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==Overview==
==Overview==
'''Intraocular lymphoma''' is a rare subtype of primary central nervous system lymphoma. Intraocular lymphoma may affect the eye secondarily from metastasis from a non-ocular tumor or may arise within the eye primarily. According to the World Health Organization (WHO) classification, intraocular lymphomas are most commonly a diffuse large B-cell immunohistologic subtype of [[Non-Hodgkin lymphoma|non-Hodgkin's lymphoma]]. The most common symptoms of intraocular lymphoma are blurred or decreased vision. In the majority of patients, [[central nervous system]] involvement only accounts for 20% of primary central nervous system lymphomas. The median age at diagnosis among patients with intraocular lymphoma is between 50-60 years.  The pathogenesis of intraocular lymphoma is characterized by the affection of the sub-retinal pigment epithelium, which is normally involved in the light absorption.  On fluorescein angiography, findings may reveal "leopard spot" patterns due to sub-retinal pigment epithelium infiltrates that stain early and progressively or mottling of the sub-retinal pigment epithelium due to hyper- and hypo-fluorescent window defects.  The initial therapy for patients with intraocular lymphoma is corticosteroids.
'''Intraocular lymphoma''' is a rare subtype of [[primary central nervous system lymphoma]]. Intraocular lymphoma may affect the eye secondarily from [[metastasis]] from a non-[[ocular]] tumor or may arise within the eye primarily. According to the [[World Health Organization]] (WHO) classification, intraocular lymphomas are most commonly a [[Diffuse large B cell lymphoma|diffuse large B-cell]] immunohistologic subtype of [[Non-Hodgkin lymphoma|non-Hodgkin's lymphoma]]. The most common symptoms of intraocular lymphoma are [[Blurred vision|blurred]] or decreased vision. In the majority of patients, [[central nervous system]] involvement only accounts for 20% of [[Primary central nervous system lymphoma|primary central nervous system lymphomas]]. The median age at diagnosis among patients with intraocular lymphoma is between 50-60 years.  The [[pathogenesis]] of intraocular lymphoma is characterized by the affection of the sub-[[retinal pigment epithelium]], which is normally involved in the light absorption.  On fluorescein angiography, findings may reveal "leopard spot" patterns due to sub-[[retinal pigment epithelium]] infiltrates that [[stain]] early and progressively or [[mottling]] of the sub-[[retinal pigment epithelium]] due to hyper- and hypo-[[fluorescent]] window defects.  The initial therapy for patients with intraocular lymphoma is [[Corticosteroid|corticosteroids]].


==Historical Perspective==
==Historical Perspective==
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Intraocular lymphoma may be classified according to its location into 2 subtypes:<ref name="CouplandDamato2008">{{cite journal|last1=Coupland|first1=Sarah E|last2=Damato|first2=Bertil|title=Understanding intraocular lymphomas|journal=Clinical & Experimental Ophthalmology|volume=36|issue=6|year=2008|pages=564–578|issn=14426404|doi=10.1111/j.1442-9071.2008.01843.x}}</ref>
Intraocular lymphoma may be classified according to its location into 2 subtypes:<ref name="CouplandDamato2008">{{cite journal|last1=Coupland|first1=Sarah E|last2=Damato|first2=Bertil|title=Understanding intraocular lymphomas|journal=Clinical & Experimental Ophthalmology|volume=36|issue=6|year=2008|pages=564–578|issn=14426404|doi=10.1111/j.1442-9071.2008.01843.x}}</ref>


* Retinal
*[[Retinal]]
**Retinal
**Retinal
**Vitreoretinal
**Vitreoretinal
**Vitreal
**[[Vitreous|Vitreal]]
* Uveal
*[[Uvea (anatomy)|Uveal]]
**Iridal
**[[Iris|Iridal]]
**Ciliary
**[[Ciliary Muscle|Ciliary]]
**Choroidal
**[[Choroidal]]
 
 
 




Line 40: Line 37:
==Pathophysiology==
==Pathophysiology==


* Intraocular lymphoma arises from B cell, which are normally involved in immune system.
* Intraocular lymphoma arises from [[B cell]], which are normally involved in [[immune system]].


