In patients with Uhthoff sign, cooling the body by drinking ice water or taking a cold shower will often reverse the deficit (Scherokman et al 1985). Some patients respond to 4-aminopyridine, a drug that increases the duration of the action potential in demyelinated axons by blocking potassium efflux (van Diemen et al 1992b). Red wine, possibly by reducing levels of endothelin-1 and thereby increasing ocular blood flow, temporarily increases visual acuity (Haufschild et al 2003).
High-dose intravenous glucocorticoids speed recovery, especially if started early in the course of neuritis. The typical dose is 1 g of intravenous methylprednisolone per day for 3 days. Inexpensive alternatives are oral dexamethasone, 98 mg twice a day for 3 days, or drinking a 1 g vial of methylprednisolone mixed into an iced fruit drink once a day for 3 days. Oral absorption of steroids is equivalent to IV absorption. Some insurers are not aware of this alternative and do not allow use of the oral forms even though they are 1/100 the cost of a hospital admission. Glucocorticoid boluses are sometimes followed by oral prednisone, tapered from 60 to 5 mg over 3 weeks. High-dose steroids were claimed to reduce the risk of developing further attacks of optic neuritis (Spoor and Rockwell 1988; Beck et al 1992) and reduce progression to multiple sclerosis (Beck et al 1993c). However, later studies showed that steroids did not lead to long-term improvement (Hickman et al 2002; 2003) and did not prevent optic nerve atrophy, a position taken by the American Academy of Neurology in 2000. Nonetheless, neurologists (87%) are more likely than ophthalmologists (48%) to use the high-dose steroid bolus (Biousse et al 2009).
Oral steroids at moderate doses of approximately 60 mg/day, with a relatively abrupt taper, actually seemed to provoke twice as many attacks of multiple sclerosis compared to high-dose intravenous steroids or placebo in the optic neuritis treatment trial (ONTT). (Beck and Gal 2008). These differential effects vanished over 5 years, but oral steroids at this dose are no longer used to treat optic neuritis. An abrupt discontinuation of steroids may precipitate attacks of optic neuritis (Dutton et al 1982; Herishanu et al 1989; Farris and Pickard 1990), suggesting that glucocorticoids should be tapered over 3 weeks (Reder et al 1994). Nonetheless, 17% of ophthalmologists and neurologists treat acute optic neuritis with oral steroids and a taper; this group is less likely to know the results of the ONTT (Biousse et al 2009; Pula and Javed 2009).
Some of the information on responses to steroid therapy in optic neuritis may be biased from admixing idiopathic optic neuritis with neuromyelitis optica. The latter has features of antibody-mediated connective tissue disease, and abrupt steroid discontinuations may be more dangerous in this variant. In chronic relapsing inflammatory optic neuritis (CRION), relapses occur with rapid steroid withdrawal, suggesting this is a form of neuromyelitis optica and not the idiopathic form of optic neuritis (Kidd et al 2003; Plant 2008).
Intravenous immunoglobulin was effective in relapsing-remitting multiple sclerosis patients with severe optic neuritis (vision worse than 20/400) who had failed high-dose intravenous methylprednisolone 3 months prior (Tselis et al 2008). Seventy-eight percent improved to near normal, compared to only 12% of untreated patients. Note that some of these may have been cases of neuromyelitis optica, as nearly half were African American, and this study predated the use of testing for the neuromyelitis optica antibody. In earlier studies, intravenous immunoglobulin improved vision in patients whose "visual acuity failed to recover after 6 months following acute optic neuritis" (Van Engelen et al 1992). However, in 2 controlled trials, it had little benefit (Noseworthy et al 2001; Roed et al 2005b).
Plasma exchange may be effective in some steroid-refractory patients (Roesner et al 2012). However, spontaneous recovery may explain putative efficacy (Kaur and Bennett 2007).
Multiple sclerosis is often associated with optic neuritis. The exacerbation frequency in multiple sclerosis is reduced by interferon beta (Sibley 1993) and copolymer I (glatiramer acetate). These therapies are most effective if started early. If optic neuritis is a forme fruste of multiple sclerosis or shares a similar etiology, treatment with these agents seems reasonable. Interferon beta-1a therapy of acute monosymptomatic optic neuritis with multiple sclerosis-like MRI abnormalities reduced the chance of developing multiple sclerosis (Jacobs et al 2000). In clinically isolated syndromes and optic neuritis, the chance of developing multiple sclerosis is reduced by approximately 50% with subcutaneous weekly IFN beta-1a and with every-other-day IFN beta-1b in multiple studies (Kaur and Bennett 2007). The latter is approved for treatment of clinically isolated syndrome when there is a confirmatory MRI with multi-aged lesions. In Taiwan, 44 μg of interferon beta-1a thrice weekly reduced the chance of relapses of optic neuritis in patients with multiple sclerosis (Chen et al 2010). Relapses fell from 1.01 per year in the 4 years prior to therapy to 0.21 relapses per year in the 3 years after therapy. There was no paired placebo group, but in this group of Asian patients, interferon did not cause exacerbations.
“High risk” patients with concomitant MRI lesions have a two thirds chance of developing multiple sclerosis within 5 years, but some will not. Conversely, only 10% of patients with optic neuritis with a negative brain MRI will develop multiple sclerosis. An intensive history and examination, as well as MRI, spinal fluid, and patient psychology must be integrated into the decision to start long-term, expensive therapy.
Future treatments include antibodies to very late activation antigen (VLA-4) on immune cells (natalizumab) and neuroprotective agents such as erythropoietin--which prevents retinal nerve fiber layer thinning, ciliary neurotrophic factor, flupirtine (a Kv7 channel activator; in contrast, 4-aminopyridine is a K channel blocker), memantine (high-concentration-NMDA blocker), and sirtuin/SIRT1 activators (histone deacetylases). Three- to six-month pulses of interferon or other nonsteroidal multiple sclerosis drugs have not been tested. Inflammation in the eye can induce trophic factors from Muller cells.
Vitamin D3 supplementation (50,000 U/week x 1 year) reduced MRI lesions and conversion to clinically definite multiple sclerosis in a small study (Derakhshandi et al 2012).
Statins improved visual evoked potentials and latency in acute optic neuritis (Tsakiri et al 2012). However, significant mismatch in baseline function, despite randomization, makes the benefit questionable (Johnson and Cadavid 2012).
Antitumor necrosis therapy (infliximab, adalimumab, etanercept) can occasionally trigger multiple sclerosis and optic neuritis.