Moshfeghi TE, Merchant TE, Pratt CB. relieve her symptoms. Schirmer test- Financial Disclosure: None. Multiagent chemotherapy as neoadjuvant treat- ment for multifocal intraocular retinoblastoma. ing with topical anesthesia showed Correspondence: Dr Chu, Doc- . 2001;108:2106-2115. 6 mm of tearing in the right eye and tor’s Office Center, Sixth Floor, 90 9. Madreperla SA, Hungerford JL, Cooling RJ, Bergen St, Newark, NJ 07103 (chuda Sullivan P, Gregor Z. Repair of late retinal de- 5.5 mm in the left. Subsequent bi- tachment after successful treatment of lateral inferior punctual plug place- @umdnj.edu). retinoblastoma. . 2000;20:28-32. ment provided some relief, but her 10. Baumal CR, Shields CL, Shields JA, Tasman WS. ϩ Surgical repair of rhegmatogenous retinal de- symptoms and superficial punctate 1. Ho DD, Cao Y, Zhu T, et al. Idiopathic CD4 T- tachment after treatment for retinoblastoma. persisted. In addition to the lymphocytopenia: immunodeficiency without Ophthalmology. 1998;105:2134-2139. evidence of HIV infection. N Engl J Med. 1993; 11. Honavar SG, Shields CL, Shields JA, Demirci aggressive use of artificial , other 328:380-385. ϩ H, Naduvilath TJ. Intraocular surgery after treat- modalities (corticosteroid eye drops 2. Kirtava Z, Blomberg J, Bredberg A, et al. CD4 ment of retinoblastoma. Arch Ophthalmol. 2001; and systemic doxycycline adminis- T-lymphocytopenia without HIV infection: in- 119:1613-1621. crease prevalence among patients with primary 12. Portellos M, Buckley EG. surgery and tration) were employed, but the pa- Sjogren’s syndrome. Clin Exp Rheumatol. 1995; intraocular implantation in patients with tient’s condition did not improve. 13:609-616. retinoblastoma. Arch Ophthalmol. 1998;116: 3. Laurence J, Mitra D, Steiner M, et al. Apoptotic ϩ ϩ 449-452. A diagnosis of Sjogren syndrome depletion of CD4 T-cells in idiopathic CD4 was confirmed after testing showed T-lymphocytopenia. J Clin Invest. 1996;97:672- 680. a Sjogren syndrome antigen anti- 4. Signorini S, Pirovano S, Fiorentini S, et al. Re- -؉ body level of 13.1 (range, 0-4.9 striction of T-cell receptor repertoires in idio Idiopathic CD4 ϩ U/mL). The patient then began a pathic CD4 lymphocytopenia. Br J Haematol. Lymphocytopenia 2000;110:434-437. and Sjogren Syndrome course of cevimeline hydrochloride (30 mg by mouth 3 times a day), and ϩ her symptoms improved consider- Idiopathic CD4 lymphocytopenia (ICL) is a rare syndrome that is ably. Furthermore, her superficial ϩ punctate keratitis diminished appre- marked by a CD4 count that is less Advanced 3 ciably. She remains stable and com- than 300 cells/mm without human With Descemetocele immunodeficiency virus infection.1 fortable on this regimen with the use in an Infant Its course differs from that of AIDS of artificial tears 4 times per day. With Cystic Fibrosis in that although patients with this dis- ϩ order may develop opportunistic in- Comment. Idiopathic CD4 lym- phocytopenia is a rare disorder of Xerophthalmia refers to the spec- fections, the majority of them re- ϩ main stable. No transmissible agent CD4 lymphocytopenia without hu- trum of ocular