*Intraocular lymphoma can be either primary or secondary central nervous system lymphoma (oculocerebral lymphoma) that mainly affects the [[optic nerve]] and the eye.<ref name="wiki">Intraocular lymphoma. Wikipedia. https://en.wikipedia.org/wiki/Intraocular_lymphoma</ref>
*Intraocular lymphoma can be either [[Primary central nervous system lymphoma|primary]] or secondary central nervous system lymphoma (oculocerebral lymphoma) that mainly affects the [[optic nerve]] and the eye.<ref name="wiki">Intraocular lymphoma. Wikipedia. https://en.wikipedia.org/wiki/Intraocular_lymphoma</ref>
*The pathogenesis of intraocular lymphoma is characterized by the affection of the sub-retinal pigment epithelium, which is normally involved in the light absorption.<ref name="PIOL">Hanson JA, Alexandru D and Bota DA: The evaluation and treatment of primary intraocular lymphoma. journal of Cancer Therapeutics and Research 2013, 2:15 http://dx.doi.org/10.7243/2049-7962-2-15</ref>
*The [[pathogenesis]] of intraocular lymphoma is characterized by the affection of the sub-[[retinal pigment epithelium]], which is normally involved in the light absorption.<ref name="PIOL">Hanson JA, Alexandru D and Bota DA: The evaluation and treatment of primary intraocular lymphoma. journal of Cancer Therapeutics and Research 2013, 2:15 http://dx.doi.org/10.7243/2049-7962-2-15</ref>
*Genes associated with the development of intraocular lymphoma, include:<ref name="wiki">Intraocular lymphoma. Wikipedia. https://en.wikipedia.org/wiki/Intraocular_lymphoma</ref>
*[[Gene|Genes]] associated with the development of intraocular lymphoma, include:<ref name="wiki">Intraocular lymphoma. Wikipedia. https://en.wikipedia.org/wiki/Intraocular_lymphoma</ref>


:*[[C-myc|C-MYC gene]]
:*[[C-myc|C-MYC gene]]
Line 51: Line 48:
*On microscopic histopathological analysis, characteristic findings of intraocular lymphoma, include:<ref name="wiki">Intraocular lymphoma. Wikipedia. https://en.wikipedia.org/wiki/Intraocular_lymphoma</ref>
*On microscopic histopathological analysis, characteristic findings of intraocular lymphoma, include:<ref name="wiki">Intraocular lymphoma. Wikipedia. https://en.wikipedia.org/wiki/Intraocular_lymphoma</ref>


:*Marginal zone (52%)
:*[[Marginal zone]] (52%)
:*Follicular (23%)
:*Follicular (23%)
:*Atypical lymphocytes (gold standard)
:*[[Atypical lymphocytes]] ([[Gold standard (test)|gold standard]])
:*Elevated interleukin [[IL-10]]   According to the World Health Organization (WHO) classification, intraocular lymphomas are most commonly a diffuse large B-cell immunohistologic subtype of non-Hodgkin's lymphoma.<ref name="PIOL" />
:*Elevated interleukin [[IL-10]]. According to the [[World Health Organization]] (WHO) classification, intraocular lymphomas are most commonly a [[Diffuse large B-cell lymphoma|diffuse large B-cell]] immunohistologic subtype of [[Non-Hodgkin lymphoma|non-Hodgkin's lymphoma]].<ref name="PIOL" />


