Intraocular lymphoma

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

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.

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

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

• Retinal
  • Retinal
  • Vitreoretinal
  • Vitreal
• Uveal
  • Iridal
  • Ciliary
  • Choroidal

Intraocular lymphoma

Retinal

Uveal

Retinal

Vitreoretinal

Vitreal

Iridal

Ciliary

Choroidal

Primary

Secondary

• 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.^[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]

• C-MYC gene
• CCND1 gene

• On microscopic histopathological analysis, characteristic findings of intraocular lymphoma, include:^[3]

• Marginal zone (52%)
• Follicular (23%)
• Atypical lymphocytes (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.^[4]

• There are no established causes of intraocular lymphoma.

• Intraocular lymphoma must be differentiated from other diseases that cause chronic loss of vision, or headaches, such as:^[4][5]

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

• The prevalence of intraocular lymphoma remains unknown.^[4][6]

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

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

• There is no racial predilection for intraocular lymphoma.

• Common risk factors in the development of intraocular lymphoma, include:^[7][8]

• Toxoplasma gondii infection
• EBV infection
• HHV8 infection

• 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]

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

• Burning of the eye
• Redness of the eye
• Visual field defect
• Blurred vision
• Photophobia or sensitivity to light
• Eye pain
• Floaters
• Headache

• 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

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

• 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

• 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 is the mainstay of therapy for intraocular lymphoma.

• 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]