From the Cole Eye Institute (CDL, EIT, BHJ) and the Center for Pediatric Neurology (DAR), Cleveland Clinic, Cleveland, Ohio.
The authors have no financial or proprietary interest in the materials presented herein.
Supported in part by a Research to Prevent Blindness Challenge Grant, Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine; NIH 1KL2 RR024990; and the Multidisciplinary Clinical Research Training Award (BHJ).
Address correspondence to Bennie H. Jeng, MD, Department of Ophthalmology, University of California, 10 Koret Way, K-304, San Francisco, CA 94143-0730. E-mail: firstname.lastname@example.org.
Worldwide, vitamin A deficiency is a significant cause of childhood blindness and mortality. However, symptomatic vitamin A deficiency is rare in developed countries and limited to isolated case reports.1–8 Patients with a restricted range of food intake and those with malabsorption syndromes are at risk for otherwise rare vitamin deficiency states. We present a case of xerophthalmia and idiopathic intracranial hypertension secondary to vitamin A deficiency that resulted from an abnormal diet in a boy with autism.
A 10-year-old boy with autism was referred to the cornea and external disease service for evaluation and management of severe dry eyes. His parents reported that his eyes had been red for several weeks, and they observed a recent onset of frequent eye rubbing. The patient stated that his eyes were “gunky” in the morning and were sore to the touch. He had been recently examined by an ophthalmologist and prescribed erythromycin ointment four times daily for dry eyes. He was referred to our service after his symptoms failed to improve.
The patient’s medical history was significant for moderately severe autism and a well-controlled seizure disorder. Four months prior to the current presentation, he was evaluated for persistent headaches and found to have mild optic nerve head edema. A subsequent lumbar puncture revealed an elevated opening pressure of 25 mm Hg with an otherwise unremarkable cerebral spinal fluid composition (the upper limit of normal intracranial pressure in children 6 to 16 years of age is 12.9 mm Hg9). He was diagnosed as having idiopathic intracranial hypertension and prescribed oral acetazolamide. His other medications included paroxetine, carbamazepine, risperidone, amphetamine mixed salts, and cyproheptadine.
His visual acuity was 20/50 in both eyes, compared with a previously recorded visual acuity of 20/20 in both eyes 4 months prior. Slit-lamp biomicroscopy revealed a nearly keratinized appearance to the bulbar conjunctiva, a dull appearance of the corneal surface, and an absent tear lake bilaterally. Staining with fluorescein and rose bengal stains demonstrated diffuse, dense interpalpebral punctate epithelial erosions bilaterally (Figure). Ophthalmoscopic examination revealed mild papilledema in both eyes.
Figure. (A) Slit-Lamp Photograph Demonstrating Dull-Appearing Corneal Surface. (B) Fluorescein Staining Revealed Diffuse Interpalpebral Punctate Epithelial Erosions.
Given the extreme dryness of the ocular surface, we suspected a vitamin A deficiency and obtained a detailed food history. The patient’s parents reported that he was a picky eater and only ate potatoes and a few other food items.
Laboratory testing revealed a serum vitamin A level of less than 3 μg/dL, well below the normal range of 20 to 120 μg/dL. Based on the patient’s history, clinical findings, and laboratory results, he was diagnosed as having systemic vitamin A deficiency with xerophthalmia. He was given oral vitamin A supplementation and started topical all-trans-retinoic acid 0.01% ointment nightly. At the 6-week follow-up appointment, the ocular surface had normalized and the visual acuity returned to 20/20 in both eyes.
Globally, vitamin A deficiency is the leading cause of childhood blindness, accounting for 350,000 cases per year.10 In addition, children with vitamin A deficiencies have a substantially increased morbidity and mortality rate from common infectious diseases such as measles, diarrheal disease, and malaria due to an impaired immune response.11,12 However, symptomatic vitamin A deficiency is rare in developed countries and usually occurs in the setting of a severely restricted diet or malabsorption syndrome.1,3–5,8
The ocular manifestations of vitamin A deficiency typically occur in a reliable sequence. The earliest symptom is night blindness, followed by conjunctival and corneal dryness, or xerosis. Bitôt spots, foamy triangular patches composed of keratinized debris and the by-products of the gas-producing Corynebacterium xerosis, may be seen, most commonly on the temporal interpalpebral conjunctiva. If the hypovitaminosis is left untreated, corneal ulceration and keratomalacia may follow, leading to corneal perforation or scarring. Retinal degeneration may occur but is generally a late finding characterized by a pigmentary retinopathy.2 Although our patient may have had difficulties with night vision, he could not communicate that symptom and his parents were not aware of it.
