Excerpts
From: The International Glaucoma
Review, Volume 9-1, 2007
(Nineth in a Series)
Measurement of IOP
- Precision and agreement of tonometry devices should be
reported in a standardized format. Under ideal circumstances
for measurement, precision figures for Goldmann applanation
tonometry (GAT) are intraobserver variability: 2.5mmHg (two
readings by the same observer will be within this figure
for 95% of the subjects)
- Correction nomograms that adjust GAT IOP based solely on
CCT are neither valid nor useful in individual patients.
M & T Commentary
These nomograms are not completely useless as they can give
a general idea of what the true IOP might be; however, they
should not be heavily relied upon to pseudointellectually
micromanage the GAT readings.
IOP as a Risk Factor
- There is currently insufficient evidence to support 24-hour
IOP fluctuation as a risk factor for glaucoma development
or progression.
M & T Commentary
It has long been debated as to whether IOP fluctuation is or
is not a risk factor. Good old-fashioned horse sense would
tell an astute thinker that if a factor cannot be determined
yea or nay, then it’s probably not a significant factor in
the overall risk assessment.
IOP Fluctuation
- The propensity for IOP fluctuation increases with higher
mean IOP. This relationship needs to be addressed and corrected
for when conducting a risk factor analysis of fluctuation.
M & T Commentary
We’re not sure what to make of this, other than to be sure
to check IOP on two or three separate occasions at different
times of the day in an attempt to determine the “peak” IOP.
Target IOP
- The determination of a target IOP is based upon consideration
of the amount of glaucoma damage, the IOP at which the damage
has occurred, the life expectancy of the patient, and other
factors including status of the fellow eye and family history
of severe glaucoma. At present, the target IOP cannot be
determined with any certainty in any patient.
Functional and Structural Progression Detection of Glaucoma
- Longitudinal analysis of 44 glaucomatous eyes revealed
poor agreement between structural (OCT) and functional (VF)
progression detection. Detectable structural changes frequently
may not precede detectable functional changes.
M & T Commentary
Patients are highly unique, and no one theory or biological
marker will hold true for all people. This observation underscores
the imperative of evaluating each component of the glaucoma
evaluation independently.
IOP and CCT
- Whether CCT is exerting its influence solely as a confounder
of tonometry or is linked at a more fundamental level to
the underlying pathophysiology of glaucoma remains unknown.
Swimming Goggles and IOP Elevation
- Most swimming goggles generate a significant and sustained
rise in IOP over 20 minutes of up to 9mmHg. Multiple linear
regression analysis demonstrated that smaller goggle area
was associated with greater IOP elevation.
Ocular Perfusion Pressure
- Ocular perfusion pressure is the pressure difference between
blood pressure in the ophthalmic arteries and IOP. Ocular
perfusion pressure may be regarded as a combined factor of
systemic blood pressure and IOP. A fluctuation in ocular
perfusion pressure represents a fluctuation in local blood
supply to the globe. There is still a gap whether or not
a change in ocular blood supply lead to a change in the actual
blood flow and tissue perfusion in intraocular structures
critical to glaucoma, such as the optic nerve. Further well-designed
studies on ocular blood flow in patients with normal-tension
glaucoma should be encouraged.
M & T Commentary
You would think by 2008, this relationship would be fully elucidated,
but it is not. The assessment of ocular blood flow as it
relates to glaucoma is still under investigation, and is
not yet clinically applicable in patient care.
Perimetric Technology
- Compare the ability of conventional automated perimetry
using the SITA Standard 24-2 test procedure and the Humphrey
Matrix frequency doubling technology (FDT) perimetry using
the 24-2 test pattern to distinguish between patients with
glaucomatous-appearing optic discs (GAOD) and normal control
subjects. The overall findings suggest that both perimetric
techniques were able to provide similar information in a
reasonably comparable amount of time.
Hypertension and IOP Progression
- Punjabi et al. seeks to answer a longstanding question
related to the care of glaucoma patients: does the treatment
of systemic hypertension alter glaucomatous progression?
The first point that the authors correctly make is that this
is not an analysis to establish the benefit of treating systemic
hypertension. The aim of this study is to see if the comorbidity
of systemic hypertension (in this case treated) represents
a risk factor for progression of glaucoma. While acknowledging
the shortcomings of a retrospective cohort study, the authors
found that treated systemic hypertension was a risk factor
for progressive optic nerve cupping and retinal nerve fiber
layer loss over time. This finding does not advocate for
or against the treatment of systemic hypertension, but instead
begs the question, is the apparent progression due to the
treatment or the disease? The relative contribution of ocular
blood flow parameters to the health of the optic nerve remains
evasive, but we are slowly understanding that systemic cardiovascular
disease and glaucoma are almost certainly intertwined.
M & T Commentary
This may be why there is a lot of talk about having patients
on systemic hypertensive therapy NOT take evening doses of
such meds: it might cause excessively low diastolic pressure,
which could result in counterproductive hypoperfusion of
the optic nerve during sleep.
Myopia and Glaucoma
- Xu et al. Report an association of glaucoma prevalence
with high (>8 D) and marked (6-8 D) myopia as compared
to lower grades of myopia, emmetropia, and hyperopia, in
the Beijing Eye Study. There were two separate definitions
of glaucoma based on 1) optic nerve appearance; and 2) glaucomatous
visual field loss (on FDT), respectively. Within the criteria
of these definitions, the authors have convincingly demonstrated
a strong correlation of optic nerve head and perimetric glaucoma
with myopia > 6 D.
