January 2014




Cornea editor's corner of the world

Diagnosing and treating CMV anterior uveitis and endotheliitis

by Ellen Stodola EyeWorld Staff Writer


Clara C. Chan, MD

Common viruses that we consider frequently that affect the anterior segment include the herpes simplex virus (HSV) and the herpes zoster virus (HZV). However, cytomegalovirus (CMV) infections should also be considered, especially in patients of Asian descent. When ophthalmologists think about CMV infections, they usually think of retinal complications in immuno-compromised patients. However, CMV infections of the anterior segment can manifest in otherwise healthy patients. CMV anterior uveitis and endotheliitis are entities that a clinician should be aware of and the diagnosis may be missed without a high level of suspicion. Furthermore, they can masquerade as corneal graft rejection or failure. Aqueous fluid analysis via polymerase chain reaction (PCR) for CMV DNA can be done to confirm the diagnosis, and oral antivirals are effective. This month's "Cornea editor's corner of the world" has Soon-Phaik Chee, MD, and Donald T.H. Tan, MD, discussing their experience in the diagnosis, treatment, and sequelae of CMV anterior uveitis and endotheliitis.  

Clara C. Chan, MD, cornea editor

white keratic precipitates

This slit lamp photograph shows a mixture of medium and small sized white keratic precipitates on the central and inferior aspect of the corneal endothelium. This is typical of CMV acute hypertensive anterior uveitis.

small keratic precipitates This slit lamp photograph shows a swollen cornea with Descemet's folds and small keratic precipitates in an eye with CMV endotheliitis.

Source (all): Soon-Phaik Chee, MD

Knowing key features can help identify and treat patients

CMV acute anterior uveitis and endotheliitis can be identified by a number of features and patient characteristics. Diagnosing and preventing recurrence is extremely important to determine the best treatment option and reduce the risk of a worsening condition in these cases. Soon-Phaik Chee, MD, Singapore National Eye Centre, and associate professor, Department of Ophthalmology, National University of Singapore, and Donald T.H. Tan, MD, head and senior consultant, Singapore National Eye Centre, commented on some of the key features, diagnosis, and treatment.

Key ophthalmic features and patient characteristics

Dr. Tan said that the spectrum of CMV infection in the anterior segment includes acute recurrent infection (similar to features of Posner-Schlossman Syndrome), sector iris atrophy with iritis, chronic infection (similar to Fuchs' heterochromic iridocyclitis) or corneal endotheliitis. "The key features of CMV endotheliitis are the presence of fine or medium-sized keratic precipitates (KPs), which characteristically (but may not always) adopt a ring or linear pattern, and may or may not be pigmented," he said. "One classic hallmark of CMV is the presence of white, opalescent nodular endothelial lesions, which may be confused with the nodules seen in posterior polymorphous corneal dystrophy."

Dr. Tan said that patients are usually in the adult or elderly age group. "In patients with CMV infection post-transplant, endotheliitis may occur anytime after the PK or DSAEK. Oftentimes there is a preceding history of previous uveitis or uveitic glaucoma such as Fuchs' heterochromic cyclitis, and bilateral involvement can occur," he said. "Previous indications for the transplant may vary from post-surgical causes of corneal decompensation, such as pseudophakic bullous keratopathy or post-glaucoma or post-laser peripheral iridotomy cases; [patients may] have a previous history of Fuchs' endothelial dystrophy."

Dr. Chee detailed the spectrum of CMV infection. "CMV acute anterior uveitis tends to be unilateral, relapsing in nature and associated with a raised intraocular pressure of more than 40 mm Hg in many patients," she said. Patients between the ages of 20 and 40 may present with sudden blurring of vision, halos, and ipsilateral headaches, she said, indicating that about two-thirds of patients who present with these problems are male. The eyes in these cases may be minimally red with small and medium sized KPs over the inferocentral cornea, which may form a ring pattern. "These KPs may be seen linearly arranged inferiorly," she said.

