Mechanisms of Retinal Fluid Accumulation and Blood-Retinal Barrier Breakdown

Macular edema is the swelling of the central portion of the human retina and it is associated with increased retinal thickness. It can be simply defined as an excess of fluid within the retinal tissue. It must be realized that the normal retina possesses a functional extracellular space. With regard to the extracellular volume of the retina, there have been few physiologic studies, but there are reported values of 24.8% for the cerebrum and 23.6% for the cerebellum. It is accepted that the retinal extracellular space is similar to the brain. It is generally agreed that the proximate cause of macular edema and retinal fluid accumulation is a breakdown of the blood-retinal barrier (BRB). When there is a breakdown of the BRB, retinal edema can be interpreted in terms of basic principles of capillary filtration (Starling's law). Therefore, the main factors influencing retinal edema formation are BRB permeability, capillary hydrostatic pressure, tissue hydrostatic pressure, tissue osmotic pressure, and plasma osmotic pressure. Active transport by the retinal pigment epithelium is necessary to remove water that percolates through the retina from intraocular pressure and is also as a safety mechanism against fluid accumulation in disease. Clinical evaluation of the BRB and retinal edema can be performed noninvasively by using an OCT-based method designated OCT-Leakage, which is capable of identifying and quantifying sites of alteration of the BRB, and by mapping sites of low optical reflectivity, i.e., changes in the retinal extracellular fluid.