Author

Jerald A Bell, MD Staff Physician, Department of Ophthalmology, Billings Clinic

Jerald A Bell, MD is a member of the following medical societies: American Academy of
Ophthalmology
Cited on : May 2015
Available on : http://emedicine.medscape.com/article/1206147-overview#showall
Primary Open-Angle Glaucoma
Practice Essentials
Primary open-angle glaucoma is described distinctly as a multifactorial optic neuropathy that
is chronic and progressive, with a characteristic acquired loss of optic nerve fibers. Such loss
develops in the presence of open anterior chamber angles, characteristic visual field
abnormalities, and intraocular pressure that is too high for the continued health of the eye. It
manifests by cupping and atrophy of the optic disc (see the image below), in the absence of
other known causes of glaucomatous disease.[1, 2]

Advanced glaucomatous damage with increased cupping and substantial pallor of the optic
nerve head. Courtesy of M. Bruce Shields, MD.
Essential update: Visual field test may miss early central macular damage in glaucoma
In some patients with glaucoma, the addition of a 10-2 visual field (VF) test to the standard
24-2 VF test or modification of the 24-2 VF equipment to assess more test points may help to
detect early central macular damage.[3, 4] In a prospective observational study of 100 eyes from
74 patients with glaucomatous optic neuropathy and a 24-2 VF test with mean deviation
better than 6 dB, Traynis et al found that the 24-2 VF test failed to detect early
glaucomatous damage in the central macula in 13 of 83 hemifields (15.7%) subsequently
shown to be abnormal on 10-2 VF testing. Thus, the 10-2 VF test revealed abnormalities in
22.7% of the 22 eyes that appeared normal with 24-2 VF testing. [4] Among the abnormal

hemifields on 10-2 VF testing, 68% were classified as arcuatelike, 8% as widespread, and

25% as other.[3, 4]
Signs and symptoms
Because of the silent nature of glaucoma, patients usually dont present with any symptoms
or visual complaints until late in the disease course, particularly with primary open-angle
glaucoma. However, narrow/closed-angle glaucoma and secondary glaucomas can cause
rapid closure of the trabecular meshwork, with an equally rapid rise in intraocular pressure,
which is usually symptomatic, particularly when intraocular pressure is 35 mm Hg or more.
Significant attention should be given to the following in the patients clinical history:

Past ocular history

Previous ocular surgery, including photocoagulation or refractive procedures

Ocular/head trauma

Past medical history

Current medications

Risk factors for glaucomatous optic neuropathy

See Clinical Presentation for more detail.
Diagnosis
Screening the general population for primary open-angle glaucoma is most effective if
targeted toward those at high risk, such as African Americans and elderly individuals,
especially if the screening consists of intraocular pressure measurements combined with
assessment of optic nerve status.
Examination of patients with suspected primary open-angle glaucoma includes the following:

Slit lamp examination of the anterior segment

Fundoscopy

Tonometry

Gonioscopy

Pachymetry
Lab Tests
Laboratory tests that may be used to rule other causes for optic neuropathy in patients
suspected of having normal-tension glaucoma include the following:

CBC count

Erythrocyte sedimentation rate

Serology for syphilis (micro-hemagglutination- Treponema pallidum [MHA-TP], not

Venereal Disease Research Laboratory [VDRL] test)

Rarely, serum protein electrophoresis: For individuals with potential autoimmune etiology
for some glaucomatous optic neuropathies
Imaging studies
The following imaging studies may be used to evaluate patients with suspected primary openangle glaucoma:

Fundus photography

Retinal nerve fiber layer imaging on high-contrast black and white film using red-free
techniques

Confocal scanning laser ophthalmoscopy

Scanning laser polarimetry

Optical coherence tomography

Neuroimaging, if suggested by the patients pattern of visual field loss

Investigational imaging modalities in the evaluation and management of patients with
primary open-angle glaucoma include the following:

Fluorescein angiography

Ocular blood flow analysis via laser Doppler flowmetry

Color vision measurements

Contrast sensitivity testing

Electrophysiologic tests

Ultrasound biomicroscopy
See Workup for more detail.
Management
Current medical therapy for primary open-angle glaucoma is limited toward lowering
intraocular pressure. A rational approach to choosing antiglaucoma medications should
minimize the number of medications and the probability of significant adverse effects.
If one medication is not adequate in reaching the target pressure, a second medication should
be chosen that has a different mechanism of action, so that the 2 drug therapies will have an
additive effect.
Pharmacotherapy
Medications used in the management of primary open-angle glaucoma include the following:

