B12 deficiency, optic neuropathy and cyanocobalamin nasal spray.

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Editor, Vitamin B12 in the form of cyanocobalamin (CNCbl) nasal spray was approved in 2005 (Nascobal® FDA). This is the first report describing the evolution of optic neuropathy in a patient whose low serum vitamin B12 was supplemented by CNCbl nasal spray. A 60-year-old man with chronic tobacco and alcohol use noted progressive visual blur in his left eye. Blood testing revealed mild macrocytosis (107 fl; reference 81–99 fl) and low vitamin B12 (116 pmol/l; reference 138–652 pmol/l). Due to longstanding gastric problems, vitamin B12 supplementation was started by nasal spray (CNCbl 500 μg/0.1 ml in one nostril once per week). The cause of visual blur was not determined at this time. Subsequent ophthalmologic examination showed visual acuity of 20/20 in the right eye (RE) and 20/32 in the left eye (LE). Biomicroscopy and funduscopy were normal. Macular and optic nerve optical coherence tomography was normal. Visual field testing showed small bilateral central scotomas (Fig. 1Α) and an optic neuropathy was suspected. Neuroimaging, serologic testing and molecular analysis excluded other causes of optic neuropathy. The patient confirmed taking vitamin B12 supplementation. Two months later, the patient was referred for neuro-ophthalomologic consultation. Visual acuity was 20/40 RE and counting fingers LE with enlarging central scotomas (Fig. 1Β). Bilateral dyschromatopsia and early optic atrophy were noted. Serum level of vitamin B12 was still low (holotranscobalamin 36 pmol/l; reference> 50 pmol/l). Treatment was changed to intramuscular hydroxycobalamin (OHCbl). One week later, visual acuity was improved to 20/32 RE and 20/100 LE. Three months later, serum B12 level was normalized (holotranscobalamin level > 128 pmol/l). Six months later, central scotomas were nearly resolved (Fig. 1C) and acuity was 20/25 RE and 20/40 LE. The CNCbl (B12) nasal spray is recommended for maintenance therapy after intramuscular B12 treatment in adult patients with pernicious anaemia without neurologic involvement or as primary treatment of adult patients with vitamin B12 deficiency not due to pernicious anaemia (Nascobal® FDA). In a small case series, CNCbl nasal spray effectively increased serum B12 levels and improved symptomatic paresthesias (Zamuner et al. 2014). In contrast to synthetically derived CNCbl, OHCbl is a natural form with better tissue bioavailability (Paul & Brady 2017). In patients with asymptomatic B12 deficiency who were given three consecutive weekly doses of 1500 μg OHCbl nasal spray, a sustained increase in serum level was noted after one dose and became normalized following the second dose (Slot et al. 1997). OHCbl is not, however, commercially available as nasal spray. Our patient’s persistently low serum level of B12 after 2 months of CNCbl nasal spray suggests that it does not share the same pharmacokinetics as OHCbl nasal spray (Slot et al.1997; Paul & Brady 2017). Ophthalmologists are likely less familiar with vitamin B12 in nasal spray form as they do not routinely prescribe B12 supplements. Our patient did not specify nasal spray usage and assumption was that he was taking oral supplementation. Oral CNCbl administration has been shown to successfully treat mild neurologic symptoms related to vitamin B12 deficiency (Kuzminski et al. 1998). The role of nasal spray administration for mild neurologic symptoms is unclear as the literature is limited to a single report noting resolution of paresthesias with CNCbl nasal spray treatment (Zamuner et al. 2014). Our patient’s clinical evolution contradicts that report as his mild unilateral visual blur became significant bilateral visual loss during use of nasal spray. This is the first report to describe the development and progression of optic neuropathy in a patient with low B12 level using CNCbl nasal spray and thus does not lend evidence to support nasal spray administration as a treatment of B12 deficiency optic neuropathy.