Physiology of vitreous surgery

Abstract

Vitreous surgery has various physiological and clinical consequences, both beneficial and harmful. Vitrectomy reduces the risk of retinal neovascularization, while increasing the risk of iris neovascularization, reduces macular edema and stimulates cataract formation. These clinical consequences may be understood with the help of classical laws of physics and physiology. The laws of Fick, Stokes-Einstein and Hagen-Poiseuille state that molecular transport by diffusion or convection is inversely related to the viscosity of the medium. When the vitreous gel is replaced with less viscous saline, the transport of all molecules, including oxygen and cytokines, is facilitated. Oxygen transport to ischemic retinal areas is improved, as is clearance of VEGF and other cytokines from these areas, thus reducing edema and neovascularization. At the same time, oxygen is transported faster down a concentration gradient from the anterior to the posterior segment, while VEGF moves in the opposite direction, making the anterior segment less oxygenated and with more VEGF, stimulating iris neovascularization. Silicone oil is the exception that proves the rule: it is more viscous than vitreous humour, re-establishes the transport barrier to oxygen and VEGF, and reduces the risk for iris neovascularization in the vitrectomized-lentectomized eye. Modern vitreous surgery involves a variety of treatment options in addition to vitrectomy itself, such as photocoagulation, anti-VEGF drugs, intravitreal steroids and release of vitreoretinal traction. A full understanding of these treatment modalities allows sensible combination of treatment options. Retinal photocoagulation has repeatedly been shown to improve retinal oxygenation, as does vitrectomy. Oxygen naturally reduces VEGF production and improves retinal hemodynamics. The VEGF-lowering effect of photocoagulation and vitrectomy can be augmented with anti-VEGF drugs and the permeability effect of VEGF reduced with corticosteroids. Starling's law explains vasogenic edema, which is controlled by osmotic and hydrostatic gradients between vessel and tissue. It explains the effect of VEGF-induced vascular permeability changes on plasma protein leakage and the osmotic gradient between vessel and tissue. At the same time, it takes into account hemodynamic changes that affect the hydrostatic gradient. This includes the influence of arterial blood pressure, and the effect oxygen (laser treatment) has in constricting retinal arterioles, increasing their resistance, and thus reducing the hydrostatic pressure in the microcirculation. Reduced capillary hydrostatic pressure and increased osmotic gradient reduce water fluxes from vessel to tissue and reduce edema. Finally, Newton's third law explains that vitreoretinal traction decreases hydrostatic tissue pressure in the retina, increases the pressure gradient between vessel and tissue, and stimulates water fluxes from vessel into tissue, leading to edema.

Vitreoretinal influences on lens function and cataract

“…The gel state of the vitreous body assures that the movement of molecules within it occurs only by diffusion [34,35]. Measurements made with oxygen microelectrodes or nuclear magnetic resonance spectroscopy showed that oxygen diffuses into the vitreous from the retinal vessels [19,36].…”

Disappearance of central confluent soft drusen following vitrectomy and ILM peeling

“…Stimulating factors might be the surgically induced PVD, peeling of epiretinal membranes, gas tamponade, and increased oxygenation following vitrectomy. 8 The additional ILM peeling in the here reported case might have enhanced the stimulation, resulting in an almost complete phagocytosis of drusen. Remarkably, postoperative new drusen formation spared the central area where compact drusen material had been present preoperatively.…”

A new model for in vitro testing of vitreous substitute candidates

“…There is, however, evidence of a more intricate and purposeful composition [10] with important physiological implications on the micro-milieu of the retina including the upkeep of salt and nutrient gradients, physical support and more [35,36]. An ideal vitreous substitute would replicate these influences on the neuroretina and surrounding tissues as well as provide a tamponading effect after vitrectomy [10].…”