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Acute Retinal Necrosis

Last Updated: June 22, 2006
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Synonyms and related keywords: ARN, BARN, bilateral ARN, Kirisawa's uveitis

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Author: Andrew A Dahl, MD, Residency Director, Ophthalmology, Kingston Hospital, Assistant Professor of Surgery (Ophthalmology), Department of Ophthalmology, Mid Hudson Family Practice Institute

Coauthor(s): David T Wong, MD, FRCSC, Assistant Professor of Ophthalmology, Department of Ophthalmology, St Michael's Hospital, University of Toronto, Canada; Saad Waheeb, MD, FRCSC, Consulting Staff, Department of Ophthalmology, King Abdulaziz University Hospital

Andrew A Dahl, MD, is a member of the following medical societies: Alpha Omega Alpha, American Academy of Ophthalmology, American College of Surgeons, American Medical Association, American Society of Cataract and Refractive Surgery, and Wilderness Medical Society

Editor(s): Brian A Phillpotts, MD, Former Vitreo-Retinal Service Director, Former Program Director, Clinical Assistant Professor, Department of Ophthalmology, Howard University College of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Steve Charles, MD, Director of Charles Retina Institute; Clinical Professor, Department of Ophthalmology, University of Tennessee College of Medicine; Lance L Brown, OD, MD, Ophthalmologist, Regional Eye Center, Affiliated With Freeman Hospital and St John's Hospital, Joplin, Missouri; and Hampton Roy, Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Disclosure


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Background: Acute retinal necrosis was first described in the Japanese literature in 1971 and termed Kirisawa uveitis. During the past 2 decades, acute retinal necrosis syndrome (ARN) has been a source of fear, frustration, and fascination for many ophthalmologists. Unfortunately, it usually is a visually devastating condition for the patient.

Pathophysiology: ARN may be a result of dormant viral reactivation in the retina. The exact etiology of this reactivation is still elusive; however, there is likely an immunogenetic predisposition to the disease.

Frequency:

  • In the US: ARN accounts for 5.5% of uveitis cases over a 10-year period.
  • Internationally: In Switzerland, ARN accounts for 1.7% of uveitic cases.

Mortality/Morbidity: Significant visual loss may occur. Retinal detachment complicates most cases (64%) and is a major cause of legal blindness in ARN.

Race: No racial predilection exists.

Sex: This condition appears to have a predilection for males; however, it is not clear to what extent.

Age: ARN is a disease of young healthy individuals aged 20-50 years.

  • A bimodal age distribution possibly exists, which may be related to differences between the various etiologic agents.
  • When varicella-zoster virus or herpes simplex virus type 1 is involved, the median age is 57 and 47 years, respectively.
  • When herpes simplex virus type 2 is involved, the median age is 20 years.


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History: Typically, this is a disease of immunocompetent individuals. Initially, patients may complain of the following:

  • Red eye
  • Periorbital pain
  • Hazy decreased vision
  • Other areas of previous infections
    • Primary varicella infections
    • Herpes zoster

Physical:

  • Episcleritis or scleritis
  • Keratic precipitates
    • Fine
    • Granulomatous
  • Occlusive retinal vasculitis involving arteries and veins
  • One or more focus of retinitis, resulting in necrosis with discrete borders located in the retinal periphery with circumferential spread
  • Vitritis
  • Optic neuropathy

Causes: Most cases of ARN have been reported to be caused by the following:

  • Varicella-zoster virus
  • Herpes simplex type I
  • Herpes simplex type 2
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Behcet Disease
Endophthalmitis, Fungal
HIV
Ocular Manifestations of Syphilis
Retinitis, CMV
Sarcoidosis
Toxoplasmosis


Other Problems to be Considered:

Reticulum cell sarcoma

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Lab Studies:

  • ARN is a clinical diagnosis and laboratory tests may not be conclusive.
  • Viral titers may be helpful.
    • Herpes simplex virus 1
    • Herpes simplex virus 2
    • Varicella-zoster virus
  • For baseline
    • Complete blood count
    • Renal function
    • Liver function

Imaging Studies:

  • Fluorescein angiography
    • Not diagnostic
    • Early decrease in choroidal perfusion
    • May show delayed arterial filling
    • Hypofluorescence in areas of active lesions
  • Ocular ultrasound
    • Can rule out retinal detachment in the presence of media opacity
    • May show enlarged optic nerve sheath
  • CT scan may show optic nerve sheath enlargement.
  • MRI may demonstrate concurrent lesions of the optic tract and the lateral geniculate body suggesting axonal spread.

