- Prognosis is generally good, with malignancy usually confined to primary site.
- Systemic dissemination occurs in 5%–10% of cases, especially rare in patients with conjunctival lymphoma.
- Some anecdotal cases of spontaneous tumor remission have been reported.
- Assumes that patients have not been treated with topical steroids or antibiotics
- Some patients experience multiple relapses, involving contralateral orbit and distant extranodal organs.
- Reliable prognostic factors remain to be defined.
- "Wait and watch" strategy after resection or biopsy in patients with stage I-disease produces results similar to treatment with radiotherapy, with 10-year survival of 94%.
Universally accepted guidelines for the medical management of ocular adnexal MALT lymphoma do not exist.
The eradication of chlamydial infection with doxycycline (100 mg orally twice a day for 3 weeks) has been proposed as a valid therapeutic strategy (Ferreri, JCO 2009; Ferreri, JCO 2012).
Half of patients experience objective lymphoma regression, which is more evident and long-lasting when the bacterial eradication is verified (Ferreri, JCO 2012).
Clinical trials have confirmed that doxycycline is a fast, safe, cost-effective therapy for chlamydia-positive patients.
Reinfection due to prolonged contact with infected pets or the effect of other concomitant infections (i.e., hepatitis C virus) could result in reduced efficacy of this biological treatment.
Antiviral combination therapy with peginterferon and ribavirine has produced encouraging results in HCV-positive patients with OAML.
Macrolide antibiotics in particular have a direct antiproliferative effect, and 2 small prospective trials have shown that half of patients achieve lymphoma regression with a prolonged exposure to oral clarithromycin.
Experience with chemotherapy is still limited.
Combination therapy with alkylating agents such as bendamustine and chlorambucil and the anti-CD20 monoclonal antibody rituximab is associated with a 90%–100% overall response rate and a 5-year relapse-free survival of 90%.
The efficacy of monotherapy in MALT lymphoma patients is significantly lower.
Radiotherapy is the most extensively studied treatment in ocular adnexal MALT lymphoma, but a universally accepted radiation schedule does not exist.
Recent studies suggest a radiation field including a gross tumor volume with 0.5- to 1‑cm margin for a planning target volume and a dose of 25–30 Gy in 10 to 15 fractions (minimal target dose > 25 Gy).
Electron beams (4-12 MeV) and 4-9 megavolt photon beams are advisable in conjunctival and orbital lymphomas, respectively.
A single anterior field or a wedge pair of anterior fields have been used in most series.
In conjunctival lymphoma, the entire conjunctiva and eyelid should be irradiated.
Preliminary data seem to suggest that the entire orbit should be irradiated in patients with intra-orbital lymphoma.
Response is usually slow and gradual.
In-field relapses are rare and seem to be related to low radiation doses or to the use of shielding lens.
Relapse rate at 4 years is 20-25%; half of relapses involve the contralateral orbit.
90Y-ibritumomab tiuxetan (Zevalin®), an anti-CD20 radioimmunoconjugate has been used in a few cases of limited disease and is an alternative.
Surgical biopsy is a necessary diagnostic step.
Some tumors might be amenable to primary resection.
Surgery is an option for aesthetic reasons in cases.
Other management considerations
Intralesional injection of biological agents like interferon and rituximab might have efficacy.
Common treatment responses, follow-up strategies
Less than 5% of ocular adnexal lymphoma patients die of lymphoma, with a 5-year cause-specific and overall survival of 100% and > 90%, respectively.
Local control rates vary according to therapy, with a 5-year relapse-free survival of about 65%.
Relapses of limited-stage OAML are usually in the primary sites of disease.
Examination and gadolinium-enhanced MRI of the orbits should be performed every six months for the first five years of follow-up and once a year afterward.
Specific investigation of distant organs is indicated only with clinical suspicion.
Treatment of relapsing disease depends on patient's age and comorbidity, previous antilymphoma therapies, extension and site of relapse, as well as duration of response to the previous treatment.
Local therapies for orbital or conjunctival relapses include surgical resection and intralesional therapies, whereas orbital reirradiation is associated with high risk of complications.
Systemic therapies include chemotherapy, immunotherapy and antibiotics; importantly, these therapies can be repeated in the case of previous long-lasting responses.