Lázaro‑Rodríguez et al. BMC Ophthalmology (2022) 22:47 https://doi.org/10.1186/s12886-022-02272-7 CASE REPORT Open Access A case report of isolated primary herpes-simplex virus neuroretinitis in an immunocompetent adult Víctor Lázaro‑Rodríguez1,2, Halima Berrada1,2* and María José Capella1,2 Abstract Background: Herpes simplex virus (specifically HSV-1 and HSV-2) are greatly prevalent viruses that can cause con‑ junctivitis, keratitis and other rarer ocular disorders such as acute retinal necrosis syndrome or neuroretinitis. We report a case of an isolated unilateral neuroretinitis with primary HSV infection in an immunocompetent adult without other related clinical features. Case presentation: A 60-year-old immunocompetent woman presented with sudden painless central vision loss in her left eye (best corrected visual acuity was 20/200) showing optic disc edema, submacular fluid and a delayed development of a macular star. The macular optical coherence tomography (OCT) showed a serous retinal detach‑ ment. Arterial hypertension or exposure to ionizing radiation were ruled out and the microbiological blood test bat‑ tery was only positive for immunoglobulin M (IgM) for HSV-1 which allowed etiological treatment with oral valacyclo‑ vir. Complete resolution and good visual results were found within 3 months. Conclusions: The present case of isolated neuroretinitis as a primary HSV infection in an immunocompetent patient was resolved with good functional results after valacyclovir treatment. Presence of HSV IgM in absence of other labo‑ ratory results could be enough evidence to start HSV treatment in immunocompetent patients with a macular star, as an isolated lesion, after ruling out other non-infectious causes, such as arterial hypertension or exposure to ionizing radiation. Rare infectious agents in immunocompetent patients must be considered in the differential diagnosis of neuroretinitis, even if there are no other typical symptoms or signs that could suggest the disease. Keywords: Herpes simplex virus, Neuroretinitis, Primoinfection, Macular star, Case report Background infection with reactivations. Other ocular disorders such Herpes simplex viruses (specifically HSV-1 and HSV- as acute retinal necrosis syndrome or neuroretinitis [2, 3] 2) are greatly prevalent. In 2016, a 66.6% of the world’s are rare occurrences for these pathogens. Asymptomatic population aged 15–49 years were living with HSV type primary infection is the most frequent form observed in 1 infection and 13.2% with HSV type 2. The spectrum of patients with herpes simplex virus (HSV) [1]. disease includes primary and recurrent infections that We report the case of an isolated unilateral neurore- causes cutaneous or genital herpes, encephalitis, con- tinitis as manifestation of a primary HSV infection in an junctivitis, and keratitis [1], establishing a lifelong latent immunocompetent adult without encephalitis or other related clinical features. *Correspondence: berrada.halima7@gmail.com 1 Centro de Oftalmología Barraquer, Muntaner 314, 08021 Barcelona, Spain Full list of author information is available at the end of the article © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://​creat​iveco​mmons.​org/​licen​ses/​by/4.​0/. The Creative Commons Public Domain Dedication waiver (http://​creat​iveco​ mmons.​org/​publi​cdoma​in/​zero/1.​0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Lázaro‑Rodríguez et al. BMC Ophthalmology (2022) 22:47 Page 2 of 4 Case presentation 2 weeks with a decrease of the symptoms and progres- A 60-year-old immunocompetent woman with no sig- sive resolution of the fundus signs (Fig. 1 B1, B2, C1 and nificant medical nor surgical history presented with C2). After 48 h of antiviral treatment, oral tapered pred- sudden scotoma and painless central vision loss in her nisone regimen was added for 6 weeks and valacyclovir left eye. Her medical history revealed cataract sur- was decreased to 1 g per day until discontinuation of oral gery in both eyes 1 year prior and myocardial infarction prednisone (length of antiviral treatment of 10 weeks). 