• Users Online: 169
  • Print this page
  • Email this page

Table of Contents
Year : 2021  |  Volume : 3  |  Issue : 1  |  Page : 24

Simultaneous amplification of herpes simplex virus type 2 and Epstein–Barr virus in an immunocompetent host with acute retinal necrosis

Department of Ophthalmology, School of Medicine and Health Sciences, Tecnologico de Monterrey, Monterrey, Mexico

Date of Submission10-Jun-2021
Date of Decision20-Jun-2021
Date of Acceptance21-Jun-2021
Date of Web Publication13-Jul-2021

Correspondence Address:
Dr. Carlos Alvarez-Guzman
School of Medicine and Health Science, Tecnologico de Monterrey, Av. Ignacio Morones Prieto 3000, Colonia Los Doctores, CP 64710, Monterrey, Nuevo León
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/pajo.pajo_99_21

Rights and Permissions

Acute retinal necrosis (ARN) is an ocular inflammatory disease characterized by panuveitis and retinal vasculitis. Herpes virus is strongly associated with ARN and can often be detected by polymerase chain reaction (PCR) of vitreous samples. The authors report a case of ARN associated with herpes simplex virus-2 (HSV-2) and Epstein–Barr virus (EBV) in an immunocompetent host. A 72-year-old man with a history of herpes zoster ophthalmicus presented with sudden vision loss in the left eye in the setting of hypertensive anterior uveitis and severe vitreous inflammation. ARN was diagnosed and antiviral and steroid treatment was initiated. Vitritis improved 1 week later and foci of retinal necrosis with occlusive vasculitis were observed. Three days later, a rhegmatogenous retinal detachment developed. Pars plana vitrectomy with retinopexy was performed and a vitreous PCR test was positive for both HSV-2 and EBV. Despite retinal reattachment, visual acuity did not improve. Prophylactic antiviral therapy was continued for the fellow eye. The coexistence of more than one virus in the ARN context is exceedingly rare and might be associated with poor visual outcomes.

Keywords: Acute retinal necrosis, Epstein–Barr virus, herpes simplex virus, infectious uveitis, necrotizing retinitis, posterior uveitis

How to cite this article:
Ortiz-Morales G, Ruiz-Lozano RE, Garza-Garza LA, Rodriguez-Valdes PJ, Alvarez-Guzman C. Simultaneous amplification of herpes simplex virus type 2 and Epstein–Barr virus in an immunocompetent host with acute retinal necrosis. Pan Am J Ophthalmol 2021;3:24

How to cite this URL:
Ortiz-Morales G, Ruiz-Lozano RE, Garza-Garza LA, Rodriguez-Valdes PJ, Alvarez-Guzman C. Simultaneous amplification of herpes simplex virus type 2 and Epstein–Barr virus in an immunocompetent host with acute retinal necrosis. Pan Am J Ophthalmol [serial online] 2021 [cited 2022 May 28];3:24. Available from: https://www.thepajo.org/text.asp?2021/3/1/24/321301

  Introduction Top

Acute retinal necrosis (ARN) is a potentially blinding retinitis characterized by unilateral retinal vasculitis and panuveitis often leading to retinal detachment (RD). The diagnosis relies on clinical criteria supported by polymerase chain reaction (PCR) analysis of aqueous or vitreous samples when testing is available. The most frequently isolated herpes viruses are varicella-zoster virus (VZV) followed by herpes simplex virus (HSV) and a few cases of Epstein–Barr virus (EBV).[1],[2] Simultaneous detection of more than one virus is possible but exceedingly rare. We report the case of a 72-year-old male with ARN who tested positive for both HSV-2 and EBV.

