Optic Neuritis Differential Diagnosis Study (ONDDS)

Optic Neuritis Differential Diagnosis Study (ONDDS)

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.

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis; Optic Neuritis; Neuromyelitis Optica
• Intervention / Treatment: Diagnostic test: Neuro-ophtalmology examination

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.

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Philippe CABRE, PhD; Phone Number: +596 0596552261; Email: philippe.cabre@chu-martinique.fr
• Study Contact Backup: Name: Harold MERLE, MD; Phone Number: +596 0596552251; Email: harold.merle@chu-martinique.fr

Study Locations

• France
  • Fort-de-France, France, 97261
    • Recruiting
    • CHU of Martinique
    • Contact: Philippe Cabre, MD, PhD
    • Principal Investigator: Philippe Cabre, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Patients with optic neuritis

Diagnostic test: Neuro-ophtalmology examination; 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 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Final diagnosis using MS (McDonald, 2010) - Spatial dissemination	One T2 lesion ore more in at least two of the four central nervous system territories considered to be characteristic of MS: juxtacortical,; periventricular,; sub-tentorial,; medullary (in case of medullary syndrome or brain stem, symptomatic lesions are excluded from the diagnostic criteria and do not participate in the lesion count).	12 months
Final diagnosis using MS (McDonald, 2010) - Time dissemination	A new lesion in T2 and / or a lesion taking gadolinium on a follow-up MRI regardless of the time of initial MRI.; The simultaneous presence of asymptomatic lesions raised and not elevated by gadolinium at any time.	12 months
NMO diagnosis criteria (Wingerchuk, 2015) - Diagnosis of NMO-SD with positive anti-AQP4 Antibody	At least one main clinical criterion (1); Exclusion of other diagnoses	12 months
NMO diagnosis criteria (Wingerchuk, 2015) - Diagnosis of NMO-SD with anti-AQP4 negative antibody	At least 2 main clinical criteria occurring in the context of one or more clinical outbreaks and meeting the following criteriaAt least 1 of the 2 main clinical criteria should be optic neuritis, extensive longitudinal myelitis or area postrema syndrome.Dissemination in space (at least 2 main criteria)Respect of MRI imaging criteria (2); Anti-AQP4 negative antibodies; Exclusion of differential diagnoses	12 months

Collaborators and Investigators

• Sponsor: University Hospital Center of Martinique
• Collaborators: University Hospital Center of Guadeloupe; Hospital Center of Cayenne (French Guyana)
• Investigators: Principal Investigator: Philippe CABRE, PhD, Centre Hospitalier Universitaire de Martinique

Study record dates

Study Major Dates

• Study Start (Actual): June 7, 2019
• Primary Completion (Anticipated): June 1, 2024
• Study Completion (Anticipated): June 1, 2025

Study Registration Dates

• First Submitted: October 20, 2017
• First Submitted That Met QC Criteria: December 7, 2017
• First Posted (Actual): December 13, 2017

Study Record Updates

• Last Update Posted (Actual): February 24, 2022
• Last Update Submitted That Met QC Criteria: February 22, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: multiple sclerosis; optic neuritis; neuromyelitis optica; plasma exchange; emergent treatment of optic neuritis; optic neuritis disease modifying therapy; optic neuritis treatment trial
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Eye Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; Optic Nerve Diseases; Cranial Nerve Diseases; Myelitis, Transverse; Multiple Sclerosis; Sclerosis; Neuritis; Optic Neuritis; Neuromyelitis Optica
• Other Study ID Numbers: 17/B/01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No