Excerpts From: The International Glaucoma Review, Volume
7-2, 2005:
World Glaucoma Congress
(Third in a Series From This Publication)
Noteworthy Information
- All commonly employed methods of LTP appear to be equivalent
with respect to short-term side effects and IOP lowering.
- There is no longer follow-up data available for argon laser
trabeculoplasty (ALT) than for selective laser trabeculoplasty
(SLT). Randomized studies comparing these two modalities are
not yet available.
M & T Commentary:
While SLT is generally hyped to be superior to ALT, it appears
that either type of laser trabeculoplasty is equally effective.
Hopefully a prospective, randomized study will one day determine
the winner of this (probably insignificant) horserace [debate?].
- Six percent of patients with NTG have positive neuroimaging
of compressive lesions; 60% of NTG progress despite 30% IOP
lowering treatment.
- Five dB loss with SAP equates to 25% RGC loss, 10 dB loss
to 40% RGC loss, a paracentral scotoma with 5 dB loss equates
to 50% RGC loss.
Structural Progression
Medeiros et al. report a group of patients with impending glaucoma
who showed a change in the disc configuration over time,
compared to another group with good ocular health who did
not show change. They found that about half of those with
changed discs also had visual field defect, but the others
did not. The GDx VCC scanning laser polarimetry was able
to discriminate rather well those with emerging glaucoma
(changing discs) from those who were healthy.
Two conclusions are reached by the authors: that GDx is
able to pick up some cases of emerging glaucoma before field
defects are recognized, and that a changing disc, even if not
yet definitively abnormal, can be used as a sign of early glaucoma
to validate any instrument’s ability to recognize early glaucoma.
The paper highlights that there are two ways to recognize
glaucoma. The first is the traditional approach to define
‘abnormality’ (disease) as being outside the bounds of findings
in 95% of a healthy population - whether it be disc configuration,
nerve fiber measurements, or visual field parameters. The
problem with any measurement has been that the range of normal
overlaps that found in patients with early glaucoma, so that
any cut-off point has false-positives and false-negatives.
One idea behind improved technology is to find some measurement
that has less overlap between eyes with early glaucoma and
those in perfect health. As cases of glaucoma are heterogeneous,
it may be inescapable that some will show one abnormal feature
first and others another feature, for example disc abnormality
before field abnormality, or field abnormality before disc
abnormality. The second way to diagnosis emerging glaucoma
is to recognize a ‘change’ over time, perhaps while the feature
being observed or measured is still ‘in the normal range.’
This principle of early diagnosis by documenting a change over
time is demonstrated by the authors for disc configuration,
and needs study with regard to visual fields and new technologies
being developed to quantify nerve fibers. This method requires
repeat examinations over some period of time, is potentially
most useful for early diagnosis, and is rationale for images
or quantified baseline measurements in those at high risk for
developing glaucoma.
The predictive utility of the NFI [Nerve Fiber Index] on the
GDx-VCC was greatest when it was <15 (negative prediction)
or >50 (positive prediction). But even when the NFI lay
between 35 and 50, the likelihood of pre-perimetric glaucoma
was increased by more than eightfold compared to controls.
This paper is to be commended on several grounds. It demonstrated
that GDx VCC was capable of providing useful information for
clinicians who face the diagnostic challenge of an optic disc
morphology suspicious for glaucoma but without a reproducible
visual field defect on standard automated perimetry.
M & T Commentary:
Note that we underlined “providing useful information,” because
we want to unrelentingly stress that all current diagnostic
instruments do just that. None make a diagnosis; it is
the skilled clinician who makes a diagnosis!
Progression: Predictive Factors
For patients with elevated IOP, significantly predictive factors
for progression were older age, advanced perimetric damage,
small neuroretinal rim, and larger area of x-zone of peripapillar
atrophy. In contrast, in NPG patients, a significant predictive
factor was presence of optic disc hemorrhages at baseline.
