Treatment of branch retinal vein occlusion

I n this issue of Acta, Crafoord et al. (2008) report on sheathotomy in the treatment of branch retinal vein occlusion (BRVO), as did Wrigstad & Algvere (2006) and Shimura et al. (2007) in recent reports in Acta. While Crafoord et al. suggest that sheathotomy may be beneficial, they also point out that it is difficult to distinguish between the effect of the sheathotomy and that of the vitreous humour removal (vitrectomy), which takes place at the same time. In fact, treatment of BRVO frequently takes advantage of several treatment possibilities – laser, vitrectomy, intravitreal anti-vascular endothelial growth factor (VEGF) and steroids – and we need to understand how these treatment modalities work together. BRVO involves decreased blood flow in the involved area with decreased supply of oxygen and nutrients. Hypoxia induces the production of VEGF, increasing vessel permeability and stimulating new vessel growth. At the same time venous occlusion increases venous and capillary pressure, helping to push water from the vessel into the tissue according to Starling’s law (Stefánsson 2006). In order to reverse this pathophysiology, we must on the one hand inhibit VEGF – either by improving the hypoxic situation or directly with VEGF antibodies (Spandau et al. 2006, 2007) – and on the other hand decrease the venous congestion and the high hydrostatic pressure in the venules and capillaries. While we can inhibit VEGF with antibodies, this is temporary and must be repeated every 4–6 weeks. Reducing VEGF by improving the hypoxic condition offers more permanent solutions. This includes retinal photocoagulation and vitreous surgery. Laser photocoagulation destroys some of the photoreceptors, reduces the oxygen consumption of the outer retina and re-establishes a balance between supply and demand of oxygen (Stefánsson et al. 1981), thereby correcting the hypoxia (Pournaras 1995) – at least in part. In some cases, this treatment alone is adequate to stop the macular oedema and ⁄or neovascularization. In cases where laser photocoagulation in not enough, we can use vitreous surgery to further improve the supply of oxygen to the ischaemic area of retina (Stefánsson et al. 1981; Holekamp et al. 2005). Removal of the vitreous gel and its replacement with water increases the rate of diffusion and convection currents, because of the lower viscosity according to the laws of Stokes–Einstein and Hagen Poisuelle (Stefánsson & Loftsson 2006; Barton et al. 2007). This means that oxygen moves more quickly from well-perfused areas to the ischaemic zones and also that VEGF and other cytokines escape faster from the ischaemic areas into the vitreous cavity (Stefánsson 2006; Shimura et al. 2008). The effect of vitrectomy on VEGF production is twofold: reducing hypoxia decreases VEGF production and VEGF is cleared away from the retina more quickly. The sheathotomy itself is meant to reduce the venous congestion and improve blood flow. To understand the importance of venous congestion, we must invoke Starling’s law. It states that the hydrostatic pressure difference between vessel and tissue contributes to the water flux into the tissue and the formation of oedema (Stefánsson 2006). Decreasing the venous congestion therefore influences the oedema formation through the hydrostatic pressure, and possibly through improved blood flow and oxygen supply. Intravitreal steroid injection has also been used against oedema in retinal venous occlusions (Gelston et al. 2006; Sivaprasad et al. 2006; Vinten et al. 2007). Triamcinolone reduces the permeability effect of VEGF and thereby reduces the leakage of osmotically active molecules from the vessel into the tissue, which is essential in oedema formation according to Starling’s law.