Acute retinal necrosis
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Faizan Sheraz, M.D. [2]; Luke Rusowicz-Orazem, B.S.
Overview
Acute retinal necrosis is a type of retinitis which can be associated with viral infections.
It was first characterized in 1971.[1][2]
One study indicated an incidence of 1 per 1.6 to 2.0 million.[3]
Historical Perspective
- Acute retinal necrosis was first officially classified as bilateral acute retinal necrosis in 1978 by N.J. Young and A.C. Bird.[4]
- The classification was applied to 4 cases of bilateral necrotizing retinitis, of which the patients developed bilateral confluent retinitis progressing to retinal detachment and phthisis despite corticosteroid and antibiotic therapy.[5]
- The first extension of the classification of acute retinal necrosis to unilateral cases was given in 1983 by Hayasaka S. et al.[6]
- They identified that cases of bilateral acute retinal necrosis and cases of Kirisawa-type uveitis presented nearly identical characteristics:[2][4]
- Periarteritis
- Opaque, dense vitreous
- Peripheral retinal exudates
- Retinal detachment
- Vision loss
- Resistance to antibiotic therapy
- Negative test results for bacterial infection
- They identified that cases of bilateral acute retinal necrosis and cases of Kirisawa-type uveitis presented nearly identical characteristics:[2][4]
- In the 1980s, emergence of pathological and electron findings from analysis of vitrectomy and enucleation specimens led to the discovery of acute retinal necrosis' cause as members of the herpes virus family.
- The official diagnostic criteria for acute retinal necrosis was proposed by the American Uveitis Society in 1994.
Classification
- Acute retinal necrosis (ARN) may be classified by staging and severity into the following:[7]
- Acute stage: Occurs at onset of disease and usually progresses past acute classification after a few weeks.
- Presents with coalescence of white, necrotic tissue in the peripheral retina.
- Vaso-occlusive retinal vasculitis is usually present.
- The optic nerve head of the affected eye will appear swollen, but the posterior pole will usually not be affected during the acute stage.
- Late stage: Is the natural progression of the disease and will present differentiating characteristics after a few weeks up to a few months.
- Characterized by a regression of the coalesced necrosis in the peripheral retina, presenting starkly contrasted necrotic/non-necrotic tissue and mild pigmentation scarring and increased vitreous debris
- Retinal detachment, severe vision loss, and potential blindness in the affected eye is indicative of late stage ARN.
- If the infection is bilateral, the second eye will usually present signs of ARN in the weeks and months following the initial symptom manifestation in the first eye.
- Acute stage: Occurs at onset of disease and usually progresses past acute classification after a few weeks.
- Acute retinal necrosis can also be classified by severity into the following:[8]
- Mild: Is used to characterize ARN that is stable and non-progressive.
- There is usually no sign of retinal detachment.
- Fulminant: ARN that is progressive and will usually lead to retinal detachment and further complications if untreated.
- Mild: Is used to characterize ARN that is stable and non-progressive.
Pathophysiology
Pathogenesis
- The pathogenesis of Acute retinal necrosis is characterized by retinal inflammation due to ocular viral infection:[9]
- Particles from Herpes simplex virus 1 (HSV-1), Herpes simplex virus 2 (HSV-2), and Varicella zoster virus (VZV) infiltrate the retina via various modes of transmission:[10]
- Epithelial penetration of the skin: transmitted through the ophthalmic branch of the Trigeminal nerve.
- Epithelial penetration of the conjunctiva: transmitted directly through the optic nerve.
- Epithelial penetration of the cornea: transmitted through the maxillary branch of the Trigeminal nerve.
- Epithelial penetration of the nasal cavity: transmitted through the Olfactory nerve in the Subarachnoid space.
- Acute retinal necrosis develops from HSV-1, HSV-2, and VZV due to the viruses' unique ability to transmit and replicate in the Central Nervous System (CNS), as well as their ability to transport anterograde through the optic nerve, establish latency, reactivate, and cause retinal inflammation.[11]
- Retinal inflammation is caused by the up-regulated production of cytokines.
