Progressive outer retinal necrosis: Difference between revisions
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==Historical Perspective== | ==Historical Perspective== | ||
* | *In 1987, a clinical presentation of [[necrotizing]] [[retinitis]] occurring specifically in [[immunocompromised]] individuals was first documented by Jabs DA et al.<ref name="pmid3602608">{{cite journal |vauthors=Jabs DA, Schachat AP, Liss R, Knox DL, Michels RG |title=Presumed varicella zoster retinitis in immunocompromised patients |journal=Retina (Philadelphia, Pa.) |volume=7 |issue=1 |pages=9–13 |year=1987 |pmid=3602608 |doi= |url=}}</ref> | ||
* | *In 1990, progressive outer retinal necrosis (PORN) was first identified by Forster, DJ et al. <ref name="pmid2220967">{{cite journal |vauthors=Forster DJ, Dugel PU, Frangieh GT, Liggett PE, Rao NA |title=Rapidly progressive outer retinal necrosis in the acquired immunodeficiency syndrome |journal=Am. J. Ophthalmol. |volume=110 |issue=4 |pages=341–8 |year=1990 |pmid=2220967 |doi= |url=}}</ref> | ||
**It was identified and differentiated from [[acute retinal necrosis]] by its rapid progression, unresponsiveness to [[antiviral]] therapy [[Acyclovir (injection)|(acyclovir)]], and resultant [[retinal detachment]]. | **It was identified and differentiated from [[acute retinal necrosis]] by its rapid progression, unresponsiveness to [[antiviral]] therapy [[Acyclovir (injection)|(acyclovir)]], and resultant [[retinal detachment]]. | ||
**A study of two [[HIV]]-positive individuals led to the identification of [[Varicella-zoster infection]] as the cause of PORN | **A study of two [[HIV]]-positive individuals led to the identification of [[Varicella-zoster infection]] as the cause of PORN | ||
**[[Immunocompromised]] status was recognized as an important means of differentiating PORN patients from [[acute retinal necrosis]] patients | **[[Immunocompromised]] status was recognized as an important means of differentiating PORN patients from [[acute retinal necrosis]] patients | ||
==Classification== | ==Classification== | ||
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==Pathophysiology== | ==Pathophysiology== | ||
===Pathogenesis=== | ===Pathogenesis=== | ||
The pathogenesis of progressive outer retinal necrosis (PORN) is characterized by [[retinal]] [[necrosis]] due to ocular [[viral]] infection.<ref name="MoorthyWeinberg1997">{{cite journal|last1=Moorthy|first1=R. S|last2=Weinberg|first2=D. V|last3=Teich|first3=S. A|last4=Berger|first4=B. B|last5=Minturn|first5=J. T|last6=Kumar|first6=S.|last7=Rao|first7=N. A|last8=Fowell|first8=S. M|last9=Loose|first9=I. A|last10=Jampol|first10=L. M|title=Management of varicella zoster virus retinitis in AIDS|journal=British Journal of Ophthalmology|volume=81|issue=3|year=1997|pages=189–194|issn=0007-1161|doi=10.1136/bjo.81.3.189}}</ref> | |||
[[Viral]] particles infiltrate the [[retina]] via various modes of transmission:<ref name="pmid22889540">{{cite journal |vauthors=Grose C |title=Acute retinal necrosis caused by herpes simplex virus type 2 in children: reactivation of an undiagnosed latent neonatal herpes infection |journal=Semin Pediatr Neurol |volume=19 |issue=3 |pages=115–8 |year=2012 |pmid=22889540 |pmc=3419358 |doi=10.1016/j.spen.2012.02.005 |url=}}</ref> | |||
*[[Epithelial]] penetration of the skin: transmitted through the [[Ophthalmic nerve|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|maxillary]] branch of the [[trigeminal nerve]] | |||
*[[Epithelial]] penetration of the [[nasal cavity]]: transmitted through the [[olfactory nerve]] in the [[subarachnoid space]] | |||
[[Retinal]] [[inflammation]] is caused by the up-regulated production of [[cytokines]]. | |||
*[[Retinal]] [[necrosis]] occurs due to the [[vascular]] [[occlusion]] resulting in white-yellow [[necrotic]] [[lesions]] that begin in the [[outer]] layers of the [[retina]], coalesce, and spread inward without intervention.<ref name="YuFreund2015">{{cite journal|last1=Yu|first1=Suqin|last2=Freund|first2=K. Bailey|title=Could Progressive Outer Retinal Necrosis Begin With Retinal Deep Capillary Ischemia?|journal=JAMA Ophthalmology|volume=133|issue=1|year=2015|pages=110|issn=2168-6165|doi=10.1001/jamaophthalmol.2014.3548}}</ref> | |||
===Associated Conditions=== | ===Associated Conditions=== | ||
Progressive outer retinal necrosis is associated with the following ocular conditions: | |||
*[[Acute retinal necrosis]]<ref name="pmid22889540">{{cite journal |vauthors=Grose C |title=Acute retinal necrosis caused by herpes simplex virus type 2 in children: reactivation of an undiagnosed latent neonatal herpes infection |journal=Semin Pediatr Neurol |volume=19 |issue=3 |pages=115–8 |year=2012 |pmid=22889540 |pmc=3419358 |doi=10.1016/j.spen.2012.02.005 |url=}}</ref> | |||
**[[Uveitis]]<ref name="urlFacts About Uveitis | National Eye Institute">{{cite web |url=https://nei.nih.gov/health/uveitis/uveitis |title=Facts About Uveitis | National Eye Institute |format= |work= |accessdate=}}</ref> | **[[Uveitis]]<ref name="urlFacts About Uveitis | National Eye Institute">{{cite web |url=https://nei.nih.gov/health/uveitis/uveitis |title=Facts About Uveitis | National Eye Institute |format= |work= |accessdate=}}</ref> | ||
*[[Cytomegalovirus retinitis]]<ref name="urlCMV retinitis: MedlinePlus Medical Encyclopedia">{{cite web |url=https://medlineplus.gov/ency/article/000665.htm |title=CMV retinitis: MedlinePlus Medical Encyclopedia |format= |work= |accessdate=}}</ref> | |||
*Toxoplasmic chorioretinitis<ref name="pmid22116459">{{cite journal |vauthors=Davis JL |title=Diagnostic dilemmas in retinitis and endophthalmitis |journal=Eye (Lond) |volume=26 |issue=2 |pages=194–201 |year=2012 |pmid=22116459 |pmc=3272204 |doi=10.1038/eye.2011.299 |url=}}</ref> | |||
*[[Endophthalmitis]] | |||