Beta-adrenergic blockers (eg, levobunolol 0.25%, 0.5%; timolol maleate/hemihydrate;

carteolol ophthalmic; betaxolol ophthalmic; metipranolol hydrochloride; levobetaxolol)

Adrenergic agonists (eg, brimonidine; apraclonidine 0.5%, 1%)

Less-selective sympathomimetics (eg, dipivefrin, epinephrine, memantine)

Carbonic

anhydrase

inhibitors

(eg,

dorzolamide,

brinzolamide,

acetazolamide,

methazolamide)

Beta-blocker/carbonic anhydrase inhibitor combination (eg, dorzolamide HCl/timolol

maleate)

Prostaglandin analogs (eg, latanoprost 0.005%, bimatoprost, travoprost ophthalmic

solution, unoprostone, tafluprost)

Miotic agents (eg, pilocarpine ophthalmic)

Hyperosmotic agents (eg, isosorbide dinitrate, mannitol, glycerin)

Beta-blocker/alpha agonist combination (eg, brimonidine/timolol)

Surgery
Surgery is indicated in primary open-angle glaucoma when glaucomatous optic neuropathy
worsens (or is expected to worsen) at any given level of intraocular pressure and the patient is
on maximum tolerated medical therapy.
The following are surgical options that may be used for primary open-angle glaucoma:

Argon laser trabeculoplasty

Selective laser trabeculoplasty

Trabeculectomy

Drainage implant (ie, seton/tube/shunt) surgery

Ciliary body ablation

Newer techniques that hold potential as surgical options in primary open-angle glaucoma
include the following:

Deep sclerectomy/viscocanalostomy/with or without collagen implant

360-degree suture canaloplasty

See Treatment and Medication for more detail.
Background
The definition of glaucoma has changed drastically since its introduction around the time of
Hippocrates (approximately 400 BC). The word glaucoma came from the ancient Greek
word glaucosis, meaning clouded or blue-green hue, most likely describing a patient having

corneal edema or rapid evolution of a cataractprecipitated by chronic elevated pressure. Over

the years, extensive refinement of the concept of glaucoma has continued, accelerating,
especially in the last 100 years, to the present date.
Glaucoma is currently defined as a disturbance of the structural or functional integrity of the
optic nerve that causes characteristic atrophic changes in the optic nerve, which may also lead
to specific visual field defects over time. This disturbance usually can be arrested or
diminished by adequate lowering of intraocular pressure (IOP). Nevertheless, some
controversy still exists as to whether IOP should be included in the definition, as some
subsets of patients can exhibit the characteristic optic nerve damage and visual field defects
while having an IOP within the normal range. The generic term glaucoma should only be
used in reference to the entire group of glaucomatous disorders as a whole, because multiple
subsets of glaucomatous disease exist. A more precise term should be used to describe the
glaucoma, if the specific diagnosis is known.
Primary open-angle glaucoma (POAG) is described distinctly as a multifactorial optic
neuropathy that is chronic and progressive with a characteristic acquired loss of optic nerve
fibers. Such loss develops in the presence of open anterior chamber angles, characteristic
visual field abnormalities, and IOP that is too high for the continued health of the eye. It
manifests by cupping and atrophy of the optic disc (shown in the image below), in the
absence of other known causes of glaucomatous disease.[1, 2]

Advanced glaucomatous damage with increased cupping and substantial pallor of the optic
nerve head. Courtesy of M. Bruce Shields, MD.
Note that the definition of POAG is not synonymous or solely defined by the presence of
elevated IOP, but that increased IOP is a risk factor associated with the development of the
disease, and is not the disease itself. Patients could develop optic neuropathy of glaucoma in
the absence of documented elevated IOP. This condition has been termed normal-tension or
low-tension glaucoma.
People who maintain elevated pressures in the absence of nerve damage or visual field loss
exist. They are considered at risk for glaucoma and have been termed glaucoma suspects or

