Excerpts From: The International Glaucoma Review, Volume
7-3, 2006
(Fourth in a Series)
Noteworthy Information
- In the Normal Tension Glaucoma (NTG) Study, 50 percent of
the NTG patients achieved a 30 percent IOP reduction without
surgery.
- It is entirely possible that the so-called functional reserve
is an artifact created by the discrepancy between structural
and functional measurements.
- Perhaps disc size and not race is the determining difference
between African-Americans and other ethnicities. Regardless,
results of the CSLO Ancillary Study to the OHTS highlight the
need to consider optic disc size when evaluating the appearance
of the optic disc in glaucoma.
M & T Commentary:
Yost Jonas, an extraordinarily talented glaucoma subspecialist
in Germany, speaks of this concept in a most pragmatic way.
In the September 2006 AJO, Dr. Jonas says make “xa quick,
crude estimate of whether the disc in question is average-sized
(medium), smaller-than-average, or larger- than-average.”
We totally agree. There is little reason to actually measure
(or have measured via a “glaucoma scanning instrument”) the
horizontal and vertical dimensions of the optic nerve. Just
take a careful look, and observe whether the nerve head is
larger than usual, about normal, or smaller than usual.
SWAP, more variable than standard perimetry, is difficult
for some patients.
M & T Commentary
Now that SITA-SWAP is available, this test is less arduous
than the original rendition. Paraphrasing Bengtsson and Heijl
in Ophthalmic, July 2006: “Surprisingly, there was no significant
difference between conventional SAP (standard automated perimetry)
and SWAP (short wavelength automated perimetry), or the new
SITA-SWAP in diagnostic sensitivity.” They go on to say that,
“SITA-Fast has previously been reported to be able to identify
at least as much significant glaucomatous field loss as SITA-Standardx
and to have a diagnostic sensitivity of more than 90%.” Summarizing,
“Our results indicate that there may be some differences
in sensitivity between SWAP and SAP, but those differences
are probably smaller that what has been previously believed.”
It will be interesting to see if future research supports,
or refutes, this study.
Management of Glaucoma in Infancy and Childhood
- Beta-blockers have been associated with apnea, and alpha-2
agonists with central nervous system depression in infants.
- Topical carbonic anhydrase inhibitors have been shown to be
safe and effective in children. Prostaglandin analogs are also
supposed to be safe, but their long-term efficacy is yet to
be determined.
Angle-Closure Glaucoma
- Angle-closure accounts for about half of all glaucoma cases.
Most cases of angle-closure glaucoma are asymptomatic.
M & T Commentary
This certainly underscores two essential steps in the glaucoma
evaluation: one, carefully study the optic nerve anatomy
so as to not miss suspicious cupping, and two, perform gonioscopy,
especially in those patients having apparent narrowing upon
the Van Herrick assessment.
- Once extensive synechiae or glaucomatous optic neuropathy
associated with angle-closure glaucoma have occurred, iridotomy
is less effective in achieving IOP control.
- PACG is a big health problem in China.
M & T Commentary
We assume this would be the case for people of Chinese ancestry
throughout the world.
- Following angle-closure, the trabecular meshwork function
may remain impaired as a consequence of inflammatory processes,
regardless of whether peripheral anterior synechiae develop
or not.
Screening for Open-Angle Glaucoma
- Mass or community screenings are typically performed on unselected
populations such as community centers, shopping centers, churches,
or on partially selected populations, such as all volunteer
employees working in a large corporate building.
- A 1996 statement from the United States Preventive Task Force
(USPST) stated that insufficient evidence was found to recommend
for or against glaucoma screening in primary care practices.
For its latest recommendation (released in March 2005), the
USPST concluded that the evidence is insufficient to determine
the extent to which screening – leading to earlier detection
and treatment of people with elevated IOP or open-angle glaucoma
– would reduce impairment in vision-related function or quality
of life. Given the uncertainty of the magnitude of benefit
from early treatment and given the known harms of early treatment
(i.e., local eye irritation and an increased risk for cataracts),
the USPST could not determine the balance between the benefits
and harms of screening for glaucoma. It concluded that the
evidence is insufficient to recommend for or against routine
screening.
M & T Commentary
We simply recommend doing mass screenings for “at risk” groups
such as older persons, especially those of African descent.
We still do not know whether delaying treatment of elevated
IOP affects the rate of progression to POAG, and whether delaying
treatment of POAG affects the rate of visual field progression.
M & T Commentary
It really does not matter as long as, once the disease is detected,
the patient is followed carefully by an eye doctor and treated
appropriately if there is evidence of progression.
The best screening results found were sensitivity of 93 percent
and specificity of 88 percent for automated perimetry.
M & T Commentary
Of course, functional assessment of visual field loss will
only detect moderate to advanced glaucomatous optic neuropathy.
