Parkinson's Disease

Parkinson’s Disease (PD) is one of the most common neurodegenerative diseases worldwide, affecting 1% of the population older than 65³. The evaluation of oculo-motor function may provide valuable information regarding early disease detection or disease progression⁴. Studies report an abnormal oculomotor function in 75-87.5% of Parkinson’s disease (PD) patients^1,2. These dysfunctions may precede or follow motor symptoms.

The most common reported oculomotor dysfunctions are impairments in saccades, smooth pursuit, and vergence^1,2,5. The Substantia Nigra pars reticulata is thought to modulate both saccades and smooth pursuit eye movements⁶. Therefore, the degeneration of this region in PD results in both saccades and smooth pursuit impairments⁷.

Voluntary saccades are hypometric in PD, which occurs more in the vertical than in the horizontal place^{8,9,4,10–12}. The ability to inhibit unwanted saccades is also impaired^4,10, which may be associated with dopaminergic depletion in the prefrontal cortex. Reaction times and the maximum saccadic velocity of horizontal gaze are slower in PD than controls^11,14 and correlate with increased reaction time of finger movement for the finger ipsilateral to the direction of horizontal gaze, but not for the contralateral finger, which indicates that bradykinesia also exists in eye movements in PD¹¹.

Fixation stabilization may also be impaired¹³. In addition, antisaccades are also altered in PD. In a meta-analysis, the authors reported a significantly increased antisaccade latency and error rate in Parkinson’s¹⁵. In addition, a prospective study concluded that antisaccade latency is a predictive marker of the 5 year onset of freezing of gait in PD patients, a PD sign associated with disease severity and progression¹⁶.

Smooth pursuit abnormalities have been found in almost 70% of PD patients¹¹. Patients show a reduced smooth pursuit gain and abnormalities in smooth pursuit may be correlated with disease severity⁵. Smooth pursuit movements may be interrupted by small unwanted saccades^5,11,14. In addition, smooth pursuit eye movements could be affected in early PD¹⁷.

Studies report an abnormal convergence in about 70% of PD patients¹¹, which can often result in double vision¹⁸. Pupil reactivity is also affected in PD. Pupil diameters are larger and have unequal sizes after light adaptation¹⁹. In addition, light reflex latency was significantly increased, whereas amplitude, maximum constriction velocity, and maximum acceleration were decreased in PD patients^19–21. In fact, a recent clinical study found that the pupillary contraction velocity decreased with disease progression, which suggests that pupil constriction velocity could identify PD progression. All these findings suggest an autonomic imbalance in PD involving the parasympathetic system. Autonomic dysfunction can be an early manifestation of PD and be present in the prodomal stages at least 5 years before diagnosis and as long as 20 years before defined disease²². Therefore, changes in pupil reaction could be present in the prodromal phase¹⁴. Pupillometry is a fast, objective, noninvasive, and low-cost technique, which makes pupillary abnormalities an attractive prospect as potential nonmotor biomarkers for early PD detection and monitoring of disease progression²³. Eye-tracking tasks could be useful as potential biomarkers for motor or cognitive disease burden in Parkinson's disease²⁴.

1. Corin MS, Elizan TS, Bender MB. Oculomotor function in patients with Parkinson’s disease. J Neurol Sci. 1972;15(3):251-265. doi:10.1016/0022-510X(72)90068-8

2. Cipparrone L, Ginanneschi A, Degl’Innocenti F, Porzio P, Pagnini P, Marini P. Electro-oculographic routine examination in Parkinson’s disease. Acta Neurol Scand. 1988;77(1):6-11. doi:10.1111/j.1600-0404.1988.tb06966.x

3. Wirdefeldt K, Adami HO, Cole P, Trichopoulos D, Mandel J. Epidemiology and etiology of Parkinson’s disease: a review of the evidence. Eur J Epidemiol. 2011;26 Suppl 1:S1-58. doi:10.1007/s10654-011-9581-6 

4. Jung I, Kim JS. Abnormal Eye Movements in Parkinsonism and Movement Disorders. J Mov Disord. 2019;12(1):1-13. doi:10.14802/jmd.18034

5. Frei K. Abnormalities of smooth pursuit in Parkinson’s disease: A systematic review. Clin Park Relat Disord. 2021;4:100085. doi:10.1016/j.prdoa.2020.100085

6. Basso MA, Pokorny JJ, Liu P. Activity of substantia nigra pars reticulata neurons during smooth pursuit eye movements in monkeys. Eur J Neurosci. 2005;22(2):448-464. doi:10.1111/j.1460-9568.2005.04215.x

