" Visual Characterization of Parkinson's Patients and Oculomotor or Perceptual Therapy"

Parkinson Disease Clinical Trial

Official title:

"Characterization of Visual Problems in Patients With Parkinson's Disease and Application of an Oculomotor and/or Perceptual Therapy Program"

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06032130
• Other study ID #: 2161984
• Status: Recruiting
• Start date: September 29, 2023
• Est. completion date: June 1, 2026

Study information

• Verified date: November 2023
• Source: University of Valencia
• Contact: María Amparo Díez-Ajenjo, PhD
• Phone: (+34) 963 86 41 00
• Email: amparo.diez[@]uv.es
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Parkinson's disease (PD) is the second most common neurodegenerative condition worldwide, characterised by motor symptoms, but with other symptoms such as visual impairment.

The aim is to compare visual function between PD patients and healthy subjects in order to adequately characterise the visual capabilities of the PD population and perform oculomotor or perceptual therapy to find optometric solutions to slow down the visual impairment they suffer from or minimise their visual symptoms.

In the first phase, non-invasive tests will be carried out, such as measuring visual acuity, refraction, pupil diameter in different lighting conditions, sensory dominance, contrast sensitivity, colour vision, stereopsis, reading speed, binocular vision, eye movements and influence on quality of life.

In the second, visual oculomotor or perceptual exercises will be performed in a group of PD patients to assess whether there is stabilisation of impairment or improvement of these visual skills. These will be performed in a non-invasive way using simple and easy-to-use instruments or an application on an electronic device could be used.

Finally, in the third phase, those visual skills that have been treated will be re-evaluated to assess possible changes, compared with a group of PD patients who have not undergone the visual exercises.

Description:

Parkinson's disease (PD) is the second most common neurodegenerative condition worldwide. It is a movement disorder characterised by tremor, rigidity, bradykinesia and postural instability. However, 78% of PD patients report visual problems such as dry eye, reduced visual acuity, visual field defects, impaired contrast sensitivity (CS), impaired eye movements, diplopia, convergence insufficiency, impaired colour vision, visual hallucinations and problems in visual-spatial orientation. In fact, visual dysfunction is one of the initial symptoms of PD. A recent study has found that dopaminergic neurons affected in PD show physiological dysfunctions, but do not die. Currently, there is no cure for PD; treatments consist of controlling symptoms, and the earlier the disease is detected and administered, the more effective they are.

It is hypothesised that a programme of visual oculomotor therapy and/or visual perceptual learning (VPL) could slow or halt the deterioration of oculomotor ability and/or CS in these patients. Visual perceptual learning or VPL is a long-term improvement in performance on a visual task, any relatively permanent change in perception that arises from visual experience. Contrast Sensitivity or CS is the ability of the visual system to differentiate an object from the background in which it is located by the difference in contrast. It is the ability to detect differences in luminance between adjacent areas in an image.

If the results confirm the hypothesis, this study will have a great impact on the PD population because it could slow down the deterioration of oculomotor ability that 75% of them suffer from. It could also slow down the decline in CS that they suffer, as demonstrated by several studies. Consequently, patients would also experience an improvement in their quality of life, as they would be able to continue to perform activities of daily living that are affected by visual impairment such as walking, reading, driving and cooking. This would have a major impact on society as PD affects many people worldwide. In Europe, the prevalence and incidence rates of PD are estimated to be approximately 108-257/100 000 and 11-19/100 000 per year, respectively. Furthermore, this project would expand scientific knowledge because to date there is no literature that has evaluated VPL in patients with PD. However, there is research on amblyopia, Stargardt's disease and other neural pathologies, such as Huntington's disease. Likewise, with regard to oculomotor therapy, there is still a lot of research to be done, as there are few studies on this subject.