It is noteworthy that the presence of an optic disc hemorrhage
at baseline was the only parameter significantly associated
with increased frequency of progression in NPG. Thus, chronic
open-angle glaucoma and NPG differ in predictive factors for
eventual progression of glaucomatous optic neuropathy.
RNFL and Obstructive Sleep Apnea Syndrome
Prior reports have suggested an association between obstructive
sleep apnea syndrome (OSAS) and glaucoma. The mechanism
has been thought to involve intermittent upper airway obstruction
during sleep producing relative hypoxia, vascular dysregulation,
and secondary ischemic optic nerve damage.
[The study by Kargi et al.] adds further evidence that patients
with OSAS may be at risk for the development of glaucomatous
optic neuropathy. The authors correctly point out that ischemia
injury may represent a possible mechanism for RNFL loss.
An alternative hypothesis that may co-exist in such patients
is that intermittent upper airway obstruction may produce increased
intra-thoracic pressure resulting in increased episcleral venous
pressure and increased nocturnal IOP.
M & T Commentary:
Also keep in mind that obese patients with OSAS are at risk
for Floppy Eyelid Syndrome (and vice versa), so be attentive
for symptomatic complaints of unilateral eye irritation in
this subgroup of patients.
Cooperation with Medical Therapy
Olthoff et al. reviewed many of the papers on cooperation
with medical glaucoma therapy. They conclude that we know
the following facts:
- Noncompliance with prescribed therapy is common;
- it may be a cause of worse visual outcomes;
- no patient characteristics accurately identify non-compliers;
- patients underreport their non-compliance;
- monitoring ideally should use mechanical devices;
- pharmacy refill data are probably less accurate predictors
of cooperation;
- educational efforts may be useful in improving compliance;
- compliance may be better with simpler regimens (fewer drops/day,
less complex schedules of medications);
- patients probably comply better if they make more doctor visits.
M & T Commentary:
Regarding #5 in the above list, these are about to become available
for general use. It will be interesting to learn just how
helpful such devices can be.
Target Pressure
Malerbi et al. conducted a retrospective analysis of their
clinical data of 65 patients with POAG. Patients had four
IOP measurements between 8:00 am and 5:00 pm; so these measurements
are clearly not diurnal, by definition. Not surprisingly,
additional pressure measurements yielded a wider range of
IOPs, some of which were above the individual’s target pressure.
The main message is that additional IOP measurements will
reveal a wider range of IOP fluctuation. It is not clear,
however, how to use this finding in practice. There is accumulating
evidence that long-term IOP fluctuation is an important risk
factor for glaucomatous progression.
Prostaglandins
In a well powered randomized clinical trial the addition of
topical bimatoprost to latanoprost significantly raises,
rather than lowers IOP. Despite [the trials] not having demonstrated
a precise mechanism of why the co-administration of these
two individually potent drugs should result in an elevated
IOP, the message that latanoprost and bimatoprost should
not be used together is still compelling.
M & T Commentary:
It is probably reasonable to assume that none of the prostaglandins
should be used together, and that no prostaglandin should
be used more than once daily.
Statins and Glaucoma
Do statins prevent the development of glaucoma, as well as
lower your cholesterol? Statins not only decrease synthesis
of cholesterol, but have ‘spin-off’ effects due to decreasing
other molecules in the cholesterol synthesis pathway. One
such change is the cytoskeleton, causing cells to change
shape. A number of other cytoskeletal acting drugs have
been studied in the eye, and many lower IOP; statins appear
to be another in this category.
M & T Commentary:
The chatter about statins having a beneficial effect on IOP
continues. We await larger, longitudinal studies to determine
the clinical significance, if any, of these drugs relative
to glaucoma protection.
Iridotomy in Pigmentary Glaucoma
One might argue if eyes, showing already an increased IOP and
a pigment dispersion, are the best candidate for iridotomy.
In fact, pigment-induced TM damage has already occurred in
such eyes. The potential benefit of iridotomy is then greatly
reduced.
The issue of laser iridotomy in pigmentary glaucoma is still
unresolved. Until prospective, well designed, randomized and
properly controlled clinical trials will be available, we will
not be allowed to deny (or trace) any role for laser iridotomy
in eyes showing a pigmentary glaucoma.
