|Year : 2021 | Volume
| Issue : 1 | Page : 10-20
Ophthalmological findings in movement disorders
Sahil Mehta, Aastha Takkar, Sucharita Ray, Vivek Lal
Department of Neurology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
|Date of Submission||21-Jul-2020|
|Date of Decision||30-Sep-2020|
|Date of Acceptance||18-Dec-2020|
|Date of Web Publication||17-Apr-2021|
Dr. Vivek Lal
Department of Neurology, PGIMER, Chandigarh.
Source of Support: None, Conflict of Interest: None
Ocular manifestations form an important clinical component of several movement disorders. Both hypokinetic and hyperkinetic movement disorders can involve the eye. Ophthalmological manifestations can arise due to dysfunction at the level of retina, optic nerves, oculomotor system, or subcortical or visual cortex. Ophthalmological findings help in differentiating various movement disorders and give a clue about their severity. These follow or may precede the diagnosis of movement disorders. Basal ganglia and its various nuclei especially substantia nigra pars reticulata play an important role in the genesis of eye movements through its connections with the superior colliculus. Eye movement abnormalities using quantitative recording techniques are now being considered as noninvasive biomarkers not only for the diagnosis but also to track the progression of disease as well as to study the effects of therapies in various movement disorders. Moreover, there is ample evidence of presence of retinal degeneration in various neurodegenerative diseases evaluated using optical coherence tomography. Various patterns of retinal thinning have been described in different movement disorders and have been found to have a correlation with the stage and severity of the disorder. In this review, we discuss ophthalmological findings of common hypokinetic and hyperkinetic movement disorders.
Keywords: Eye movements, Huntington’s disease, multiple system atrophy, ophthalmological, Parkinson’s disease, progressive supranuclear palsy, spinocerebellar ataxia, Wilson disease
|How to cite this article:|
Mehta S, Takkar A, Ray S, Lal V. Ophthalmological findings in movement disorders. Ann Mov Disord 2021;4:10-20
| Introduction|| |
Basal ganglia and its various nuclei especially substantia nigra pars reticulata (SNpr) play an important role in the genesis of eye movements. The basal ganglia controls saccadic eye movements through its connections with the superior colliculus (SC). The cortical projections from the frontal eye fields reach the SC through two pathways. One of them is the direct pathway which is excitatory. The second pathway reaches the SC through various synapses in the basal ganglia nuclei. This pathway is also excitatory; however, GABAergic output from basal ganglia ultimately results in inhibition or disinhibition of neurons in the colliculus. The caudate nucleus sends inhibitory projections to substantia nigra whose further inhibitory influence on the SC results in transient disinhibition of the SC which drives the brainstem nuclei to generate a saccade.,,[Figure 1] and [Figure 2] depict the anatomical pathways involved in the generation of saccades and pursuits.
|Figure 2: Central pathway for generation of smooth pursuit eye movement to left|
Click here to view
Both hypokinetic and hyperkinetic movement disorders can involve the eye., Ophthalmological manifestations can arise due to dysfunction at the level of retina, optic nerves, oculomotor system, or subcortical or visual cortex. Ophthalmological findings help in differentiating various movement disorders and give a clue about their severity. These follow or may precede the diagnosis of movement disorders. Eye movement abnormalities using quantitative recording techniques are now being considered as noninvasive biomarkers to study the natural progression of disease and effects of different therapies in various movement disorders with particular reference to Parkinson’s disease (PD) and Huntington’s disease.,,,, Abnormalities in eye movements rather have diagnostic and prognostic implications and hold promise for future research.
In this review, we will discuss ophthalmological findings of common hypokinetic and hyperkinetic movement disorders.
| Search Strategy and Selection Criteria|| |
We reviewed articles regarding ophthalmological findings in various movement disorders by searching literature published in electronic databases like Pub Med until July 2020 using the following keywords “Ocular abnormalities AND Movement Disorders,” “Ocular Features AND Parkinson’s disease,” “ Eye movement abnormalities AND Parkinson’s disease,” “ Eye movement abnormalities AND Progressive supranuclear palsy,” “Ocular Features AND Multiple System Atrophy,” ”Eye movement abnormalities AND Huntington’s disease,” Eye movement abnormalities AND Corticobasal degeneration,” “Eye movement abnormalities AND Spinocerebellar ataxia,” “ Eye movement abnormalities AND Wilson disease,” “ Eye movement abnormalities AND inborn error of metabolism,” “Retinal Thinning AND Parkinson’s disease,” “Retinal Thinning AND Progressive supranuclear palsy,” “Retinal thinning AND Multiple System Atrophy,” “Retinal Thinning AND Wilson disease,” Retinal thickening and ARSACS.” The cross references from the articles were also selected if found relevant. A total of 1672 articles were found using the keywords. Articles with full text and published in English were only included. Finally, a total of 95 articles were included for the review based on their relevance to the topic [Table 1]. Inclusion of all the articles was beyond the scope of this review.
| Parkinson’s Disease|| |
Besides the cardinal motor symptoms of bradykinesia, rigidity and tremor, a plethora of nonmotor symptoms occur in PD. A variety of ophthalmological abnormalities have been described in PD.
Visual and pupillary dysfunction
Oculo-visual symptoms have been reported in early stages of PD., These range from defects in visual acuity, color vision, contrast sensitivity, abnormal pupil reactivity, and visuo-spatial disturbances. They occur as a result of dysfunction at both the level of retina and subcortical-cortical connections. Reduced retinal dopamine levels, aberrant retinal dopamine signaling, retinal neuronal loss, and alpha-synuclein aggregation are some of the pathological mechanisms underlying these manifestations.