This is an analytical, longitudinal, prospective and observational study. In the first phase, to characterise the vision of the population with Parkinson's disease, non-invasive tests would be performed, such as measuring visual acuity, refraction, contrast sensitivity, colour vision, depth vision, the state of binocular vision and visual pathways and eye movements. Simultaneously, a control population will be measured to compare the data obtained in PD patients.

In a second phase, visual oculomotor and/or perceptual exercises would be performed in a group of PD patients to assess whether there is stabilisation of the impairment and/or improvement of these visual skills.

Finally, in the third phase, those visual skills that have been treated would be re-evaluated to assess possible changes, compared with a group of PD patients who have not undergone the visual exercises.

The research will be carried out at the Laboratory of Vision and Colour Sciences of the Department of Optics, Optometry and Vision Sciences of the University of Valencia, at the Arnau de Vilanova Hospital and at the Parkinson's Association of Valencia. These are the institutions from which the participants who take part in the study will come. They will do so voluntarily, will not be coerced to participate in any way and will be free to choose whether they want to participate or not, after having been explained to them what this project consists of. Furthermore, they will be able to revoke their signed consent at any time, so that they will automatically be excluded from the study and their data will not be used in the study if the patient so wishes. Furthermore, this project does not harm the patient's health and does not bring any financial benefit to the patient.

Only the members of the project will have access to the original study data. These data will be collected on paper, and the original source will be kept under lock and key in the laboratory of Vision and Colour Sciences of the Department of Optics, Optometry and Vision Sciences of the University of Valencia. For data analysis, the principal investigator will extract the data into a computer document in which each patient will be identified by a two-letter code (GP: control group; PD: Parkinson's patient) and three numbers. Not even the initials of the name will appear. Under this code, the data of each patient will be entered. This is the data that the rest of the group will see and have access to. Adverse event reporting and change management will be carried out through the Reservio platform, which will be used for appointment planning and online booking.

Data analysis will be carried out using the SPSS (Statistical Package for Social Sciences) statistical software and the Matlab numerical calculation system. The statistical analysis plan is as follows: the mean, standard deviation and normality of the samples will be performed with the Shapiro-Wilk test. Statistical comparison between groups will be performed with Student's t-test if the data follow a normal distribution or with the U-Mann-Whitney test otherwise. The statistical test used for qualitative variables will be Pearson's chi-square test.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 160
• Est. completion date: June 1, 2026
• Est. primary completion date: June 1, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 30 Years to 100 Years

Eligibility

Inclusion Criteria:

• Subjects without neurodegenerative diseases or systemic illnesses or ocular pathologies.

• Subjects not taking medication with visual side effects.

• Subjects able to perform the tests.

• Subjects of similar age and sex as their corresponding Parkinson's patient so that both samples are age and gender matched.

• Subjects diagnosed with Parkinson's disease.

• Parkinson's patients classified according to the Hoehn & Yahr Scale.

Exclusion Criteria:

• Subjects with ocular pathologies (such as Glaucoma, Age-Related Macular Degeneration, Retinopathies, Corneal Opacifications, Senile Cataracts, Severe Palpebral Ptosis) or systemic illnesses that may affect the visual system and alter the results (such as Severe Cardiopathies, Diabetes Mellitus, oncological diseases, systemic tissue disorders, chronic infectious diseases or conditions after organ or tissue transplantation).

• Subjects with neurodegenerative or neural diseases other than the study itself, such as Alzheimer's disease, Devic's disease, Huntington's disease, Creutzfeldt-Jakob disease, epilepsy, ataxia, multiple sclerosis or amyotrophic lateral sclerosis.

• Subjects taking medication that may alter any visual ability such as anxiolytics, antidepressants, sleeping pills.

• Subjects with problems in understanding and following the tests.

• Patients who have been previously treated under a vision therapy program.

