A patient with floaters and blurred vision is treated repeatedly for presumed uveitis. Steroids help, but only temporarily. As inflammation recurs, suspicion shifts slowly away from benign inflammatory disease toward a more serious masquerade. For vitreoretinal specialists, this scenario is often the first clinical clue of primary vitreoretinal lymphoma (PVRL).
At the 2026 Retina World Congress in Fort Lauderdale, Florida, Kapil Mishra, MD, a clinical assistant professor of ophthalmology, vitreoretinal surgery, and ocular oncology at the Gavin Herbert Eye Institute of the University of California, Irvine, reviewed diagnostic and therapeutic strategies for intraocular lymphoma. His presentation focused on the persistent challenge of distinguishing the disease from chronic inflammatory conditions and the growing role of molecular testing and targeted therapy.
Figure 1. Symptoms of primary vitreoretinal lymphoma include blurred vision, floaters, and photopsias, as well as examination findings of vitritis and vitreous haze.
PVRL is a B-cell malignancy closely linked to primary central nervous system (CNS) lymphoma. “These cases occur in patients in their 60s and 70s, with a slight female preponderance,” Dr. Mishra observed. “It is usually bilateral, although it can present in just one eye. In maybe a quarter of cases, patients will present with brain involvement . If they do not present with brain involvement initially, a larger percentage will develop CNS involvement over the course of their disease, especially without systemic prophylaxis.”
The clinical presentation often resembles chronic uveitis, he said. Patients report floaters, blurred vision, and occasionally photopsias (Figure 1). On examination, vitreous cells and haze are common, but retinal findings may also be present, including infiltrates below the retinal pigment epithelium (RPE) and subtle lesions that can be easily missed.
One of the major diagnostic challenges is partial responsiveness to corticosteroids. “They may respond to steroids, but not completely, or they will recur pretty quickly when the steroids are tapered,” Dr. Mishra said. This pattern often delays definitive diagnosis and contributes to repeated treatment for inflammatory disease.
Multimodal imaging supports clinical suspicion but is rarely diagnostic on its own (Figure 2). Optical coherence tomography (OCT) may show hyperreflective vitreous clumps and RPE-adjacent thickening, while autofluorescence and other imaging modalities may provide additional clues. Dr. Mishra emphasized the importance of integrating imaging findings with clinical context. “If a patient does not have cystoid macular edema, is older, has bilateral disease, and predominantly vitritis, lymphoma should certainly be on the differential,” he said.
Figure 2. Multimodal imaging, including optical coherence tomography and fundus autofluorescence, can aid in the evaluation of primary vitreoretinal lymphoma.
Definitive diagnosis relies on vitreous biopsy, typically performed via pars plana vitrectomy.
Systemic evaluation is essential once ocular lymphoma is suspected or confirmed. This includes brain MRI, lumbar puncture for cerebrospinal fluid cytology, and systemic imaging to exclude extraocular disease. Baseline laboratory testing is also recommended, particularly in patients who may require chemotherapy, and evaluation for infectious comorbidities is standard. Care is coordinated closely with hematology and oncology.
Treatment remains individualized and depends on whether disease is confined to the eye or involves the CNS. Intravitreal methotrexate is the most common local therapy. It is typically administered at a dose of 400 µg per 0.1 mL on an intensive schedule that tapers over time. Dr. Mishra noted that a response is often seen after several injections. The main drawback of methotrexate is the risk of corneal epithelial toxicity; therefore, rituximab is an alternative intravitreal agent for patients who cannot tolerate methotrexate.
“Regarding emerging treatments, BTK inhibitors have an important role, particularly because of their CNS penetration,” Dr. Mishra said. “These include ibrutinib and zanubrutinib. Early case series and trials suggest efficacy. There are also studies evaluating rituximab and lenalidomide. Immune checkpoint inhibitors have limited ocular data but are an area of growing interest. Autologous stem cell transplant is also being explored.”
“In summary, this is a challenging condition, but survival has improved significantly over the past few decades,” Dr. Mishra concluded (Figure 3). “There are increasing therapeutic options, including chemotherapeutic regimens with efficacy, although further trials are needed.” RP
Figure 3. Management of primary vitreoretinal lymphoma is guided by whether disease is isolated to the eye or involves the central nervous system.