Combined Central Retinal Vein and Cilioretinal Artery Occlusion in the Setting of Intravenous Immunoglobulin Administration

Abstract

Purpose:

This work reports a case of combined vascular occlusion in the setting of intravenous immunoglobulin (IVIg) administration.

Methods:

The authors describe a case of combined central retinal vein and cilioretinal artery that occurred in the setting of IVIg administration.

Results:

A 52-year-old White man presented with a unilateral subjective scotoma that began during IVIg administered for the treatment of statin-induced necrotizing autoimmune myopathy. Examination and optical coherence tomography imaging revealed a combined nonischemic central retinal vein and cilioretinal artery occlusion.

Conclusions:

To the authors’ review and knowledge, this is the first reported case of combined central retinal vein and cilioretinal artery occlusion occurring in the setting of IVIg administration. This rare adverse effect is an entity to be considered in patients who are treated with IVIg.

Introduction

Central retinal vein occlusions (CRVOs) are classically seen in older patients with underlying vasculopathic risk factors such as hypertension, diabetes, and hyperlipidemia. In addition, they may also be manifestations of hemodynamic abnormalities including hyperviscosity syndrome. We present the first published case to our knowledge of a patient with incident symptoms and retinal findings of unilateral combined CRVO and cilioretinal artery occlusion (CILRAO) in the setting of intravenous immunoglobulin (IVIg) administration in the management of statin-induced necrotizing autoimmune myopathy (SINAM).

Methods

Case Report

A 52-year-old White man without hypertension or chronic diabetes presented with a 2-day history of visual disturbance described as “a blotch” in his left eye. Symptoms included weakness and pain in the upper and lower extremities for the past year. His medical history included hyperlipidemia treated with statins for 6 years and recent prednisone-related diabetes. The patient had been diagnosed with SINAM 5 months prior to presentation owing to positive results from a biopsy of the left biceps and high levels of circulating anti–β-hydroxy-β-methylglutaryl-CoA reductase antibodies. The patient was initially treated with apheresis and corticosteroids with no improvement, and he was subsequently switched to IVIg at a dose of 50 g daily on 3 consecutive days per month for 6 months. He was in the infusion clinic completing the last day of his fifth cycle when the visual disturbance began.

His visual acuity at presentation was 20/20 OD and 20/30 OS. The anterior segment demonstrated no neovascularization or inflammation. Dilated fundoscopic examination revealed numerous perivenular flame hemorrhages, dilated and tortuous veins, and nasal macular whitening consistent with a nonischemic CRVO and CILRAO in the left retina (Figure 1). Optical coherence tomography confirmed nasal macular thickening in the temporal peripapillary region sparing the fovea (Figure 2). Fluorescein angiography was not able to be performed at this time.

Figure 1.

Montage color fundus photograph of the left eye (OS). Fundus examination demonstrated a nonglaucomatous optic nerve, dilated and tortuous veins, nasal macular retinal whitening, and scattered hemorrhages consistent with nonischemic central retinal vein occlusion.

Figure 2.

Spectral domain–optical coherence tomography macula horizontal raster of the left eye. Peripapillary inner retinal thickening was found in the area of cilioretinal artery occlusion sparing the fovea.

Results

Based on a discussion with the rheumatology department regarding the risk of further retinal vascular events and the benefits of IVIg for the treatment of SINAM, the patient continued receiving IVIg as planned. Laboratory workup was negative for thrombophilic conditions and paraproteinemia including cryoglobulinemia, macroglobulinemia, myeloma, antithrombin III deficiency, and Factor V Leiden. Laboratory studies for serum viscosity were deferred because of recent administration of IVIg, and no further neuroimaging was performed because of lack of neurologic symptoms. At 1-month follow-up the patient had subjective visual improvement and improved visual acuity of 20/30 OS. No further retinal occlusions were noted, no intravitreal injections were necessary, and neovascular glaucoma did not present on monthly follow-up.

Conclusions

Hyperviscosity syndrome is caused by increased cells or proteins in circulating vasculature, which increases resistance to shear forces. Etiologies include Waldenström macroglobulinemia, multiple myeloma, polycythemia vera, leukemia, immunoglobulin G4–related disease, and types I and II cryoglobulinemia. ¹ Iatrogenic causes include the use of IVIg, which is a blood product used in the treatment of a wide spectrum of pathophysiology either for antibody replacement or immunomodulation. ² CRVO and combined CRVO/CILRAO have been reported in patients with many causes of hyperviscosity including macroglobulinemia and cryoglobulinemia. ^3,4 Although there is no certainty that the CRVO or impending CRVO was not present prior to symptom onset in this case, or that it may have precipitated the CILRAO, hyperviscosity is a known precipitant of retinal vascular events. Thus, especially in patients with underlying vasculopathic risk factors, retinal damage may be caused by blood viscosity alteration as a result of IVIg treatment.

SINAM is a relatively new diagnosis for which the mainstay of treatment includes statin discontinuation and immunotherapy including IVIg. ⁵ Patients with SINAM, underlying dyslipidemia, and commonly, comorbidities of diabetes and hypertension should be counseled and dosed judiciously, with the understanding that retinal vascular occlusion may occur with IVIg treatment. Collaboration in a multidisciplinary approach is vital in determining the individualized necessity of IVIg, given specific patient co-morbidities and availability of alternative agents.