==Causes==
==Causes==
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==Differentiating Intraocular Lymphoma from Other Diseases==
==Differentiating Intraocular Lymphoma from Other Diseases==
*Intraocular lymphoma must be differentiated from other diseases that cause chronic loss of vision, or headaches, such as:<ref name="PIOL">Hanson JA, Alexandru D and Bota DA: The evaluation and treatment of primary intraocular lymphoma. journal of Cancer Therapeutics and Research 2013, 2:15 http://dx.doi.org/10.7243/2049-7962-2-15</ref><ref name="SenBodaghi2009">{{cite journal|last1=Sen|first1=H. Nida|last2=Bodaghi|first2=Bahram|last3=Hoang|first3=Phuc Le|last4=Nussenblatt|first4=Robert|title=Primary Intraocular Lymphoma: Diagnosis and Differential Diagnosis|journal=Ocular Immunology and Inflammation|volume=17|issue=3|year=2009|pages=133–141|issn=0927-3948|doi=10.1080/09273940903108544}}</ref>
*Intraocular lymphoma must be differentiated from other diseases that cause chronic [[loss of vision]], or [[headaches]], such as:<ref name="PIOL">Hanson JA, Alexandru D and Bota DA: The evaluation and treatment of primary intraocular lymphoma. journal of Cancer Therapeutics and Research 2013, 2:15 http://dx.doi.org/10.7243/2049-7962-2-15</ref><ref name="SenBodaghi2009">{{cite journal|last1=Sen|first1=H. Nida|last2=Bodaghi|first2=Bahram|last3=Hoang|first3=Phuc Le|last4=Nussenblatt|first4=Robert|title=Primary Intraocular Lymphoma: Diagnosis and Differential Diagnosis|journal=Ocular Immunology and Inflammation|volume=17|issue=3|year=2009|pages=133–141|issn=0927-3948|doi=10.1080/09273940903108544}}</ref>


:* Pigmented [[nevi]]
:* Ocular [[metastasis]] (most common)
:* [[Congenital]] [[hypertrophy]] of the [[retinal pigment epithelium]]
:*Pigmented [[nevi]]
:*[[Congenital]] [[hypertrophy]] of the [[retinal pigment epithelium]]
:* Optic disc melanocytoma
:* Optic disc melanocytoma
:* [[Hypertrophy]] of the [[retinal pigment epithelium]]
:*[[Hypertrophy]] of the [[retinal pigment epithelium]]
:* [[Hyperplasia]] of [[retinal pigment epithelium]]
:*[[Hyperplasia]] of [[retinal pigment epithelium]]
:* [[Choroidal]] [[hemangioma]]
:*[[Choroidal]] [[hemangioma]]
:* [[Choroidal]] [[metastasis]]
:*[[Choroidal]] [[metastasis]]
:* [[Choroidal]] [[osteoma]]
:*[[Choroidal]] [[osteoma]]
:* Peripheral [[exudative]] hemorrhagic chorioretinopathy
:* Peripheral [[exudative]] hemorrhagic chorioretinopathy
:* [[Choroidal]] [[hemorrhage]]
:*[[Choroidal]] [[hemorrhage]]
:* Hemorrhagic detachment of [[retina]] and [[retinal pigment epithelium]]
:* Hemorrhagic detachment of [[retina]] and [[retinal pigment epithelium]]
:* [[Posterior]] [[nodular]] [[scleritis]]
:*[[Posterior]] [[nodular]] [[scleritis]]
:* Intraocular [[leiomyoma]]
:* Intraocular [[leiomyoma]]
:* [[Adenoma]] of [[retinal pigment epithelium]]
:*[[Adenoma]] of [[retinal pigment epithelium]]
:* [[Retinoblastoma]]
:*[[Retinoblastoma]]
:* Uveal [[metastases]]
:* Uveal [[metastases]]
:* [[Choroidal]] detachment
:*[[Choroidal]] detachment
:* [[Choroidal]] [[cyst]]
:*[[Choroidal]] [[cyst]]
:* Uveal [[neurofibroma]]
:* Uveal [[neurofibroma]]
:* Uveal [[schwannoma]]
:* Uveal [[schwannoma]]
:*Ocular metastasis (most common)
:*Choroidal hemangioma
:*Choroidal hemangioma
:*Vitrous lymphoma
:*Vitrous lymphoma
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=== Prevalence ===
=== Prevalence ===


