Skip to main content

Advertisement

Log in

Cytomegalovirus Keratouveitis: Charted and Uncharted Territory

  • Ocular Microbiology and Immunology (B Jeng and L Schocket, Section Editors)
  • Published:
Current Ophthalmology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

This report provides an overview of the current understanding of cytomegalovirus (CMV) keratouveitis: pathophysiology, clinical features, management, and gaps in knowledge.

Recent Findings

The wide availability of polymerase chain reaction (PCR) testing of ocular fluid has demonstrated that CMV is an important cause of keratouveitis. PCR has more recently been used to offer a microbiologic indicator (viral load), which has the potential to be correlated to clinical severity and corneal endothelial cell density. This knowledge may be used to help guide management of this chronic disease.

Summary

Overlapping clinical features of viral keratouveitis, such as ocular hypertension and keratic precipitates, present a challenge in distinguishing CMV from other viral etiologies. Important findings suggestive of CMV include “coin-shaped” precipitates and diffuse iris atrophy. Definitive diagnosis requires identifying CMV using molecular testing. While multiple treatment options appear effective in controlling flares, one challenge is preventing long-term morbidity associated with recurrent inflammation. Thus, further studies on CMV keratouveitis are warranted to understand the relationship between viral burden, clinical features, and the most appropriate antiviral therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Chan CC. Molecular pathology of primary intraocular lymphoma. Trans Am Ophthalmol Soc. 2003;101:275–92.

    PubMed  PubMed Central  Google Scholar 

  2. Adland E, Klenerman P, Goulder P, Matthews PC. Ongoing burden of disease and mortality from HIV/CMV coinfection in Africa in the antiretroviral therapy era. Front Microbiol. 2015;6:1016. https://doi.org/10.3389/fmicb.2015.01016.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Bate SL, Dollard SC, Cannon MJ. Cytomegalovirus seroprevalence in the United States: the national health and nutrition examination surveys, 1988-2004. Clin Infect Dis. 2010;50(11):1439–47. https://doi.org/10.1086/652438.

    Article  PubMed  Google Scholar 

  4. Chee SP, Jap A. Treatment outcome and risk factors for visual loss in Cytomegalovirus endotheliitis. Graefes Arch Clin Exp Ophthalmol. 2012;250(3):383–9. https://doi.org/10.1007/s00417-011-1813-7.

    Article  PubMed  CAS  Google Scholar 

  5. Sobolewska B, Deuter C, Doycheva D, Zierhut M. Long-term oral therapy with valganciclovir in patients with Posner-Schlossman syndrome. Graefes Arch Clin Exp Ophthalmol. 2014;252(1):117–24. https://doi.org/10.1007/s00417-013-2535-9.

    Article  PubMed  CAS  Google Scholar 

  6. Borkar DS, Gonzales JA, Tham VM, Esterberg E, Vinoya AC, Parker JV, et al. Association between atopy and herpetic eye disease: results from the pacific ocular inflammation study. JAMA Ophthalmol. 2014;132(3):326–31. https://doi.org/10.1001/jamaophthalmol.2013.6277.

    Article  PubMed  Google Scholar 

  7. Prabriputaloong T, Margolis TP, Lietman TM, Wong IG, Mather R, Gritz DC. Atopic disease and herpes simplex eye disease: a population-based case-control study. Am J Ophthalmol. 2006;142(5):745–9. https://doi.org/10.1016/j.ajo.2006.06.050.

    Article  PubMed  Google Scholar 

  8. • Koizumi N, Inatomi T, Suzuki T, Shiraishi A, Ohashi Y, Kandori M, 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(1):54–8. https://doi.org/10.1136/bjophthalmol-2013-304625. This reference establishes clinical features of CMV endotheliitis in a Japanese population.

    Article  PubMed  Google Scholar 

  9. 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(5):834–40. https://doi.org/10.1016/j.ajo.2007.12.015.

    Article  PubMed  Google Scholar 

  10. Zheng X, Yamaguchi M, Goto T, Okamoto S, Ohashi Y. Experimental corneal endotheliitis in rabbit. Invest Ophthalmol Vis Sci. 2000;41(2):377–85.

    PubMed  CAS  Google Scholar 

  11. •• Miyazaki D, Uotani R, Inoue M, Haruki T, Shimizu Y, Yakura K, et al. Corneal endothelial cells activate innate and acquired arm of anti-viral responses after cytomegalovirus infection. Exp Eye Res. 2017;161:143–52. https://doi.org/10.1016/j.exer.2017.06.017. This reference demonstrates the innate immune priming induced by CMV-infected human corneal endothelial cells.

    Article  PubMed  CAS  Google Scholar 

  12. Su CC, Hu FR, Wang TH, Huang JY, Yeh PT, Lin CP, et al. Clinical outcomes in cytomegalovirus-positive Posner-Schlossman syndrome patients treated with topical ganciclovir therapy. Am J Ophthalmol. 2014;158(5):1024–31 e2. https://doi.org/10.1016/j.ajo.2014.08.007.

