With age, the neuronal population of the retina is progressively erroded.11
There is also a progressive increase in inflammation and deposition of extracellular material.2
The origin of this material is unclear but, ultimately, it may due to failure of the ageing RPE to appropriately digest the photoreceptor outer segments. These deposits accumulate on the outer segments and on the BM.3
In both cases, they contain neurotoxic amyloid and, in the case of those on the BM, they progressively restrict metabolic flow.13
The deposits that accumulate on the BM differ depending on the location and some probably lead to drusen formation. Central drusen can be large and confluent and appear opaque in fundus photographs.4
Those in equatorial regions are more focal, hard and smaller, with different fluorescent signatures.5
This implies that deposits at the two locations have different biochemical characteristics. However, neither has the characteristics found in the peripheral deposits described in this study, which were clear and lenticular both before and after dehydration. Internally, they appeared to contain spherical bodies; they also seemed to be firmly attached to the BM, as they generally swept away the RPE isolating the retina.
These deposits maybe related to the lens zonules radiating towards the ciliary muscles. This would explain not only their geographic origin, but also the marked difference in their physical characteristics, being unlike the drusen that are found more centrally; however, this remains to be demonstrated. While ciliary muscles remain contractile with age, a number of changes take place including reductions in unaccommodated muscle diameter14
and a watershed of changes that occur over the age of 70 years, which include decreased cross-sectional area, increased connective tissue content and reduced nuclei numbers.15
Deposits in the CB have been noted before; in some cases they can appear as small white nodules called Fuch's adenoma, which can be associated with cataracts;16
however, these do not fit the description of the material described in this study. Furthermore, the existence of lipid-rich deposits at this location has also been noted previously, although their impact on the retina, their internal structure and physical characteristics were not described.9
were the first to establish the term ‘cystoid degeneration’ which describes the accumulation of transparent materials within the retina, but the impact of these on adjacent tissue was largely left unaddressed.
One of the key reasons why the lesions described here have received so little attention is that it is thought they have little direct impact on vision. However, two specific features of the far-anterior retina are affected by the progressive development of these deposits and the subsequent loss of retinal function at extreme eccentricities. First, the human far-anterior retina is cone dominated.17–19
The reason for this is unclear but probably relates to the fact that during development, at any retinal location, cones are generated before rods.20
Hence termination of cell production in the peripheral retina will result in a relatively cone-rich region. These cones tend to be large17–19
and are almost certainly only subject to diffuse illumination, but it is possible that they have a functional role that does not relate to spatial vision.
Second, this region also contains a plexus of melanopsin containing cells and their processes that course around the retinal rim.21
Melanopsin containing cells are heterogeneous.22
In addition, it has been argued that some may mediate crude pattern vision.24
But cells located at the retinal rim will be unable to do this because they are located at the extremities; like the cones, they will not receive spatial information, only diffuse illumination. Consequently, their primary role must be that originally ascribed to the melanopsin system—that of circadian regulation.25
Many of these peripheral melanopsin cells may be lost because of the progression of the deposits described here and their loss may contribute to reduced circadian behaviour in older humans.25