M & T Commentary
Apparently, the higher the myopia (above 6D), the greater the
risk of glaucomatous injury.
- Optic nerve head findings of tilted discs and peripapillary
atrophy are common features found in myopic eyes. Corresponding
visual field defects may or may not be present. As a result,
establishment of glaucomatous damage and progression monitoring
becomes more difficult bringing about uncertainties in glaucoma
diagnosis and management. In one study of mostly myopes
with optic disc cupping and visual field abnormalities suggestive
of glaucoma, their condition was found to be stable during
7 years follow-up. This is not surprising, considering the
fact that the subjects on the average belong to the young
and middle aged group. It is also worth mentioning that 56%
of the subjects received treatment (IOP lowering medications).
This opens the question whether the threshold for instituting
treatment should be lowered or raised. For this particular
group, withholding treatment is a good option.
M & T Commentary
We often encounter patients being treated for a disease they
do not have. Remember, glaucoma is a “progressive” optic
neuropathy. We might be wise to definitively determine progression
prior to the institution of therapy!
Pregnancy and Glaucoma
- A survey by Viadeanu and Fraser underscores the lack of
consensus among consultant ophthalmologists with regard to
treatment of glaucoma during pregnancy. In this study, 605
questionnaires were sent out, with 208 (47%) returned. Of
the respondents, only 26% had previously treated a pregnant
patient with glaucoma. When asked what they had done in this
setting, of those who had dealt with this previously, 71%
continued the pre-pregnancy management, and when all respondents
were asked what they would do in this clinical situation,
a full 31% responded that they were unsure. These figures
suggest that the majority of clinicians have little expertise
in this circumstance, and that there is no widely accepted
algorithm to consult when the situation arises. Despite the
fact that all of the current IOP lowering drugs are pregnancy
category C with the exception of brimonidine, it is interesting
that a full 71% of respondents who had treated pregnant patients
continued with their pre-pregnancy medication management.
Also, when the respondents who stated what treatments they
would use if they needed to lower IOP, 45% stated they would
use a beta blocker, 33% would use a prostaglandin, and 22%
would start with some other medication. These widely varying
treatment plans highlight our current lack of a strategy
with demonstrated safety and efficacy in this patient population.
The September, 2007 issue of Focal Points, by the American
Academy of Ophthalmology, is entitled “Drugs and Pregnancy.”
The following quotes are from this excellent source:
- “When an eye doctor is faced with the treatment of glaucoma
in the woman who is pregnant or might become pregnant, no
published guidelines exist to aid in the decision-making
process.”
- “The American Academy of Pediatrics listed timolol as a
‘maternal medication usually compatible with breast feeding.’”
Beta-blockers are Category C.
- “Brimonidine tartrate is the only commonly used glaucoma
medication categorized as pregnancy Category B.”
- “It is unknown whether brimonidine is excreted in human
milk.”
- “Brimonidine can have significant systemic side effects
in neonates and infants, including CNS depression, somnolence,
and apnea, thereby raising the concern for these side effects
if it is indeed secreted in human breast milk.” All prostaglandins
are Category C.
- “Given their potential effects on uterine muscle contractility,
[prostaglandins] should be avoided in women who are pregnant
and in those who desire to become pregnant.”
Prostaglandin Analogs (PG) without Benzalkonium Chloride (BAC)
- The introduction of preservative-free topical beta blockers
and carbonic anhydrase inhibitors has proved extremely useful
in the management of patients requiring anti-glaucomatous
therapy who have intolerance, or allergy, to the most commonly
used preservative, namely BAC.
Prostaglandin analogs are now commonly prescribed as first-line
topical anti-glaucomatous agents, since they are highly efficacious
with few side effects. However, no preservative-free prostaglandin
is currently available for clinical use. The Travoprost BAC-free
Study Group should therefore be congratulated on their study,
which elegantly demonstrated that travoprost 0.004% without
BAC is equivalent to travoprost 0.004% with BAC in both safety
and efficacy. Adverse effects were similar for both treatment
groups, hyperemia being less common in the BAC-free group (6.4%
cf 9.0%). There is now evidence that BAC-free travoprost is
an effective and safe formulation that if made available would
be beneficial to patients with BAC intolerance.
Mechanism of Extrascleral Prostaglandin Analogs
- Mediated by the FP receptor, prostaglandins lead to increased
synthesis and release of various matrix metalloproteinases
and consequent degradation of and remodeling of collagen
in the ciliary muscle, root of the iris and the sclera external
to the ciliary muscle. These PG-induced changes underlie
their ability to increase uveoscleral outflow, and demonstrate
that the sclera itself is active and responsive, rather than
just a passive component of the uveoscleral pathway.
M & T Commentary
NSAIDs inhibit the enzyme cyclooxygenase, which catalyzed the
production of prostaglandins. NSAIDs do not exert any direct
influence on prostaglandins once they are formed. Therefore,
these two pharmacologic groups can be used concurrently,
if necessary – but this is rarely indicated.. One should
note that topically applied prostaglandins enhance uveoscleral
outflow by potentiating the activity of resident extracellular
matrix metalloproteinases, which then remodel the collagen
structure within the uveoscleral tissues making them more
porous, thus enhancing outflow.
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