PORN is often associated with [[HIV AIDS|AIDS]] as a complication of [[immunocompromised]] status.<ref name="pmid8824984">{{cite journal |vauthors=Galindez OA, Sabates NR, Whitacre MM, Sabates FN |title=Rapidly progressive outer retinal necrosis caused by varicella zoster virus in a patient infected with human immunodeficiency virus |journal=Clin. Infect. Dis. |volume=22 |issue=1 |pages=149–51 |year=1996 |pmid=8824984 |doi= |url=}}</ref> | |||
==Causes== | ==Causes== | ||
Progressive outer retinal necrosis (PORN) is primarily caused by [[Varicella zoster virus]] (VZV), and is less commonly caused by [[Cytomegalovirus]] (CMV), [[Herpes simplex virus|Herpes simplex virus 1]], and rarely BK Virus. PORN usually appears in [[immunocompromise|immunocompromised]] individuals, usually as a complication of diseases such as [[AIDS]] or from [[chemotherapy]].<ref name="pmid8090452">{{cite journal |vauthors=Engstrom RE, Holland GN, Margolis TP, Muccioli C, Lindley JI, Belfort R, Holland SP, Johnston WH, Wolitz RA, Kreiger AE |title=The progressive outer retinal necrosis syndrome. A variant of necrotizing herpetic retinopathy in patients with AIDS |journal=Ophthalmology |volume=101 |issue=9 |pages=1488–502 |year=1994 |pmid=8090452 |doi= |url=}}</ref><ref name="pmid11137426">{{cite journal |vauthors=Austin RB |title=Progressive outer retinal necrosis syndrome: a comprehensive review of its clinical presentation, relationship to immune system status, and management |journal=Clin. Eye Vis. Care |volume=12 |issue=3-4 |pages=119–129 |year=2000 |pmid=11137426 |doi= |url=}}</ref> | |||
===Viral=== | |||
*[[Varicella zoster virus]] | |||
*[[Cytomegalovirus]]<ref name="pmid26209386">{{cite journal |vauthors=Sfeir M |title=Cytomegalovirus implicated in a case of progressive outer retinal necrosis (PORN) |journal=J. Clin. Virol. |volume=69 |issue= |pages=86–90 |year=2015 |pmid=26209386 |doi=10.1016/j.jcv.2015.04.006 |url=}}</ref> | |||
*[[Herpes simplex virus|Herpes simplex virus 1]] (HSV-1)<ref name="GoreGore2012">{{cite journal|last1=Gore|first1=Daniel M.|last2=Gore|first2=Sri K.|last3=Visser|first3=Linda|title=Progressive Outer Retinal Necrosis|journal=Archives of Ophthalmology|volume=130|issue=6|year=2012|issn=0003-9950|doi=10.1001/archophthalmol.2011.2622}}</ref> | |||
*BK Virus<ref name="pmid25846017">{{cite journal |vauthors=Turno-Kręcicka A, Boratyńska M, Tomczyk-Socha M, Mazanowska O |title=Progressive outer retinal necrosis in immunocompromised kidney allograft recipient |journal=Transpl Infect Dis |volume=17 |issue=3 |pages=400–5 |year=2015 |pmid=25846017 |doi=10.1111/tid.12386 |url=}}</ref> | |||
==Differentiating {{PAGENAME}} from Other Diseases== | ==Differentiating {{PAGENAME}} from Other Diseases== | ||
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*Abnormal [[retinal]] [[pigmentation]] | *Abnormal [[retinal]] [[pigmentation]] | ||
*Absence or minimal presence of [[anterior chamber]] or [[vitreous]] [[inflammation]], as well as absence of [[scleritis]]<ref name="pmid24926266">{{cite journal |vauthors=Coisy S, Ebran JM, Milea D |title=Progressive outer retinal necrosis and immunosuppressive therapy in myasthenia gravis |journal=Case Rep Ophthalmol |volume=5 |issue=1 |pages=132–7 |year=2014 |pmid=24926266 |pmc=4036147 |doi=10.1159/000362662 |url=}}</ref> | *Absence or minimal presence of [[anterior chamber]] or [[vitreous]] [[inflammation]], as well as absence of [[scleritis]]<ref name="pmid24926266">{{cite journal |vauthors=Coisy S, Ebran JM, Milea D |title=Progressive outer retinal necrosis and immunosuppressive therapy in myasthenia gravis |journal=Case Rep Ophthalmol |volume=5 |issue=1 |pages=132–7 |year=2014 |pmid=24926266 |pmc=4036147 |doi=10.1159/000362662 |url=}}</ref> | ||
**This is an important | **This is an important for differentiating progressive outer retinal necrosis from [[acute retinal necrosis]] | ||
===Laboratory Findings=== | ===Laboratory Findings=== | ||
Laboratory findings associated with progressive outer retinal necrosis (PORN) are those used to | Laboratory findings associated with progressive outer retinal necrosis (PORN) are those used to confirm the [[Varicella zoster virus]] (VZV) infection, obtained from [[aqueous humor]] or the [[vitreous]]. Useful laboratory techniques may include:<ref name="pmid17505729">{{cite journal |vauthors=Matos K, Muccioli C, Belfort Junior R, Rizzo LV |title=Correlation between clinical diagnosis and PCR analysis of serum, aqueous, and vitreous samples in patients with inflammatory eye disease |journal=Arq Bras Oftalmol |volume=70 |issue=1 |pages=109–14 |year=2007 |pmid=17505729 |doi= |url=}}</ref> | ||
*Qualitative and | *Qualitative and real-time [[polymerase chain reaction]] may produce genomic evidence of VZV infection with high specificity<ref name="pmid24926266">{{cite journal |vauthors=Coisy S, Ebran JM, Milea D |title=Progressive outer retinal necrosis and immunosuppressive therapy in myasthenia gravis |journal=Case Rep Ophthalmol |volume=5 |issue=1 |pages=132–7 |year=2014 |pmid=24926266 |pmc=4036147 |doi=10.1159/000362662 |url=}}</ref><ref name="pmid23035203">{{cite journal |vauthors=Wilson DA, Yen-Lieberman B, Schindler S, Asamoto K, Schold JD, Procop GW |title=Should varicella-zoster virus culture be eliminated? A comparison of direct immunofluorescence antigen detection, culture, and PCR, with a historical review |journal=J. Clin. Microbiol. |volume=50 |issue=12 |pages=4120–2 |year=2012 |pmid=23035203 |pmc=3502980 |doi=10.1128/JCM.06753-11 |url=}}</ref> | ||
*Viral cultures may reveal evidence of VZV infection indicative of PORN | *Viral cultures may reveal evidence of VZV infection indicative of PORN | ||
