Skip to main content

Advertisement

SpringerLink
Log in

Development of cytomegalovirus retinitis after negative conversion of cytomegalovirus antigenemia due to systemic antiviral therapy

  • Inflammatory Disorders
  • Published:
Graefe's Archive for Clinical and Experimental Ophthalmology Aims and scope Submit manuscript

A Correction to this article was published on 12 December 2020

This article has been updated

Abstract

Purpose

Cytomegalovirus (CMV) antigenemia assays have been widely used as adjunct tests to diagnose tissue invasive CMV diseases, including cytomegalovirus retinitis (CMVR). In this study, we examined CMVR cases to assess the presence of CMV in sera and aqueous humor and antiviral therapy received prior to the onset of CMVR.

Methods

A total of 37 eyes from 26 different cases of CMVR in patients who visited Hokkaido University Hospital between 2007 and 2015 were enrolled. The diagnosis of CMVR was established based on characteristic ophthalmoscopic findings and the presence of local and/or systemic CMV infection. Among the 26 cases, 3 cases (12%) were HIV-positive, while the other 23 cases (88%) were HIV-negative. The records of clinical and laboratory results were reviewed from clinical charts retrospectively.

Results

CMV antigenemia was positive at the onset of CMVR in 14 cases (53.8%) and negative in the other 12 cases. In 9 cases among the antigenemia-negative cases (75.0%), the antigenemia had been previously positive and had turned negative before the onset of CMVR. In 12 of the 14 antigenemia-positive cases (85.7%) and in 8 of the 9 antigenemia-negative cases (88.9%) that were previously positive, systemic antiviral therapies had never been used or had been used before but had been discontinued prior to the onset of CMVR.

Conclusion

Even if viremia turns negative, the risk of developing CMVR exists for more than several weeks after the completion of systemic therapy.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Change history

References

  1. Palestine AG, Rodrigues MM, Macher AM, Chan CC, Lane HC, Fauci AS, Masur H, Longo D, Reichert CM, Steis R (1984) Ophthalmic involvement in acquired immunodeficiency syndrome. Ophthalmology 91:1092–1099. https://doi.org/10.1016/s0161-6420(84)34201-4

    Article  CAS  PubMed  Google Scholar 

  2. Dioverti MV, Razonable RR (2016) Cytomegalovirus. Microbiol Spectr 4(4). https://doi.org/10.1128/microbiolspec.DMIH2-0022-2015

  3. Holland GN, Buhles WC, Mastre B, Kaplan HJ (1989) A controlled retrospective study of ganciclovir treatment for cytomegalovirus retinopathy. Use of a standardized system for the assessment of disease outcome. UCLA CMV Retinopathy. Study Group. Arch Ophthalmol 107:1759–1766. https://doi.org/10.1001/archopht.1989.01070020841024

    Article  CAS  PubMed  Google Scholar 

  4. Holland GN, Vaudaux JD, Jeng SM et al (2008) Characteristics of untreated AIDS-related cytomegalovirus retinitis. I. Findings before the era of highly active antiretroviral therapy (1988 to 1994). Am J Ophthalmol. 145(1):5–11. https://doi.org/10.1016/j.ajo.2007.09.023

    Article  PubMed  Google Scholar 

  5. Holland GN, Shuler JD (1992) Progression rates oy cytomegalovirus retinopathy in ganciclovir – treated and untreated patients. Arch Ophtalmol. 10:1435–1442. https://doi.org/10.1001/archopht.1992.01080220097029

    Article  Google Scholar 

  6. Somsanguan A, Jeremy DK, Sakarin A et al (2012) Clinical features of diagnosed cytomegalovirus retinitis in northern Thailand. Am J Ophthalmol. 153(3):923–931. https://doi.org/10.1016/j.ajo.2011.10.012

    Article  Google Scholar 

  7. Kuppermann BD, Petty JG, Richman DD, Mathews WC, Fullerton SC, Rickman LS, Freeman WR (1993) Correlation between CD4+ counts and prevalence of cytomegalovirus retinitis and human immunodeficiency virus-related noninfectious retinal vasculopathy in patients with acquired immunodeficiency syndrome. Am J Ophthalmol 115:575–582. https://doi.org/10.1016/s0002-9394(14)71453-9

    Article  CAS  PubMed  Google Scholar 

  8. Wei LL, Park SS, Skiest DJ (2002) Prevalence of visual symptoms among patients with newly diagnosed cytomegalovirus retinitis. Retina 22:278–282. https://doi.org/10.1097/00006982-200206000-00004

    Article  PubMed  Google Scholar 

  9. Chiou SH, Liu CY, Hsu WM, Chan YJ, Chou CK, Chung YM, Liu JH, Liu WT, Chen SC, Wong WW (2000) Ophthalmic findings in patients with acquired immunodeficiency syndrome. J Microbiol Immunol Infect 33:45–48

    CAS  PubMed  Google Scholar 

  10. Jabs DA, Ahuja A, Van Natta ML, Lyon AT, Yeh S, Danis R, Group SotOCoAR (2015) Long-term outcomes of cytomegalovirus retinitis in the era of modern antiretroviral therapy: results from a United States cohort. Ophthalmology 122:1452–1463. https://doi.org/10.1016/j.ophtha.2015.02.033

