Elsevier

Ophthalmology

Volume 108, Issue 5, May 2001, Pages 869-876
Ophthalmology

Herpes simplex virus type 2 as a cause of acute retinal necrosis syndrome in young patients

https://doi.org/10.1016/S0161-6420(01)00556-5Get rights and content

Abstract

Purpose

To determine the causative virus in acute retinal necrosis (ARN) syndrome in a series of patients by calculation of modified Witmer coefficients.

Design

Noncomparative case series.

Participants

Ten patients with ARN syndrome from four medical centers.

Methods

Aqueous samples, vitreous samples, or both were collected prospectively during surgery from patients with a clinical diagnosis of ARN syndrome. Serologic measures of intraocular and serum antibodies to potentially causative viruses were measured by enzyme-linked immunosorbent assay.

Main outcome measures

Modified Witmer coefficients (immunoglobulin G and immunoglobulin A) for herpes simplex virus types 1 (HSV-1) and 2 (HSV-2), varicella zoster virus (VZV), and cytomegalovirus (CMV), as well as adenovirus type 2, were calculated from aqueous or vitreous samples, or both.

Results

Intraocular antibody measurements were strongly suggestive of a single diagnosis in 9 of 10 patients tested. Modified Witmer coefficients demonstrated intraocular antibody production to HSV in five patients and antibodies to VZV in four patients, and the measurement was inconclusive in one patient. No patients were positive for adenovirus or CMV. Strain-specific antibody titers demonstrated that all HSV-positive patients were reactive only to HSV-2. Herpes simplex virus type 2 was found predominantly in younger patients with ARN syndrome (mean age, 21.2 ± 10 years; range, 17–39 years), whereas VZV was more commonly seen in older patients (mean age, 40.8 ± 12.2 years; range, 29–58 years; P = 0.033). Immunoglobulin A testing confirmed immunoglobulin G testing in all patients examined.

Conclusions

Although VZV is thought to be the most common cause of ARN syndrome, HSV-2 is an important cause of ARN syndrome, particularly in younger patients. Because infection with HSV-2 has important medical ramifications, these results suggest that determination of a causal agent should be considered in some cases of ARN syndrome.

Section snippets

Patient population

Ten patients with a clinical diagnosis of ARN syndrome, from whom intraocular fluid could be obtained, were recruited from four centers. Five patients were recruited at Emory University in Atlanta (patients 5, 6, 7, 8, and 9), two from Bascom Palmer Eye Institute (patients 3 and 4), two from Jules Stein Eye Institute (patients 1 and 2), and one from Detroit, Michigan (patient 10). Vitreous samples were obtained at the time of surgery for repair of retinal detachment. Aqueous samples were

Patient population

Patient demographics and clinical presentations of ARN syndrome in the 10 patients studied are shown in Table 1. The patients studied ranged in age from 15 to 65 years at the time of diagnosis. None of the patients had evidence of underlying immunocompromised status at presentation. At presentation, all had the classic manifestations of ARN syndrome defined by the American Uveitis Society criteria.4 Seven patients had bilateral ARN syndrome, but none of these patients had fluid removed from

Discussion

Measurement of intraocular antibody titers and calculation of modified Witmer coefficients identified a probable causal agent for ARN syndrome in 9 of the 10 patients tested. In these nine patients, a clear increase in relative antibody levels to one virus compared with all others was observed. Immunoglobulin A testing confirmed the diagnosis suggested by the IgG testing in each of the five cases in which it was performed. Two viruses, HSV-2 and VZV, accounted for all cases. Interestingly, of

Acknowledgements

The authors thank William W. Culbertson, Mary L. Lewis, Mark S. Blumenkranz, and Gary Cowan, for contributing patient samples and histories to this study, and Allan E. Kreiger, Lindsey Reese, Andre Nahmias, and Francis K. Lee for analysis of the intraocular specimens. The authors also thank Fei Yu, of the Center for Eye Epidemiology of the Jules Stein Eye Institute, for assistance with statistical analyses performed in this study.

References (45)

  • J.H de Boer et al.

    Serologic and polymerase chain reaction analysis of intraocular fluids in the diagnosis of infectious uveitis

    Am J Ophthalmol

    (1996)
  • J.B Ganatra et al.