To do a meaningful community screening, we recommend at least
two procedures: measure the IOP, and above all, stereoscopically
examine the optic nerve head.
- Two rationales for glaucoma screening are that of promoting
public awareness of the disease, and in many medically underserved
communities where ophthalmologic services are not readily available,
glaucoma screening may offer an avenue for detecting a wide
range of vision disorders.
- Among individuals who test positive based on the screening,
only a small percentage will actually have the disease, and
most will have undergone costly, unproductive work-ups. Thus,
screening may only be justified in certain “high-risk” groups.
Cooperation with Medical Therapy
As with other chronic medical conditions, the cooperation
of patients with prescribed medical regimens is less than
ideal. Issues that seem immediately relevant to explaining
poor patient cooperation with therapy include (among others):
lack of symptoms, slow progressive change in visual function,
delay in loss of quality of life until late in the disease,
poor patient understanding of the disorder, lack of adequate
physician educational efforts, cost of medication, frequent
dosage, and multi-drug regimens.
M & T Commentary
Probably the most important thing we can do is redouble our
efforts to inform, educate, and encourage our patients.
Regarding compliance interventions:
- Knowledge is a key factor. Patients who do not understand
the disease are not as likely to comply with treatment.
- Approaches to help forgetful patients have not been highly
successful.
- Close follow-up in the time period immediately after initiating
therapy is needed, as this seems to be a critical period when
many stop taking medications. Other interventions that have
been proposed are: video/DVD of proper drop instillation; providing
a three-month supply to the patient of whatever medication
is prescribed; and having a technician call the patient at
one week and one month intervals to administer a brief, structured
interview to ask about drop taking issues and to answer questions.
Identifying Narrow Angles
In the Tajimi study (Yamamoto, et al.) limbal chamber depth
assessment (LCD – the Van Herrick test) was used as a method
to identify subjects with anatomically narrow angles. The
authors cite the high sensitivity of LCD in identifying people
with very narrow angles. The omission of gonioscopy for all
subjects was an understandable pragmatic decision. Preliminary
evidence points toward a greater, undetected burden of angle
closure. Ultimately, a shift in mindset is needed, away from
requiring that angle closure is proven to exist, and towards
proving that angle closure is not occurring. This would probably
improve the prognosis of many patients who have this disease,
which is preventable in most cases, but remains unrecognized
in the asymptomatic majority.
M & T Commentary
As stated earlier if the Van Herrick estimation is at all suspicious,
then perform a definitive gonioscopic analysis.
Identifying Glaucoma
- Reliance on cup to disc ratio for defining glaucoma is problematic
since cup to disc ratios are influenced by disc size, which
is not considered.
M & T Commentary
As mentioned earlier, we do need to be cognizant of the nerve
head size when assessing the cup anatomy.
- One finding of a study conducted by Harasymowycz et al. found
the agreement between clinical examination and HRT II MRA to
be poor. This is in keeping with previous studies. The poor
agreement between the HRT and clinical examination highlights
the differences in diagnostic technique between imaging devices
and clinical examination. Previous studies suggest clinicians
are not so reliable at estimating rim area or cup-disc ratio.
Without independent verification of glaucoma using both structural
and functional measures, we do not know which of the two techniques
compared in this study most accurately identify subjects with
glaucoma.
M & T Commentary
In assessing the C/D ratio, it is very important to critically
examine for any neuroretinal rim tissue erosion. Remember
the ISN’T rule: In normal, healthy optic nerve heads, the
Inferior rim should be the thickest, followed by the Superior
rim. The Nasal rim should be a bit thinner than the superior
rim, and the Temporal rim should demonstrate the thinnest
rim. While not 100% sensitive and specific, the ISN’T rule
is a good standard to help assess the status of the optic
nerve head.
Assessing Risk Factors For Predicting the Development of
Glaucomatous Damage
- The choice of the level of risk for which treatment should
be considered is arbitrary and potentially dangerous. We all
know that the risk of falsely labeling a patient as glaucomatous
may have a negative impact on her/his quality of life due to
diagnosis (especially if it is a wrong diagnosis) and more
important, to treatment. So which is the level of risk deserving
treatment? This, of course, must be left to the clinician’s
judgment. Making our decisions on the basis of untreated IOP,
no doubt, is really good sense. Risk models are useful as far
as they are applied with good sense.
M & T Commentary
But it’s not as simple as “untreated IOP.” Family history,
patient age and health status, status of the optic nerve,
and central corneal thickness all play into the risk assessment.
