eMedicine Specialties > Ophthalmology > Retina

Acute Retinal Necrosis

Andrew A Dahl, MD, Director of Ophthalmology Teaching, Mid-Hudson Family Practice Institute, The Institute for Family Health; Assistant Professor of Surgery (Ophthalmology), New York College of Medicine
David T Wong, MD, FRCS(C), Associate Professor of Ophthalmology, Director of Fellowship Programs, Department of Ophthalmology, St Michael's Hospital, Faculty of Medicine, University of Toronto, Canada; Saad Waheeb, MB, BCh, FRCS(C), Consulting Staff, Department of Ophthalmology, King Abdulaziz University Hospital

Updated: Jan 21, 2009

Introduction

Background

Acute retinal necrosis (ARN) can lead to uveitis, retinal detachment, and blindness. Acute retinal necrosis was first described in the Japanese literature in 1971 and termed Kirisawa uveitis. During the past 3 decades, acute retinal necrosis syndrome has been a source of fear, frustration, and fascination for many ophthalmologists. Unfortunately, it usually is a visually devastating condition for the patient.

The white area is necrotic retina.

Pathophysiology

Acute retinal necrosis may be a result of dormant herpes simplex virus 1 (HSV-1), herpes simplex virus 2 (HSV-2), or varicella-herpes zoster virus (VZV) viral reactivation in the retina. The exact etiology of this reactivation is still elusive; however, an immunogenetic predisposition to the disease is likely.

Frequency

United States

Acute retinal necrosis accounts for 5.5% of uveitis cases over a 10-year period.¹

International

In Switzerland, acute retinal necrosis accounts for 1.7% of uveitic cases.

Mortality/Morbidity

Significant visual loss may occur. Retinal detachment complicates most cases (~75%) and is a major cause of legal blindness in acute retinal necrosis.

Race

No clear racial predilection exists.

Sex

This condition appears to have a predilection for males; however, the extent is not clear.

Age

Acute retinal necrosis is a disease of young healthy individuals aged 20-50 years.

• A bimodal age distribution possibly exists, peaking at approximately ages 20 and 50 years. This distribution may be related to differences in 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.

Clinical

History

Typically, acute retinal necrosis 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

Severe vitritis with occlusive arteriolitis.

Causes

Most cases of acute retinal necrosis have been reported to be caused by the following:²

• Varicella-zoster virus
• Herpes simplex type 1
• Herpes simplex type 2³

Differential Diagnoses

Other Problems to Be Considered

Reticulum cell sarcoma

Workup

Laboratory Studies

• Acute retinal necrosis (ARN) is a clinical diagnosis,^4,5 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, obtain the following:
  • Complete blood cell count
  • Renal function tests
  • Liver function tests

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 sheath⁶
• 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

Treatment

Medical Care

Acute retinal necrosis (ARN) treatment consists of the following:⁷

• Antiviral therapy, including intravenous acyclovir, oral valacyclovir, oral famciclovir, or intravitreal foscarnet, valacyclovir, or famciclovir.^8,9,10,11
• 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).
• C₃ F₈ (octafluoropropane/perfluoropropane) or other fluoridated gases for temporary absorbable intraocular tamponade

Consultations

Infectious disease specialist or internist

Medication

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Antivirals

Antivirals reduce progression of virus in affected eye as well as protection of the other eye.

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.

Dosing

Adult

1500 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

Not established; discuss with pediatrician or infectious disease specialist

Interactions

Concomitant use of probenecid or zidovudine prolongs half-life and increases CNS toxicity of acyclovir

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in renal failure or when using nephrotoxic drugs

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.

Dosing

Adult

5 mg/kg IV q12h for 2 wk
4.5 mg intravitreal implant for 5 to 8 mo; following depletion of ganciclovir, as evidenced by progression of retinitis, implant may be removed and replaced

Pediatric

Not established; discuss with pediatrician or infectious disease specialist

Interactions

Concomitant 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

Contraindications

Documented hypersensitivity; do not use if absolute neutrophil count <500 million cells/L or the platelet count is <25 x 10⁹ cells/L

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Clinical 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

Valacyclovir (Valtrex)

Prodrug rapidly converted to the active drug acyclovir. More expensive but has a more convenient dosing regimen than acyclovir.

