Ocular Surface Disease Secondary to Vitamin a Deficiency in the Developed World

SMALL CASE SERIES

diffuse punctate epithelial erosions tion. Her symptoms and staining pat- Ocular Surface Disease in both eyes, she had a peripheral tern improved significantly over 1 Secondary to Vitamin A corneal ulcer in the left eye, which month. Deficiency in the was treated with topical antibiot- Case 3. A 9-year-old autistic boy Developed World: ics. Five days later, the ulcer had pro- was referred for visual loss, in addi- It Still Exists gressed to a small perforation. This tion to red eyes and decreased night was managed with cyanoacrylate vision, over the past 4 months as glue and a bandage contact lens. Her noted by his mother. He had been di- Vitamin A deficiency remains a lead- vitamin A level was 20 µg/dL (to agnosed as having chronic conjunc- ing cause of preventable blindness convert to micromoles per liter, mul- tivitis, which was unsuccessfully worldwide but has only rarely been tiply by 0.0349) (reference range, treatedwithacorticosteroid-antibiotic reported within the past 2 decades 38-98 µg/dL). After intramuscular vi- combination. On examination under in the United States where nutri- tamin A administration, the pa- anesthesia, he had chronic bilateral tional deficiencies are not largely en- tient’s ocular condition stabilized, nonhealing epithelial defects, a rela- demic. We describe 4 patients in the and she was discharged to follow up tive afferent pupillary defect in the left United States who had ocular sur- with her local ophthalmologist. eye, and profound optic atrophy in face disease as a result of vitamin A Case 2. A 54-year-old woman with the left eye greater than in the right deficiency (Table). a 10-year history of primary biliary eye. His visual acuity was not attain- cirrhosis was referred for severe dry able because of lack of cooperation. Report of Cases. Case 1. A 79-year- eyes starting 6 months prior, which It was later discovered that his diet old woman with a 15-year history of were unsuccessfully treated with cy- consisted exclusively of french fries. primary biliary cirrhosis and sec- closporine A, 0.05%, and frequent lu- His vitamin A level was 3 µg/dL. His ondary Sjo¨gren syndrome pre- brication. On examination, her vi- epithelialdefectshealedwithfrequent sented with a 1-year history of sual acuity was 20/25 OD and 20/30 lubrication and remained healed with chronic conjunctivitis refractory to OS. Schirmer I test results were ab- oral vitamin A supplementation. treatment with topical antibiotics. normal in both eyes. She had diffuse Case 4. A 26-year-old homeless Three months prior, the patient un- punctate epithelial erosions with fila- and severely depressed woman pre- derwent a tectonic penetrating kera- ments in both eyes and interpalpe- sented with recurrent corneal ul- toplasty in her right eye because of bral lissamine green staining. Her vi- cers and corneal perforation neces- a perforated corneal ulcer. She had tamin A level was 11 µg/dL, and she sitating penetrating keratoplasty in nyctalopia for 2 years. Her visual started treatment with vitamin A oint- the right eye. Her ocular condition acuity was 20/200 OD and count- ment, 0.01%, once daily at bedtime was thought to be secondary to se- ing fingers at 3 ft OS. In addition to and oral vitamin A supplementa- vere atopic disease. On examina-

Table. Patients With Vitamin A–Induced Ocular Surface Disease

Age at Vitamin A Response Duration of Patient Underlying Presentation, Level, Ocular Disease at Route of Vitamin A to Treatment Follow-up, No. Condition y µg/dLa Presentation Nyctalopia Supplementation (Time Course) mo 1 Primary biliary 79 20 Bilateral corneal ϩ Intramuscular Stabilization (1 mo) 2 cirrhosis perforations 2 Primary biliary 54 11 Keratoconjunctivitis Unknown Oral and topical Improvement in 10 cirrhosis sicca symptoms and signs (1 mo) 3 Autism, 9 3 Bilateral nonhealing ϩ Oral Healing of epithelial 7 malnutrition (diet corneal epithelial defects (healed with of french fries defects lubrication alone in 1 only) wk, remained stable only on vitamin A supplementation) 4 Depression, 26 5 Bilateral corneal melt ϩ Oral Stabilization (2 mo) 2 malnutrition

Abbreviation: ϩ, present. SI conversion factor: To convert vitamin A to micromoles per liter, multiply by 0.0349 a Reference range, 38-98 µg/dL.

