Cytomegalovirus Corneal Endotheliitis Research Articles

Mapping owl’s eye cells of patients with cytomegalovirus corneal endotheliitis using in vivo laser confocal microscopy

To produce a two-dimensional reconstruction map of owl's eye cells using in vivo laser confocal microscopy in patients with cytomegalovirus (CMV) corneal endotheliitis, and to demonstrate any association between owl's eye cells and coin-shaped lesions observed with slit-lamp biomicroscopy. Two patients (75- and 77-year-old men) with polymerase chain reaction-proven CMV corneal endotheliitis were evaluated in this study. Slit-lamp biomicroscopy and in vivo laser confocal microscopy were performed. Images of owl's eye cells in the endothelial cell layer were arranged and mapped into subconfluent montages. Montage images of owl's eye cells were then superimposed on a slit-lamp photo of the corresponding coin-shaped lesion. Degree of concordance between the confocal microscopic images and slit-lamp photos was evaluated. In both eyes, a two-dimensional reconstruction map of the owl's eye cells was created by computer software using acquired confocal images; the maps showed circular patterns. Superimposing montage images of owl's eye cells onto the photos of a coin-shaped lesion showed good concordance in the two eyes. This study suggests that there is an association between owl's eye cells observed by confocal microscopy and coin-shaped lesions observed by slit-lamp biomicroscopy in patients with CMV corneal endotheliitis. The use of in vivo laser confocal microscopy may provide clues as to the underlying causes of CMV corneal endotheliitis.

Cytomegalovirus and the eye

Following primary infection, cytomegalovirus (CMV) establishes latent infection in myeloid progenitor cells and intermittent viral reactivation from activated macrophages or dendritic cells, which is brought under control by strong virus-specific CD4+ T-cell and CD8+ T-cell responses. CMV retinitis characterized by spreading retinal necrosis due to viral cytopathic effect occurs in patients who have impaired T-cell function as a result of transplantation, AIDS, or immuno-suppressive treatment. The diagnosis of CMV retinitis can be confirmed by PCR amplification of viral DNA in aqueous. When administered intravenously, the antiviral drugs Ganciclovir and Foscarnet have modest penetration into the vitreous compared with direct intra-vitreal injection. In randomized trials of HIV-associated CMV retinitis, a Ganciclovir implant was consistently superior to intravenous Ganciclovir in preventing progression of retinitis. CMV is also implicated in two forms of anterior segment disease in immuno-competent adults, namely CMV anterior uveitis and CMV corneal endotheliitis.

Clinical Significance of Owl Eye Morphologic Features by In Vivo Laser Confocal Microscopy in Patients With Cytomegalovirus Corneal Endotheliitis

To demonstrate the clinical significance of owl eye morphologic features observed by in vivo laser confocal microscopy in patients with cytomegalovirus (CMV) corneal endotheliitis. Observational case series. participants: Six eyes of 6 patients (6 men; mean age, 73.3 years) with cytomegalovirus corneal endotheliitis diagnosed by clinical manifestations together with polymerase chain reaction from aqueous humor samples. intervention: All patients were examined by slit-lamp biomicroscopy and in vivo laser confocal microscopy. main outcome measures: Clinical manifestations were summarized by reviewing medical records. Selected confocal images of corneal layers were evaluated qualitatively for shape and degree of light reflection of abnormal cells and deposits. All patients had long histories of anterior uveitis with intraocular pressure elevation, corneal edema with keratic precipitates, and decrease of endothelial cell densities. Coin-shaped lesions were observed by slit lamp only in 1 patient at the first visit and in 2 additional patients at subsequent follow-up. In all patients, confocal microscopy demonstrated reduced subepithelial nerves, subepithelial opacity, increased reflectivity of keratocytes, highly reflective dots, and needle-shaped bodies. Owl eye morphologic features were observed consistently in all patients at the initial visit, and highly reflective round bodies were detected in 5 patients; most notably, these confocal features were reversible after resolution of endotheliitis. Owl eye morphologic features and highly reflective round bodies observed by confocal microscopy may be useful as an adjunct for the noninvasive diagnosis of cytomegalovirus corneal endotheliitis. Reversibility of these features after resolution of endotheliitis may be useful for monitoring the therapeutic effects without multiple anterior chamber tap.

Recurrent Cytomegalovirus Corneal Endotheliitis after Penetrating Keratoplasty

To report a case of recurrent cytomegalovirus (CMV) corneal endotheliitis after penetrating keratoplasty. Penetrating keratoplasty (PK) was performed in a 49-year-old man with bullous keratopathy. Pigmented keratic precipitates (KPs) were found in the corneal endothelium of the graft 13 days after surgery, with the subsequent appearance of coin-shaped lesions. Confocal microscopy was performed on the corneal endothelium. Aqueous humor was analyzed for viral DNA by polymerase chain reaction (PCR). CMV DNA was detected from the excised corneal button, and aqueous humor revealed positive results for CMV and HSV1 by PCR. Confocal microscopy showed large corneal endothelial cells, consistent with the typical owl's eye morphology of CMV endotheliitis. After systemic ganciclovir was administered, the pigmented KPs and coin-shaped lesions gradually decreased. Stress from surgery and corticosteroid usage can revitalize CMV activity. PCR and confocal microscopy are valuable for the diagnosis of CMV corneal endotheliitis.

