Food Aversion Leading to Nutritional Optic Neuropathy in a Child With Severe Vitamin A Deficiency

A 9-year-old boy presented with photophobia and blurred vision. He had no medical or ocular history. The best-corrected visual acuity (BCVA) was counting fingers in both eyes. Anterior segment examination in both eyes was significant for conjunctival and corneal xerosis with diffuse punctate epithelial erosions. Pupils were round and reactive in both eyes without an afferent pupillary defect (APD). Intraocular pressure was normal to finger tension in both eyes.

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Caroline Froment, MD, PhD An-Guor Wang, MD Food Aversion Leading to Nutritional Optic Neuropathy in a Child With Severe Vitamin A Deficiency Maureen C. Farrell, MS, Stephanie J. Weiss, DO, Clifford Goodrich, MD, Maria Patricia Martinez Lehmann, MD, Nicole Delarato, MD A 9-year-old boy presented with photophobia and blurred vision. He had no medical or ocular history. The best-corrected visual acuity (BCVA) was counting fingers in both eyes. Anterior segment examination in both eyes was significant for conjunctival and corneal xerosis with diffuse punctate epithelial erosions. Pupils were round and reactive in both eyes without an afferent pupillary defect (APD). Intraocular pressure was normal to finger tension in both eyes. Funduscopic examination in both eyes was unremarkable with healthy appearing optic nerves. The serum vitamin A level was ,2 mg/dL (reference range, 26– 49 mg/dL). It was recommended he begin vitamin A supplementation and aggressive lubrication with artificial tear drops and ointment. The patient did not return for further treatment. Three years after initial presentation, the patient, now 12 years old, presented with severe malnutrition, eye pain, photophobia, and blurred vision. He did not endorse nyctalopia or aversion to low light environments, nor did his parents. His parents reported a history consistent with severe food aversion and resultant malnutrition. Socioeconomic and developmental limitations resulted in a diet consisting predominantly of processed instant ramen noodles for several years. On examination, the BCVA was 20 of 400 in the right eye and counting fingers at 2 feet in the left eye. Pupillary examination revealed a 1+ APD in the left eye. Anterior segment examination was significant for severely decreased tear film, conjunctival xerosis, diffuse punctate epithelial erosions, and mild corneal haze in both Drexel University College of Medicine (MCF), Philadelphia, Pennsylvania; Department of Ophthalmology (SJW), Retina Service, Weill Cornell Medical College, New York, New York; Department of Ophthalmology (CG), The University of Texas Southwestern Medical Center, Dallas, Texas; Department of Ophthalmology and Visual Sciences (MPML), West Virginia University Eye Institute, Morgantown, West Virginia; and Department of Ophthalmology (ND), St. Christopher’s Hospital for Children, Philadelphia, Pennsylvania. The authors report no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www. jneuro-ophthalmology.com). Address correspondence to Stephanie J. Weiss, DO, Department of Ophthalmology, Retina Service, Weill Cornell Medical College, 1305 York Avenue, New York, NY 10021; E-mail: stephanieweiss33@ gmail.com e718 eyes. Funduscopic examination was significant for grade 3+ optic nerve pallor in the right eye and grade 4+ optic nerve pallor in the left eye. There was no clinically evident retinal atrophy or other retinal pathology in both eyes, although an electroretinogram was not performed so subclinical retinal pathology cannot be entirely excluded. At this time, the vitamin A level was undetectable, the vitamin E level was normal at 7 mg/L, vitamin D 25hydroxycholecalciferol was normal at 34.6 ng/mL, vitamin B9 (folic acid) was normal at 14.6 ng/mL, and vitamin B12 (cyanocobalamin) was normal at 492 pg/mL. Vitamins B6 (pyridoxine), B1 (thiamine), and B2 (riboflavin) were also within normal limits. Dental examination was significant for severe enamel erosion, dental caries, and tooth loss likely caused by vitamin A deficiency. His dental status further contributed to his malnutrition and dietary restrictions resulting in a cyclical decline in nutrition over a period of at least 3 years. He was diagnosed with severe vitamin A deficiency with resultant xerophthalmia and nutritional optic neuropathy. He was treated with vitamin A supplementation (200,000 IU per day for 2 days followed by 20,000 IU per day for 2 months) and aggressive ocular lubrication with artificial tear gel every hour. As part of his treatment, he began therapy to improve his eating habits, and he was removed from his current living situation where his caregivers were deemed unfit to provide appropriate nutritional, medical, and psychosocial support. Of note, he had no other medical history or relevant birth history, and his family history was noncontributory. He did not carry a diagnosis of autism but was found to have global developmental delays. The etiology of his development delays was unknown but was felt to be multifactorial and likely related to his poor psychosocial environment and neglect as well as longstanding malnutrition. No other source or underlying pathology was identified. After aggressive vitamin A supplementation, vitamin A levels normalized to 31 mg/dL. Supplements were stopped, and he was started on a diet rich in vitamin A from pureed pumpkin. On follow-up 5.5 months later, the BCVA was 20 of 80 in the right eye and 20 of 400 in the left eye. A stable 1+ APD in the left eye remained. Anterior segment examination revealed white and quiet conjunctiva and a clear cornea without fluorescein staining in both eyes. Farrell et al: J Neuro-Ophthalmol 2021; 41: e718-e719 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence Funduscopic examination was significant for stable optic atrophy in both eyes. The challenging