**Retinochoroidal [[biopsy]] may be performed to obtain a culture sample, in addition to direct sampling from the [[aqueous humor]] | **Retinochoroidal [[biopsy]] may be performed to obtain a culture sample, in addition to direct sampling from the [[aqueous humor]]<ref name="pmid8824984">{{cite journal |vauthors=Galindez OA, Sabates NR, Whitacre MM, Sabates FN |title=Rapidly progressive outer retinal necrosis caused by varicella zoster virus in a patient infected with human immunodeficiency virus |journal=Clin. Infect. Dis. |volume=22 |issue=1 |pages=149–51 |year=1996 |pmid=8824984 |doi= |url=}}</ref> | ||
**Diagnosis via viral culture alone is not recommended due to the low specificity and sensitivity (53.7% and 46.3%, respectively), indicating a high chance of obtaining a false-negative.<ref name="pmid23035203">{{cite journal |vauthors=Wilson DA, Yen-Lieberman B, Schindler S, Asamoto K, Schold JD, Procop GW |title=Should varicella-zoster virus culture be eliminated? A comparison of direct immunofluorescence antigen detection, culture, and PCR, with a historical review |journal=J. Clin. Microbiol. |volume=50 |issue=12 |pages=4120–2 |year=2012 |pmid=23035203 |pmc=3502980 |doi=10.1128/JCM.06753-11 |url=}}</ref> | **Diagnosis via viral culture alone is not recommended due to the low specificity and sensitivity (53.7% and 46.3%, respectively), indicating a high chance of obtaining a false-negative.<ref name="pmid23035203">{{cite journal |vauthors=Wilson DA, Yen-Lieberman B, Schindler S, Asamoto K, Schold JD, Procop GW |title=Should varicella-zoster virus culture be eliminated? A comparison of direct immunofluorescence antigen detection, culture, and PCR, with a historical review |journal=J. Clin. Microbiol. |volume=50 |issue=12 |pages=4120–2 |year=2012 |pmid=23035203 |pmc=3502980 |doi=10.1128/JCM.06753-11 |url=}}</ref> | ||
*[[ | *[[Immunofluorescence]] may reveal [[antibodies]] indicative of VZV infection<ref name="pmid18159535">{{cite journal |vauthors=Singh A, Preiksaitis J, Ferenczy A, Romanowski B |title=The laboratory diagnosis of herpes simplex virus infections |journal=Can J Infect Dis Med Microbiol |volume=16 |issue=2 |pages=92–8 |year=2005 |pmid=18159535 |pmc=2095011 |doi= |url=}}</ref> | ||
*Detection of indicative [[Varicella zoster virus]] [[antibodies]] via Goldmann- | *Detection of indicative [[Varicella zoster virus]] [[antibodies]] via Goldmann-Witmer coefficient<ref name="pmid16458686">{{cite journal |vauthors=De Groot-Mijnes JD, Rothova A, Van Loon AM, Schuller M, Ten Dam-Van Loon NH, De Boer JH, Schuurman R, Weersink AJ |title=Polymerase chain reaction and Goldmann-Witmer coefficient analysis are complimentary for the diagnosis of infectious uveitis |journal=Am. J. Ophthalmol. |volume=141 |issue=2 |pages=313–8 |year=2006 |pmid=16458686 |doi=10.1016/j.ajo.2005.09.017 |url=}}</ref> | ||
===Imaging Findings=== | ===Imaging Findings=== | ||
*[[Ophthalmoscopy]] is the imaging modality of choice for | *[[Ophthalmoscopy]] is the imaging modality of choice for progressive outer retinal necrosis and is characterized by the following findings:<ref name="pmid24926266">{{cite journal |vauthors=Coisy S, Ebran JM, Milea D |title=Progressive outer retinal necrosis and immunosuppressive therapy in myasthenia gravis |journal=Case Rep Ophthalmol |volume=5 |issue=1 |pages=132–7 |year=2014 |pmid=24926266 |pmc=4036147 |doi=10.1159/000362662 |url=}}</ref><ref name="pmid17460434">{{cite journal |vauthors=You YS, Lee SJ, Lee SH, Park CH, Kwon OW |title=Progressive outer retinal necrosis combined with vitreous hemorrhage in a patient with acquired immunodeficiency syndrome |journal=Korean J Ophthalmol |volume=21 |issue=1 |pages=51–4 |year=2007 |pmid=17460434 |pmc=2629688 |doi=10.3341/kjo.2007.21.1.51 |url=}}</ref><ref name="pmid8824984">{{cite journal |vauthors=Galindez OA, Sabates NR, Whitacre MM, Sabates FN |title=Rapidly progressive outer retinal necrosis caused by varicella zoster virus in a patient infected with human immunodeficiency virus |journal=Clin. Infect. Dis. |volume=22 |issue=1 |pages=149–51 |year=1996 |pmid=8824984 |doi= |url=}}</ref><ref name="pmid25100911">{{cite journal |vauthors=Al-Dhibi HA, Al-Mahmood AM, Arevalo JF |title=A systematic approach to emergencies in uveitis |journal=Middle East Afr J Ophthalmol |volume=21 |issue=3 |pages=251–8 |year=2014 |pmid=25100911 |pmc=4123279 |doi=10.4103/0974-9233.134687 |url=}}</ref> | ||
**[[Retinal]] opacity | **[[Retinal]] opacity | ||
**Superficial [[retinal]] [[hemorrhage]] | **Superficial [[retinal]] [[hemorrhage]] | ||
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**[[Retinal]] and [[choroidal]] detachment | **[[Retinal]] and [[choroidal]] detachment | ||
**White-yellow, multifocal [[retinal]] [[lesions]] with "cherry red spot" central [[macula]] | **White-yellow, multifocal [[retinal]] [[lesions]] with "cherry red spot" central [[macula]] | ||
**Absence of [[vitreous]] or [[anterior chamber]] [[inflammation]], important in | **Absence of [[vitreous]] or [[anterior chamber]] [[inflammation]], which is important in differentiating PORN from [[acute retinal necrosis]] | ||
*Fundus autofluorescence may present with the following findings, indicative of | *Fundus autofluorescence may present with the following findings, indicative of progressive outer retinal necrosis:<ref name="pmid20337261">{{cite journal |vauthors=Yeh S, Wong WT, Weichel ED, Lew JC, Chew EY, Nussenblatt RB |title=Fundus Autofluorescence and OCT in the Management of Progressive Outer Retinal Necrosis |journal=Ophthalmic Surg Lasers Imaging |volume= |issue= |pages=1–4 |year=2010 |pmid=20337261 |pmc=3265678 |doi=10.3928/15428877-20100216-14 |url=}}</ref> | ||
**Hyper and hypo-fluorescence of the [[retina]] from visible tissue degradation from the accumulation of [[lipofuscin]] | **Hyper- and hypo-fluorescence of the [[retina]] from visible tissue degradation from the accumulation of [[lipofuscin]] | ||
***The changes are indicative of [[photoreceptor]] death and inflammatory tissue | ***The changes are indicative of [[photoreceptor]] death and inflammatory tissue | ||
*Optical coherence tomography may present with the following findings: | *[[Optical coherence tomography]] may present with the following findings: | ||