The treatment of xerophthalmia is vitamin A supplementation. The initial replenishment dose is 200,000 IU daily for 2 days. To hasten ocular surface recovery, topical vitamin A supplementation can be added, as in the current case, in the form of all-trans-retinoic acid ointment. The night blindness, xerosis, and fundus lesions typically resolve completely with adequate vitamin A supplementation, although complications from corneal ulcers or keratomalacia may produce permanent vision loss.
Interestingly, our patient was also recently diagnosed as having intracranial hypertension. For reasons not well understood, both hypervitaminosis and hypovitaminosis A are associated with intracranial hypertension.1,13 For example, Panozzo et al. reported the case of a woman who developed xerophthalmia and idiopathic intracranial hypertension after biliopancreatic bypass surgery; her symptoms resolved with vitamin A supplementation.1
Despite the overall rare incidence of vitamin A deficiency, multiple case reports describe symptomatic vitamin A deficiency in children with autism.3,4,6,8 Patients with autism may become malnourished due to dietary restrictions that are either self-imposed, externally imposed, or a combination of both, as is likely in the current case. Interestingly, in four of the five reported cases, including the current case, the patient’s diet consisted almost entirely of potatoes.4,6,8
Although rare in developed countries, xerophthalmia may occur in patients with severely restricted diets or malabsorption syndromes. A high level of suspicion of hypovitaminosis A is required in such patients if they present with early signs and symptoms of the disease, such as in the current case. Prompt diagnosis and treatment with vitamin A supplementation can prevent permanent vision loss.
- Panozzo G, Babighian S, Bonora A. Association of xerophthalmia, flecked retina, and pseudotumor cerebri caused by hypovitaminosis A. Am J Ophthalmol. 1998;125:708–710. doi:10.1016/S0002-9394(98)00011-7 [CrossRef]
- Smith J, Steinemann TL. Vitamin A deficiency and the eye. Int Ophthalmol Clin. 2000;40:83–91. doi:10.1097/00004397-200010000-00007 [CrossRef]
- Steinemann TL, Christiansen SP. Vitamin A deficiency and xerophthalmia in an autistic child. Arch Ophthalmol. 1998;116:392–393.
- Basti S, Schmidt C. Vitamin a deficiency. Cornea. 2008;27:973. doi:10.1097/ICO.0b013e318177011a [CrossRef]
- Cooney TM, Johnson CS, Elner VM. Keratomalacia caused by psychiatric-induced dietary restrictions. Cornea. 2007;26:995–997. doi:10.1097/ICO.0b013e3180959a5d [CrossRef]
- Clark JH, Rhoden DK, Turner DS. Symptomatic vitamin A and D deficiencies in an eight-year-old with autism. JPEN J Parenter Enteral Nutr. 1993;17:284–286. doi:10.1177/0148607193017003284 [CrossRef]
- Fiore P, De Marco R, Sacco O, Priolo E. Nightblindness, xerophthalmia, and severe loss of visual acuity due to unnecessary dietary restriction. Nutrition. 2004;20:477. doi:10.1016/j.nut.2004.01.014 [CrossRef]
- Uyanik O, Dogangun B, Kayaalp L, Korkmaz B, Dervent A. Food faddism causing vision loss in an autistic child. Child Care Health Dev. 2006;32:601–602. doi:10.1111/j.1365-2214.2006.00586.x [CrossRef]
- Wiegand C, Richards P. Measurement of intracranial pressure in children: a critical review of current methods. Dev Med Child Neurol. 2007;49:935–941. doi:10.1111/j.1469-8749.2007.00935.x [CrossRef]
- Whitcher JP, Srinivasan M, Upadhyay MP. Corneal blindness: a global perspective. Bull World Health Organ. 2001;79:214–221.
- Glasziou PP, Mackerras DE. Vitamin A supplementation in infectious diseases: a meta-analysis. BMJ. 1993;306:366–370. doi:10.1136/bmj.306.6874.366 [CrossRef]
- Sommer A, Tarwotjo I, Djunaedi E, et al. Impact of vitamin A supplementation on childhood mortality: a randomised controlled community trial. Lancet. 1986;1:1169–1173. doi:10.1016/S0140-6736(86)91157-8 [CrossRef]
- Ball AK, Clarke CE. Idiopathic intracranial hypertension. Lancet Neurol. 2006;5:433–442. doi:10.1016/S1474-4422(06)70442-2 [CrossRef]