Keratomalacia in a Patient with Psychogenic Vitamin a Deficiency

CASE REPORT

Keratomalacia in a Patient With Psychogenic Vitamin A Deﬁciency

Sidney M. Gospe III, MD, PhD,* Bozho Todorich, MD, PhD,*† Yevgeniya G. Foster, MD,‡ Gary Legault, MD,*§ Suzanne K. Woods, MD,‡¶ Alan D. Proia, MD, PhD,*k and Melissa Daluvoy, MD*

corrected promptly. We report a rare example of a patient Purpose: ﬁ To report the clinical and histopathological ndings of with subacute painful bilateral vision loss arising from a patient with bilateral keratomalacia arising from severe vitamin A keratomalacia from severe VAD secondary to malnutrition deﬁciency from panic disorder-related malnutrition. related to a psychiatric disorder. Methods: Case report.

Results: A 47-year-old male with panic disorder presented with 1 CASE REPORT month of painful vision loss sequentially affecting the right and left A 47-year-old white man presented to the emergency eyes. He exhibited bilateral conjunctival xerosis with complete department complaining of 1 month of pain, redness, photophobia, corneal melt in the right eye and a large corneal epithelial defect with and decreased vision in the right eye (OD), with similar symptoms underlying anterior chamber inflammation in the left eye. Laboratory starting in the left eye (OS) 1 week later. Over-the-counter vasoconstrictor eyedrops did not relieve his symptoms, and his investigation revealed undetectable serum vitamin A levels attributed vision had progressively deteriorated bilaterally with worsening eye to self-induced vomiting and starvation. He was treated with high- pain. He denied ocular trauma or contact lens use. dose vitamin A, but the right eye required enucleation. The The patient had a medical history of gastroesophageal reflux histological findings are reported. disease and severe panic disorder with agoraphobia that had left him Conclusions: fi homebound for the past 20 years. Review of systems was notable for Vitamin A de ciency in the absence of organic a 60-pound weight loss over the preceding 4 months and daily gastrointestinal abnormalities is exceedingly rare in the developed nonbilious, nonbloody vomiting associated with severe burning world. A strong index of suspicion and thorough review of systems epigastric pain refractory to 1 full bottle of calcium-carbonate tablets are invaluable in evaluating patients with unexplained corneal melt. per day. He denied fevers, chills, and night sweats. He had a remote Key Words: fi 30-pack-year smoking history but did not abuse drugs or alcohol. On keratomalacia, xerophthalmia, vitamin A de ciency, presentation, the patient was cachectic and ill-appearing. Visual histopathology acuity was hand-motion OD and counting fingers at 12 inches OS. (Cornea 2016;35:405–407) Slit-lamp examination (Fig. 1) revealed diffusely chemotic and keratinized conjunctiva in both eyes (OU) with xerosis but no Bitot spots. The right cornea was Seidel-negative but demonstrated near- fi total melt from limbus to limbus, with a collapsed anterior chamber itamin A de ciency (VAD) is a leading cause of and a large descemetocele apposed to a beefy-red and purulent iris Vpreventable blindness worldwide, but is very rare in that was affixed to the lens by extensive posterior synechiae. The left developed nations, where it typically arises because of lipid eye had a 6-mm circular epithelial defect overlying edematous malabsorption secondary to hepatic, pancreatic, or intestinal corneal stroma with inferior corneal neovascularization but no abnormalities.1 Its most severe ocular manifestation is infiltrate. There was a 1-mm hypopyon OS. There was no view of keratomalacia, or melting of the corneal stroma, that may the posterior segment OU, and B-scan ultrasonography revealed result in scarring or perforation when the deficiency is not large serous choroidal detachments OD and no evidence of vitritis OU. He was admitted to the internal medicine service for further Received for publication October 15, 2015; revision received November 3, evaluation. His weight loss and vomiting prompted an extensive 2015; accepted November 3, 2015. Published online ahead of print workup for occult malignancy and a search for infectious, rheuma- January 19, 2016. tologic, and nutritional causes associated with corneal melt. His From the *Department of Ophthalmology, Duke University Medical laboratory studies demonstrated only weakly positive antinuclear Center, Durham, NC; †Associated Retinal Consultants, P.C. and antibodies (1:40 titer) and negative serum rheumatoid factor, anti- William Beaumont Hospital, Royal Oak, MI; ‡Department of Internal cyclic citrullinated peptide, neutrophil cytoplasmic antibody, and Medicine, Duke University Medical Center, Durham, NC; §Depart- human immunodeficiency virus and Helicobacter pylori serologies. ment of Ophthalmology, William Beaumont Army Medical Center, El Urine toxicology screening confirmed no drug use. Serum levels of Paso, TX; and Departments of ¶Pediatrics, and kPathology, Duke University Medical Center, Durham, NC. fat-soluble vitamins A, E, and 25-hydroxy vitamin D were below The authors have no funding or conflicts of interest to disclose. detectable limits, although normal coagulation studies suggested Reprints: Melissa Daluvoy, MD, Duke Eye Center, DUMC 3802, Durham, sufficient vitamin K. Esophagogastroduodenoscopy with duodenal NC 27710 (e-mail: [email protected]). biopsy and CT of the chest, abdomen, and pelvis revealed neither Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. evidence of malignancy nor other organic etiologies of dysphagia or

