This
article will look at current management of open angle glaucoma, commenting
on diagnosis and therapeutic options.
Diagnosis
Primary
open angle glaucoma (POAG) is an optic neuropathy, associated with a characteristic
deformity of the optic nerve head, recognised clinically as 'glaucomatous
cupping'. This deformity s associated with loss of visual function, characterised
by 'retinal nerve fibre' loss and visual field defects. Glaucomatous cupping
can be identified before visual loss becomes detectable by white on white
perimetry but other tests of visual function which may detect visual loss
earlier are not yet universally accepted.
Aetiological
Risk Factors
There
are a number of 'risk factors' predisposing to the development of glaucomatous
cupping, the most important being elevated intraocular pressure (IOP).
However, approximately 30% of newly diagnosed patients with open angle
glaucoma will have IOP measurements within the 'normal range' (1) The relative
risk for elevated IOP causing glaucoma increases significantly once the
level exceeds 30mmHg (1) making prophylactic h hypotensive treatment advisable.
Other
risk factors implicated in the development of chronic glaucoma include
age, optic disc morphology, black race (2), an abnormal blood pressure
(hypertension in the young and hypotension in the elderly) (3), myopia,
increased blood viscosity, vasospasm and a family history for glaucoma.
With respect to the latter, the development of open angle glaucoma is likely
to relate to the presence of one or more of the genes associated with primary
open angle glaucoma (4-6, 7). These genes are also important in certain
forms of secondary open angle glaucoma, such as pigment dispersion syndrome
and pseudoexfoliation (8).
|
Table
1: DIAGNOSTIC INDICATORS
|
| ABSOLUTE: |
Glaucomatous
visual field defect |
|
Glaucomatous
optic nerve head damage |
| RELATIVE: |
Major: |
Elevated
IOP |
|
|
Increasing
age |
|
|
Genetic
predisposition (includes race) |
|
Other: |
Myopia |
|
|
Cardiovascular/haematological
factors |
|
|
Optic
nerve head morphology |
|
|
Unknown |
Therapeutic
Options
The current
options available to treat open angle glaucoma are limited to methods of
lowering IOP which include medical, laser and surgical treatments. In the
UK there have been three studies comparing medicine vs. surgery as first
line treatment, the third of which also included primary laser treatment
as an option (9-11). All three studies suggested, with varying degrees
of certainty, that primary surgery was the most efficacious. However the
advent of newer, more potent, topically applied hypotensive glaucoma drugs
has maintained medical treatment as the first line treatment for POAG.
Medical
Therapy
The options
available in the UK include topically applied beta antagonists, various
miotics, a carbonic anhydrase inhibitor, alpha receptor agonists and a
prostaglandin analogue. The most extensively tested of all these is the
non-selective beta antagonist timolol. Timolol will produce a long term
IOP lowering of 4-5mmHg (1,2). If the hypotensive activity of this drug
is taken as the benchmark, ranking of the hypotensive effect is as shown
in Table 2.
Individual
patient responses may vary and overturn the generalisations outlined in
Table 2. Drug combinations may produce an additive hypotensive effect with
the probable exception of a beta-antagonist and an alpha-agonist. Somewhat
surprisingly, miotics and latanoprost can have an additive effect (13).
The
required frequency of instillation varies. Any drug that needs to be instilled
more than twice a day is liable to have the mid-day instillation missed
or delayed. This apples to both miotic drops and dorzolamide. When combined
with timolol, the same drugs seemingly have optotensive activity throughout
the day as a twice a day preparation, although this needs to be confirmed
for the individual patient. Latanoprost need only be given once a day,
last thing at night. beta-antagonists can provide an 18 hour hypotensive
effect. These drugs should be instilled first in the morning for when applied
at night they (unlike carbonic anhydrase inhibitors) do not have much effect
on aqueous secretion, and therefore on IOP (14).
The
number of medications that will be comfortably tolerated will vary from
patient to patient, and as a general rule patient quality of life falls
when more than two types are used.
All
the drugs produce side effects. The ocular side effects are usually recognised.