9 months prior to her visit. Best corrected visual acu- The treatment was well tolerated and no adverse events ity (BCVA) was 20/20 in the right eye and 20/200 in the occurred. The patient recovered over 3 months without left eye. On general examination, there were no charac- any sign of intraocular inflammation (Fig.1 D1 and D2) teristic herpetic skin lesions. On ocular examination, and an improvement of BCVA up to 20/25. optic disc edema and juxtapapillary hemorrhages in the left eye were detected. There were no other signs of Discussion and conclusions intraocular inflammation and the right eye features were Neuroretinitis cases have been related to a variety of unremarkable. infectious agents [4]. Other rare pathogens should be In view of its characteristics, the first approach was considered when more common etiologies such as Bar- within an ischemic context. Arteritic and non-arteritic tonella henselae have been excluded. Infectious neu- anterior ischemic optic neuropathy (AION) needed to be roretinitis in immunosuppressed patients are usually ruled out by analyzing the patient’s history, complemen- common. However, in immunocompetent patients a few tary tests, and medical assessments. Arteritic AION was cases with mild systemic signs or symptoms that were excluded based on normal erythrocyte sedimentation resolved with antiviral agents have been reported. Spe- rate and absence of extraocular clinical signs. The possi- cifically, a previously published report of a 28-year-old bility of a non-arteritic AION was considered, and close male with signs of neuroretinitis, chickenpox and posi- monitoring was maintained. tive titer of immunoglobulin G (IgG) for varicella zoster Two weeks later, the Goldmann visual field exam virus without polymerase chain reaction (PCR) analysis revealed no abnormality. The left eye fundus revealed an was completely resolved with oral acyclovir [2]. Moreo- optic disc edema, submacular fluid and a delayed devel- ver, a 48-year-old female with neuroretinitis was positive opment of a macular star (Fig. 1. A1). The macular optical using PCR and IgG positive for both cytomegalovirus coherence tomography (OCT) showed a serous retinal and HSV-1 with previous history of flu symptoms was detachment (Fig.1 A2). successfully treated with intravenous and intravitreal The macular star observed in the fundus helped to ganciclovir [3]. Here, we present an unusual case of neu- establish a new differential diagnosis that included dis- roretinitis in an immunocompetent patient with no other eases like hypertensive or radiation-induced retinopathy systemic symptoms or signs in a primary HSV infection. and secondary or idiopathic neuroretinitis. There was no When a patient shows typical manifestations of HSV history of arterial hypertension nor exposure to ionizing infection, a clinical diagnosis might be enough. In an radiation. The neuroretinitis path was comprehensively immunocompetent patient with atypical manifestations analyzed and clinical and biological examinations were like neuroretinitis, biological examinations could be use- made. ful, such as blood tests for specific antibodies or nucleic Contact risks, including food habits, recent travel, acid amplifications tests. A PCR test is often a very useful sexual experience, and animal contacts were thoroughly tool to confirm a diagnosis of HSV. It is worth mention- explored. A detailed physical examination was performed ing that, the reliability of a PCR test on ocular fluids has to note sites with rashes or inoculation spots but was been reported to be lower in immunocompetent than in unremarkable. Concerning laboratory tests, immune immunosuppressed patients [5]. Specifically, a negative profile, tuberculin skin test and serological evaluation PCR result cannot reliably rule out the infection in immu- were performed, including Bartonella, Epstein-Barr nocompetent patients but a positive result, certainly, can virus, Rickettsia, Lyme disease, histoplasmosis, syphi- confirm it. Unfortunately, a PCR test at the acute stage lis, chlamydia, human immunodeficiency virus, toxo- for our patient was not performed, so we based the diag- plasmosis, brucellosis, viral hepatitis B and C, HSV-1, nosis on positive IgM with negative IgG titers for HSV-1. and HSV-2. The only clinical abnormality was a positive This was also