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Other:
• Clinical measurements
Optometric measurements
• Oculomotor or perceptual therapy
Oculomotor or perceptual visual learning exercices

Locations

Country	Name	City	State
Spain	Hospital Arnau de Vilanova	Valencia

Sponsors (3)

Lead Sponsor	Collaborator
University of Valencia	Asociación Parkinson Valencia, Hospital Arnau de Vilanova

Country where clinical trial is conducted

Spain, 

References & Publications (16)

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Armstrong RA. Visual symptoms in Parkinson's disease. Parkinsons Dis. 2011;2011:908306. doi: 10.4061/2011/908306. Epub 2011 May 25. — View Citation

Balestrino R, Schapira AHV. Parkinson disease. Eur J Neurol. 2020 Jan;27(1):27-42. doi: 10.1111/ene.14108. Epub 2019 Nov 27. — View Citation

Beste C, Wascher E, Dinse HR, Saft C. Faster perceptual learning through excitotoxic neurodegeneration. Curr Biol. 2012 Oct 23;22(20):1914-7. doi: 10.1016/j.cub.2012.08.012. Epub 2012 Sep 13. — View Citation

Borm CDJM, Visser F, Werkmann M, de Graaf D, Putz D, Seppi K, Poewe W, Vlaar AMM, Hoyng C, Bloem BR, Theelen T, de Vries NM. Seeing ophthalmologic problems in Parkinson disease: Results of a visual impairment questionnaire. Neurology. 2020 Apr 7;94(14):e1539-e1547. doi: 10.1212/WNL.0000000000009214. Epub 2020 Mar 11. — View Citation

Campbell FW, Robson JG. Application of Fourier analysis to the visibility of gratings. J Physiol. 1968 Aug;197(3):551-66. doi: 10.1113/jphysiol.1968.sp008574. — View Citation

Ekker MS, Janssen S, Seppi K, Poewe W, de Vries NM, Theelen T, Nonnekes J, Bloem BR. Ocular and visual disorders in Parkinson's disease: Common but frequently overlooked. Parkinsonism Relat Disord. 2017 Jul;40:1-10. doi: 10.1016/j.parkreldis.2017.02.014. Epub 2017 Feb 21. — View Citation

Fahle M. Perceptual learning: a case for early selection. J Vis. 2004 Oct 26;4(10):879-90. doi: 10.1167/4.10.4. — View Citation

Gonzalez-Rodriguez P, Zampese E, Stout KA, Guzman JN, Ilijic E, Yang B, Tkatch T, Stavarache MA, Wokosin DL, Gao L, Kaplitt MG, Lopez-Barneo J, Schumacker PT, Surmeier DJ. Disruption of mitochondrial complex I induces progressive parkinsonism. Nature. 2021 Nov;599(7886):650-656. doi: 10.1038/s41586-021-04059-0. Epub 2021 Nov 3. Erratum In: Nature. 2022 Mar;603(7899):E1. — View Citation

Han G, Han J, Han K, Youn J, Chung TY, Lim DH. Visual Acuity and Development of Parkinson's Disease: A Nationwide Cohort Study. Mov Disord. 2020 Sep;35(9):1532-1541. doi: 10.1002/mds.28184. Epub 2020 Jul 25. — View Citation

Huang CB, Zhou Y, Lu ZL. Broad bandwidth of perceptual learning in the visual system of adults with anisometropic amblyopia. Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):4068-73. doi: 10.1073/pnas.0800824105. Epub 2008 Mar 3. — View Citation

Kaur M, Saxena R, Singh D, Behari M, Sharma P, Menon V. Correlation Between Structural and Functional Retinal Changes in Parkinson Disease. J Neuroophthalmol. 2015 Sep;35(3):254-8. doi: 10.1097/WNO.0000000000000240. — View Citation

Sasaki Y, Nanez JE, Watanabe T. Advances in visual perceptual learning and plasticity. Nat Rev Neurosci. 2010 Jan;11(1):53-60. doi: 10.1038/nrn2737. Epub 2009 Dec 2. — View Citation