Biousse et al. studied 30 early untreated PD patients and found that complaints suggestive of ocular surface irritation like photophobia, tearing, and gritty sensation were more common in PD compared with controls. Other visual symptoms significantly more common in PD patients were hallucinations, blepharospasm, decreased blink rates, dry eyes, and decreased convergence amplitudes. The authors suggested that these visual symptoms occur due to PD itself and are not induced by medications.
Dry eyes occur in PD as a result of decreased blink rate as well as decreased production of tears secondary to autonomic dysfunction.
Changes in contrast sensitivity are related to retinal dopamine deficiency and improve with levodopa treatment., Similarly, impaired color vision measured with Farnsworth- Munsell 100 Hue and D-15 tests is also characteristically present in PD patients. Both these abnormalities are progressive and correlate with clinical motor severity.Pupillary abnormalities related to autonomic dysfunction and cataracts due to alpha-synuclein accumulation are common in PD. Diplopia can occur in approximately 30% patients with PD and is attributed to convergence insufficiency, strabismus, off periods, and related to visual hallucinations.
Blepharospasm with or without apraxia of eye lid opening can also occur in PD with prevalence of approximately 3%. These can predate the development of PD or may occur as a complication of dopaminergic therapy or deep brain stimulation.,
Video 1 [Additional file 1] depicts a patient of PD with Meige’s syndrome.
Retinal layer thinning measured by optical coherence tomography has been described in PD across various studies. Retinal thinning is most commonly seen in inferior and temporal quadrants and correlates with both clinical severity as well as dopaminergic neuronal loss in substantia nigra as measured by DAT scanning. Because of preferential degeneration of neurons within the inner retinal layers in Lewy body diseases, parafoveal thinning of ganglion cell-inner plexiform complex has been considered a relevant noninvasive imaging biomarker for diseases like PD.Few studies have also indicated the retinal nerve layer thinning to be related to visual hallucinations in patients with PD.
Ocular movement disorders in PD
Although eye movement abnormalities are more commonly and more severely affected in atypical parkinsonian disorders, subtle abnormalities do occur in PD. These abnormalities are more apparent on laboratory recordings using video oculography.,
| Clinical Findings|| |
Clinically, impairment of voluntary saccades mainly in the upward direction and impaired smooth pursuits can be seen in patients with PD. This is due to increased inhibition of superior colliculus through abnormal substantia nigra pars reticulata which is more involved in voluntary saccades than visually guided saccadic movements. Reflexive saccades are usually preserved in early stages of PD.
| Laboratory Findings|| |
Other saccadic abnormalities described in PD in the laboratory eye recordings include multistep or staircase saccades, delayed latency of voluntary saccades, errors in antisaccade and square wave jerks. White et al. documented abnormalities of saccadic initiation and trajectory and smooth pursuit gain in 14 PD patients using photoelectric infrared oculography. The severity of oculomotor dysfunction also correlated with the severity and duration of the disease.
Treatment-related ocular symptoms in PD
Treatment of PD can also produce visual symptoms. Amantadine can produce visual dysfunction due to corneal edema.Surgical treatments in the form of lesioning or deep brain stimulation can produce various ocular side effects depending upon the site. For example, subthalamic nucleus stimulation can cause skew deviation, torsional nystagmus, apraxia of eye lid opening, blepharospasm, and visual hallucinations. Posteroventral pallidotomy can cause homonymous hemianopia.
| Progressive Supranuclear Palsy|| |
Progressive supranuclear palsy (PSP) is a tauopathy usually characterized by symmetrical parkinsonism, axial rigidity, falls in the first year of disease, retrocollis, and frontal lobe involvement. It is known for a myriad of ocular findings due to the location of its pathology. The earliest eye movement abnormality seen in PSP is slowing of vertical saccades. Vertical supranuclear gaze palsy is considered the hallmark of the disease. Abnormalities in the downward saccades are picked up the earliest using optokinetic nystagmus.However, horizontal saccades are also affected in the advanced stages leading to complete ophthalmoplegia. Other abnormalities include moderately impaired smooth pursuit, prominent square wave jerks, markedly diminished blink rate, blepharospasm, and presence of apraxia of eye opening and closing. The “round the house sign” is often described in the context of vertical supranuclear gaze palsy. Both internuclear ophthalmoplegia and wall eyed bilateral internuclear ophthalmoplegia have also been reported in PSP. Blepharospasm and apraxia of eye lid opening are more commonly seen in PSP (30%) compared with PD (3%). Vertical supranuclear gaze palsy is not specific to PSP and has also been described in other inherited parkinsonian disorders such as Perry syndrome and Kufor Rakeb disease.,
Similarly, square wave jerks are frequently seen in PSP with prevalence ranging from 60 to 100% on the basis of various studies but can also occur in multiple system atrophy and corticobasal ganglionic degeneration though less commonly when compared with PSP.,,
Respondek et al. analyzed retrospective clinical data from an autopsy confirmed cohort of 206 PSP patients. The authors found vertical supranuclear gaze palsy in 67% patients throughout the disease course in pathologically confirmed PSP patients. The prevalence of abnormal saccades (defined as abnormal saccades in saccadic or smooth pursuit eye movements) was 62% and nonspecific visual symptoms (defined as painful eyes, dry eyes, visual blurring, diplopia, blepharospasm, ptosis, reduced blinking rate, and eyelid apraxia) were observed in 35% patients.