socioeconomic and psychological factors that lead to food aversion in this child ultimately resulted in a longstanding vitamin A deficiency associated with permanent optic neuropathy. This clinical correspondence was conducted in compliance with the United States Health Insurance Portability and Privacy Act. Vitamin A deficiency in children typically presents with nyctalopia, conjunctival xerosis, Bitot spots, and corneal xerosis (1). Bitot spots are keratinized plaques of conjunctival debris that form around the limbus in association with xerosis (1). Progression to keratomalacia, the most severe manifestation of vitamin A deficiency, is marked by liquefactive necrosis of the stroma, corneal scarring, and opacification (1,2). Although these ocular manifestations of vitamin A deficiency are well described, vitamin A deficiency associated with optic neuropathy as seen in the present case has rarely been described (2–4). Importantly, most described cases of nutritional optic neuropathy have been associated with deficiencies in vitamins B12, B6, B1, B2, B9, or copper rather than vitamin A (3,4). The few reports of vitamin A associated optic neuropathy that exist involve malnourishment in refugees in developing countries, extreme dietary restrictions or food intolerances, and postoperative malabsorptive bariatric surgery patients (5–11). The present case describes the rare occurrence of optic neuropathy secondary to longstanding vitamin A deficiency in a child living in the United States. Interestingly, despite a severely restricted diet, all of the other vitamin levels tested (vitamins E, D, B9, B12, B6, B1, and B2) were found to be within normal limits. This child’s regimented diet consisted mainly of instant ramen noodles which contain 1% of the percent daily value of vitamin A, 11% vitamin E, 0% vitamin D, 25% B9, 3% B6, 26% B1, and 13% B2 (Maruchan Ramen Noodle) (see Supplemental Digital Content 1, Table E1, http://links.lww.com/WNO/A447). The pathogenesis of optic nerve damage in human patients with vitamin A deficiency remains unknown. Interestingly, animal studies of rats with diabetic neuropathy have shown increased levels of nerve growth factor, retinoic acid receptor beta, and reversion of sensorineural disturbances in peripheral nerves after treatment with vitamin A (12). In addition, retinoic acid, a vitamin A derivative, has been shown to play a role in neural development, maintenance, and axon regeneration in cell culture (13). Taken together, these findings suggest a putative role for vitamin A in maintaining the integrity of the optic nerve. This case provides a unique example of permanent optic neuropathy secondary to longstanding vitamin A deficiency occurring within the United States. Although rare in the Farrell et al: J Neuro-Ophthalmol 2021; 41: e718-e719 developed world, given the potential for irreversible vision loss and the need for timely diagnosis, it is important to consider vitamin A deficiency among potential causes when evaluating patients presenting with optic neuropathy. This report also highlights the importance of obtaining a thorough social history to identify socioeconomic and psychological factors that may contribute to adverse health consequences. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: M. C. Farrell, S. J. Weiss, C. Goodrich, M. P. Martinez Lehmann, and N. Delarato; b. Acquisition of data: M. C. Farrell, S. J. Weiss, M. P. Martinez Lehmann; c. Analysis and interpretation of data: M. C. Farrell, S. J. Weiss, and C. Goodrich. Category 2: a. Drafting the manuscript: M. C. Farrell, S. J. Weiss, C. Goodrich, M. P. Martinez Lehmann, and N. Delarato; b. Revising it for intellectual content: M. C. Farrell, S. J. Weiss, C. Goodrich, M. P. Martinez Lehmann, and N. Delarato. Category 3: a. Final approval of the completed manuscript: M. C. Farrell, S. J. Weiss, C. Goodrich, M. P. Martinez Lehmann, and N. Delarato. REFERENCES 1. Harris EW, Loewenstein JI, Azar D. Vitamin A deficiency and its effects on the eye. Int Ophthalmol Clin. 1998;38:155–161. 2. Sommer A, Sommer A. Vitamin A Deficiency and Its Consequences: A Field Guide to Detection and Control. 3rd edition. Geneva, Switzerland: World Health Organization, 1995. 3. Orssaud C, Roche O, Dufier JL. Nutritional optic neuropathies. J Neurol Sci. 2007;262:158–164. 4. Sadun AA. Metabolic optic neuropathies. Semin Ophthalmol. 2002;17:29–32. 5. Stroh C, Weiher C, Hohmann U, Meyer F, Lippert H, Manger T. Vitamin A deficiency (VAD) after a duodenal switch procedure: a case report. Obes Surg. 2010;20:397–400. 6. Ram D, Smith TW, Tan HJ. Vitamin A deficiency mimicking CNS demyelination. Eur J Paediatr Neurol. 2017;21:e116. 7. Simkin SK, Tuck K, Garrett J, Dai S. Vitamin A deficiency—an unexpected cause of visual loss. Lancet. 2016;387:93–94. 8. McCartney F, Berkenstock M, Ackert JM. Vitamin A deficiency as a cause of optic neuropathy. Invest Ophthalmol Vis Sci. 2014;55:6231. 9. Smets RM, Waeben M. Unusual combination of night blindness and optic neuropathy after biliopancreatic bypass. Bull Soc Belge Ophtalmol. 1999;271:93–96. 10. McAbee GN, Prieto DM, Kirby J, Santilli AM, Setty R. Permanent visual loss due to dietary vitamin A deficiency in an autistic adolescent. J Child Neurol. 2009;24:1288–1289. 11. Chiarello F, Marini E, Ballerini A, Ricca V. Optic neuropathy due to nutritional deficiency in a male adolescent with Avoidant/Restrictive Food Intake Disorder: a case report. Eat Weight Disord. 2018;23:533–535. 12. Hernández-Pedro N, Granados-Soto V, Ordoñez G, Pineda B, Rangel-López E, Salazar-Ramiro A, Arrieta O, Sotelo J. Vitamin A increases nerve growth factor and retinoic acid receptor beta and improves diabetic neuropathy in rats. Transl Res. 2014;164:196–201. 13. Maden M, Gale E, Zile M. The role of vitamin A in the development of the central nervous system. J Nutr. 1998;128(2 suppl):471S–475S. e719 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.