Distinguishing Features of Anterior Uveitis Caused by Herpes Simplex Virus, Varicella-Zoster Virus, and Cytomegalovirus

Published:March 24, 2021DOI:


      To determine distinguishing features of the clinical characteristics of anterior uveitis (AU) caused by herpes simplex virus (HSV), varicella-zoster virus (VZV), and cytomegalovirus (CMV).


      Retrospective, multicenter case series.


      Consecutive patients with herpetic AU examined at 11 tertiary centers in Japan between January 2012 and December 2017 and who were followed for ≥3 months were evaluated. Diagnosis was made by polymerase chain reaction (PCR) for HSV, VZV, or CMV in the aqueous humor, or classical signs of herpes zoster ophthalmicus.


      This study enrolled 259 herpetic AU patients, including PCR-proven HSV-AU (30 patients), VZV-AU (50), and CMV-AU (147), and herpes zoster ophthalmicus (32). All HSV-AU and VZV-AU patients were unilateral, while 3% of CMV-AU patients were bilateral. Most HSV-AU and VZV-AU patients were sudden onset with an acute clinical course, while CMV-AU had a more insidious onset and chronic course. There were no significant differences for all surveyed symptoms, signs, and complications between HSV-AU and VZV-AU. However, significant differences were detected for many items between CMV-AU and the other two herpetic AU types. Ocular hyperemia and pain, blurring of vision, ciliary injection, medium-to-large keratic precipitates (KPs), cells and flare in the anterior chamber, and posterior synechia significantly more often occurred in HSV-AU and VZV-AU vs CMV-AU. In contrast, small KPs, coin-shaped KPs, diffuse iris atrophy, elevated intraocular pressure, and glaucoma surgery were significantly more frequent in CMV-AU vs HSV-AU and VZV-AU.


      This multicenter, retrospective study identified distinguishing features of HSV-AU, VZV-AU, and CMV-AU.
      To read this article in full you will need to make a payment


