title: Diabetic macular edema.
abstract: A variety of treatment options are available for the treatment of diabetic macular edema. They include laser photocoagulation, anti-VEGF drugs, intravitreal steroids, and vitrectomy with or without release of vitreoretinal traction. A full understanding of the physiological mechanisms 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 thereby decreases leakage of plasma proteins from capillaries into the tissue. In addition, vitrectomy allows faster clearance of cytokines, such as VEGF, from the retina into the vitreous cavity. The VEGF-lowering effect of photocoagulation and vitrectomy can be augmented with anti-VEGF drugs and corticosteroids reduce the effect of VEGF on capillary permeability. Starling's law explains vasogenic edema, which is controlled by osmotic and hydrostatic gradients between vessel and tissue. It explains how VEGF-induced vascular permeability causes plasma protein to leak into the tissue interstitial space, thus decreasing the osmotic pressure gradient between vessel and tissue, resulting in water accumulation, i.e. edema. This is reversed by reducing VEGF production, which is achieved with laser treatment; or by removing VEGF with antibodies or vitrectomy; or by reducing the permeability effect with steroids. At the same time, Starling's law takes into account hemodynamic changes that affect the hydrostatic gradient. High arterial blood pressure and hypoxic vasodilatation increase the hydrostatic pressure in the microcirculation, which increases water flux from vessel to tissue and induce edema. Treatment of arterial hypertension or reversal of retinal hypoxia with laser reverses this pathophysiology and reduces edema. 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. Release of vitreoretinal traction reverses this mechanism and reduces edema.
authors: University of Iceland, National University Hospital, 101 Reykjavı´k, Iceland.
authors: Einar
authors: E
authors: Stefánsson
keywords: Edema; Laser treatment; Macular edema; Oxygen; Starling’s law; Steroids; Vascular endothelial growth factor; Vitrectomy; Water
references: Acta Ophthalmol Scand. 2005 Dec;83(6):645-63
references: 16396641
references: Ophthalmology. 1992 May;99(5):753-9
references: 1594222
references: Trans Am Ophthalmol Soc. 1981;79:307-34
references: 7200671
references: Am J Ophthalmol. 2007 Dec;144(6):878-885
references: 17936715
references: Retina. 2008 Mar;28(3):420-6
references: 18327133
references: Invest Ophthalmol Vis Sci. 2009 Jun;50(6):2953-5
references: 19060271
references: Am J Ophthalmol. 2005 Feb;139(2):302-10
references: 15733992
references: Retina. 2008 Oct;28(8):1053-60
references: 18779710
references: Acta Ophthalmol. 2009 May;87(3):285-9
references: 18507724
references: Invest Ophthalmol Vis Sci. 2004 Feb;45(2):617-24
references: 14744906
references: Acta Ophthalmol Scand Suppl. 1997;(223):1-76
references: 9559048
references: Acta Ophthalmol. 2008 Nov;86(7):800-5
references: 18547274
references: Acta Ophthalmol Scand. 2005 Feb;83(1):67-70
references: 15715560
references: Am J Ophthalmol. 1986 Jun 15;101(6):657-64
references: 3717248
references: Acta Ophthalmol. 2008 Jun;86(4):365-71
references: 18028237
references: Ophthalmology. 1990 Oct;97(10):1329-33
references: 2243683
references: Br J Ophthalmol. 2008 Dec;92(12):1581-90
references: 18952646
references: Surv Ophthalmol. 2006 Jul-Aug;51(4):364-80
references: 16818083
references: Am J Ophthalmol. 1977 Jul;84(1):62-6
references: 409296
references: Exp Eye Res. 1990 Mar;50(3):289-96
references: 2318273
references: Acta Ophthalmol Scand. 2000 Aug;78(4):374-85
references: 10990036
references: Invest Ophthalmol Vis Sci. 1985 Oct;26(10):1410-4
references: 4044168
references: Invest Ophthalmol Vis Sci. 1987 Jul;28(7):1078-85
references: 3596988
references: Acta Ophthalmol Scand. 2006 Dec;84(6):722-33
references: 17083528
references: Acta Ophthalmol Scand. 2006 Oct;84(5):624-30
references: 16965492
references: Retina. 1982;2(3):167-75
references: 6891097
references: Acta Ophthalmol Scand. 2001 Oct;79(5):435-40
references: 11594975
references: Curr Diabetes Rev. 2006 Feb;2(1):99-112
references: 18220620
references: Invest Ophthalmol Vis Sci. 2005 Mar;46(3):988-99
references: 15728557
references: Invest Ophthalmol Vis Sci. 2008 Jan;49(1):380-9
references: 18172116
references: Ophthalmologica. 2009;223(1):17-23
references: 18849632
references: Ophthalmology. 2009 Mar;116(3):497-503
references: 19167079
references: Acta Ophthalmol. 2008 Feb;86(1):34-9
references: 17651471
references: Retina. 2008 Mar;28(3):410-9
references: 18327132
references: Ophthalmology. 2008 Nov;115(11):1869-75
references: 18584872
references: Am J Ophthalmol. 1992 Jan 15;113(1):36-8
references: 1728144
references: Eur J Ophthalmol. 2008 Nov-Dec;18(6):941-8
references: 18988166
references: Exp Eye Res. 2005 Feb;80(2):249-58
references: 15670803
references: Graefes Arch Clin Exp Ophthalmol. 1997 Mar;235(3):168-75
references: 9085112
references: Acta Ophthalmol. 2008 Feb;86(1):105-10
references: 17608830
references: Graefes Arch Clin Exp Ophthalmol. 2009 Feb;247(2):147-63
references: 19034481
references: Graefes Arch Clin Exp Ophthalmol. 1996 Aug;234 Suppl 1:S66-9
references: 8871152
references: Klin Monbl Augenheilkd. 1985 Jun;186(6):500-1
references: 4046460
references: Invest Ophthalmol Vis Sci. 1990 Feb;31(2):284-9
references: 2303330