On the basis of levels of certainty, ocular motor dysfunction has been characterized into three levels according to the latest MDS-PSP criteria with lower level contributing a higher certainty to the diagnosis of PSP. O1 refers to presence of vertical supranuclear gaze palsy. O2 refers to slow velocity of vertical saccades and O3 means presence of frequent macro square wave jerks or “apraxia of eye lid opening.”
[Table 2] depicts the various ocular abnormalities across different stages of PSP. Video 2 [Additional file 2] depicts the classical vertical supranuclear gaze palsy in a patient of PSP. Video 3 [Additional file 3] shows the presence of apraxia of eyelid opening in a patient of PSP.
Anagnostou et al. studied eye movements in 12 patients with PSP using infrared corneal reflection device and correlated the occurrence of square wave jerks to the atrophy in the superior and inferior temporal gyri and not to the mid-brain atrophy seen on voxel based morphometric MRI studies.
Changes in retinal morphology have also been documented in PSP using spectral domain optical coherence tomography (SD-OCT). Stemplewitz et al. demonstrated retinal thinning in the inferior nasal and inferior temporal areas as well as reduced macular thickness in 22 patients with PSP. However, retinal changes did not correlate with disease duration or severity. Albrecht et al. found that the ratio between outer nuclear layer and outer plexiform layer with a cutoff of 3.1 and thickness of inner nuclear layer less than 46 µm had a sensitivity of 96% with specificity of 70% in differentiating PSP from PD.
| Multiple System Atrophy|| |
Multiple system atrophy is an adult onset oligodendrogliopathy characterized by presence of autonomic failure, symmetrical parkinsonism, cerebellar and pyramidal signs in varied combination.
Eye movement abnormalities
The eye movement abnormalities seen in MSA-C are those seen in cerebellar dysfunction such as gaze evoked nystagmus and impaired smooth pursuit. Other types of nystagmus described in MSA-C include downbeat and rebound nystagmus. Positional downbeat nystagmus and perverted head-shaking nystagmus (vertical nystagmus on horizontal head oscillation) is present in one-third of patients with MSA.,
On the contrary, MSA-P shows abnormalities in the form of excessive square wave jerks, mild to moderate saccadic hypometria, and impairment of VOR suppression and smooth pursuit. Saccadic velocities are normal in MSA-P. A minority of patients may also show mild vertical supranuclear gaze palsy.
Autonomic dysfunction can result in dry eyes and abnormal pupillary reactivity. Patients with ocular findings including conjugate eye movement abnormalities and ocular misalignment have shorter life expectancy signifying advanced or aggressive form of the disease.
A systematic review and meta-analysis found pooled difference in the average thickness of retinal nerve fiber layer in patients with MSA and controls to be –5.48 μm. Various studies have found significant thinning of retinal nerve fiber layers in all the quadrants except the temporal quadrant. Patients with MSA have a preferential loss of retinal ganglion cells which project to the magnocellular pathway (M- cells) vis-à-vis PD patients who have a preferential loss of retinal ganglion cells which project to the Parvocellular pathway (P-cells). M cells are mainly located in the peripheral retina and are not essential for visual acuity, whereas P-cells are predominantly located in the macula and relay colour discrimination and visual acuity. Patients with MSA have more affection of nasal sector of retinal nerve fiber layer and less atrophy of macula when compared with PD. A longitudinal study of 13 MSA patients found progressive thinning of retinal nerve fiber layer and macular ganglion cell complex in conjunction with relative preservation of temporal retinal nerve fiber layer over a duration of more than 1 year. The reduction in retinal thickness significantly correlates with disease severity and is more pronounced in MSA-P as compared to MSA-C.
| Corticobasal Syndrome|| |
Corticobasal syndrome is characterized by gradually progressive asymmetrical cortical and extrapyramidal dysfunction in the form of ideomotor limb apraxia, cortical myoclonus, alien limb phenomenon, and cortical sensory loss. It is a pathologically heterogeneous entity and can be a presenting syndrome of PSP, Corticobasal ganglionic degeneration, Picks disease, Alzheimer’s disease, Frontotemporal lobar degeneration, Dementia with lewy body, and Creutzfeldt Jacob disease.
Electrooculographic recordings in patients with corticobasal degeneration have shown increased latency of reflexive visually guided saccades.,The increase in the horizontal saccadic latency is more marked on the side of ideomotor apraxia. Another key abnormality apart from saccadic apraxia is increase in antisaccade errors. The velocity of saccades is usually normal in corticobasal degeneration., This is in contrast to PSP where prominent abnormalities are slow saccades (vertical > horizontal) and square wave jerks. Smooth pursuits are also impaired in corticobasal syndromes but less compared with PSP. Paralysis of vertical saccades occurs in advanced stages of the disease in comparison to PSP in which it is an early feature.
Albrecht et al. studied retinal nerve fiber layer thickness in 10 patients with corticobasal syndrome using spectral domain OCT. The authors found large variations in retinal parameters and macular thickness possibly owing to different underlying pathologies in these patients. A notable finding was increased thickness of outer nuclear layer.
| Huntington’s Disease|| |
Huntington’s disease is an autosomal dominant disorder caused by expanded cytosine-adenine-guanine (CAG) repeat in Huntingtin gene on chromosome 4. It is the most common cause of genetic chorea and is characterized by a triad of movement disorders, cognitive impairment, and neuropsychiatric manifestations.
