SEP 2013

EyeWorld is the official news magazine of the American Society of Cataract & Refractive Surgery.

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60 EW CORNEA September 2013 Tracking cytomegalovirus endotheliitis by Vanessa Caceres EyeWorld Contributing Writer 64-year-old patient three months after his second endothelial graft for Fuchs' dystrophy. Retroillumination reveals new fine keratic precipitates. Allograft rejection was diagnosed and the frequency of topical corticosteroids increased. Rare condition most often appears as allograft rejection O phthalmologists may already be aware of cytomegalovirus (CMV) retinitis in immunocompromised patients or CMV uveitis. However CMV endotheliitis is not as well known. CMV endotheliitis is an underrecognized problem that can masquerade as allograft rejection, said Sadeer B. Hannush, MD, attending surgeon, cornea service, Wills Eye Institute; Department of Ophthalmology, Jefferson Medical College; and medical director, Lions Eye Bank of Delaware Valley, Philadelphia. What is CMV endotheliitis? Although it's a rare condition, CMV endotheliitis appears to occur most often after corneal transplantation surgeries such as Descemet's stripping endothelial keratoplasty (DSEK) or penetrating keratoplasty (PK). A patient with an endothelial graft may present with swelling of the host cornea and a few keratic precipitates on the graft. "You suspect rejection and increase steroids," said Dr. Hannush, who reported on two patients with CMV endotheliitis in a 2012 Association for Research in Vision and Ophthalmology abstract.1 However, steroids actually make the condition worse. In one of his patients, the endothelial cell count went from 1,500 to almost nothing over two weeks, and the host cornea continued to swell up. In the two patients he treated, the grafts had to be repeated. Dr. Hannush and coinvestigators suspected allograft rejection, but they also submitted the original endothelial grafts for ocular pathology. "We stained for CMV and they lit up like New York City," he said. An anterior chamber aqueous tap for a polymerase chain reaction (PCR) test also showed CMV in both patients. Both patients received oral valganciclovir (Valcyte, Genentech, South San Francisco) and topical ganciclovir; the repeat grafts remain in good condition, said Dr. Hannush. Typical treatment for CMV infection in graft patients is 900 mg of oral valganciclovir twice a day for three months, said Donald T.H. Tan, FRCOphth, head and senior consultant, Singapore National Eye Centre, Singapore. Dr. Tan also recommends the use of IV ganciclovir, topical valganciclovir gel and ganciclovir drops, and monitoring corneal clarity and endothelial cell count. Dr. Tan cautioned that it is important to distinguish CMV endotheliitis from corneal graft rejection and endothelial decompensation. An anterior chamber tap and PCR test can help identify active infection, Dr. Tan said, and to test that the infection has cleared, generally one month after starting treatment. After seven months of treatment with corticosteroids, the graft fails with secondary host corneal edema. Anterior chamber tap was performed and sent for polymerase chain reaction for CMV, revealing 2,500,000 DNA copies/ml. Oral valganciclovir 900 mg twice a day was initiated and the patient scheduled for regrafting. Tracking CMV endotheliitis elsewhere Although the abstract from Dr. Hannush and coinvestigators is the first known report in the United States of CMV endotheliitis appearing as allograft rejection, there are other published reports, mostly from Singapore and Japan, Dr. Tan said. For instance, Soon Phaik Chee, MD, senior consultant and head, cataract service and ocular inflammation and immunology service, Singapore National Eye Centre, and associate professor, Department of Ophthalmology, National University of Singapore, who has done extensive work with CMV uveitis, began to urge her corneal team to have a high index of suspicion for CMV endotheliitis as well. "This was underrecognized and often mismanaged with steroid treatment, which can lead to rapid graft decompensation," Dr. Chee said. Dr. Chee points to her study in the August issue of Cornea that highlights CMV-positive corneal stromal edema after penetrating keratoplasty (PK).2 The case-control study used aqueous humor samples of all eyes with corneal stromal edema and keratic precipitates after PK that were seen at the Singapore National Eye Centre from 2007 to 2010. Dectecting CMV DNA via PCR, Dr. Chee and coinvestigators found that of 11 eligible eyes, seven were CMV positive. These patients did not have graft rejection. Although the CMVpositive eyes received ganciclovir, all of the grafts failed. The development of stromal edema and keratic precipitates after PK are possible signs of CMV endotheliitis, the authors concluded. "Heavy endothelial pigmentation, Descemet membrane folds, and the absence of donor vascularization may aid in the diagnosis of CMV in the event that aqueous analysis is not possible," they wrote. Another landmark CMV endotheliitis paper that Dr. Chee worked on along with Dr. Tan and co-investigators reported four cases of CMV endotheliitis after Descemet's stripping automated endothelial keratoplasty (DSAEK).3 The four immunocompetent Chinese male patients had DSAEK. They then experienced localized corneal edema, increased IOP, and keratic precipitates with minimal or no anterior chamber involvement. A decreased endothelial cell count occurred in three of the patients. All patients were CMV positive and received oral valganciclovir. "A heightened awareness is required to exclude CMV endotheliitis as the cause for endothelial decompensation or unexplained, sudden reduction in endothelial cell count post-DSAEK in the absence of other complications, and it should be differentiated from allograft rejection in view of the critical difference in treatment," the investigators wrote.

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