A. Pathogenesis

As a leading cause of blindness in the USA it is responsible for severe life style dislocation. Let's examine the pathogenesis of this condition.

Normal vision requires the coordinated activities of several specialized retinal cell types, including cone and rod photoreceptors, horizontal, bipolar, amacrine and ganglion neurons, and glial cells, which are organized in a topographically precise laminar pattern in the mature retina.

Why does this degeneration occur only in the macular zone?

As best we can tell, this is the zone of highest retinal metabolic activity with the lowest direct vessel density. This requires that the RPE / choroidal (RPE/C) metabolic complex supplies all the nutrition to the outer segments of the rods and cones.

The turnover of the outer photoreceptor segments is slow and only 10 to 15%of them cyclically participate in this daily activity. A single RPE cell services 30 to 50 receptors. The RPE is nourished by passive or gradient diffusion across the Bruch's membrane from the choriocapillaris. Ingestion of shedded outer segment discs by the RPE demands high cell metabolism.

The foveal RPE is partially protected by the Xanthophyll pigment, but over time, light energy induces RPE cell damage and cell malfunction due to the release of free radicals such as singlet O2 and OH molecules. It follows that if removal of all cellular outer segment debris falters, this cellular system stalls and constipation follows.

The subsequent response of the RPE/C complex is limited and not specific for aging macular degeneration. There is an accumulation of membranous debris on both sides of the RPE basement membrane and accumulation of intracellular material (phagolysosmes) and lipidization of Bruch's membrane.

Therefore a failure of the RPE cell appears to be the initiator of the RPE/C complex failure, which results in RPE and choriocapillaris atrophy, drusen formation, lipofuscin accumulation (derived from incomplete digestion of the outer segments). This cellular "traffic jam" induces apoptosis, cellular damage and initiates an inflammatory response. These distressed cells start producing basal laminar deposits on Bruch's membrane and increased amounts of non-collagenous proteins. With Bruch's membrane malfunctioning there is an extracellular accumulation of lipid and drusen formation. A series of vasoactive substances are released that stimulate neovascularization from the choriocapillaris. These vessels grow at about 7 to 15 microns per day, along cleavage planes formed by the new deposits along the Bruch's membrane.

Once they break into the sub-retinal space they readily bleed as there is no supportive tissue. It follows that any visual disturbance reported by the patient should be taken seriously, as this may be your only chance to actively diagnose and treat this condition prior to loss of vision.