- Particles from Herpes simplex virus 1 (HSV-1), Herpes simplex virus 2 (HSV-2), and Varicella zoster virus (VZV) infiltrate the retina via various modes of transmission:[10]
Genetics
- There is evidence of genetic predisposition to Acute retinal necrosis:
- Possession of the above antigens in their respective demographics are correlated to impaired immunity and increased predisposition to infection.
Associated Conditions
- Acute retinal necrosis is associated with the following ocular conditions:
Causes
- Acute retinal necrosis (ARN) is usually caused by the reactivation of the following pathogenic viruses in the Herpesviridae family:[17]
- Herpes simplex virus 1 (HSV-1)
- Herpes simplex virus 2 (HSV-2)
- Varicella-zoster virus (VZV)
- Less commonly, ARN can be caused by Epstein-Barr virus and cytomegalovirus.[9]
- VZV and HSV-1 are usually the causes of ARN in individuals older than 25 years.
- The majority of the ARN cases for individuals older than 50 years are caused by VZV and HSV-1.[8]
- HSV-2 is usually the cause of ARN in individuals younger than 25 years.
Differentiating Acute retinal necrosis from Other Diseases
- Acute retinal necrosis must be differentiated from other diseases that cause eye pain, conjunctival infection, photophobia, and vision loss. Accurate and prompt diagnosis is critical to prevent blindness and complications.[16][18][19][20]
- Differentiating Acute retinal necrosis from other diseases is crucial due to varying etiologies of ocular diseases, particularly to ensure the best prognosis by applying the proper therapy.
Epidemiology and Demographics
Incidence
- Research in the United Kingdom resulted in an estimated incidence of approximately 6.3 per 100,000 individuals.[22]
- There is evidence that this incidence is underestimated due to biases in case adjudication and under-reporting of data.[3]
- Worldwide, the increase of immunocompromised and aged populations in most countries evidences an increase in Acute retinal necrosis.
Age
- Acute retinal necrosis (ARN) developed from Herpes simplex virus 1 and Varicella-zoster virus is most common among patients older than 50 years.[8]
- Herpes simplex virus (HSV) 2 infection is more common among children and adolescents; the incidence of HSV-2 caused ARN is highest in children and young adults between age 9 and 22 years.
Gender
- There is no gender predisposition to Acute retinal necrosis.
Race
- There is no racial predisposition to Acute retinal necrosis.
Risk Factors
- Risk factors for the development of Acute retinal necrosis (ARN) include the following:
- For caucasian populations: possessing the HLA-DQw7, HLA-Bw62, and HLA-DR4 antigens are correlated to genetic predisposition to ARN.[12]
- For Japanese populations: possessing the HLA-Aw33, HLA-B44, and HLA-DRw6 antigens are correlated to genetic predisposition to ARN.[8]
- Experiencing encephalitis from herpes simplex virus[23]
- Immunocompromise from prior or concurrent disease.[24]
- Immunosuppresion from extended corticosteroid therapy.[25]
Screening
Natural History, Complications, and Prognosis
Natural History
Complications
Prognosis
Diagnosis
Diagnostic Criteria
The diagnosis of acute retinal necrosis is made when the following criteria are met:[26]
- One or more discrete foci of peripheral retinal necrosis, located outside of the major temporal vascular arcades
- Circumferential spread if antiviral therapy has not been administered
- Occlusive retinal vasculopathy
- A prominent vitreous or anterior chamber inflammation
- Rapid disease progression in the absence of therapy
Symptoms
- Symptoms of Acute retinal necrosis include the following:[3]
- Vision loss
- Blindness may be present in more severe cases
- Excessive sensitivity to light
- Ocular pain
- Flu symptoms