Most topically applied drugs have been implicated in causing blurring of
vision, although the mechanism is not always clear. Allergies are produced
most frequently by the adrenergics, and next most commonly the miotics.
All topically applied drugs use benzalonium as a preservative; for any
patient allergic to this preservative there are only a limited number of
preservative free preparations available.
| TABLE
2: DRUG POTENCIES RELATIVE TO TIMOLOL |
| LESS
POTENT |
EQUIPOTENT |
MORE
POTENT |
| Betaxolol |
Timolol |
Latanoprost |
| Dorzolamide |
Brimonidine |
Acetazolamide |
| Certain
miotics* |
Adrenaline
preparations |
Certain
miotics* |
|
Dipivefrin |
|
|
Apraclonidine |
|
|
All
non-selective beta-blockers |
|
|
Certain
miotics* |
|
| *depending
on type and concentration (Carbachol > Pilocarpine 4% > Pilocarpine 1%) |
The
prostaglandin analogue, latanoprost will produce eye-lash growth in some,
and iris hyper-pigmentation in the hazel-eyed. Neither effect has proved
to be a bar to the use of the drug from most patients' viewpoint. Of more
importance for the long term use of this drug is the development of macular
oedema and uveitis. The former may develop in the aphakic and possibly
the pseudophakic patient. Latanoprost will also produce uveitis in the
eye with a poor blood aqueous barrier.
Systemic
side affects are most commonly seen with topical (-antagonist use with
respiratory side effects being common in the elderly using non selective
beta-antagonists. The same drugs may induce significant bradycardia in
those with a naturally slow pulse rate. All the adrenergics, with the possible
exception of dipivefrin, may produce a tachycardia.
First
line treatment will be to consider beta-antagonists (singly or in combination),
although they should be avoided if the side effects noted above are likely.
Latanoprost is approved for use as a second line drug. The majority of
patients requiring hypotensive treatment are managed by medical treatment
but laser or surgical approaches should be considered if the 'target IOP'
is not met or side effects preclude continued use. Target pressures for
high tension glaucoma are increasingly being set in the mid to low 'teens'
following the recognition that for many patients progressive loss of visual
field will continue at higher levels of IOP.
Laser
Therapy
Argon
laser trabeculoplasty is of use as a supplement to medical treatment, and
may produce a further IOP reduction with some if not all of the topically
applied preparations. It is most effective in eyes with trabecular pigmentation,
and the elderly, but only 50% of those initially responding will continue
to do so at 5 years. Repeat laser treatment does not usually last and is
rarely useful. The treatment is of most use in the elderly, the arthritic,
and the amnesiac patient for whom a moderate IOP fall is needed.
Surgical
Therapy
Fistulising
surgery (trabeculectomy) should be considered for all patients when the
'target IOP' is not met with other therapeutic options, and the expected
rate of visual loss will affect the patient during their lifetime. The
younger the patient the more likely this will be, and surgery should probably
be considered in all patients aged 50 or below. Scar tissue formation after
surgery will prejudice the IOP reduction, therefore anti-proliferatives
need be considered for all eyes with risk factors for failure. Peroperative
5-fluorouracil should be considered in patients considered at risk because
of youth, and prior glaucoma treatment for more than 3 years, while peroperative
5-fluorouracil or mitomycin-C needs consideration in the eye with previous
conjunctival surgery, aphakia, uveitis or in black races.
Excess
bulk outflow of aqueous immediately following filtration surgery is responsible
for a large number of post operative complications. The more tightly the
superficial scleral flap is sutured to its bed, the fewer these will be.
If required post-operatively, aqueous flow around the cut edge of the flap
can be promoted by displacement of the edge by massage (indenting the overlying
eyelid with a cotton tip applicator), lessening suture tension (cutting
one or more sutures with the argon laser or a needle) or by using releasable
scleral flap sutures.
Roger
Hitchings
References
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Tielsch JM, Sommer A, Katz J, Royall RM, Quigley HA, Javitt J. Racial
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