February 2015




Challenges in the management of acute retinal necrosis

by Matt Young and Gloria D. Gamat EyeWorld Contributing Writers


Montage photos showing peripheral acute retinal necrosis with typical whitish retinitis with scalloped edges and adjacent vasculitis.

Temporal retinitis with defined white edges and hazy view due to dense overlying vitritis.

Source (all): Stephen Teoh, MD

Rare retinal condition continues to puzzle, but there are ways to treat

It was called Kirisawa uveitis when first described in the Japanese literature in 1971. Since then, acute retinal necrosis (ARN) syndrome has puzzled ophthalmologists. ARN is an extremely rare condition with characteristic fundal appearances that nevertheless troubles eye specialists because of its potential to become a visually devastating condition for those affected. ARN can lead to uveitis, retinal detachment, and blindness. Its incidence rate is estimated at 1 case per 2 million people per year, as reported in recent years by surveys from the U.K. In the past 3 decades, the literature on the diagnosis and management of ARN has expanded, and the understanding, diagnosis, and management (both medical and surgical) of the condition have also improved.

The uveitis that puzzles

Although an immunogenetic predisposition to the disease is being suggested by various studies, ARN is largely a result of dormant herpes simplex virus 1 (HSV-1), herpes simplex virus 2 (HSV-2), or varicella-herpes zoster virus (VZV) reactivation in the retina. However, the exact etiology of such a reactivation remains a puzzle. VZV is the causative agent in 70% of ARN cases, while HSV is in 30% of the cases. Typically, ARN occurs in young immunocompetent individuals, 20 to 50 years of age; the age of manifestation depends on the causative agent. Data published in the American Journal of Ophthalmology by JB Ganatra and colleagues in 2000 suggested that VZV or HSV-1 causes ARN in patients older than 25 years, whereas HSV-2 causes ARN in patients younger than 25 years. The study looked into the viral causes of ARN with respect to patient age and central nervous system disease. Additionally, a history of central nervous system infection in an ARN patient suggests that herpes simplex virus is likely to be the viral cause.

The pathogenesis occurs in young, apparently healthy adults with no other systemic illness, usually not in any other form of immunosuppresion, said Stephen Teoh, MD, director of vitreoretina surgery at the Eagle Eye Centre, Singapore, who presented a controversial case of ARN at the recent National Healthcare Group Eye Institute 7th International Ophthalmology Congress in Singapore. Other studies have suggested that B- and T-cell imbalance in the immunity of these healthy individuals impacts the type and severity of the disease, ranging from ARN to progressive outer retinal necrosis, he said. In the United States, ARN accounts for 5.5% of uveitis cases over a 10-year period, and in Switzerland, it accounts for 1.7% of uveitic cases. Adding to the puzzle of ARN, there are other syndromes that might present like it: CMV (cytomegalovirus), toxoplasmosis, Behcets disease, acute multifocal hemorrhagic retinal vasculitis, sarcoidosis, and intraocular lymphoma. As a result, these possibilities should be considered before making the diagnosis of ARN.

How to diagnose and treat

Drug resistance is uncommon in ARN treatment. Antiviral drugs may have few side effects, but special attention needs to be paid to patients who have underlying renal disease, are pregnant, or are immunocompromised.

Imaging studies (i.e., fluorescein angiography, ocular ultrasound) have resulted in a significant improvement in the visual prognosis for affected patients. However, according to Dr. Teoh, identifying the infective root cause of ARN determines the appropriate course of treatment. Diagnosis in this day and age is largely [based] on polymerase chain reaction (PCR) that gives very rapid results [within 48 to 72 hours], and can be done on very small samples and typically taken from aqueous or vitreous fluid, Dr. Teoh said. PCR can be done both qualitatively and quantitatively, which can be used to monitor the viral activity in response to therapeutics. Other investigation methods are more complicated and time consuming, so PCR probably remains the most common and fastest method. While confirming the diagnosis by performing an anterior chamber paracentesis and immunofluorescence studies to assess local VZV and HSV antibody production might be a newer alternative, these are experimental methods. The specificity and sensitivity of the procedure remains to be defined. The rarity of ARN cases is a major factor in the lack of prospective clinical studies. While a few studies have defined the viral causes and therapeutic principles, most observations are derived from small case series, and homogenous international guidelines for therapy remain lacking.

According to Dr. Teoh, while the recommended 34 month duration of therapy has shown good outcomes, either using traditional acyclovir or newer antiviral treatment such as valacyclovir, it is unclear what duration of antiviral treatment is necessary to prevent involvement of the fellow eye. In ARN, which generally begins as a unilateral disease, the second eye becomes involved in one-third of the cases. The interval reported between the initial episode and involvement of the second eye averages 16 weeks but has been reported to be as long as 34 years. Evaluating the antiviral selection in the management of ARN, Patrick MK Tam and colleagues stated in Clinical Ophthalmology that there is no consensus on the optimal antiviral regimen in the management of ARN, and the current gold standard is based on retrospective case series. While some antiviral agents have been proven to achieve therapeutic concentrations in the vitreous at conventional doses, the choice would still be based on experience and safety profile. The exact duration of treatment remains unknown. The traditional treatment of acyclovir [oral and intravenous] and other new treatments as well have had very good outcomes, although there are no published prospective randomized trials conducted to possibly determine which one is the best method, Dr. Teoh said.


Cochrane TF, Silvestri G, McDowell C, et al. Acute retinal necrosis in the United Kingdom: results of a prospective surveillance study. Eye (Lond). 2012;26(3):370378.

Ganatra JB, Chandler D, Santos C, et al. Viral causes of the acute retinal necrosis syndrome. Am J Ophthalmol. 2000;129(2):16672.

Tam PM, Hooper CY, Lightman S. Antiviral selection in the management of acute retinal necrosis. Clin Ophthalmol. 2010;4:1120.

Editors note: Dr. Teoh has no financial interests related to his comments.

Contact information

Teoh: stephenteoh@eagleeyecentre.com.sg

Challenges in the management of acute retinal necrosis Challenges in the management of acute retinal necrosis
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