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==Overview==
==Overview==
The exact pathogenesis of uveitis is not fully understood. It is thought that uveitis is mediated by a genetic predisposition and an acquired cross immunity to infectious agents, or cross immunity to self-[[antigens]] due to underlying [[autoimmune]] diseases. It is estimated that 35% to 50% of cases of uveitis are [[idiopathic]].<ref name="pmid8619771">{{cite journal| author=Rodriguez A, Calonge M, Pedroza-Seres M, Akova YA, Messmer EM, D'Amico DJ et al.| title=Referral patterns of uveitis in a tertiary eye care center. | journal=Arch Ophthalmol | year= 1996 | volume= 114 | issue= 5 | pages= 593-9 | pmid=8619771 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8619771  }} </ref><ref name="pmid20943722">{{cite journal| author=Guly CM, Forrester JV| title=Investigation and management of uveitis. | journal=BMJ | year= 2010 | volume= 341 | issue=  | pages= c4976 | pmid=20943722 | doi=10.1136/bmj.c4976 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20943722  }} </ref> Development of uveitis is hypothesized to be the result of a genetic predisposition for acquiring the disease; contributions of several [[human leukocyte antigen|human leukocyte antigen (HLA)]] alleles are most commonly implicated.<ref name="pmid20943722">{{cite journal| author=Guly CM, Forrester JV| title=Investigation and management of uveitis. | journal=BMJ | year= 2010 | volume= 341 | issue=  | pages= c4976 | pmid=20943722 | doi=10.1136/bmj.c4976 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20943722  }} </ref><ref name="pmid26438050">{{cite journal| author=Przeździecka-Dołyk J, Węgrzyn A, Turno-Kręcicka A, Misiuk-Hojło M| title=Immunopathogenic Background of Pars Planitis. | journal=Arch Immunol Ther Exp (Warsz) | year= 2016 | volume= 64 | issue= 2 | pages= 127-37 | pmid=26438050 | doi=10.1007/s00005-015-0361-y | pmc=4805694 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26438050  }} </ref>
==Pathogenesis==
==Pathogenesis==
The exact pathogenesis of uveitis is not fully understood. It is thought that uveitis is mediated by either genetic factors, infectious agents, or autoimmune/inflammatory conditions. Up to 35% of cases of uveitis are idiopathic. (REFERENCES)
The exact pathogenesis of uveitis is not fully understood. It is thought that uveitis is mediated by a genetic predisposition combined with cross immunity to infectious agents, or cross immunity to self-[[antigens]] due to underlying [[autoimmune]] diseases. It is estimated that 35-50% of cases of uveitis are [[idiopathic]].<ref name="pmid8619771">{{cite journal| author=Rodriguez A, Calonge M, Pedroza-Seres M, Akova YA, Messmer EM, D'Amico DJ et al.| title=Referral patterns of uveitis in a tertiary eye care center. | journal=Arch Ophthalmol | year= 1996 | volume= 114 | issue= 5 | pages= 593-9 | pmid=8619771 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8619771  }} </ref><ref name="pmid20943722">{{cite journal| author=Guly CM, Forrester JV| title=Investigation and management of uveitis. | journal=BMJ | year= 2010 | volume= 341 | issue=  | pages= c4976 | pmid=20943722 | doi=10.1136/bmj.c4976 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20943722  }} </ref>
For infectious etiologies of uveitis, it is postulated that the immune reaction directed against foreign molecules or antigens may injure the uveal tract vessels and cells.
Uveitis, in the setting of underlying infectious diseases, is hypothesized to be secondary to a [[T-cell]] mediated [[hypersensitivity reaction]] resulting in immunoactivating [[cytokine]] production by proliferating Tн17 and Tн1 cells.<ref name="pmid26438050">{{cite journal| author=Przeździecka-Dołyk J, Węgrzyn A, Turno-Kręcicka A, Misiuk-Hojło M| title=Immunopathogenic Background of Pars Planitis. | journal=Arch Immunol Ther Exp (Warsz) | year= 2016 | volume= 64 | issue= 2 | pages= 127-37 | pmid=26438050 | doi=10.1007/s00005-015-0361-y | pmc=4805694 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26438050  }} </ref><ref name="pmid25089078">{{cite journal| author=Urban B, Bakunowicz-Łazarczyk A, Michalczuk M| title=Immune recovery uveitis: pathogenesis, clinical symptoms, and treatment. | journal=Mediators Inflamm | year= 2014 | volume= 2014 | issue=  | pages= 971417 | pmid=25089078 | doi=10.1155/2014/971417 | pmc=4096001 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25089078  }} </ref> A similar mechanism is hypothesized for [[autoimmune]] etiologies of uveitis with the exception of an unknown source of the triggering [[antigen]].<ref name="pmid25742774">{{cite journal| author=Sun D, Liang D, Kaplan HJ, Shao H| title=The role of Th17-associated cytokines in the pathogenesis of experimental autoimmune uveitis (EAU). | journal=Cytokine | year= 2015 | volume= 74 | issue= 1 | pages= 76-80 | pmid=25742774 | doi=10.1016/j.cyto.2014.12.017 | pmc=4457592 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25742774  }} </ref><ref name="pmid25769932">{{cite journal| author=Bi HS, Liu ZF, Cui Y| title=Pathogenesis of innate immunity and adaptive immunity in the mouse model of experimental autoimmune uveitis. | journal=J Chin Med Assoc | year= 2015 | volume= 78 | issue= 5 | pages= 276-82 | pmid=25769932 | doi=10.1016/j.jcma.2015.01.002 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25769932  }} </ref><ref name="pmid21787221">{{cite journal| author=Horai R, Caspi RR| title=Cytokines in autoimmune uveitis. | journal=J Interferon Cytokine Res | year= 2011 | volume= 31 | issue= 10 | pages= 733-44 | pmid=21787221 | doi=10.1089/jir.2011.0042 | pmc=3189550 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21787221  }} </ref><ref name="pmid19234216">{{cite journal| author=Ke Y, Liu K, Huang GQ, Cui Y, Kaplan HJ, Shao H et al.| title=Anti-inflammatory role of IL-17 in experimental autoimmune uveitis. | journal=J Immunol | year= 2009 | volume= 182 | issue= 5 | pages= 3183-90 | pmid=19234216 | doi=10.4049/jimmunol.0802487 | pmc=3275433 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19234216  }} </ref>