Procedures:

  • Lumbar puncture may show cerebrospinal fluid pleocytosis.
Staging:
  • Stage 1 - Necrotizing retinitis
    • Stage 1a - Discrete areas of peripheral retinitis
    • Stage 1b - Confluent areas of peripheral retinitis, papillitis, macular edema
  • Stage 2 - Vitreous opacification or organization
  • Stage 3 - Regression of retinal necrosis, secondary pigmentation of the lesion with condensation of the vitreous base
  • Stage 4 - Retinal detachment
    • Stage 4a - Acute retinal tears or detachment with traction or proliferative vitreoretinopathy
    • Stage 4b - Chronic retinal detachment
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Medical Care: ARN treatment consists of the following:

  • Antiviral therapy
  • Anti-inflammatory therapy
  • Antithrombotic therapy
  • Retinal detachment prophylaxis

Surgical Care: Surgery is required when retinal detachment occurs.

  • Vitrectomy
  • Endolaser
  • Possible scleral buckle
  • Intraocular tamponade - Silicone oil is the usual choice due to the multiple necrotic/atrophic retinal holes (Swiss cheese appearance).
  • C3F8 (octafluoropropane/
    perfluoropropane) or other fluoridated gases for temporary absorbable intraocular tamponade.

Consultations: Infectious disease specialist or internist
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The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Drug Category: Antivirals -- Reduce progression of virus in affected eye as well as protection of the other eye.
Drug Name
Acyclovir (Zovirax) -- Has affinity for viral thymidine kinase and once phosphorylated causes DNA chain termination when acted on by DNA polymerase. Patients experience less pain and faster resolution of cutaneous lesions when used within 48 h from rash onset. May prevent recurrent outbreaks. Early initiation of therapy is imperative.
Adult Dose1500 mg/m2/d IV divided tid for 7-10 d, followed by 800 mg PO 5 times/d for 14 wk to reduce risk of bilateral involvement
Pediatric DoseNot established; discuss with pediatrician or infectious disease specialist
ContraindicationsDocumented hypersensitivity
InteractionsConcomitant use of probenecid or zidovudine prolongs half-life and increases CNS toxicity of acyclovir
Pregnancy B - Usually safe but benefits must outweigh the risks.
PrecautionsCaution in renal failure or when using nephrotoxic drugs
Drug Name
Ganciclovir (Cytovene, Vitrasert) -- Synthetic guanine derivative active against cytomegalovirus (CMV). An acyclic nucleoside analog of 2'-deoxyguanosine that inhibits replication of herpes viruses both in vitro and in vivo.
Levels of ganciclovir-triphosphate are as much as 100-fold greater in CMV-infected cells than in uninfected cells, possibly due to preferential phosphorylation of ganciclovir in virus-infected cells.
For patients who experience progression of CMV retinitis while receiving a maintenance treatment with either dosage form of ganciclovir, the re-induction regimen should be administered.
Adult Dose5 mg/kg IV q12h for 2 wk
Pediatric DoseNot established; discuss with pediatrician or infectious disease specialist
ContraindicationsDocumented hypersensitivity; do not use if absolute neutrophil count <500 million cells/L or the platelet count is <25 x 109 cells/L
InteractionsConcomitant administration with cytotoxic drugs such as dapsone, vinblastine, Adriamycin, pentamidine, flucytosine, vincristine, amphotericin B, trimethoprim/sulfamethoxazole combinations, or other nucleoside analogs may result in additive toxicity in bone marrow, spermatogonia, and germinal layers of skin and GI mucosa (coadminister only if potential benefits outweigh risks); coadministration with imipenem-cilastatin may cause generalized seizures (use only if potential benefits outweigh risks); serum creatinine may increase following concurrent use of ganciclovir with either cyclosporine or amphotericin B; in presence of probenecid, ganciclovir renal clearance is reduced; bioavailability may increase when didanosine is administered either 2 h prior to or simultaneously with ganciclovir; bioavailability of ganciclovir may decrease in presence of zidovudine, while bioavailability of zidovudine is increased in presence of ganciclovir
Pregnancy C - Safety for use during pregnancy has not been established.
PrecautionsClinical toxicity of ganciclovir includes granulocytopenia, anemia, and thrombocytopenia;
since oral ganciclovir is associated with higher rate of CMV retinitis progression, compared to IV formulation, use only when benefits outweigh risks (advanced HIV disease); half-life and plasma/serum concentrations of ganciclovir may be increased as a result of reduced renal clearance; dosages >6 mg/kg IV may result in increased toxicity; rapid infusions may result in increased toxicity; initially, reconstituted solutions of IV ganciclovir have a high pH (11); phlebitis or pain may occur at site of IV infusion despite further dilution in IV fluids; administration of ganciclovir should be accompanied by adequate hydration; photosensitization (photoallergy or phototoxicity) may occur
Drug Category: Anti-inflammatory agents -- Systemically interfere with events leading to inflammation.
Drug Name
Prednisone (Deltasone, Orasone, Meticorten) -- May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.
Adult Dose0.5-1 mg/kg/d PO qd or divided bid for 8 wk
Ophthalmic: 1 gtt q1h to qid
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections and fungal or tubercular skin infections; GI disease
InteractionsCoadministration with estrogens may decrease prednisone clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Pregnancy B - Usually safe but benefits must outweigh the risks.
PrecautionsAbrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use
Drug Category: Antiplatelets -- Inhibit the cyclooxygenase system, decreasing the level of thromboxane A2, which is a potent platelet activator.
Drug Name
Aspirin (Bayer Aspirin, Ascriptin, Anacin) -- Treats mild to moderate pain and headache. Inhibits prostaglandin synthesis, which prevents formation of platelet-aggregating thromboxane A2.
Adult Dose325 mg PO qd
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; liver damage, hypoprothrombinemia, vitamin K deficiency, bleeding disorders, nasal polyps, asthma; due to association of aspirin with Reye syndrome, do not use in children (<16 y) with flu
InteractionsEffects may decrease with antacids and urinary alkalinizers; corticosteroids decrease salicylate serum levels; additive hypoprothrombinemic effects and increased bleeding time may occur with coadministration of anticoagulants; may antagonize uricosuric effects of probenecid and increase toxicity of phenytoin and valproic acid; doses >2 g/d may potentiate glucose lowering effect of sulfonylurea drugs
Pregnancy D - Unsafe in pregnancy
PrecautionsMay cause transient decrease in renal function and aggravate chronic kidney disease; avoid use in patients with severe anemia, with history of blood coagulation defects, or taking anticoagulants
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Further Inpatient Care:

