006;77:1047-53 pubmed..Our patients with the ROBO3 E319Kappa mutation show normal perceptual and cognitive functions and have both crossed and uncrossed motor, sensory and auditory pathways. ..
- Wong A, Musallam S, Tomlinson R, Shannon P, Sharpe J. Opsoclonus in three dimensions: oculographic, neuropathologic and modelling correlates. J Neurol Sci. 2001;189:71-81 pubmed..Malfunction of Purkinje cells in the dorsal vermis, which inhibit the FOR, may cause opsoclonus by disinhibiting it. ..
- Nelles G, Pscherer A, de Greiff A, Forsting M, Gerhard H, Esser J, et al. Eye-movement training-induced plasticity in patients with post-stroke hemianopia. J Neurol. 2009;256:726-33 pubmed publisher..A relative decrease of activation was found in the left FEF. In this group of patients, eye-movement training induced altered brain activation in the striate and extrastriate cortex as well as in oculomotor areas...
- Haller S, Wetzel S, Lütschg J. Functional MRI, DTI and neurophysiology in horizontal gaze palsy with progressive scoliosis. Neuroradiology. 2008;50:453-9 pubmed publisher..Moving-head fMRI studies in the future might show whether the compensatory head movements instead of normal eye movements activate the eye-movement network. ..
- Ko M, Dalmau J, Galetta S. Neuro-ophthalmologic manifestations of paraneoplastic syndromes. J Neuroophthalmol. 2008;28:58-68 pubmed publisher..Most of these disorders are related to immunologic mechanisms presumably triggered by the neoplastic expression of neuronal proteins. Accurate recognition is essential to appropriate management. ..
- Shaikh A, Ramat S, Optican L, Miura K, Leigh R, Zee D. Saccadic burst cell membrane dysfunction is responsible for saccadic oscillations. J Neuroophthalmol. 2008;28:329-36 pubmed publisher..Our simulations suggest that alterations in membrane properties that lead to an increase in PIR, a reduction in external glycinergic inhibition, or both can cause saccadic oscillations. ..
- Gallaway M, Scheiman M, Malhotra K. The effectiveness of pencil pushups treatment for convergence insufficiency: a pilot study. Optom Vis Sci. 2002;79:265-7 pubmed..Only one subject became asymptomatic. PPT resulted in some improvement in both objective findings and symptoms for some subjects. Compliance with the recommended home therapy protocol was poor. ..
- Amouri R, Nehdi H, Bouhlal Y, Kefi M, Larnaout A, Hentati F. Allelic ROBO3 heterogeneity in Tunisian patients with horizontal gaze palsy with progressive scoliosis. J Mol Neurosci. 2009;39:337-41 pubmed publisher..This study extends the molecular spectrum of the ROBO3 gene and the geographic origin of patients with ROBO3 gene mutations, and underlines the homogeneity of the motor ocular syndrome whatever type of mutation is encountered. ..
- Proudlock F, Gottlob I. Physiology and pathology of eye-head coordination. Prog Retin Eye Res. 2007;26:486-515 pubmed..We provide evidence for this based on changes in eye-head coordination dependant on the context and expectation of presented visual stimuli, as well as from changes in eye-head coordination caused by frontal lobe dysfunction. ..
- Maples W, Hoenes R. Near point of convergence norms measured in elementary school children. Optom Vis Sci. 2007;84:224-8 pubmed..The NPC break and recovery criteria described here should be tentatively used as one of the benchmarks in the diagnosis of convergence insufficiency. ..
- Morgan C, Huddy V, Lipton M, Curran H, Joyce E. Is persistent ketamine use a valid model of the cognitive and oculomotor deficits in schizophrenia?. Biol Psychiatry. 2009;65:1099-102 pubmed publisher..The absence of any other oculomotor or cognitive deficit present in schizophrenia suggests that chronic self-administration of ketamine may not be a good model of these aspects of the disorder. ..
- Husain M, Parton A, Hodgson T, Mort D, Rees G. Self-control during response conflict by human supplementary eye field. Nat Neurosci. 2003;6:117-8 pubmed
- Hufner K, Stephan T, Kalla R, Deutschlander A, Wagner J, Holtmannspotter M, et al. Structural and functional MRIs disclose cerebellar pathologies in idiopathic downbeat nystagmus. Neurology. 2007;69:1128-35 pubmed..Our data are in line with experiments in primates showing that ablation of the floccular and parafloccular lobes disrupts smooth pursuit and causes DBN. ..
- Rouse M, Borsting E, Mitchell G, Cotter S, Kulp M, Scheiman M, et al. Validity of the convergence insufficiency symptom survey: a confirmatory study. Optom Vis Sci. 2009;86:357-63 pubmed publisher..These results also confirm the validity of a cut-point of > or = 16 in distinguishing children with symptomatic CI from those with NBV. ..
- Khan A, Oystreck D, Al Tassan N, Al Sharif L, Bosley T. Bilateral synergistic convergence associated with homozygous ROB03 mutation (p.Pro771Leu). Ophthalmology. 2008;115:2262-5 pubmed publisher..The author(s) have no proprietary or commercial interest in any materials discussed in this article. ..
- Ringman J, Saver J, Woolson R, Adams H. Hemispheric asymmetry of gaze deviation and relationship to neglect in acute stroke. Neurology. 2005;65:1661-2 pubmed..There was no difference in its rate of co-occurrence with neglect between right- and nonright-handed patients. ..