**Thickened retinal opacification | **Thickened retinal opacification | ||
**Lower reflectivity and disorganization of the outer [[retina]], displaying signs of [[inflammation]] and degradation | **Lower reflectivity and disorganization of the outer [[retina]], displaying signs of [[inflammation]] and degradation | ||
===Other Diagnostic Studies=== | ===Other Diagnostic Studies=== | ||
There are no other diagnostic studies associated with | There are no other diagnostic studies associated with progressive outer retinal necrosis. | ||
==Treatment== | ==Treatment== | ||
===Medical Therapy=== | ===Medical Therapy=== | ||
The mainstay of therapy for | The mainstay of therapy for progressive outer retinal necrosis (PORN) is [[HIV AIDS medical therapy|Highly Active Anti-Retroviral Therapy]] (HAART), consisting of the following regimens:<ref name="pmid9135381">{{cite journal |vauthors=Moorthy RS, Weinberg DV, Teich SA, Berger BB, Minturn JT, Kumar S, Rao NA, Fowell SM, Loose IA, Jampol LM |title=Management of varicella zoster virus retinitis in AIDS |journal=Br J Ophthalmol |volume=81 |issue=3 |pages=189–94 |year=1997 |pmid=9135381 |pmc=1722141 |doi= |url=}}</ref><ref name="pmid8824984">{{cite journal |vauthors=Galindez OA, Sabates NR, Whitacre MM, Sabates FN |title=Rapidly progressive outer retinal necrosis caused by varicella zoster virus in a patient infected with human immunodeficiency virus |journal=Clin. Infect. Dis. |volume=22 |issue=1 |pages=149–51 |year=1996 |pmid=8824984 |doi= |url=}}</ref> | ||
*'''Empiric antimicrobrial therapy''' | *'''Empiric antimicrobrial therapy''' | ||
**Preferred regimen: [[Ganciclovir]] 5mg/kg IV q24h {{and}} [[Foscarnet]] 90-120mg/kg IV q24h | **Preferred regimen: [[Ganciclovir]] 5mg/kg IV q24h {{and}} [[Foscarnet]] 90-120mg/kg IV q24h | ||
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**Alternative regimen (2): [[Acyclovir]] 15 mg/kg IV q8h {{or}} [[Acyclovir]] 15 mg/kg IV q8h | **Alternative regimen (2): [[Acyclovir]] 15 mg/kg IV q8h {{or}} [[Acyclovir]] 15 mg/kg IV q8h | ||
*Note: The combination antimicrobial therapy of [[Ganciclovir]] and [[Foscarnet]] is recommended as the most effective treatment regiment for halting progression of PORN. Single antimicrobrial therapy is not usually recommended.<ref name="pmid9547773">{{cite journal |vauthors=Ciulla TA, Rutledge BK, Morley MG, Duker JS |title=The progressive outer retinal necrosis syndrome: successful treatment with combination antiviral therapy |journal=Ophthalmic Surg Lasers |volume=29 |issue=3 |pages=198–206 |year=1998 |pmid=9547773 |doi= |url=}}</ref> | *Note: The combination antimicrobial therapy of [[Ganciclovir]] and [[Foscarnet]] is recommended as the most effective treatment regiment for halting the progression of PORN. Single antimicrobrial therapy is not usually recommended.<ref name="pmid9547773">{{cite journal |vauthors=Ciulla TA, Rutledge BK, Morley MG, Duker JS |title=The progressive outer retinal necrosis syndrome: successful treatment with combination antiviral therapy |journal=Ophthalmic Surg Lasers |volume=29 |issue=3 |pages=198–206 |year=1998 |pmid=9547773 |doi= |url=}}</ref> | ||
===Surgery=== | ===Surgery=== | ||
Surgery is not the first-line treatment option for patients with | Surgery is not the first-line treatment option for patients with progressive outer retinal necrosis; it is primarily indicated when there is risk of complications, including [[retinal detachment]] and tissue [[atrophy]].<ref name="pmid26035758">{{cite journal |vauthors=Shantha JG, Weissman HM, Debiec MR, Albini TA, Yeh S |title=Advances in the management of acute retinal necrosis |journal=Int Ophthalmol Clin |volume=55 |issue=3 |pages=1–13 |year=2015 |pmid=26035758 |pmc=4567584 |doi=10.1097/IIO.0000000000000077 |url=}}</ref> | ||
===Vitrectomy=== | ===Vitrectomy=== | ||
*[[Vitrectomy]] may be indicated both before and after occurrence of [[retinal detachment]] to improve visual prognosis.<ref name="pmid22937510">{{cite journal |vauthors=Luo YH, Duan XC, Chen BH, Tang LS, Guo XJ |title=Efficacy and necessity of prophylactic vitrectomy for acute retinal necrosis syndrome |journal=Int J Ophthalmol |volume=5 |issue=4 |pages=482–7 |year=2012 |pmid=22937510 |pmc=3428546 |doi=10.3980/j.issn.2222-3959.2012.04.15 |url=}}</ref> | *[[Vitrectomy]] may be indicated both before and after occurrence of [[retinal detachment]] to improve visual prognosis.<ref name="pmid22937510">{{cite journal |vauthors=Luo YH, Duan XC, Chen BH, Tang LS, Guo XJ |title=Efficacy and necessity of prophylactic vitrectomy for acute retinal necrosis syndrome |journal=Int J Ophthalmol |volume=5 |issue=4 |pages=482–7 |year=2012 |pmid=22937510 |pmc=3428546 |doi=10.3980/j.issn.2222-3959.2012.04.15 |url=}}</ref> | ||
**[[Prophylactic]] [[vitrectomy]] can be effective in removing [[inflammation]] factors | **[[Prophylactic]] [[vitrectomy]] can be effective in removing [[inflammation]] factors and preventing [[retinal detachment]] by removing or preventing the spread of pre-existing [[lesions]] and [[necrotic]] tissue.<ref name="pmid18584565">{{cite journal |vauthors=Kawaguchi T, Spencer DB, Mochizuki M |title=Therapy for acute retinal necrosis |journal=Semin Ophthalmol |volume=23 |issue=4 |pages=285–90 |year=2008 |pmid=18584565 |doi=10.1080/08820530802111192 |url=}}</ref> | ||
**Remedial [[ | **Remedial [[vitrectomy]] in patients experiencing [[retinal detachment]] can lead to improved visual prognosis by [[retinal]] reattachment.<ref name="pmid1873262">{{cite journal |vauthors=McDonald HR, Lewis H, Kreiger AE, Sidikaro Y, Heckenlively J |title=Surgical management of retinal detachment associated with the acute retinal necrosis syndrome |journal=Br J Ophthalmol |volume=75 |issue=8 |pages=455–8 |year=1991 |pmid=1873262 |pmc=1042429 |doi= |url=}}</ref> | ||
===Prophylactic Laser Retinopexy=== | ===Prophylactic Laser Retinopexy=== | ||