- Redness of the affected eye
- Floaters[27]
- Flashes[28]
- Vision loss
Physical Examination
Physical examination for acute retinal necrosis is remarkable for the following:[8]
Laboratory Findings
Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
- Empiric antimicrobial therapy
- Alternative regimen (1): Acyclovir 10 mg/kg IV q8h for 1-2 weeks followed by Valacyclovir 1 g IV q8h for 6 weeks to several months followed by Acyclovir 400 mg PO bid for chronic maintenance
- Alternative regimen (2), unresponsive: Foscarnet 1.2-2.4 mg/0.1 mL intravitreal injection 1-3 times per week AND (Ganciclovir 5 mg/kg IV q12 for 2 weeks followed by 5 mg/kg q24h for 5-7 weeks OR Foscarnet 60 mg/kg IV q8h for 2 weeks followed by 90-120 mg/kg IV q24h OR Cidofovir 5 mg/kg IV for 2 weeks followed by 5 mg/kg IV q2weeks) followed by (Acyclovir 400 mg PO bid for chronic maintenance OR Valganciclovir 900 mg PO qd for chronic maintenance)
- Note: Ganciclovir is administered for patients with suspected CMV acute retinal necrosis. Whereas Foscarnet is administered for patients who are not immunocompromised
- Pathogen-directed antimicrobial therapy
- HSV or VZV
- Preferred regimen: Acyclovir 10 mg/kg IV q8h for 1-2 weeks followed by Acyclovir 400 mg PO bid for chronic maintenance
- Alternative regimen: Acyclovir 10 mg/kg IV q8h for 1-2 weeks followed by Valacyclovir 1 g IV q8h for 6 weeks to several months followed by Acyclovir 400 mg PO bid for chronic maintenance
- Cytomegalovirus
- Preferred regimen: Foscarnet 1.2-2.4 mg/0.1 mL intravitreal injection 1-3 times per week AND Ganciclovir 5 mg/kg IV q12 for 2 weeks followed by 5 mg/kg q24h for 5-7 weeks followed by Valganciclovir 900 mg PO qd for chronic maintenance
Surgery
Prevention
See also
External links
- http://www.iceh.org.uk/files/tsno8/text/18.htm
- http://www.eyepathologist.org/disease.asp?IDNUM=301330
References
- ↑ "eMedicine - Acute Retinal Necrosis : Article by Andrew A Dahl, MD". Archived from the original on 16 February 2008. Retrieved 2008-02-05.
- ↑ 2.0 2.1 Urayama A, Yamada N, Sasaki T: Unilateral acute uveitis with retinal periarteritis and detachment. Jpn J Clin Ophthalmol 1971; 25: 607.
- ↑ 3.0 3.1 3.2 3.3 Muthiah MN, Michaelides M, Child CS, Mitchell SM (2007). "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. 91 (11): 1452–5. doi:10.1136/bjo.2007.114884. PMC 2095441. PMID 17504853.
- ↑ 4.0 4.1 Young NJ, Bird AC (1978). "Bilateral acute retinal necrosis". Br J Ophthalmol. 62 (9): 581–90. PMC 1043304. PMID 708676.
- ↑ 5.0 5.1 Flaxel CJ, Yeh S, Lauer AK (2013). "Combination systemic and intravitreal antiviral therapy in the management of acute retinal necrosis syndrome (an American Ophthalmological Society thesis)". Trans Am Ophthalmol Soc. 111: 133–44. PMC 3868412. PMID 24385671.
- ↑ Hayasaka S, Asano T, Yabata K, Ide A (1983). "Acute retinal necrosis". Br J Ophthalmol. 67 (7): 455–60. PMC 1040094. PMID 6860612.
- ↑ Gartry DS, Spalton DJ, Tilzey A, Hykin PG (1991). "Acute retinal necrosis syndrome". Br J Ophthalmol. 75 (5): 292–7. PMC 1042358. PMID 1645179.
- ↑ 8.0 8.1 8.2 8.3 8.4 8.5 Brydak-Godowska J, Borkowski P, Szczepanik S, Moneta-Wielgoś J, Kęcik D (2014). "Clinical manifestation of self-limiting acute retinal necrosis". Med. Sci. Monit. 20: 2088–96. doi:10.12659/MSM.890469. PMC 4226315. PMID 25356955.
- ↑ 9.0 9.1 Ganatra JB, Chandler D, Santos C, Kuppermann B, Margolis TP (2000). "Viral causes of the acute retinal necrosis syndrome". Am. J. Ophthalmol. 129 (2): 166–72. PMID 10682968.
- ↑ Grose C (2012). "Acute retinal necrosis caused by herpes simplex virus type 2 in children: reactivation of an undiagnosed latent neonatal herpes infection". Semin Pediatr Neurol. 19 (3): 115–8. doi:10.1016/j.spen.2012.02.005. PMC 3419358. PMID 22889540.