CMV chronic anterior uveitis tends to be unilateral, like the acute condition, however, it also occurs bilaterally in 7% of patients. These patients are usually older, between the ages of 50 and 80, Dr. Chee said, and are predominantly male. Characteristics of patients include gradual blurring of vision due to the small KPs that are diffusely scattered over the endothelium or from cataract formation. These can sometimes be arranged in a ring pattern. In regard to CMV endotheliitis, Dr. Chee said this should be excluded in any case where there is unexplained corneal edema. The majority of these patients are male. It is bilateral in about one fifth of cases and may present at any age. Dr. Chee said that slit lamp examination typically shows an area of corneal edema with Descemet's folds with fine and medium KPs on the endothelial surface taking on a ring pattern, or the KPs may be linearly displayed at the edge of a patch of endotheliitis. CMV endotheliitis in post-corneal transplantation (penetrating keratoplasty and DSAEK) can present differently or may mimic transplant rejection, Dr. Chee said and should be excluded, as the management is very different. A rapid unexplained drop in the endothelial cell count should alert the clinician to the possibility of CMV infection, which may have preceded the graft surgery or be induced possibly by transplanting CMV-infected endothelium, she said.

Finally, in CMV infected penetrated keratoplasty, Dr. Chee said the area of involvement arises from the host-graft junction, and the KPs may be seen as coin-like lesions on both the donor and host cornea and may be pigmented. "There is minimal anterior chamber activity and the intraocular pressure may be elevated," she said.

Verifying diagnosis

"For transplant patients, a high index of suspicion is needed, but often is only suspected after a presumed graft rejection responds poorly to topical steroids," Dr. Tan said. "The current method to verify the diagnosis is to confirm the presence of CMV DNA in the aqueous humor. An AC tap sent for RT-PCR (real-time polymerase chain reaction) for CMV DNA is the most common method used today, but there is evidence that PCR may only be able to detect 40% of cases." Dr. Tan said improvement in corneal signs upon treatment with oral valganciclovir or topical valganciclovir gel together with a reduction in topical steroids can help with diagnosis. Multiple serial AC taps could be needed to monitor the condition, he said.

Best treatment and risk of recurrence

Oral valganciclovir 900 mg twice a day for six weeks followed by 900 mg every morning for six weeks is an effective treatment for patients with CMV endotheliitis, Dr. Chee said. "Repeat tap of the aqueous should be done to demonstrate response to therapy." After this, a decision can be made to continue or discontinue medication. When dealing with CMV acute or chronic uveitis, she said that although a 75% response is seen with antiviral therapy administered by a variety of routes over three months, there is also a 75% relapse rate once the medication is stopped. "Thus, we advocate using topical ganciclovir gel 0.15% five times daily," she said. The duration of this treatment is indefinite and frequency may be reduced. Treatment with specific antivirals should be accompanied by prescribing mild anti-inflammatory therapy, such as topical NSAIDs, Dr. Chee said.

Difference between CMV and HSV infections

Dr. Tan said that HSV and CMV endotheliitis can be difficult to distinguish, and an AC tap tests for both. "CMV endotheliitis appears to carry a worse prognosis than other forms of endotheliitis, including HSV, with a higher rate of recurrence and a higher risk of graft failure," he said.

PCR is often the simplest and surest way to tell them apart, Dr. Chee said. "Sometimes aqueous sampling may be met with false negatives, and testing for local intraocular antibody production should be done where available (Goldmann-Witmer coefficient)," she said.

Dr. Chee noted several helping points in differentiating CMV and HSV, including that anterior chamber activity tends to be more severe in HSV and could be accompanied by hypopyon formation. Flare is heavy in HSV and there is accompanying risk of posterior synechiae formation, unlike with CMV where there is minimal flare and no posterior synechiae.

Editors' note: Dr. Chee has financial interests with Bausch + Lomb Technolas (Singapore) and Hoya Surgical Optics Singapore. Dr. Tan has no financial interests related to this article.

Contact information

: chee.soon.phaik@snec.com.sg
Tan: donald.tan.t.h@snec.com.sg

Diagnosing and treating CMV anterior uveitis and endotheliitis Diagnosing and treating CMV anterior uveitis and endotheliitis
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