What is the treatment for vitreoretinal lymphoma?

Treatment of Vitreoretinal Lymphoma

For patients with vitreoretinal lymphoma (PVRL), treatment should include high-dose methotrexate-based chemotherapy combined with intravitreal therapy to prevent central nervous system dissemination, which is the main cause of death in these patients. 1

Understanding Vitreoretinal Lymphoma

• Vitreoretinal lymphoma (VRL) is a rare variant of primary central nervous system lymphoma (PCNSL), mostly diffuse large B-cell lymphoma, affecting the retina and/or vitreous 2
• Up to 90% of patients with PVRL develop CNS dissemination within 30 months, which is the main cause of death 1
• Median survival appears to be longer when patients are treated at the time of PVRL diagnosis rather than at CNS relapse 1

Treatment Algorithm

First-Line Treatment for Fit Patients

• High-dose methotrexate (HD-MTX)-based induction chemotherapy should be used for fit patients with PVRL, using the same combinations proposed for other PCNSL patients 1
• Intravitreal methotrexate injections can be added if rapid regression of intraocular disease is needed 1
• Patients achieving complete or partial response to HD-MTX-based induction can receive consolidation with low-dose bilateral ocular radiotherapy 1
• Consolidation with autologous stem cell transplantation (ASCT) can be considered for selected patients 1

Local Therapy Options

• Intravitreal injections of antitumor drugs (usually methotrexate or rituximab) can be used under local anesthesia 1
• Intravitreal rituximab (1 mg/0.1 mL) has shown efficacy with complete remission in 64.6% of eyes after a median of 3 injections 3
• Local treatments are effective for controlling intraocular disease but fail to prevent CNS relapses, and ocular relapses remain frequent 1
• External beam ocular radiotherapy is rarely used alone as first-line treatment but may be considered for bilateral ocular involvement or as salvage treatment for elderly patients 1

Treatment for Relapsed/Refractory Disease

• Intensive thiotepa-based chemotherapy followed by autologous stem cell transplantation (ASCT) is feasible and effective in fit patients with relapsed/refractory PVRL 1
• Alternative therapies for relapsed/refractory disease include:
  • Temozolomide 1
  • Lenalidomide (alone or combined with rituximab) 1
  • Ibrutinib 1, 4
  • Pomalidomide 4

Special Considerations

• For patients with bilateral ocular involvement without CNS involvement, intravitreal chemotherapy with methotrexate and/or rituximab may be sufficient 2
• Encouraging results have been reported with combination of bilateral ocular radiotherapy and HD-MTX-based chemotherapy 1
• Vitrectomy may be helpful as a debulking procedure before initiating chemotherapy 4
• Monitoring for treatment response should include slit lamp and fundus examination during and after treatment 1

Potential Complications and Monitoring

• Intravitreal rituximab may cause complications in approximately 25% of treated eyes, but significant visual acuity loss (2-line loss of Snellen) occurs in only about 4.2% of cases 3
• Aqueous levels of IL-10 are helpful in monitoring for recurrence of local disease 4
• Regular assessment of therapeutic response should be performed using slit lamp and fundus examination 1

Common Pitfalls to Avoid

• Delaying treatment at PVRL diagnosis, as earlier treatment is associated with longer survival 1
• Using only local treatments without systemic therapy, as this fails to prevent CNS dissemination in most patients 1
• Failing to consider the patient's overall fitness for intensive chemotherapy regimens, as treatment approaches differ significantly between fit and unfit patients 1
• Overlooking the need for multispecialty coordination involving ophthalmologists, hematologists, and oncologists 5