Interventions for the management of CMV-associated anterior segment inflammation

Anshu, Arundhati; Tan, Donald; Mehta, J. S.; Htoon, Hla Myint

doi:10.1002/14651858.cd011908.pub2

Cited by 11 publications

(7 citation statements)

References 18 publications

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“…However, certain inflammatory conditions, such as uveitis and virus-induced anterior segment inflammation, can predispose to glaucoma (49, 50). Indeed, several viruses, such as herpes simplex virus (HSV), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV), have been linked to causing either primary or secondary glaucoma (50–53). Recently, several clinical case reports from ZIKV-affected countries have linked ZIKV infection to causing congenital glaucoma.…”

Section: Discussionmentioning

confidence: 99%

Zika Virus Infects Trabecular Meshwork and Causes Trabeculitis and Glaucomatous Pathology in Mouse Eyes

Singh

Kasetti

Zode

et al. 2019

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Zika virus (ZIKV) infection during pregnancy leads to devastating fetal outcomes, including neurological (microcephaly) and ocular pathologies such as retinal lesions, optic nerve abnormalities, chorioretinal atrophy, and congenital glaucoma. Only clinical case reports have linked ZIKV infection to causing glaucoma, a major blinding eye disease. In the present study, we have investigated the role of ZIKV in glaucoma pathophysiology using in vitro and in vivo experimental models. We showed that human primary trabecular meshwork (Pr. TM) cells, as well as a human GTM3 cell line, were permissive to ZIKV infection. ZIKV induced the transcription of various genes expressing pattern recognition receptors (TLR2, TLR3, and RIG-I), cytokines/chemokines (TNF-α, IL-1β, CCL5, and CXCL10), interferons (IFN-α2, IFN-β1, and IFN-γ), and interferon-stimulated genes (ISG15 and OAS2) in Pr. TM cells. ZIKV infection in IFNAR1−/− and wild-type (WT) mouse eyes resulted in increased intraocular pressure (IOP) and the development of chorioretinal atrophy. Anterior chamber (AC) inoculation of ZIKV caused infectivity in iridocorneal angle and TM, leading to the death of TM cells in the mouse eyes. Moreover, anterior segment tissue of infected eyes exhibited increased expression of inflammatory mediators and interferons. Furthermore, ZIKV infection in IFNAR1−/− mice resulted in retinal ganglion cell (RGC) death and loss, coinciding with optic nerve infectivity and disruption of anterograde axonal transport. Because of similarity in glaucomatous pathologies in our study and other experimental glaucoma models, ZIKV infection can be used to study infectious triggers of glaucoma, currently an understudied area of investigation. IMPORTANCE Ocular complications due to ZIKV infection remains a major public health concern because of their ability to cause visual impairment or blindness. Most of the previous studies have shown ZIKV-induced ocular pathology in the posterior segment (i.e., retina) of the eye. However, some recent clinical reports from affected countries highlighted the importance of ZIKV in affecting the anterior segment of the eye and causing congenital glaucoma. Because glaucoma is the second leading cause of blindness worldwide, it is imperative to study ZIKV infection in causing glaucoma to identify potential targets for therapeutic intervention. In this study, we discovered that ZIKV permissively infects human TM cells and evokes inflammatory responses causing trabeculitis. Using a mouse model, we demonstrated that ZIKV infection resulted in higher IOP, increased RGC loss, and optic nerve abnormalities, the classical hallmarks of glaucoma. Collectively, our study provides new insights into ocular ZIKV infection resulting in glaucomatous pathology.

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Section: Discussionmentioning

confidence: 99%

Zika Virus Infects Trabecular Meshwork and Causes Trabeculitis and Glaucomatous Pathology in Mouse Eyes

Singh

Kasetti

Zode

et al. 2019

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“…Currently, there are no guidelines for treatment of uveitis related to HCMV in immunocompetent patients. 45 A previous study showed that ganciclovir topical ointment is effective in preventing relapses, 21,46 whereas oral valganciclovir seems more useful to treat acute episodes. 47,48 We showed here that oral valganciclovir is effective as treatment of acute manifestations and in reducing the number of relapses.…”

Section: Discussionmentioning

confidence: 99%

Clinical Features and Diagnosis of Anterior Segment Inflammation Related to Cytomegalovirus in Immunocompetent African, Asian, and Caucasian Patients

