Intraocular lymphoma is a rare form of cancer that originates within the eye. It is a type of non-Hodgkin lymphoma, which means it develops from lymphocytes, a type of white blood cell that is part of the immune system. Early and accurate detection is important for effective management and improved outcomes.
Understanding Intraocular Lymphoma
Intraocular lymphoma (IOL) is a rare malignancy where lymphocytes proliferate abnormally inside the eye, affecting the retina, vitreous, and uvea. There are two main types: primary intraocular lymphoma (PIOL), which originates directly in the eye, and secondary intraocular lymphoma (SIOL), which occurs when lymphoma spreads to the eye from another part of the body.
PIOL is closely associated with primary central nervous system (CNS) lymphoma (PCNSL). Most cases of PIOL will eventually involve the CNS, with 60% to 80% of PIOL patients developing CNS disease. Conversely, ocular involvement is seen in 15% to 25% of patients with PCNSL.
The most common type of PIOL is diffuse large B-cell lymphoma, a high-grade, fast-growing cancer. Genetic mutations, such as those affecting the MYD88 gene, and immune system dysfunction have been identified as potential risk factors. PIOL typically affects older adults, with a median age at diagnosis ranging from 55 to 65 years.
Recognizing the Signs
The symptoms of intraocular lymphoma are often non-specific, making diagnosis challenging as they can resemble common inflammatory eye conditions like uveitis. This similarity can lead to delays in diagnosis while patients are initially treated for inflammation. A common sign is uveitis, or eye inflammation, occurring in approximately 75% of cases.
Blurred or decreased vision is a frequent symptom, often due to tumor cells accumulating in the vitreous humor. Patients may also notice floaters, which are small specks or cobweb-like images drifting in their visual field. Other symptoms include redness or swelling in the eye, increased sensitivity to light (photophobia), and, less commonly, eye pain.
Symptoms can affect one or both eyes, with 80% to 90% of PIOL cases eventually affecting both eyes, though initial presentation might be unilateral or asymmetric. In advanced cases, the tumor can cause double vision, or make the eye appear larger or pushed forward.
How It’s Diagnosed
Diagnosing intraocular lymphoma involves a thorough and multidisciplinary approach. The process begins with a comprehensive eye examination by an ophthalmologist, including a slit-lamp exam and ophthalmoscopy. During ophthalmoscopy, creamy yellow-to-orange subretinal infiltrates may be observed.
Specialized imaging tests are also performed. A magnetic resonance imaging (MRI) scan of the brain and orbits is conducted to check for central nervous system involvement, as PIOL has a strong association with brain lymphoma. Fluorescein angiography can reveal “leopard spot” patterns due to sub-retinal pigment epithelium infiltrates, while optical coherence tomography (OCT) can visualize subretinal layers and detect lesions.
The definitive diagnosis of PIOL requires a vitreous biopsy, where fluid or tissue samples are collected from the eye for pathological analysis. This procedure allows for cytology to identify atypical lymphoid cells, flow cytometry to characterize cell types, and genetic testing for lymphoma markers. If CNS lymphoma is suspected, a lumbar puncture (spinal tap) is performed to collect cerebrospinal fluid (CSF) for cytological examination, as lymphoma cells can be identified in approximately 25% of CSF samples from patients with PCNSL.
Treatment Approaches
Treatment for intraocular lymphoma is tailored to each individual, considering the extent of the disease and central nervous system involvement. Systemic chemotherapy is a primary treatment, often involving high-dose methotrexate delivered intravenously. This approach aims to treat both ocular and potential CNS disease, as systemic therapy is often considered even if the disease appears limited to the eye.
Intrathecal chemotherapy involves injecting drugs directly into the spinal fluid, which can be used to treat or prevent CNS involvement. Localized treatments, such as intraocular injections of chemotherapeutic agents like methotrexate or rituximab directly into the eye, are utilized. These injections provide high drug concentrations within the eye and are often used for isolated ocular disease or recurrences.
External beam radiation therapy to the eye and/or brain is a treatment option. Its use has evolved due to potential complications like radiation retinopathy and cataracts. Proton therapy, a more precise form of radiation, may also be considered. Treatment plans are multidisciplinary, involving ophthalmologists, oncologists, and radiation oncologists working together to manage the disease.
Outlook and Management
The prognosis for intraocular lymphoma, particularly when there is concurrent central nervous system involvement, can be challenging. However, advancements in diagnostic techniques and treatment strategies have led to improved outcomes. Factors influencing the outlook include the stage of the disease, the presence and extent of CNS involvement, and the type of lymphoma. Patients without CNS involvement at diagnosis generally experience a better prognosis.
Long-term management involves diligent follow-up and monitoring for recurrence in both the eye and the CNS. Regular complete ophthalmic examinations are important. MRI scans of the brain are used to screen for the development or progression of CNS disease.
Managing potential treatment side effects and providing supportive care are important aspects of long-term management to maintain a patient’s quality of life. While the optimal treatment strategy continues to be refined through ongoing research, a collaborative approach between specialists aims to achieve sustained remission and address any recurrences promptly.