- ↑ Whitley, Richard; Kimberlin, David W.; Prober, Charles G. (2007). Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis. Cambridge, UK: Cambridge University Press. ISBN 978-0511545313.
- ↑ 12.0 12.1 Holland GN, Cornell PJ, Park MS, Barbetti A, Yuge J, Kreiger AE, Kaplan HJ, Pepose JS, Heckenlively JR, Culbertson WW (1989). "An association between acute retinal necrosis syndrome and HLA-DQw7 and phenotype Bw62, DR4". Am. J. Ophthalmol. 108 (4): 370–4. PMID 2801857.
- ↑ 13.0 13.1 Coisy S, Ebran JM, Milea D (2014). "Progressive outer retinal necrosis and immunosuppressive therapy in myasthenia gravis". Case Rep Ophthalmol. 5 (1): 132–7. doi:10.1159/000362662. PMC 4036147. PMID 24926266.
- ↑ 14.0 14.1 14.2 "Facts About Uveitis | National Eye Institute".
- ↑ 15.0 15.1 "CMV retinitis: MedlinePlus Medical Encyclopedia".
- ↑ 16.0 16.1 16.2 Davis JL (2012). "Diagnostic dilemmas in retinitis and endophthalmitis". Eye (Lond). 26 (2): 194–201. doi:10.1038/eye.2011.299. PMC 3272204. PMID 22116459.
- ↑ Pikkel YY, Pikkel J (2014). "Acute retinal necrosis in childhood". Case Rep Ophthalmol. 5 (2): 138–43. doi:10.1159/000363130. PMC 4049010. PMID 24932179.
- ↑ Dart JK (1986). "Eye disease at a community health centre". Br Med J (Clin Res Ed). 293 (6560): 1477–80. PMC 1342247. PMID 3099921.
- ↑ Leibowitz HM (2000). "The red eye". N Engl J Med. 343 (5): 345–51. doi:10.1056/NEJM200008033430507. PMID 10922425.
- ↑ University of Michigan Eyes Have it (2009)http://kellogg.umich.edu/theeyeshaveit/red-eye/
- ↑ Abu El-Asrar AM, Herbort CP, Tabbara KF (2009). "Differential diagnosis of retinal vasculitis". Middle East Afr J Ophthalmol. 16 (4): 202–18. doi:10.4103/0974-9233.58423. PMC 2855661. PMID 20404987.
- ↑ Cochrane TF, Silvestri G, McDowell C, Foot B, McAvoy CE (2012). "Acute retinal necrosis in the United Kingdom: results of a prospective surveillance study". Eye (Lond). 26 (3): 370–7, quiz 378. doi:10.1038/eye.2011.338. PMC 3298997. PMID 22281865.
- ↑ Vandercam T, Hintzen RQ, de Boer JH, Van der Lelij A (2008). "Herpetic encephalitis is a risk factor for retinal necrosis". Neurology. 71 (16): 1268–74. doi:10.1212/01.wnl.0000327615.99124.99. PMID 18852442.
- ↑ Moutschen MP, Scheen AJ, Lefebvre PJ (1992). "Impaired immune responses in diabetes mellitus: analysis of the factors and mechanisms involved. Relevance to the increased susceptibility of diabetic patients to specific infections". Diabete Metab. 18 (3): 187–201. PMID 1397473.
- ↑ Yamamoto JH, Boletti DI, Nakashima Y, Hirata CE, Olivalves E, Shinzato MM, Okay TS, Santo RM, Duarte MI, Kalil J (2003). "Severe bilateral necrotising retinitis caused by Toxoplasma gondii in a patient with systemic lupus erythematosus and diabetes mellitus". Br J Ophthalmol. 87 (5): 651–2. PMC 1771672. PMID 12714420.
- ↑ Holland GN (1994). "Standard diagnostic criteria for the acute retinal necrosis syndrome. Executive Committee of the American Uveitis Society". Am. J. Ophthalmol. 117 (5): 663–7. PMID 8172275.
- ↑ Ford JR, Tsui E, Lahey T, Zegans ME (2013). "Question: Can you identify this condition? Acute retinal necrosis". Can Fam Physician. 59 (12): 1307, 1308–10. PMC 3860929. PMID 24336545.
- ↑ "American Academy of Ophthalmology".