manifestations of vi- has been implicated in the pathogen- man immunodeficiency virus infec- tamin A deficiency. It represents the esis of ICL. The ocular manifesta- tion. The ophthalmic sequelae of this leading cause of childhood blind- tions of ICL have only rarely been de- syndrome have not yet been eluci- ness worldwide but is uncommon in 1 scribed,2 and there are no reports of dated. In this report, we describe the industrialized countries, where xe- ICL in ophthalmology literature. We characteristics and clinical courses rophthalmia is more often the re- report the case of a patient with ICL of a patient with ICL and Sjogren sult of malabsorption than malnu- and Sjogren syndrome. syndrome. trition due to poverty. Cystic fibrosis The underlying pathophysiology (CF) is an autosomal recessive dis- Report of a Case. A 52-year-old of ICL results from apoptosis of CD4ϩ ease with hyperviscosity of mucus woman was referred to the ophthal- cells,3 with subsequent limitations on secretions causing chronic pulmo- mology department because of a sev- therepertoireoftheT-cellpopulation.4 nary changes and pancreatic insuf- 2 eral-year history of burning and sting- Autoimmune processes such as Sjo- ficiency. Anderson was the first to ing in both eyes. Her medical history grensyndromemayresultfromrestric- note the association between xe- was significant for ICL, with 5 CD4ϩ tionofT-celldiversity,whichmaylead rophthalmia and CF, now thought counts during 6 years ranging from to a subsequent decrease in immune to be due to fat malabsorption re- 93 to 253, despite 3 negative human surveillance. This scenario would al- sulting in fat-soluble vitamin defi- immunodeficiency virus test re- lowautoantibodiesthatmayotherwise ciency. Advanced xerophthalmia has sults. Additionally, assays for Epstein- been reported as an initial sign of be cleared from systemic circulation 3,4 5 Barr virus, cytomegalovirus, and hu- to flourish. Kirtava et al2 found an in- CF. A recent review article sum- man herpesviruses 6 and 8 were all creased prevalence of ICL among pa- marized the ocular findings of CF to negative. At the time, her visual acu- tients with Sjogren syndrome. include xerophthalmia, tear film ab- ity was 20/20 OD and 20/25 OS. The Insummary,bothophthalmologists normalities, , and nyc- talopia. To our knowledge, this is the patient had marked superficial punc- and internists should be aware of the first clinicopathologic report of kera- tate keratitis and abundant mucus connectionbetweenSjogrensyndrome tomalacia with a descemetocele re- production in both eyes, and as a re- and patients with ICL. Further evalu- quiring keratoplasty as the initial sult, she began a course of applying ation is necessary to determine other manifestation of CF. artificial tears to both eyes every 2 ocular manifestations of ICL. hours with only minimal relief. During the ensuing months, a Edward J. Wladis, MD Report of a Case. A 5-month-old girl bandage contact lens was placed over Rajendra Kapila, MD from Juarez, Mexico, was admitted the patient’s left eye, but it failed to David S. Chu, MD to a hospital in Las Cruces, NM, with

