Excerpts
From: The International Glaucoma
Review, Volume 11-1, 2009
Effects of brimonidine on retinal ganglion cell survival in
an optic nerve crush model
Currently, the only proven clinical neuroprotectant in glaucoma
management acts indirectly by unclear mechanisms: reduction
of the intraocular pressure
- Whether or not brimonidine is
a clinically significant direct neuroprotectant requires
further study.
- Unfortunately, not only in neuronal diseases, but also
in glaucoma, many candidate drugs have not shown any definite
evidence for neuroprotection in a clinical study.
- The present study may, therefore, be taken only as a hint,
but not at all as an evidence, of a potentially neuroprotective
effect of brimonidine.
M & T:
While brimonidine was originally marked as being a neuroprotectant,
such is not the case. Used t.i.d. (or b.i.d. in addition to
a prostaglandin), it can reduce IOP about 25%. Note that both
the original 0.2% and the later generation 0.15% concentrations
are generically available. We recommend the 0.15% concentration.
From our 2001 Drug Guide, we share the following authoritative
quotes:
“Some drugs have some very interesting properties in experimental
and animal models, but I know of no evidence that these results
are necessarily relevant to glaucoma. I don’t believe we have
a drug that has a proven benefit in glaucoma beyond its IOP-lowering
effect.”
Robert D. Fechtner, MD
New Jersey University of Medicine & Dentistry
Eye World, January, 2001, page 33
“We do not have neuroprotective drugs that we can prescribe.
We do not have devices for retarding ganglion cell loss as
of yet, with the exception of pressure-lowering agents.”
Evan Dreyer, MD, Ph.D.
Scheie Eye Institute, University of Pennsylvania
Primary Care Optometry News, February, 2001
“At this time, there is not a drug available to you that has
known neuroprotective features.”
Harry Quigley, MD
Wilmer Ophthalmological Institute
Audio-Digest Ophthalmology, April, 1998
“Although the data on neuroprotection with brimonidine in animal
models is compelling, there is not yet any data regarding
neuroprotection with Alphagan in glaucoma patients.”
Louis Cantor, MD
Annenberg Center For Health & Sciences at Eisenhower
Neuroprotection in Glaucoma, December, 2000
“In the field of glaucoma, this past year [1999] was characterized
by a lot of hoopla and some substance. Leading the hoopla camp
is the whole area of neuroprotection.”
“…one of the most important questions that needs to be answered
has to do with why some nerves are sensitive, and other nerves
are resistant to the damaging effects of intraocular pressures.”
George Spaeth, MD
Wills Eye Hospital
Yearbook of Ophthalmology, 2000
“There is currently no solid evidence that any drug that has
a blood-flow change or a neuroprotective aspect has any advantage
in the treatment of our glaucoma patients.”
Thom Zimmerman, MD, Ph.D.
Audio Digest Ophthalmology”, February 21, 2000
The scope of glaucoma in China
Although it has been widely accepted that lower IOP is the
only effective treatment for glaucoma, the level to which
the IOP should be lowered in order to stop further glaucomatous
damage is still a controversial topic. The concept of target
IOP is of great importance for the glaucoma doctors, because
it emphasizes that there is a certain level of IOP that should
be established and then modified based on individual patients’
needs.
The issue of cost-effectiveness is important for the clinicians
to consider particularly in underdeveloped areas. Thus, beta
blockers still dominate in the medical treatment of glaucoma.
Large-scale, randomized, controlled trials are urgently needed
to test the effectiveness and appropriateness of treatment
in Chinese people.
M & T:
Although discussing the need of the Chinese people, these two
principles of target pressure and the cost effectiveness of
topical timolol apply to U.S. practices as well.
Risk factors for motor vehicle collision involvement
Do eye diseases and, more specifically, visual impairment have
a direct impact on the ability to drive safely? With respect
to eye diseases, there was no significant association between
any of the conditions examined (cataract, glaucoma, macular
degeneration and diabetic retinopathy) and any type of MVC
(motor vehicle collision). The overall prevalence of these
conditions was very close to the prevalence in the aging
general population. More interestingly, there was no significant
association between binocular visual acuity and MCV involvement.
Similarly, there was no hint of an association between MVCs
and reduced contrast sensitivity. The take-home message of
this pooled-data analysis with respect to visual disturbances
is that we may be using the wrong visual tests for granting
driving licenses.
Water-drinking test, pulse amplitude and choroidal thickness
Eighty years following the initial observation by Schmidt that
intraocular pressure (IOP) increases following ingestion
of water, there is a resurgence of interest in the role of
the water-drinking test (WDT) in the investigation of glaucoma.
The impetus behind these studies is the view that IOP spikes
and diurnal IOP variations are important in the progression
of glaucoma and that a single IOP measurement in the clinic
does not necessarily reflect what is happening to an individual’s
IOP through the course of the day. DeMores, et al. hypothesize
that an increase in choroidal volume occurs following the
WDT and that this explains, in part, the elevation which
may be associated with this test.
Tonometry
Goldmann Applanation Tonometry (GAT) is no longer on a pedestal
as a ‘gold standard’ instrument. We now recognize that IOP
is a noisy value (it fluctuates minute to minute, hour to
hour, asleep and awake with body position, breath-holding
and a long list of other physiologic parameters) and that
a single snapshot of this noisy value provides limited clinical
information. Couple this with the recognition that the instruments
we use to measure IOP are themselves noisy (with artifact
introduced by CCT, corneal material properties, refractive
surgery, etc.) the clinician is left wondering what to do.
Until we have 24-hour monitoring of IOP with a technique
less affected by corneal properties, all we can do is try
to get the best performance out of the instruments we have.
Surveys performed in the United Kingdom have shown that few
clinicians have a protocol in place to verify calibration
of the GATs in their offices. They should. Instead of leaving
the tonometer calibration bar collecting dust in a drawer
somewhere, clinicians should have a protocol in the office
to regularly verify calibration of their Goldmann tonometers.
M & T:
Good advice. But, we do not need to obsess over and micromanage
IOP measurements; it is only a part of the comprehensive glaucoma
evaluation. If the only single metric we had was the IOP evaluation,
then meticulous obsession might be appropriate. Thankfully,
we have numerous metrics that, taken collectively, lead to
highly sensitive and specific decision-making.
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