Clinical Evaluation of Intravitreal Injection of Ganciclovir in Refractory Corneal Endotheliitis

ABSTRACT

Purpose: To evaluate the efficacy and safety of intravitreal ganciclovir (GCV) injection in refractory endotheliitis.

Methods: Retrospectively recruited 25 eyes with endotheliitis, proved by clinical manifestations, positive PCR for viral DNA and responded poor to topical and systemic antiviral medications. All patients received additional continued intravitreal GCV injections.

Results: Cytomegalovirus (CMV), varicella zoster virus (VZV), and herpes simplex virus (HSV) DNA were detected in 64.0%, 28.0%, and 8.0% of the eyes, respectively. Within 2 weeks after the last injection, 16/25 eyes recovered corneal clarity; active keratic precipitates (KPs) were eliminated in 21/25 eyes; intraocular pressure (IOP) was controlled in 12/15 eyes with elevated IOP on study entry. Best-corrected visual acuity increased at the last follow-up (p = 0.016). Clinical recurrence occurred in three patients. No complications were detected.

Conclusions: CMV endotheliitis was the main type of refractory endotheliitis. Despite its invasive nature, intravitreal GCV injection appears to be an effective method for refractory 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.     

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.     

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.     

Clinical characteristics and treatment outcomes of cytomegalovirus anterior uveitis and endotheliitis: A systematic review and meta-analysis

Cytomegalovirus (CMV) anterior uveitis is the most common form of ocular manifestation of CMV in immunocompetent individuals. The difficulty in diagnosing CMV anterior uveitis may delay adequate treatment and affect outcomes. We sought to review systemically the overall clinical characteristics and compare treatment outcomes in CMV anterior uveitis and endotheliitis. A literature search was performed, and studies describing clinical characteristics, treatment regimens, and outcomes that included more than 5 treated eyes were included. In these 23 studies, acute CMV anterior uveitis commonly presented with high intraocular pressure (95.31%, 95% CI 90.45–98.60) and mild anterior chamber inflammation (cells >2+ = 3.18%, 95% CI 0.21–0.54). About two-thirds of CMV endotheliitis cases presented with high intraocular pressure and coin-shaped corneal lesions. Acute CMV anterior uveitis showed good clinical response to topical 0.15% ganciclovir (GCV) gel or oral valganciclovir (VGCV) (90%, 95% CI 74–100% and 95%, 95% CI 88–100%, respectively). For chronic CMV anterior uveitis, both topical GCV and oral VGCV yielded comparable results. Topical 0.5–2% GCV or a combination of topical and oral VGCV for CMV endotheliitis both resulted in good clinical response. Recurrence of inflammation was common after cessation of maintenance therapy. Overall, topical GCV resulted in an optimal outcome for CMV anterior uveitis. Escalated concentration and frequency of usage are needed for chronic CMV anterior uveitis and endotheliitis. Adequate induction and maintenance phases of anti-CMV treatment seem necessary to prevent recurrences.     

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 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.     

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.     

Demonstration of "owl's eye" morphology by confocal microscopy in a patient with presumed cytomegalovirus corneal endotheliitis

PURPOSE: To report confocal microscopic observations of characteristic corneal endothelial lesions in a patient with presumed cytomegalovirus (CMV) corneal endotheliitis. DESIGN: Case report. METHODS: 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. RESULTS: 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. CONCLUSIONS: Confocal microscopy can detect the owl's eye morphology in the corneal endothelium of patients with presumed CMV corneal endotheliitis.     

Herpetic Anterior Uveitis – Analysis of Presumed and PCR Proven Cases

Purpose: To describe the demographics and clinical characteristics of patients with herpetic anterior uveitis (HAU), and compare characteristics by pathogen, recurrence, and association to iris atrophy.

Methods: Multicenter, retrospective study of AU patients diagnosed clinically and by polymerase chain reaction (PCR).

Results: The study included 112 eyes in 109 patients: 54 (48.2%) HSV, 34 (30.4%) VZV, 2 (1.8%) CMV, and 22 (19.6%) unspecified diagnosis. HSV eyes, compared to VZV, had a higher recurrence rate, corneal involvement, KPs, iris atrophy, elevated IOP and posterior synechia (p < 0.05). VZV patients had more frequent immunomodulatory treatments and history of systemic herpetic disease (p < 0.05). Fifty-nine (52.7%) eyes had recurrent disease. Iris atrophy was associated with a higher prevalence of posterior synechia, dilated distorted pupil, and high IOP (p < 0.05).