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Figure 1. Corneal opacities with ulceration in a 5-month-old girl. A, Xerotic (dry) of the right eye. There is a large paracentral with ulceration and approximately 30% stromal loss. B, More advanced ulceration in the left eye, with evidence of a 4-mm descemetocele. Well-demarcated, inferonasal, cylindrical ulcers are typical of stromal loss in xerophthalmic keratomalacia.

A B

Figure 2. Conjunctivas and 3 days after dosing, showing increasing luster and less xerosis. A, The ulceration in the right eye is beginning to heal. B, Cyanoacrylate tissue adhesive with bandage contact lens is in place over the descemetocele of the left eye.

corneal opacities, vomiting, pneu- (less than the fifth percentile for Onhospitalday4,neurosurgeonsper- monia, and failure to thrive, with al- weight and height). The diagnosis of formed a ventriculoperitoneal shunt most no weight gain since birth. The keratomalacia was made, and xeroph- because of hydrocephalus with bra- diagnosis of bilateral ulcerative kera- thalmia was suspected. She was im- dycardia, lethargy, and a bulging fon- titis was made. Corneal cultures were mediately given an intramuscular tanel. Microscopic evaluation of the obtained and treatment was started dose of 50 000 IU of water-miscible patient’s stool showed 60 to 80 fatty with hourly fortified cefazolin so- vitamin A palmitate after serum vi- acid droplets (reference range, Ͻ60 dium (50 mg/mL) and tobramycin tamin A levels were drawn. The fol- droplets), prompting a workup for fat (14 mg/mL) eyedrops. Cultures lowing day, the patient underwent an malabsorption. She was also deficient yielded light growth of Staphylococ- ocular examination under anesthe- in vitamins D, E, and K. The result cus aureus. Five days later, the in- sia in which corneal scrapings were of a stool Giardia enzyme immuno- fant was transferred to the Univer- performed for microbiology. Cyano- assay test was positive, and a course sity of New Mexico Health Sciences acrylate tissue adhesive with a ban- of metronidazole was initiated. Center, Albuquerque, because of im- dage contact lens was applied to the The patient underwent penetrat- pending perforation of the left left . Fortified topical antibi- ing keratoplasty in the left eye on cornea. otics were tapered. hospital day 8. Gross examination Examination of her eyes showed A serum vitamin A level of 0.02 of the specimen showed a hazy roving eye movements and marked mg/L confirmed 8-mm corneal button with central xerosis (Figure 1). The right cor- (reference range, 0.2-0.5 mg/L). thinning and uveal tissue adherent nea had a large paracentral opacity Figure 2 demonstrates the marked to the endothelial surface. Figure 3 with ulceration. The left cornea had improvement in the xerosis 3 days af- demonstrates the histopathologic ap- more advanced ulceration and a ter vitamin A repletion. The patient pearance of the specimen. Tissue 4-mm descemetocele. The infant underwent an extensive pediatric Gram stain and silver stain failed to weighed 3.8 kg and was 55 cm long evaluation because of failure to thrive. demonstrate any organisms. By post-

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©2005 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/25/2021 tion. Although giardiasis was initially A suspected as the cause of malabsorp- tion, it was not sufficient to explain her failure to thrive. The malabsorp- tion 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 muta- tions, and one copy of the ␦-F508 mutation was identified. After initia- tion of a CF regimen (supplemental pancreatic enzymes, albuterol nebu- lizer treatments, and chest physical therapy) and placement of a percu- taneous endoscopic gastrostomy tube B for dysphagia, the patient began to thrive and grow. She underwent weekly examina- tions under anesthesia to monitor the graft and remove loose sutures. All sutures were removed by 6 weeks postoperatively. Eight weeks post- operatively, the patient had a cor- neal graft rejection episode that was aggressively treated with a single pulse of methylprednisolone intra- venously, 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 C right eye was initiated for 6 months. Part-time patching of the right eye and spectacle correction were initi- ated. The patient’s near-target fixa- tion remained central, steady, and maintained in both eyes 1½ years af- ter keratoplasty. Figure 5 shows her eyes 1 year after initial examina- tion.

Comment. Xerophthalmia is a leading cause of blindness world- wide, affecting 5 million children.1 Risk factors include low socioeco- nomic status, poor nutrition, pre- school age, and pregnancy. Other Figure 3. Histopathologic specimens of corneal tissue. A, Histopathologic examination of corneal button showing thinning with uveal tissue adherent to endothelial tissue (hematoxylin-eosin, original precipitating factors in western magnification ϫ2). B, Thickened and disorganized corneal epithelium. Corneal stroma has been replaced countries include alcoholism, CF, by a dense infiltrate of vessels, nongranulomatous inflammatory cells, and fibrocytes. is seen other malabsorption states (sprue, adherent to the endothelial surface (hematoxylin-eosin, original magnification ϫ40). C, Higher-power intestinal nematodes, and giardia- view of the infiltrate showing polymorphonuclear leukocytes (arrowhead), macrophages (arrow), and blood vessels (hematoxylin-eosin, original magnification ϫ200). sis), and food faddism. The spec- trum of ocular manifestations has operative day 5, the graft still had a shows the appearance of the eyes 17 been described and staged by the 90% epithelial defect. A bandage days after keratoplasty. World Health Organization as fol- contact lens was placed and the cor- Despite nasogastric feeding, the in- lows: nightblindness, XN; conjunc- neal graft slowly reepithelialized dur- fant gained only several ounces dur- tival xerosis, X1A; Bitot spots, X1B; ing the following 2 weeks. Figure 4 ing the first 2 months of hospitaliza- corneal xerosis, X2; keratomalacia,

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Figure 4. Appearance 17 days after keratoplasty. A, Diminished corneal opacity of the right eye. B, Clear corneal graft in the left eye. The ocular surface in both eyes has regained normal luster.

A B

Figure 5. Appearance 1 year after keratoplasty. A, Markedly reduced corneal scar in the right eye. B, Corneal graft in the left eye. Despite a rejection episode, the graft is still clear superiorly, and near-target fixation remains central and steady.

