Clinical trial NCT03370965: Optic Neuritis Differential Diagnosis Study
Official title: Optic Neuritis Differential Diagnosis Study (ONDDS)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Optic Neuritis
Neuromyelitis Optica
Multiple Sclerosis
Keywords: optic neuritis
neuromyelitis optica
multiple sclerosis
emergent treatment of optic neuritis
optic neuritis disease modifying therapy
optic neuritis treatment trial
plasma exchange
Lead sponsor: University Hospital Center of Martinique
Sponsor class: OTHER
Collaborators: name: University Hospital Center of Guadeloupe
name: Hospital Center of Cayenne (French Guyana)
First posted: 2017-12-13
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: Background: Optic neuritis is a frequent cause of vision loss encountered by ophthalmologists in the Caribbean. The diagnosis is made on clinical grounds. Optic neuritis can occur either in an isolated manner or, most often, as the first symptom of multiple sclerosis (MS) or neuromyelitisoptica (NMO). These 2 demyelinating disorders differ by many means, including treatment and prognosis. MS can cause severe long-term disability while NMO is a short-term sight- and life-threatening condition causing potential relapses, which may require plasma exchanges. Furthermore, disease-modifying therapies used in NMO are different from those used in MS, which can worsen the natural history of NMO. Early differential diagnosis of these diseases is thus crucial for preventing severe visual loss and disability.

Detailed description: Background: Optic neuritis is a frequent cause of vision loss encountered by ophthalmologists in the Caribbean. The diagnosis is made on clinical grounds. Optic neuritis can occur either in an isolated manner or, most often, as the first symptom of multiple sclerosis (MS) or neuromyelitisoptica (NMO). These 2 demyelinating disorders differ by many means, including treatment and prognosis. MS can cause severe long-term disability while NMO is a short-term sight- and life-threatening condition causing potential relapses, which may require plasma exchanges. Furthermore, disease-modifying therapies used in NMO are different from those used in MS, which can worsen the natural history of NMO. Early differential diagnosis of these diseases is thus crucial for preventing severe visual loss and disability.

Purpose: The investigators aim to identify early predictive factors (clinical, biological and radiological) of NMO occurrence in patients presenting with optic neuritis and with no prior history of demyelinating diseases.

Method: The investigators will conduct a multicentric prospective study including all patients of 18 years or older, with no prior history of demyelinating disorders and presenting with a diagnosis of optic neuritis in Martinique, Guadeloupe, French Guiana, Saint-Martin and Saint-Barthélemy. Patients will first undergo a full neuro-ophthalmic examination which includes visual acuity, contrast vision, color vision, slit-lamp anterior segment and fundus examination as well as automatized visual field and optical coherence tomography of the optic nerves and retina. Patients will then be admitted to the Neurology and Ophthalmologic Department of the University Hospital of Martinique for optic neuritis emergency treatment, 3-Tesla brain and medullar MRIs, and ancillary testing. Specific NMO antibodies (AQP-4 and MOG) will be tested in all patients. Neuro-ophthalmic examination will be repeated after 3 days of IV steroids in order to decide on further treatment. Patients will be further monitored at 1, 6 and 12 months so as to determine the most likely etiology of optic neuritis with the aid of MS and NMO diagnosis criteria.

Eligibility criteria: Inclusion Criteria:

1. Patient aged 18 years or older at time of inclusion.
2. Table of unilateral or bilateral optic neuritis defined as follows (clinical diagnosis):

   1. Visual sharpness (acuity and / or visual field) experienced acutely or subacutely (\<1 month) unilateral or bilateral, not corrected by optical correction.
   2. Absence of ophthalmologic lesion which may explain the visual loss.
   3. Examination of the normal fundus or showing a pallor or papular edema.
   4. Presence of relative pupillary deficit relative if unilateral attack.
3. Patient (s) affiliated to a social security scheme (beneficiary or beneficiary).
4. Patient who has given free and written consent.

Exclusion Criteria:

1. Patients known to have an inflammatory disease of the central nervous system (MS, NMO, EMAD).
2. Known history of inflammatory pathology (lupus or sarcoidosis) or infectious pathology (syphilis, HIV) that may give rise to optical neuropathy.
3. Table suggestive of Leber's hereditary optic neuropathy (genetically confirmed).
4. Treatment in progress known to give optical neuropathies.
5. Consumption of toxic known to give optical neuropathies.
6. Drinking more than 3 alcohol drinks per day for men and 2 alcohol drinks per day for women over a period of more than 15 years.
7. Arguments for non-arteritic ischemic optic neuropathy defined by all of the following criteria:

   1. Absence of pain in eye movements.
   2. Altitudinal deficit of the visual field.
   3. Choroidal ischemia with fluorescein angiography.
   4. Presence of cardiovascular risk factors.
   5. Absence of neurological signs related to inflammatory disease of the central nervous system.
8. Arguments for arterial ischemic optic neuropathy defined by all of the following criteria:

   1. Absence of pain in eye movements.
   2. Altitudinal deficit of the visual field.
   3. Choroidal ischemia with fluorescein angiography.
   4. Presence of symptoms suggestive of Horton's disease.
   5. Absence of neurological signs related to inflammatory disease of the central nervous system.
9. Pregnant and lactating patients.

Primary outcomes:
measure: Final diagnosis using MS (McDonald, 2010) - Spatial dissemination
timeFrame: 12 months
measure: Final diagnosis using MS (McDonald, 2010) - Time dissemination
timeFrame: 12 months
measure: NMO diagnosis criteria (Wingerchuk, 2015) - Diagnosis of NMO-SD with positive anti-AQP4 Antibody
timeFrame: 12 months
measure: NMO diagnosis criteria (Wingerchuk, 2015) - Diagnosis of NMO-SD with anti-AQP4 negative antibody
timeFrame: 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Fort-de-France
country: France
facility: CHU of Martinique
Study officials:
affiliation: Centre Hospitalier Universitaire de Martinique
name: Philippe CABRE, PhD
role: PRINCIPAL_INVESTIGATOR
References: