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 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).
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Table
1: DIAGNOSTIC INDICATORS
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ABSOLUTE:
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Glaucomatous
visual field defect
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Glaucomatous
optic nerve head damage
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RELATIVE:
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Major:
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Elevated
IOP
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Increasing
age
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Genetic
predisposition (includes race)
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Other:
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Myopia
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Cardiovascular/haematological
factors
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Optic
nerve head morphology
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Unknown
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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.
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TABLE
2: DRUG POTENCIES RELATIVE TO TIMOLOL
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LESS
POTENT
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EQUIPOTENT
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MORE
POTENT
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Betaxolol
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Timolol
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Latanoprost
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Dorzolamide
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Brimonidine
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Acetazolamide
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Certain
miotics*
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Adrenaline
preparations
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Certain
miotics*
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Dipivefrin
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Apraclonidine
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All
non-selective beta-blockers
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Certain
miotics*
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*depending
on type and concentration (Carbachol > Pilocarpine 4% >
Pilocarpine 1%)
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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
1.
Wilson MR, Martone J. Epidemiology of chronic open angle glaucoma.
In: Ritch, Shields MB, Krupin T, Eds. The Glaucomas. 1st Ed. St
Louis, Mosby. 1996: 753-68.
2.
Tielsch JM, Sommer A, Katz J, Royall RM, Quigley HA, Javitt J. Racial
variations in the prevalence of primary open angle glaucoma.
JAMA. 1991: 266: 369-74.
3.
Tielsch JM, Katz J, Sommer A, Quigley HA, Javitt JC. Hypertension,
perfusion pressure, and primary open angle glaucoma. A population-based
assessment. Arch Ophthalmol. 1995; 113:216-21.
4.
Morissette J, Cote G, Anctil JL, et al. A common gene for
juvenile and adult-onset primary open-angle glaucomas confined on
chromosome lq. Am. J. Hum. Genet. 1995.56: 1431-42.
5.
Sarfarazi M, Akarsu AN, Hossain A, et al. Assignment of a
locus (GLC3A) for primary congenital glaucoma (Buphthalmos) to 2p21
and evidence for genetic heterogeneity. Genomics. 1995; 30:
171-7.
6.
Ortego J, Escribano J, Coca-Prados M. Cloning and characterisation
of subtracted cDNAs from a human ciliary body library encoding TIGR,
a protein involved in juvenile open angle glaucoma with homology
to myosin and olfactomedin. FEBS Lett. 1997; 413: 349-53.
7.
Bennett SR, Alward WL, Folberg R. An autosomal dominant form
of low-tension glaucoma. Am. J. Ophthalmol. 1989; 108: 238-44.
8.
Anderson KL, Lewis RA, Bejjani BA, et al. A gene for primary
congenital glaucoma is not linked to the locus on chromosome lq
for autosomal dominant juvenile-onset open angle glaucoma.
J. Glaucoma. 1996; 5: 416-21.
9.
Smith RJ. The Lang lecture 1986. The enigma of primary open-angle
glaucoma. Trans. Ophthalmol. Soc. U.K. 1986; 105: 618-33.
10.
Jay JL, Murray SB. Early trabeculectomy versus conventional
management in primary open angle glaucoma. Br. J. Ophthalmol.
1988; 72: 881-9.
11.
Migdal C, Gregory W, Hitchings R. Long-term functional outcome
after early surgery compared with laser and medicine in open-angle
glaucoma. Ophthalmology. 194; 101: 1651-6.
12.
Schulzer M, Drance SM, Douglas GR. A comparison of treated
and untreated glaucoma suspects (see comments). Ophthalmology.
1991; 98: 3001-7.
13.
Linden C, Alm A. Latanoprost and physostigmine have mostly
additive ocular hypotensive effects in human eyes (see comments).
Arch. Ophthalmol. 1997; 115: 857-61.
14.
McCannel CA, Heinrich SR, Brubaker RF. Acetazolamide but not
timolol lowers aqueous humor flow in sleeping humans. Graefes
Arch. Clin. Exp. Ophthalmol. 1992; 230: 518-20.
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