CORNEA Vitamin B12 deficiency evaluation and treatment in severe dry eye disease with neuropathic ocular pain Serkan Ozen 1 & Murat Atabey Ozer 1 & Mehmet Orçun Akdemir 2 Received: 17 November 2016 /Revised: 8 February 2017 /Accepted: 6 March 2017 # Springer-Verlag Berlin Heidelberg 2017 Abstract Purpose This study aims to understand the effect of vitamin B12 deficiency on neuropathic ocular pain (NOP) and symp- toms 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 (artifi- cial 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 fre- quency 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 enroll- ment 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 statis- tically significant; however, the decrease in the OSDI ques- tionnaire 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 defi- ciency 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 top- ical treatment. Keywords Vitamin B12 . Neuropathic ocular pain . Dry eye disease Introduction Dry eye is a multifactorial disease of the tears and ocular surface that results in symptoms such as discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface [1]. Blurred vision, irritation, and ocular pain are the main symptoms of dry eye disease (DED). The symptoms associated with DED are chronic and require visits to an ophthalmologist, and their treatment has significant cost implications [2]. Within dry eye-associated ocular pain, some patients report transient pain and others, chronic pain. When ocular pain in DED patients persists for more than 6 months, it is considered chronic ocular pain [3]. Pain in patients with chronic DED show characteristics of chronic neuropathic oc- ular pain (NOP). In DED’ s chronic stage, changes occur in the ocular sensory apparatus. If ocular surface damage persists, changes may occur in the central nervous system (CNS), * Serkan Ozen serkan_zen@hotmail.com 1 Section of Surgical Sciences, Department of Ophthalmology, Faculty of Medicine, Giresun University, Debboy 28100, Giresun, Turkey 2 Section of Surgical Sciences, Department of Ophthalmology, Faculty of Medicine, Bülent Ecevit University Zonguldak, 67600 Zonguldak, Turkey Graefes Arch Clin Exp Ophthalmol DOI 10.1007/s00417-017-3632-y