Overview
- Definition
Intraocular lymphoma mimicking intermediate, posterior, or panuveitis in older patients not responsive to steroid therapy; typical subtype is diffuse, large B-cell, non-Hodgkin’s
Primary intraocular lymphoma (PIOL) denotes absence of central nervous system (CNS) involvement
- Symptoms
Blurry vision
Floaters
Scotoma
Frank inflammatory symptoms such as redness, pain, and photophobia are rare unless there is significant anterior segment infiltration
- Laterality
80% bilateral
- Course
Insidious and progressive
- Age of onset
50–60 years (range 15–85)
- Gender/race
Slight female and Caucasian predilection
- Systemic association: CNS lymphoma
20% of CNS lymphoma patients have ocular disease at the time of diagnosis; however
If intraocular lymphoma is diagnosed first, 60–80% develop CNS disease after 2–3 years
Overall, intraocular-CNS lymphoma makes up only 1% of all non-Hodgkin’s lymphoma in immunocompetent patients (200 cases diagnosed a year in the United States)
Higher incidence of intraocular-CNS lymphoma in acquired immunodeficiency syndrome (AIDS), post-organ transplant, and congenital immunodeficiencies
Exam: Ocular
Anterior Segment
No or very mild external sign of inflammation
Conjunctival hyperemia
Keratic precipitates
Mild Anterior Chamber reaction
Posterior Segment
Large clumps or sheets of cells in vitreous
Mild to very dense vitritis
Multifocal, large, yellow sub-RPE or subretinal infiltrates
Exam: Systemic
Headache
Personality change
Alertness alteration
Memory loss
Nausea/vomiting
Gait imbalance
Weakness
Seizure
Imaging
OCT: Sub-RPE hyper-reflective material; no CME
FA: RPE granularity and possible blockage corresponding to sub-RPE infiltrates, but no vasculitis, papillitis, or macular leakage that would be expected in inflammatory syndromes
Laboratory and Radiographic Testing
- Gold standard for ocular diagnosis is either
- Vitreous biopsy or sub-RPE aspirate via pars plana vitrectomy; not uncommon to need repeat biopsy if first one negative; ALL following analyses are recommended to have best yield
Undiluted sample for cytopathology
- Diluted sample for molecular genetics to look for monoclonality
IgH gene rearrangement: B-cell lymphoma
T-cell receptor gene rearrangement: T-cell lymphoma
- Diluted sample for interleukin (IL)-6 and -10 levels
High IL-10/6 consistent with lymphoma
- Chorioretinal biopsy
Used when there is obvious, focal chorioretinal lesion but little vitreous cellularity
Significantly higher ocular morbidity than vitreous biopsy alone (retinal detachment, vitreous hemorrhage, proliferative vitreoretinopathy, etc.)
- MRI brain to assess extent of any CNS involvement
Deep brain structures, especially front lobe, are more often involved than cerebral cortex compared to other brain tumors (thus change in personality and alertness).
Supratentorial and multicentric in half the cases; characteristically dense and diffuse enhancement with distinct borders.
Positron emission tomography (PET) (may not detect Primary intraocular lymphoma [PIOL])
Lumbar puncture: Required in all patients suspected of CNS lymphoma
Differential Diagnosis
Sarcoidosis
Tuberculosis
- White dot syndromes, especially Birdshot
White dot syndrome in an older patient ➔ think lymphoma
Viral retinitis
Lymphoid hyperplasia of the uvea (usually unilateral and responds well to steroids)
Amelanotic uveal melanoma
Uveal metastasis
Treatment
- Local therapies
Intravitreal methotrexate (MTX) 400 mcg/0.1 cc or rituximab (RTX) 1 mg/0.1 cc weekly for 6 weeks, extended as needed if cellularity or lesion persists; repeat cycles as needed
If subretinal lymphoma is threatening macula and there is little suspicion for infectious uveitis, then empiric intravitreal MTX may be appropriate before biopsy result is available
External beam radiation
Given the high rate of eventual CNS involvement, we recommend systemic chemotherapy as prophylaxis even if there is no CNS involvement at the time of diagnosis
Referral/Co-management
Neuro-oncology
Radiation oncology
Neurology