Dosing

Adult

1 g tid until resolution; taper over 3-6 mo

Pediatric

<12 years: Not established
>12 years: Administer as in adults

Interactions

Probenecid, zidovudine, or cimetidine coadministration prolongs half-life and increases CNS toxicity of valacyclovir

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in renal failure (decrease dose) and coadministration of nephrotoxic drugs; associated with onset of hemolytic uremic syndrome

Famciclovir (Famvir)

After ingestion, drug is rapidly biotransformed into active compound penciclovir and phosphorylated by viral thymidine kinase. By competition with deoxyguanosine triphosphate, penciclovir triphosphate inhibits viral polymerase subsequently inhibiting viral DNA synthesis/replication.
Adjust dose in patients with renal insufficiency or hepatic disease.
Used against herpes simplex and varicella-zoster viruses.

Dosing

Adult

500 mg PO tid until resolution; taper over 3-6 mo

Pediatric

Not established

Interactions

Coadministration of probenecid or cimetidine may increase toxicity; coadministration increases bioavailability of digoxin

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in renal failure or coadministration of nephrotoxic drugs

Foscarnet (Foscavir)

Analog of pyrophosphate. Inhibits DNA polymerase of CMV and reverse transcriptase of HIV. Virostatic; renal excretion. As effective as ganciclovir. Median time to relapse on Rx is 53 d. Foscarnet/ganciclovir CMV retinitis trial: 234 newly diagnosed patients randomized. Same efficacy for controlling retinitis and preserving vision. Survival with foscarnet 12.6 mo versus 8.5 for ganciclovir group; mortality risk 1.79x. Controlling for antiretroviral use, still better survival with foscarnet. Foscarnet has anti-HIV activity but has more dose-limiting toxicity.

Dosing

Adult

Intravitreal injection: 2400 mcg/0.1 mL qwk

Pediatric

Administer as in adults

Interactions

Avoid administration with potentially nephrotoxic drugs (eg, aminoglycosides, amphotericin B, IV pentamidine) may increase nephrotoxicity (do not administer unless potential benefits outweigh risks); coadministration with IV pentamidine may cause hypocalcemia

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May cause decline in renal function; for correct dosing, obtain 24-h serum creatinine at baseline and continue to monitor (discontinue if serum creatinine <0.4 mL/min/kg); hydration may reduce nephrotoxicity
Carefully monitor electrolytes (eg, calcium, magnesium); assess for electrolyte and mineral level abnormalities if mild perioral numbness, paresthesias symptoms, or seizures; granulocytopenia and anemia may occur (regularly monitor CBC)
Infuse foscarnet solutions into veins with adequate blood flow to avoid local irritation; to avoid toxicity do not administer by rapid or bolus IV injection

Anti-inflammatory agents

These agents systemically interfere with events leading to inflammation.

Prednisone (Deltasone, Orasone, Meticorten)

May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.

Dosing

Adult

0.5-1 mg/kg/d PO qd or divided bid for 8 wk
Ophthalmic: 1 gtt q1h to qid

Pediatric

Not established

Interactions

Coadministration 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

Contraindications

Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections and fungal or tubercular skin infections; GI disease

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Abrupt 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

Antiplatelets

Antiplatelets inhibit the cyclooxygenase system, decreasing the level of thromboxane A₂, which is a potent platelet activator.

Aspirin (Bayer Aspirin, Ascriptin, Anacin)

Treats mild to moderate pain and headache. Inhibits prostaglandin synthesis, which prevents formation of platelet-aggregating thromboxane A2.

Dosing

Adult

325 mg PO qd

Pediatric

Not established

Interactions

Effects 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

Contraindications

Documented 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

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

May 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

Follow-up

Further Inpatient Care

• Check blood work.

Further Outpatient Care

• Observe patients for reactivation or retinal detachment.

