Cytomegalovirus in aqueous humor from an eye with corneal endotheliitis

PURPOSE: To report cytomegalovirus (CMV) DNA in aqueous humor from a patient with unilateral corneal endotheliitis. DESIGN: Case report. METHODS: A 51-year-old man presented with unilateral corneal endotheliitis with linear keratic precipitates and coin-shaped lesions. Tear and aqueous humor samples were subjected to polymerase chain reaction to look for DNA from herpes simplex virus (HSV), varicella zoster virus (VZV), and CMV. RESULTS: Aqueous humor from the diseased eye contained DNA from CMV but not HSV or VZV. Its specificity was confirmed by Southern blot tests. Intravenous ganciclovir treatment resulted in the localization of his corneal edema and the reduction in keratic precipitates. There was severe destruction of corneal endothelial cells. CMV DNA was not detected in tears or control samples. CONCLUSIONS: In this healthy man with corneal endotheliitis, we detected CMV DNA in aqueous humor from the affected eye, but not HSV or VZV. This suggests that CMV may cause corneal endotheliitis in patients without immunodeficiency.     

DNA of cytomegalovirus detected by PCR in aqueous of patient with corneal endotheliitis after penetrating keratoplasty

PURPOSE: Corneal endotheliitis often leads to severe endothelial dysfunction and can be caused by herpes simplex virus (HSV), varicella zoster virus (VZV), and other viruses (eg, the mumps virus). We report a case of corneal endotheliitis caused by cytomegalovirus (CMV) that developed after a penetrating keratoplasty. METHODS: A complete ophthalmologic examination was performed on a patient with corneal endotheliitis that developed after a penetrating keratoplasty. To determine the cause of the endotheliitis, polymerase chain reaction (PCR) was used to amplify the DNA of HSV, VZV, and CMV in samples of the aqueous humor. RESULTS: Slit-lamp biomicroscopy showed a moderate stromal edema in the upper temporal part of the transplanted cornea along with keratic precipitates (KPs) arranged in a coin-shaped pattern. Repeated treatments with steroids and acyclovir were only temporarily successful. PCR detected the DNA of CMV in an aqueous sample, and the treatment was switched to topical and systemic application of ganciclovir. This resulted in the disappearance of the KPs and resolution of the stromal edema within 2 weeks. CONCLUSIONS: From the PCR results and the favorable response to ganciclovir, the corneal endotheliitis was most likely caused by cytomegalovirus in this case.     

Identification of cytomegalovirus and human herpesvirus-6 DNA in a patient with corneal endotheliitis

Purpose

To report the case of a patient with unilateral corneal endotheliitis in which both cytomegalovirus (CMV) and human herpesvirus-6 (HHV6) DNA was identified in the aqueous humor.

Case

A 67-year-old man with corneal endotheliitis OD was referred to us for decreased visual acuity. Local corneal stromal edema, pigmented keratic precipitates, a coin-shaped lesion and minimal anterior chamber reaction were observed by slit-lamp biomicroscopy. Cells with owl’s eye appearance in the endothelial cell layer were observed by in vivo laser confocal microscopy. The patient had rheumatoid arthritis, which was treated by oral prednisolone and intravenous abatacept. Polymerase chain reaction analysis of aqueous humor samples detected both CMV and HHV6 DNA, but not other HHVs. Treatment with topical ganciclovir and systemic valganciclovir resulted in a clear cornea.

Conclusions

A patient with corneal endotheliitis had both CMV and HHV6 DNA identified in the aqueous humor. Although both viruses were identified in this case, clinical manifestations resembled CMV corneal endotheliitis, and it was unclear whether HHV6 could affect the clinical course. Systemic abatacept and corticosteroid therapy might play a positive role in cases with both CMV and HHV6 DNA in this corneal endotheliitis.     

Cytomegalovirus-related corneal endotheliitis: A review article

Cytomegalovirus (CMV)-related corneal endotheliitis is an inflammation of the corneal endothelium caused by CMV. It typically presents as coin-shaped keratic precipitates (KPs), with or without corneal edema, in otherwise healthy individuals. It may be associated with anterior uveitis and raised intraocular pressure (IOP). Patients with CMV-related corneal endotheliitis respond to systemic and topical ganciclovir with the use of topical steroid. Making an accurate early diagnosis is crucial in preventing loss of corneal endothelial cells and unnecessary treatment resulting from misdiagnosis in these patients.     