*Prophylactic laser retinopexy may be indicated to prevent [[retinal detachment]] by [[Laser photocoagulation|photocoagulation]], creating posterior chorioretinal adhesions.<ref name="pmid18723739">{{cite journal |vauthors=Park JJ, Pavesio C |title=Prophylactic laser photocoagulation for acute [[retinal]] [[necrosis]]. Does it raise more questions than answers? |journal=Br J Ophthalmol |volume=92 |issue=9 |pages=1161–2 |year=2008 |pmid=18723739 |doi=10.1136/bjo.2008.147181 |url=}}</ref> | *Prophylactic laser retinopexy may be indicated to prevent [[retinal detachment]] by [[Laser photocoagulation|photocoagulation]], creating posterior chorioretinal adhesions.<ref name="pmid18723739">{{cite journal |vauthors=Park JJ, Pavesio C |title=Prophylactic laser photocoagulation for acute [[retinal]] [[necrosis]]. Does it raise more questions than answers? |journal=Br J Ophthalmol |volume=92 |issue=9 |pages=1161–2 |year=2008 |pmid=18723739 |doi=10.1136/bjo.2008.147181 |url=}}</ref> | ||
**The procedure is contraindicated if there is [[vitreous]] [[inflammation]] or obstructed view and access to the [[posterior pole]]. | **The procedure is contraindicated if there is [[vitreous]] [[inflammation]] or obstructed view of and access to the [[posterior pole]]. | ||
*Due to reported occurrences of [[retinal detachment]] from prophylactic laser photocoagulation, more research is necessary to determine the ideal indications for the procedure.<ref name="pmid18723739">{{cite journal |vauthors=Park JJ, Pavesio C |title=Prophylactic laser photocoagulation for acute retinal necrosis. Does it raise more questions than answers? |journal=Br J Ophthalmol |volume=92 |issue=9 |pages=1161–2 |year=2008 |pmid=18723739 |doi=10.1136/bjo.2008.147181 |url=}}</ref> | *Due to reported occurrences of [[retinal detachment]] from prophylactic laser photocoagulation, more research is necessary to determine the ideal indications for the procedure.<ref name="pmid18723739">{{cite journal |vauthors=Park JJ, Pavesio C |title=Prophylactic laser photocoagulation for acute retinal necrosis. Does it raise more questions than answers? |journal=Br J Ophthalmol |volume=92 |issue=9 |pages=1161–2 |year=2008 |pmid=18723739 |doi=10.1136/bjo.2008.147181 |url=}}</ref> | ||
**If performed on patients with excessive [[inflammation]] and [[vitreous]] opacity, there is evidence of photocoagulation worsening prognosis of Progressive outer retinal necrosis, leading to [[retinal detachment]] and [[blindness]].<ref name="pmid18584565">{{cite journal |vauthors=Kawaguchi T, Spencer DB, Mochizuki M |title=Therapy for acute retinal necrosis |journal=Semin Ophthalmol |volume=23 |issue=4 |pages=285–90 |year=2008 |pmid=18584565 |doi=10.1080/08820530802111192 |url=}}</ref> | **If performed on patients with excessive [[inflammation]] and [[vitreous]] opacity, there is evidence of photocoagulation worsening prognosis of Progressive outer retinal necrosis, leading to [[retinal detachment]] and [[blindness]].<ref name="pmid18584565">{{cite journal |vauthors=Kawaguchi T, Spencer DB, Mochizuki M |title=Therapy for acute retinal necrosis |journal=Semin Ophthalmol |volume=23 |issue=4 |pages=285–90 |year=2008 |pmid=18584565 |doi=10.1080/08820530802111192 |url=}}</ref> | ||
===Prevention=== | ===Prevention=== | ||
Effective measures for prevention of | Effective measures for the prevention of progressive outer retinal necrosis include the following: | ||
*Avoiding proximity to individuals infected with [[Varicella zoster virus]] (VZV) to avoid contact with pathogenic respiratory droplets | *Avoiding proximity to individuals infected with [[Varicella zoster virus]] (VZV) to avoid fluid contact and contact with pathogenic respiratory droplets | ||
* | *Preventative measures to avoid [[HIV infection]] and other infectious sources of [[immunocompromised]] status | ||
==Source== | ==Source== | ||
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[[Category:Ophthalmology]] | [[Category:Ophthalmology]] | ||
[[Category:Emergency medicine]] | |||
[[Category:Disease]] | |||
[[Category:Up-To-Date]] | |||
Latest revision as of 23:49, 29 July 2020
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Luke Rusowicz-Orazem, B.S.
Synonyms and keywords: PORN syndrome
Overview
Progressive outer retinal necrosis, also known as PORN syndrome, is a form of necrotizing retinitis that primarily affects severely immunocompromised individuals. It is primarily caused by Varicella zoster virus infection, most commonly manifesting in patients who have AIDs or are undergoing chemotherapy. Symptoms of PORN syndrome primarily include vision loss—progressing to blindness if untreated—as well as other visual symptoms such as floaters and flashes. The clinical presentation of progressive outer retinal necrosis includes white-yellow necrotic lesions that coalesce to form a single film, as well as opacification of the retina and abnormal pigmentation. Unlike the associated condition acute retinal necrosis, PORN syndrome does not usually manifest with anterior chamber or vitreous inflammation, nor do patients usually experience eye pain. It is important to differentiate PORN syndrome from other ocular conditions to prevent complications, including blindness, retinal detachment, and cataracts. If left untreated, the prognosis of PORN syndrome for visual acuity is poor: approximately 67% of cases will lead to blindness in the affected eye (and 61% cases of PORN syndrome will spread to the previously unaffected eye). Medical therapy should be started as early as possible to stop the progression of symptoms. The mainstay of therapy is intravenous antimicrobial therapy, usually a combination of Ganciclovir and Foscarnet. Individual uses of the two therapies, in addition to Ancyclovir, may be indicated for less severe cases.