    Article  PubMed  Google Scholar 

  11. Teoh SC, Wang PX, Wong EP (2012) The epidemiology and incidence of cytomegalovirus retinitis in the HIV population in Singapore over 6 years. Invest Ophthalmol Vis Sci 53:7546–7552. https://doi.org/10.1167/iovs.12-10349

    Article  PubMed  Google Scholar 

  12. Kuo IC, Kempen JH, Dunn JP, Vogelsang G, Jabs DA (2004) Clinical characteristics and outcomes of cytomegalovirus retinitis in persons without human immunodeficiency virus infection. Am J Ophthalmol 138:338–346. https://doi.org/10.1016/j.ajo.2004.04.015

    Article  PubMed  Google Scholar 

  13. Shapira Y, Mimouni M, Vishnevskia-Dai V (2018) Cytomegalovirus retinitis in HIV-negative patients - associated conditions, clinical presentation, diagnostic methods and treatment strategy. Acta Ophthalmol 96:e761–e767. https://doi.org/10.1111/aos.13553

    Article  PubMed  Google Scholar 

  14. Chawla R, Venkatesh P, Garg SP, Mandal S, Tewari HK (2005) Cytomegalovirus retinitis in a patient with non-Hodgkin's lymphoma: a diagnostic dilemma. Eur J Ophthalmol 15:153–157

    Article  Google Scholar 

  15. Davis JL, Haft P, Hartley K (2013) Retinal arteriolar occlusions due to cytomegalovirus retinitis in elderly patients without HIV. J Ophthalmic Inflamm Infect 3:17. https://doi.org/10.1186/1869-5760-3-17

    Article  PubMed  PubMed Central  Google Scholar 

  16. Delyfer MN, Rougier MB, Hubschman JP, Aouizérate F, Korobelnik JF (2007) Cytomegalovirus retinitis following intravitreal injection of triamcinolone: report of two cases. Acta Ophthalmol Scand 85:681–683. https://doi.org/10.1111/j.1600-0420.2007.00915.x

    Article  PubMed  Google Scholar 

  17. Derzko-Dzulynsky LA, Berger AR, Berinstein NL (1998) Cytomegalovirus retinitis and low-grade non-Hodgkin's lymphoma: case report and review of the literature. Am J Hematol 57:228–232. https://doi.org/10.1002/(sici)1096-8652(199803)57:3<228::aid-ajh9>3.0.co;2-x

    Article  CAS  PubMed  Google Scholar 

  18. Downes KM, Tarasewicz D, Weisberg LJ, Cunningham ET (2016) Good syndrome and other causes of cytomegalovirus retinitis in HIV-negative patients-case report and comprehensive review of the literature. J Ophthalmic Inflamm Infect 6:3. https://doi.org/10.1186/s12348-016-0070-7

    Article  PubMed  PubMed Central  Google Scholar 

  19. Gupta S, Vemulakonda GA, Suhler EB, Yeh S, Albini TA, Mandelcorn E, Flaxel CJ (2013) Cytomegalovirus retinitis in the absence of AIDS. Can J Ophthalmol 48:126–129. https://doi.org/10.1016/j.jcjo.2012.12.002

    Article  PubMed  Google Scholar 

  20. Iu LP, Fan MC, Lau JK, Chan TS, Kwong YL, Wong IY (2016) Long-term follow-up of cytomegalovirus retinitis in non-HIV immunocompromised patients: clinical features and visual prognosis. Am J Ophthalmol 165:145–153. https://doi.org/10.1016/j.ajo.2016.03.015

    Article  PubMed  Google Scholar 

  21. Jeon S, Lee WK (2015) Cytomegalovirus retinitis in a human immunodeficiency virus-negative cohort: long-term management and complications. Ocul Immunol Inflamm 23:392–399. https://doi.org/10.3109/09273948.2014.985385

    Article  PubMed  Google Scholar 

  22. Jeon S, Lee WK, Lee Y, Lee DG, Lee JW (2012) Risk factors for cytomegalovirus retinitis in patients with cytomegalovirus viremia after hematopoietic stem cell transplantation. Ophthalmology 119:1892–1898. https://doi.org/10.1016/j.ophtha.2012.03.032

    Article  PubMed  Google Scholar 

  23. Karkhaneh R, Lashay A, Ahmadraji A (2016) Cytomegalovirus retinitis in an immunocompetent patient: a case report. J Curr Ophthalmol 28:93–95. https://doi.org/10.1016/j.joco.2015.12.003

    Article  PubMed  PubMed Central  Google Scholar 

  24. Radwan A, Metzinger JL, Hinkle DM, Foster CS (2013) Cytomegalovirus retinitis in immunocompetent patients: case reports and literature review. Ocul Immunol Inflamm 21:324–328. https://doi.org/10.3109/09273948.2013.786095