ocular hypertensives (see Ocular Hypertension). POAG is a major worldwide health concern,
because of its usually silent, progressive nature, and because it is one of the leading
preventable causes of blindness in the world. With appropriate screening and treatment,
glaucoma usually can be identified and its progress arrested before significant effects on
vision occur.
Pathophysiology
The exact cause of glaucomatous optic neuropathy is not known, although many risk factors
have been identified, to include the following: elevated IOP, family history, race, age older
than 40 years, and myopia.
Elevated IOP is the most studied of these risk factors because it is the main clinically
treatable risk factor for glaucoma. Multiple theories exist concerning how IOP can be one of
the factors that initiates glaucomatous damage in a patient. Two of the major theories include
the following: (1) onset of vascular dysfunction causing ischemia to the optic nerve, and (2)
mechanical dysfunction via cribriform plate compression of the axons.
In addition to vascular compromise and mechanically impaired axoplasmic flow,
contemporary hypotheses of possible pathogenic mechanisms that underlie glaucomatous
optic neuropathy include excitotoxic damage from excessive retinal glutamate, deprivation of
neuronal growth factors, peroxynitrite toxicity from increased nitric oxide synthase activity,
immune-mediated nerve damage, and oxidative stress. The exact role that IOP plays in
combination with these other factors and their significance to the initiation and progression of
subsequent glaucomatous neuronal damage and cell death over time is still under debate; the
precise mechanism is still a hot topic of discussion.
However, IOP is the only clinical risk factor that has been able to be successfully manipulated
to date. Categorizing and managing patients based on their IOP and when IOP should be
treated to prevent optic nerve damage became the forefront issue of glaucoma management
for most of the last half of the 20th century.
Several studies over the years have shown that as IOP rises above 21 mm Hg, the percentage
of patients developing visual field loss increases rapidly, most notably at pressures higher
than 26-30 mm Hg. A patient with an IOP of 28 mm Hg is about 15 times more likely to
develop field loss than a patient with a pressure of 22 mm Hg. Therefore, a patient population
of those with elevated IOP should not be thought of as homogeneous. Furthermore, before
initiating treatment of a patient based on a specific IOP measurement, the following factors
should be considered regarding that IOP level obtained:

Variability of tonometry measurements per examiner (usually found to be about 10%, or 1-2
mm Hg)

Effect corneal thickness has on accuracy of IOP measurements (see Other Tests)

Diurnal variation of IOP (often highest in the early morning hours, but maximum IOP can
be at any time of day in some patients)

In addition, remember that while normal eyes have a diurnal variation of approximately 3-4
mm Hg, glaucomatous eyes have even higher variation (>10 mm Hg). Note: Multiple
readings should be taken over time and should be considered with correlative evidence of
visual field and optic nerve examination before any diagnosis or therapy is rendered.
A study by Costa et al supports the need to more accurately assess the relationship of 24-hour
IOP to 24-hour diastolic perfusion pressure in patients with glaucoma. Future methodology
that performs noninvasive, real-time IOP measurements throughout the 24 hours of the day
may enable a more complete understanding of the roles that IOP and blood pressure have to
the etiology of glaucomatous damage and progression of the disease.[5]
Other points of importance when considering a diagnosis of POAG are described below.
Disc cupping and nerve fiber layer losses of up to 40% have been shown to occur before
actual visual field loss has been detected. Therefore, visual field examination cannot be the
sole tool used to determine when a patient has begun to sustain undeniable glaucomatous
damage, and it should not be used in isolation as the benchmark for treatment.
In cases where POAG is associated with increased IOP, the cause for the elevated IOP
generally is accepted to be decreased facility of aqueous outflow through the trabecular
meshwork. Occurrence of this increase in resistance to flow has been suggested by multiple
theories, to include the following:

An obstruction of the trabecular meshwork by accumulated material

A loss of trabecular endothelial cells

A reduction in trabecular pore density and size in the inner wall endothelium of the
Schlemm canal

A loss of giant vacuoles in the inner wall endothelium of the Schlemm canal

A loss of normal phagocytic activity

Disturbance of neurologic feedback mechanisms

Other processes thought to play a role in resistance to outflow include altered corticosteroid
metabolism, dysfunctional adrenergic control, abnormal immunologic processes, and
oxidative damage to the meshwork.
Numerous other undetermined factors are considered to be at work in the pathogenesis of
glaucoma. Basic and clinical science research continues to play a role in the search for such
factors that contribute to the development and prognosis of the patient with POAG.
Epidemiology
Frequency United States
Multiple population studies (eg, Framingham, Beaver Dam, Baltimore, Rotterdam, Barbados,
Egna-Neumarkt) have been performed to estimate the prevalence of eye disease, including
that of POAG and those individuals with ocular hypertension (OHT) who are at risk for
POAG.
Estimates of the prevalence of glaucoma in studies involving only the United States suggest
the following: glaucoma is a leading cause of irreversible blindness, second only to macular
degeneration; only one half of the people who have glaucoma may be aware that they have
the disease; and more than 2.25 million Americans aged 40 years and older have POAG.
More than 1.6 million have significant visual impairment, with 84,000-116,000 bilaterally
blind in the United States alone. These statistics emphasize the need to identify and closely
monitor those at risk of glaucomatous damage.
In a white population at risk for glaucoma, visual field loss can be expected to develop in
about 3% of subjects over 10 years of follow up without treatment. Risk increases with age
and IOP.[6]
In the United States, 3-6 million people, including 4-10% of the population older than 40
years, are currently without detectable signs of glaucomatous damage using present-day
clinical testing, but they are at risk due to IOP of 21 mm Hg or higher. Roughly 0.5-1% per
year of those individuals with elevated IOP will develop glaucoma over a period of 5-10
years. The risk may be declining to less than 1% per year, now that ophthalmoscopic and
perimetric techniques for detecting glaucomatous damage have improved significantly.

Diagram showing the relative proportion of people in the general population who have
elevated pressure (horizontally shaded lines) and/or damage from glaucoma (vertically
shaded lines). Notice that most have elevated pressure but no sign of damage (ie, ocular
hypertensives), but there are also those with normal pressures who still have damage from
glaucoma (ie, normal tension glaucoma). Courtesy of M. Bruce Shields, MD.OHT =
horizontal lines only NTG = vertical lines only POAG and other glaucomas with both
elevated intraocular pressure and damage = overlapping horizontal and vertical lines.

Diagram of intraocular pressure distribution, with a visible skew to the right (somewhat
exaggerated compared to the actual distribution). Note that, while uncommon, field loss
among individuals with pressures in the upper teens can occur. Also, note that the average
pressure among those with glaucomas is in the low 20s, even though most individuals with
pressures in the low 20s do not have glaucoma. Used by permission from Survey of
Ophthalmology.
International

Glaucoma is

the second leading cause of blindness in the world (surpassed only by cataracts, a reversible condition). More than

3 million

people are bilaterally blind from POAG worldwide, and more than 2 million people will
develop POAG each year.
Mortality/Morbidity
Over a 5-year period, several studies have shown the incidence of new onset of glaucomatous
damage in previously unaffected patients to be about 2.6-3% for IOPs 21-25 mm Hg, 12-26%
incidence for IOPs 26-30 mm Hg, and approximately 42% for those higher than 30 mm Hg.
The Ocular Hypertension Treatment Study (OHTS) found that the overall risk for patients
with IOPs ranging from 24-31 mm Hg but with no clinical signs of glaucoma have an average
risk of 10% of developing glaucoma over 5 years, with that risk being cut in half if patients
are preemptively started on IOP-lowering therapy. Significant subsets of higher and lower
risk exist when pachymetry (central corneal thickness [CCT]) is taken into account (see the
image below).

Ocular hypertension study (OHTS). Percentage of patients who developed glaucoma during
this study, stratified by baseline intraocular pressure (IOP) and central corneal thickness
(CCT).
Some patients' first sign of morbidity from elevated IOP can be presentation with sudden loss
of vision due to a central retinal vein occlusion (CRVO), the second most common risk factor
for CRVO behind systemic hypertension.
See References for additional resources.
Race
Prevalence of POAG is 3-4 times higher in blacks than in Caucasians; in addition, blacks are
up to 6 times more susceptible to optic disc nerve damage than Caucasians. A higher

prevalence of larger cup-to-disc ratios exists in the normal black population as compared with
white controls.
Glaucoma is the most common cause of blindness among people of African descent. They are
more likely to develop glaucoma early in life, and they tend to have a more aggressive form
of the disease.

The Barbados Eye Study over 4 years showed a 5 times higher incidence of developing
glaucoma in a group of black ocular hypertensives as compared with a predominantly white
population.

Some population studies have found the mean IOP in blacks to be higher than Caucasian
controls. Other studies (eg, Baltimore) found no difference. Consequently, further study
needs to be conducted to clarify this issue.

Furthermore, the OHTS has suggested that black patients overall may have a thinner
average central corneal thickness, thereby leading to underdiagnosis of elevated pressure,
and consequently, exposure to higher risk of developing glaucoma. Therefore, pachymetry
measurement is particularly important in establishing a baseline for African-American
patients who are glaucoma suspects.
Sex
Reports on sex predilection also differ. Although some age-controlled studies have reported
significantly higher mean IOP values in women than in men, others have failed to find such a
difference, while others have even shown males to have a higher prevalence of glaucoma.
Age
Age older than 40 years is a risk factor for the development of POAG, with up to 15% of
people affected by the seventh decade of life.

Consequently, glaucoma is found to be more prevalent in the aging population, even after
compensating for the fact that mean IOP slowly rises with increasing age.

However, the disease itself is not limited to only middle-aged and elderly individuals.
History
The initial patient interview is extremely important in the evaluation for POAG or other
ocular diseases secondarily causing elevated IOP.
Because of the silent nature of glaucoma, patients will not usually present with any symptoms
or visual complaints until late in the disease course, particularly with POAG. However,

narrow/closed angle glaucoma and secondary glaucomas can cause rapid closure of the
trabecular meshwork, with an equally rapid rise in IOP, which is usually symptomatic,
particularly when IOP is equal to or greater than 35 mm Hg.
Significant attention should be given to the patient's past ocular history and other factors.
Past ocular history includes the following:

History of eye pain or redness

Multicolored halos

Headache

Previous ocular disease, including cataracts

Uveitis

Diabetic retinopathy

Vascular occlusions
Other factors include the following:

Previous ocular surgery, including photocoagulation or refractive procedures

Ocular/head trauma

Past medical history - Any surgeries or pertinent vasculopathic systemic illnesses

Current medications, including any hypertensive medications (which may indirectly cause
fluctuation of IOP) or topical/systemic corticosteroids
Risk factors for glaucomatous optic neuropathy
Strong implications are as follows:

History of elevated IOP; advanced age, particularly after 50 years; African American
descent; positive family history of glaucoma (first-degree relative, especially correlative
if present in a sibling; relative risk 3.7-fold higher than if no family history of glaucoma);
myopia

Be specific when asking family history (Which family members? Was there actual
visual loss from glaucoma or other causes of visual field loss? Are they under control on
one or more medications? Did they require surgery for adequate control?)
Possible implications are as follows:

Systemic cardiovascular disease

Diabetes mellitus

Migraine headache

Systemic hypertension

Vasospasm
Anecdotal risk factors are as follows:

Obesity

Smoking

Alcohol

History of stress

Anxiety

Risk factors for rapid glaucoma progression

Patients with open-angle glaucoma who have a worse mean deviation to their visual field, a
greater vertical cup-to-disc ratio at baseline, or who are older are significantly more likely to
experience a rapid decay of their visual field, according to a recent study of 767 eyes from
566 participants in the Advanced Glaucoma Intervention Study.[7] Rapid progression was
defined as a rate of changes in the visual field of at least 36% per year. Other factors
associated with an increased risk for progression that did not reach significance included
being male and having worse baseline visual acuity.[7]
Physical
Screening the general population for POAG is most effective if targeted toward those at high
risk, such as African Americans and elderly individuals, especially if the screening consists of
IOP measurements combined with assessment of optic nerve status.

Perform screening at least every 3-5 years in asymptomatic patients aged 40 years or younger
and more often if the person is African American or older than 40 years. For those with
multiple risk factors, evaluate and monitor on a more frequent basis, as appropriate.
Perform a standard comprehensive eye examination, such as that outlined in the American
Academy of Ophthalmology (AAO) Preferred Practice Patterns, on the initial visit. If any
visual field or optic nerve changes consistent with early glaucoma are present, then diagnose
the patient as having such.
A flowchart for evaluation of suspected glaucoma is shown below.

Flowchart for evaluation of a patient with suspected glaucoma. Used by permission of the
American Academy of Ophthalmology.
Emphasize the following points during the examination to distinguish POAG from either
secondary causes of glaucoma or from OHT in patients with only elevated IOP and no
damage.

Compare visual acuity with previous known acuities. If declining, rule out secondary
causes of vision loss, whether it is from cataracts, age-related macular degeneration
(ARMD), ocular surface disorders (eg, dry eye), or adverse effects from topical medications
(especially if using miotics).

Pupils - Test for presence/absence of afferent pupillary defect (Marcus Gunn pupil).

