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Woman presents with worsening floaters, right-hand clumsiness and word-finding difficulties
Dilated fundus exam of the left eye revealed a hazy media with vitreous stranding and clumping.
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A 77-year-old white woman presented to the emergency department with worsening floaters and decreased vision in the left eye. She reported that she initially noticed floaters in the left eye 6 months ago, but over the past few months, the floaters had turned brown and coalesced to form a dark cloud. Her husband also noticed new right-hand clumsiness and word-finding difficulties for the past 3 days. She denied fevers, chills, weight loss and shortness of breath.
The patient had never had any eye problems or eye surgery in the past. She was diagnosed with visually significant cataracts 6 months ago, and her surgery was scheduled for the following week. Her medical history was significant for hypertension, obstructive sleep apnea and anxiety. She had no known drug allergies, and current home medications included vitamin D3 supplements and lorazepam as needed. She was retired and lived at home with her husband. She had a 37 pack-year smoking history but quit more than 30 years ago. She drank occasionally and denied illicit drugs.
Source: Huan Mills, MD, and Fina Barouch, MD
Examination
Best corrected visual acuity was 20/30 in the right eye and 20/40 in the left eye. IOP was normal at 11 mm Hg in the right and 12 mm Hg in the left. Pupils were equal, round and reactive bilaterally without afferent pupillary defect. Extraocular movements and confrontation visual fields were full bilaterally. The external exam was normal in both eyes. Anterior segment exam revealed a deep and quiet chamber bilaterally with 2+ nuclear sclerotic cataract and 2+ cortical cataract in both eyes. Dilated fundus exam of the right eye revealed a clear media with a healthy-appearing optic nerve and normal macula and vessels. She had a pigmented superonasal nevus with overlying drusen. Dilated fundus exam of the left eye revealed a hazy media with vitreous stranding and clumping (Figure 1). She also had 3+ pigmented cells floating in the vitreous.
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Pigmented vitreous floaters
The recent onset of right-hand clumsiness and word-finding difficulties was concerning for an acute stroke, which must be ruled out first. Given the patient’s age, primary vitreoretinal lymphoma was high on our differential because of the appearance of the pigmented floaters on dilated fundus exam coupled with acute-onset neurological deficits. Metastatic disease was also considered, but the patient did not have any distinct choroidal lesions on dilated fundus exam and she also lacked a history of cancer. Other causes of vitreous floaters that were considered included tuberculosis, syphilis and sarcoidosis.
Workup and management
MRI/MRA was obtained urgently in the emergency room and was negative for acute stroke. Imaging did, however, reveal multiple enhancing lesions (Figure 2) in the subcortical white matter in the left frontal, temporal and parietal lobes with surrounding edema and diffusion restriction concerning for a neoplastic process. A follow-up CT scan of the chest, abdomen and pelvis was negative for primary cancers that may have metastasized to the brain. Bone marrow biopsy with flow cytometry analysis was negative for abnormal cells. Labs for HIV, syphilis, tuberculosis and sarcoidosis were negative.
The central nervous system (CNS) lesions coupled with vitreous floaters in the left eye were concerning for primary CNS lymphoma with vitreoretinal lymphoma. A vitreoretinal biopsy was done to obtain a tissue diagnosis in order to initiate treatment. During the surgery, an undiluted vitreous sample was obtained by vitrectomy and stored in culture medium for flow cytometry analysis. A subsequent dilute sample with the vitreous wash fluid was sent for culture and cytokine levels. Vitreous biopsy results (Figure 3) revealed 84% abnormal lymphocytes with scant basophilic cytoplasm and large hypersegmented nuclei with prominent nucleoli concerning for large B-cell lymphoma. Flow cytometry revealed the abnormal cells were CD19 and CD20 positive, confirming B-cell lymphoma.
Discussion
Primary CNS lymphoma primarily affects older patients, and the usual onset is normally in the fifth or sixth decade of life. There is a slight predilection for women. Patients with HIV or who are on long-term immunosuppression can present at an earlier age. Primary vitreoretinal lymphoma often occurs concurrently with primary CNS lymphoma. Approximately 25% of patients with CNS lymphoma have ocular involvement, and approximately 90% of patients with primary vitreoretinal lymphoma will develop CNS lymphoma within 29 months. Diagnosis can be made with either a vitreous or brain biopsy. Both methods of biopsy have equivalent sensitivity of 80% to 95%, but a vitreous biopsy is much less invasive compared with a brain biopsy, which carries an 8% risk of intracranial hemorrhage or postoperative neurological deficit.
First-line treatment for CNS lymphoma is chemotherapy. Whole brain radiation used to be performed, but it resulted in a high incidence of severe dementia with no survival benefit when compared with chemotherapy alone. Primary vitreoretinal lymphoma usually responds to chemotherapy, but if there is no ocular response to systemic therapy, localized intravitreal injection of methotrexate and/or rituximab can be performed. Progression-free survival is usually around 1 year, and overall survival is usually around 3 years.
Clinical course continued
Since her initial diagnostic and therapeutic vitrectomy, the patient did not have any recurrence of floaters. However, she experienced worsening cataracts after vitrectomy and rescheduled cataract surgery in the left eye. The patient was initiated on chemotherapy with high-dose methotrexate, rituximab and temozolomide therapy. She initially responded well with resolution of right-hand weakness and word-finding difficulties, but MRI at 6 months revealed evidence of CNS disease progression. She was subsequently transitioned to ibrutinib monotherapy and is currently doing well.
Summary
Primary vitreoretinal lymphoma is a masquerade syndrome that often mimics chronic uveitis. One should always consider lymphoma in the workup of an elderly patient with worsening vitreous floaters. CNS lymphoma has a high incidence of ocular involvement, and all patients with suspected CNS lymphoma should get a full dilated exam to look for ocular spread. If a patient with CNS lymphoma has had the disease spread to the vitreous, a vitreous biopsy is a good diagnostic tool compared with a brain biopsy, and it also carries much less risk.
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- For more information:
- Huan Mills, MD, and Fina Barouch, MD, can be reached at New England Eye Center, Tufts University School of Medicine. 800 Washington Street, Box 450, Boston, MA 02111; website: www.neec.com.
- Edited by Adam T. Chin, MD, and Omar Dajani, MD. They can be reached at the New England Eye Center, Tufts University School of Medicine, 800 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.