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©2011 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/26/2021 tion, she had hand motions vision that improved only with vitamin A Author Affiliations: Department of OU, a failed corneal graft with cor- supplementation. The association Ophthalmology, University of Cali- neal thinning and an epithelial de- between xerophthalmia and iatro- fornia, San Francisco. fect in the right eye, and severe genically induced malabsorption Correspondence: Dr Jeng, Depart- corneal thinning with a corneal per- syndromes in obese patients who ment of Ophthalmology, Univer- foration in the left eye. The corneal have undergone bariatric surgery is sity of California, San Francisco, 10 perforation in the left eye was man- also noteworthy given the increas- Koret Way, K-304, San Francisco, aged with cyanoacrylate glue and a ing rate of obesity in the United CA 94143-0730 ([email protected] bandage contact lens. The patient States.6 .edu). was malnourished because of her so- Primary biliary cirrhosis is an au- Financial Disclosure: None re- cial situation and psychiatric dete- toimmune condition characterized ported. rioration, with a vitamin A level of by the progressive destruction of in- Funding/Support: This work was 5 µg/dL. After improving nutri- trahepatic biliary canaliculi, ulti- supported in part by an unre- tional intake, both eyes improved, mately resulting in malabsorption of stricted grant from Research to Pre- with resolution of the epithelial de- fat-soluble vitamins. A significant vent Blindness and a That Man May fect in the right eye and stabiliza- proportion of patients with pri- See grant to the Department of Oph- tion of the perforation in the left eye. mary biliary cirrhosis also have sec- thalmology, University of Califor- She was discharged with recommen- ondary Sjo¨gren syndrome. In the pa- nia, San Francisco. dations to continue oral vitamin A tients who have developed vitamin Previous Presentation: This study supplementation. A deficiency, mucin deficiency oc- was presented in part at the Asso- curs as a result of abnormal termi- ciation for Research in Vision and Comment. The World Health Or- nal differentiation of the conjuncti- Ophthalmology annual meeting; ganization lists vitamin A defi- val goblet cells in which vitamin A May 3, 2010; Fort Lauderdale, ciency as one of the most impor- plays a crucial role, and aqueous tear Florida. tant causes of preventable childhood deficiency from secondary Sjo¨gren 1 1. World Health Organization. Global Prevalence blindness. Dysfunction of corneal syndrome compounds the effect of of Vitamin A Deficiency in Populations at Risk and conjunctival epithelial cell dif- mucin deficiency on corneal health. 1995–2005. WHO Global Database on Vitamin A ferentiation governed by vitamin A Deficiency. Geneva, Switzerland: World Health In cases 2 and 3, although anti-Ro Organization; 2009. results in graded abnormalities in the and anti-La antibody tests were not 2. Heinz C, Steuhl KP, Meller D. Corneal perfora- ocular surface ranging from punc- performed, given that clinical im- tion associated with vitamin-A-deficiency [in German]. Ophthalmologe. 2004;101(6):614- tate epithelial erosions to corneal provement was only seen after ini- 617. 2,3 perforation. It can be initially mis- tiation of vitamin A therapy, we be- 3. Smith J, Steinemann TL. Vitamin A deficiency diagnosed since the signs are easily and the eye. Int Ophthalmol Clin. 2000;40(4): lieve that the vitamin A deficiency 83-91. mistaken for epithelial erosions played a more significant role than 4. Cooney TM, Johnson CS, Elner VM. Keratoma- seen in keratoconjunctivitis sicca or the secondary Sjo¨gren syndrome in lacia caused by psychiatric-induced dietary exposure keratopathy. Without restrictions. Cornea. 2007;26(8):995-997. the development of the clinical 5. Lewis CD, Traboulsi EI, Rothner AD, Jeng BH. treating the underlying vitamin A de- findings. Xerophthalmia and intracranial hypertension in an ficiency, these ocular surface con- In all 4 cases, the underlying vi- autistic child with vitamin A deficiency [published online March 26, 2010]. J Pediatr Ophthalmol ditions are progressive and refrac- tamin A deficiency was not recog- Strabismus. 2010:1-3. doi:10.3928/01913913- tory to lubricating therapy or even nized until severe ocular surface 20100318-04. surgical intervention. 6. Lee WB, Hamilton SM, Harris JP, Schwab IR. disease was seen, in many cases re- Ocular complications of hypovitaminosis a af- In the developed world where vi- quiring surgical intervention. This ter bariatric surgery. Ophthalmology. 2005;112 tamin A deficiency is thought to be may be because of the perception (6):1031-1034. nearly eradicated, severe ocular sur- that vitamin A deficiency does not face disease due to vitamin A defi- occur in developed nations. How- ciency has been isolated to cases of ever, our cases remind us that in re- malnutrition in patients with psy- fractory cases of ocular surface dis- Retinal Dystrophy chiatric conditions or malabsorp- ease not amenable to standard tion syndromes due to chronic liver treatments, especially in the setting in 2 Brothers 2,4 ␣ or gastrointestinal disease. Cooney of psychiatric conditions, autistic With -Mannosidosis and associates4 described a malnour- children, and malabsorption syn- ished psychiatric patient who, like dromes, one should consider vita- ␣-Mannosidosis is a rare, autoso- case 4, had bilateral corneal perfo- min A deficiency. Complications of mal, recessive, lysosomal storage dis- rations secondary to vitamin A de- this condition are preventable with ease that arises from a deficiency in ficiency before she was diagnosed vitamin A supplementation by the lysosomal ␣-mannosidase. It oc- and treated with the appropriate appropriate route. curs in approximately 1 in 500 000 supplementation. Lewis and col- births and can be caused by 40 dif- leagues,5 similar to case 3, de- Phoebe Lin, MD, PhD ferent mutations in the gene, scribed an autistic child with a diet Robert E. Fintelmann, MD MAN2B1, which is located on chro- restricted mainly to carbohydrates Yousuf M. Khalifa, MD mosome 19. Clinical characteris- who developed xerophthalmia due Mohammed Rami Bailony, BS tics include cognitive, motor, and to profound vitamin A deficiency Bennie H. Jeng, MD hearing impairment, facial and skel-

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