Controversies in Neuro-Ophthalmology: Where the Evidence Leads Us

American Journal of Ophthalmology, 2000

Optic neuritis (ON) is an inflammatory disorder of the optic nerve. Most cases are idiopathic or associated with MS. ON can be associated with a variety of systemic or ocular disorders and is the most common acute optic neuropathy in adults younger than 46 years. Among high-risk populations for MS, the incidence of ON is about 3 per 100,000 population per year, whereas in other areas the incidence is about 1 per 100,000 population per year. 1-13 Acute ON often presents as an isolated clinical event without contributory systemic abnormalities (monosymptomatic ON). Clinical features include periocular pain, abnormal visual acuity and fields, reduced color vision, a relative afferent pupillary defect, and abnormal visual evoked potentials. The fundus may appear normal or demonstrate edema of the optic nerve head (papillitis). 12-18 MRI white matter abnormalities identical to those seen in MS are found in 50 to 70% of monosymptomatic ON cases. 19-22 The visual deficit of ON may worsen over 1 to 2 weeks and usually begins improving over the next month. Lack of improvement in visual function by 30 days is unusual. 23 However, most patients have some residual visual function deficit, even if visual acuity improves to 20/20. 1-18 Differential diagnosis includes compressive, ischemic, hereditary, toxic, or other inflammatory optic neuropathies (e.g., sarcoid). These conditions usually do not exhibit the same clinical pattern (table 1) or rate of recovery as monosymptomatic ON. 1-13 Treatment of monosymptomatic ON has included oral, retrobulbar, and IV steroids, immunoglobulin, and acupuncture. 23-77 Monosymptomatic acute ON is not rare and because the usefulness of oral prednisone in this disorder has recently been questioned, 23,78-82 this practice parameter was developed to provide recommendations regarding the management of this common neurologic problem. Evidence review. A literature search was conducted using Medline and Healthstar from 1966 to July 1, 1999. ON was cross-referenced with treatment and therapy. Citations earlier than 1966 were searched by cross-referencing techniques and an Index Medicus hand search. A total of 582 different citations dealing with ON and some aspect of therapy were identified and reviewed. Only literature published in well-disseminated journals dealing specifically with MS-related or idiopathic ON involving at least three patients was retained. Both retrospective and prospective data were reviewed. Citations were excluded when they simply described a small number of individual case reports or reviewed "ON" due to diseases such as sarcoid, lupus, anterior ischemic optic neuropathy, trauma, hereditary optic neuropathy, optic nerve compression, or other unrelated optic neuropathy. Definitions for the classification of evidence. Class I. Evidence provided by well-designed, randomized, controlled clinical trials, including overviews (meta-analyses) of such trials. Class II. Evidence provided by well-designed observational studies with concurrent controls (e.g., case control and cohort studies). Class III. Evidence provided by expert opinion, case series, case reports, and studies with historical controls. All pertinent studies are listed in table 2. Results. Several studies were identified, the largest of which was the National Eye Institute-sponsored Optic Neuritis

The Open Ophthalmology Journal, 2012

The aim of this review is to summarize the latest information about optic neuritis, its differential diagnosis and management. Optic Neuritis (ON) is defined as inflammation of the optic nerve, which is mostly idiopathic. However it can be associated with variable causes (demyelinating lesions, autoimmune disorders, infectious and inflammatory conditions). Out of these, multiple sclerosis (MS) is the most common cause of demyelinating ON. ON occurs due to inflammatory processes which lead to activation of T-cells that can cross the blood brain barrier and cause hypersensitivity reaction to neuronal structures. For unknown reasons, ON mostly occurs in adult women and people who live in high latitude. The clinical diagnosis of ON consists of the classic triad of visual loss, periocular pain and dyschromatopsia which requires careful ophthalmic, neurologic and systemic examinations to distinguish between typical and atypical ON. ON in neuromyelitis optica (NMO) is initially misdiagnosed as ON in MS or other conditions such as Anterior Ischemic Optic Neuropathy (AION) and Leber's disease. Therefore, differential diagnosis is necessary to make a proper treatment plan. According to Optic Neuritis Treatment Trial (ONTT) the first line of treatment is intravenous methylprednisolone with faster recovery and less chance of recurrence of ON and conversion to MS. However oral prednisolone alone is contraindicated due to increased risk of a second episode. Controlled High-Risk Subjects Avonex ® Multiple Sclerosis Prevention Study "CHAMPS", Betaferon in Newly Emerging Multiple Sclerosis for Initial Treatment "BENEFIT" and Early Treatment of MS study "ETOMS" have reported that treatment with interferon-1a,b results in reduced risk of MS and MRI characteristics of ON. Contrast sensitivity, color vision and visual field are the parameters which remain impaired mostly even after good recovery of visual acuity.

Journal of Neurology, Neurosurgery & Psychiatry

Acta Clin Croat, 2007

Idiopathic optic neuritis is idiopathic inflammation of the optic nerve. Multiple sclerosis is a chronic inflammatory demyelinating process of the central nervous system that affects mostly women aged 20-40. Modern diagnostic methods (MRI, VEP, and computerized perimetry) can confirm or exclude demyelinating etiology of the process. The study included 31 patients with optic neuritis hospitalized at University Department of Ophthalmology, Split University Hospital in Split, Croatia, between January 1, 2004 and December 31, 2005. The incidence of idiopathic optic neuropathy at Department was 3.2/ 100,000 in 2004 and 3.4/100,000 in 2005. The majority of patients were in the 20-40 age group. In 22 (84.62%) patients, MRI showed brain demyelinating lesions. Most patients had prolonged VEP latencies. The incidence of idiopathic optic neuropathy has shown a significant increase in the last two years. Brain MRI was the key diagnostic method, along with significant symptoms and signs of idiopathic optic neuropathy. High dose corticosteroid pulse therapy, as described before, was demonstrated to have a beneficial effect on quick recovery of visual acuity and lengthening of relapse-free period.