A Case of CMV Endotheliitis Treated with Intravitreal Ganciclovir Injection

We report a case of CMV corneal endotheliitis that was treated with intravitreal ganciclovir injection. A 56-year-old man who has suffered from uveitis was referred to our clinic due to corneal endothelial abnormality. Slit lamp examination showed a localized sectoral corneal edema and linear keratic precipitates along the boundary of edema. In spite of treatment with oral steroid and acyclovir, the disease progressed and two new coin-like lesions were developed. After topical ganciclovir and intavitreal injection of ganciclovir, the corneal lesions disappeared.     

Histopathology of herpetic corneal endotheliitis - a case report

BACKGROUND: Clinically, corneal endotheliitis is characterized by endothelial cell edema associated with immune precipitates. It is supposed to be triggered by a humoral or cellular immunologic reaction against antigens of the corneal endothelium. As yet, only few histopathologic studies of this disease have been performed. PATIENT: A 42-years-old patient developed a complete corneal nebula with neovascularizations due to relapsing herpetic keratitis. He underwent perforating keratoplasty. The inflammatory infiltrate lining Descemet's membrane and the corneal endothelium consisted mostly of CD 45 R0-positive T-lymphocytes with only few neutrophils, macrophages and CD 20-positive B-lymphocytes. We could not demonstrate any viral particles in the removed corneal tissue by either electron microscopy or using antibodies against Herpes simplex type I or II. CONCLUSIONS: Histologically, herpetic endotheliitis appears to correspond to corneal endotheliitis due to graft rejection. Complete virus particles are not necessarily required in case of long-standing inflammation and corneal neovascularizations.     

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

Purpose

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.

Method

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.

Results

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.

Conclusions

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.     

Herpes simplex virus in the trabeculum of an eye with corneal endotheliitis

PURPOSE: To report an eye with corneal endotheliitis and increased intraocular pressure in which the trabeculum demonstrated immunoreactivity for herpes simplex virus. METHOD: Case report. A 62-year-old man presented with increased intraocular pressure, keratic precipitates, and corneal stromal edema in his left eye. The tissue excised during trabeculectomy was immunohistochemically examined for herpetic viruses. RESULT: Immunoreactivity for herpes simplex virus was identified in the trabeculum. CONCLUSION: Herpes simplex virus may cause trabeculitis and increased intraocular pressure in patients with corneal endotheliitis.     

The Effect of Topical Ganciclovir and Corticosteroid on Cytomegalovirus Corneal Endotheliitis in Korean Patients

Purpose: To report long-term outcomes of topical ganciclovir (GCV) and corticosteroids in Korean patients with cytomegalovirus (CMV) corneal endotheliitis.

Methods: This retrospective study included 13 eyes from 13 patients with CMV corneal endotheliitis, with a follow-up period of 24.5 ± 8.2 months. The patients were consistently maintained with topical 2% GCV and 1% prednisolone acetate eyedrop.

Results: All patients demonstrated unilateral typical coin-shaped keratic precipitates (KPs) or linear KP, and positive CMV polymerase chain reaction of aqueous humor. After 2 weeks of treatment, all patients showed decrease of clinical signs. During the follow-up, four patients developed mild anterior chamber inflammation with increased intraocular pressure without typical coin-shaped KPs or edema, started to use the initial dose, and resolved the clinical signs. One patient showed recurrence of corneal edema twice, and was administered systemic valgancyclovir for 2 weeks upon second recurrence with resolution of clinical signs.

Conclusion: Long-term maintenance therapy with topical GCV and corticosteroids are effective and maintain corneal endothelial function in Korean patients with CMV endotheliitis.     

