Vitamin B12 deficiency evaluation and treatment in severe dry eye disease with neuropathic ocular pain

Graefes Arch Clin Exp Ophthalmol. 2017 Jun;255(6):1173-1177. doi: 10.1007/s00417-017-3632-y. Epub 2017 Mar 15.


Purpose: This study aims to understand the effect of vitamin B12 deficiency on neuropathic ocular pain (NOP) and symptoms in patients with dry eye disease (DED).

Methods: Patients with severe DED (without receiving topical artificial tears treatment) and ocular pain were enrolled (n = 90). Patients with severe DED and vitamin B12 deficiency (group 1, n = 45) received parenteral vitamin B12 supplement + topical treatment (artificial tears treatment + cyclosporine), and patients with severe DED and normal serum vitamin B12 level (group 2, n = 45) received only topical treatment (artificial tears treatment + cyclosporine). Patients were evaluated by the ocular surface disease index (OSDI) questionnaire, 3rd question (have you experienced painful or sore eyes during last week?) score of OSDI as a pain determiner and pain frequency measure), tear break up time (TBUT), and Schirmer's type 1 test. We compared the groups' OSDI, TBUT, and Schirmer's test recordings at the first visit and after 12 weeks retrospectively.

Results: The OSDI score, 3rd OSDI question score, TBUT, and Schirmer's test results improved after 12 weeks (p < 0.001 for each group). The mean vitamin B12 level at enrollment was 144.24 ±43.36 pg/ml in group 1 and 417.53 ±87.22 pg/ml in group 2. The mean vitamin B12 level in group 1 reached to 450 ±60.563 pg/ml after 12 weeks of treatment. The mean score changes between the groups were not statistically significant; however, the decrease in the OSDI questionnaire score (-30.80 ±5.24) and 3rd OSDI question score (-2.82 ±0.53) were remarkable in group 1 (Table 2). The mean TBUT increase was +7.98 ±2.90 s and Schirmer's test result increase was +12.16 ±2.01 mm in group 1. The mean TBUT increase was +6.18 ±1.49 s and Schirmer's test result increase was +6.71 ±1.47 mm in group 2.

Conclusions: These findings indicate that vitamin B12 deficiency is related with NOP. It may be important to consider measuring the serum vitamin B12 level in patients with severe DED presenting with resistant ocular pain despite taking topical treatment.

Keywords: Dry eye disease; Neuropathic ocular pain; Vitamin B12.

MeSH terms

  • Administration, Topical
  • Adult
  • Chronic Pain
  • Dry Eye Syndromes / complications
  • Dry Eye Syndromes / drug therapy*
  • Dry Eye Syndromes / metabolism
  • Eye Pain / drug therapy*
  • Eye Pain / etiology
  • Female
  • Follow-Up Studies
  • Humans
  • Lubricant Eye Drops / administration & dosage*
  • Male
  • Retrospective Studies
  • Treatment Outcome
  • Vitamin B 12 / administration & dosage*
  • Vitamin B 12 / pharmacokinetics
  • Vitamin B 12 Deficiency / complications*
  • Vitamin B 12 Deficiency / drug therapy
  • Vitamin B 12 Deficiency / metabolism
  • Vitamin B Complex / administration & dosage
  • Vitamin B Complex / pharmacokinetics


  • Lubricant Eye Drops
  • Vitamin B Complex
  • Vitamin B 12