Ocular lymphoma is the most common malignant tumor within the orbit in adults, and its pathological diagnosis and classification are complex, often leading to missed and misdiagnosed cases. Improving the diagnosis rate of ocular lymphoma to better protect patients’ ocular and overall health is a significant challenge for ophthalmologists. On March 30, 2024, the inaugural academic forum of the Ocular Lymphoma Collaborative Group was successfully held in Beijing, hosted by the Beijing Tongren Hospital affiliated with Capital Medical University, the Chinese Association for the Promotion of Human Health Science and Technology, the Beijing Public Health Science Popularization Association, and the Beijing Chen Jumei Charity Foundation, and organized by the Cell Immunotherapy Committee of the Chinese Association for the Promotion of Human Health Science and Technology. Renowned experts and scholars from home and abroad actively exchanged and vigorously discussed the latest advances and hot issues in the diagnosis and treatment of ocular lymphoma. Professor Liang Wang, the group leader of the collaborative group from Beijing Tongren Hospital and chairman of the conference, was specially invited by the journal “Oncology Frontier – Hematology Frontier” for an interview to share the latest research developments and achievements in ocular lymphoma.
“Oncology Frontier – Hematology Frontier”: As the chairman of this conference, could you please share with us the latest research results or developments in ocular lymphoma?
Professor Liang Wang: I am very pleased that today we can witness this exciting moment—the official establishment of the Ocular Lymphoma Collaborative Group. The group, led by Professor Wei Wenbin and Professor Wang Jingwen from Beijing Tongren Hospital affiliated with Capital Medical University as honorary leaders, and myself and Director Ma Jianmin as group leaders, consists of over 90 experts from more than 30 provinces and cities nationwide. The ultimate goal of establishing this collaborative group is to promote the standardized diagnosis and treatment of ocular lymphoma, helping ophthalmologists and hematologists across the country deepen their understanding of ocular lymphoma. This will lead to more standardized and rational treatment plans and achieve better treatment outcomes, which was our original intention in setting up the group.
Regarding the progress in ocular lymphoma, first, recently, our team in collaboration with the radiation oncology team from the Chinese Academy of Medical Sciences Cancer Hospital, published long-term survival data of patients with ocular lymphoma in both hospitals in the top hematology journal—Leukemia. The data shows that the survival of patients with marginal zone lymphoma of ocular adnexa is actually consistent with that of similar-aged healthy individuals, indicating that ocular lymphoma is not as dangerous as once thought, which gives patients significant confidence; the data also shows that with our appropriate medical interventions, patients gain a survival benefit. Second, there has been significant optimization in the radiation doses for ocular adnexal lymphoma. Previous radiation doses were generally 24-30 Gy, which could cause adverse effects such as dry eyes, conjunctivitis, and even cataracts three to four years post-treatment, requiring many patients to undergo secondary cataract surgery. In recent years, many experts, including our team, have been researching to improve the radiation dose, reducing it from 20 Gy to 4 Gy. Studies have confirmed that the efficacy of these two doses is similar, but the reduced dose significantly decreases adverse reactions, greatly improving patients’ long-term quality of life. Third, ocular lymphoma also includes a rare type, vitreoretinal lymphoma, which occurs in less than 1,000 cases annually in China. Therefore, ophthalmologists have less awareness of vitreoretinal lymphoma. Typically, ophthalmologists treat this disease with intravitreal injections of low-dose methotrexate, which has been effective, but many patients later experience brain relapse. Once brain relapse occurs, the patient’s survival period is significantly shortened. Our preliminary research shows that new oral BTK inhibitors (such as obinutuzumab and zebutinib) control the intraocular lesions well and may even be as effective as multiple injections of low-dose methotrexate. Moreover, these new oral targeted drugs can enter the central nervous system and effectively prevent brain relapse, which are the results of our recent studies. Of course, there are many unmet clinical needs we hope to address through a series of prospective studies to continuously explore better and optimized treatment plans, aiming to extend the survival, significantly improve the quality of life, and ensure the ocular health of patients with ocular and intraocular lymphoma, which are our future goals.
“Oncology Frontier – Hematology Frontier”: Regarding the treatment of ocular adnexal lymphoma, what are the current treatment strategies, and how do they differ from traditional strategies?
Professor Liang Wang: Marginal zone lymphoma of the ocular adnexa is a type of indolent lymphoma, and its treatment strategy differs slightly from that of aggressive lymphomas. Most patients are referred to hematology or radiation oncology after ophthalmic surgery, and we choose subsequent treatment plans based on whether the patient has symptoms. If the patient has few symptoms and only some residual lymphoma in the eye, our approach is regular observation without active intervention. This is because ocular adnexal lymphoma generally cannot be cured and there is a possibility of recurrence. Early treatment may not significantly improve survival; if the patient has symptoms, we generally use low-dose radiation therapy to control the tumor. Of course, tumor recurrence is possible three, five, or even ten years after surgery, but most recurrences are confined to the eye. After recurrence, we can perform surgery and radiation therapy again. However, for patients with a high tumor load behind the eyeball, we can use early induction therapy, such as CD20 monoclonal antibody combined with obinutuzumab, to quickly shrink the tumor, followed by radiation therapy to consolidate the treatment, thus preserving the patient’s vision and reducing some of the adverse effects associated with radiation therapy.
The treatment strategy for intraocular lymphoma differs from that for ocular adnexal lymphoma. Intraocular lymphoma, or vitreoretinal lymphoma, is a special type of central nervous system lymphoma. Treatment strategies include intravitreal injections of low-dose methotrexate and the use of new targeted drugs, such as the BTK inhibitors (obinutuzumab, zebutinib, etc.) I mentioned earlier, which can penetrate the blood-eye barrier to control intraocular lesions and the blood-brain barrier to prevent recurrence of brain lesions. There is a blood-eye barrier in intraocular lymphoma, which makes it difficult for ordinary drugs to enter, requiring high-dose intravenous chemotherapy, such as high-dose methotrexate. Many studies, both domestic and international, have shown that high-dose methotrexate can control lesions in both the eye and the brain. As our understanding of the pathogenesis of intraocular lymphoma and subsequent treatment deepens, I believe there will be increasingly optimized treatment plans that can be applied to patients, thus improving quality of life and extending survival.
Expert Profile
Professor Liang Wang
– Director of Hematology, Beijing Tongren Hospital affiliated with Capital Medical University
– Chief Physician, Doctoral Supervisor
– Member of the 11th Youth Committee of the Hematology Branch of the Chinese Medical Association
– Chairman of the Cell Immunotherapy Committee of the Chinese Association for the Promotion of Human Health Science and Technology
– Executive Member of the Myeloma Committee of the Chinese Medical Education Association
– Vice Chairman of the Expert Committee on Precision Diagnosis and Treatment of Hematologic Malignancies of the Beijing Health Promotion Association
– Executive Member of the Lymphoma Immunotherapy Committee of the Beijing Cancer Prevention and Treatment Society
– Associate Editor of Cancer Medicine
– Chief Editor for China, European Journal of Haematology
– Specializes in the diagnosis and treatment of hematologic malignancies such as lymphoma
– Principal investigator of four National Natural Science Foundation projects, author of over 40 SCI-indexed publications
