Mark L. Nelson
• Infectious retinitis caused by members of the herpes virus family, predominantly Varicella Zoster Virus and Herpes Simplex Virus
• Syndrome characterized by anterior uveitis, vitritis, peripheral foci of retinal necrosis that extend posteriorly and circumferentially, retinal vasculopathy, and retinal detachment
• Approximately 1 case in 1.6/2.0 million, although there are few significant epidemiologic studies.
• Generally affects healthy, immunocompetent hosts
• Bimodal distribution with peaks at 20 and 50 years of age
• Previous ocular herpetic infections including HSV keratitis, Herpes Zoster Ophthalmicus; as well as systemic herpetic infections such as cold sores, chickenpox, encephalitis, and shingles
• Immunodeficiency may play a role, although the majority of cases occur in immunocompetent patients.
• Vary within different ethnicities: In the US, Caucasian patients often manifest HLA-DQw7 antigen; Japanese patients tend to manifest HLA-Aw33, B44, and DRw6.
• Cases with more fulminant presentation are sometimes associated with HLA-DR9.
• Remains to be fully described; latent viral reactivation and primary infection with Herpes virus have been reported to migrate by axonal transport to the retina and surrounding tissues.
• On histopathology, there is intranuclear accumulation of viral particles at multiple foci, with subsequent granulomatous and non-granulomatous inflammation and necrosis.
Several members of the Herpes virus family cause the inciting infection; VZV accounts for the majority of cases (reported at approximately 50%), but HSV-1, HSV-2, CMV, and EBV have also been reported.
• Presenting symptoms may be minimal and include irritation, redness, photophobia, periorbital pain, and floaters.
• One epidemiologic study noted sudden visual loss as the main presenting complaint in 85% of cases; photophobia is reported in over half of patients, whereas ocular pain and flu-like symptoms are present in one-quarter of cases; a minority of patients (16%) presented with a red eye.
• It is a clinical diagnosis:
– The American Uveitis Society criteria include:
One or more discrete foci of peripheral retinal necrosis
Occlusive arteriolar retinopathy
Prominent vitreous or anterior chamber inflammatory reaction
Rapid disease progression in the absence of therapy
• Inspect for anterior uveitis including episcleritis, scleritis, and/or keratic precipitates. At presentation, over 80% of patients have anterior chamber activity, vitreous activity, or peripheral retinal involvement.
• Posterior segment manifestations typically develop within 2 days of initial symptoms and appear as well-defined, multifocal patches of yellowish–white or cream colored retinal infiltrates.
• Vascular sheathing and perivascular intraretinal hemorrhages may develop.
• Retinal necrosis progresses rapidly and spreads circumferentially and posteriorly; the macula is often spared.
• 6–12 weeks after infection, proliferative vitreoretinopathy may lead to retinal holes at the border of normal and affected retina. Rhegmatogenous retinal detachment may occur in over 50% of affected eyes, usually within 1–2 months, although it can occur anytime from 1 week to around 6 months.
• 20% of patients have bilateral infection at presentation. Spread to the contralateral eye typically occurs within 3 months of symptom onset. Systemic antiviral therapy reduces the risk of infection in the second eye from roughly 65–17%.
DIAGNOSTIC TESTS & INTERPRETATION
Initial lab tests
• Diagnostic confirmation can be made by polymerase chain reaction (PCR) analysis of aqueous sample or vitreous biopsy. PCR has the highest specificity and sensitivity of▒available laboratory studies.
– Other laboratory methods that have been used and may suggest an etiologic agent or diagnosis include local and/or systemic antibody titers, Goldmann-Witmer coefficient, fluorescent antibody techniques, or tissue culture. These tests are indicative but not usually considered diagnostic.
Follow-up & special considerations
Detailed examination of the both eyes at each visit is critical as the infectious process can spread bilaterally.
Color photographs are useful to follow disease progression.
