Keywords

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