Historical Perspective
- In 1987, a clinical presentation of necrotizing retinitis occurring specifically in immunocompromised individuals was first documented by Jabs DA et al.[1]
- In 1990, progressive outer retinal necrosis (PORN) was first identified by Forster, DJ et al. [2]
- It was identified and differentiated from acute retinal necrosis by its rapid progression, unresponsiveness to antiviral therapy (acyclovir), and resultant retinal detachment.
- A study of two HIV-positive individuals led to the identification of Varicella-zoster infection as the cause of PORN
- Immunocompromised status was recognized as an important means of differentiating PORN patients from acute retinal necrosis patients
Classification
There is no official classification schema for progressive outer retinal necrosis.
Pathophysiology
Pathogenesis
The pathogenesis of progressive outer retinal necrosis (PORN) is characterized by retinal necrosis due to ocular viral infection.[3] Viral particles infiltrate the retina via various modes of transmission:[4]
- 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
Retinal inflammation is caused by the up-regulated production of cytokines.
- Retinal necrosis occurs due to the vascular occlusion resulting in white-yellow necrotic lesions that begin in the outer layers of the retina, coalesce, and spread inward without intervention.[5]
Associated Conditions
Progressive outer retinal necrosis is associated with the following ocular conditions:
- Acute retinal necrosis[4]
- Cytomegalovirus retinitis[7]
- Toxoplasmic chorioretinitis[8]
- Endophthalmitis
PORN is often associated with AIDS as a complication of immunocompromised status.[9]
Causes
Progressive outer retinal necrosis (PORN) is primarily caused by Varicella zoster virus (VZV), and is less commonly caused by Cytomegalovirus (CMV), Herpes simplex virus 1, and rarely BK Virus. PORN usually appears in immunocompromised individuals, usually as a complication of diseases such as AIDS or from chemotherapy.[10][11]
Viral
- Varicella zoster virus
- Cytomegalovirus[12]
- Herpes simplex virus 1 (HSV-1)[13]
- BK Virus[14]
Differentiating Progressive outer retinal necrosis from Other Diseases
- Progressive outer retinal necrosis (PORN) 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 other complications.[8][15][16][17]
- PORN is differentiated from acute retinal necrosis by its occurrence primarily in immunocompromised individuals; acute retinal necrosis will also develop in immunocompetent individuals.
Epidemiology and Demographics
Epidemiological and demographic data for progressive outer retinal necrosis (PORN) are closely tied to that of AIDS, of which PORN is often a complication.
Gender
- Females are more likely than males to develop progressive outer retinal necrosis.[19]
Age
- Progressive outer retinal necrosis occurs more frequently in individuals over the age of 35.[19][20]
Developing countries
- Incidences of PORN are higher in developing countries, particularly those in Africa, due to the higher local prevalence of AIDS.[19]
Risk Factors
Risk factors for progressive outer retinal necrosis include the following:
- Immunocompromised status from prior or concurrent disease, particularly AIDS[21][10][19]
- Immunosuppresion from extended corticosteroid use or chemotherapy[22]
- Being female
- Being older than 35 years
Screening
There is no established, diagnostic screening procedure for progressive outer retinal necrosis.
Natural History, Complications, and Prognosis
Natural History
- Early clinical findings of progressive outer retinal necrosis (PORN) include white-yellow necrotic peripheral and macular retinal lesions, as well as opacification of non-necrotic tissue, indicative of the onset of disease.[3]
- Without treatment, the necrotic lesions will rapidly coalesce into a unified film, progressing to complete retinal necrosis.[10]
- Complete retinal detachment will usually occur between 30 days and 3 months after onset.[11]
- PORN will usually spread to the previously unaffected eye within 4 weeks.
Complications
The following complications of progressive outer retinal necrosis occur, if left untreated, from complete retinal necrosis:[11]
- Retinal detachment
- Cataracts
- Retinal atrophy[23]
- Permanent vision loss and blindness[23]
- Pigmentation scarring
Prognosis
- Without treatment, the prognosis for vision acuity in the affected eyes is poor and it is highly likely that it will become bilateral.[3]
- Approximately 67% of progressive outer retinal necrosis cases will progress to blindness if left untreated.[10]
- Approximately 70% of progressive outer retinal necrosis cases will progress to retinal detachment.
- Approximately 61% of progressive outer retinal necrosis cases will become bilateral.
- With treatment, the prognosis varies:[23]
- Foscarnet and ganciclovir antiviral intravenous therapy can improve the prognosis if administered during the early stages of the disease.
- Vitrectomy can successfully prevent retinal detachment.