What do we know about laser iridotomy in pigmentary glaucoma?
We know that laser iridotomy straightens the iris in patients
with posterior bowing and pigment dispersion. It is presumed
this straightening reduces pigment shedding ultimately leading
to better intraocular pressure (IOP) control.
In conclusion, if you are an ‘iridotomist,’ based on this
paper [by Reistad et al.] there is little reason for you to
stop your current practice. However, the evidence for a clinical
effect on IOP with iridotomy remains very weak and indeed is
not supported by this paper. [Commentator Graham Trope states
that hex] “will continue with my practice of not performing
iridotomy until such time as I see some convincing evidence
from a randomized prospective study to support such intervention.”
M & T Commentary:
In patients with increasing IOP and/or progressive ONH changes
over time, laser iridotomy should be considered in an effort
to allow the iris diaphragm to move forward, thus halting
(or minimizing) iris pigment epithelial shedding. This could
allow the mechanisms within the trabecular meshwork to reestablish
more physiologic aqueous flow, and ultimately IOP reduction.
We agree that once pigmentary glaucoma is firmly established,
little is accomplished by performing an LPI - the opportunity
for earlier and therapeutically meaningful intervention has
been missed.
Cataract Extraction and IOP
In this study, Issa et al. measure central anterior chamber
depth (ACD), lens thickness, and axial length in 103 non-glaucomatous
eyes pre- and post-cataract surgery and try to correlate
these measures with the change in intraocular pressure (IOP).
The most notable finding was the extent of reduction in IOP
following surgery was inversely related to the preoperative
ACD.
The assumption can be made that it is a widening of the angle
that is responsible for the relationship between shallow preoperative
anterior chamber and a subsequent decrease in IOP.
Glaucoma Risk Analysis
[Study] results suggest that adjusted IOP, as calculated using
current algorithms, is not useful within glaucoma risk analysis
since adjusted IOP was unable to predict either presence
or severity of glaucomatous visual-field loss in this study.
CCT, conversely, was found to be a robust and independent
predictor of glaucomatous visual-field loss. These findings,
while supporting routine CCT measurements for all glaucoma
suspects, do not support routine clinical computation of
adjusted IOP values using current algorithms.
Increased CCT may lead to falsely high values of IOP measure
with Goldmann applanation tonometer. In this study, when IOP
values of the OHT group were redefined according to the formulae
regarding the CCT, the authors noted that one third of them
were normal. Determination of the CCT in OHT cases is crucial
since it has great impact on IOP values, measured with applanation
tonometer, which is the main parameter in the diagnosis and
follow-up of glaucoma.
M & T Commentary:
It is the stand-alone CCT that helps enable risk quantification
in the context of glaucoma. Attempting to use CCT to yield
a CCT-adjusted IOP appears to be minimally useful. Thin
corneas are at greater risk for glaucoma that thick corneas.
Thick corneas cause inflated IOP readings, which may lead
inattentive (or naïve) doctors to initiate unnecessary ocular
hypertensive therapy. Always cerebrally analyze all the data
obtained during the course of a comprehensive glaucoma evaluation,
and do not let one isolated factor inappropriately sway your
judgment.
IOP Measurements in the Management of Glaucoma
Day-long measurements are useful in selected patients who demonstrate
progressive glaucomatous damage. Early morning measurements
are most frequently highest. The range of IOP may be as important,
or more important than, the peak IOP level.
Any single intraocular pressure measurement taken between
7 am and 9 pm has a higher than 75% chance to miss the highest
point of a diurnal curve. Intraocular pressures may be measured
at different times of the day to have the best chance of observing
the maximal value.
Goldmann applanation tonometers are not as accurate as the
manufacturer’s recommended calibration error tolerance of ±
0.5mmHg would suggest. Calibration error of less than .5mmHg
is clinically acceptable. Calibration error checks should be
carried out once monthly and tonometers with calibration errors
greater than ± 2.5mmHg returned to the manufacturer for recalibration.
