Advanced Keratomalacia With Descemetocele in an Infant With Cystic Fibrosis

Xerophthalmia refers to the spectrum of ocular manifestations of vitamin A deficiency. It represents the leading cause of childhood blindness worldwide but is uncommon in industrialized countries,¹ where xerophthalmia is more often the result of malabsorption than malnutrition due to poverty. Cystic fibrosis (CF) is an autosomal recessive disease with hyperviscosity of mucus secretions causing chronic pulmonary changes and pancreatic insufficiency. Anderson² was the first to note the association between xerophthalmia and CF, now thought to be due to fat malabsorption resulting in fat-soluble vitamin deficiency. Advanced xerophthalmia has been reported as an initial sign of CF.^3,4 A recent review article⁵ summarized the ocular findings of CF to include xerophthalmia, tear film abnormalities, papilledema, and nyctalopia. To our knowledge, this is the first clinicopathologic report of keratomalacia with a descemetocele requiring keratoplasty as the initial manifestation of CF.

A 5-month-old girl from Juarez, Mexico, was admitted to a hospital in Las Cruces, NM, with corneal opacities, vomiting, pneumonia, and failure to thrive, with almost no weight gain since birth. The diagnosis of bilateral ulcerative keratitis was made. Corneal cultures were obtained and treatment was started with hourly fortified cefazolin sodium (50 mg/mL) and tobramycin (14 mg/mL) eyedrops. Cultures yielded light growth of Staphylococcus aureus. Five days later, the infant was transferred to the University of New Mexico Health Sciences Center, Albuquerque, because of impending perforation of the left cornea.

Examination of her eyes showed roving eye movements and marked xerosis (Figure 1). The right cornea had a large paracentral opacity with ulceration. The left cornea had more advanced ulceration and a 4-mm descemetocele. The infant weighed 3.8 kg and was 55 cm long (less than the fifth percentile for weight and height). The diagnosis of keratomalacia was made, and xerophthalmia was suspected. She was immediately given an intramuscular dose of 50 000 IU of water-miscible vitamin A palmitate after serum vitamin A levels were drawn. The following day, the patient underwent an ocular examination under anesthesia in which corneal scrapings were performed for microbiology. Cyanoacrylate tissue adhesive with a bandage contact lens was applied to the left cornea. Fortified topical antibiotics were tapered.

A serum vitamin A level of 0.02 mg/L confirmed vitamin A deficiency (reference range, 0.2-0.5 mg/L). Figure 2 demonstrates the marked improvement in the xerosis 3 days after vitamin A repletion. The patient underwent an extensive pediatric evaluation because of failure to thrive. On hospital day 4, neurosurgeons performed a ventriculoperitoneal shunt because of hydrocephalus with bradycardia, lethargy, and a bulging fontanel. Microscopic evaluation of the patient’s stool showed 60 to 80 fatty acid droplets (reference range, <60 droplets), prompting a workup for fat malabsorption. She was also deficient in vitamins D, E, and K. The result of a stool Giardia enzyme immunoassay test was positive, and a course of metronidazole was initiated.

The patient underwent penetrating keratoplasty in the left eye on hospital day 8. Gross examination of the specimen showed a hazy 8-mm corneal button with central thinning and uveal tissue adherent to the endothelial surface. Figure 3 demonstrates the histopathologic appearance of the specimen. Tissue Gram stain and silver stain failed to demonstrate any organisms. By postoperative day 5, the graft still had a 90% epithelial defect. A bandage contact lens was placed and the corneal graft slowly reepithelialized during the following 2 weeks. Figure 4 shows the appearance of the eyes 17 days after keratoplasty.

Despite nasogastric feeding, the infant gained only several ounces during the first 2 months of hospitalization. Although giardiasis was initially suspected as the cause of malabsorption, it was not sufficient to explain her failure to thrive. The malabsorption workup confirmed CF. Results of successive sweat chloride tests were elevated both times at 89 mEq/L and 96 mEq/L (reference range, 0-40 mEq/L). The patient’s DNA was tested for the 87 known CF mutations, and one copy of the δ-F508 mutation was identified. After initiation of a CF regimen (supplemental pancreatic enzymes, albuterol nebulizer treatments, and chest physical therapy) and placement of a percutaneous endoscopic gastrostomy tube for dysphagia, the patient began to thrive and grow.