7. Tanaka M. Involvement of the central thalamus in the control of smooth pursuit eye movements. J Neurosci Off J Soc Neurosci. 2005;25(25):5866-5876. doi:10.1523/JNEUROSCI.0676-05.2005

8. Terao Y, Fukuda H, Hikosaka O. What do eye movements tell us about patients with neurological disorders? — An introduction to saccade recording in the clinical setting —. Proc Jpn Acad Ser B. 2017;93(10):772-801. doi:10.2183/pjab.93.049
   
   

9. Kassavetis P, Kaski D, Anderson T, Hallett M. Eye Movement Disorders in Movement Disorders. Mov Disord Clin Pract. 2022;9(3):284-295. doi:10.1002/mdc3.13413

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11. Shibasaki H, Tsuji S, Kuroiwa Y. Oculomotor abnormalities in Parkinson’s disease. Arch Neurol. 1979;36(6):360-364. doi:10.1001/archneur.1979.00500420070009

12. Shaikh AG, Ghasia FF. Saccades in Parkinson’s disease: Hypometric, slow, and maladaptive. Prog Brain Res. 2019;249:81-94. doi:10.1016/bs.pbr.2019.05.001

13. Ba F, Sang TT, He W, Fatehi J, Mostofi E, Zheng B. Stereopsis and Eye Movement Abnormalities in Parkinson’s Disease and Their Clinical Implications. Front Aging Neurosci. 2022;14:783773. doi:10.3389/fnagi.2022.783773

14. Armstrong RA. Oculo-Visual Dysfunction in Parkinson’s Disease. J Park Dis. 2015;5(4):715-726. doi:10.3233/JPD-150686

15. Waldthaler J, Stock L, Student J, Sommerkorn J, Dowiasch S, Timmermann L. Antisaccades in Parkinson’s Disease: A Meta-Analysis. Neuropsychol Rev. 2021;31(4):628-642. doi:10.1007/s11065-021-09489-1

16. Gallea C, Wicki B, Ewenczyk C, et al. Antisaccade, a predictive marker for freezing of gait in Parkinson’s disease and gait/gaze network connectivity. Brain. 2021;144(2):504-514. doi:10.1093/brain/awaa407

17. Bares M, Brázdil M, Kanovský P, et al. The effect of apomorphine administration on smooth pursuit ocular movements in early Parkinsonian patients. Parkinsonism Relat Disord. 2003;9(3):139-144. doi:10.1016/s1353-8020(02)00015-9

18. Śmiłowska K, Wowra B, Sławek J. Double vision in Parkinson’s Disease: a systematic review. Neurol Neurochir Pol. 2020;54(6):502-507. doi:10.5603/PJNNS.a2020.0092

19. Micieli G, Tassorelli C, Martignoni E, et al. Disordered pupil reactivity in Parkinson’s disease. Clin Auton Res Off J Clin Auton Res Soc. 1991;1(1):55-58. doi:10.1007/BF01826058
    
    
20. Giza E, Fotiou D, Bostantjopoulou S, Katsarou Z, Karlovasitou A. Pupil Light Reflex in Parkinson’s Disease: Evaluation With Pupillometry. Int J Neurosci. 2011;121(1):37-43. doi:10.3109/00207454.2010.526730
    
    
21. Biousse V, Skibell BC, Watts RL, Loupe DN, Drews-Botsch C, Newman NJ. Ophthalmologic features of Parkinson’s disease. Neurology. 2004;62(2):177-180. doi:10.1212/01.wnl.0000103444.45882.d8
    
    
22. Postuma RB, Gagnon JF, Pelletier A, Montplaisir J. Prodromal autonomic symptoms and signs in Parkinson’s disease and dementia with Lewy bodies. Mov Disord Off J Mov Disord Soc. 2013;28(5):597-604. doi:10.1002/mds.25445
    
    
23. Guo L, Normando EM, Shah PA, De Groef L, Cordeiro MF. Oculo-visual abnormalities in Parkinson’s disease: Possible value as biomarkers. Mov Disord Off J Mov Disord Soc. 2018;33(9):1390-1406. doi:10.1002/mds.27454
    
    

24. Crotty GF, Chwalisz BK. Ocular motor manifestations of movement disorders. Curr Opin Ophthalmol. 2019;30(6):443-448. doi:10.1097/ICU.0000000000000605