When uveitis is found in association with autoimmune disorders, the mechanism may be a hypersensitivity reaction involving immune complex deposition within the uveal tract.
==Genetics==
==Genetics==
Development of uveitis is hypothesized to be the result of a genetic predisposition for acquiring the disease. Contributions of several [[human leukocyte antigen|human leukocyte antigen (HLA)]] alleles are most commonly implicated. This includes [[HLA-B27]] in [[seronegative spondyloarthropathies]], [[HLA-A29]] in [[birdshot chorioretinopathy]], [[HLA-B51]] in [[Behcet syndrome]] and [[multiple sclerosis]], [[HLA-B8]], [[HLA-DR15]], and [[HLA-DR2]].<ref name="pmid20943722">{{cite journal| author=Guly CM, Forrester JV| title=Investigation and management of uveitis. | journal=BMJ | year= 2010 | volume= 341 | issue=  | pages= c4976 | pmid=20943722 | doi=10.1136/bmj.c4976 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20943722  }} </ref><ref name="pmid26438050">{{cite journal| author=Przeździecka-Dołyk J, Węgrzyn A, Turno-Kręcicka A, Misiuk-Hojło M| title=Immunopathogenic Background of Pars Planitis. | journal=Arch Immunol Ther Exp (Warsz) | year= 2016 | volume= 64 | issue= 2 | pages= 127-37 | pmid=26438050 | doi=10.1007/s00005-015-0361-y | pmc=4805694 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26438050  }} </ref>