Full-thickness retinal necrosis with eosinophilic intranuclear inclusions. Choroidal inflammation can be granulomatous and usually underlies areas of retinitis. The optic nerve, iris, and ciliary body may be also infiltrated with plasma cells, eosinophils, or macrophages.
• Progressive outer retinal necrosis
• Cytomegalovirus retinitis
• Behcet’s disease
• Toxoplasmosis retinochoroiditis
• Large cell lymphoma
• Syphillic neuroretinitis
• Candida albicans endophthalmitis
• Historically, ARN was first managed with intravenous acyclovir at 500 mg/m2 3 times daily for 7–10 days followed by oral acyclovir at 800 mg 5 times daily for up to 14 weeks.
• Newer antivirals have been used in different combinations such as:
– Valacyclovir 1–2 g 3 times daily
– Famciclovir 250–500 mg twice daily
– Valganciclovir 450–900 mg twice daily
– IV acyclovir with intravitreal injection of foscarnet or ganciclovir
– Oral valacyclovir or famciclovir followed by IV acyclovir
• Intravitreal injections of foscarnet (1.2–2.4 mg per 0.1 mL) and ganciclovir (200–2000 μg per 0.1 mL) have been used as adjunctive therapy.
• Systemic corticosteroids (often prednisone 30–80 mg daily) are used in more than half of patients.
• Most patients receive topical corticosteroids in the initial treatment period anywhere from every 1–6 hours.
Issues for Referral
Patients with suspected ARN require prompt referral to a uveitis/retinal specialist because of the rapid, severe sequelae of untreated infection and due to the possible need for vitrectomy and/or laser retinopexy.
• Prophylactic argon laser retinopexy has been found in some studies to reduce the incidence of secondary RD by approximately half, whereas others find no significant difference.
• Vitrectomy is usually performed for dense vitreous opacities, vitreous hemorrhage, or after secondary retinal detachment.
No clear admission criteria have been elucidated. Such decisions are typically made based on the clinical situation.
• Risk factors for poor outcomes and worse final visual acuity include initial visual acuity and subsequent retinal detachment.
• Retinal detachment occurs with similar frequency in the newer antiviral era when compared with the acyclovir-only era.
• Final visual acuity of patients with ARN is significantly worsened despite the advent of new antiviral medications and surgical interventions with some studies showing half of patients having acuity worse than 20/200 by 3 months and 75% having acuity worse than 20/200 by 5 years.
Retinal detachment, optic nerve involvement, vitreous hemorrhage, retinal neovascularization, and blindness.
• Tibbetts MD, Shah CP, Young LH, et al. Treatment of acute retinal necrosis. Ophthalmology 2010;117(4):818–824.
• Muthiah MN, Michaelides M, Child CS, et al. Acute retinal necrosis: A national population-based study to assess the incidence, methods of diagnosis, treatment strategies and outcomes in the UK. Br J Ophthalmol 2007;91(11):1452–1455.
• Lau CH, Missotten T, Salzmann J, et al. Acute retinal necrosis features, management, and outcomes. Ophthalmology 2007;114(4):756–762.
• Hillenkamp J, Nolle B, Bruns C, et al. Acute retinal necrosis: clinical features, early vitrectomy, and outcomes. Ophthalmology 2009;116(10):1971–1975.
• Chang S, Young LH. Acute retinal necrosis: An overview. Int Ophthalmol Clin 2007;47(2):145–152.
• Aizman A, Johnson MW, Elner SG. Treatment of acute retinal necrosis syndrome with oral antiviral medications. Ophthalmology 2007;114(2):307–312.
• 053.29 Herpes zoster with other ophthalmic complications
• 364.3 Unspecified iridocyclitis
• 379.29 Other disorders of vitreous
• Acute retinal necrosis can present in an insidious manner and easily be misdiagnosed as an anterior uveitis if a dilated fundus examination is not performed.
• The other eye can frequently become involved, so systemic antiviral therapy and close monitoring of the other eye is very important.
• Diagnosis is made by clinical findings alone, but testing such as PCR can help if there is a diagnostic dilemma.