角膜内皮炎共焦显微镜形态学分析

目的:观察角膜内皮炎的共焦显微镜下形态学特征。方法:应用Confoscan 4.0共焦显微镜对24例24眼角膜内皮炎患者的角膜进行扫描检查,记录并分析各层角膜图像。结果:所有患者前部基质混浊,角膜深基质层可见基质细胞排列紊乱及条索状高反光结构,深基质层中还可见低反光带为后弹力层皱褶,角膜内皮细胞前可见斑片状大小不等的高反光结构,病变区角膜内皮细胞水肿、变性呈无结构暗区,内皮细胞呈多形性改变。4眼角膜上皮细胞边界不清,排列疏松,细胞较大,细胞核呈高反光结构,其中可见泡状暗区。结论:共焦显微镜可活体检查角膜内皮炎患者角膜组织各层结构,起到类似病理组织切片的作用;角膜内皮炎以深基质层及内皮细胞层损害为特征;共焦显微镜检查对角膜内皮炎具有一定的参考价值。     

The validity of clinical feature profiles for cytomegaloviral anterior segment infection

Background  

Anterior segment cytomegalovirus (CMV) infection, which can be presented as anterior uveitis and corneal endotheliitis, has recently been reported in immunocompetent patients. We would like to access the validity of two presumed characteristic clinical profiles: profile 1, non-herpes simplex virus (HSV)/varicella zoster virus (VZV) corticosteroid-recalcitrant inflammatory ocular hypertensive syndrome (IOHS), and profile 2, corneal endotheliitis with specific coin-shaped keratic precipitates (KPs), that could be helpful in identifying CMV anterior segment intraocular infection.     

Corneal endotheliitis

Corneal endotheliitis is an intriguing clinical entity manifested by corneal edema, keratic precipitates, and mild anterior chamber reaction, and can be defined as a spectrum of the disorder in which the corneal endothelium is the primary site of the inflammation. The disease etiology consists of accumulating evidence of various viral infections including herpes simplex virus, varicella zoster virus, and cytomegalovirus. Corneal endotheliitis can be classified clinically into four forms: linear, sectorial, disciform, and diffuse. Antiviral treatment in combination with topical corticosteroids is generally effective to suppress the inflammation; however, irreversible corneal endothelial dysfunction may develop in some cases.     

Corneal Endotheliitis

Corneal endotheliitis is an intriguing clinical entity manifested by corneal edema, keratic precipitates, and mild anterior chamber reaction, and can be defined as a spectrum of the disorder in which the corneal endothelium is the primary site of the inflammation. The disease etiology consists of accumulating evidence of various viral infections including herpes simplex virus, varicella zoster virus, and cytomegalovirus. Corneal endotheliitis can be classified clinically into four forms: linear, sectorial, disciform, and diffuse. Antiviral treatment in combination with topical corticosteroids is generally effective to suppress the inflammation; however, irreversible corneal endothelial dysfunction may develop in some cases.     

Diagnosis of epithelial ingrowth after penetrating keratoplasty with confocal microscopy

PURPOSE: To report confocal microscopy use in the clinical diagnosis of epithelial ingrowth after penetrating keratoplasty (PKP). METHODS: A 36-year-old female patient with keratoconus developed a well-delimited posterior hazy membrane covering the inferior two thirds of the cornea 3 months after an uneventful PKP. A posterior corneal line was present resembling an endothelial graft rejection line, but with no keratic precipitates or corneal edema. Ocular hypertension was not observed. Confocal microscopy was performed to elucidate the diagnosis. RESULTS: Confocal microscopy showed epithelium and stroma with normal findings. Two distinct cellular types were presented at the endothelium layer. Enlarged endothelial cells were observed in the superior part of the cornea up to the leading edge of the hazy membrane. In the middle and inferior part of the graft, the cells were larger, with polygonal shape and easily recognizable hyperreflective nuclei, suggestive of epithelial cells. With these confocal microscopy findings, the patient was promptly submitted to another PKP. Histologic analysis confirmed the diagnosis of epithelial ingrowth. CONCLUSION: Confocal microscopy imaging technique seems to be a useful tool in the early diagnosis of epithelial ingrowth after PKP.     

