Central Retinal Vein Occlusion After Intense Exercise: Response to Intravitreal Bevacizumab

Introduction

Central retinal vein occlusion (CRVO) is the second most common retinal vasculopathy. It presents as a sudden painless loss of vision with four-quadrant retinal hemorrhages and dilated, tortuous retinal veins on fundus examination. CRVO predominantly occurs in individuals older than 60 years with associated risk factors of hypertension, diabetes mellitus, and glaucoma.¹ Younger individuals who develop CRVO usually have a predisposing etiology such as coagulopathy, blood dyscrasia, autoimmune vasculitis, obstructive sleep apnea, or dehydration.^1,2 Although there is a decreased risk of CRVO in individuals who exercise regularly, young healthy individuals have been reported to develop CRVO after exercise.³ We present a case of a 40-year-old man with a CRVO after intense exercise that responded favorably to treatment with intravitreal bevacizumab.

Case Report

A 40-year-old male athlete was referred to the retina service at Bascom Palmer Eye Institute for evaluation and management of CRVO. He had a 5-week history of vision loss of the left eye that he first noticed hours after strenuous weight lifting and aerobic exercise with dehydration. He had a medical history of migraine headaches and ocular history of radial keratotomy in both eyes in 1992.

His visual acuity on initial presentation was 20/15 in the right eye and 20/400 in the left eye. Intraocular pressures were normal at 14 mm Hg in both eyes. Anterior slit-lamp examination was normal. Fundus examination showed diffuse intraretinal hemorrhages and dilated, tortuous retinal vessels consistent with CRVO (Fig. 1). Spectral-domain optical coherence tomography confirmed cystoid macular edema with a central retinal thickness of 641 microns (Fig. 1).

Figure 1. Fundus photograph (A) and spectral-domain optical coherence tomography (B and C) of the left eye demonstrating initial presentation with four quadrants of retinal hemorrhage, vessel tortuosity, and macular edema.

Three weeks earlier, the patient had a thorough medical evaluation at the recommendation of his primary ophthalmologist, who had first diagnosed the CRVO. The evaluation included blood count and chemistry, hypercoaguable work-up (lipid profile, factor V Leiden, activated protein C resistance, lupus anticoagulant, protein C and S, and antithrombin III) and imaging (magnetic resonance imaging, magnetic resonance venography, and magnetic resonance angiography of head, carotid ultrasound, and transthoracic echocardiogram). All test results were normal.

Intravitreal bevacizumab 1.25 mg/.05 mL was given to the left eye. Central macular thickness decreased and visual acuity gradually improved to 20/20 after 11 injections over a 24-month period (Fig. 2). Rebound macular edema occurred at regular 6- to 8-week intervals after each intravitreal bevacizumab injection but resolved with repeat injections (Table 1). The patient has continued daily exercise but ensures adequate hydration.

Figure 2. Fundus photograph (A) and spectral-domain optical coherence tomgraphy (B and C) of the left eye demonstrating marked improvement of retinal hemorrhages and macular edema.

Table 1: Injection Schedule With VA and CMT

Discussion

Recent case series have described CRVO after exercise in young, otherwise healthy patients (Table 2). The 11 reported cases had a mean age of 36 years. The young age of these patients contrasts with a mean age of 70 years in the CRUISE trial.⁴ All 11 patients were otherwise healthy with systemic evaluations revealing no additional risk factors except for sickle cell trait in one male patient and a history of oral contraceptive use in one female patient. The temporal association between exercise and CRVO in these cases suggests exercise and dehydration may play a causative role. These cases contrast with the Eye Disease Case Control Study Group findings of a decreased risk of CRVO in individuals who exercise regularly.¹

Table 2: Current Case Reports of CRVO After Exercise in Young Patients

Exercise has different short-term and long-term effects on blood viscosity. In the short-term, exercise may cause hyperviscosity or hemoconcentration due to fluid shifts and an increase in erythrocyte rigidity and aggregability.⁵ This acute increase in blood viscosity is heightened by dehydration and may increase the risk of vascular events such as CRVO in susceptible individuals. Gaudard et al. showed a more pronounced hemorheological response to exercise (increased blood viscosity, hematocrit, and red cell aggregation) in an individual who had a CRVO after a marathon run.⁶ In the long term, however, exercise has the opposite effect on blood viscosity. Athletes have a lower plasma viscosity and hematocrit and a reduced red cell rigidity and aggregability compared to controls.⁵ The reduced blood viscosity in those who exercise regularly may decrease the risk of CRVO, as identified by the Eye Disease Case Control Study Group.¹

The prognosis of CRVO after exercise in young, healthy patients is variable.^6–9 Of the 11 reported cases, 5 had good mean presenting and final visual acuities of 20/28 and 20/25, respectively, and none required regular intravitreal anti-vascular endothelial growth factor therapy. In contrast, 2 of the 11 reported cases developed neovascular glaucoma with final visual acuities of light perception and no light perception. The other 4 cases ranged from 20/100 to 20/200 at final follow-up (Table 2).

The current case is the first documented CRVO after exercise in a young patient to receive regularly administered anti-vascular endothelial growth factor therapy. At 6 months, the patient gained 20 letters from baseline with five intravitreal injections of bevacizumab. This gain is consistent with outcomes reported by Gregori et al., who showed a 9-letter gain at 6 months with intravitreal treatment of bevacizumab.¹⁰ Similarly, the CRUISE trial showed a mean gain of 14 letters at 6 months with monthly intravitreal ranibizumab.⁴ The current case highlights both the effectiveness of anti-vascular endothelial growth factor therapy and the potential need for continued therapy over a long period of time due to recurrent edema.

In counseling young, healthy patients with CRVO, ophthalmologists should clearly warn them of the risk of dehydration while also advocating the benefits of regular exercise. In addition to the reduced long-term risk of CRVO, exercise plays a major role in the control and prevention of systemic hypertension, diabetes mellitus, hyperlipidemia, and their associated health complications.^1,11