Author: Claude (AI), from PubMed abstracts · Reviewed by: Dr Mina Abdelmseih · Reviewed: 2026-11-15 · Review due: 2027-11-15

Educational content only. Not personalised medical advice. Clinical decisions remain the responsibility of the treating clinician.

Ocular adnexal lymphoma

Ocular adnexal lymphoma (OAL) affects the orbit, conjunctiva, lacrimal gland and eyelid, and is almost always of B-cell origin [S5] [S7]. Extranodal marginal zone (MALT) lymphoma is the commonest subtype and carries a good prognosis, while high-grade subtypes do worse [S5] [S7]. Radiotherapy gives excellent local control for localised low-grade disease [S4].

Key points - MALT lymphoma made up 75% of cases in a review of 2009 treated patients [S4], 67.9% in Taiwan [S7] and 71.6% in Slovenia [S11]. - Subtype and stage are the best indicators of prognosis [S5] [S7]. - Radiotherapy gave average local control of 95.9% for MALT lymphoma, with 5-year overall survival of 93.8% [S4]. - Ultra-low-dose radiotherapy (4 Gy in 2 fractions) gave complete response in 90.0% in a phase 2 trial with no grade 3 or higher toxicity [S10]. - Doxycycline, targeting Chlamydophila psittaci, is an option for stage I MALT lymphoma, with lower response rates than radiotherapy [S1] [S4].

Evidence last checked: 2026-10-17 (PubMed abstracts).

Red flags

• High-grade subtype or advanced stage. Diffuse large B-cell and mantle cell lymphomas carry a poor prognosis [S5]; high-grade subtype and advanced stage predicted worse outcomes in Taiwan [S7].
• Systemic disease. Ocular manifestation was the first sign of lymphoma in 78.4% of a Slovenian cohort, but the ocular adnexa were the only site in 67.6% [S11]; systemic examination is therefore needed [S6].
• Relapse years later. Progression-free survival fell from 86.2% at 5 years to 44.6% at 15 years [S7].

Recognise it

• Orbital lymphoma is primarily a disease of the elderly [S5]; median age at diagnosis was 68 years in Slovenia [S11] and mean 59.0 years in Taiwan [S7].
• Sites in a Taiwanese series: orbit 39.3%, conjunctiva 27.7%, lacrimal gland 25.0%, eyelid 7.1% [S7].
• MALT and follicular lymphoma show a female predominance; mantle cell lymphoma is 80% male [S5].
• Clinical signs are not described in these abstracts.

Confirm it

• Diagnosis is histological; all patients in the cohorts had histologically confirmed disease [S2] [S11].
• Subtype the lymphoma: in orbital lymphoma, 97% are B-cell, with marginal zone 59%, diffuse large B-cell 23%, follicular 9% and mantle cell 5% [S5].
• Stage the disease systemically [S6]; TNM stage independently predicted progression-free survival after doxycycline [S2].
• C. psittaci DNA was found in 89% of biopsies of stage I ocular adnexal MALT lymphoma in an Italian-led trial and can be monitored in conjunctival swabs and blood [S1].
• High-resolution OCT can be used for diagnosis and follow-up of conjunctival lymphoma [S6].

Manage it

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Tier A (primary care / no specialist)

• Refer an older adult with a new orbital, lacrimal or conjunctival mass to an eye clinic (see Refer when).

Tier B (general eye clinic)

• Arrange biopsy with histology through a service with pathology support, and refer for haematology or oncology staging [S6].
• Where radiotherapy is unavailable, note that doxycycline has been used first-line in stage I MALT lymphoma [S1] [S2]; the decision should involve a lymphoma team.

Tier C (specialist centre)

1. Radiotherapy for localised low-grade disease. Radiotherapy is the treatment of choice for solitary low-grade lymphoma [S5]. Complete response occurred in 75-90% and local relapse in 3.5-5% across 25 studies; lens shielding was associated with better 5-year progression-free survival, and cataract risk rose above 30 Gy [S8].
2. Ultra-low-dose radiotherapy. In a phase 2 trial of 50 patients, 4 Gy in 2 fractions, as reported in [S10], gave a 2-year local control of 89.4%; persistent disease received an additional 20 Gy in 10 fractions [S10]. A systematic review of 10 studies (591 patients) found complete response in 50% to 95% and no grade 3 or higher toxicity [S12].
3. Doxycycline. In a phase 2 trial, doxycycline gave an overall response rate of 65% and 5-year progression-free survival of 55%; eradication of C. psittaci was associated with better response (86% vs 47%) [S1]. In a Korean cohort of 90 patients, doxycycline 100 mg twice daily for 3 weeks (one or two cycles), as reported in [S2], gave 5-year progression-free survival of 60.9%; failures were salvaged with chemotherapy and/or radiotherapy [S2]. The AAO review reported complete responses of only 4.4% to 13% with doxycycline [S4].
4. Disseminated or high-grade disease. Chemotherapy with or without radiotherapy should be chosen [S5].
5. Rituximab. In pooled conjunctival lymphoma cases, systemic rituximab gave complete response in 63% and intralesional rituximab in 75% [S9].
6. Side effects. Cataract (12.1%) and dry eye (8.5%) were the commonest treatment complications [S4]; acute dry eye usually settled with artificial tears [S8].

Refer when

Pitfalls

• Treating the eye without systemic staging [S6].
• Assuming all OAL behaves like MALT lymphoma: high-grade subtypes have a poor prognosis [S5].
• Using standard-dose radiotherapy without considering lower-dose options for indolent disease [S10] [S12].
• Stopping follow-up at 5 years: late progression occurs [S7].

Evidence notes

• There are no RCTs comparing treatments; there is no consensus on the best upfront treatment [S3].
• Doxycycline response varies widely between sources [S1] [S2] [S4]; reasons are not explained in these abstracts.
• Not covered by these sources: clinical signs, regional C. psittaci prevalence, imaging protocols, staging investigations, chemotherapy regimens, and evidence-based referral timings.

Related articles

• Idiopathic Orbital Inflammation and IgG4-Related Orbital Disease
• Vitreoretinal lymphoma

References

See the numbered source list below. Each marker [S#] links to its PubMed and DOI record.