Do Vaccines Cause Optic Neuritis or Neuromyelitis Optica?

Conclusion | Epidemiological Evidence | Proposed Biological Mechanism | Archives | References

Vaccines currently routinely recommended to the general population in the U.S.* have not been shown to cause optic neuritis or neuromyelitis optica (NMO).

The 2012 report by the Institute of Medicine (IOM) [1], now called the National Academy of Medicine (NAM), described two studies assessing optic neuritis and MMR, influenza, hepatitis B, diphtheria and tetanus vaccines [2, 3], but these studies did not provide convincing evidence due to a lack of validity and precision. The IOM found no relevant studies of quality in the literature assessing optic neuritis and pertussis vaccine or NMO and MMR, influenza, hepatitis B or HPV vaccines [1].

Studies published since the 2012 IOM report have not found evidence of an association between vaccination and optic neuritis. A prospective cohort study of 189,629 females receiving quadrivalent HPV vaccine (Gardasil®) in California did not find a statistically significant association with optic neuritis [4]. A Vaccine Safety Datalink study found no cases of optic neuritis in over 200,000 pregnant women within 42 days after receiving trivalent inactivated influenza vaccine [5]. A claims-based retrospective matched cohort analysis of females 9-26 years of age did not find an association between HPV vaccine and optic neuritis [6]. A cohort study of 3,983,824 females 10-44 years of age in Denmark and Sweden found no association between quadrivalent HPV vaccine and demyelinating diseases including optic neuritis and neuromyelitis optica [7]. A case-centered analysis in a large integrated Californian health plan population did not find an association between vaccines and optic neuritis [8]. A recent literature review found no increase in risk of optic neuritis after vaccination [9].

Anti-phosphatidylcholine antibodies have been suggested as a potential cause of optic neuritis [10]. A highly specific immunoglobulin G autoantibody that targets aquaporin-4 is present in up to 80% of patients with NMO [11, 12]. One possible mechanism for this is molecular mimicry, which refers to the possibility that similar epitopes shared between self-peptides and foreign peptides (introduced via infection or immunization) inadvertently cause the activation of autoreactive T or B cells, leading to autoimmunity. Another possible mechanism is activation of the complement system, in which a cascade of proteolysis and successive release of cytokines functions to amplify the immune response but can damage host cells if not properly regulated. Other mechanisms that could contribute to optic neuritis or NMO include formation of immune complexes, as well as direct or persistent viral infection. Natural infection with wild-type measles, mumps or rubella viruses has been associated with optic neuritis, albeit very rarely [1].

The 2012 IOM report described two cases of optic neuritis after MMR [13, 14], two cases of optic neuritis after influenza vaccine showing a reoccurrence of symptoms after vaccine rechallenge [15, 16], and one case of NMO after rubella vaccine [17]; however, even when considering knowledge about the aforementioned natural infections, the IOM concluded that this mechanistic evidence was weak. The IOM also concluded that there was no mechanistic evidence for an association between optic neuritis and hepatitis B, diphtheria, tetanus or pertussis vaccines, or between NMO and influenza, hepatitis B, HPV, measles or mumps vaccines [1].

1. Institute of Medicine. In: Stratton K, Ford A, Rusch E, Clayton EW, eds. Adverse Effects of Vaccines: Evidence and Causality. Washington (DC): National Academies Press (US); 2012.
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