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Chronic Varicella-Zoster Virus Epithelial Keratitis in Patients with Acquired Immunodeficiency Syndrome

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Chronic Varicella-Zoster Virus Epithelial Keratitis in Patients with Acquired Immunodeficiency Syndrome CLINICAL SCIENCES Chronic Varicella-zoster Virus Epithelial Keratitis in Patients With Acquired Immunodeficiency Syndrome Kenneth C. Chern, MD; Diana Conrad, MBBS, FRACO; Gary N. Holland, MD; Douglas S. Holsclaw, MD; Lee K. Schwartz, MD; Todd P. Margolis, MD, PhD Objective: To characterize further a chronic epithelial fluorescein and rose bengal. The peripheral and midpe- keratitis caused by varicella-zoster virus infection in pa- ripheral cornea was most commonly affected, and, in 13 tients with acquired immunodeficiency syndrome (AIDS). of the 16 patients, the lesions crossed the limbus. Pain was a prominent feature, occurring in 12 of 16 patients. Methods: Patients with AIDS and chronic epithelial In 9 of 12 patients tested, varicella-zoster virus was iden- keratitis associated with varicella-zoster virus from 3 in- tified by culture, direct fluorescent antibody testing, poly- stitutions were identified. Patient records were reviewed merase chain reaction testing, or a combination of these retrospectively for the following data: medical and demo- studies, with direct fluorescent antibody testing (6 of 8 graphic characteristics, techniques of diagnosis, physical positive results) and polymerase chain reaction testing findings, course, response to treatment, and outcome. (3 of 3 positive results) appearing to be the most sensi- tive. Response to antiviral medication was variable. Results: Sixteen patients were studied. CD4+ T- lymphocyte cell counts were available in 11 patients, with Conclusions: In patients with AIDS, varicella-zoster vi- a median of 0.034 3 109/L (range, 0-0.094 3 109/L ). Two rus may cause a chronic infection of the corneal epithe- patients had no history of a zosteriform rash. In the re- lium. The keratitis is characterized by dendriform le- maining patients, the interval between rash and kerati- sions, prolonged course, and frequently by extreme pain. tis ranged from 0 days to 6 years. In all cases, the kera- It can occur without an associated dermatitis. titis was chronic and characterized by gray, elevated, dendriform epithelial lesions that stained variably with Arch Ophthalmol. 1998;116:1011-1017 1 N 1988, Engstrom and Holland re- RESULTS ported a case of chronic varicella- zoster virus (VZV) keratitis that oc- The clinical and laboratory features of 16 curred in a patient with acquired patients with AIDS and chronic epithe- immunodeficiency syndrome lial keratitis associated with VZV are sum- I(AIDS). The keratitis was characterized by marized in Table 1. dendriform epithelial lesions and underly- All patients were men, ranging in age ing anterior stromal haze. Varicella-zoster from 25 to 65 years (median, 36 years). virus was cultured from corneal scraping, CD4+ T-lymphocyte cell counts were avail- and the keratitis responded to topical acy- able in 11 patients and ranged from 0 to clovir ointment therapy, thus distinguish- 0.094 3 109/L (median, 0.034 3 109/L). ing this form of VZV keratitis from the late There was a history of VZV infection pseudodendrites or mucus plaque keratopa- in 15 of the 16 patients. Fourteen patients thy that has been described as a late com- From The Francis I. Proctor had cutaneous herpes zoster. Eight pa- Foundation and Department of plication of herpes zoster ophthalmicus. We tients had herpes zoster ophthalmicus that Ophthalmology, University of have since examined 16 patients with AIDS began between 1 and 3 months before de- California San Francisco who developed chronic epithelial dendri- velopment of the keratitis. One patient had Medical Center (Drs Chern, form keratitis in which VZV was the likely an episode of herpes zoster ophthalmicus Holsclaw, and Margolis and cause of the keratitis. In many of the pa- 6 years before keratitis. In 1 additional pa- Ms Conrad), the University of tients, the clinical findings resemble those tient, the onset of dendriform keratitis oc- California Los Angeles Ocular described by Engstrom and Holland and dif- curred concurrently with active herpes zos- Inflammatory Disease Center, fer from previous descriptions of the acute ter ophthalmicus. Two patients had thoracic the Jules Stein Eye Institute, and chronic corneal epithelial manifesta- herpes zoster preceding the keratitis by 1 Department of Ophthalmology, University of California Los tions of VZV infection in immune- month and 18 months. One patient had pri- Angeles School of Medicine competent patients. In this report, we fur- mary VZV infection (chickenpox) 8 months (Dr Holland), and the Mount ther describe the chronic dendriform before developing the keratitis. Two pa- Zion Hospital, San Francisco keratitis associated with VZV in patients tients had no history of zosteriform rash. (Dr Schwartz). with AIDS. Two patients, 1 with and 1 without a his- ARCH OPHTHALMOL / VOL 116, AUG 1998 1011 ©1998 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/30/2021 PATIENTS AND METHODS positive for VZV