PubMed, 2009

Acute demyelinating optic neuritis (ON) is the initial presentation in approximately 20% of cases of multiple sclerosis (MS) and is characterized by unilateral, subacute, painful visual loss without systemic or neurological symptoms. The Optic Neuritis Treatment Trial (ONTT) has provided valuable insights into both the natural history and clinical course of demyelinating ON with respect to treatment. Visual function improves spontaneously over weeks and within 12 months 93% have recovered to a visual acuity of at least 20/40. Treatment with high-dose corticosteroids may accelerate visual recovery, but has little impact on long-term visual outcome. In the ONTT the 10-year risk of recurrence of demyelinating ON was 35%. The presence of white matter lesions on the initial magnetic resonance image of the brain has been identified as the strongest predictor for the development of MS. The 15-year risk of developing MS in the ONTT was 25% with no lesions, but 75% with one or more lesions. Since there is evidence of early axonal damage in acute demyelinating ON, disease-modifying drugs should be considered in patients at high risk of developing MS in the future as prophylaxis against permanent neurological impairment.

BMC Neurology

Background: To investigate visual recovery after treatment of acute optic neuritis (ON) with either oral or intravenous high-dose methylprednisolone, in order to establish the best route of administration. Methods: Retrospective analysis of patients treated with oral or intravenous high-dose (≥500 mg per day) methylprednisolone for acute ON of unknown or demyelinating etiology. Twenty-eight patients were included in each treatment group. Visual acuity was measured with the Snellen letter chart, color vision with Boström-Kugelberg pseudo-isochromatic plates, and visual field with a Humphrey Field Analyzer. Results: The treatment results were similar in the two groups at follow-up, with no significant difference in visual acuity (p = 0.54), color vision (p = 0.18), visual field mean deviation (p = 0.39) or the number of highly significantly depressed test points (p = 0.46). Conclusions: The results show no clinical disadvantage of using oral high-dose corticosteroids compared to intravenous administration in the treatment of acute ON, which would facilitate the clinical management of these patients.

American Journal of Ophthalmology, 2005

Journal of Neurology, Neurosurgery & Psychiatry, 2014

Clinical case reports and prospective trials have demonstrated a reproducible benefit of hypothalamicpituitary-adrenal (HPA) axis modulation on the rate of recovery from acute inflammatory central nervous system (CNS) demyelination. As a result, corticosteroid preparations and adrenocorticotrophic hormones are the current mainstays of therapy for the treatment of acute optic neuritis (AON) and acute demyelination in multiple sclerosis.

Japanese Journal of Ophthalmology, 2006

Multiple sclerosis (MS) is an infl ammatory disease of the central nervous system (CNS) characterized by localized myelin destruction. MS is no longer considered to be an unmanageable disease. 1 During the last decade, interferon β-1a, a new drug produced by recombinant DNA technology, has demonstrated a benefi cial effect in modifying the disease course of MS. Both Avonex (Biogen Idec, Cambridge, MA, USA) and Rebif (Serono, Geneva, Switzerland) are recombinant interferon β-1a preparations that are glycosylated and have amino acid sequences identical to natural human interferon β. 1 Treatment with Rebif has reduced the relapse rate of MS by 29% and 32% after 2 years with lower and higher doses, respectively. 2 Treatment with Rebif has also reduced the number of severe relapses, steroid courses, and hospital admissions for MS. 2,3 It has a demonstrated statistically signifi cant benefi t in terms of delaying the progression of disability. Rebif also has shown marked benefi cial effects in terms of magnetic resonance image (MRI) parameters, particularly in the number of enhancing lesions and new or enlarging T2 lesions. 3 Jpn Abstract Purpose: The incidence of multiple sclerosis (MS) is relatively rare in Chinese. The benefi cial effect of interferon β-1a in modifying the disease course of MS has been rarely analyzed in Chinese patients. The aim of this study was to investigate the clinical response to interferon β1-a in Chinese patients with MSassociated optic neuritis (ON).

Journal of Clinical Medicine

We aimed to assess the efficacy of biologic therapy in refractory non-Multiple Sclerosis (MS) Optic Neuritis (ON), a condition more infrequent, chronic and severe than MS ON. This was an open-label multicenter study of patients with non-MS ON refractory to systemic corticosteroids and at least one conventional immunosuppressive drug. The main outcomes were Best Corrected Visual Acuity (BCVA) and both Macular Thickness (MT) and Retinal Nerve Fiber Layer (RNFL) using Optical Coherence Tomography (OCT). These outcome variables were assessed at baseline, 1 week, and 1, 3, 6 and 12 months after biologic therapy initiation. Remission was defined as the absence of ON symptoms and signs that lasted longer than 24 h, with or without an associated new lesion on magnetic resonance imaging with gadolinium contrast agents for at least 3 months. We studied 19 patients (11 women/8 men; mean age, 34.8 ± 13.9 years). The underlying diseases were Bechet’s disease (n = 5), neuromyelitis optica (n = 3)...