Waldenstrom macroglobulinemia (WM) is a lymphoplasmacytic lymphoma characterized by malignant B cells and monoclonal IgM overproduction. The clinical manifestations of WM are largely secondary to elevated circulating IgM and the deposition of IgM into various tissues, the latter of which can cause lymphadenopathy (25%), hepatomegaly (24%), and splenomegaly (19%).1,2 A study assessing 217 patients with WM found that the most common symptoms causing patients with WM to seek care were anemia (38%), symptoms including fever, night sweats, and weight loss (23%), bleeding (23%), and neurologic symptoms (22%). However, 27% of patients with WM were diagnosed incidentally and did not express any signs or symptoms before diagnosis.1
Because IgM is a large pentameric protein that aggregates easily, elevated serum IgM can cause hyperviscosity syndrome, leading to ocular sequelae. In one series, funduscopic abnormalities were noted in 34% of patients; furthermore, approximately 8% of patients with WM report visual disturbances at the time of diagnosis.1,3 Classic funduscopic findings include dilated, segmented, and tortuous retinal veins, retinal hemorrhages, exudates, papilledema, and central retinal vein thrombosis. Higher IgM levels—and thus increased serum viscosity—are associated with increased retinal vessel diameters and central retinal changes.4 Occasionally, patients with WM develop serous macular detachments, which have been previously described in case reports.5,6 A case series by Baker et al7 proposes that disruption of the outer retina within the macular detachment allows for IgM to pass into the subretinal space, causing an osmotic fluid shift and subsequent serous retinal detachment. However, the exact mechanism by which IgM enters the subretinal space remains under debate.6–8
The present case describes a woman with WM who developed blurry vision secondary to serous macular detachment. As IgM levels rose, her vision progressively worsened, but she did not seek ophthalmic care. The serous macular detachments became impressively chronic and severe as IgM levels remained high, and she slowly responded to systemic treatment for WM. As IgM levels normalized, serous macular fluid resorbed.
Report of a Case
A 56-year-old woman was diagnosed with WM after presenting with chest discomfort, fatigue, dyspnea on exertion, and weight loss. Investigation showed significant anemia that required transfusion, pancytopenia, and elevated IgM with lymphoplasmacytoid cellular infiltration of the bone marrow. Serum viscosity was elevated. She underwent plasmapheresis and was subsequently treated with a 7-week course of Velcade and methylprednisolone and a 4-week course of Rituxan. The patient had been seen by an outside ophthalmologist in the first month of her diagnosis of WM and was noted to have bilateral mild serous macular detachments with a visual acuity of 20/40 bilaterally. Autologous stem cell transplant (SCT) was performed 6 months after diagnosis, and an allogeneic SCT from the patient's sister was performed 3 months later, in addition to a course of radiation treatment. Prednisone 15 mg to 20 mg daily was maintained the year after SCT treatment.
The patient's IgM level at initial presentation to her oncologist was 1,150 mg/dL (normal range 40–230 mg/dL). This increased steadily for the next 2 months to a peak of 3,800, which was thought to be from a rebound effect after plasmapheresis. After autologous SCT and chemotherapy 6 months after diagnosis, her IgM fell to 824. Her IgM level normalized to 225 ten months after initial diagnosis. This trend continued—at 1 year, her IgM was 75. Levels then stabilized to 50 to 60 at the time of this publication.
The patient presented to our office 21 months after the diagnosis of WM. Visual acuity was counting fingers in the right eye and 20/300 in the left eye. Intraocular pressures were 24 in both eyes. Dilated fundus examination showed a large oval area of pigmentary change and macular fluid involving the fovea in both eyes (Figure 1). Fluorescein angiography showed a mixed hyperfluorescent and hypofluorescent pattern in these lesions. No definite leakage was noted. Indocyanine green angiography did not show any leakage and in fact demonstrated hypofluorescence of the lesions. Autofluorescent imaging showed mixed hyperautofluorescence and hypoautofluorescence. Optical coherence tomography showed a marked loss of the outer retinal layers, along with remarkable macular fluid in both eyes (Figure 2). These changes resembled stalagmites and stalactites.
As the patient's IgM level dropped and eventually normalized ten months later, the macular fluid began to resorb and the retinal architecture improved (Figure 3). This improvement in fluid is still occurring six months later and the fluid is almost gone. However, the visual acuity remained poor.
This case report highlights the importance of prompt IgM control in WM to help preserve retinal function that is impaired by serous macular detachments. Given the hyperviscosity, this fluid is abnormally thick, especially if IgM levels stay elevated for a long period of time. In our case, the prolonged elevation is likely responsible for a gradual decline in vision to severe vision loss and the unusual stalagmite and stalactite appearance as observed on optical coherence tomography. In addition, the patient presented had been taking no less than 15 mg of prednisone daily after SCT, which may have contributed to serous macular fluid. The serous macular detachments were present well before prednisone therapy was instituted.
Initial treatment of symptomatic patients with WM should be aimed toward IgM reduction through plasmapheresis. Plasmapheresis has been shown to significantly reduce serum IgM and serum viscosity, leading to improvement in hyperviscosity-related retinopathy. In a case series of 9 patients, retinal vein engorgement decreased by an average of 15.3 ± 5.8%.9 Furthermore, retinal venous blood speed increased significantly as vessel diameters decreased.
Various authors have advocated for concurrent use of intravitreal anti–vascular endothelial growth factor and intravitreal injection of dexamethasone implants in the management of WM-associated serous macular detachments, with varying levels of improvement in anatomical resolution and/or in visual acuity.10–12 It should be noted however that Besirli and Johnson13 reported a case of immunogammopathy maculopathy where conventional macular edema treatments (i.e., anti–vascular endothelial growth factor and corticosteroids) provided no additional benefit for reversing the maculopathy beyond systemic WM treatment. Early initiation of systemic therapy for WM—specifically plasmapheresis and cancer therapy—remains the cornerstone of therapy.
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Keywords:© 2019 by Ophthalmic Communications Society, Inc.
maculopathy; serous macular detachment; retinal detachment; Waldenstrom macroglobulinemia