      Subscribe to American Journal of Ophthalmology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Hogan MJ
        • Kimura SJ
        • Thygeson P.
        Pathology of herpes simplex kerato-iritis.
        Am J Ophthalmol. 1964; 57: 551-564
        • O'Connor GR
        Recurrent herpes simplex uveitis in humans.
        Surv Ophthalmol. 1976; 21: 165-170
        • Liesegang TJ.
        Diagnosis and therapy of herpes zoster ophthalmicus.
        Ophthalmology. 1991; 98: 1216-1229
        • DeGroot-Mijnes JD
        • Rothova A
        • Van Loon AM
        • et al.
        Polymerase chain reaction and Goldmann-Witmer coefficient analysis are complimentary for the diagnosis of infectious uveitis.
        Am J Ophthalmol. 2006; 141: 313-318
        • Sugita S
        • Shimizu N
        • Watanabe K
        • et al.
        Use of multiplex PCR and real-time PCR to detect human herpes virus genome in ocular fluids of patients with uveitis.
        Br J Ophthalmol. 2008; 92: 928-932
        • Sugita S
        • Ogawa M
        • Shimizu N
        • et al.
        Use of a comprehensive polymerase chain reaction system for diagnosis of ocular infectious diseases.
        Ophthalmology. 2013; 120: 1761-1768
        • Chronopoulos A
        • Roquelaure D
        • Souteyrand G
        • Seebach JD
        • Schutz JS
        • Thumann G.
        Aqueous humor polymerase chain reaction in uveitis - utility and safety.
        BMC Ophthalmology. 2016; 16: 189
        • Mochizuki M
        • Sugita S
        • Kamoi K
        • Takase H.
        A new era of uveitis: impact of polymerase chain reaction in intraocular inflammatory diseases.
        Jpn J Ophthalmol. 2017; 61: 1-20
        • Miyazaki D
        • Shimizu D
        • Shimizu Y
        • et al.
        Diagnostic efficacy of real-time PCR for ocular cytomegalovirus infections.
        Graefes Arch Clin Exp Ophthalmol. 2018; 256: 2413-2420
        • De Simone L
        • Belloni L
        • Aldigeri R
        • et al.
        Aqueous tap and rapid diagnosis of cytomegalovirus anterior uveitis: the Reggio Emilia experience.
        Graefes Arch Clin Exp Ophthalmol. 2019; 257: 181-186
        • Chee SP
        • Bacsal K
        • Jap A
        • Se-Thoe SY
        • Cheng CL
        • Tan BH.
        Clinical features of cytomegalovirus anterior uveitis in immunocompetent Patients.
        Am J Ophthalmol. 2008; 145: 834-840
        • Takase H
        • Kubono R
        • Terada Y
        • et al.
        Comparison of the ocular characteristics of anterior uveitis caused by herpes simplex virus, varicella-zoster virus, and cytomegalovirus.
        Jpn J Ophthalmol. 2014; 58: 473-482
        • Babu K
        • Kini R
        • Philips M
        • Subbakrishna DK.
        Clinical profile of isolated viral anterior uveitis in a South Indian patient population.
        Ocul Immunol Inflamm. 2014; 22: 356-359
        • Wensing B
        • Mochizuki M
        • De Boer JH.
        Clinical characteristics of herpes simplex virus associated anterior uveitis.
        Ocul Immunol Inflamm. 2018; 26: 333-337
        • Sakai J
        • Usui Y
        • Suzuki J
        • Kezuka T
        • Goto H.
        Clinical features of anterior uveitis caused by three different herpes viruses.
        Int Ophthlmol. 2019; 39: 2785-2795
        • Hsiao YT
        • Kuo MT
        • Chiang WY
        • Chao TL
        • Kuo HK.
        Epidemiology and clinical features of viral anterior uveitis in southern Taiwan-diagnosis with polymerase chain reaction.
        BMC Ophthalmol. 2019; 19: 87
        • Neumann R
        • Barequet D
        • Rosenblatt A
        • et al.
        Herpetic anterior uveitis- analysis of presumed and PCR proven cases.
        Ocul Immunol Inflamm. 2019; 27: 211-218
        • Qian Z
        • Fan H
        • Tao Y
        • Li W
        • Gu W.
        Herpetic anterior uveitis in a Chinese Referral Center: Clinical manifestations and laboratory test results.
        Ocul Immunol Inflamm. 2020; 28: 758-763
        • Koizumi N
        • Inatomi T
        • Suzuki T
        • et al.
        Clinical features and management of cytomegalovirus corneal endotheliitis: analysis of 106 cases from the Japan corneal endotheliitis study.
        Br J Ophthalmol. 2015; 99: 54-58
        • Miyanaga M
        • Sugita S
        • Shimizu N
        • et al.
        A significant association of viral loads with corneal endothelial cell damage in cytomegalovirus anterior uveitis.
        Br J Ophthalmol. 2010; 94: 336-340
        • Kido S
        • Sugita S
        • Horie S
        • et al.
        Association of varicella zoster virus load in the aqueous humor with clinical manifestations of anterior uveitis in herpes zoster ophthalmicus and zoster sine herpete.
        Br J Ophthalmol. 2008; 92: 505-508
      1. Standardization of Uveitis Nomenclature (SUN) Working Group. Standardization of uveitis nomenclature for reporting clinical data. Results of the first international workshop.
        Am J Ophthalmol. 2005; 140: 509-516
        • Kanda Y.
        Investigation of the freely available easy-to-use software 'EZR' for medical statistics.
        Bone Marrow Transplant. 2013; 48: 452-458
        • Johnson LN
        • Guy ME
        • Krohel GB
        • Madsen RW.
        Levodopa may improve vision loss in recent-onset, nonarteritic anterior ischemic optic neuropathy.
        Ophthalmology. 2000; 107: 521-526
        • Shimizu D
        • Miyazaki D
        • Shimizu Y
        • Hosogai M
        • Kosugi I
        • Inoue Y.
        Infection of endotheliotropic human cytomegalovirus of trabecular meshwork cells.
        Jpn J Ophthalmol. 2018; 62: 667-676
        • Mori I
        • Nishiyama Y.
        Herpes simplex virus and varicella-zoster virus: why do these human alphaherpesviruses behave so differently from one another?.
        Rev Med Virol. 2005; 15: 393-406
        • Cheung AK
        • Abendroth A
        • Cunningham AL
        • Slobedman B.
        Viral gene expression during the establishment of human cytomegalovirus latent infection in myeloid progenitor cells.
        Blood. 2006; 108: 3691-3699
        • Goodrum F
        • Reeves M
        • Sinclair J
        • High K
        • Shenk T.
        Human cytomegalovirus sequences expressed in latently infected individuals promote a latent infection in vitro.
        Blood. 2007; 110: 937-945