The cardinal oculomotor abnormality seen in Huntington’s disease is saccadic apraxia which may be accompanied by head thrusts. These saccadic abnormalities are more on verbal instructions rather than visual cues. Saccades are slow and hypometric. Vertical saccades are affected more than the horizontal saccades. There is mild to moderate impairment of smooth pursuits. Slowing of saccades is prominently seen in Westphal variant of Huntington’s disease.
Video 4 [Additional file 4] depicts classical saccadic apraxia with head thrusts in a patient of Huntington’s disease with positive family history.
Eye movement recordings can also show prolonged saccadic latency and problems in antisaccades and memory guided saccades. Various studies have also shown saccadic abnormalities in the form of increased latency of saccades and errors in antisaccades and memory guided saccades in presymptomatic HD patients. All these saccadic abnormalities correlate with earlier onset of clinical symptoms in presymptomatic patients.,
Kersten et al. studied morphology of optic nerve and macula in 39 patients with Huntington’s disease using spectral domain optical coherence tomography. The authors found reduced thickness of retinal nerve fiber layer in the temporal sector as well as macula. A significant negative correlation was demonstrated between thickness of temporal retinal nerve fiber layer and macular volumes with disease duration and severity.
| Spinocerebellar Ataxias|| |
Spinocerebellar ataxias are autosomal dominant trinucleotide repeat disorders which display clinical, pathological, and genetic heterogeneity but are characterized by many extrapyramidal manifestations in addition to ataxia.
A variety of eye movement abnormalities occur in SCAs. These range from gaze evoked nystagmus, dysmetric saccades, slow saccades, ophthalmoparesis, abnormalities of smooth pursuits, and square wave jerks.,, Slowing of saccades occur prominently in SCA 2, the most common form of SCA in India. However, these can also occur to a lesser extent in SCA3, SCA4, and SCA 28. Wadia et al. have described slowing of horizontal saccades in the early stages of SCA 2 when compared with other eye movement abnormalities., Degeneration of excitatory burst neurons in the pontine tegmentum is the most likely cause of slow horizontal saccades in SCA 2. Errors in antisaccades and memory guided saccades occur due to cognitive, in particular, executive deficits and are seen in SCA2 and SCA 17. Pigmentary retinopathy is usually seen in SCA 7 and ophthalmoplegia is quite specific of SCA 28. Lesions of the cerebellar oculomotor vermis (lobules VI and VII), fastigial nucleus, and flocculus lead to impaired horizontal smooth pursuit, whereas damage to oculomotor circuit involving oculomotor vermis and fastigial nucleus is associated with dysmetric horizontal saccades.
Reticulotegmental nucleus of the pons (RTTG) also called as nucleus of Bechtrew receives oculomotor afferents from the cerebral cortex’s frontal eye field, supplementary eye field, and from the superior colliculus and conveys information to the cerebellar flocculus, fastigial nucleus, and oculomotor vermis. RTTG plays a crucial role in the accuracy of horizontal saccades and generation of horizontal smooth pursuits. Pathological studies have implicated degeneration of RTTG in the development of dysmetric horizontal saccades and impaired smooth pursuits in SCAs especially SCA-1, SCA-2, and SCA-3.
Video 5 [Additional file 5] depicts ocular motor abnormalities in a patient with SCA-2.
Pula et al. performed OCT in 24 patients with genetically proven SCA. The authors found significant thinning at the peripapillary retinal nerve fiber layer in SCA2 and SCA 3 while perifoveal macula had significant thinning in SCA1, SCA3, and SCA 6 compared with controls. A significant negative correlation was found between disease severity as measured by SARA score (Scale for the Assessment and Rating of Ataxia) and retinal nerve fiber layer thickness in patients with SCA 2 and SCA 3.
On the contrary, abnormal retinal thickening and retinal striations has been reported in autosomal recessive-spastic ataxia of Charlevoix-Saguenay (ARSACS). A cut-off value of 119 μm in average peripapillary retinal nerve fiber layer thickness has a sensitivity of 100% and specificity of 99.4% in differentiating ARSACS from other causes of genetic ataxia.
| Wilson’s Disease|| |
Wilson’s disease is a disorder of copper metabolism that causes widespread effects on the body, predominantly hepatic and neurological. The neurological manifestations are characterized by tremor, dystonia, ataxia, and parkinsonism.
Involvement of cornea and lens
The two distinct ocular manifestations seen in Wilson disease are Kayser Fleischer’s rings (KF rings) and sunflower cataract and occur due to excess deposition of copper. KF rings due to deposition of copper in the Descemet’s membrane usually start superiorly, then inferiorly and then become circumferential. These can be the presenting feature of Wilson’s disease and may disappear with treatment.,
Eye movement abnormalities
Eye movement abnormalities generally do not occur in Wilson’s disease clinically. However, electrooculographic recordings have shown that oculomotor system can be affected in Wilson’s disease. Ingster-Moati et al. studied ocular motility defects in 34 patients with Wilson disease by electrooculography. 91% of their study cohort had abnormalities of ocular motility. Abnormalities of vertical smooth pursuit were seen in 85% patients. The authors concluded that in Wilson disease: Vertical movements are affected more than horizontal eye movements, and pursuits are affected more than saccades. Lesniak et al. found impaired voluntary control of saccades and disturbances in smooth pursuit eye movements on electrographic recordings in their study of 50 patients with Wilson disease while there was sparing of reflexive saccades.,
Visual impairment can occur in Wilson’s disease secondary to retinal degeneration and vitamin A malabsorption. Electrophysiological studies have demonstrated prolonged latencies with decreased amplitudes on pattern reversal visual evoked potential recordings and electroretinograms. These abnormalities also improve partially pari passu with the clinical improvement after decoppering therapy.
