Biology Reference
In-Depth Information
heads and elevated IOP, and treatment of the disease has relied on lowering
IOP with drugs, laser surgery, or conventional surgery. Such treatment was
shown to be effective in randomized clinical trials (
Heijl, Leske, Bengtsson,
Hyman, & Hussein, 2002
).
The recognition that some patients had the glaucomatous phenotype but
an IOP in the same range as nonglaucomatous subjects led to the definition
of “normal-tension glaucoma.” However, a major change in the view of
glaucoma took place over the past several years with the recognition that
the proportion of patients with statistically “normal” IOP was remarkably
high, ranging from 40% to 90% depending on the region of the world
and the ethnic heritage of the constituents. The high frequency of
normal-range IOP in patients with clinical glaucomatous optic neuropathy
does not mean that the IOP itself is irrelevant. Randomized placebo-
controlled clinical trials studying the effect of lowering IOP showed that
treatment also benefits patients with IOP in the normal range, implying that
the IOP itself is causal in the chain of disease pathophysiology. Thus, sep-
arating normal-tension glaucoma from high-tension glaucoma is artificial,
and both can be considered together in understanding how the disease
develops (
Sommer, 2011
). Unfortunately, the animal models for studying
glaucoma in the laboratory are almost entirely reliant on raising the IOP,
suggesting that we still do not completely understand how IOP causes
the axonal injury when it does not differ from that of normals. One possi-
bility is that there are spikes or other elevations in IOP that are not measured
clinically in typical office visits or during the day. To address this possibility,
researchers are developing methods for continuous measurement of IOP in
animals and humans (
Downs et al., 2011
).
A second informative risk factor for understanding glaucoma pathophys-
iology is age. Glaucoma can occur at any age, but is predominantly a disease
of aging, with a geometrically increasing prevalence with respect to age. This
feature is similar to that of several other neurodegenerations and presumably
reflects either change in susceptibility of the affected tissues to injury with
advancing age, deposition or increased levels of one or more substances that
increases toxicity, the loss of protective substances, or some other mecha-
nism. There may be shared mechanisms for axonal changes between
glaucomatous optic neuropathy and Alzheimer disease, Parkinson disease,
and other neurodegenerations (
McKinnon, 2012; McKinnon et al., 2002
).
Other risk factors for glaucoma include myopia, race, family history, and
recently, collagen-related genes (
Vithana et al., 2011
). It is likely that one of
the effects of these risk factors relates to changes in the biomechanics of the
