Clinical Investigation on the Blood Oxygenation at the Optic Nerve Head in Fabry Patients

Clinical Investigation on the Blood Oxygenation at the Optic Nerve Head in Relation With Visual Field Loss in Fabry Patients

This study aims to evaluate blood oxygenation at the optic nerve head in relation with visual field losses observed in many Fabry patients. Data collected will allow to evaluate if there is a link between these two entities.

Study will last up to 2 years during which a limited number of Fabry patients will be compared to a control group to confirm any relationship between blood flow and field losses, and to see if these results vary over time.

HYPOTHESIS

1. Fabry patients will present significant differences in visual fields compared to control 2 There will be variability of the visual field defects on the long term but not on the short term 3 Blood oxygenation will be higher for Fabry patients 4 Blood volume at the optic nerve head will be the same for both groups.

Study Overview

• Status: Completed
• Conditions: Fabry Disease
• Intervention / Treatment: Procedure: Contrast sensitivity measurement; Procedure: Slit Lamp assessment and intra-ocular pressure measurement; Procedure: Visual field testing; Procedure: Oxygen flow at the optic nerve head measurement; Drug: Tropicamide; Device: OSOME

Detailed Description

The first subjects who meet the following criteria will be enrolled in the study.

Inclusion criteria (Fabry group ):

• Aged over 18 years old

• Being diagnosed with Fabry disease

  • 3 subjects will be under enzyme replacement treatment for the treatment of Fabry disease.
  • 3 subjects will not receive enzyme replacement treatment
• Is fit to give legal consent.
• Is available for a period of 2 years

Inclusion criteria (CONTROL group ):

• Matched for age and sex with group A - 6 participants
• Being healthy, with no known chronic systemic disease nor acute disease at the moment of the recruitment
• Is fit to give legal consent.
• Is available for a period of 2 years

Exclusion criteria (Both groups):

• Presents with an active pathological ocular condition
• Presence of an abnormal optic nerve (congenital or acquired)
• Usage of topical ocular drug(s) at the time of selection
• To have known allergy to topical diagnostic drugs used in this study
• Usage of systemic medication with known effect on the visual field

• Study Type: Observational
• Enrollment (Actual): 8

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3T1P1
      • Université de Montréal

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients known as Fabry patients, already followed at Universite de Montréal eye clinic. COntrol will come from the normal clinical population seen at the same site.

Description

Inclusion Criteria:

Inclusion criteria (Fabry group):

• Aged over 18 years old

• Being diagnosed with Fabry disease

  • 3 subjects will be under enzyme replacement treatment for the treatment of Fabry disease.
  • 3 subjects will not receive enzyme replacement treatment
• Is fit to give legal consent.
• Is available for a period of 2 years

Inclusion criteria (CONTROL group):

• Matched for age and sex with group A - 6 participants
• Being healthy, with no known chronic systemic disease nor acute disease at the moment of the recruitment
• Is fit to give legal consent.
• Is available for a period of 2 years

Exclusion Criteria:( both groups):

• Presents with an active pathological ocular condition
• Presence of an abnormal optic nerve (congenital or acquired)
• Usage of topical ocular drug(s) at the time of selection
• To have known allergy to topical diagnostic drugs used in this study
• Usage of systemic medication with known effect on the visual field