Prevalence and Features of Keratitis with Quantitative Polymerase Chain Reaction Positive for Cytomegalovirus

To assess corneal scrapings and aqueous humor samples analyzed by polymerase chain reaction (PCR) that were positive for cytomegalovirus (CMV) in patients with keratitis of unknown origin and to investigate their clinical manifestations. Retrospective, interventional case series. Seventy-eight patients with epithelial (n=37), stromal (n=12), or endothelial keratitis (n=29) of unknown origin examined at the Osaka University Medical Hospital. Clinical examination and tears, corneal scrapings, and aqueous humor specimens were evaluated by real-time PCR for CMV. Quantification of CMV DNA at the diagnosis of each type of keratitis with unknown origin and monitoring during the therapeutic course for CMV-positive cases. No cases of epithelial or stromal keratitis had CMV DNA. Seven of 29 corneal endotheliitis cases (24.1%) were positive for CMV. Cytomegalovirus-positive cases of corneal endotheliitis characterized by localized corneal edema and keratic precipitates included 4 patients who had undergone penetrating keratoplasty and were refractory to the treatment for graft rejection and 3 patients with idiopathic endotheliitis. Cytomegalovirus DNA copy numbers were estimated and ranged from 6.3x10(4) to 3.6x10(6)/ml. In all positive cases, the numbers of CMV DNA copies decreased within weeks during treatment with systemic and topical ganciclovir (GCV) combined with a topical steroid. Five eyes (62.5%) had clinical improvement. In cases of endothelial keratitis, diabetes mellitus was significantly higher in patients positive for CMV (71.4%) than in patients negative for CMV (18.2%, P=0.016, chi-square test). A total of 24.1% of cases with corneal edema of unknown origin were CMV positive and should be included in the differential diagnosis of idiopathic corneal endotheliitis or graft edema after penetrating keratoplasty, especially for bullous keratopathy. Real-time PCR for CMV, based on the diagnosis and monitoring of the clinical course, may be useful. Cytomegalovirus corneal endotheliitis requires early appropriate treatment using GCV. Because clinical remission after GCV may depend on the area of normal endothelium, early diagnosis and therapy are important for CMV corneal endotheliitis.

Cytomegalovirus as an Etiologic Factor in Corneal Endotheliitis

To investigate clinical manifestations and response to antiviral therapy of 8 patients with cytomegalovirus (CMV)-induced corneal endotheliitis who were diagnosed and treated at 2 university hospitals in Japan. Retrospective, consecutive, multicenter case series. Eight eyes of 8 patients diagnosed with active CMV corneal endotheliitis at Kyoto Prefectural University of Medicine and Ehime University School of Medicine. The diagnosis was made based on the detection by polymerase chain reaction assay of CMV, but not herpes simplex virus (HSV) and varicella zoster virus (VZV) DNA, in the aqueous humor from the affected eye. Retrospective review of the clinical manifestations and responses to antiviral treatment. Patient profiles, including duration of corneal endotheliitis, systemic disease, intraocular pressure, and clinical manifestation of anterior and posterior segments. The clinical response to systemic and topical antiviral treatment was evaluated by slit-lamp examination. Corneal endothelial density was examined by specular microscopy. The average observation period after CMV detection was 10.4 months (range, 2-24 months). None of the patients had systemic immunodeficiency. Corneal manifestations included linear keratic precipitates associated with multiple coin-shaped lesions and local corneal stromal edema. Of the 8 patients, 4 had undergone penetrating corneal transplantation. Systemic ganciclovir therapy was used in 7 patients, and in 1 patient, valacyclovir was administered, with the corneal endotheliitis responding quickly to the early administration of galovir. At the final examination, 6 eyes had a clear cornea, but 2 eyes had bullous keratopathy. Besides HSV and VZV, CMV must be considered as an etiologic agent in patients with corneal endotheliitis. Cytomegalovirus corneal endotheliitis may be a newly identified clinical entity of reactivated CMV in the anterior chamber of individuals free of accompanying systemic symptoms.

Demonstration of “Owl’s Eye” Morphology by Confocal Microscopy in a Patient With Presumed Cytomegalovirus Corneal Endotheliitis

To report confocal microscopic observations of characteristic corneal endothelial lesions in a patient with presumed cytomegalovirus (CMV) corneal endotheliitis. Case report. A 77-year-old, immunocompetent man was admitted with corneal edema, keratic precipitates, and coin-shaped lesions in the right eye. Confocal microscopy was performed to examine the corneal endothelium. Polymerase chain reaction (PCR) was used to identify viral DNA in an aqueous humor sample. CMV DNA was detected by PCR. Confocal microscopy showed large corneal endothelial cells with an area of high reflection in the nucleus surrounded by a halo of low reflection. This "owl's eye" morphology is characteristic of CMV infection. Topical and intravenous ganciclovir treatment resulted in rapid resolution of the corneal precipitates and edema, followed by disappearance of the owl's eye morphology. Confocal microscopy can detect the owl's eye morphology in the corneal endothelium of patients with presumed CMV corneal endotheliitis.