Diagnosis
Diagnostic Criteria
The following standardized criteria are used to officially diagnose progessive outer retinal necrosis:[10]
- Presence of multifocal lesions without granular borders in the deep retinal layers
- Evidence that the infection started in the peripheral retina with or without focal involvement
- Extremely rapid progression
- Presence of minimal intraocular infection
History and Symptoms
History
A history of immunocompromising disease and/or therapy may be present in progressive outer retinal necrosis patients, particularly the following:[21][10][19][22]
Symptoms
Symptoms of progressive outer retinal necrosis include the following:[10]
- Blurred vision
- Loss of peripheral vision
- Blindness
- Floaters
- Flashes
Physical Examination
Physical examination for progressive outer retinal necrosis may be remarkable for the following:
- White-yellow necrotic peripheral and macular retinal lesions, coalescing to form a single film[3]
- Deep opacification of the peripheral retina[10]
- Abnormal retinal pigmentation
- Absence or minimal presence of anterior chamber or vitreous inflammation, as well as absence of scleritis[24]
- This is an important for differentiating progressive outer retinal necrosis from acute retinal necrosis
Laboratory Findings
Laboratory findings associated with progressive outer retinal necrosis (PORN) are those used to confirm the Varicella zoster virus (VZV) infection, obtained from aqueous humor or the vitreous. Useful laboratory techniques may include:[25]
- Qualitative and real-time polymerase chain reaction may produce genomic evidence of VZV infection with high specificity[24][26]
- Viral cultures may reveal evidence of VZV infection indicative of PORN
- Retinochoroidal biopsy may be performed to obtain a culture sample, in addition to direct sampling from the aqueous humor[9]
- Diagnosis via viral culture alone is not recommended due to the low specificity and sensitivity (53.7% and 46.3%, respectively), indicating a high chance of obtaining a false-negative.[26]
- Immunofluorescence may reveal antibodies indicative of VZV infection[27]
- Detection of indicative Varicella zoster virus antibodies via Goldmann-Witmer coefficient[28]
Imaging Findings
- Ophthalmoscopy is the imaging modality of choice for progressive outer retinal necrosis and is characterized by the following findings:[24][29][9][30]
- Retinal opacity
- Superficial retinal hemorrhage
- Optic disk swelling
- Vitritis
- Retinal and choroidal detachment
- White-yellow, multifocal retinal lesions with "cherry red spot" central macula
- Absence of vitreous or anterior chamber inflammation, which is important in differentiating PORN from acute retinal necrosis
- Fundus autofluorescence may present with the following findings, indicative of progressive outer retinal necrosis:[31]
- Hyper- and hypo-fluorescence of the retina from visible tissue degradation from the accumulation of lipofuscin
- The changes are indicative of photoreceptor death and inflammatory tissue
- Hyper- and hypo-fluorescence of the retina from visible tissue degradation from the accumulation of lipofuscin
- Optical coherence tomography may present with the following findings:
- Thickened retinal opacification
- Lower reflectivity and disorganization of the outer retina, displaying signs of inflammation and degradation
Other Diagnostic Studies
There are no other diagnostic studies associated with progressive outer retinal necrosis.
Treatment
Medical Therapy
The mainstay of therapy for progressive outer retinal necrosis (PORN) is Highly Active Anti-Retroviral Therapy (HAART), consisting of the following regimens:[23][9]
- Empiric antimicrobrial therapy
- Preferred regimen: Ganciclovir 5mg/kg IV q24h AND Foscarnet 90-120mg/kg IV q24h
- Alternative regimen (1): Ganciclovir 5mg/kg IV q12h for 1-2 weeks, followed by Ganciclovir 5mg/kg IV q24h OR Foscarnet 60 mg/kg q8h for 2 weeks, then 90-120 mg/kg q24h
- Alternative regimen (2): Acyclovir 15 mg/kg IV q8h OR Acyclovir 15 mg/kg IV q8h
- Note: The combination antimicrobial therapy of Ganciclovir and Foscarnet is recommended as the most effective treatment regiment for halting the progression of PORN. Single antimicrobrial therapy is not usually recommended.[32]
Surgery
Surgery is not the first-line treatment option for patients with progressive outer retinal necrosis; it is primarily indicated when there is risk of complications, including retinal detachment and tissue atrophy.[33]
Vitrectomy
- Vitrectomy may be indicated both before and after occurrence of retinal detachment to improve visual prognosis.[34]
- Prophylactic vitrectomy can be effective in removing inflammation factors and preventing retinal detachment by removing or preventing the spread of pre-existing lesions and necrotic tissue.[35]
- Remedial vitrectomy in patients experiencing retinal detachment can lead to improved visual prognosis by retinal reattachment.[36]
Prophylactic Laser Retinopexy
- Prophylactic laser retinopexy may be indicated to prevent retinal detachment by photocoagulation, creating posterior chorioretinal adhesions.[37]
- The procedure is contraindicated if there is vitreous inflammation or obstructed view of and access to the posterior pole.
- Due to reported occurrences of retinal detachment from prophylactic laser photocoagulation, more research is necessary to determine the ideal indications for the procedure.[37]
- If performed on patients with excessive inflammation and vitreous opacity, there is evidence of photocoagulation worsening prognosis of Progressive outer retinal necrosis, leading to retinal detachment and blindness.[35]
Prevention
Effective measures for the prevention of progressive outer retinal necrosis include the following:
- Avoiding proximity to individuals infected with Varicella zoster virus (VZV) to avoid fluid contact and contact with pathogenic respiratory droplets
- Preventative measures to avoid HIV infection and other infectious sources of immunocompromised status
Source
American Academy of Ophthalmology
See also
- Acute retinal necrosis
- Cytomegalovirus retinitis
- List of eye diseases and disorders
- List of systemic diseases with ocular manifestations
References
- ↑ Jabs DA, Schachat AP, Liss R, Knox DL, Michels RG (1987). "Presumed varicella zoster retinitis in immunocompromised patients". Retina (Philadelphia, Pa.). 7 (1): 9–13. PMID 3602608.
- ↑ Forster DJ, Dugel PU, Frangieh GT, Liggett PE, Rao NA (1990). "Rapidly progressive outer retinal necrosis in the acquired immunodeficiency syndrome". Am. J. Ophthalmol. 110 (4): 341–8. PMID 2220967.
- ↑ 3.0 3.1 3.2 3.3 3.4 Moorthy, R. S; Weinberg, D. V; Teich, S. A; Berger, B. B; Minturn, J. T; Kumar, S.; Rao, N. A; Fowell, S. M; Loose, I. A; Jampol, L. M (1997). "Management of varicella zoster virus retinitis in AIDS". British Journal of Ophthalmology. 81 (3): 189–194. doi:10.1136/bjo.81.3.189. ISSN 0007-1161.
- ↑ 4.0 4.1 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.
- ↑ Yu, Suqin; Freund, K. Bailey (2015). "Could Progressive Outer Retinal Necrosis Begin With Retinal Deep Capillary Ischemia?". JAMA Ophthalmology. 133 (1): 110. doi:10.1001/jamaophthalmol.2014.3548. ISSN 2168-6165.
- ↑ 6.0 6.1 6.2 "Facts About Uveitis | National Eye Institute".
- ↑ 7.0 7.1 "CMV retinitis: MedlinePlus Medical Encyclopedia".
- ↑ 8.0 8.1 8.2 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.
- ↑ 9.0 9.1 9.2 9.3 9.4 Galindez OA, Sabates NR, Whitacre MM, Sabates FN (1996). "Rapidly progressive outer retinal necrosis caused by varicella zoster virus in a patient infected with human immunodeficiency virus". Clin. Infect. Dis. 22 (1): 149–51. PMID 8824984.
- ↑ 10.0 10.1 10.2 10.3 10.4 10.5 10.6 10.7 Engstrom RE, Holland GN, Margolis TP, Muccioli C, Lindley JI, Belfort R, Holland SP, Johnston WH, Wolitz RA, Kreiger AE (1994). "The progressive outer retinal necrosis syndrome. A variant of necrotizing herpetic retinopathy in patients with AIDS". Ophthalmology. 101 (9): 1488–502. PMID 8090452.