Optical coherence tomography studies have demonstrated retinal degeneration in patients with Wilsons disease in the form of reduced thickness of peripapillary retinal nerve fiber layer, macula, inner plexiform layer, and inner nuclear layer. Another study of 58 patients not only demonstrated reduced thickness of retinal nerve fiber layer and macula but also found significant negative correlation between OCT parameters and neurological severity. Langwinska et al. also found significantly thinner retinal nerve fiber layer and macular volume in patients who have a positive MRI compared with those with negative MRI findings.
| Other Inborn Errors of Metabolism|| |
Eye movement abnormalities can be an important clinical diagnostic clue in differentiating amongst various inborn errors of metabolism. Vertical supranuclear gaze palsy is seen in Niemann Pick C, whereas horizontal gaze palsy is seen in Gaucher’s disease., “The round the house” sign has also been described in the context of Niemann Pick type C. This sign is not specific but suggests rostral interstitial nucleus of medial longitudinal fasciculus (riMLF) dysfunction. Eye involvement in Cerebrotendinous xanthomatosis include presence of abnormal pursuits, increased saccadic intrusions, multistep saccades and antisaccade deficits. This is due to the affection of dentate nuclei.
| Conclusion|| |
Movement disorders can affect any part of visual pathways ranging from optic nerves, retina, visual cortex, and most importantly ocular motor system. Eye examination plays a pivotal role in the field of movement disorders. It helps in narrowing the differential diagnosis in complex presentations of both hypokinetic as well as hyperkinetic movement disorders. Recent studies are now shedding light on the role of retina in neurodegenerative disorders and its value as a biomarker. Hence, it is crucial to have a knowledge of the various aspects of neuro-ophthalmological examination while evaluating movement disorders. [Table 3] depicts salient neuroophthalmological features in common movement disorders.
|Table 3: Salient neuroophthalmological features of common movement disorders|
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| References|| |
Basso MA, Sommer MA. Exploring the role of the substantia nigra pars reticulata in eye movements. Neuroscience 2011;198:205-12. Doi: 10.1016/j.neuroscience.2011.08.026
Shires J, Joshi S, Basso MA. Shedding new light on the role of the BG-SC pathway in eye movements. Curr Opin Neurobiol 2010;20:717-25.
Hikosaka O, Takikawa Y, Kawagoe R. Role of the basal ganglia in the control of purposive saccadic eye movements. Physiol Rev 2000;80:953-78.
Puri S, Shaikh AG. Basic and translational neuro-ophthalmology of visually guided saccades: Disorders of velocity. Expert Rev Ophthalmol 2017;12:457-73. doi: 10.1080/17469899.2017.1395695
Watanabe M, Munoz DP. Probing basal ganglia functions by saccade eye movements. Eur J Neurosci 2011;33:2070-90.
Lal V, Truong D. Eye movement abnormalities in movement disorders. Clin Park Relat Disord 2019;1:54-63. doi: 10.1016/j.prdoa.2019.08.004
Jung I, Kim J-S. Abnormal eye movements in parkinsonism and movement disorders. J Mov Disord 2019;12:1-13.
Termsarasab P, Thammongkolchai T, Rucker JC, Frucht SJ. The diagnostic value of saccades in movement disorder patients: A practical guide and review. J Clin Mov Disord. 2015;2:1-10. doi: 10.1186/s40734-015-0025-4
Shaikh AG, Zee DS. Eye movement research in the twenty-first century—a window to the brain, mind, and more. Cerebellum 2018;17:252-8.
Blekher T, Weaver M, Rupp J, Nichols WC, Hui SL, Gray J, et al
. Multiple step pattern as a biomarker in Parkinson disease. Park Relat Disord 2009;15:506-10. doi: 10.1016/j.parkreldis.2009.01.002
Michell AW, Xu Z, Fritz D, Lewis SJG, Foltynie T, Williams-Gray CH, et al
. Saccadic latency distributions in Parkinson’s disease and the effects of L-DOPA. Exp Brain Res 2006;174:7-18.
Antoniades CA, Xu Z, Mason SL, Carpenter RHS, Barker RA. Huntington’s disease: Changes in saccades and hand-tapping over 3 years. J Neurol 2010;257:1890-8.
Anderson TJ, MacAskill MR. Eye movements in patients with neurodegenerative disorders. Nat Rev Neurol 2013;9:74-85. doi: 10.1038/nrneurol.2012.273
Guo L, Normando EM, Shah PA, De Groef L, Cordeiro MF. Oculo-visual abnormalities in Parkinson’s disease: Possible value as biomarkers. Mov Disord 2018;33:1390-406.
Ekker MS, Janssen S, Seppi K, Poewe W, de Vries NM, Theelen T, et al
. Ocular and visual disorders in Parkinson’s disease: Common but frequently overlooked. Park Relat Disord 2017;40:1-10. doi: 10.1016/j.parkreldis.2017.02.014
Biousse V, Skibell BC, Watts RL, Loupe DN, Drews-Botsch C, Newman NJ. Ophthalmologic features of Parkinson’s disease. Neurology 2004;62:177-80.
Tamer C, Melek IM, Duman T, Öksüz H. Tear film tests in Parkinson’s disease patients. Ophthalmology 2005;112:1795.e1-8.
Thomas Hutton JT, Morris JL, Elias JW. Levodopa improves spatial contrast sensitivity in Parkinson’s disease. Arch Neurol 1993;50:721-4.