Leleu

Jhanji

Touhami

et al. 2019

Ocular Immunology and Inflammation

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To report the clinical features and treatment outcomes in immunocompetent patients with anterior segment inflammation (ASI) related to human cytomegalovirus (HCMV) depending on their ethnic origin. Material and Methods: Multicenter retrospective study of 38 patients with at least one test, either HCMV-positive PCR or GWc. Results: Features of Posner-Schlossman syndrome were observed in 50% of the eyes, Fuchs heterochromic iridocyclitis in 13% of the eyes, chronic nonspecific anterior uveitis in 21% of the eyes, and corneal endotheliitis in 18% of the eyes. PCR and GWc were positive for HCMV in 50% and 96.2% of the eyes, respectively. Glaucoma was diagnosed in 50% of eyes. Treatment was oral valganciclovir in about half of the patients. Other treatments were intravenous ganciclovir and/or ganciclovir topical ointment and/or intravitreal ganciclovir. Conclusions: No obvious association of specific clinical features with individual ethnicity could be identified. We found a high rate of glaucoma in all ethnic groups. There was a delay in diagnosis and specific treatment of HCMV in most patients.

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“…This suggested that, to some extent, CMV had a more negative influence on ECs in eyes that underwent PKP [19] . Moreover, a significant difference in graft ECD between the CMV+ and virus-groups appeared earlier in the PKP subgroup than in the DSAEK subgroup (6mo after PKP vs 12mo after DSAEK), suggesting that CMV replication had a shorter cycle in eyes that underwent PKP, which may be related to a stronger immunosuppressive effect of PKP on the anterior segment [20] . Previous studies found that anterior-segment CMV infections could occur after PKP [10,21] , DSAEK [22][23] , and Descemet's membrane endothelial keratoplasty (DMEK) [18] , but were most common following the PKP procedure.…”

Section: Graft Endothelial Cell Density and Endothelial Cellmentioning

confidence: 93%

Destructive effects on endothelial cells of grafts in cytomegalovirus DNA-positive patients after keratoplasty

Zang¹,

Ben²,

Qu³

et al. 2023

Int J Ophthalmol

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AIM: To investigate corneal graft survival rate and endothelial cell density (ECD) loss after keratoplasty in cytomegalovirus (CMV) positive patients. METHODS: This was a retrospective cohort study. We analyzed the clinical data of patients who underwent viral DNA detection in aqueous humor/corneal tissue collected during keratoplasty from March 2015 to December 2018 at the Peking University Third Hospital, Beijing, China. To further evaluate the effect of CMV on graft survival rate and ECD loss, patients were divided into three groups: 1) CMV DNA positive (CMV+) group; 2) viral DNA negative (virus-) group, comprising virus- group eyes pairwise matched to eyes in the CMV+ group according to ocular comorbidities; 3) control group, comprising virus- group eyes without ocular comorbidities. The follow-up indicators including graft survival rate, ECD, ECD loss, and central corneal thickness (CCT), were analyzed by Tukey honestly significant difference (HSD) test. RESULTS: Each group included 29 cases. The graft survival rate in CMV+ group were lowest among the three groups (P=0.000). No significant difference in donor graft ECD was found among three groups (P=0.54). ECD in the CMV+ group was lower than the virus- group at 12 (P=0.009), and 24mo (P=0.002) after keratoplasties. Furthermore, ECD loss was higher in the CMV+ group than in the virus- group in the middle stage (6-12mo) post-keratoplasty (P=0.017), and significantly higher in the early stage (0-6mo) in the virus- group than in the control group (P=0.000). CONCLUSION: CMV reduces the graft survival rate and exerts persistent detrimental effects on the ECD after keratoplasty. The graft ECD loss associate with CMV infection mainly occurrs in the middle stage (6-12mo postoperatively), while ocular comorbidities mainly affects ECD in the early stage (0-6mo postoperatively).

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Interventions for the management of CMV-associated anterior segment inflammation

Abstract: There is currently no good-quality evidence on the management of CMV-associated anterior segment inflammation. Ideally, a well-designed RCT is needed to evaluate the effectiveness of different anti-CMV medications as well as the optimal dose and duration.

Cited by 11 publications

References 18 publications

Zika Virus Infects Trabecular Meshwork and Causes Trabeculitis and Glaucomatous Pathology in Mouse Eyes

Zika Virus Infects Trabecular Meshwork and Causes Trabeculitis and Glaucomatous Pathology in Mouse Eyes

Clinical Features and Diagnosis of Anterior Segment Inflammation Related to Cytomegalovirus in Immunocompetent African, Asian, and Caucasian Patients

Destructive effects on endothelial cells of grafts in cytomegalovirus DNA-positive patients after keratoplasty

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