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.

Vitreoretinal lymphoma

Vitreoretinal lymphoma (VRL) is a rare malignancy, usually a diffuse large B-cell lymphoma, that forms a subset of primary central nervous system lymphoma (PCNSL) [S1] [S11]. It commonly masquerades as posterior uveitis, so diagnosis is often delayed [S1] [S10]. Most patients eventually develop CNS lymphoma, which is the main cause of death [S1] [S8].

Key points - Suspect VRL in an older adult with "uveitis" showing vitreous cells in sheets or clumps and creamy-white outer retinal lesions [S7]. - Diagnostic vitrectomy should be performed, and systemic corticosteroids stopped at least 2 weeks before surgery, according to an international Delphi consensus [S7]. - An IL-10:IL-6 ratio greater than 1 had the highest pooled sensitivity (89.39%) among diagnostic tests [S10]. - Local treatment (intravitreal methotrexate or rituximab, or ocular radiotherapy) clears the eye but does not prevent CNS relapse [S8]. - Consider VRL in HIV-positive people presenting with intermediate or posterior uveitis [S5].

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

Red flags

• "Uveitis" in an older person that does not behave as expected. VRL commonly masquerades as posterior uveitis and mostly affects elderly people [S1].
• Severe vitreous infiltration without macular oedema. This is the most likely presentation [S7].
• Steroid use before sampling. Systemic corticosteroids should be discontinued at least 2 weeks before diagnostic surgery [S7].
• Neurological symptoms. 65%-90% of patients with VRL develop CNS lymphoma [S1].

Recognise it

• Symptoms: floaters and painless loss of vision [S7].
• Signs: vitreous cells organised into sheets or clumps; multifocal creamy or white outer retinal lesions; "leopard-skin" retinal lesions and RPE atrophy [S7]. Lesions may lie beneath the RPE, in the subretinal space or within the retina [S11].
• In HIV-related VRL, patients are relatively young with very low CD4 counts, and vitritis with subretinal or sub-RPE infiltrates is typical [S5].
• Among people with VRL, 41% have non-ocular CNS involvement at diagnosis and 69% over the course of disease [S4].

Confirm it

• Sampling. Diagnostic vitrectomy is recommended [S7]. Vitreous cytology is the gold standard, supplemented by flow cytometry, genetic analyses and interleukin-10 measurement [S5]. Lymphoma cells are fragile and cannot always be identified, so close coordination with cytologists is needed [S8].
• Tests (sensitivity in a systematic review of 29 retrospective studies): IL-10:IL-6 ratio >1, 89.39%; vitreous flow cytometry, 88.00%; monoclonal IgH rearrangement by PCR, 85.10%; MYD88 L265P mutation, 70.00%; CD79B mutation, 35.09% [S10].
• Imaging. OCT and fundus autofluorescence are recommended [S7].
• Neuroimaging and CNS staging. Required because of frequent CNS involvement [S4]; the specific workup is not detailed in these abstracts.

Manage it

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Tier A (primary care / no specialist)

• Refer any older adult or HIV-positive person with persistent floaters, blurred vision or uveitis to an eye clinic [S5] [S7].
• Avoid starting systemic corticosteroids for presumed uveitis without an ophthalmic diagnosis, as steroids should be stopped before diagnostic surgery [S7].

Tier B (general eye clinic)

• Suspect VRL when "uveitis" shows the features above, especially without macular oedema [S7].
• Refer to a centre able to perform diagnostic vitrectomy with cytology and interleukin testing (see Refer when) [S7] [S8].
• In HIV-positive patients, ensure linkage to antiretroviral therapy, which is part of treatment [S5].

Tier C (specialist centre)

1. Multispecialty care. Management involves a team coordinating intraocular chemotherapy, ocular irradiation, systemic chemotherapy and/or autologous stem cell transplantation [S3].
2. Intravitreal chemotherapy. Methotrexate and rituximab are the most commonly injected drugs; several schedules exist but none has been tested in a randomised trial [S3]. Dosing is not covered here; follow local protocols.
3. Systemic therapy. High-dose methotrexate-based chemotherapy, with or without local treatment, might reduce CNS relapse [S8]. Systemic chemotherapy alone gives high response rates but a high relapse rate [S1]. In a small series of 12 patients, bilateral radiotherapy (30-40 Gy, as reported in [S2]) followed by methotrexate-based chemotherapy produced complete response in all, and median survival had not been reached at 68 months [S2].
4. Laterality. CNS progression did not differ between bilateral and unilateral VRL (pooled RR 1.12) [S9].
5. Prognosis. Despite high ocular control with intravitreal agents, 65-85% of patients eventually die of CNS disease, and the role of adjuvant therapy is unknown [S6].
6. Relapse. Intensive consolidation chemotherapy with stem cell transplantation can be considered; ibrutinib, lenalidomide and temozolomide are effective at relapse [S8].

Refer when

Pitfalls

• Treating presumed uveitis with corticosteroids before diagnostic sampling [S7].
• Taking a negative cytology result as excluding lymphoma [S8].
• Relying on MYD88 or CD79B mutation testing alone: sensitivity is lower than other tests [S10].
• Treating the eye only and forgetting CNS surveillance [S6] [S8].

Evidence notes

• Proportions of patients developing CNS disease vary between sources (65%-90% [S1]; 69% [S4]; 65-85% dying of CNS disease [S6]).
• No randomised trials of VRL treatment exist in these sources; treatment evidence is retrospective or from small cohorts [S3] [S8].
• The diagnostic systematic review reports sensitivity only, not specificity [S10].
• Not covered by these sources: drug doses for intravitreal or systemic therapy, CNS staging protocol, follow-up schedules, and validated referral timings.

Related articles

• Ocular adnexal lymphoma
• Cytomegalovirus Retinitis

References

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