Conclusion: Different HAU-causing Herpesviridae produce common clinical findings; therefore, PCR should be used more often to confirm specific diagnosis. Iris atrophy was associated with more severe disease.     

Diagnosis of Cytomegalovirus Anterior Uveitis in Two European Referral Centers

Purpose: To evaluate diagnostic methods and clinical signs of CMV anterior uveitis (AU), a rarely described entity in Europe.

Methods: We included patients with clinical characteristics of CMV AU and positive PCR and/or Goldmann-Witmer coefficient (GWc) for CMV.

Results: We report 21 patients with unilateral uveitis (100%) and signs of Posner-Schlossman syndrome (PSS) (n = 20, 95.2%), Fuchs uveitis syndrome (FUS) (n = 1, 4.7%), and endotheliitis (n = 4, 19,04%). PCR was positive in 15/21 (71.4%) and GWc in 8/9 patients (88.9%) in aqueous for CMV. GWc was the only positive test in 6/9 patients (66,6%). When PCR alone was performed (without GWc) in the first tap, repeated aqueous taps were needed, twice in five cases and thrice in one case.

Conclusion: Combining PCR and GWc were very helpful to confirm the clinical diagnosis of CMV AU. In case of very high clinical suspicion and negative results, repeated tap seems to be recommended.     

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.     

Mumps-induced corneal endotheliitis

OBJECTIVE: To report two cases of corneal endotheliitis following mumps parotitis. METHODS: Observational case reports of two patients presenting with sudden unilateral diminution of vision while they were in the resolution phase of mumps parotitis. RESULTS: Central corneal edema with no associated epithelial involvement or iridocyclitis was confirmed on slit-lamp biomicroscopy. Specular microscopy confirmed an increased corneal thickness with corneal endothelial abnormalities. The diagnosis of mumps virus infection was established through detection of IgM antibody in serum samples of the patients using enzyme-linked immunosorbent assay (ELISA). The routine investigations for other systemic diseases were negative. CONCLUSIONS: Corneal endotheliitis as a sequela to mumps is a new reported association. Timely treatment with topical steroids led to resolution of the disease with full visual recovery without any residual symptoms or signs.     

角膜内皮炎治疗的临床观察

目的探讨局部联合全身应用抗病毒及皮质类固醇激素治疗角膜内皮炎的疗效。方法回顾分析2011年11月至2013年9月在十堰市太和医院眼科诊断为角膜内皮炎并接受住院治疗患者的病例资料。结果本研究中的角膜内皮炎患者23例（23只眼）,盘状型角膜内皮炎15例,弥漫型角膜内皮炎8例,均达到治愈标准,平均治愈时间为（8.6±5.4）d。盘状型和弥漫型两组角膜内皮炎治愈时间分别为（8.3±4.5）d和（9.1±6.2）d,两组间差异无统计学意义（P〉0.05）。治愈后除1例黄斑变性、2例白内障患者最佳矫正视力分别为0.2,0.4和0.5外,其余患者最佳矫正视力均≥0.8。结论局部联合全身应用抗病毒及激素药物可以有效、快速治愈角膜内皮炎,获得良好的视力。     

角膜内皮炎60例疗效分析

目的 探讨局部抗病毒及激素药物治疗对不同类型角膜内皮炎的疗效.设计前瞻性病例系列.研究对象江苏大学附属人民医院眼科2008年1月到2010年6月间收治的角膜内皮炎患者60例.方法 60例角膜内皮炎患者包括盘状型、弥漫型和线状型,随机分为局部药物治疗组和局部联合全身药物治疗组,局部药物治疗组应用更昔洛韦眼用凝胶和妥布霉素...     

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.     