- ↑ 11.0 11.1 11.2 Austin RB (2000). "Progressive outer retinal necrosis syndrome: a comprehensive review of its clinical presentation, relationship to immune system status, and management". Clin. Eye Vis. Care. 12 (3–4): 119–129. PMID 11137426.
- ↑ Sfeir M (2015). "Cytomegalovirus implicated in a case of progressive outer retinal necrosis (PORN)". J. Clin. Virol. 69: 86–90. doi:10.1016/j.jcv.2015.04.006. PMID 26209386.
- ↑ Gore, Daniel M.; Gore, Sri K.; Visser, Linda (2012). "Progressive Outer Retinal Necrosis". Archives of Ophthalmology. 130 (6). doi:10.1001/archophthalmol.2011.2622. ISSN 0003-9950.
- ↑ Turno-Kręcicka A, Boratyńska M, Tomczyk-Socha M, Mazanowska O (2015). "Progressive outer retinal necrosis in immunocompromised kidney allograft recipient". Transpl Infect Dis. 17 (3): 400–5. doi:10.1111/tid.12386. PMID 25846017.
- ↑ 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.
- ↑ 19.0 19.1 19.2 19.3 19.4 Gore DM, Gore SK, Visser L (2012). "Progressive outer retinal necrosis: outcomes in the intravitreal era". Arch. Ophthalmol. 130 (6): 700–6. doi:10.1001/archophthalmol.2011.2622. PMID 22801826.
- ↑ Sittivarakul W, Aui-aree N (2009). "Clinical features, management and outcomes of progressive outer retinal necrosis (PORN) in southern Thailand". J Med Assoc Thai. 92 (3): 360–6. PMID 19301729.
- ↑ 21.0 21.1 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.
- ↑ 22.0 22.1 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.
- ↑ 23.0 23.1 23.2 23.3 23.4 23.5 Moorthy RS, Weinberg DV, Teich SA, Berger BB, Minturn JT, Kumar S, Rao NA, Fowell SM, Loose IA, Jampol LM (1997). "Management of varicella zoster virus retinitis in AIDS". Br J Ophthalmol. 81 (3): 189–94. PMC 1722141. PMID 9135381.
- ↑ 24.0 24.1 24.2 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.
- ↑ Matos K, Muccioli C, Belfort Junior R, Rizzo LV (2007). "Correlation between clinical diagnosis and PCR analysis of serum, aqueous, and vitreous samples in patients with inflammatory eye disease". Arq Bras Oftalmol. 70 (1): 109–14. PMID 17505729.
- ↑ 26.0 26.1 Wilson DA, Yen-Lieberman B, Schindler S, Asamoto K, Schold JD, Procop GW (2012). "Should varicella-zoster virus culture be eliminated? A comparison of direct immunofluorescence antigen detection, culture, and PCR, with a historical review". J. Clin. Microbiol. 50 (12): 4120–2. doi:10.1128/JCM.06753-11. PMC 3502980. PMID 23035203.
- ↑ Singh A, Preiksaitis J, Ferenczy A, Romanowski B (2005). "The laboratory diagnosis of herpes simplex virus infections". Can J Infect Dis Med Microbiol. 16 (2): 92–8. PMC 2095011. PMID 18159535.
- ↑ De Groot-Mijnes JD, Rothova A, Van Loon AM, Schuller M, Ten Dam-Van Loon NH, De Boer JH, Schuurman R, Weersink AJ (2006). "Polymerase chain reaction and Goldmann-Witmer coefficient analysis are complimentary for the diagnosis of infectious uveitis". Am. J. Ophthalmol. 141 (2): 313–8. doi:10.1016/j.ajo.2005.09.017. PMID 16458686.
- ↑ You YS, Lee SJ, Lee SH, Park CH, Kwon OW (2007). "Progressive outer retinal necrosis combined with vitreous hemorrhage in a patient with acquired immunodeficiency syndrome". Korean J Ophthalmol. 21 (1): 51–4. doi:10.3341/kjo.2007.21.1.51. PMC 2629688. PMID 17460434.
- ↑ Al-Dhibi HA, Al-Mahmood AM, Arevalo JF (2014). "A systematic approach to emergencies in uveitis". Middle East Afr J Ophthalmol. 21 (3): 251–8. doi:10.4103/0974-9233.134687. PMC 4123279. PMID 25100911.
- ↑ Yeh S, Wong WT, Weichel ED, Lew JC, Chew EY, Nussenblatt RB (2010). "Fundus Autofluorescence and OCT in the Management of Progressive Outer Retinal Necrosis". Ophthalmic Surg Lasers Imaging: 1–4. doi:10.3928/15428877-20100216-14. PMC 3265678. PMID 20337261.
- ↑ Ciulla TA, Rutledge BK, Morley MG, Duker JS (1998). "The progressive outer retinal necrosis syndrome: successful treatment with combination antiviral therapy". Ophthalmic Surg Lasers. 29 (3): 198–206. PMID 9547773.
- ↑ Shantha JG, Weissman HM, Debiec MR, Albini TA, Yeh S (2015). "Advances in the management of acute retinal necrosis". Int Ophthalmol Clin. 55 (3): 1–13. doi:10.1097/IIO.0000000000000077. PMC 4567584. PMID 26035758.
- ↑ Luo YH, Duan XC, Chen BH, Tang LS, Guo XJ (2012). "Efficacy and necessity of prophylactic vitrectomy for acute retinal necrosis syndrome". Int J Ophthalmol. 5 (4): 482–7. doi:10.3980/j.issn.2222-3959.2012.04.15. PMC 3428546. PMID 22937510.
- ↑ 35.0 35.1 Kawaguchi T, Spencer DB, Mochizuki M (2008). "Therapy for acute retinal necrosis". Semin Ophthalmol. 23 (4): 285–90. doi:10.1080/08820530802111192. PMID 18584565.
- ↑ McDonald HR, Lewis H, Kreiger AE, Sidikaro Y, Heckenlively J (1991). "Surgical management of retinal detachment associated with the acute retinal necrosis syndrome". Br J Ophthalmol. 75 (8): 455–8. PMC 1042429. PMID 1873262.
- ↑ 37.0 37.1 Park JJ, Pavesio C (2008). "Prophylactic laser photocoagulation for acute retinal necrosis. Does it raise more questions than answers?". Br J Ophthalmol. 92 (9): 1161–2. doi:10.1136/bjo.2008.147181. PMID 18723739.