Keratomalacia in a Patient with Psychogenic Vitamin A Deficiency
Sidney M. Gospe III, MD, PhD1
Bozho Todorich, MD, PhD1,5
Yevgeniya G. Foster, MD2
Gary Legault, MD1,6
Suzanne K. Woods, MD2,3
Alan D. Proia, MD, PhD1,4
Melissa Daluvoy, MD1
Departments of 1Ophthalmology, 2Internal Medicine, 3Pediatrics, and 4Pathology
Duke University Medical Center, Durham, NC
5Associated Retinal Consultants, P.C. and William Beaumont Hospital, Royal Oak, MI
6Department of Ophthalmology, William Beaumont Army Medical Center, El Paso, TX.
Corresponding author:
Melissa Daluvoy, MD
Duke Eye Center
DUMC 3802
Durham, NC 27710
melissa.daluvoy@dm.duke.edu
919 684 5769
Conflicts of Interest: None of the authors report any competing interests.
Key Words:
Keratomalacia, xerophthalmia, vitamin A deficiency, histopathology
Funding sources: None
Abstract
Purpose: To report the clinical and histopathological findings of a patient with bilateral keratomalacia due
to severe vitamin A deficiency from panic disorder-related malnutrition.
Methods: Case report.
Results: A 47-year-old male with panic disorder presented with one month of painful vision loss
sequentially affecting the right and left eyes. He exhibited bilateral conjunctival xerosis with complete
corneal melt in the right eye and a large corneal epithelial defect with underlying anterior chamber
inflammation in the left eye. Laboratory investigation revealed undetectable serum vitamin A levels
attributed to self-induced vomiting and starvation. He was treated with high-dose vitamin A, but the right
eye required enucleation. The histological findings are reported.
Conclusions: Vitamin A deficiency in the absence of organic gastrointestinal abnormalities is exceedingly
rare in the developed world. A strong index of suspicion and thorough review of systems are invaluable
in evaluating patients with unexplained corneal melt.
Vitamin A deficiency (VAD) is a leading cause of preventable blindness worldwide, but is
very rare in developed nations, where it typically arises due to lipid malabsorption secondary to
hepatic, pancreatic, or intestinal abnormalities.1 Its most severe ocular manifestation is
keratomalacia, or melting of the corneal stroma, that may result in scarring or perforation when
the deficiency is not corrected promptly. We report a rare example of a patient with subacute
painful bilateral vision loss due to keratomalacia from severe VAD secondary to malnutrition
related to a psychiatric disorder.
CASE REPORT
A 47-year-old Caucasian man presented to the emergency department complaining of
one month of pain, redness, photophobia, and decreased vision in the right eye (OD), with
similar symptoms starting in the left eye (OS) one week later. Over-the-counter vasoconstrictor
eyedrops did not relieve his symptoms, and his vision had progressively deteriorated bilaterally
with worsening eye pain. He denied ocular trauma or contact lens use.
The patient had a medical history of gastroesophageal reflux disease (GERD) and severe
panic disorder with agoraphobia that had left him homebound for the past 20 years. Review of
systems was notable for a 60-pound weight loss over the preceding four months and daily nonbilious, non-bloody vomiting associated with severe burning epigastric pain refractory to one
full bottle of calcium-carbonate tablets per day. He denied fevers, chills, and night sweats. He
had a remote 30-pack-year smoking history but did not abuse drugs or alcohol. On
presentation, the patient was cachectic and ill-appearing. Visual acuity was hand-motion OD
and counting-fingers at twelve inches OS. Slit-lamp examination (Figure 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-total melt from limbus to limbus, with
a collapsed anterior chamber and a large descemetocele apposed to a beefy-red and purulent
iris that was affixed to the lens by extensive posterior synechiae. The left eye had a 6 mm
circular epithelial defect overlying edematous corneal stroma with inferior corneal
neovascularization but no infiltrate. There was a 1 mm hypopyon OS. There was no view of the
posterior segment OU, and B-scan ultrasonography revealed large serous choroidal
detachments OD and no evidence of vitritis OU.
He was admitted to the internal medicine service for further evaluation. His weight loss
and vomiting prompted an extensive workup for occult malignancy, as well as a search for
infectious, rheumatologic, and nutritional causes associated with corneal melt. His laboratory
studies demonstrated only weakly positive antinuclear antibodies (1:40 titer) and negative
serum rheumatoid factor, anti-cyclic citrullinated peptide, neutrophil cytoplasmic antibody, and
human immunodeficiency virus and Helicobacter pylori serologies. Urine toxicology screening
confirmed no drug use. Serum levels of fat-soluble vitamins A, E, and 25-hydroxy vitamin D
were below detectable limits, though normal coagulation studies suggested sufficient vitamin
K. Esophagogastroduodenoscopy with duodenal biopsy and CT of the chest, abdomen, and
pelvis revealed neither evidence of malignancy nor other organic etiologies of dysphagia or
malabsorption. A thorough psychiatric evaluation revealed a longstanding history of severe,
debilitating anxiety related to physical abuse by his father, who had repeatedly pointed a gun
into the patient’s throat when he was a child. The patient’s recent GERD symptoms reminded
him of this pharyngeal stimulation and led to panic attacks with dysphagia relieved only by
inducing vomiting and drastically limiting food intake. Given the otherwise negative workup,
the patient’s ocular pathology was attributed to severe vitamin A deficiency resulting from
psychogenic malnutrition. Treatment was initiated in form of 200,000 units of vitamin A
palmitate administered by mouth in divided doses for two days and repeated two weeks later.