She underwent weekly examinations under anesthesia to monitor the graft and remove loose sutures. All sutures were removed by 6 weeks postoperatively. Eight weeks postoperatively, the patient had a corneal graft rejection episode that was aggressively treated with a single pulse of methylprednisolone intravenously, a sub-Tenon injection of triamcinolone acetonide, and hourly 1% prednisolone acetate eyedrops, with significant improvement in the corneal decompensation. Four weeks after vitamin repletion, 0.1% fluorometholone once daily in the right eye was initiated for 6 months. Part-time patching of the right eye and spectacle correction were initiated. The patient’s near-target fixation remained central, steady, and maintained in both eyes 1½ years after keratoplasty. Figure 5 shows her eyes 1 year after initial examination.

Xerophthalmia is a leading cause of blindness worldwide, affecting 5 million children.¹ Risk factors include low socioeconomic status, poor nutrition, preschool age, and pregnancy. Other precipitating factors in western countries include alcoholism, CF, other malabsorption states (sprue, intestinal nematodes, and giardiasis), and food faddism. The spectrum of ocular manifestations has been described and staged by the World Health Organization as follows: nightblindness, XN; conjunctival xerosis, X1A; Bitot spots, X1B; corneal xerosis, X2; keratomalacia, X3; corneal scar, XS; and xerophthalmic fundus, XF. (Xerophthalmic fundus is largely a clinical oddity and does not necessarily correlate to severity of disease.¹)

Xerophthalmia is treated with 2 oral doses of oil-miscible vitamin A, 200 000 IU. Intramuscular administration of 100 000 IU of water-miscible vitamin A retinol palmitate may replace the first dose if parenteral replacement is required. Considered equally effective, the oral dose is generally preferred in developing countries because of lower cost and higher safety (no needles). Infants younger than 12 months require only half the dose.

Children with undiagnosed CF may show signs of xerophthalmia and failure to thrive. Bulging fontanelles have been described in association with both vitamin A deficiency and CF.⁶ Early reports of CF reported a high incidence of corneal ulceration without pancreatic enzyme and vitamin A supplementation.⁴ Our patient’s other medical problems may have contributed to the marked xerophthalmia.

Immediate vitamin A replacement is important for the restoration of the ocular surface. This case illustrates the importance of giving vitamin A several days before keratoplasty. Although the keratoplasty was performed 8 days after vitamin A repletion, reepithelialization of the graft took longer than 2 weeks. Although the xerosis may improve within days of vitamin A repletion, the delay in reepithelialization in our case suggests that weeks may be required for the epithelial dysfunction and ocular surface to recover. Serial photographs of our patient’s right eye document the remarkable degree of remodeling and scar reduction that may occur in the infant cornea after vitamin A supplementation. Vajpayee et al⁷ reported poor outcome after penetrating keratoplasty performed for keratomalacia in preschool children, with clear grafts seen in only 57% of cases at a mean follow-up of 6.4 months. Immediate corneal grafting may not be indicated except in the setting of descemetocele or perforation given the challenges of pediatric keratoplasty.

Histopathologic specimens of isolated xerophthalmic keratomalacia are rare; Sommer¹ reported 1 well-studied case with sharply demarcated edges, a paucity of inflammatory cells, intact but keratinized epithelium, and an absence of bacteria. Our case, however, demonstrated an acute and chronic inflammatory response localized to the area of ulceration and iridocorneal adhesion. The pathophysiology of xerophthalmic keratomalacia is poorly understood and requires further investigation.

Correspondence: Dr Mootha, Department of Ophthalmology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9057 (vinod.mootha@utsouthwestern.edu).

Funding/Support: This study was supported by an unrestricted grant from Research to Prevent Blindness, New York, NY.