* The prevalence of intraocular lymphoma remains unknown.<ref name="PIOL">Hanson JA, Alexandru D and Bota DA: The evaluation and treatment of primary intraocular lymphoma. journal of Cancer Therapeutics and Research 2013, 2:15 http://dx.doi.org/10.7243/2049-7962-2-15</ref><ref name="MochizukiSingh2009">{{cite journal|last1=Mochizuki|first1=Manabu|last2=Singh|first2=Arun D.|title=Epidemiology and Clinical Features of Intraocular Lymphoma|journal=Ocular Immunology and Inflammation|volume=17|issue=2|year=2009|pages=69–72|issn=0927-3948|doi=10.1080/09273940902957305}}</ref>
* The [[prevalence]] of intraocular lymphoma remains unknown.<ref name="PIOL">Hanson JA, Alexandru D and Bota DA: The evaluation and treatment of primary intraocular lymphoma. journal of Cancer Therapeutics and Research 2013, 2:15 http://dx.doi.org/10.7243/2049-7962-2-15</ref><ref name="MochizukiSingh2009">{{cite journal|last1=Mochizuki|first1=Manabu|last2=Singh|first2=Arun D.|title=Epidemiology and Clinical Features of Intraocular Lymphoma|journal=Ocular Immunology and Inflammation|volume=17|issue=2|year=2009|pages=69–72|issn=0927-3948|doi=10.1080/09273940902957305}}</ref>


===Age===
===Age===
Line 100: Line 97:


===Race===
===Race===
*There is no racial predilection for intraocular lymphoma.
*There is no [[racial]] predilection for intraocular lymphoma.


==Risk Factors==
==Risk Factors==
*Common risk factors in the development of intraocular lymphoma, include:<ref name="ShenHerbort2001">{{cite journal|last1=Shen|first1=De Fen|last2=Herbort|first2=Carl P|last3=Tuaillon|first3=Nadine|last4=Buggage|first4=Ronald R|last5=Egwuagu|first5=Charles E|last6=Chan|first6=Chi-Chao|title=Detection of Toxoplasma Gondii DNA in Primary Intraocular B-Cell Lymphoma|journal=Modern Pathology|volume=14|issue=10|year=2001|pages=995–999|issn=0893-3952|doi=10.1038/modpathol.3880424}}</ref><ref name="pmid14971583">{{cite journal |vauthors=Chan CC |title=Molecular pathology of primary intraocular lymphoma |journal=Trans Am Ophthalmol Soc |volume=101 |issue= |pages=275–92 |date=2003 |pmid=14971583 |pmc=1358994 |doi= |url=}}</ref>
*Common [[risk factors]] in the development of intraocular lymphoma, include:<ref name="ShenHerbort2001">{{cite journal|last1=Shen|first1=De Fen|last2=Herbort|first2=Carl P|last3=Tuaillon|first3=Nadine|last4=Buggage|first4=Ronald R|last5=Egwuagu|first5=Charles E|last6=Chan|first6=Chi-Chao|title=Detection of Toxoplasma Gondii DNA in Primary Intraocular B-Cell Lymphoma|journal=Modern Pathology|volume=14|issue=10|year=2001|pages=995–999|issn=0893-3952|doi=10.1038/modpathol.3880424}}</ref><ref name="pmid14971583">{{cite journal |vauthors=Chan CC |title=Molecular pathology of primary intraocular lymphoma |journal=Trans Am Ophthalmol Soc |volume=101 |issue= |pages=275–92 |date=2003 |pmid=14971583 |pmc=1358994 |doi= |url=}}</ref>


:*Toxoplasma gondii infection
:*[[Toxoplasma gondii]] infection
:*EBV infection
:*[[EBV infection]]
:*HHV8 infection
:*HHV8 infection