Inpatient & Outpatient Medications

• Antivirals
  • Acyclovir, valacyclovir
  • Ganciclovir, famciclovir, foscarnet
• Anti-inflammatories
  • Start 24-48 hours after antiviral therapy is initiated.
  • Prednisone
• Antiplatelets (aspirin) - Start 24-48 hours after beginning antiviral therapy.

Deterrence/Prevention

• Prophylactic barrier laser to the peripheral retina posterior to the areas of retinal necrosis is required to reduce the risk of retinal detachment.

Complications

• Retinal detachment (75%)
• Anterior ischemic neuropathy
• Central retinal artery occlusion
• Cataract - From inflammation or steroids
• Glaucoma - From inflammation or steroids

Prognosis

• Visual prognosis is guarded if retinal detachment, anterior ischemic optic neuropathy, or central retinal artery occlusion occur.^12,1

Miscellaneous

Medicolegal Pitfalls

• The other eye must be observed.

Multimedia

Media file 1: The white area is necrotic retina.

Media file 2: Severe vitritis with occlusive arteriolitis.

References

1. Muthiah MN, Michaelides M, Child CS, Mitchell SM. 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. Nov 2007;91(11):1452-5. [Medline].

2. Walters G, James TE. Viral causes of the acute retinal necrosis syndrome. Curr Opin Ophthalmol. Jun 2001;12(3):191-5. [Medline].

3. Moesen I, Khemka S, Ayliffe W. Acute retinal necrosis secondary to herpes simplex virus type 2 with preexisting chorioretinal scarring. J Pediatr Ophthalmol Strabismus. Jan-Feb 2008;45(1):59-61. [Medline].

4. Duker JS, Blumenkranz MS. Diagnosis and management of the acute retinal necrosis (ARN) syndrome. Surv Ophthalmol. Mar-Apr 1991;35(5):327-43. [Medline].

5. Holland GN. Standard diagnostic criteria for the acute retinal necrosis syndrome. Executive Committee of the American Uveitis Society. Am J Ophthalmol. May 15 1994;117(5):663-7. [Medline].

6. Sergott RC, Belmont JB, Savino PJ, Fischer DH, Bosley TM, Schatz NJ. Optic nerve involvement in the acute retinal necrosis syndrome. Arch Ophthalmol. Aug 1985;103(8):1160-2. [Medline].

7. Aizman A. Treatment of acute retinal necrosis syndrome. Drugs Today (Barc). Aug 2006;42(8):545-51. [Medline].

8. Aizman A, Johnson MW, Elner SG. Treatment of acute retinal necrosis syndrome with oral antiviral medications. Ophthalmology. Feb 2007;114(2):307-12. [Medline].

9. Blumenkranz MS, Culbertson WW, Clarkson JG, Dix R. Treatment of the acute retinal necrosis syndrome with intravenous acyclovir. Ophthalmology. Mar 1986;93(3):296-300. [Medline].

10. Emerson GG, Smith JR, Wilson DJ, Rosenbaum JT, Flaxel CJ. Primary treatment of acute retinal necrosis with oral antiviral therapy. Ophthalmology. Dec 2006;113(12):2259-61. [Medline].

11. Khurana RN, Charonis A, Samuel MA, Gupta A, Tawansy KA. Intravenous foscarnet in the management of acyclovir-resistant herpes simplex virus type 2 in acute retinal necrosis in children. Med Sci Monit. Dec 2005;11(12):CS75-8. [Medline].

12. Lau CH, Missotten T, Salzmann J, Lightman SL. Acute retinal necrosis features, management, and outcomes. Ophthalmology. Apr 2007;114(4):756-62. [Medline].

13. Carney MD, Peyman GA, Goldberg MF, et al. Acute retinal necrosis. Retina. Spring-Summer 1986;6(2):85-94. [Medline].

14. Fisher JP, Lewis ML, Blumenkranz M, et al. The acute retinal necrosis syndrome. Part 1: Clinical manifestations. Ophthalmology. Dec 1982;89(12):1309-16. [Medline].