Cornea Volume 35, Number 3, March 2016 www.corneajrnl.com | 405

Copyright Ó 2016 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. Gospe et al Cornea Volume 35, Number 3, March 2016

FIGURE 1. A, An external photograph of the right eye, demonstrating severe xerosis and hyperemia of the conjunctiva and mucopurulent discharge at the inferior limbus. There is total corneal melt with descemetocele formation over inflamed iris tissue that is fixed to a cataractous lens. B, Slit-lamp photograph of the right eye demonstrating complete corneal melt with obliteration of the anterior chamber. C, External photograph of the left eye demonstrating perilimbal xerosis, a large central corneal epithelial defect, stromal edema, and hypopyon. malabsorption. A thorough psychiatric evaluation revealed a long- keratinized epithelium, and a large, full-thickness central corneal standing history of severe, debilitating anxiety related to physical ulcer plugged by inflamed iris tissue partly resurfaced by corneal abuse by his father, who had repeatedly pointed a gun into the epithelium. Iris neovascularization was identified, producing patient’s throat when he was a child. The patient’s recent gastro- peripheral anterior synechiae. Focal disruption of the anterior esophageal reflux disease symptoms reminded him of this pharyn- capsule of a cataractous crystalline lens had produced a granulo- geal stimulation and led to panic attacks with dysphagia relieved matous response (“phacoanaphylaxis”) causing adhesion of the only by inducing vomiting and drastically limiting food intake. lens to the posterior surface of the iris. The posterior segment Given the otherwise negative workup, the patient’s ocular pathology demonstrated an epiretinal membrane (not shown) but was without was attributed to severe vitamin A deficiency resulting from any specificstigmataofvitaminAdeficiency. psychogenic malnutrition. Treatment was initiated in the form of The left corneal epithelial defect was treated with topical 200,000 units of vitamin A palmitate administered by mouth in moxifloxacin and placement of an amniotic membrane. At the time divided doses for 2 days and repeated 2 weeks later. of discharge, the epithelial defect had nearly resolved, with some Because of severe pain and poor visual potential, the patient mild underlying stromal thinning. Follow-up examination could opted for enucleation OD with placement of an orbital implant not be performed, as the patient repeatedly refused to return to the over a heroic attempt to spare the eye. Histopathologic analysis of clinic because of agoraphobia. When contacted by phone 60 days the right eye (Figs. 2A–D) revealed keratomalacia with scarring after discharge, he reported near-baseline vision OS and no and vascularization of the peripheral cornea with hyperplastic and ocular discomfort.

FIGURE 2. A, The enucleated right eye had an ill-defined junction of the corneal edge (arrowhead) with iris that had been resurfaced by corneal epithelium (arrow); acute inflammatory exudate (asterisk) was adherent focally to the iris surface. B–D, A large corneal defect (corneal edges marked with arrowheads) was plugged with iris (arrow) that was mostly resurfaced by hyperplastic corneal epithelium or covered by acute inflammatory exudate (asterisk). Cataractous lens (diamond) with focal anterior capsular disruption and resultant granulomatous inflammation was adherent to the posterior iris surface. Higher magnification images (C, D) better demonstrate the epithelialization of the iris plug, granulomatous reaction in the disrupted lens, and fibrosis and vascularization of residual peripheral cornea. Magnification bars in all photomicrographs = 1 mm.