- Medeiros et al. conclude, “The relative weight of central
corneal thickness as a risk factor is four times higher than
IOP risk in the given range, and nearly three times higher
for vertical cup disc ratio and twice as high for pattern standard
deviation as compared to IOP risk in the given range. Vertical
cup disc ratio and pattern standard deviation are subject to
high variation in patients with reduced compliance and therefore
might artificially influence outcome, in particular as they
have high relative weight in the calculation model. Vertical
cup disc ratio has to be exactly defined before being incorporated
in such a model. In addition, the vertical cup disc ration
depends large upon the size of the optic nerve head (macro
disc versus micro disc). Hence, the factors with high reproducibility
will be age, IOP and CCT.”
IOP and Caffeine
Regarding the association between caffeine intake and intraocular
pressure, an Australian study found that those who drank
coffee had a higher IOP than those who didn’t in both the
univariate and multivariate analyses. The amount of coffee
consumed did not correlate with the level of IOP in the multivariate
analysis. While findings of the study are interesting, a
further confirmatory survey or study would be needed for
one to conclude that coffee or caffeine consumption is significantly
related to IOP in open-angle glaucoma patients. At the present
time, patients with open-angle glaucoma who consume caffeinated
products should not be told to stop for the purpose of better
IOP control.
Tight Neckties and IOP
In a study conducted by Talty and O'Brien, they concluded that
a tight necktie worn over an extended period of time is neither
a confounder to IOP measurement nor a factor leading to erroneous
diagnosis of glaucoma, and that avoidance of wearing a tight
necktie over an extended period is not necessary in patients
with glaucoma. Yet, it would seem that some patients do have
sustained IOP rises under these conditions that may serve
to be a confounder in measuring IOP, and could potentially
adversely affect their condition. From a practical point
of view then, it would seem that having glaucomatous patients
not wear uncomfortably tight neckties would serve to obviate
the entire issue.
CCT Measurement: Once is Not Enough
Recent studies show that optical dorzolamide treatment increases
CCT without affecting corneal endothelial morphology, and
that topical prostaglandins reduce CCT significantly. Thus,
it is recommended that CCT measurements be repeated at least
once to enhance the confidence that the true CCT values is
obtained. Contrary to previous thoughts, one measurement
of CCT in a patient’s lifetime is probably not adequate.
M & T Commentary
This may indeed be true in a few patients, but we doubt such
additional measurements will reach clinical significance
in the vast majority of patients. It certainly does no harm
to repeat such an inexpensive test, but we doubt the yield
from such additional measures will have any meaningful impact
on patient care.
Enhancing Benefits of Medical Therapy
A well-written publication by Costagliola et al. describes
a well-designed study with interesting findings. The study
demonstrates that diclofenac, a nonsteroidal anti-inflammatory
drug (NSAID), enhances the ocular hypotensive effect of latanoprost
(LP). The mechanism proposed for this finding is that, by
inhibiting the production of prostaglandins (PGs), NSAIDs
up-regulate the expression of prostanoid receptors that might
respond to LP to further reduce intraocular pressure (IOP).
Many studies have evaluated the role of NSAIDs in INHIBITING
(not enhancing) the hypotensive effect of other modalities
of glaucoma therapy.
M & T Commentary
Interesting, but probably of no clinical significance. We await
further research.
NSAIDs are expected to inhibit the effect of a therapeutic
modality that reduces IOP by stimulating the endogenous synthesis
of PGs from their precursor, arachidonic acid. However, they
should not block the effect of a PG analog that acts directly
on prostanoid receptors to reduce IOP.
M & T Commentary
To clarify, NSAIDs do not have any direct effects on the prostaglandin
receptors. They simply inhibit the enzyme, cyclooxygenase,
which catalyzes the production of prostaglandins from arachidonic
acid.
The interaction between NSAIDs and PGs has been evaluated
in may other studies. Almost all of these studies have demonstrated
no significant effect. Despite the preponderance of evidence
failing to demonstrate potentiation of the PG-induced IOP reduction
by NSAIDs, these recent studies indicate that more studies
are required to determine whether inhibition, potentiation,
or no effect occurs when NSAIDs and PG analogs are used in
combination.
SLT and Medical Therapy
Three hundred and sixty degree SLT may be an effective alternative
to medication as first line of therapy; however, additional
studies are needed with more patients, assessment of outcome
measures such as disc and visual field status, and longer term
follow-up before a definitive conclusion can be reached on
this issue. Utilizing SLT to reduce the burden of medication
un appropriate patients with OAG does seem justified.
Future studies with SLT will need to shed light on other important
questions such as whether SLT is repeatable, and whether it
is as effective as ALT in pigmentary and pseudoexfoliation
related glaucomas. Many studies have shown that SLT successfully
lowers IOP, although not significantly better than ALT. Older
studies on ALT have already shown that when treating advanced
glaucoma, surgery rather than laser trabeculoplasty should
be the primary option for treatment.
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