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CASE REPORT Table of Contents  
Ahead of print publication
Acute posterior multifocal placoid pigment epitheliopathy associated with infectious mononucleosis: A rare presentation

1 Department of Ophthalmology, Derince Training and Research Hospital, University of Health Sciences, w, Turkey
2 Department of Medical Microbiology, Kocaeli University Kocaeli, Turkey
3 Department of Ophthalmology, Kocaeli University Kocaeli, Turkey

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Date of Submission27-Apr-2021
Date of Decision10-Jun-2021
Date of Acceptance11-Jun-2021
Date of Web Publication17-Nov-2021


This case report describes the association between acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and Epstein–Barr virus (EBV) infection. A 26-year-old female presented with acute bilateral blurred vision and paracentral scotoma. The patient also had prodromal flu-like symptoms. Funduscopic examination showed bilateral yellow-white placoid lesions at the level of retinal pigment epithelium (RPE). Fluorescein Angiography showed characteristic early hypofluorescence and late hyperfluorescence of the lesions. The diagnosis of APMPPE was made based on these findings. Laboratory investigation showed a positive result for EBV serology test. Severe dry eye symptoms were presented at the end of 6-month follow-up. APMPPE may be associated with acute systemic EBV infection.

Keywords: Acute posterior multifocal placoid pigment epitheliopathy, Epstein–Barr virus, placoid lesions

How to cite this URL:
Tokuc EO, Yumuk Z, Karabas V L. Acute posterior multifocal placoid pigment epitheliopathy associated with infectious mononucleosis: A rare presentation. Saudi J Ophthalmol [Epub ahead of print] [cited 2023 Jan 30]. Available from: https://www.saudijophthalmol.org/preprintarticle.asp?id=330526

  Introduction Top

Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is an inflammatory disease and typically affects young healthy adults.[1],[2] It has been reported that APMPPE is associated with inflammation in the retina pigment epithelium (RPE) and a hypersensitivity reaction against a foreign antigen in the choriocapillaris.[1],[3],[4]

Epstein–Barr virus (EBV) can directly cause infectious retinitis using RPE cells as reservoirs or trigger autoimmune-associated inflammatory retinitis.[5]

To the best of our knowledge, this relationship has never been reported for APMPPE, although EBV may cause other choroiditis. We aimed to present a patient with APMPPE with a history of infectious mononucleosis.

  Case Report Top

A 26-year-old female presented with a blurred vision of both eyes over 10 days. She started illness flu-like symptoms with fevers, chills, and joint pain about a week prior to visual symptom. Family history of the patient was unremarkable.

On examination, best-corrected visual acuity was 20/20 in both eyes. Light reflex was normal for both eyes. Schirmer tests: 11 mm in the right eye (RE) and 12 mm in the left eye (LE). Slit-lamb examination of the anterior segment did not show any disorder in both eyes. There was no vitritis in fundus examination. Dilated fundus examination revealed that multiple yellow-white chorioretinal placoid lesions at the posterior pole of both eyes at the first examination. In the color fundus photographs which were taken 5 days after the patient's initial visit, the lesions were in the healing phase with central hyperpigmentation in both eyes [Figure 1]a and [Figure 1]d.
Figure 1: Fundus images at initial presentation (top, right eye; bottom, left eye). (a and d) The color fundus photographs, which were taken 5 days after the first visit, show that lesions begin to heal with hyperpigmented plaques. (b and e) Fundus autofluorescence. (c and f) Late-phase fluorescein angiography

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The retinal vessels and optic disc were normal. The placoid lesions with disruption of the RPE and external limiting membrane were observed in spectral-domain optical coherence tomography [Figure 2]a and [Figure 2]b. Fundus autofluorescence revealed the placoid lesions that exhibit hypoautofluorescence center with hyperautofluorescence edges [Figure 1]b and [Figure 1]e. Fluorescein Angiography showed characteristic early hypofluorescence and late hyperfluorescence of the lesions [Figure 1]c and [Figure 1]f. Clinical and radiographic features of this choroiditis confirmed the diagnosis of APMPPE. Visual fields analysis using by the Humphrey field analyzer 30-2 test showed bilateral paracentral scotoma.
Figure 2: (a and b) Fundus autofluorescence photographs at 6 months showing hypoautofluorescent lesions

