Nutritional Optic Neuropathy From Chronic Omeprazole Use

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Caroline Froment, MD, PhD An-Gour Wang, MD Nutritional Optic Neuropathy From Chronic Omeprazole Use Ahmad Rehmani, DO, Isha Mehta, DO, Nga Yan Siu, DO, Edward Smith, MD N utritional optic neuropathy is a condition characterized by progressive, painless, symmetrical loss of vision, in the form central or cecocentral scotomas, due to a deficiency in certain essential nutrients. It can also present with dyschromatopsia, decreased contrast sensitivity, and temporal optic disc pallor. In recent years, it has been classified under the umbrella of mitochondrial optic neuropathies, which include both inherited (Leber’s hereditary optic neuropathy and dominant optic atrophy) and acquired (nutritional and toxic optic neuropathies). Regardless of the underlying etiology, studies have shown that nutritional neuropathies share a selective damage and loss of retinal ganglion cells due to mitochondrial dysfunction in the prelaminar area of the optic nerve (1). Here, we present a case of nutritional optic neuropathy from vitamin B12 deficiency. This was the sequela of chronic oral proton pump inhibitor (PPI) use; moreover, it was found to be reversible with supplementation of vitamin B12 and cessation of the PPI. CASE A 38-year-old woman presented with a chief complaint of blurry vision and “dullness of colors” for 2 weeks. She had a medical history of gastrointestinal reflux disease with over 20 years of daily omeprazole use. On examination, her best-corrected visual acuity was 20/50 in the right eye and 20/50+ in the left eye. Color plates were 0/11 and 1/11 by Ishihara in the right and left eyes, respectively. The patient’s anterior segment examination was unremarkable, and intraocular pressures were 17 in both eyes. Fundus examination revealed temporal pallor, greater in the right eye than the left eye (Fig. 1). Otherwise, the dilated examination was within normal limits. A 24-2 Humphrey visual field revealed central scotomas in both eyes (Fig. 2). MRI of the brain and orbits showed no intraorbital or optic nerve abnormality and no evidence of intracranial heme, mass lesions, or infarcts. The paDepartment of Ophthalmology, Kingsbrook Jewish Medical Center, Brooklyn, New York. The authors report no conflicts of interest. Address correspondence to Ahmad Rehmani, DO, Department of Ophthalmology, Kingsbrook Jewish Medical Center, 327 Beach 19th Street, Far Rockaway, NY 11691; E-mail: [e-mail] Rehmani et al: J Neuro-Ophthalmol 2021; 41: e169-e171 tient’s blood work revealed normal antinuclear antibody, angiotensin-converting enzyme, quantiferon gold, protein S, and protein C levels and, however, showed a total vitamin B12 level of 459 (normal reference range 200–1,100). Thus, vitamin B12 supplementation was initiated, as well as alcohol and omeprazole cessation. Remarkably, 2 weeks later, the patient’s visual acuity improved to 20/30 + 2 in the right eye and 20/30-1 in the left eye with resolution of central scotoma on repeat Humphrey visual field. Her color vision also improved to 11/11 in the right eye and 8/11 in the left eye by ishihara. DISCUSSION Nutritional optic neuropathy is a characteristic progressive, painless, symmetrical visual impairment, as a result of selective effects on the papillomacular bundle (PMB) of the optic nerve, secondary to deprivation of an essential nutrient. Visual loss is usually in the form of a central or cecocentral scotoma. Other symptoms typically include dyschromatopsia and loss of contrast sensitivity (2). On examination, the optic nerve can appear swollen or hyperemic early in the disease course and show optic disc pallor and PMB nerve fiber layer loss in later stages. Etiologies are numerous, but the most commonly implicated vitamins include B12, B1, and copper deficiencies. Other vitamins such as B2, B3, B6, and folate can also play a role (2,3). Patients at particular risk of nutritional optic neuropathy include alcoholics, vegans, those with a history of gastrointestinal bypass surgery, inflammatory bowel disease, pernicious anemia, and certain food avoidance patterns, such as in patients with autism and depression (2). Despite understanding the etiology, the exact pathophysiology of nutritional optic neuropathy is not well defined. It has been shown that mitochondrial dysfunction underlies the selective degeneration of the nerve fibers in the PMB in hereditary (i.e., Leber’s hereditary optic neuropathy), and acquired (i.e., nutritional and toxic) optic neuropathies (4). Rizzo (5) proposed that deficiency of adenosine triphosphate (ATP) might be a unifying etiology for several types of optic neuropathy. It is generally accepted that retinal metabolism is impaired through mitochondrial injury from an imbalance of intracellular and extracellular-free radical homeostasis within retinal ganglion cells (2). e169 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 1. Fundus photographs of right (A) and left (B) eyes, demonstrating temporal pallor. Vitamin B12 deficiency in particular leads to accumulation of formic acid, which inhibits the electron transport chain, mitochondrial function, and ATP synthesis (3). Our patient presented with a B12 level in the lower end of the reference range of normal and was symptomatic. Although total serum vitamin B12 measurement is commonly used due to cost-effectiveness, it has limited sensitivity and specificity, especially in persons with vitamin B12 concentrations ,400 pmol/L (6). Further- more, studies have shown clinical signs of vitamin B12 deficiency can be seen in persons with vitamin B12 concentrations within normal reference range. These patients may still have low B12 tissue levels despite relatively normal serum levels (9). In our patient, daily use of the PPI omeprazole contributed to the development of subnormal levels of vitamin B12. PPIs may lead to vitamin B12 malabsorption due to interference in a digestive system pathway (7). FIG. 2. Humphrey visual field 24-2 of right (A) and left (B) eyes, demonstrating central scotomas. e170 Rehmani et al: J Neuro-Ophthalmol 2021; 41: e169-e171 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence First, vitamin B12 requires enzymatic cleavage by pepsin from dietary proteins, which requires gastric acid for activation. Next, vitamin B12 is bound by R-proteins to prevent pancreatic digestion and passes into the upper small intestine. Here R-protein is degraded and B12 immediately forms a complex with intrinsic factor. This complex travels through the small intestine to the ileum where it attaches to selective membrane receptors present on epithelial cells and subsequently enters the bloodstream (7,8). PPIs are the most potent inhibitors of gastric acid secretion due to their multiple actions. They can lead to hypochlorhydria and inadequate cleavage of B12 from dietary proteins. In addition, they have also been shown to decrease intrinsic factor production (9). Chronic use of these gastric medications can thus lead to B12 deficiency. In our patient, chronic omeprazole use for 20 years led to symptomatic vitamin B12 deficiency. Two weeks after the cessation of omeprazole and supplementation with B12, the patient’s visual symptoms improved significantly with resolution of the central scotoma and near normalization of color vision. Although her B12 levels were not subnormal, literature has shown that serum B12 levels do not necessarily reflect tissue B12 levels; hence, levels in the lower normal reference range do not rule out vitamin B12 deficiency (2,6,10). Thus, when nutritional optic neuropathy is suspected, it is wise to treat patients prophylactically. To the best of our knowledge, this is the first reported case of toxic optic neuropathy due in part to vitamin B12 deficiency caused by chronic PPI use. Rehmani et al: J Neuro-Ophthalmol 2021; 41: e169-e171 STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: A. Rehmani; b. Acquisition of data: A. Rehmani; c. Analysis and interpretation of data: A. Rehmani. Category 2: a. Drafting the manuscript: I. Mehta, N. Y. Siu and E. Smith; b. 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