单纯疱疹病毒性角膜炎内皮型的诊治

目的:探讨单纯疱疹病毒性角膜炎内皮型的诊治措施。方法:选取40例50眼角膜炎患者,结合患者临床症状、体征,并行普通的裂隙灯显微镜检查及角膜激光共聚焦显微镜检查,均确诊为单纯疱疹病毒性角膜炎内皮型,将40例50眼患者随机分为两组,20例24眼采用单纯抗病毒治疗作为对照组,20例26眼采用抗病毒联合糖皮质激素治疗作为观察组,观察两组患者治疗效果。结果:两组患者均顺利完成整个治疗计划,观察组患者在治疗期间未出现角膜溃疡扩大、加深,也无溃疡穿孔等并发症。观察组治疗有效18眼,总有效率为70%,对照组治疗有效12眼,总有效率为50%,两组差异具有统计学意义(P<0.05)。结论:单纯疱疹病毒性角膜炎内皮型易与临床上多种眼病混淆,临床上应结合患者病史、临床症状及辅助检查确诊,可采用抗病毒治疗联合糖皮质激素治疗,提高治疗效果。     

更昔洛韦胶囊治疗病毒性角膜内皮炎的疗效观察

目的:探讨更昔洛韦胶囊治疗病毒性角膜内皮炎的临床疗效。方法:收集2011-10/2012-10在中国医科大学附属第一院眼科门诊确诊的病毒性角膜内皮炎患者14例14眼,排除高血压病史、白细胞、血小板减少及肝肾功异常后,予更昔洛韦胶囊1.0g,3次/d,口服,持续2～4wk后,改为0.5g,3次/d,口服,持续4wk后停药;同时联合眼部应用1.5g/L更昔洛韦凝胶及10g/L醋酸泼尼松龙滴眼液点眼;观察用药后眼痛、视物模糊、畏光、异物感、视力、结膜充血、角膜水肿、角膜后弹力层皱褶及角膜后沉着物(KP)等指标,评价治疗有效率与治愈率,并观察用药后复发情况。治疗前后评分比较采用秩和检验方法。结果:采用更昔洛韦胶囊口服治疗后眼部症状及眼部体征从第1wk开始逐渐好转,评分由治疗前的19.14±4.57逐渐下降为第1wk的11.43±3.86,第2wk的6.93±2.59,第4wk的0.29±0.87;至治疗后第8wk14例患者眼部症状及体征完全消失。第1,2,4,8wk有效率分别为71%,100%,100%,100%。与发病之前比较,14例患者中10例视力完全恢复,3例轻度下降,1例视力明显下降。14例患者随访观察中均未见复发。结论:更昔洛韦胶囊联合眼部用药治疗病毒性角膜内皮炎有效,并且可以预防复发。     

综合治疗病毒性角膜内皮炎的临床效果和形态学分析

目的：观察糖皮质激素联合抗病毒药物综合治疗病毒性角膜内皮炎的临床效果和角膜内皮形态学的变化,并探讨治疗方案的安全性。

方法：回顾性分析2014-01/2015-12就诊于西安市第四医院的48例48眼病毒性角膜内皮炎患者的发病诱因、病史和临床表现,采用自身对照研究,比较糖皮质激素联合抗病毒药物综合治疗后3mo患者的治愈率、复发情况和角膜内皮形态学的变化。

结果：病毒性角膜内皮炎发病诱因较多,患者均有眼红、眼疼、畏光、流泪和视力下降、视物模糊等症状,临床表现包括视力下降、结膜睫状充血或混合充血、角膜水肿,可有角膜上皮小水泡、后弹力层皱褶、灰白色或羊脂状KP、眼压升高、虹膜后粘连,反复发作者发生角膜大泡。治疗1mo有效率达100%,治愈率达88%,且未见复发病例; 治疗2mo有效率和治愈率达100%,共1眼(2%)复发; 治疗3mo共2眼(4%)复发。治疗3mo后治疗组的细胞计数(t=2.952,P=0.004)和OCT角膜厚度(t=2.584,P=0.011)均低于对照组,差异有统计学意义; 治疗组的细胞多形性变异率(45.85%±6.29%)高于对照组(40.62%±5.16%),差异有统计学意义(t=4.458,P<0.001)。治疗前治疗组的视力差于对照组,差异有统计学意义(Z=-5.766,P<0.001); 治疗后治疗组的视力恢复到0.20(0.10～0.40)LogMAR,治疗前后差异有统计学意义(Z=-6.089,P<0.001)。

结论：病毒性角膜内皮炎的临床表现和病因复杂多样,应用抗病毒药物和糖皮质激素联合治疗,能够取得良好疗效,但是治疗后角膜内皮计数和角膜厚度减少,为治疗的安全性提出了更高的要求。