Intense exercise causing central retinal vein occlusion in a young patient: case report and review of the literature.

We report a 19-year-old patient who developed a central retinal vein occlusion (CRVO) with significant macular edema and visual impairment following intense exercise and dehydration. The patient was treated with 3 intravitreal bevacizumab injections with complete resolution. A review of the literature on the cause and treatment for CRVO in young patients was performed, focusing on the role of intense exercise and dehydration as a rare pathogenesis mechanism of CRVO.

Introduction

Central retinal vein occlusion (CRVO) is the second most common retinal vasculopathy and predominantly occurs in patients over 60 years of age with associated risk factors, such as vascular disease, hypertension and glaucoma [1]. A minority of patients with CRVO are young adults, under 40 years of age. In most of these cases, CRVO occurs without the presence of the typical risk factors, and a comprehensive workup is warranted [2]. Unusual causes for CRVO in young patients include hypercoagulability states, collagen vascular diseases, lymphoproliferative disorders, malignant hypertension, medications (most notably oral contraceptives and isotretinoin), and trauma [2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13]. A recent study has demonstrated that hyperlipidemia and hyperhomocysteinemia were the most significant risk factors for CRVO in patients under 40 [14].

Intense exercise and associated dehydration have rarely been reported to cause CRVO in young patients [15, 16, 17]. We report a patient who suffered CRVO following intense exercise and was treated with intravitreal bevacizumab injections with complete resolution.

Case Report

A 19-year-old man was referred to our clinic due to decreased visual acuity (VA) in his left eye. The patient had no previous systemic or ocular medical history and did not use any medication. His complaint of decreased VA acutely started 1 week prior to his presentation, after several days of intense physical activity (long distance running and weight lifting performed outdoors during the summer). He remained stable during the time of exercise.

On initial examination, his best corrected VA was 20/20 in the right eye and 20/150 in the left eye. His intraocular pressure was 12 mm Hg in both eyes, the range of ocular movements was fully bilateral, and there was no relative afferent pupillary defect. A dilated fundus examination of the right eye and both anterior segments were normal. Fundus examination of the left eye was significant for a swollen disc, numerous retinal hemorrhages, macular edema (ME) and tortuous dilated retinal vasculature (fig. 1a). Fluorescein angiography demonstrated hyperfluorescence compatible with disc hyperemia, ME, and areas of blocked fluorescense compatible with the retinal hemorrhages. Acapillary nonperfusion was not observed (fig. 1b). A significant ME was demonstrated by optical coherence tomography (fig. 1c).

Fig. 1

At presentation, a diagnosis of CRVO was made based on the ocular findings, which included a swollen disc, multiple retinal hemorrhages and tortuous, dilated retinal vessels (a). Fluorescein angiography demonstrated disc hyperemia, ME and blocked hypofluorescence compatible with the hemorrhages (b). Optical coherence tomography demonstrated significant ME with subretinal fluid (c). Following treatment with 3 bevacizumab injections, the ocular findings had disappeared, and the fundus examination and fluorescein angiography returned to normal (d, e). The macular edema had resorbed completely and normal macular architecture was restored (f).

Our young patient was diagnosed with CRVO. Our workup included a normal complete blood count, blood chemistry, lipid profile and coagulation tests (PT and PTT). The erythrocyte sedimentation rate was normal (5 mm/h), and a complete collagenogram, including the rheumatic factor, antinuclear antibodies and antineutrophil cytoplasmic antibodies, was also normal. Hemoglobin electrophoresis, the complete neurological examination and the head CT were also normal, as was the further workup for an increased coagulability (including tests for hyperhomocysteinemia, antiphospholipid antibodies, factor V Leiden mutation and β2-glycoprotein).

The patient was treated with 3 monthly intravitreal injections of bevacizumab (1.25 mg/0.05 ml). Following these 3 injections, VA in the left eye had improved to 20/20, the hemorrhages had resorbed, and the fundus examination returned to normal (fig. 1d, e). The ME had also been completely resorbed with the restoration of a normal macular architecture (fig. 1f). The patient was observed for an additional year with no recurrence.

Discussion

The natural history of eyes with CRVO is associated with a poor visual prognosis, especially in cases with nonperfused CRVO [19, 20]. Until recently, treatment of ME in patients with CRVO had been guided by the historic Central Vein Occlusion Study that recommended mere observation in these cases [21]. However, significant advances had been made in recent years, and there are now several effective treatment options for the affected eyes. These include intravitreal injections of steroidal agents, such as triamcinolone acetate [22] and the ozurdex slow-release dexamethasone implant [23], and anti-vascular endothelial growth factor agents such as ranibizumab [24], bevacizumab [25, 26] and aflibercept [27].

In contrast to older patients, CRVO in young adults has a much more favorable natural history. At presentation, VA is typically not reduced and a spontaneous resolution over several months is possible. However, it should be noted that some of these eyes suffer a significant and permanent visual impairment and may develop complications such as chronic ME, retinal neovascularization and vitreal hemorrhage [2]. Due to the rarity of CRVO in young patients, randomized controlled trials of the various treatment options for these patients has not yet been performed, and there are currently no established guidelines for the treatment of these patients.

Dehydration due to either fasting or intense exercise has been infrequently reported as a cause of CRVO in young patients [15, 16, 17, 18]. Out of the 11 patients reported in these works, only 1 had been treated with bevacizumab. This was a 40-year-old male athlete with CRVO that occurred following intense exercise and secondary dehydration. The patient was treated with 11 bevacizumab injections and he experienced significant visual improvements [17]. The patient we described had no previous medical or ocular history and underwent a comprehensive investigation that revealed no causative factor for CRVO. Since the symptoms started after a period of intense exercise, it is likely that the patient had been dehydrated and that was the cause for the occurrence of CRVO. During dehydration, the blood hematocrit increases, which results in a temporary hyperviscosity state. The central retinal vein is susceptible for thrombosis in the presence of hyperviscosity, which reduces the blood flow, especially at the point it goes through the lamina cribrosa [28]. This mechanism may explain the occurrence of CRVO secondary to intense exercise and dehydration.

We describe a second case of a young patient with CRVO, caused by intense exercise, that was treated with bevacizumab. After 3 monthly injections, a complete resolution with a restoration of 20/20 vision was achieved, and no recurrence occurred following cessation of treatment. Although it is possible that a spontaneous resolution would have occurred even without treatment in this patient, it should be noted that ME was significant and his VA was reduced in an otherwise healthy and young patient. Initiating treatment may have improved the natural history or hastened the visual recovery. Repeated intravitreal injections of anti-vascular endothelial growth factor agents have been established as a safe and effective treatment method for ME in CRVO [24, 25, 26] and may very well be beneficial in young patients with CRVO.

This case report should raise awareness to the possibility of intense exercise as a possible cause for CRVO in young patients. In the absence of an established treatment regimen for these cases, we suggest that treatment can be initiated despite the possibility of a spontaneous resolution. Intravitreal bevacizumab injections seem to be a safe and effective treatment option for such cases.

Disclosure Statement

The authors declare that there are no conflicts of interest regarding the publication of this article.