Chromatic Pupillometry to Assess the Melanopsin-Light Pathway in Progressive Supranuclear Palsy

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Brief Title

Chromatic Pupillometry to Assess the Melanopsin-Light Pathway in Progressive Supranuclear Palsy

Official Title

Functional Assessment of the Melanopsin-Containing Retinal Ganglion Cells in Progressive Supranuclear Palsy Using Chromatic Pupillometry

Brief Summary

      The specific aim of this study is to investigate rod, cone and melanopsin driven pupillary
      light response in individuals with progressive supranuclear palsy (PSP), age-matched healthy
      controls and individuals with other neurodegenerative diseases using chromatic pupillometry,
      with special interest in assessing melanopsin-driven post-illumination pupil response (PIPR)
      as an identifier for PSP.

      The study addresses the following hypotheses:

        1. Chromatic pupil responses, including rod/cone-driven rapid phase constriction and
           melanopsin-driven PIPR, are reduced in subjects with PSP compared to age-matched normal
           healthy control subjects,

        2. Pupil parameters of the melanopsin-driven PIPR are abnormal in PSP subjects without
           supranuclear palsy, which is indicative of a subclinical physiological deficit of the
           OPN in the early stages of PSP.

      If these hypotheses are upheld, chromatic pupillometry to measure the PIPR promises to be a
      reliable in vivo, non-invasive, convenient and inexpensive technique to detect asymptomatic
      pupillomotor impairment in advance of diagnostic oculomotor signs and deterioration of
      cognitive function.
    

Detailed Description

      In 1963, Richardson, Steele and Olszewski published a landmark clinical report on 8 cases of
      supranuclear ophthalmoplegia, pseudobulbar palsy, nuchal dystonia and dementia and
      established the syndrome of heterogeneous system degeneration as a clinicopathological entity
      now known as PSP. The disease has a characteristic onset in the sixth decade (range 45 to 75
      years) with some combination of impaired balance, abrupt falls, visual disturbances, slurred
      speech, dysphasia and vague changes in personality.

      Slowing of voluntary vertical saccades, either down, up or both are a diagnostic marker of
      PSP and later impairment of voluntary horizontal saccades are characteristic in more than
      half of the cases. However, a proportion of PSP patients do not demonstrate these eye signs
      for a year or more after the onset of the disease.

      This pilot study will use chromatic pupillometry to determine whether such a novel
      methodology may be used as an objective in vivo identifier of PSP. The rationale for the
      study is based in part on:

        1. Clinicopathological correlation between the key clinical signs of a supranuclear gaze
           palsy with pathological verification that the degenerative process affects the pretectum
           and rostral midbrain,

        2. The melanopsin-signaling pathway from ipRGCs (intrinsically photosensitive retinal
           ganglion cells) in the eye projects to the OPN (olivary pretectal nucleus) in the
           midbrain,

        3. Chromatic pupillometry is a non-invasive technique suitable for elderly subjects with or
           without dementia.
    


Study Type

Observational


Primary Outcome

Maximal Pupil Constriction


Condition

PSP - Progressive Supranuclear Palsy

Intervention

Pupillometry

Study Arms / Comparison Groups

 Neurodegenerative Diseases
Description:  Individuals with neurodegenerative diseases

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Diagnostic Test

Estimated Enrollment

56

Start Date

November 1, 2017

Completion Date

October 1, 2019

Primary Completion Date

October 1, 2019

Eligibility Criteria

        Inclusion Criteria:

          1. Individuals that meet the clinical criteria for PSP. Core features include:

               -  Recurrent falls and unsteady gait

               -  Axial and nuchal rigidity

               -  Pseudobulbar palsy

               -  Bilateral lid retraction

               -  Supranuclear vertical gaze palsy

               -  Atrophy of the midbrain tegmentum (the hummingbird sign on brain MRI,

          2. Individuals that fit the criteria for the second PSP phenotype (which resembles PD)
             that has asymmetric findings, tremors and poor responses to treatment with Levodopa,

          3. Individuals that meet the clinical criteria for PD with:

               -  Progressive bradykinesia

               -  Postural instability and frequent falls

               -  Festinating gait with loss of associated movements

               -  Cogwheel rigidity and mask-like face

               -  Rest tremor,

          4. Individuals who carry a diagnosis of Alzheimer' disease who present with progressive
             impairment of memory and cognitive domains such as language and visuospatial
             perception.

        Diagnoses will be confirmed by the review of health/medical records of patients recruited
        from the Frontotemporal Disorders Unit clinic. In the case of participants recruited from
        research studies, diagnoses will be confirmed by the review of the research diagnoses
        indicated on the individuals' research records.

        Exclusion Criteria:

          1. Individuals who are frail or in questionable health,

          2. Individuals with cataracts or with posterior pole ocular pathology such as age-related
             macular degeneration and optic neuropathies, including open angle high intraocular
             pressure glaucoma,

          3. Individuals with photophobia (i.e., painful light sensitivity) when exposed to bright
             light, including those with ophthalmological conditions such as keratitis (herpes
             simplex), uveitis or Achromatopsia,

          4. Individuals with advanced dementia with inability to sit erect, hold the eyes open,
             incontinence,

          5. Individuals with epilepsy,

          6. Individuals diagnosed with major depression or other severe psychiatric disorders
      

Gender

All

Ages

55 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Shirley H Wray, MD, PhD, 617-726-5539, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT03330353

Organization ID

2017p001603


Responsible Party

Principal Investigator

Study Sponsor

Massachusetts General Hospital

Collaborators

 NeurOptics Inc.

Study Sponsor

Shirley H Wray, MD, PhD, Principal Investigator, Massachusetts General Hospital


Verification Date

November 2017