  Case Report Top

A 72-year-old man was referred to our ocular immunology service with a 2-day history of red eye, sudden vision loss, and pain in the left eye (OS). He had been diagnosed with herpes zoster ophthalmicus 9 days earlier, and 4 g QD of oral acyclovir (ACV) was started. His past medical history was only remarkable for nonalcoholic fatty liver disease and chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs). He had cataract surgery in both eyes 5 years earlier. No history of malignancy, autoimmune disease, or immunodeficiency disorders was found. At presentation, the best-corrected visual acuity was 20/20 in the right eye and light perception (LP) in the OS. Slit-lamp examination [Figure 1]a, [Figure 1]b, [Figure 1]c of the OS revealed marked ciliary injection, granulomatous keratic precipitates, an anterior chamber reaction or +3 cells with dense vitritis of +4, and an intraocular pressure of 42 mmHg. B-scan ultrasonography showed dense vitreous opacities [Figure 1]d. Laboratory workup showed acute kidney injury with a serum creatinine of 1.4 mg/dl and mild leukocytosis. Serological testing for hepatitis B, hepatitis C, tuberculin purified protein derivative, fluorescent treponemal antibody absorption, C-reactive protein, and erythrocyte sedimentation rate were unremarkable. A brain magnetic resonance imaging showed no signs of encephalitis. Oral treatment was started with valacyclovir (VCV) 1 g TID, prednisone 60 mg QD, and prednisolone acetate 1% every 3 h. After 3 weeks, the vitritis decreased and posterior pole examination was possible. Occlusive vasculitis with foci of retinal necrosis was identified. Three days later, the visual acuity worsened and a rhegmatogenous RD was identified. Pars plana vitrectomy and retinopexy with laser and silicone oil tamponade were scheduled. Intraoperatively, a rhegmatogenous RD, extensive peripheral confluent retinal necrosis, and occlusive arteriolitis were noted. Vitreous samples taken for real-time PCR analysis were positive for both HSV-2 and EBV. Oral VCV was continued as maintenance therapy at a dose of 1000 mg QD. At a 3-month follow-up, despite resolution of intraocular inflammation [Figure 1]e and [Figure 1]f, visual acuity of OS remained at LP. There were no signs of the disease in his fellow eye.
Figure 1: Slit-lamp photographs and B-scan ultrasonography of the left eye. Ciliary injection (a, black arrow) and granulomatous keratic precipitates with (b, black arrow) and without retro-illumination (c, black arrow) are visible. Ultrasound revealed an inferior retinal detachment with scattered punctate echoes in the vitreous cavity (d). Retinal images after vitrectomy with scarring of previously active areas of necrosis (e and f)

Click here to view

  Discussion Top

In patients with suspected ARN, PCR has shown a positivity rate for VZV or HSV ranging from 79% to 100%.[1] Whether the sample for PCR testing must come from aqueous or vitreous remains undefined. In our case, PCR testing of a vitreous sample amplified for both HSV-2 and EBV. The amplification plots were inspected and compared to controls to rule out a false detection of both herpes viruses. The presence of more than one viral agent by PCR testing has been documented previously [Table 1].[1],[3],[4],[5],[6] The pathogenicity of EBV has been controversial since 20% of cadaveric eye tissue may amplify to EBV through PCR testing without a history of ARN.[7] Currently, there are some reports on exclusively EBV-associated ARN by PCR testing or by fluorescence in situ hybridization, which may support the hypothesis of the pathogenicity of EBV.[8] Only one of these cases occurred in a previously immunocompetent host. Baltinas et al. reported two eyes that amplified to both HSV and EBV.[5] Sampling, immune status, and type of HSV of these eyes were not specified in their report.
Table 1: Studies reporting simultaneous polymerase chain reaction amplification of viral etiologic agents in acute retinal necrosis

Click here to view

In this case, the results of the quantitative PCR support the viral replication of EBV and might suggest a causative role of EBV in the development of ARN.[9] However, since the pathogenicity of EBV in ARN has not been well established, other possibilities need to be addressed, such as the release of latent EBV DNA from necrotic cells or cells present in the vitreous during the sampling. Complementary analysis of ocular samples with the Goldmann–Witmer coefficient has been advocated to understand the pathogenicity of viruses in this setting, however, antibody testing is not widely available and was not performed in this case.[9] Furthermore, EBV-associated ARN seems to be less responsive to ACV-based therapies, which might be attributed to higher in vitro inhibitory ACV concentrations in EBV compared to HSV and the fact that EBV can use the host cell's polymerase in latent infection, eluding the inhibition of DNA polymerase caused by ACV.[10]

Rhegmatogenous RD, which occurs in up to 85% of eyes with ARN, results from breaks caused by necrotic cells in the boundaries of the inflamed and healthy retina.[11] Early pars plana vitrectomy (PPV) before RD has been advocated since it may potentially reduce vitreous inflammatory mediators and allow for a thorough laser demarcation to the necrotic retina; however, current evidence does not support its role in preventing RD.[1],[4] In our case, PPV and silicone tamponade were performed 3 weeks after the onset of symptoms resulted in anatomic reattachment, but the vision remained poor. The latter is like the findings of the other reported EBV-ARN and supports the evidence that these cases seem to be associated with adverse visual outcomes despite prompt treatment.[4],[8]