supported by the good response to antiviral immunoglobulin M (IgM) for HSV-1, which in absence treatment, as in the previously reported cases in immu- of any other systemic clinical feature allowed etiological nocompetent patients [2, 3]. diagnosis. In conclusion, we report a case of isolated neuroretini- A treatment regimen with valacyclovir 1 g every 8 h tis as a primary HSV infection in an immunocompetent was started and we observed a clinical improvement at patient with resolution and good functional results after Lázaro‑Rodríguez et al. BMC Ophthalmology (2022) 22:47 Page 3 of 4 Fig. 1 Color retinography images showing a macular star (A1) and its progressive reduction (B1 at 2 weeks, C1 at 1 month, and D1 at 3 month). Optical coherence tomography images showing serous retinal detachment (A2), and its progressive resolution (B2 at 2 weeks, C2 at 1 month, and D2 at 3 month) valacyclovir treatment. Presence of HSV IgM in absence Abbreviations AION: Anterior ischemic optic neuropathy; BCVA: Best corrected visual acuity; of other laboratory results could be enough evidence to HSV: Herpes simplex virus; HSV-1: herpes simplex virus type 1; HSV-2: herpes start HSV treatment in immunocompetent patients with simplex virus type 2; IgG: Immunoglobulin G; IgM: Immunoglobulin M; OCT: a macular star, as an isolated lesion, after ruling out other Optical coherence tomography; PCR: Polymerase chain reaction. non-infectious causes, such as arterial hypertension or Acknowledgements exposure to ionizing radiation. Rare infectious agents in Dr. Michael J. Edel of Centro de Oftalmología Barraquer for the English edition immunocompetent patients must be considered in the of the manuscript. differential diagnosis of neuroretinitis, even if there are Financial disclosure no other typical symptoms or signs that could suggest the The authors have no financial, proprietary or commercial interest in any mate‑ disease. rials presented herein." was removed. Please check if correct. Lázaro‑Rodríguez et al. BMC Ophthalmology (2022) 22:47 Page 4 of 4 Authors’ contributions VLR had the conception and design of the study. MJC carried out the clinical management of this patient. HB collected the data and drafted the case report. VLR and HB wrote the manuscript with support from MJC. MJC encour‑ aged VLR and HB to investigate the use and relevance of the reliability of PCR tests on ocular fluids and supervised the findings of this work revising it critically for important intellectual content. All authors provided critical feed‑ back and helped shape the research and manuscript. All authors discussed the results and contributed to the final manuscript. The author(s) read and approved the final manuscript. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Availability of data and materials Not applicable. Declarations Ethics approval and consent to participate The authors obtained written informed consent to participate from the patient. Consent for publication Written informed consent was obtained from the patient for publication of this Case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal. Competing interests The authors declare that they have no competing interests. Author details 1 Centro de Oftalmología Barraquer, Muntaner 314, 08021 Barcelona, Spain. 2 Institut Universitari Barraquer, Universitat Autònoma de Barcelona, Barcelona, Spain. Received: 4 August 2021 Accepted: 25 January 2022 References 1. Liesegang TJ. Herpes simplex virus epidemiology and ocular importance. Cornea. 2001;20(1):1–13 2. 2. Tsao WS, He MS, Tsai RK. Varicella zoster virus-associated neuroretinitis. Taiwan J Ophthalmol. 2015;5:189–91. 3. Thitiwichienlert S, Leeamornsiri S. Combined cytomegalovirus and her‑ pes simplex virus-related Neuroretinitis in an Immunocompetent patient. Korean J Ophthalmol. 2019;33(4):395–6. 4. Purvin V, Sundaram S, Kawasaki A. Neuroretinitis: review of the literature and new observations. J Neuroophthalmol. 2011;31:58–68. 5. Harper TW, Miller D, Schiffman JC, Davis JL. Polymerase chain reaction analysis of aqueous and vitreous specimens in the diagnosis of posterior segment infectious uveitis. Am J Ophthalmol. 2009;147(1):140–147.e2. 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