Sasso P, Silvestri V, Sulfaro M, Scupola A, Fasciani R, Amore F. Perceptual learning in patients with Stargardt disease. Can J Ophthalmol. 2019 Dec;54(6):708-716. doi: 10.1016/j.jcjo.2019.03.012. Epub 2019 May 31. — View Citation

Savitt J, Aouchiche R. Management of Visual Dysfunction in Patients with Parkinson's Disease. J Parkinsons Dis. 2020;10(s1):S49-S56. doi: 10.3233/JPD-202103. — View Citation

Shibasaki H, Tsuji S, Kuroiwa Y. Oculomotor abnormalities in Parkinson's disease. Arch Neurol. 1979 Jun;36(6):360-4. doi: 10.1001/archneur.1979.00500420070009. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Anamnesis	Ocular and perceptual characterization of Parkinson's Disease visual capabilities with the following measurements (1-12).; Anamnesis: Asking age, allergies, ocular and systemic pathologies, family background, current treatment (if proceed), consumption of tobacco, alcohol, drugs, coffee, tea, performance of physical activity, state on the Hoehn & Yahr classification, date of Parkinson's diagnosis and other observations.	1 year
Primary	Visual Acuity	Using an EDTRS (Early Treatment Diabetic Retinopathy Study) test for distance and near vision with the patient's optical correction, scale: LogMAR.	1 year
Primary	Refraction	Doing ocular compensation with trial frame refraction, units: diopters (D).	1 year
Primary	Pupillary diameter	Under photopic and mesopic illumination conditions using a specific millimetric ruler, units: millimeters (mm).	1 year
Primary	Ocular sensory dominance	Using the red filter test.	1 year
Primary	Binocular vision status	Using the Cover Test Cover Test, Modified Thorington Test Card to phoria measurement and fusional vergence measurement with prism bar, units: prismatic diopters (?).	1 year
Primary	Achromatic CSF (Contrast Sensitivity Funtion)	Under photopic and mesopic illumination conditions using the FACT (Funtional Acuity Contrast Test) test of the FVA (Functional Visual Analyzer) device of Stereo Optical Co., Inc.	1 year
Primary	Stereopsis	Using the Wirth points of the Titmus test, units: seconds of arc (").	1 year
Primary	Colour vision	Using the Farnsworth-Munsell 100 Hue sorting test and the Chromatic Threshold Measurement test.	1 year
Primary	Eye movements quality	Using aDEMd (adult Developmental Eye Movement with distractors) test and NSUCO (Northeastern State University College of Optometry) test. Units: seconds (s).	1 year
Primary	Reading speed	Using Radner-Vissum test, units: seconds (s).	1 year
Primary	Life quality assessment	Scoring the National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25). Higher scores mean a better outcome. Minimum value: 0, maximum value: 100.	1 year
Secondary	Pursuit eye movements	Would be performed noninvasively using simple, easy-to-use instruments such as flashlights, pointers, slates, Marsden's ball, rotating devices and Groffman's visual tracing test. If financial resources permit, an application on an electronic device could also be used.; From these exercises, the following variables will be collected: time spent in the performance of the exercises in seconds (s) and errors made. These will be compared before and after the therapy.; In addition, the patients would be given indications for the work of these exercises at home.	1 year
Secondary	Saccadic eye movements	Would be performed noninvasively using simple, easy-to-use instruments such as flashlights, pointers, slates, Hart's charts, ARB charts and Ann Arbor tracing sheets. If financial resources permit, an application on an electronic device could also be used.; From these exercises, the following variables will be collected: time spent in the performance of the exercises in seconds (s) and errors made. These will be compared before and after the therapy.; In addition, the patients would be given indications for the work of these exercises at home.	1 year
Secondary	Perceptual learning technique	Perceptual learning exercises could also be performed on an electronic device with a program that displays Gabor patches. This technique consists of a task with low-contrast, progressively decreasing, sustained attention, demanding and repetitive stimuli.	1 year