Bulens C, Meerwaldt JD, Van der Wildt GJ, Van Deursen JBP. Effect of levodopa treatment on contrast sensitivity in Parkinson’s disease. Ann Neurol 1987;22:365-9.
Weil RS, Schrag AE, Warren JD, Crutch SJ, Lees AJ, Morris HR. Visual dysfunction in Parkinson’s disease. Brain 2016;139:2827-43.
Klettner A, Richert E, Kuhlenbäumer G, Nölle B, Bhatia KP, Deuschl G, et al
. Alpha synuclein and crystallin expression in human lens in Parkinson’s disease. Mov Disord 2016;31:600-1.
Schindlbeck KA, Schönfeld S, Naumann W, Friedrich DJ, Maier A, Rewitzer C, et al
. Characterization of diplopia in non-demented patients with Parkinson’s disease. Park Relat Disord 2017;45:1-6. doi: 10.1016/j.parkreldis.2017.09.024
Rana AQ, Kabir A, Dogu O, Patel A, Khondker S. Prevalence of blepharospasm and apraxia of eyelid opening in patients with parkinsonism, cervical dystonia and essential tremor. Eur Neurol 2012;68:318-21.
Micheli F, Scorticati MC, Folgar S, Gatto E. Development of Parkinson’s disease in patients with Blepharospasm. Mov Disord 2004;19:1069-72.
Ramírez-Gómez CC, Zúñiga-Ramírez C, Contartese ML, Montilla V, Gramajo J, Micheli F. Blepharospasm as a manifestation of peak of dose dyskinesia in Parkinson disease. Clin Neuropharmacol 2019;42:14-6.
Ahn J, Lee JY, Kim TW, Yoon EJ, Oh S, Kim YK, et al
. Retinal thinning associates with nigral dopaminergic loss in de novo Parkinson disease. Neurology 2018;91:e1003-12.
Murueta-Goyena A, del Pino R, Reyero P, Galdós M, Arana B, Lucas-Jiménez O, et al
. Parafoveal thinning of inner retina is associated with visual dysfunction in Lewy body diseases. Mov Disord 2019;34:1315-24.
Lee JY, Kim JM, Ahn J, Kim HJ, Jeon BS, Kim TW. Retinal nerve fiber layer thickness and visual hallucinations in Parkinson’s disease. Mov Disord 2014;29:61-7.
White OB, Saint-Cyr JA, Tomlinson RD, Sharpe JA. Ocular motor deficits in parkinson’s disease. II. Control of the saccadic and smooth pursuit systems. Brain 1983;106 (Pt 3):571-87.
Jeng BH, Galor A, Lee MS, Meisler DM, Hollyfield JG, Schoenfield L, et al
. Amantadine-associated corneal edema potentially irreversible even after cessation of the medication. Ophthalmology 2008;115:1540-4.
Baizabal-Carvallo JF, Jankovic J. Movement disorders induced by deep brain stimulation. Parkinsonism Relat Disord 2016;25:1-9.
Biousse V, Newman NJ, Carroll C, Mewes K, Vitek JL, Bakay RA, et al
. Visual fields in patients with posterior gpi pallidotomy. Neurology 1998;50:258-65.
Litvan I, Agid Y, Calne D, Campbell G, Dubois B, Duvoisin RC, et al
. Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): Report of the NINDS-SPSP international workshop. Neurology 1996;47:1-9.
Phokaewvarangkul O, Bhidayasiri R. How to spot ocular abnormalities in progressive supranuclear palsy? A practical review. Transl Neurodegener 2019;8:1-14.
Garbutt S, Riley DE, Kumar AN, Han Y, Norwood MB, Leigh RJ. Abnormalities of optokinetic nystagmus in progressive supranuclear palsy. J Neurol Neurosurg Psychiatry 2004;75:1386-94.
Quinn N, Leigh RJ. The “round the houses” sign in progressive supranuclear palsy. Ann Neurol 1996;40:951.
Ushio M, Iwasaki S, Chihara Y, Murofushi T. Wall-eyed bilateral internuclear ophthalmoplegia in a patient with progressive supranuclear palsy. J Neuro-Ophthalmology 2008;28:93-6.
Golbe LI, Lepore FE, Davis PH. Eyelid movement abnormalities in progressive supranuclear palsy. Mov Disord 1989;4:297-302.
Mishima T, Fujioka S, Tomiyama H, Yabe I, Kurisaki R, Fujii N, et al
. Establishing diagnostic criteria for Perry syndrome. J Neurol Neurosurg Psychiatry 2018;89:482-7.
Williams DR, Hadeed A, Najim al-Din AS, Wreikat AL, Lees AJ. Kufor Rakeb disease: Autosomal recessive, levodopa-responsive Parkinsonism with pyramidal degeneration, supranuclear gaze palsy, and dementia. Mov Disord 2005;20:1264-71.
Rascol O, Sabatini U, Simonetta-Moreau M, Montastruc JL, Rascol A, Clanet M. Square wave jerks in Parkinsonian syndromes. J Neurol Neurosurg Psychiatr 1991;54:599-602.
Vidailhet M, Rivaud S, Gouider-khouja N, Pillon B, Bonnet A, Gaymard B, et al
. Eye movements in pmhnsonian syndromes. Ann Neurol 1994;35:420-6.
Respondek G, Kurz C, Arzberger T, Compta Y, Englund E, Ferguson LW, et al
. Which ante mortem clinical features predict progressive supranuclear palsy pathology? Mov Disord 2017;32:995-1005.
Höglinger GU, Respondek G, Stamelou M, Kurz C, Josephs KA, Lang AE, et al
. Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria. Mov Disord 2017;32:853-64.