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Laboratory tests showed the elevation of C reactive protein and lymphocytosis. Angiotensin-converting enzyme dosage was normal. Serological test for syphilis, toxoplasma gondii were normal. Purified protein derivative skin test for tuberculosis was negative. Antistreptolizin O test performed to evaluate previous  Streptococcus pyogenes Scientific Name Search ion was negative. The laboratory serology data was positive for EBV immunoglobulin G (IgG).

On first admission, EBV serology was very well correlated with recent infection (anti-VCA IgM positive, anti-VCA IgG positive, anti-EBNA positive and anti-p22 negative). On the second admission where there was high suspicious of APMPPE, the EBV serology was requested secondly. The second evaluation of the EBV serology confirmed the patients EBV infection approximately 6 months old (anti-VCA IgM negative, anti-VCA IgG positive, anti-EBNA positive, and anti-p22 positive). Anti-CMV IgG antibodies were also positive then the avidity was negative. All the samples were assayed by commercial immunoblot (Euroline IgM and IgG; Euroimmun, Germany) method.

Autoantibodies test including antiglomerular basement membrane antibody, antinuclear antibody, anti-DNA antibody, and cANCA (antineutrophil cytoplasmic antibody in cytoplasmic pattern) were negative. Laboratory tests showed absence HLA B7 and HLA DR2. Workup included negative for HIV, hepatitis B surface antigen and hepatitis C virus tests. Abdominal ultrasound examination included mesenteric nonspecific lymphadenopathies. Computed tomography of the brain and chest radiography was unremarkable. Due to the good visual acuity and absence of foveal involvement, we observed the clinical course without intervention.

Subsequently, lesions in both eyes were regressed, leaving only a scattered pigment epithelial reaction [Figure 2] and [Figure 3]. There was no recurrence of lesions and blurred vision improved. On follow-up at 6 months, she presented with stinging burning and redness in both eyes. The schirmer test was repeated: 1 mm (LE), 0 mm (RE). Ocular surface disease index (OSDI) dry-eye questionnaire was evaluated. The total score of OSDI was 81.25 and consistent with severe dry eye disease. Topical medical treatment was insufficient therefore punctal plug was implanted in the both eyes, upper and lower punctum of the patient.
Figure 3: Optical coherence tomography (OCT) through fovea at presentation (a and b) and 6-month follow-up (c and d). (a and b) On initial visit, optical coherence tomography shows outer retinal architectural disruption. (c and d) At 6-month follow-up, optical coherence tomography demonstrates partial restoration of the ellipsoid zone

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  Discussion Top

In the presented case, systemic infection of EBV, which indicates the association between infectious mononucleosis and APMPPE, was confirmed by EBV antibody serology tests in acute phase and second phase of APMPPE.

APMPPE may develop following hepatitis B vaccination, mumps, swine flu vaccination and bacterial infection.[6] T lymphocytes activation and type IV hypersensitivity reaction is evident in these cases. The findings of previous studies demonstrated a relation between recurrences and hypersensitivity reactions against various pathogens.

The majority of people with APMPPE present a sudden, painless loss of central vision. The posterior pole contains large, creamy yellow-white placoid lesions. The lesions disappear over time, leaving different degrees of hyperpigmentation and in some cases, RPE atrophy.[1],[2],[3] In the presented case, the lesions were regressed and leaving just a pigment epithelial reaction.

