Central retinal vein occlusion : treatment with bevacizumab and its seasonal characteristics

Abstract

Central retinal vein occlusion (CRVO) is a retinal vascular disorder that may cause severe visual impairment. When CRVO occurs the venous blood flow is impeded with elevated intraluminal pressure upstream to the occlusion. The increased hydrostatic pressure causes extravasation of fluid to the extracellular space that compromises arterial perfusion inducing retinal hypoxia. This will release vascular endothelial growth factor (VEGF) and inflammatory mediators that in turn induce macular edema (ME) and ocular neovascularization. A seasonal variation in cardiovascular disease onset has been shown previously with a higher incidence during the winter season than in the summer. Serum vitamin D levels are known to have a significant seasonal variation with a peak occurring in the summer. A few studies have suggested a seasonal onset of CRVO with more cases presenting during winter, but no study has investigated vitamin D levels in these patients.

In paper I we studied prospectively if repeated intravitreal bevacizumab (IVB) injections every 6 weeks for 6 months could improve visual acuity as compared to sham-treated control patients with ME secondary to CRVO. After 24 weeks 18/30 (60.0%) patients in the study group had gained ≥15 letters compared with 6/30 (20.0%) patients in the control group (p=0.003). At the end of follow up patients in the study group improved 14.1 letters compared to a loss of 2.0 letters in the control group (p<0.01). We showed for the first time in a randomized prospective study the superiority of IVB treatment compared to sham injections in CRVO.

In paper II both groups received treatment with 4 IVB injections every 6 weeks for 6 months. The objectives were to investigate if this regime could maintain visual acuity and to elucidate the impact of delaying treatment for 6 months in patients with ME secondary to CRVO. In the original IVB group a further gain of 2.0 letters was seen with the fixed injection schedule during week 24 to 48. The original sham group, improved to a vision gain of 4.6 letters at week 48 (p<0.05). Disease duration seemed to have a critical impact on visual outcome. Patients initially on a sham-regime in paper I improved with IVB treatment after 24 weeks but significantly less than the original IVB group.

In paper III we investigated retrospectively the seasonality in CRVO onset and the yearly incidence of CRVO in Stockholm, Sweden. Every year during the 6 year study the highest CRVO onset occurred during the winter-spring period and was significantly higher than during the other seasons reaching its lowest levels in autumn. We found that the CRVO incidence was 2/10000 for persons aged over 40 years. The annual incidence increased from 0.25/10000 at 45 years of age up to 7/10000 above 80 years of age.

In paper IV we tested prospectively the hypothesis that patients with CRVO had an increased risk of vitamin D deficiency compared to matched controls. We found that more than 50% of the patients with CRVO had deficient vitamin D levels. In the complete data set no significant differences in vitamin D levels were found between the study groups. Patients less than 75 years old had significantly lower vitamin D levels compared to controls.