    Article  PubMed  CAS  Google Scholar 

  13. •• Doan T, Wilson MR, Crawford ED, Chow ED, Khan LM, Knopp KA, et al. Illuminating uveitis: metagenomic deep sequencing identifies common and rare pathogens. Genome Med. 2016;8(1):90. https://doi.org/10.1186/s13073-016-0344-6. This reference highlights the utility of metagenomic deep sequencing for identifying mutations in infectious pathogen genomes as well as potential regional variations.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Jabs DA, Nussenblatt RB, Rosenbaum JT. Standardization of uveitis nomenclature working g. Standardization of uveitis nomenclature for reporting clinical data. Results of the first international workshop. Am J Ophthalmol. 2005;140(3):509–16.

    Article  PubMed  Google Scholar 

  15. Shimazaki J, Harashima A, Tanaka Y. Corneal endotheliitis with cytomegalovirus infection of corneal stroma. Eye (Lond). 2010;24(6):1105–7. https://doi.org/10.1038/eye.2009.240.

    Article  CAS  Google Scholar 

  16. Chee SP, Jap A. Presumed fuchs heterochromic iridocyclitis and Posner-Schlossman syndrome: comparison of cytomegalovirus-positive and negative eyes. Am J Ophthalmol. 2008;146(6):883–9.e1. https://doi.org/10.1016/j.ajo.2008.09.001.

    Article  PubMed  Google Scholar 

  17. Shiraishi A, Hara Y, Takahashi M, Oka N, Yamaguchi M, Suzuki T, et al. Demonstration of “owl’s eye” morphology by confocal microscopy in a patient with presumed cytomegalovirus corneal endotheliitis. Am J Ophthalmol. 2007;143(4):715–7. https://doi.org/10.1016/j.ajo.2006.11.026.

    Article  PubMed  Google Scholar 

  18. Kobayashi A, Yokogawa H, Higashide T, Nitta K, Sugiyama K. Clinical significance of owl eye morphologic features by in vivo laser confocal microscopy in patients with cytomegalovirus corneal endotheliitis. Am J Ophthalmol. 2012;153(3):445–53. https://doi.org/10.1016/j.ajo.2011.07.026.

    Article  PubMed  Google Scholar 

  19. Yokogawa H, Kobayashi A, Sugiyama K. Mapping owl’s eye cells of patients with cytomegalovirus corneal endotheliitis using in vivo laser confocal microscopy. Jpn J Ophthalmol. 2013;57(1):80–4. https://doi.org/10.1007/s10384-012-0189-5.

    Article  PubMed  Google Scholar 

  20. Chee SP, Bacsal K, Jap A, Se-Thoe SY, Cheng CL, Tan BH. Corneal endotheliitis associated with evidence of cytomegalovirus infection. Ophthalmology. 2007;114(4):798–803. https://doi.org/10.1016/j.ophtha.2006.07.057.

    Article  PubMed  Google Scholar 

  21. Daicker B. Cytomegalovirus panuveitis with infection of corneo-trabecular endothelium in AIDS. Ophthalmologica. 1988;197(4):169–75.

    Article  PubMed  CAS  Google Scholar 

  22. Hoffer KJ, Kraff MC. Normal endothelial cell count range. Ophthalmology. 1980;87(9):861–6.

    Article  PubMed  CAS  Google Scholar 

  23. Trivedi D, Denniston AK, Murray PI. Safety profile of anterior chamber paracentesis performed at the slit lamp. Clin Exp Ophthalmol. 2011;39(8):725–8. https://doi.org/10.1111/j.1442-9071.2011.02565.x.

    Article  PubMed  Google Scholar 

  24. Kandori M, Inoue T, Takamatsu F, Kojima Y, Hori Y, Maeda N, et al. Prevalence and features of keratitis with quantitative polymerase chain reaction positive for cytomegalovirus. Ophthalmology. 2010;117(2):216–22. https://doi.org/10.1016/j.ophtha.2009.06.059.

    Article  PubMed  Google Scholar 

  25. Su CC, Wang IJ, Chen WL, Lin CP, His B, Hu FR. Topical ganciclovir treatment in patients with cytomegalovirus endotheliitis receiving penetrating keratoplasty. Clin Exp Ophthalmol. 2013;41(4):339–47. https://doi.org/10.1111/j.1442-9071.2012.02888.x.

    Article  PubMed  Google Scholar 

  26. Kandori M, Miyazaki D, Yakura K, Komatsu N, Touge C, Ishikura R, et al. Relationship between the number of cytomegalovirus in anterior chamber and severity of anterior segment inflammation. Jpn J Ophthalmol. 2013;57(6):497–502. https://doi.org/10.1007/s10384-013-0268-2.

    Article  PubMed  Google Scholar 

  27. Faulds D, Ganciclovir HRC. A review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy in cytomegalovirus infections. Drugs. 1990;39(4):597–638.

    Article  PubMed  CAS  Google Scholar 

  28. •• Fan NW, Chung YC, Liu YC, Liu CJ, Kuo YS, Lin PY. Long-term topical ganciclovir and corticosteroids preserve corneal endothelial function in cytomegalovirus corneal endotheliitis. Cornea. 2016;35(5):596–601. https://doi.org/10.1097/ico.0000000000000791. This reference demonstrates an increase in corneal endothelial count after long-term use of topical 0.5% ganciclovir and low-frequency topical corticosteroid.