EBV may be located in salivary glands and lacrimal glands as a latent infection following primary infection.[7] This latent infection may be resulted as a salivary gland and lacrimal gland infection due to the reactivation of virus.[8] According to Pflugfelder et al.,[8] reduction in aqueous tear production and severe dry eye disease progression may be related to lacrimal gland lymphocytic proliferation in Sjogren syndrome caused by EBV infection. Therefore, severe dry eye symptoms may be associated with previous EBV infection in the presented case.

Hence, the majority of EBV infections are subclinical, serology data of EBV is important for the investigation of EBV exposure and acute infection clinically. In this case, the patient showed seropositive EBV capsid antigen (EB VCA) IgG antibody, and titer of IgG antibody was compatible with previous infectious mononucleosis 6 months ago.

The relation between EBV and eye pathology can be explained by two hypothesis including infectious or autoimmunogenicity potential of the virus in the literature.[5] Besides, retinitis may developed due direct effect of the virus to RPE cells.[5] According to other hypotheses, EBV may trigger autoimmune-mediated inflammatory retinitis in genetic susceptible hosts.[5] The autoantibody of immune response to the protein of EBV may attack the ocular tissue such as photoreceptors, RPE cells, and choroid. Multifocal choroiditis, punctate retinitis, and multiple evanescent White dot syndrome with devious acute EBV infection have been reported.[9] In the presented case, we proposed that subclinical EBV infection may have induced an autoimmune or inflammatory response in retina that led to retinal involvement of APMPPE.

Although APMPPE can be the cause for a post-viral blurring of vision. Fortunately, the disease is self-limiting with good visual prognosis provided that the macula is not involved. Prospective epidemiological studies are required to link APMPPE occurrence and EBV.

Declaration of patient consent

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

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Conflicts of interest

There are no conflicts of interest.

  References Top

Deutman AF, Oosterhuis JA, Boen-Tan TN, Aan de Kerk AL. Acute posterior multifocal placoid pigment epitheliopathy. Pigment epitheliopathy of choriocapillaritis? Br J Ophthalmol 1972;56:863-74.  Back to cited text no. 1
Chiquet C, Lumbroso L, Denis P, Papo T, Durieu I, Lehoang P. Acute posterior multifocal placoid pigment epitheliopathy associated with Wegener's granulomatosis. Retina 1999;19:309-13.  Back to cited text no. 2
Gass JD. Acute posterior multifocal placoid pigment epitheliopathy. Arch Ophthalmol 1968;80:177-85.  Back to cited text no. 3
Kersten DH, Lessell S, Carlow TJ. Acute posterior multifocal placoid pigment epitheliopathy and late-onset meningo-encephalitis. Ophthalmology 1987;94:393-6.  Back to cited text no. 4
Yang CS, Hsieh MH, Su HI, Kuo YS. Multiple evanescent white dot syndrome following acute epstein-barr virus infection. Ocul Immunol Inflamm 2019;27:244-50.  Back to cited text no. 5
Branisteanu D, Bilha A. Acute posterior multifocal placoid pigment epitheliopathy following influenza vaccination. Rom J Ophthalmol 2015;59:52-8.  Back to cited text no. 6
Cohen JI. Epstein-Barr virus infection. N Engl J Med 2000;343:481-92.  Back to cited text no. 7
Pflugfelder SC, Crouse CA, Atherton SS. Ophthalmic manifestations of Epstein-Barr virus infection. Int Ophthalmol Clin 1993;33:95-101.  Back to cited text no. 8
Raymond LA, Wilson CA, Linnemann CC Jr., Ward MA, Bernstein DI, Love DC. Punctate outer retinitis in acute Epstein-Barr virus infection. Am J Ophthalmol 1987;104:424-6.  Back to cited text no. 9

Correspondence Address:
Ecem O Tokuc,
Department of Ophthalmology, Derince Training and Research Hospital, University of Health Sciences, İbni Sina Mahallesi Lojman Sokak, 41900 Derince, Kocaeli
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/SJOPT.SJOPT_95_21


  [Figure 1], [Figure 2], [Figure 3]


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