Fabry Disease
Conditions
Keywords
Visual field defect, Blood oxygenation, Optic nerve Head
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.
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
Interventions
PROCEDUREContrast 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.
PROCEDURESlit 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.)
PROCEDUREVisual 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.
PROCEDUREOxygen 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.
DRUGTropicamide
Used to dilate patient's pupil during testing
DEVICEOSOME
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.
Sponsors
Genzyme, a Sanofi Company
Université de Montréal
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Blood Oxygenation at the Optic Nerve Head | 2 years | OSOME measurement of the blood oxygenation at the optic nerve head |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Field Defect | 2 years | Visual field defect using Frequency Doubling Technology (FDT) Results from FDT perimetry are reported using decibels of sensitivity. FDT perimetry has a manufacturer-provided internal normative database. (Deviation Plot). Results are compared to the normative database are shown on a gray scale plot based on probability levels. Screening tests preformed with the -5 screening test index ranges from P≥5% (worst) to P\<1% (better) The global indices that are reported are the mean deviation (MD) and pattern standard deviation (PSD). MD values that fall below 5%, 2% 1% or 0.5 % normal probability levels are indicated with the appropriate label. Pattern Standard Deviation (PSD) represents how evenly the field loss is spread across the VF, thus indicative of localized loss. The PSD can only be equal to or greater than zero. The higher the PSD value, the greater the amount of irregularities with steeper slopes in the VF. |
Countries
Canada
Participant flow
Recruitment details
Treatment group (Fabry) were actively recruited
Pre-assignment details
Historic control group. Data collected from the files of patients - matched for age and sex- who consulted at Clinique Universitaire de la Vision. No active recruitment due to constraints in budget and manpower.
Participants by arm
| Arm | Count |
|---|---|
| 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) | 8 |
| 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) | 8 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | FABRY Group | CONTROL Group | Total |
|---|---|---|---|
| Age, Categorical Hemizygotes- males <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Hemizygotes- males >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Hemizygotes- males Between 18 and 65 years | 3 Participants | 3 Participants | 6 Participants |
| Age, Categorical Heterozygotes- females <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Heterozygotes- females >=65 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical Heterozygotes- females Between 18 and 65 years | 4 Participants | 4 Participants | 8 Participants |
| Age, Continuous | 46 years STANDARD_DEVIATION 14.8 | 43 years STANDARD_DEVIATION 11.5 | 46 years STANDARD_DEVIATION 14.8 |
| Region of Enrollment Canada | 8 participants | 8 participants | 16 participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 5 Participants | 5 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 0 / 8 | 0 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 |
Outcome results
Primary
Blood Oxygenation at the Optic Nerve Head
OSOME measurement of the blood oxygenation at the optic nerve head
Time frame: 2 years
Population: Fabry disease patients
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fabry | Blood Oxygenation at the Optic Nerve Head | 60.8 percentage of oxygen saturation | Standard Deviation 5.4 |
| CONTROL Group | Blood Oxygenation at the Optic Nerve Head | 65.3 percentage of oxygen saturation | Standard Deviation 5.2 |
Secondary
Field Defect
Visual field defect using Frequency Doubling Technology (FDT) Results from FDT perimetry are reported using decibels of sensitivity. FDT perimetry has a manufacturer-provided internal normative database. (Deviation Plot). Results are compared to the normative database are shown on a gray scale plot based on probability levels. Screening tests preformed with the -5 screening test index ranges from P≥5% (worst) to P\<1% (better) The global indices that are reported are the mean deviation (MD) and pattern standard deviation (PSD). MD values that fall below 5%, 2% 1% or 0.5 % normal probability levels are indicated with the appropriate label. Pattern Standard Deviation (PSD) represents how evenly the field loss is spread across the VF, thus indicative of localized loss. The PSD can only be equal to or greater than zero. The higher the PSD value, the greater the amount of irregularities with steeper slopes in the VF.
Time frame: 2 years
Population: Fabry patients vs historic database
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fabry | Field Defect | 98.4 Visual field Index (VFI) | Standard Deviation 1.1 |
| CONTROL Group | Field Defect | 99.6 Visual field Index (VFI) | Standard Deviation 0.6 |