antigen. Viral cultures were positive for VZV. Herpes simplex virus (HSV) was not detected with either direct fluorescent antibody staining or culture. We retrospectively reviewed the clinical records of 16 pa- Six months after the onset of the epithelial keratitis, tients with AIDS and chronic VZV keratitis at 3 institu- therapy with oral sorivudine, 40 mg/d, was started. Within tions. Patients were included if they had documented AIDS, 10 days, the patient noted marked relief in symptoms and chronic dendriform epithelial keratitis, and either derma- resolution of the epithelial lesions with a faint residual stro- tomal zoster within 6 months or laboratory evidence of VZV mal haze contiguous with the limbus with no intervening in corneal epithelial scrapings. Symptoms and signs at ini- clear zone. On day 17 of therapy with sorivudine, the epi- tial evaluation, treatment, diagnostic tests, course, and out- thelial pseudodendrites in the left eye recurred (Figure 1, come were studied. B). By day 29 of sorivudine therapy, the pain had returned and multiple pseudodendrites were present on the left cor- REPRESENTATIVE CASE REPORTS nea. To control pain, Hess drops (0.5% cocaine and 3% epi- nephrine in a 2% boric acid solution) were administered Patient 2 every 4 to 6 hours with oral narcotics. Neither topical trifluridine, oral acyclovir, topical 10% acetylcysteine, nor A 35-year-old man with AIDS (CD4+ T-lymphocyte cell an increase in the dose of oral sorivudine to 80 mg/d had count, 0.094 3 109/L) developed progressive outer retinal any apparent therapeutic benefit. The patient died 6 weeks necrosis syndrome of the right eye. He was treated with in- later. travenous (IV) acyclovir and then received oral acyclovir. Two months later, he noted a foreign-body sensation in the Patient 4 left eye. Pseudodendrites present on the left cornea per- sisted for the next 5 months, despite therapy with topical A 35-year-old man with AIDS (CD4+ T-lymphocyte cell trifluridine and IV acyclovir. He complained of chronic burn- count, 0.024 3 109/L) developed decreased vision, irrita- ing pain of the left eye that was unaffected by cycloplegia tion, and redness of his right eye. One month before, he or oral amitriptyline hydrochloride, but completely re- had a thoracic rash of unknown cause, but no recent facial lieved by topical proparacaine hydrochloride. He had no dermatitis. history of dermatomal herpes zoster. On examination, the bulbar conjunctiva of the right Examination of the left eye revealed multiple el- eye was congested, most notably temporal to the limbus. evated, gray corneal pseudodendrites that crossed the lim- Multiple, gray, raised dendriform lesions of the corneal epi- bus and stained well with rose bengal, but poorly with fluo- thelium stained poorly with fluorescein but well with rose rescein dye (Figure 1, A). There was no inflammation in bengal. There was a faint haze in the temporal corneal the anterior chamber or vitreous. Combined antiviral therapy stroma, extending from the limbus with no intervening clear (IV acyclovir and either topical trifluridine, topical vid- zone. Corneal sensation was normal except over the re- arabine, or topical acyclovir) was ineffective in resolving gion of corneal stromal haze, where sensation was moder- the signs or symptoms. All antiviral drug therapy was ately decreased. The pseudodendrites were de´brided, and stopped for 2 days, and the corneal lesions were scraped tissue samples sent for laboratory analysis. Giemsa stain- and cultured. Cytological examination revealed multinucle- ing revealed multinucleated giant cells, direct immuno- ated giant cells and direct fluorescent antibody staining was fluorescence test result was negative for HSV antigen, but tory of dermatomal herpes zoster, had progressive outer responding to the epithelial lesions. One patient had mild retinal necrosis syndrome 3 and 8 weeks before develop- stromal haze and corneal edema. An additional patient ing the dendriform keratitis. developed subepithelial infiltrates. The corneal epithelial lesions were usually mul- In 12 of the 16 patients, pain was an important man- tiple, elevated, gray dendriform in pattern and most com- agement issue. Corneal pain was variably described as a monly seen in the corneal periphery and midperiphery foreign-body sensation, reminiscent of a paper cut, or se- (Figure 3). The number and distribution of lesions vere burning. For the 7 patients in whom the effect of changed with time. In 13 of the 16 patients, the corneal topical anesthetics on the pain was documented, the an- epithelial lesions were observed to cross the limbus on esthetic provided relief in all cases. The pain was diffi- at least 1 examination. The lesions stained variably with cult to control in 3 patients, who required systemic nar- fluorescein (Figure 4) and rose bengal, but, in most pa- cotics (2 patients), chronic topical anesthetic drops (3 tients, staining with rose bengal was more prominent. patients), and retrobulbar alcohol (1 patient). There was variable loss of corneal sensation in 8 pa- Varicella-zoster virus was identified in the corneal tients; 2 patients had normal corneal sensation.
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