Due to severe pain and poor visual potential, the patient opted in favor of enucleation
OD with placement of an orbital implant over a heroic attempt to spare the eye.
Histopathologic analysis of the right eye (Figure 2A-D) revealed keratomalacia with scarring and
vascularization of a peripheral cornea with hyperplastic and keratinized epithelium, and a large,
full-thickness central corneal ulcer plugged by inflamed iris tissue partly resurfaced by corneal
epithelium. Iris neovascularization was identified, producing peripheral anterior synechiae.
Focal disruption of the anterior capsule of a cataractous crystalline lens had produced a
granulomatous response (“phacoanaphylaxis”) causing adhesion of the lens to the posterior
surface of the iris. The posterior segment demonstrated an epiretinal membrane (not shown)
but was without any specific stigmata of vitamin A deficiency.
The left corneal epithelial defect was treated with topical moxifloxacin and placement of
an amniotic membrane. At the time of discharge, the epithelial defect had nearly resolved, with
some mild underlying stromal thinning. Follow-up examination could not be performed, as the
patient repeatedly refused to return to clinic due to agoraphobia. When contacted by phone 60
days after discharge, he reported near-baseline vision OS and no ocular discomfort.
DISCUSSION
VAD causes a spectrum of ocular disease known as xerophthalmia, which includes
changes in both the anterior and posterior segments.1-3 Conjunctival xerosis with keratinizing
squamous metaplasia, loss of goblet cells, and heaped accumulations of keratin (Bitot spots)
are characteristic, and corneal pathology can range from mild epitheliopathy to fulminant
keratomalacia resulting in blindness.1-3 Vitamin A-derived retinoids are thought to regulate
production of mucins by the stratified epithelium of the conjunctiva and cornea as well as the
conjunctival goblet cells.4 As hydrophilic glycoproteins, mucins maintain the epithelium-tear
film interface that keeps the ocular surface moist. Retinoid 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 to down-regulation of collagenase and other
protease secretion that leads to stromal thinning when unchecked.6 The most common
posterior manifestation of VAD is nyctalopia from depletion of the retinaldehyde chromophore
from retinal photoreceptors; subsequent photoreceptor degeneration and patchy fundus
depigmentation from focal retinal pigment epithelial loss may occur in very severe cases. 3
Our patient provided a rare but illuminating opportunity to assess the manifestations of
VAD via histological analysis. To our knowledge, there is only one prior report in which an
enucleation specimen was obtained from a living patient with keratomalacia.7 Fulminant
anterior segment pathology with severe corneal xerosis, stromal melt and perforation was
observed in the specimen from our patient, while the posterior segment did not demonstrate
outer retinal thinning that would be suggestive of permanent photoreceptor degeneration.
VAD is easily overlooked in the United States due to its infrequency in the developed
world. However, especially with the rise of bariatric surgery and its associated malabsorptive
complications, this is an increasingly important consideration in the differential diagnosis in
patients demonstrating conjunctival dryness and corneal pathology.8 VAD in the context of
psychiatric disease is usually related to alcoholism, generally with a component of lipid
malabsorption due to hepatic and pancreatic disease. Cases of VAD purely from psychogenic
malnutrition (e.g. anorexia nervosa, food faddism, or panic disorder as in our case) are
exceedingly rare.9, 10 Our case illustrates the importance of obtaining a thorough nutritional
history and review of systems in patients with corneal melt. A high index of suspicion for VAD
with prompt initiation of vitamin A supplementation is required to improve visual prognosis in
these patients.
REFERENCES
1.
McLaughlin S, Welch J, MacDonald E, et al. Xerophthalmia--a potential epidemic on our
doorstep? Eye (Lond). 2014;28:621-623.
2.
McLaren DS, Oomen HA, Escapini H. Ocular manifestations of vitamin-A deficiency in man. Bull
World Health Organ. 1966;34:357-361.
3.
Smith J, Steinemann TL. Vitamin A deficiency and the eye. Int Ophthalmol Clin. 2000;40:83-91.
4.
Hori Y, Spurr-Michaud SJ, Russo CL, et al. Effect of retinoic acid on gene expression in human
conjunctival epithelium: secretory phospholipase A2 mediates retinoic acid induction of MUC16. Invest
Ophthalmol Vis Sci. 2005;46:4050-4061.
5.
Samarawickrama C, Chew S, Watson S. Retinoic acid and the ocular surface. Surv Ophthalmol.
2015;60:183-195.
6.
Twining SS, Hatchell DL, Hyndiuk RA, et al. Acid proteases and histologic correlations in
experimental ulceration in vitamin A deficient rabbit corneas. Invest Ophthalmol Vis Sci. 1985;26:31-44.
7.
Suan EP, Bedrossian EH, Jr., Eagle RC, Jr., et al. Corneal perforation in patients with vitamin A
deficiency in the United States. Arch Ophthalmol. 1990;108:350-353.
8.
Donaldson KE, Fishler J. Corneal ulceration in a LASIK patient due to vitamin A deficiency after
bariatric surgery. Cornea. 2012;31:1497-1499.
9.
Cooney TM, Johnson CS, Elner VM. Keratomalacia caused by psychiatric-induced dietary
restrictions. Cornea. 2007;26:995-997.
10.
Collins CE, Koay P. Xerophthalmia because of dietary-induced vitamin A deficiency in a young
Scottish man. Cornea. 2010;29:828-829.
FIGURE LEGENDS
Figure 1. A, 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.
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.