This is a prospective single arm phase II study, and the purpose of this study is to evaluate the efficiency of R2 regimen (rituximab & lenalidomide) combined with intravitreal methotrexate and followed by lenalidomide maintenance in newly-diagnosed primary intraocular lymphoma. Progression free survival (PFS) of the cohort is the primary endpoint.

All the patients will be treated with R2 regimen （Rituximab 375mg/m2 IV d1, lenalidomide 25mg d1-21, 28 days per cycle) as induction regimen, meanwhile intravitreal methotrexate was given at a dose of 400ug for 16 doses.

The response will be evaluated every 3 cycles. After 3 Cycles, patients who achieved complete remission (CR) or partial remission (PR) will receive 3 more cycles of R2 regimen. The patients with stable disease (SD) or progressed disease (PD) will withdraw from the trial and receive salvage regimens. After total 6 induction cycles, the investigators evaluate the efficiency again, the patients with CR or PR will go to lenalidomide maintenance for 2 years or until progression of the disease (PD), unacceptable toxicity, or patient/investigator discretion. And the patients with SD or PD will receive salvage regimen.

During following-up, surveillance ophthalmologic examination and brain magnetic resonance imaging (MRI) scans can be performed every 3 months up to the first 2 years, followed by doctor visit every 6 months up to 5 years or the disease relapses.

Inclusion Criteria:

• Newly-diagnosed primary vitreoretinal lymphoma
• ECOG≤2
• creatinine clearance rate (CCR) ≥ 60ml/h, according to Cockcroft-Gault
• Total bilirubin < 2 upper limits of normal, alanine aminotransferase（ALT） < 3 upper limits of normal
• Sign the Informed consent
• Women of childbearing potential must understand that the study medication could have a potential teratogenic risk. They should undergo complete contraception during the study period.
• Male subjects must agree to use condoms throughout study drug therapy.

Exclusion Criteria:

• primary central nervous system lymphoma involved eyes and brain
• systemic B cell lymphoma involved eyes
• Pre-existing uncontrolled active infection
• Clinical evidence of grade 3 or 4 heart failure as defined by the New York Heart Association criteria
• Pregnancy or active lactation
• Co-existing tumors
• HIV（human immunodeficiency virus） or HBV（hepatitis B virus） or HCV（hepatitis C virus） infection