== Natural History, Complications and Prognosis==
== Natural History, Complications and Prognosis==
*The majority of patients with intraocular lymphoma are symptomatic at the time of diagnosis.  
*The majority of patients with intraocular lymphoma are [[symptomatic]] at the time of diagnosis.
*Early clinical features include symptoms of a non-resolving uveitis, and blurred vision.<ref name="PIOL">Hanson JA, Alexandru D and Bota DA: The evaluation and treatment of primary intraocular lymphoma. journal of Cancer Therapeutics and Research 2013, 2:15 http://dx.doi.org/10.7243/2049-7962-2-15</ref>
*Early clinical features include symptoms of a non-resolving uveitis, and blurred vision.<ref name="PIOL">Hanson JA, Alexandru D and Bota DA: The evaluation and treatment of primary intraocular lymphoma. journal of Cancer Therapeutics and Research 2013, 2:15 http://dx.doi.org/10.7243/2049-7962-2-15</ref>
*If left untreated, patients with intraocular lymphoma may progress to develop complete vision loss.  
*If left untreated, patients with intraocular lymphoma may progress to develop complete vision loss.  

Latest revision as of 14:15, 18 September 2019

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Fahimeh Shojaei, M.D., Maria Fernanda Villarreal, M.D. [2]

Synonyms and keywords: PIOL; Ocular Lymphoma; Primary central nervous system ocular lymphoma

Overview

Intraocular lymphoma is a rare subtype of primary central nervous system lymphoma. Intraocular lymphoma may affect the eye secondarily from metastasis from a non-ocular tumor or may arise within the eye primarily. According to the World Health Organization (WHO) classification, intraocular lymphomas are most commonly a diffuse large B-cell immunohistologic subtype of non-Hodgkin's lymphoma. The most common symptoms of intraocular lymphoma are blurred or decreased vision. In the majority of patients, central nervous system involvement only accounts for 20% of primary central nervous system lymphomas. The median age at diagnosis among patients with intraocular lymphoma is between 50-60 years. The pathogenesis of intraocular lymphoma is characterized by the affection of the sub-retinal pigment epithelium, which is normally involved in the light absorption. On fluorescein angiography, findings may reveal "leopard spot" patterns due to sub-retinal pigment epithelium infiltrates that stain early and progressively or mottling of the sub-retinal pigment epithelium due to hyper- and hypo-fluorescent window defects. The initial therapy for patients with intraocular lymphoma is corticosteroids.

Historical Perspective

  • Intraocular lymphoma was first discovered by Samuel Wilks, a British physician, in 1856.[1]

Classification

Intraocular lymphoma may be classified according to its location into 2 subtypes:[2]


 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Intraocular lymphoma
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Retinal
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Uveal
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Retinal
 
 
 
Vitreoretinal
 
 
 
Vitreal
 
 
 
Iridal
 
 
 
Ciliary
 
 
 
Choroidal
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Primary
 
Secondary


Pathophysiology

  • Intraocular lymphoma can be either primary or secondary central nervous system lymphoma (oculocerebral lymphoma) that mainly affects the optic nerve and the eye.[3]
  • The pathogenesis of intraocular lymphoma is characterized by the affection of the sub-retinal pigment epithelium, which is normally involved in the light absorption.[4]
  • Genes associated with the development of intraocular lymphoma, include:[3]
  • On microscopic histopathological analysis, characteristic findings of intraocular lymphoma, include:[3]

Causes

  • There are no established causes of intraocular lymphoma.

Differentiating Intraocular Lymphoma from Other Diseases

Epidemiology and Demographics

Prevalence

Age

  • Intraocular lymphoma is more commonly observed among patients aged 50 to 60 years old.

Gender

  • Males are more commonly affected with intraocular lymphoma than females.

Race

  • There is no racial predilection for intraocular lymphoma.

Risk Factors

Natural History, Complications and Prognosis

  • The majority of patients with intraocular lymphoma are symptomatic at the time of diagnosis.
  • Early clinical features include symptoms of a non-resolving uveitis, and blurred vision.[4]
  • If left untreated, patients with intraocular lymphoma may progress to develop complete vision loss.
  • Common complications of intraocular lymphoma, include:[3]
  • Blindness
  • Radiation-induced retinopathy
  • Neovascular glaucoma
  • Prognosis is generally good, and the 5-year survival for patients with intraocular lymphoma is between 65-80%.[3]

Diagnosis

History and Symptoms

  • Common symptoms of intraocular lymphoma include:[4][9]

Physical Examination

  • Patients with intraocular lymphoma usually appear pale or malnourished.[4]
  • Physical examination may be remarkable for:
  • Decreased visual acuity (most common)
  • Irregular pupil
  • Increased lacrimation
  • Eye redness
  • Increased intraocular pressure

Laboratory Findings

  • There are no specific laboratory findings associated with intraocular lymphoma.