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
FABRY group; contrast sensitivity measurement; slit lamp assessment and intra-ocular pressure measurement; ocular coherence tomography at the optic nerve head; visual field testing; OSOME (oxygen flow at the optic nerve head measurement); Tropicamide	Procedure: Contrast sensitivity measurement; Contrast sensitivity test is made with targets alternating black and white lines. The larger the lines are, easier it is to see them. Targets are distributed in 5 rows, each oriented at a different angle. Contrast sensitivity level is determined by the smallest target seen by the participant, line by line. This test is done under dim lightning with the habitual visual correction worn.; Procedure: Slit Lamp assessment and intra-ocular pressure measurement; Slit lamp is used to assess the presence of significant lens opacities known as Fabry cataracts. In fact, these opacities can induced a bias on the contrast sensitivity measurement and can increase the symptoms felt by the patient. A grade 2 (CFDI grading chart) of lens opacities is considered clinically significant and this will become an exclusion criteria for the following of the study. Intra-ocular pressure will be measured with a non contact tonometer (air pulsed) (Ocular Response Analyser, Reichert Instrumentation.); Procedure: Visual field testing; Visual field will be assessed with an automated perimeter (Humphrey, Texas) using a threshold strategy. This implies that the subject has to identify not only if he perceives the visual stimulus but the minimal level of this stimulus (in decibels), to be seen, is also recorded. Visual field will be tested up to 30 degrees from the central point of fixation. In order to measure immediate variability of the visual testing among Fabry subjects, this test will be done at the beginning of the testing session (in the morning) and another time 1h00 later.; Procedure: Oxygen flow at the optic nerve head measurement; Pupils will be dilated with 1 drop of 1% tropicamide. The procedure is similar to the one used for taking a photo of the retina. Each measurement session represents a continuous recording of 20 simultaneous functions of reflectometry from the optic nerve area during 10 seconds. During all recording sessions, the systemic arterial oxygen saturation will be also monitored at the right index finger using a pulse oximeter (Escort M10, Invivo, Orlando, USA). Arterial blood pressure will be also monitored before and after the testing using a manual sphygmomanometer.; Other Names: OSOME; Drug: Tropicamide; Used to dilate patient's pupil during testing; Other Names: Mydriacyl® Mydriatic Tropicamide 1% Ophthalmic Drops; DIN 00001007; Device: OSOME; The OSOME system is the only technology able to perform on line and real time capillaries blood oxygenation measurement in the eye. The system operates with 1200 discreet wavelengths between 400 nm to 700 nm with 500 millisecond integration times. It is not invasive, functioning just like a fundus camera.; Other Names: (O.S.O.M.E., US patent # 5,919,132;)
CONTROL group; contrast sensitivity measurement; slit lamp assessment and intra-ocular pressure measurement; ocular coherence tomography at the optic nerve head; visual field testing; oxygen flow at the optic nerve head measurement (OSOME); Under tropicamide	Procedure: Contrast sensitivity measurement; Contrast sensitivity test is made with targets alternating black and white lines. The larger the lines are, easier it is to see them. Targets are distributed in 5 rows, each oriented at a different angle. Contrast sensitivity level is determined by the smallest target seen by the participant, line by line. This test is done under dim lightning with the habitual visual correction worn.; Procedure: Slit Lamp assessment and intra-ocular pressure measurement; Slit lamp is used to assess the presence of significant lens opacities known as Fabry cataracts. In fact, these opacities can induced a bias on the contrast sensitivity measurement and can increase the symptoms felt by the patient. A grade 2 (CFDI grading chart) of lens opacities is considered clinically significant and this will become an exclusion criteria for the following of the study. Intra-ocular pressure will be measured with a non contact tonometer (air pulsed) (Ocular Response Analyser, Reichert Instrumentation.); Procedure: Visual field testing; Visual field will be assessed with an automated perimeter (Humphrey, Texas) using a threshold strategy. This implies that the subject has to identify not only if he perceives the visual stimulus but the minimal level of this stimulus (in decibels), to be seen, is also recorded. Visual field will be tested up to 30 degrees from the central point of fixation. In order to measure immediate variability of the visual testing among Fabry subjects, this test will be done at the beginning of the testing session (in the morning) and another time 1h00 later.; Procedure: Oxygen flow at the optic nerve head measurement; Pupils will be dilated with 1 drop of 1% tropicamide. The procedure is similar to the one used for taking a photo of the retina. Each measurement session represents a continuous recording of 20 simultaneous functions of reflectometry from the optic nerve area during 10 seconds. During all recording sessions, the systemic arterial oxygen saturation will be also monitored at the right index finger using a pulse oximeter (Escort M10, Invivo, Orlando, USA). Arterial blood pressure will be also monitored before and after the testing using a manual sphygmomanometer.; Other Names: OSOME; Drug: Tropicamide; Used to dilate patient's pupil during testing; Other Names: Mydriacyl® Mydriatic Tropicamide 1% Ophthalmic Drops; DIN 00001007; Device: OSOME; The OSOME system is the only technology able to perform on line and real time capillaries blood oxygenation measurement in the eye. The system operates with 1200 discreet wavelengths between 400 nm to 700 nm with 500 millisecond integration times. It is not invasive, functioning just like a fundus camera.; Other Names: (O.S.O.M.E., US patent # 5,919,132;)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood oxygenation at the optic nerve head	To evaluate blood oxygenation and blood volume optical density at the different optic nerve head zones in Fabry patients, presenting field defects, and to compare the results to a control group.	up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Origin of visual field defect in Fabry patients	To validate that visual field defects found in Fabry patients could be vascular in origin. AND To demonstrate that visual field testing should be included in the standard eye examination and follow-up of patients with Fabry	up to 2 years

Collaborators and Investigators

• Sponsor: Université de Montréal
• Collaborators: Genzyme, a Sanofi Company
• Investigators: Principal Investigator: Langis Michaud, OD M.Sc., Université de Montréal

Publications and helpful links

General Publications

• Pitz S, Grube-Einwald K, Renieri G, Reinke J. Subclinical optic neuropathy in Fabry disease. Ophthalmic Genet. 2009 Dec;30(4):165-71. doi: 10.3109/13816810903148004.
• Kumagai K, Mitamura Y, Mizunoya S, Fujimoto N, Yamamoto S. A case of anterior ischemic optic neuropathy associated with Fabry's disease. Jpn J Ophthalmol. 2008 Sep-Oct;52(5):421-423. doi: 10.1007/s10384-008-0572-4. Epub 2008 Nov 11. No abstract available.
• Feke GT, Riva CE. Laser Doppler measurements of blood velocity in human retinal vessels. J Opt Soc Am. 1978 Apr;68(4):526-31. doi: 10.1364/josa.68.000526.
• Diaconu V. Multichannel spectroreflectometry: a noninvasive method for assessment of on-line hemoglobin derivatives. Appl Opt. 2009 Apr 1;48(10):D52-61. doi: 10.1364/ao.48.000d52.

Helpful Links

• web site of the School of Optometry University of Montreal

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (ACTUAL): September 1, 2016
• Study Completion (ACTUAL): September 1, 2016

Study Registration Dates

• First Submitted: December 10, 2013
• First Submitted That Met QC Criteria: December 22, 2013
• First Posted (ESTIMATE): December 30, 2013

Study Record Updates

• Last Update Posted (ACTUAL): May 2, 2017
• Last Update Submitted That Met QC Criteria: May 1, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Visual field defect; Blood oxygenation; Optic nerve Head
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Cerebral Small Vessel Diseases; Lipidoses; Lipid Metabolism, Inborn Errors; Fabry Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Mydriatics; Tropicamide
• Other Study ID Numbers: GZ-2012-10918