Copyright Ó 2016 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. Cornea Volume 35, Number 3, March 2016 Psychogenic Vitamin A Deﬁciency

DISCUSSION consideration in the differential diagnosis in patients dem- VAD causes a spectrum of ocular disease known as onstrating conjunctival dryness and corneal pathology.8 xerophthalmia, which includes changes in both the anterior VAD in the context of psychiatric disease is usually related and posterior segments.1–3 Conjunctival xerosis with kerati- to alcoholism, generally with a component of lipid malab- nizing squamous metaplasia, loss of goblet cells, and heaped sorption attributed to hepatic and pancreatic disease. Cases accumulations of keratin (Bitot spots) are characteristic, and of VAD purely from psychogenic malnutrition (eg, anorexia corneal pathology can range from mild epitheliopathy to nervosa, food faddism, or panic disorder as in our case) are fulminant keratomalacia resulting in blindness.1–3 Vitamin exceedingly rare.9,10 Our case illustrates the importance A-derived retinoids are thought to regulate production of of obtaining a thorough nutritional history and review of mucins by the stratified epithelium of the conjunctiva and systems in patients with corneal melt. A high index of cornea as well as the conjunctival goblet cells.4 As hydro- suspicion for VAD with prompt initiation of vitamin A philic glycoproteins, mucins maintain the epithelium-tear film supplementation is required to improve visual prognosis in interface that keeps the ocular surface moist. Retinoid these patients. signaling is also directly involved in negatively regulating keratinizing squamous metaplasia of the epithelium.5 The role of vitamin A in maintenance of the corneal stroma is related REFERENCES to down-regulation of collagenase and other protease secre- — 6 1. McLaughlin S, Welch J, MacDonald E, et al. Xerophthalmia a potential tion that leads to stromal thinning when unchecked. The epidemic on our doorstep? Eye (Lond). 2014;28:621–623. most common posterior manifestation of VAD is nyctalopia 2. McLaren DS, Oomen HA, Escapini H. Ocular manifestations of vitamin- from depletion of the retinaldehyde chromophore from retinal Adeficiency in man. Bull World Health Organ. 1966;34:357–361. fi photoreceptors; subsequent photoreceptor degeneration and 3. Smith J, Steinemann TL. Vitamin A de ciency and the eye. Int Ophthalmol Clin. 2000;40:83–91. patchy fundus depigmentation from the focal retinal pigment 4. Hori Y, Spurr-Michaud SJ, Russo CL, et al. Effect of retinoic acid on 3 epithelial loss may occur in very severe cases. gene expression in human conjunctival epithelium: secretory phospho- Our patient provided a rare but illuminating opportunity lipase A2 mediates retinoic acid induction of MUC16. Invest Ophthalmol to assess the manifestations of VAD through histological Vis Sci. 2005;46:4050–4061. 5. Samarawickrama C, Chew S, Watson S. Retinoic acid and the ocular analysis. To our knowledge, there is only one prior report in surface. Surv Ophthalmol. 2015;60:183–195. which an enucleation specimen was obtained from a living 6. Twining SS, Hatchell DL, Hyndiuk RA, et al. Acid proteases and patient with keratomalacia.7 Fulminant anterior segment histologic correlations in experimental ulceration in vitamin A deficient pathology with severe corneal xerosis, stromal melt, and rabbit corneas. Invest Ophthalmol Vis Sci. 1985;26:31–44. perforation was observed in the specimen from our patient, 7. Suan EP, Bedrossian EH Jr, Eagle RC Jr, et al. Corneal perforation in patients with vitamin A deficiency in the United States. Arch Oph- whereas the posterior segment did not demonstrate outer thalmol. 1990;108:350–353. retinal thinning that would be suggestive of permanent 8. Donaldson KE, Fishler J. Corneal ulceration in a LASIK patient due photoreceptor degeneration. to vitamin A deficiency after bariatric surgery. Cornea. 2012;31: VAD is easily overlooked in the United States because 1497–1499. 9. Cooney TM, Johnson CS, Elner VM. Keratomalacia caused by of its infrequency in the developed world. However, espe- psychiatric-induced dietary restrictions. Cornea. 2007;26:995–997. cially with the rise of bariatric surgery and its associated 10. Collins CE, Koay P. Xerophthalmia because of dietary-induced vitamin malabsorptive complications, this is an increasingly important Adeficiency in a young Scottish man. Cornea. 2010;29:828–829.