Role of intravitreal methotrexate in the management of primary central nervous system lymphoma with ocular involvement

Ophthalmology. 2002 Sep;109(9):1709-16. doi: 10.1016/s0161-6420(02)01125-9.


Purpose: To evaluate the safety and efficacy of intravitreal methotrexate in the management of primary central nervous system lymphoma (PCNSL) involving the eye.

Design: Retrospective noncomparative interventional case series.

Participants: Sixteen human immunodeficiency virus-negative white patients (5 males and 11 females, aged 30-76 years) with intraocular B cell lymphoma treated with intravitreal methotrexate at Oregon Health & Science University or Hadassah University Hospital between August 1995 and September 2000.

Intervention: Patients were treated with intravitreal methotrexate (400 micro g/0.1 ml) according to a standard induction-consolidation-maintenance regimen and monitored by serial examinations, including measurement of visual acuity, slit-lamp biomicroscopy, and dilated funduscopy.

Main outcome measures: Clinical response to intravitreal chemotherapy, number of injections for clinical remission, visual acuity, complications during study period, length of survival from diagnosis, and cause of death.

Results: Time of follow-up from commencement of the methotrexate injections was 6 to 35 months (median, 18.5 months). Twenty-six of 26 eyes (100%) were cleared clinically of malignant cells after a maximum of 12 methotrexate injections. A second remission was induced in three patients, who were treated with a further course of intravitreal chemotherapy after their tumor recurred within the eye. Complications that occurred during the period of treatment and follow-up included cataract (73% of 26 eyes), corneal epitheliopathy (58% of 26 eyes), maculopathy (42% of 26 eyes), vitreous hemorrhage (8% of 26 eyes), optic atrophy (4% of 26 eyes), and sterile endophthalmitis (4% of 26 eyes). No patient had irreversible loss of vision that could be definitely attributed to the intravitreal injection of methotrexate.

Conclusions: Intravitreal chemotherapy with methotrexate is effective in inducing clinical remission of intraocular tumor in PCNSL with acceptable morbidity. Further study is indicated to determine whether this approach extends life expectancy.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Central Nervous System Neoplasms / drug therapy*
  • Central Nervous System Neoplasms / mortality
  • Central Nervous System Neoplasms / pathology
  • Disease-Free Survival
  • Eye Neoplasms / drug therapy*
  • Eye Neoplasms / mortality
  • Eye Neoplasms / pathology
  • Female
  • Humans
  • Lymphoma, B-Cell / drug therapy*
  • Lymphoma, B-Cell / mortality
  • Lymphoma, B-Cell / pathology
  • Male
  • Methotrexate / therapeutic use*
  • Middle Aged
  • Remission Induction
  • Retrospective Studies
  • Safety
  • Survival Rate
  • Visual Acuity
  • Vitreous Body / drug effects*


  • Antimetabolites, Antineoplastic
  • Methotrexate