    Article  PubMed  Google Scholar 

  25. Samia L, Hamam R, Dbaibo G, Saab R, El-Solh H, Abboud M, Muwakkit S (2014) Cytomegalovirus retinitis in children and young adults with acute lymphoblastic leukemia in Lebanon. Leuk Lymphoma 55:1918–1921. https://doi.org/10.3109/10428194.2013.854887

    Article  PubMed  Google Scholar 

  26. Sloan DJ, Taegtmeyer M, Pearce IA, Hart IJ, Miller AR, Beeching NJ (2008) Cytomegalovirus retinitis in the absence of HIV or immunosuppression. Eur J Ophthalmol 18:813–815. https://doi.org/10.1177/112067210801800525

    Article  CAS  PubMed  Google Scholar 

  27. Vishnevskia-Dai V, Shapira Y, Rahav G, Shimoni A, Somech R, Moisseiev J (2015) Cytomegalovirus retinitis in HIV-negative patients: a practical management approach. Ophthalmology 122:866–868. https://doi.org/10.1016/j.ophtha.2014.11.010

    Article  PubMed  Google Scholar 

  28. Piiparinen H, Höckerstedt K, Grönhagen-Riska C, Lautenschlager I (2004) Comparison of two quantitative CMV PCR tests, Cobas Amplicor CMV Monitor and TaqMan assay, and pp65-antigenemia assay in the determination of viral loads from peripheral blood of organ transplant patients. J Clin Virol 30:258–266. https://doi.org/10.1016/j.jcv.2003.12.010

    Article  CAS  PubMed  Google Scholar 

  29. Bek B, Boeckh M, Lepenies J, Bieniek B, Arasteh K, Heise W, Deppermann KM, Bornhöft G, Stöffler-Meilicke M, Schuller I, Höffken G (1996) High-level sensitivity of quantitative pp65 cytomegalovirus (CMV) antigenemia assay for diagnosis of CMV disease in AIDS patients and follow-up. J Clin Microbiol 34:457–459

    Article  CAS  Google Scholar 

  30. Schirm J, Kooistra A, van Son WJ, van der Bij W, Verschuuren E, Sprenger HG, Limburg PC, The TH (1999) Comparison of the Murex hybrid capture CMV DNA (v2.0) assay and the pp65 CMV antigenemia test for the detection and quantitation of CMV in blood samples from immunocompromised patients. J Clin Virol 14:153–165. https://doi.org/10.1016/s1386-6532(99)00063-3

    Article  CAS  PubMed  Google Scholar 

  31. Hong SI, Kim T, Park SY, Jung J, Lee JY, Chong YP, Sung H, Lee SO, Choi SH, Kim YS, Woo JH, Kim SH (2016) Sensitivity of the cytomegalovirus antigenemia assay to diagnose cytomegalovirus retinitis. Infect Chemother 48:302–308. https://doi.org/10.3947/ic.2016.48.4.302

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Asberg A, Humar A, Rollag H, Jardine AG, Mouas H, Pescovitz MD, Sgarabotto D, Tuncer M, Noronha IL, Hartmann A, Group VS (2007) Oral valganciclovir is noninferior to intravenous ganciclovir for the treatment of cytomegalovirus disease in solid organ transplant recipients. Am J Transplant 7:2106–2113. https://doi.org/10.1111/j.1600-6143.2007.01910.x

    Article  CAS  PubMed  Google Scholar 

  33. Razonable RR, Asberg A, Rollag H, Duncan J, Boisvert D, Yao JD, Caliendo AM, Humar A, Do TD (2013) Virologic suppression measured by a cytomegalovirus (CMV) DNA test calibrated to the World Health Organization international standard is predictive of CMV disease resolution in transplant recipients. Clin Infect Dis 56:1546–1553. https://doi.org/10.1093/cid/cit096

    Article  CAS  PubMed  Google Scholar 

  34. Qian Z, Li H, Tao Y, Li W (2018) Initial intravitreal injection of high-dose ganciclovir for cytomegalovirus retinitis in HIV-negative patients. BMC Ophthalmol 18:314. https://doi.org/10.1186/s12886-018-0983-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, N-15, W-7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan

    Kayo Suzuki, Kenichi Namba, Kazuomi Mizuuchi, Daiju Iwata, Takako Ito, Keitaro Hase, Nobuyoshi Kitaichi & Susumu Ishida

  2. Department of Ophthalmology, Health Sciences University of Hokkaido, Sapporo, Japan

    Takako Ito & Nobuyoshi Kitaichi

Authors
  1. Kayo Suzuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kenichi Namba
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kazuomi Mizuuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Daiju Iwata
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Takako Ito
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Keitaro Hase
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nobuyoshi Kitaichi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Susumu Ishida
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kenichi Namba.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Hokkaido University Hospital and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

The original online version of this article was revised: The published online version contain mistake for the explanation of Zone 1.

Supplementary Information

ESM 1

(DOCX 15 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Suzuki, K., Namba, K., Mizuuchi, K. et al. Development of cytomegalovirus retinitis after negative conversion of cytomegalovirus antigenemia due to systemic antiviral therapy. Graefes Arch Clin Exp Ophthalmol 259, 971–978 (2021). https://doi.org/10.1007/s00417-020-05011-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00417-020-05011-0

Keywords

Search

Navigation