    Article  PubMed  Google Scholar 

  29. Wong VW, Chan CK, Leung DY, Lai TY. Long-term results of oral valganciclovir for treatment of anterior segment inflammation secondary to cytomegalovirus infection. Clin Ophthalmol. 2012;6:595–600. https://doi.org/10.2147/opth.s30476.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Chee SP, Jap A. Cytomegalovirus anterior uveitis: outcome of treatment. Br J Ophthalmol. 2010;94(12):1648–52. https://doi.org/10.1136/bjo.2009.167767.

    Article  PubMed  Google Scholar 

  31. Posner A, Schlossman A. Syndrome of unilateral recurrent attacks of glaucoma with cyclitic symptoms. Arch Ophthalmol. 1948;39(4):517–35.

    Article  CAS  Google Scholar 

  32. Castela N, Vermerie N, Chast F, Sauvageon-Martre H, Denis J, Godard V, et al. Ganciclovir ophthalmic gel in herpes simplex virus rabbit keratitis: intraocular penetration and efficacy. J Ocul Pharmacol. 1994;10(2):439–51.

    Article  PubMed  CAS  Google Scholar 

  33. Delwig A, Keenan JD, Margolis TP. Topical valganciclovir for the treatment of hypertensive anterior uveitis. Cornea. 2015;34(11):1513–5. https://doi.org/10.1097/ico.0000000000000579.

    Article  PubMed  Google Scholar 

  34. Hwang YS, Lin KK, Lee JS, Chang SH, Chen KJ, Lai CC, et al. Intravitreal loading injection of ganciclovir with or without adjunctive oral valganciclovir for cytomegalovirus anterior uveitis. Graefes Arch Clin Exp Ophthalmol. 2010;248(2):263–9. https://doi.org/10.1007/s00417-009-1195-2.

    Article  PubMed  CAS  Google Scholar 

  35. Anshu A, Chee SP, Mehta JS, Tan DT. Cytomegalovirus endotheliitis in Descemet’s stripping endothelial keratoplasty. Ophthalmology. 2009;116(4):624–30. https://doi.org/10.1016/j.ophtha.2008.10.031.

    Article  PubMed  Google Scholar 

  36. • Fernandez Lopez E, Chan E. Descemet stripping automated endothelial keratoplasty outcomes in patients with cytomegalovirus endotheliitis. Cornea. 2017;36(1):108–12. https://doi.org/10.1097/ico.0000000000001028. This reference highlights the importance of identifying CMV as a causative agent involved in endothelial failure and the use of antiviral therapy prior to keratoplasty procedures.

    Article  PubMed  Google Scholar 

  37. El Chaer F, Mori N, Shah D, Oliver N, Wang E, Jan A, et al. Adjuvant and salvage therapy with leflunomide for recalcitrant cytomegalovirus infections in hematopoietic cell transplantation recipients: a case series. Antivir Res. 2016;135:91–6. https://doi.org/10.1016/j.antiviral.2016.08.027.

    Article  PubMed  CAS  Google Scholar 

  38. Snydman DR. Leflunomide: a small step forward in meeting the urgent need for treatment of drug-resistant cytomegalovirus infection. Transplantation. 2010;90(4):362–3. https://doi.org/10.1097/TP.0b013e3181e8a6c9.

    Article  PubMed  CAS  Google Scholar 

  39. Knight DA, Hejmanowski AQ, Dierksheide JE, Williams JW, Chong AS, Waldman WJ. Inhibition of herpes simplex virus type 1 by the experimental immunosuppressive agent leflunomide. Transplantation. 2001;71(1):170–4.

    Article  PubMed  CAS  Google Scholar 

  40. Waldman WJ, Knight DA, Lurain NS, Miller DM, Sedmak DD, Williams JW, et al. Novel mechanism of inhibition of cytomegalovirus by the experimental immunosuppressive agent leflunomide. Transplantation. 1999;68(6):814–25.

    Article  PubMed  CAS  Google Scholar 

  41. Silva JT, Perez-Gonzalez V, Lopez-Medrano F, Alonso-Moralejo R, Fernandez-Ruiz M, San-Juan R, et al. Experience with leflunomide as treatment and as secondary prophylaxis for cytomegalovirus infection in lung transplant recipients: a case series and review of the literature. Clin Transpl. 2017;32 https://doi.org/10.1111/ctr.13176.

  42. Chern KC, Chandler DB, Martin DF, Kuppermann BD, Wolitz RA, Margolis TP. Glycoprotein B subtyping of cytomegalovirus (CMV) in the vitreous of patients with AIDS and CMV retinitis. J Infect Dis. 1998;178(4):1149–53.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to John Gonzales.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Ocular Microbiology and Immunology

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Joye, A., Gonzales, J. Cytomegalovirus Keratouveitis: Charted and Uncharted Territory. Curr Ophthalmol Rep 6, 98–104 (2018). https://doi.org/10.1007/s40135-018-0170-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40135-018-0170-7

Keywords

Navigation