Self-limiting corneal edema with multiple parallel lines on the endothelium (SCEMPLE)

The purpose of this study was to report the natural course and in vivo confocal microscopy (IVCM) findings of five cases with unilateral self-limiting corneal edema and multiple parallel lines on the endothelium (SCEMPLE). This study is an observational case series. Five patients, who experienced a blurred vision due to SCEMPLE, were studied using slit-lamp examination and white-light IVCM (Confoscan 4; Nidek Technologies, Padova, Italy). IVCM of the linear deposits revealed characteristic hyperreflective material protruding between the endothelial cells. The lines also displayed spot-like holes and polygonal precipitates, which resembled dislodged endothelial cells. Because other signs of corneal inflammation, such as stromal infiltration and ciliary injection, were lacking, the condition was left untreated. After 1 day, slit-lamp examination and IVCM revealed only a small residual of the lines. Spontaneous, complete resolution occurred in all five cases within 1 week, leaving a lower endothelial cell density of the affected eyes as only sequela. SCEMPLE requires no treatment but may result in endothelial cell loss. The self-limiting character and IVCM appearance dispute SCEMPLE being a form of endotheliitis and suggest a different etiology.     

Confocal microscopy used as the definitive, early diagnostic method in Chandler syndrome

PURPOSE: To report the early, rapid diagnosis of the Chandler variant of the iridocorneal endothelial (ICE) syndrome using confocal light microscopy. METHODS: A 62-year-old man with a long history of unilateral glaucoma reported progressively blurred vision in his right eye. Examination of both eyes included visual acuity, slit-lamp examination, pneumotonometry, visual field, gonioscopy, and confocal microscopy. RESULTS: On examination, visual acuity was 20/80 and 20/20 and the IOPs were 26 and 12. The anterior segment OD revealed 1+ inferior and axial corneal edema, while the OS was normal to biomicroscopy and posterior segment. Chandler syndrome or Fuchs endothelial dystrophy was suspected. In the affected eye, confocal light microscopy clearly showed an "epithelium-like" transformation of the corneal endothelium with irregularly shaped cells and hyperreflective nuclei, establishing the diagnosis of Chandler syndrome. CONCLUSIONS: In the presence of corneal edema or haze, corneal endothelium can be clearly visualized by confocal microscopy. "Epithelium-like" endothelial cells with highly reflective nuclei characteristic of Chandler syndrome were easily identified by confocal light microscopy to establish the diagnosis, despite the presence of corneal edema. Thus, confocal microscopy is a sensitive tool for the rapid, early diagnosis of ICE syndrome and may help distinguish among its variants.     

Clinical Features of CMV-Associated Anterior Uveitis

Cytomegalovirus (CMV) anterior uveitis is the most common ocular manifestation of CMV disease in immunocompetent individuals. It is thought to be due to a local reactivation of latent CMV and is usually unilateral. The acute form presents as Posner-Schlossman Syndrome, a recurrent hypertensive anterior uveitis with few granulomatous keratic precipitates. There are geographic differences in the chronic form of CMV anterior uveitis. Asian patients commonly present as Fuchs Uveitis Syndrome with diffuse stellate keratic precipitates, while the European patients present with a chronic hypertensive anterior uveitis with fewer keratic precipitates that are brown in color and located inferiorly. Characteristic features of CMV anterior uveitis include mild anterior chamber inflammation, elevated intraocular pressure, stromal iris atrophy. Synechiae, macular edema and retinitis are typically absent. CMV disease may also be associated with the development of corneal endotheliitis with a reduced endothelial cell count. Long-term complications include glaucomatous optic neuropathy and cataract formation.     

Progressive herpetic linear endotheliitis

PURPOSE: To report the clinical course of a rare case of bilateral herpetic linear endotheliitis. METHODS: A 70-year-old man presented with bilateral circumferential bullous edema with stromal edema progressing centrally in the left cornea and bilateral sensorineural hearing impairment simultaneously. Serum immunoglobulin G (IgG) and IgM antibodies against herpes simplex virus type 1 (HSV1) were tested for, and aqueous humor from both eyes was examined separately using polymerase chain reaction for the presence of HSV1 DNA. RESULTS: Serum antibody titers against HSV1 were positive. In the polymerase chain reaction, the aqueous humor showed HSV1 DNA in both eyes. Forty milligrams of prednisolone was given per day and 200 mg of oral acyclovir was given 4 times daily, but corneal edema progressed. After penetrating keratoplasty surgery in the left eye, recurrent herpetic endotheliitis also seemed to occur. CONCLUSIONS: HSV-1 may cause bilateral corneal linear endotheliitis and hearing impairment simultaneously. Linear endotheliitis should be regarded as a manifestation of HSV1 corneal infection. There is a poor prognosis, and severe corneal edema can result if aggressive treatment is not used.