X3; corneal scar, XS; and xeroph- reported a high incidence of cor- duction that may occur in the in- thalmic fundus, XF. (Xerophthal- neal ulceration without pancreatic fant cornea after vitamin A supple- mic fundus is largely a clinical odd- enzyme and vitamin A supplemen- mentation. Vajpayee et al7 reported ity and does not necessarily correlate tation.4 Our patient’s other medical poor outcome after penetrating kera- to severity of disease.1) problems may have contributed to toplasty performed for keratomala- Xerophthalmia is treated with 2 the marked xerophthalmia. cia in preschool children, with clear oral doses of oil-miscible vitamin A, Immediate vitamin A replace- grafts seen in only 57% of cases at a 200 000 IU. Intramuscular admin- ment is important for the restora- mean follow-up of 6.4 months. Im- istration of 100 000 IU of water- tion of the ocular surface. This case mediate corneal grafting may not be miscible vitamin A palmi- illustrates the importance of giving indicated except in the setting of des- tate may replace the first dose if vitamin A several days before kera- cemetocele or perforation given the parenteral replacement is required. toplasty. Although the kerato- challenges of pediatric keratoplasty. Considered equally effective, the oral plasty was performed 8 days after vi- Histopathologic specimens of iso- dose is generally preferred in devel- tamin A repletion, reepithelialization lated xerophthalmic keratomalacia oping countries because of lower of the graft took longer than 2 weeks. are rare; Sommer1 reported 1 well- cost and higher safety (no needles). Although the xerosis may improve studied case with sharply demar- Infants younger than 12 months re- within days of vitamin A repletion, cated edges, a paucity of inflamma- quire only half the dose. the delay in reepithelialization in our tory cells, intact but keratinized Children with undiagnosed CF case suggests that weeks may be re- epithelium, and an absence of bac- may show signs of xerophthalmia quired for the epithelial dysfunc- teria. Our case, however, demon- and failure to thrive. Bulging fonta- tion and ocular surface to recover. strated an acute and chronic inflam- nelles have been described in asso- Serial photographs of our patient’s matory response localized to the area ciation with both vitamin A defi- right eye document the remarkable of ulceration and iridocorneal ad- ciency and CF.6 Early reports of CF degree of remodeling and scar re- hesion. The pathophysiology of xe-

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©2005 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/25/2021 rophthalmic keratomalacia is poorly versity of Texas Southwestern Medi- 3. Lindenmuth KA, Del Monte M, Marino L. Ad- vanced xerophthalmia as a presenting sign in cys- understood and requires further in- cal Center, 5323 Harry Hines Blvd, tic fibrosis. Ann Ophthalmol. 1989;21:189-191. vestigation. Dallas, TX 75390-9057 (vinod 4. Brooks HL Jr, Driebe WT Jr, Schemmer GG. [email protected]). Xerophthalmia and cystic fibrosis. Arch Sonja Wamsley, MD, MPH Ophthalmol. 1990;108:354-357. Funding/Support: This study was 5. Mrugacz M, Minarowska A. Eye symptoms of cys- Sarit M. Patel, MD supported by an unrestricted grant tic fibrosis [in Polish]. Klin Oczna. 2002;104: Mark G. Wood, MD from Research to Prevent Blind- 418-420. 6. Keating JP, Feigin RD. Increased intracranial pres- Robert Villalobos, MD ness, New York, NY. sure associated with probable vitamin A defi- Daniel M. Albert, MD, MS ciency in cystic fibrosis. Pediatrics. 1970;46: V. Vinod Mootha, MD 1. Sommer A. Xerophthalmia and vitamin A status. 41-46. Prog Retin Eye Res. 1998;17:9-31. 7. Vajpayee RB, Vanathi M, Tandon R, Sharma N, 2. Anderson DH. Cystic fibrosis of the pancreas, vi- Titiyal JS. Keratoplasty for keratomalacia in pre- Correspondence: Dr Mootha, De- tamin A deficiency, and bronchiectasis. J Pediatr. school children. Br J Ophthalmol. 2003;87:538- partment of Ophthalmology, Uni- 1939;5:763-771. 542.

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