16.
The Role of the Vitreous in Diabetic Macular Edema
Einar Stefánsson (Reykjavík)
Vitrectomy replaces the vitreous gel with another medium, usually an aqueous saline solution
followed by aqueous humour, or with silicone oil, air etc. In all cases the viscosity of the medium
is changed and this influences the diffusion of all molecules and fluid currents in the vitreous
cavity.
The Stokes Einstein equation shows that the diffusion coefficient depends inversely on the viscosity
of the medium in which diffusion takes place. The more viscous a solution, the slower is
diffusion through it. Similarly, the Hagen Poiseuille equation shows that fluid currents are
slower in a more viscous solution. Since diffusion and fluid currents are the only transport
mechanisms available to any molecule in the vitreous cavity, this means that the transport of
any molecule will be slower if the medium is highly viscous and faster if the medium becomes
less viscous.
Vitreous humour is many times more viscous that water or saline solutions. Reported viscosity measurements of vitreous
gel vary somewhat. Our measurements in the pig indicate that the viscosity of the vitreous humour is biphasic, with a lower
viscosity component that is about 6 centipoise, six times more viscous than water, and a higher viscosity component well
above 100 centipoise.
When we replace vitreous gel with six times less viscous saline, the transport of any molecule in the vitreous cavity becomes
six times faster. Initially our eyes were on the transport of oxygen. Stefansson et al (TAOS, 1981) reported that following
vitrectomy and lentectomy in cats the oxygen tension fell in the anterior chamber and rose in the vitreous cavity and at the
retinal surface, indicating a rapid transport of oxygen between the front and back of the one chamber eye filled with saline.
Retinal ischemia increased the oxygen transport from front to back even more.
In a vitrectomized eye, oxygen transport through the vitreous cavity can supply oxygen to an ischemic area with BRVO and
improve the retinal oxygen tension (Stefansson et al, IOVS 1990). Holekamp and Beebe (AJO 2005) have shown in the
human eye that oxygen fluxes increase following vitrectomy and oxygen tension gradients are flatter, which agrees well with
the previous reports and the classic rules of physics above. The improved transport by diffusion and fluid currents applies
to all molecules, not only oxygen. Nutrients and growth factors for example will also diffuse faster in the vitrectomized eye.
This may have significant clinical effects.
In an ischemic area of the retina, for example in BRVO or diabetic retinopathy, oxygen will diffuse to that area through the
vitrecomized vitreous cavity and at the same time VEGF will diffuse away from the area into the cavity. This reduces the concentration
of VEGF through 2 mechanisms, reduced production due to improved oxygenation and clearance away from the
tissue. This may explain the beneficial effect of vitrectomy on ischemic retinopathies and at the same time why neovascularization
may take place on the iris after vitrecomy as oxygen now diffuses away from the anterior segment while retinal
VEGF diffuses forward.
Vitrectomy influences the pathophysiology of diabetic macular edema in several ways. Firstly, by improving retinal oxygenation,
the production of VEGF decreases. Secondly, VEGF is cleared away from the retina into the vitreous cavity more rapidly
than before. The decreased VEGF concentration will decrease the permeability of the retinal microcirculation to osmotically
active molecules and counter edema formation according to Starling’s law. Thirdly, the improved oxygenation will also
constrict the arterioles (Gottfredsdottir et al, AJO 1993), decrease the hydrostatic pressure in the microcirculation and
decrease edema formation according to the hydrostatic arm of Starling’s law (Stefansson, Survey Ophth. 2006).
Finally, we may speculate that following a posterior vitreous detachment the diffusion characteristics of the vitreous cavity
will be somewhat similar to the vitrectomized eye. This may have beneficial and harmful consequences. On one hand
ischemia might be helped, as was outlined above. On the other hand the retina might be releasing important nutrients, neurotransmitters
and growth factors into the vitreous cavity at a faster rate than would be normal, when the vitreous gel is
attached. Whether some of the degenerative age related retinal diseases, such as age related macular degeneration and
glaucoma, relate to this remains to be investigated, but it is interesting that many of them seem to start at about the same
time in life many of us experience a posterior vitreous detachment.