Further Outpatient Care:

In/Out Patient Meds:

Deterrence/Prevention:

Complications:

Prognosis:

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Medical/Legal Pitfalls:

  • The other eye must be observed.
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Caption: Picture 1. The white area is necrotic retina.
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Picture Type: Photo
Caption: Picture 2. Severe vitritis with occlusive arteriolitis
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Picture Type: Photo
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  • Blumenkranz MS, Culbertson WW, Clarkson JG, Dix R: Treatment of the acute retinal necrosis syndrome with intravenous acyclovir. Ophthalmology 1986 Mar; 93(3): 296-300[Medline].
  • Carney MD, Peyman GA, Goldberg MF, et al: Acute retinal necrosis. Retina 1986 Spring-Summer; 6(2): 85-94[Medline].
  • Duker JS, Blumenkranz MS: Diagnosis and management of the acute retinal necrosis (ARN) syndrome. Surv Ophthalmol 1991 Mar-Apr; 35(5): 327-43[Medline].
  • Fisher JP, Lewis ML, Blumenkranz M, et al: The acute retinal necrosis syndrome. Part 1: Clinical manifestations. Ophthalmology 1982 Dec; 89(12): 1309-16[Medline].
  • Gariano RF, Berreen JP, Cooney EL: Progressive outer retinal necrosis and acute retinal necrosis in fellow eyes of a patient with acquired immunodeficiency syndrome. Am J Ophthalmol 2001 Sep; 132(3): 421-3[Medline].
  • Holland GN: Standard diagnostic criteria for the acute retinal necrosis syndrome. Executive Committee of the American Uveitis Society. Am J Ophthalmol 1994 May 15; 117(5): 663-7[Medline].
  • Khurana RN, Charonis A, Samuel MA: Intravenous foscarnet in the management of acyclovir-resistant herpes simplex virus type 2 in acute retinal necrosis in children. Med Sci Monit 2005 Dec; 11(12): CS75-8[Medline].
  • Nussenblatt RB, Palestine AG: Acute retinal necrosis. In: Uveitis: Fundamentals and Clinical Practice. 1989: 407-14.
  • Rodriguez A, Calonge M, Pedroza-Seres M, et al: Referral patterns of uveitis in a tertiary eye care center. Arch Ophthalmol 1996 May; 114(5): 593-9[Medline].
  • Sergott RC, Anand R, Belmont JB, et al: Acute retinal necrosis neuropathy. Clinical profile and surgical therapy. Arch Ophthalmol 1989 May; 107(5): 692-6[Medline].
  • Sergott RC, Belmont JB, Savino PJ, et al: Optic nerve involvement in the acute retinal necrosis syndrome. Arch Ophthalmol 1985 Aug; 103(8): 1160-2[Medline].
  • Severin M, Neubauer H: Bilateral acute vascular retinal necrosis. Ophthalmologica 1981; 182(4): 199-203[Medline].
  • Tan JCH D, Byles MR, Stanford PA: Acute retinal necrosis in children caused by herpes simplex virus. Retina 2001; 21(4): 344-7[Medline].
  • Urayama A, Yamada N, Sasaki T: Unilateral acute uveitis with retinal periarteritis and detachment. Jpn J Clin Ophthalmol 1971; 25: 607.
  • Walters G, James TE: Viral causes of the acute retinal necrosis syndrome. Curr Opin Ophthalmol 2001 Jun; 12(3): 191-5[Medline].
  • Young NJ, Bird AC: Bilateral acute retinal necrosis. Br J Ophthalmol 1978 Sep; 62(9): 581-90[Medline].

Acute Retinal Necrosis excerpt