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

NCT02023086 | Completed Results

• 1 other identifier: GZ-2012-10918
• Study Type: observational
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

This study aimed to evaluate blood oxygenation at the optic nerve head in relation with visual field losses observed in many Fabry patients. Data collected allowed to evaluate if there is a link between these two entities. Study lasted 2 years during which a limited number of Fabry patients had been compared to a control group to confirm any relationship between blood flow and field losses, and to see if these results varied 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.

Conditions

Fabry Disease

Keywords

Visual field defect; Blood oxygenation; Optic nerve Head

Outcome Measures

Primary Outcomes (1)

• Blood Oxygenation at the Optic Nerve Head

  OSOME measurement of the blood oxygenation at the optic nerve head

  2 years

Secondary Outcomes (1)

• Field Defect

  2 years

Study Arms (2)

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; 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

CONTROL group (Historical database)

* 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; 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

Interventions

Contrast sensitivity measurement PROCEDURE

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.

CONTROL group (Historical database); FABRY group

Slit Lamp assessment and intra-ocular pressure measurement PROCEDURE

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.)

CONTROL group (Historical database); FABRY group

Visual field testing PROCEDURE

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.

CONTROL group (Historical database); FABRY group

Oxygen flow at the optic nerve head measurement PROCEDURE

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.

Also known as: OSOME

CONTROL group (Historical database); FABRY group

Tropicamide DRUG

Used to dilate patient's pupil during testing

Also known as: Mydriacyl® Mydriatic Tropicamide 1% Ophthalmic Drops, DIN 00001007

CONTROL group (Historical database); FABRY group

OSOME DEVICE

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.

Also known as: (O.S.O.M.E., US patent # 5,919,132;)

CONTROL group (Historical database); FABRY group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• Aged over 18 years old
• Being diagnosed with Fabry disease
• subjects will be under enzyme replacement treatment for the treatment of Fabry disease.
• subjects will not receive enzyme replacement treatment
• Is fit to give legal consent.
• Is available for a period of 2 years
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Université de Montréal: lead
• Genzyme, a Sanofi Company: collaborator

Study Sites (1)

Universite de Montreal

Montreal, Quebec, H3T1P1, Canada

Location

Related Publications (4)

• 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.

  PMID: 19852573 BACKGROUND

• 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.

  PMID: 18991052 BACKGROUND

• 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.

  PMID: 671138 BACKGROUND

• 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.

  PMID: 19340124 BACKGROUND

Related Links

• web site of the School of Optometry University of Montreal

MeSH Terms

Conditions

Fabry Disease

Interventions

Visual Fields; Tropicamide; Ophthalmic Solutions

Condition Hierarchy (Ancestors)

Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Intervention Hierarchy (Ancestors)

Ocular Physiological Phenomena; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pharmaceutical Solutions; Solutions; Pharmaceutical Preparations; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Specialty Uses of Chemicals

Limitations and Caveats

The first obvious limitation is the nature of a pilot study, relying on a limited number of subjects. Sub-analysis is limited due to the fact that all except two Fabry participants have the same classic mutation (p.Ala348Pro), and all males and none women are on ERT. Consequently results analysis must be made with caution and can probably not be generalized to other Fabry's cohorts.

Results Point of Contact

• Title: Langis Michaud
• Organization: Université de Montréal

langis.michaud@umontreal.ca

5149166312

Study Officials

• Langis Michaud, OD M.Sc.

  Universite de Montreal

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Target Duration: 2 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 10, 2013
• First Posted: December 30, 2013
• Study Start: August 1, 2014
• Primary Completion: September 1, 2016
• Study Completion: September 1, 2016
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-09

Locations

CA (1)