15. 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. Sep 2001;132(3):421-3. [Medline].

16. Nussenblatt RB, Palestine AG. Acute retinal necrosis. In: Uveitis: Fundamentals and Clinical Practice. 1989:407-14.

17. Park SS, Holz HA, Ravage ZB, Merrill PT, Nguyen QD. Diagnostic and therapeutic challenges. Acute retinal necrosis syndrome. Retina. Apr 2008;28(4):660-4. [Medline].

18. Rodriguez A, Calonge M, Pedroza-Seres M, et al. Referral patterns of uveitis in a tertiary eye care center. Arch Ophthalmol. May 1996;114(5):593-9. [Medline].

19. Severin M, Neubauer H. Bilateral acute vascular retinal necrosis. Ophthalmologica. 1981;182(4):199-203. [Medline].

20. Tan JCH, Byles D, Stanford MR, Frith PA, Graham EM. Acute retinal necrosis in children caused by herpes simplex virus. Retina. 2001;21(4):344-7. [Medline].

21. Urayama A, Yamada N, Sasaki T. Unilateral acute uveitis with retinal periarteritis and detachment. Jpn J Clin Ophthalmol. 1971;25:607.

22. Young NJ, Bird AC. Bilateral acute retinal necrosis. Br J Ophthalmol. Sep 1978;62(9):581-90. [Medline].

Keywords

ARN, bilateral acute retinal necrosis, BARN, bilateral ARN, Kirisawa's uveitis, Kirisawa uveitis, blindness, retinal detachment, uveitis, red eye, eye pain, periorbital pain, decreased vision, vision problems, herpes simplex virus 1, HSV-1, herpes simplex virus 2, HSV-2, varicella-herpes zoster virus, VZV

Contributor Information and Disclosures

Author

Andrew A Dahl, MD, Director of Ophthalmology Teaching, Mid-Hudson Family Practice Institute, The Institute for Family Health; Assistant Professor of Surgery (Ophthalmology), New York College of Medicine
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
Disclosure: Nothing to disclose.

Coauthor(s)

David T Wong, MD, FRCS(C), Associate Professor of Ophthalmology, Director of Fellowship Programs, Department of Ophthalmology, St Michael's Hospital, Faculty of Medicine, University of Toronto, Canada
David T Wong, MD, FRCS(C) is a member of the following medical societies: Alpha Omega Alpha, American Academy of Ophthalmology, American Society of Retina Specialists, Association for Research in Vision and Ophthalmology, Canadian Medical Association, Canadian Ophthalmological Society, College of Physicians and Surgeons of Ontario, Ontario Medical Association, and Royal College of Physicians and Surgeons of Canada
Disclosure: Alcon Consulting fee Consulting; Novartis Consulting fee Consulting; Alcon Grant/research funds Other; Labtician Consulting fee Consulting

Saad Waheeb, MB, BCh, FRCS(C), Consulting Staff, Department of Ophthalmology, King Abdulaziz University Hospital
Saad Waheeb, MB, BCh, FRCS(C) is a member of the following medical societies: American Academy of Ophthalmology, Canadian Ophthalmological Society, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Medical Editor

Brian A Phillpotts, MD, Former Vitreo-Retinal Service Director, Former Program Director, Clinical Assistant Professor, Department of Ophthalmology, Howard University College of Medicine
Brian A Phillpotts, MD is a member of the following medical societies: American Academy of Ophthalmology, American Diabetes Association, American Medical Association, and National Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Steve Charles, MD, Director of Charles Retina Institute; Clinical Professor, Department of Ophthalmology, University of Tennessee College of Medicine
Steve Charles, MD is a member of the following medical societies: American Academy of Ophthalmology, American Society of Retina Specialists, Club Jules Gonin, Macula Society, and Retina Society
Disclosure: Alcon Laboratories Consulting fee Consulting; OptiMedica Ownership interest Consulting

CME Editor

Lance L Brown, OD, MD, Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri
Disclosure: Nothing to disclose.

Chief Editor

Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology
Disclosure: Nothing to disclose.

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