==Associated Conditions==
==Associated Conditions==
*Seronegative spondyloarthropathy
The following conditions are associated with uveitis:<ref name="pmid8619771">{{cite journal| author=Rodriguez A, Calonge M, Pedroza-Seres M, Akova YA, Messmer EM, D'Amico DJ et al.| title=Referral patterns of uveitis in a tertiary eye care center. | journal=Arch Ophthalmol | year= 1996 | volume= 114 | issue= 5 | pages= 593-9 | pmid=8619771 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8619771  }} </ref><ref name="pmid20943722">{{cite journal| author=Guly CM, Forrester JV| title=Investigation and management of uveitis. | journal=BMJ | year= 2010 | volume= 341 | issue=  | pages= c4976 | pmid=20943722 | doi=10.1136/bmj.c4976 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20943722  }} </ref><ref name=eyewikiuveitis>American Academy of Ophthalmology EyeWiki(2015)http://eyewiki.aao.org/Category:Uveitis</ref>
*Sarcoidosis
*[[Seronegative spondyloarthropathy]]
*Inflammatory bowel disease
*[[Sarcoidosis]]
*Systemic Lupus Erythematosus (SLE)
*[[Multiple sclerosis]]
*Behçet's syndrome
*[[Inflammatory bowel disease]]
*Birdshot retinochoroidopathy
*[[Systemic lupus erythematosus]] (SLE)
*Juvenile Idiopathic Arthritis (JIA)
*[[Behçet's syndrome]]
*Vogt-Koyanagi-Harada
*[[Birdshot retinochoroidopathy]]
*[[Juvenile idiopathic arthritis]] (JIA)
*[[Vogt-Koyanagi-Harada syndrome]]
*Fuch's heterochromic iridocyclitis
*Fuch's heterochromic iridocyclitis
*Lyme Disease
*[[Lymphoma]]
*Acquired Immunodeficiency Syndrome (AIDS)
*[[Lyme Disease]]
*Herpes simplex
*[[Acquired immunodeficiency syndrome]] (AIDS)
*Cytomegalovirus
*[[Herpes simplex]]
*Syphilis
*[[Varicella Zoster]]
*Toxoplasmosis
*[[Cytomegalovirus]]
*Toxocariasis
*[[Syphilis]]
*Tuberculosis
*[[Toxoplasmosis]]
*Rubella
*[[Toxocariasis]]
*Cat scratch disease (''Bartonella spp.'')
*[[Tuberculosis]]
*[[Rubella]]
*[[Cat scratch disease]] (''[[Bartonella|Bartonella spp.]]'')


==Gross Pathology==
==Gross Pathology==
'''Anterior Uveitis'''<br>
On gross pathology, redness of the eye and dilated cilliary vessels are common yet non-specific findings in uveitis. The following are images of the gross pathology of uveitis:<ref name=wikipediauveitis>Wikipedia Uveitis(2006)https://en.wikipedia.org/wiki/Uveitis#/media/File:Hypopyon.jpg</ref><ref name=umichuveitis>University of Michigan Eyes Have It(2009)http://kellogg.umich.edu/theeyeshaveit/red-eye/anterior-uveitis.html</ref>
'''Intermediate Uveitis'''<br>
<gallery>
'''Posterior Uveitis''' <br>
Image:Uveitis1.jpg|Uveitis with pus in the anterior chamber
Image:Uveitis2.jpg|Anterior Uveitis
</gallery>
 
==Microscopic Pathology==
==Microscopic Pathology==
'''Anterior Uveitis'''<br>
On microscopic histopathological analysis, [[lymphocytic]] infiltration, [[monocytic]] infiltration, epitheloid cells, and [[granulomatous]] inflammation of the [[Uvea|uveal]] structures are characteristic findings of uveitis. The following are images of the microscopic pathology of uveitis:<ref name="pmid22346110">{{cite journal| author=Arevalo JF, Garcia RA, Al-Dhibi HA, Sanchez JG, Suarez-Tata L| title=Update on sympathetic ophthalmia. | journal=Middle East Afr J Ophthalmol | year= 2012 | volume= 19 | issue= 1 | pages= 13-21 | pmid=22346110 | doi=10.4103/0974-9233.92111 | pmc=3277011 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22346110  }} </ref>
'''Intermediate Uveitis'''<br>
<gallery>
'''Posterior Uveitis''' <br>
Image:MEAJOUveitis.jpg|Uveitis with infiltration of [[lymphocytes]]
 
Image:MEAJOUveitis2.jpg|Uveitis with [[granulomatous inflammation]] and infiltration of the choroid by [[lymphocytes]] and [[macrophages]]
</gallery>


== References ==
== References ==
{{Reflist|2}}
{{Reflist|2}}
[[Category:Ophthalmology]]
[[Category:Primary care]]


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Latest revision as of 00:37, 30 July 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Tarek Nafee, M.D. [2]

Overview

The exact pathogenesis of uveitis is not fully understood. It is thought that uveitis is mediated by a genetic predisposition and an acquired cross immunity to infectious agents, or cross immunity to self-antigens due to underlying autoimmune diseases. It is estimated that 35% to 50% of cases of uveitis are idiopathic.[1][2] Development of uveitis is hypothesized to be the result of a genetic predisposition for acquiring the disease; contributions of several human leukocyte antigen (HLA) alleles are most commonly implicated.[2][3]

Pathogenesis

The exact pathogenesis of uveitis is not fully understood. It is thought that uveitis is mediated by a genetic predisposition combined with cross immunity to infectious agents, or cross immunity to self-antigens due to underlying autoimmune diseases. It is estimated that 35-50% of cases of uveitis are idiopathic.[1][2] Uveitis, in the setting of underlying infectious diseases, is hypothesized to be secondary to a T-cell mediated hypersensitivity reaction resulting in immunoactivating cytokine production by proliferating Tн17 and Tн1 cells.[3][4] A similar mechanism is hypothesized for autoimmune etiologies of uveitis with the exception of an unknown source of the triggering antigen.[5][6][7][8]