Anagnostou E, Karavasilis E, Potiri I, Constantinides V, Efstathopoulos E, Kapaki E, et al
. A cortical substrate for square-wave jerks in progressive supranuclear palsy. J Clin Neurol 2020;16:37-45.
Gulmez Sevim D, Unlu M, Gultekin M, Karaca C, Mirza M, Mirza GE. Evaluation of retinal changes in progressive supranuclear palsy and Parkinson disease. J Neuroophthalmol 2018;38:151-5.
Stemplewitz B, Kromer R, Vettorazzi E, Hidding U, Frings A, Buhmann C. Retinal degeneration in progressive supranuclear palsy measured by optical coherence tomography and scanning laser polarimetry. Sci Rep 2017;7:1-10.
Albrecht P, Müller AK, Südmeyer M, Ferrea S, Ringelstein M, Cohn E, et al
. Optical coherence tomography in parkinsonian syndromes. PLoS One2012;7(4):e34891.
Fanciulli A, Wenning GK. Multiple-system atrophy. N Engl J Med 2015;372:249-63. doi: 10.1056/NEJMra1311488
Anderson T, Luxon L, Quinn N, Daniel S, Marsden CD, Bronstein A. Oculomotor function in multiple system atrophy: Clinical and laboratory features in 30 patients. Mov Disord 2008;23:977-84.
Garcia MD, Pulido JS, Coon EA, Chen JJ. Ocular features of multiple system atrophy. J Clin Neurosci 2018;47:234-9. doi: 10.1016/j.jocn.2017.10.028
Mendoza-Santiesteban CE, Gabilondo I, Palma JA, Norcliffe-Kaufmann L, Kaufmann H. The retina in multiple system atrophy: Systematic review and meta-analysis. Front Neurol2017;8:206.
Saito A, Lee BB, Kremers J, Silveira LCL, Filho S, Kilavik BE, et al
. Morphology and physiology of primate. Prog Brain Res 2004;144:21-46. Available from: http://www.sciencedirect.com/science/article/pii/S0079612303144020
Fischer MD, Synofzik M, Heidlauf R, Schicks J, Srulijes K, Kernstock C, et al
. Retinal nerve fiber layer loss in multiple system atrophy. Mov Disord 2011;26:914-6. doi: 10.1002/mds.23523
Mendoza-Santiesteban CE, Palma JA, Martinez J, Norcliffe-Kaufmann L, Hedges TR, Kaufmann H. Progressive retinal structure abnormalities in multiple system atrophy. Mov Disord 2015;30:1944-53.
Ahn J, Lee JY, Kim TW. Retinal thinning correlates with clinical severity in multiple system atrophy. J Neurol 2016;263:2039-47.
Whitwell JL, Jack CR, Boeve BF, Parisi JE, Ahlskog JE, Drubach DA, et al
. Imaging correlates of pathology in corticobasal syndrome. Neurology 2010;75:1879-87.
Boeve BF. The multiple phenotypes of corticobasal syndrome and corticobasal degeneration: Implications for further study. J Mol Neurosci 2011;45:350-3.
Rottach KG, Riley DE, Discenna AO, Zivotofsky AZ, John Leigh R. Dynamic properties of horizontal and vertical eye movements in Parkinsonian syndromes. Ann Neurol 1996;39:368-77.
Rivaud-Péchoux S, Vidailhet M, Gallouedec G, Litvan I, Gaymard B, Pierrot-Deseilligny C. Longitudinal ocular motor study in corticobasal degeneration and progressive supranuclear palsy. Neurology 2000;54:1029-32.
Videnovic A, Shannon KM. Huntington disease and other choreas. Hyperkinetic Mov Disord 2012;23-54.
Leigh RJ, Newma SA, Folstein SE, Lasker AG, Jensen BA. Abnormal ocular motor control in Huntington’s disease. Neurology 1983;33:1268-75.
Lasker AG, Zee DS. Ocular motor abnormalities in Huntington’s disease. Vision Res 1997;37:3639-45.
Peltsch A, Hoffman A, Armstrong I, Pari G, Munoz DP. Saccadic impairments in Huntington’s disease. Exp Brain Res 2008;186:457-69.
Winder JY, Roos RAC. Premanifest Huntington’s disease: Examination of oculomotor abnormalities in clinical practice. PLoS One 2018;13:1-8.
Kersten HM, Danesh-Meyer HV, Kilfoyle DH, Roxburgh RH. Optical coherence tomography findings in Huntington’s disease: A potential biomarker of disease progression. J Neurol 2015;262:2457-65.
Soong BW, Morrison PJ. Spinocerebellar ataxias. 1st ed. Vol. 155. Handbook of Clinical Neurology. Elsevier B.V.; 2018. pp. 143-74. Available from: http://dx.doi.org/10.1016/B978-0-444-64189-2.00010-X
Stephen CD, Schmahmann JD. Eye Movement Abnormalities Are Ubiquitous in the Spinocerebellar Ataxias. Cerebellum 2019;18(6):1130-1136.
Rosini F, Pretegiani E, Battisti C, Dotti MT, Federico A, Rufa A. Eye movement changes in autosomal dominant spinocerebellar ataxias. Neurol Sci2020;41(7):1719-1734.
Moscovich M, Okun MS, Favilla C, Figueroa KP, Pulst SM, Perlman S, et al
. Clinical evaluation of eye movements in spinocerebellar ataxias: A prospective multicenter study. J Neuro-Ophthalmol 2015;35:16-21.