Data suggest that oral VCV and intravenous ACV can achieve equivalent plasma drug levels.[1] Outpatient oral treatment with VCV has shown no significant differences in the long-term visual outcome or the incidence of RD compared to intravenous ACV.[5] Further, our patient had acute kidney injury from self-medicated NSAIDs, which could have been exacerbated using parenteral ACV. Amid the SARS-CoV-2 pandemic, outpatient treatment with oral VCV was chosen based on the safety, efficacy, and current public health policies.

  Conclusions Top

To our knowledge, this is the first reported case of simultaneous HSV-2 and EBV-associated ARN in an immunocompetent host. Simultaneous viral amplification in cases of ARN seems to be uncommon and it is associated with poor visual outcomes. Clinical management of these patients remains a challenge; meanwhile, PPV and laser barricade may prove their benefits with further studies addressing these interventions.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Schoenberger SD, Kim SJ, Thorne JE, Mruthyunjaya P, Yeh S, Bakri SJ, et al. Diagnosis and treatment of acute retinal necrosis: A report by the American academy of ophthalmology. Ophthalmology 2017;124:382-92.  Back to cited text no. 1
Takase H, Goto H, Namba K, Mizuki N, Okada AA, Ohguro N, et al. Clinical characteristics, management, and factors associated with poor visual prognosis of acute retinal necrosis. Ocul Immunol Inflamm 2020;18:1-6.  Back to cited text no. 2
Lau CH, Missotten T, Salzmann J, Lightman SL. Acute retinal necrosis features, management, and outcomes. Ophthalmology 2007;114:756-62.  Back to cited text no. 3
Hillenkamp J, Nölle B, Bruns C, Rautenberg P, Fickenscher H, Roider J. Acute retinal necrosis: Clinical features, early vitrectomy, and outcomes. Ophthalmology 2009;116:1971- 5.e2.  Back to cited text no. 4
Baltinas J, Lightman S, Tomkins-Netzer O. Comparing treatment of acute retinal necrosis with either oral valacyclovir or intravenous acyclovir. Am J Ophthalmol 2018;188:173-80.  Back to cited text no. 5
Hedayatfar A, Ebrahimiadib N, Zarei M, Ashraf Khorasani M, Mahbod M, Asgari S, et al. Acute retinal necrosis: Clinical manifestation and long-term visual outcomes in a series of polymerase chain reaction-positive patients. Eur J Ophthalmol 2020;21:1-6.1120672120936181.  Back to cited text no. 6
Chodosh J, Gan YJ, Sixbey JW. Detection of Epstein-Barr virus genome in ocular tissues. Ophthalmology 1996;103:687-90.  Back to cited text no. 7
Chan EW, Sun V, Eldeeb M, Kapusta MA. Epstein-barr virus acute retinal necrosis in an immunocompetent host. Retin Cases Brief Rep 2018;15:412-6. doi: 10.1097/ICB.0000000000000819.  Back to cited text no. 8
Yamamoto S, Sugita S, Sugamoto Y, Shimizu N, Morio T, Mochizuki M. Quantitative PCR for the detection of genomic DNA of Epstein-Barr virus in ocular fluids of patients with uveitis. Jpn J Ophthalmol 2008;52:463-7.  Back to cited text no. 9
Hoshino Y, Katano H, Zou P, Hohman P, Marques A, Tyring SK, et al. Long-term administration of valacyclovir reduces the number of Epstein-Barr virus (EBV)-infected B cells but not the number of EBV DNA copies per B cell in healthy volunteers. J Virol 2009;83:11857-61.  Back to cited text no. 10
Blumenkranz MS, Culbertson WW, Clarkson JG, Dix R. Treatment of the acute retinal necrosis syndrome with intravenous acyclovir. Ophthalmology 1986;93:296-300.  Back to cited text no. 11


  [Figure 1]

  [Table 1]


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  In this article
Case Report
Article Figures
Article Tables

 Article Access Statistics
    PDF Downloaded68    
    Comments [Add]    

Recommend this journal