Genetics

Development of uveitis is hypothesized to be the result of a genetic predisposition for acquiring the disease. Contributions of several human leukocyte antigen (HLA) alleles are most commonly implicated. This includes HLA-B27 in seronegative spondyloarthropathies, HLA-A29 in birdshot chorioretinopathy, HLA-B51 in Behcet syndrome and multiple sclerosis, HLA-B8, HLA-DR15, and HLA-DR2.[2][3]

Associated Conditions

The following conditions are associated with uveitis:[1][2][9]

Gross Pathology

On gross pathology, redness of the eye and dilated cilliary vessels are common yet non-specific findings in uveitis. The following are images of the gross pathology of uveitis:[10][11]

  • Uveitis with pus in the anterior chamber

    Uveitis with pus in the anterior chamber

  • Anterior Uveitis

    Anterior Uveitis

Microscopic Pathology

On microscopic histopathological analysis, lymphocytic infiltration, monocytic infiltration, epitheloid cells, and granulomatous inflammation of the uveal structures are characteristic findings of uveitis. The following are images of the microscopic pathology of uveitis:[12]

References

  1. ↑ 1.0 1.1 1.2 Rodriguez A, Calonge M, Pedroza-Seres M, Akova YA, Messmer EM, D'Amico DJ; et al. (1996). "Referral patterns of uveitis in a tertiary eye care center". Arch Ophthalmol. 114 (5): 593–9. PMID 8619771.
  2. ↑ 2.0 2.1 2.2 2.3 2.4 Guly CM, Forrester JV (2010). "Investigation and management of uveitis". BMJ. 341: c4976. doi:10.1136/bmj.c4976. PMID 20943722.
  3. ↑ 3.0 3.1 3.2 Przeździecka-Dołyk J, Węgrzyn A, Turno-Kręcicka A, Misiuk-Hojło M (2016). "Immunopathogenic Background of Pars Planitis". Arch Immunol Ther Exp (Warsz). 64 (2): 127–37. doi:10.1007/s00005-015-0361-y. PMC 4805694. PMID 26438050.
  4. ↑ Urban B, Bakunowicz-Łazarczyk A, Michalczuk M (2014). "Immune recovery uveitis: pathogenesis, clinical symptoms, and treatment". Mediators Inflamm. 2014: 971417. doi:10.1155/2014/971417. PMC 4096001. PMID 25089078.
  5. ↑ Sun D, Liang D, Kaplan HJ, Shao H (2015). "The role of Th17-associated cytokines in the pathogenesis of experimental autoimmune uveitis (EAU)". Cytokine. 74 (1): 76–80. doi:10.1016/j.cyto.2014.12.017. PMC 4457592. PMID 25742774.
  6. ↑ Bi HS, Liu ZF, Cui Y (2015). "Pathogenesis of innate immunity and adaptive immunity in the mouse model of experimental autoimmune uveitis". J Chin Med Assoc. 78 (5): 276–82. doi:10.1016/j.jcma.2015.01.002. PMID 25769932.
  7. ↑ Horai R, Caspi RR (2011). "Cytokines in autoimmune uveitis". J Interferon Cytokine Res. 31 (10): 733–44. doi:10.1089/jir.2011.0042. PMC 3189550. PMID 21787221.
  8. ↑ Ke Y, Liu K, Huang GQ, Cui Y, Kaplan HJ, Shao H; et al. (2009). "Anti-inflammatory role of IL-17 in experimental autoimmune uveitis". J Immunol. 182 (5): 3183–90. doi:10.4049/jimmunol.0802487. PMC 3275433. PMID 19234216.
  9. ↑ American Academy of Ophthalmology EyeWiki(2015)http://eyewiki.aao.org/Category:Uveitis
  10. ↑ Wikipedia Uveitis(2006)https://en.wikipedia.org/wiki/Uveitis#/media/File:Hypopyon.jpg
  11. ↑ University of Michigan Eyes Have It(2009)http://kellogg.umich.edu/theeyeshaveit/red-eye/anterior-uveitis.html
  12. ↑ Arevalo JF, Garcia RA, Al-Dhibi HA, Sanchez JG, Suarez-Tata L (2012). "Update on sympathetic ophthalmia". Middle East Afr J Ophthalmol. 19 (1): 13–21. doi:10.4103/0974-9233.92111. PMC 3277011. PMID 22346110.

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