Wadia NH, Swami RK. A new form of heredo-familial spinocerebellar degeneration with slow eye movements (nine families). Brain 1971;94:359-74.
Wadia N, Pang J, Desai J, Mankodi A, Desai M, Chamberlain S. A clinicogenetic analysis of six Indian spinocerebellar ataxia (SCA2) pedigrees. The significance of slow saccades in diagnosis. Brain 1998;121:2341-55.
Geiner S, Horn AKE, Wadia NH, Sakai H, Büttner-Ennever JA. The neuroanatomical basis of slow saccades in spinocerebellar ataxia type 2 (Wadia-subtype). Prog Brain Res 2008;171:575-81.
Mariotti C, Brusco A, Di Bella D, Cagnoli C, Seri M, Gellera C, et al
. Spinocerebellar ataxia type 28: A novel autosomal dominant cerebellar ataxia characterized by slow progression and ophthalmoparesis. Cerebellum 2008;7:184-8.
Rüb U, Schultz C, Del Tredici K, Braak H. Early involvement of the tegmentopontine reticular nucleus during the evolution of Alzheimer’s disease-related cytoskeletal pathology. Brain Res 2001;908:107-12.
Btittner-ennever JA, Horn AK. Anatomical substrates of oculomotor control and Anja KE Hornt. Curr Opin Neurobiol 1997;7:872-9.
Rüb U, Bürk K, Schöls L, Brunt ER, De Vos RAI, Orozco Diaz G, et al
. Damage to the reticulotegmental nucleus of the pons in spinocerebellar ataxia type 1, 2, and 3. Neurology 2004;63:1258-63.
Pula JH, Towle VL, Staszak VM, Cao D, Bernard JT, Gomez CM. Retinal nerve fibre layer and macular thinning in spinocerebellar ataxia and cerebellar multisystem atrophy. Neuro-Ophthalmology 2011;35:108-14.
Yu-Wai-Man P, Pyle A, Griffin H, Santibanez-Korev M, Rita Horvath R, Chinnery PF. Abnormal retinal thickening is a common feature among patients with ARSACS-related phenotypes. Br J Ophthalmol 2014;98:711-3.
Parkinson MH, Bartmann AP, Clayton LMS, Nethisinghe S, Pfundt R, Paul Chapple J, et al
. Optical coherence tomography in autosomal recessive spastic ataxia of charlevoix-Saguenay. Brain 2018;141:989-99.
Aggarwal A, Bhatt M. The pragmatic treatment of Wilson’s disease. Mov Disord Clin Pract 2014;1:14-23.
Goel S, Sahay P, Maharana PK, Titiyal JS. Ocular manifestations of Wilson’s disease. BMJ Case Rep 2019;12:1-2.
Walshe JM. The eye in Wilson disease. QJM 2011;104:451-3.
Ingster-Moati I, Bui Quoc E, Pless M, Djomby R, Orssaud C, Guichard JP, et al
. Ocular motility and Wilson’s disease: A study on 34 patients. J Neurol Neurosurg Psychiatry 2007;78:1199-201.
Leśniak M, Członkowska A, Seniów J. Abnormal antisaccades and smooth pursuit eye movements in patients with Wilson’s disease. Mov Disord 2008;23:2067-73.
Satishohandra P, Ravishankar Naik K. Visual pathway abnormalities Wilson’s disease: an electrophysiological study using electroretinography and visual evoked potentials. J Neurol Sci 2000;176:13-20.
Albrecht P, Müller AK, Ringelstein M, Finis D, Geerling G, Cohn E, et al
. Retinal neurodegeneration in Wilson’s disease revealed by spectral domain optical coherence tomography. PLoS One 2012;7:14-6.
Langwińska-Wośko E, Litwin T, Dzieżyc K, Karlinski M, Członkowska A. Optical coherence tomography as a marker of neurodegeneration in patients with Wilson’s disease. Acta Neurol Belg 2017;117:867-71.
Langwińska-Wośko E, Litwin T, Szulborski K, Członkowska A. Optical coherence tomography and electrophysiology of retinal and visual pathways in Wilson’s disease. Metab Brain Dis 2016;31:405-15.
Koens LH, Tijssen MAJ, Lange F, Wolffenbuttel BHR, Rufa A, Zee DS, et al
. Eye movement disorders and neurological symptoms in late-onset inborn errors of metabolism. Mov Disord 2018;33:1844-56.
Gupta A, Kumar N, Saharan R, Rastogi P, Vishnu VY, Lal V. Teaching video neuro images: Vertical supranuclear ophthalmoparesis. Neurology 2016;86:e108.
Sharma S, Lal V, Das R. Horizontal gaze palsy with progressive myoclonic epilepsy: Rare presentation of Gaucher’s disease. Neurol India 2013;61:177-8.
] [Full text]
Crespi J, Bråthen G, Quist-Paulsen P, Pagonabarraga J, Roig-Arnall C. Facial dystonia with facial grimacing and vertical gaze palsy with “round the Houses” sign in a 29-year-old woman. Neuro-Ophthalmol 2016;40:37-41.
Rosini F, Pretegiani E, Mignarri A, Optican LM, Serchi V, De Stefano N, et al
. The role of dentate nuclei in human oculomotor control: Insights from cerebrotendinous xanthomatosis. J Physiol 2017;595:3607-20.
Helen L, Huw M. Progressive Supranuclear Palsy. In: Parkinson’s disease and movement disorders. 6th ed.Jankovic J, Tolosa E, editors. New Delhi: Wolters kluwer; 2015. pp. 150-60.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]