Waldenström – August 2015

August 2015

Case History

An 85-year-old Caucasian woman was self-referred to Illinois Retina Associates for second opinion. She complained of blurry vision in both eyes over the past 12 months. As per documentation of her past visits:

“She complained of decreased visual acuity in the right eye followed by the left eye with clinical picture compatible with diabetic macular edema. She received five (5) injections of Avastin in the right eye and three (3) in the left eye.”

Of note, she has a history of a right thalamic infarct stroke in 2013.

Her best corrected visual acuity was 20/200 in the right eye and 20/50-2 in the left eye. She had a relative afferent pupillary defect in the right eye. Her intraocular pressures were within normal limits. Her anterior examination was significant for posterior chamber intraocular lenses.

Posterior Segment Exam and Diagnostic Testing

Posterior segment examination revealed scattered hemorrhages in both eyes (Figure 1), a possible macroaneurysm with macular edema in her right eye, and a blunted foveal reflex in her left eye. Spectral domain optical coherence tomography revealed significant macular edema with macular detachment in the right eye greater than the left eye (Figure 2). Fluorescein angiography revealed minimal leakage with a surprising lack of macular leakage. (Figure 3, arrow) in both eyes.

Figure1
Figure1
Figure 2
Figure 2
Figure 3
Figure 3

Further History

Patient was found to be hypertensive and was placed on medications. There was no evidence of diabetes on laboratory testing. MRI revealed no evidence of malignancy. Comprehensive metabolic panel revealed monoclonal gammopathy and bone marrow biopsy confirmed the diagnosis.

Differential Diagnosis:

Retinal hemmorhages with macular thickening can be caused by a wide variety of diseases. The most common cause would certainly be diabetic retinopathy. However, when systemic lab work returns negative for diabetes in the face of macular edema and retinal hemorrhages, other causes and further exploration is required. Other common causes include the following:

  • severe hypertensive retinopathy
  • radiation retinopathy
  • ocular ischemic syndrome
  • Macular telangiectasia type 1

There are other less common conditions which look similar to diabetic retinopathy and at times must also be investigated including neoplastic, inflammatory and hyperviscosity diseases: leukemia, other blood dyscrasias (anemia, thrombocytopenia, etc), lymphoma, Waldenstrom’s macroglobulinemia, multiple myeloma, polycythemia vera, systemic lupus erythematosus, etc.

Diagnosis:

Waldenström Macroglobulinemia

Discussion

Waldenström Macroglobulinemia (WM) is a malignant lymphoproliferative B-cell disorder with overproduction of monoclonal immunoglobulin type M (IgM). IgM is a large pentamer compound which easily forms aggregates which can lead to blood hyperviscosity. Hyperviscosity syndrome occurs in approximately 17% of all patients with WM. Rarely, patients with WM and hyperviscosity syndrome develop serous macular detachments. The most common retinal findings of hyperviscosity syndrome include scattered hemorrhages, microaneurysms, vascular dilation, tortuosity, venous beading, and optic disc edema. At the time of diagnosis, about 8% of patients with WM report visual disturbance and 37% have some degree of hyperviscosity-related retinopathy.

The angiographically “silent macula” has been recognized as a hallmark of immunogammopathy-induced serous macular detachment (Figure 3).

The pathologic mechanism of macular detachments in WM is unknown however there have been multiple proposed theories:

  • Presence of IgM in the subretinal space, suggesting an increased osmotic gradient causing fluid accumulation under the retina
  • Outer retinal defects overlying a serious macular detachment could provide a pathway for immunoglobulin M molecules and intreretinal fluid to enter the subretinal space, thereby creating a serious macular detachment in the setting of a so-called silent fluorescein angiogram
  • The stability of the outer retina may fluctuate. Breakdown of the external limiting membrane theoretically is caused by cystoid macular edema-related traction on Müller cells and photoreceptors. Improvement in macular edema leads to re-establishment of outer retinal integrity.

When outer retinal defects become too large or chronic, they remain open and lead to persistent subretinal fluid. This plasticity may be the reason that some patients with Waldenström Macroglobulinemia have progressive serious retinal detachments, whereas others show stabilization or improvement over time.

Treatment Options

While many treatments including anti-VEGF, steroids and laser have been described in the literature, none have proven to improve the macular edema associated with this condition. Systemically, plasmapheresis and chemotherapy are utilized to address the hyperviscosity and can help slow and sometimes reverse the macular edema.

References

Gass J. Steroscopic atlas of macular diseases: diagnosis and treatment. St. Louis: Mosby, 1997:198

Merlini G, Baldini L, Broglia C, et al. Prognostic factors in symptomatic Waldenström Macroglobulinemia, Semin Oncol 2003:30(2):211-215

Feigl B, Sill H, Haas A. Serious detection of the neuroretina in Waldnstrom disease. A case report. Klin Monbl Augenheilkd 1999;215(1):64-67

Berta A, Beck P, Mikita J. IgM paraprotein in the subretinal fluid of a patient with recurrent retinal detachment and Waldenstrom’s macroglobulinaemia. Acta Med Hung 1985; 42(3-4):179-186

Menkie MN, Feke GT, McMeel JW, Branagan A, Hunter Z, Treon SP. Hyperviscosity-related retinopathy in waldenstrom macroglobulinemia. Arch Ophthalmol 2006;124(11):1601-1606

Caimi A, Giani A, Bottoni F, Staurenghi G. Serious macular detachment in Waldenström Macroglobulinemia: a report of 4 cases. Am J Ophthalmol. 2013 May;155(5):955-6. doi:10.1016/j.ajo.2013.02.011

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