Imaging Findings

  • Magnetic resonance image (MRI) is the imaging modality of choice for patients with intraocular lymphoma.[4]
  • On MRI, characteristic findings of intraocular lymphoma, include:[3]
  • Fat suppressed T2 and post-contrast T1 weighted images, with thin slice thickness and a reduced FOV is ideal, and should include the cavernous sinuses.
  • T1: isointense to muscle 8
  • T2: hyperintense to muscle, hypointense to fat
  • T1 C+ (GAD): enhancement present but variable

Treatment

Medical Therapy

  • The initial therapy for intraocular lymphoma is corticosteroids.[4]
  • Other medical therapies for intraocular lymphoma, may include:[4]
  • Methotrexate
  • Intravitreal rituximab
  • Localized external beam radiation therapy (EBRT)

Surgery

  • Surgery is the mainstay of therapy for intraocular lymphoma.

Primary Prevention

  • There are no primary preventive measures available for intraocular lymphoma.[4]
  • Once diagnosed and successfully treated, patients with intraocular lymphoma are followed-up periodically every 3, 6, or 12 months.
  • The average relapse rate among patients with intraocular lymphoma is 2 years.[4]

Secondary Prevention

References

  1. Ahmed S, Shahid RK, Sison CP, Fuchs A, Mehrotra B. Orbital lymphomas: a clinicopathologic study of a rare disease. Am J Med Sci. 2006 Feb. 331(2):79-83.
  2. Coupland, Sarah E; Damato, Bertil (2008). "Understanding intraocular lymphomas". Clinical & Experimental Ophthalmology. 36 (6): 564–578. doi:10.1111/j.1442-9071.2008.01843.x. ISSN 1442-6404.
  3. 3.0 3.1 3.2 3.3 3.4 3.5 Intraocular lymphoma. Wikipedia. https://en.wikipedia.org/wiki/Intraocular_lymphoma
  4. 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 Hanson JA, Alexandru D and Bota DA: The evaluation and treatment of primary intraocular lymphoma. journal of Cancer Therapeutics and Research 2013, 2:15 http://dx.doi.org/10.7243/2049-7962-2-15
  5. Sen, H. Nida; Bodaghi, Bahram; Hoang, Phuc Le; Nussenblatt, Robert (2009). "Primary Intraocular Lymphoma: Diagnosis and Differential Diagnosis". Ocular Immunology and Inflammation. 17 (3): 133–141. doi:10.1080/09273940903108544. ISSN 0927-3948.
  6. Mochizuki, Manabu; Singh, Arun D. (2009). "Epidemiology and Clinical Features of Intraocular Lymphoma". Ocular Immunology and Inflammation. 17 (2): 69–72. doi:10.1080/09273940902957305. ISSN 0927-3948.
  7. Shen, De Fen; Herbort, Carl P; Tuaillon, Nadine; Buggage, Ronald R; Egwuagu, Charles E; Chan, Chi-Chao (2001). "Detection of Toxoplasma Gondii DNA in Primary Intraocular B-Cell Lymphoma". Modern Pathology. 14 (10): 995–999. doi:10.1038/modpathol.3880424. ISSN 0893-3952.
  8. Chan CC (2003). "Molecular pathology of primary intraocular lymphoma". Trans Am Ophthalmol Soc. 101: 275–92. PMC 1358994. PMID 14971583.
  9. Coupland, Sarah E; Damato, Bertil (2008). "Understanding intraocular lymphomas". Clinical & Experimental Ophthalmology. 36 (6): 564–578. doi:10.1111/j.1442-9071.2008.01843.x. ISSN 1442-6404.