Additional checks should be made if tonometers suffer specific
damage.
M & T Commentary:
Let’s beat this dead horse one more time. When at all practical
(which is at least 90% of the time), obtain three to four
IOP measurements prior to initiating ocular hypertensive
therapy. This will enable a more complete characterization
of the diurnal curve, which can then more effectively guide
therapeutic intervention.
Threshold Testing
In a hospital eye service glaucoma clinic in which new referrals
are evaluated, threshold 24-2 FDT testing with the Humphrey
Matrix has performance characteristics similar to [standard
automated perimetry.] These findings suggest threshold testing
using the FDT Matrix and SAP is comparable when the 24-2
test pattern is used.
M & T Commentary:
While this has also been our experience, it is important to
note that the frequency doubling targets used in the Matrix
probably allow detection of visual field defects 3 to 5 years
earlier than standard perimetry. The implication of such
in patient care is yet to be determined.
Systemic Hypertension and Glaucoma
Common pathogenic mechanisms in ciliary and renal tubular epithelia
may explain coincidence of glaucoma and systemic hypertension.
The choice of cardiovascular treatment, could substantially
influence glaucoma incidence, with beta blockade protecting
and ACE inhibitors of calcium channel blockers not affecting
underlying risk.
Brinzolamide Versus Dorzolamide as Adjunctive Therapy
[This study] concluded that the efficacy of brinzolamide 1%
was equivalent to dorzolamide 1%; however, the safety of
brinzolamide 1% was superior to dorzolamide as adjunctive
therapy to the combination with latanoprost and a beta-blocker.
Neuroprotection
Although it is known that ganglion cell death causes loss of
vision in glaucoma, the pathogenesis of the disease is complex,
probably involving an initial ischemic insult to the ganglion
cell axons and glial cells with the ganglion cell bodies
eventually being affected. It may therefore be necessary
to blunt many stages in the pathogenesis of the disease to
obtain a clinically effective neuroprotective strategy.
In animal experiments, one cause of ganglion cell death in
ischemia is an overactivation of glutamate receptors and
a subsequent rise in intracellular levels of sodium and calcium
ions as well as a generation of reactive oxygen species.
In contrast, optic nerve death in ischemia is mainly caused
by an influx of sodium and reversal of the sodium/calcium
exchanger, which leads to a rise in intracellular calcium.
Thus, a substance that reduces the influx of sodium will
protect the ganglion cell axon, and if it also reduces calcium
influx and/or acts as an antioxidant, it will protect the
ganglion cell body in addition. Of all antiglaucoma drugs,
only beta-blockers have both calcium and sodium channel blocking
activity, with betaxolol being the most efficacious of those
analyzed. In addition, of the tested ophthalmic beta-blockers
only metipranolol has powerful antioxidant properties. Moreover,
laboratory studies on rats have shown that topically applied
beta-blockers attenuate ischemic injury to ganglion cells
by mechanisms that do not appear to involve an action on
beta-receptors. Thus, of the substances used to lower intraocular
pressure in glaucoma, beta-blockers have unique additional
characteristics that also give them the capacity to act as
neuroprotectants.
M & T Commentary:
Very interesting. We’re not sure what to make of this, other
than to see if further studies show a clinically significant
effect. Who knows? Beta-blockers may play an even stronger
role in glaucoma care in years to come.
Does Adjunctive Glaucoma Therapy Affect Adherence to the Primary
Therapy?
[The study concludes thatx] the statistically and clinically
significant increase in refill intervals may affect intraocular
pressure control. The authors suggest that, when adding a
second drug, physicians need to consider the possible impact
on the patient’s adherence to the first drug.
The Importance of Complete Medication Documentation by General
Physicians
[In this study] almost half of the charts of these primary
physicians had no documentation of any eyedrop use by their
patients with glaucoma. An important step in reducing drug-induced
side effects and interactions with other medications would
be better recognition by primary physicians of the ophthalmic
drugs used by their patients.
END
|