    Viral causes of acute retinal necrosis syndrome

    Am J Ophthalmol

    (2000)
  • J.D Perry et al.

    Herpes simplex encephalitis and bilateral acute retinal necrosis syndrome after craniotomy

    Am J Ophthalmol

    (1998)
  • E Ezra et al.

    Delayed fellow eye involvement in acute retinal necrosis syndrome

    Am J Ophthalmol

    (1995)
  • M.S Figueroa et al.

    Famciclovir for the treatment of acute retinal necrosis (ARN) syndrome

    Am J Ophthalmol

    (1997)
  • F.K Lee et al.

    A novel glycoprotein for detection of herpes simplex virus type 1-specific antibodies

    J Virol Methods

    (1986)
  • M.J.H Ronday et al.

    Intraocular anti-Toxoplasma gondii antibody production in patients with ocular toxoplasmosis

    Am J Ophthalmol

    (1999)
  • J.S Pepose

    The potential impact of the varicella vaccine and new antivirals on ocular disease related to varicella-zoster virus

    Am J Ophthalmol

    (1997)
  • A Urayama et al.

    Unilateral acute uveitis with retinal periarteritis and detachment

    Jpn J Clin Ophthalmol

    (1971)
  • D Willerson et al.

    Necrotizing vaso-occlusive retinitis

    Am J Ophthalmol

    (1977)
  • N.J.A Young et al.

    Bilateral acute retinal necrosis

    Br J Ophthalmol

    (1978)
  • G.N Holland

    Standard diagnostic criteria for the acute retinal necrosis syndrome. Executive Committee of the American Uveitis Society

    Am J Ophthalmol

    (1994)
  • Cited by (105)

    • Whitcup and Nussenblatt’s Uveitis: Fundamentals and Clinical Practice

      2021, Whitcup and Nussenblatt's Uveitis: Fundamentals and Clinical Practice
    • Comparing Treatment of Acute Retinal Necrosis With Either Oral Valacyclovir or Intravenous Acyclovir

      2018, American Journal of Ophthalmology
      Citation Excerpt :

      The higher percentage of eyes with a clinical diagnosis alone in the intravenous group (and, consequently lower rate of eyes with PCR-confirmed VZV ARN) might be explained by the fact that intraocular fluid aspiration and PCR was not performed as commonly in earlier practice as it is today. Given that VZV has been shown to be the most common causative agent of ARN,1,25–27 it is likely that the majority of eyes diagnosed clinically with ARN (without confirmatory PCR) also had VZV-related ARN. In accordance with the literature,25,26 this study found that HSV-related ARN occurred on average at a younger age (27.4 years) than VZV ARN (53.6 years).

    • A case of hypertrophic herpes simplex virus affecting the eyelid and cornea masquerading as IgG4-related disease

      2018, American Journal of Ophthalmology Case Reports
      Citation Excerpt :

      HSV type 2 is a common cause of sexually transmitted infection of the genital area, but is uncommonly encountered in the eye. When it is present in the eye, it usually manifests in the posterior segment, with uveitis and acute retinal necrosis.3 HSV type 2 in the anterior segment is extremely rare, but has been reported to cause keratitis in infants who were infected through a placental or maternal genital tract route. 4,5

    • Infective Uveitis, Retinitis, and Chorioretinitis

      2018, Principles and Practice of Pediatric Infectious Diseases
    • Viral posterior uveitis

      2017, Survey of Ophthalmology
    View all citing articles on Scopus

    Supported by Research to Prevent Blindness, Inc., New York, New York (RNVG, GNH); the Heed Ophthalmic Foundation (RNVG), Cleveland, Ohio; the Bernard Becker Clinician–Scientist Award (RNVG), St. Louis, Missouri; and the David May II Endowed Professorship (GNH), UCLA, Los Angeles, California. Dr. Van Gelder is recipient of a Career Development Award, and Dr. Holland is a recipient of a Lew R. Wasserman Merit Award from Research to Prevent Blindness, Inc., New York, New York. Dr. Henry Kaplan, Evans Professor of Ophthalmology, Louisville, Kentucky.

    View full text