Slit lamp examination of the anterior segment

Cornea - Signs of microcystic edema (found only with acute elevation of IOP); keratic
precipitates, pigment on endothelium (Krukenberg spindle); congenital anomalies

Anterior chamber - Cell or flare, uveitis, hyphema, angle closure

Iris - Transillumination defects, iris atrophy, synechiae, rubeosis, ectropion uveae, iris
bombe, difference in iris coloration bilaterally (eg, Fuchs heterochromic iridocyclitis),
pseudoexfoliation (PXF) material

Lens - Cataract progression (ie, signs of phacomorphic glaucoma, pseudoexfoliation,

phacolytic glaucoma with a Morgagnian cataract)

Optic nerve/nerve fiber layer - Stereoscopically examine for evidence of

glaucomatous damage, including the following: cup-to-disc ratio in horizontal and vertical
meridians (describe by color and slope, and diagram, if needed); appearance of disc;
progressive enlargement of the cup; evidence of nerve fiber layer damage with red-free filter;
notching or thinning of disc rim (see the image below), particularly at superior and inferior
poles (because nerve fibers at the superior and inferior poles of the disc can often be affected
first); pallor; presence of hemorrhage (most common inferotemporally); asymmetry between
discs; parapapillary atrophy (possible association with development of glaucoma); or

congenital nerve abnormalities.

Illustration of progressive

optic nerve damage. Notice the deepening (saucerization) along the neural rim, along with
notching and increased excavation/sloping of the optic nerve and circumlinear vessel
inferiorly. Courtesy of M. Bruce Shields, MD.

Optic nerve asymmetry in a patient with glaucomatous damage, left eye, showing optic nerve
excavation inferiorly (similar to Image 5). Courtesy of M. Bruce Shields, MD.

Glaucomatous optic nerve damage, with sloping and nerve fiber layer rim hemorrhage
at the 7-o'clock position. Hemorrhage is indicative of progressive damage, usually due to
inadequate pressure control. Further notching and pallor corresponding to the area of
hemorrhage usually is seen several weeks after resorption of the blood. Courtesy of M. Bruce
Shields, MD.

Fundus - Other abnormalities that could account for any nonglaucomatous visual field
defects or vision loss present (eg, disc drusen, optic pits, retinal disease), vitreous
hemorrhage, or proliferative retinopathy.
Baseline stereo fundus photographs for future reference/comparison; if unavailable, record
representative drawings.
Tonometry (see also Other tonometric methods in Other Tests)
IOP varies from hour-to-hour in any individual. The circadian rhythm of IOP usually causes it
to rise most in the early hours of the morning; IOP also rises with a supine posture.
When checking IOP, measurements for both eyes, the method used (Goldmann applanation is
the criterion standard), and the time of the measurement should all be recorded.
Previous tonometry readings, if available, should be reviewed (eg, Is the reading
reproducible? What method was used to obtain the reading? What time of the day was it?
Where does it fall on the diurnal pressure curve? Do both eyes have similar measurements?).
In obese patients, the possibility of a Valsalva movement causing an increased IOP should be
considered when measured in the slit lamp by Goldman applanation. Measurement should be
tried via Tono-Pen, Perkins, or pneumotonometer with the patient resting back in the
examination chair.

A difference between the 2 eyes of 3 mm Hg or more indicates greater suspicion of glaucoma.

An average of 10% difference between individual measurements should be expected. The
measurements should be repeated on at least 2-3 occasions before deciding on a treatment
plan. The measurement should be completed in the morning and at night to check the diurnal
variation, if possible. (A diurnal variation of more than 5-6 mm Hg may be suggestive of
increased risk for POAG.) Early POAG is suspected strongly when a steadily increasing IOP
is present.
Pachymetry affects applanation tonometry values and, therefore, should be checked on the
initial examination (see also Pachymetry and Other tonometric methods in Other Tests).
Gonioscopy
Perform gonioscopy to rule out angle-closure or secondary causes of IOP elevation, such as
angle recession, pigmentary glaucoma, and PXF.
Check the peripheral contour of the iris for plateau iris, and examine the trabecular meshwork
for peripheral anterior synechiae, as well as neovascular or inflammatory membranes.
The Schlemm canal may be seen with blood refluxing through the canal into the posterior
trabecular meshwork. This possibly could indicate elevated episcleral venous pressure, with
such conditions as carotid-cavernous fistula, Graves orbitopathy, or Sturge-Weber syndrome
needing to be ruled out.
Pachymetry
Pachymetry is used to measure CCT. According to the OHTS, pachymetry is now the
criterion standard for every baseline examination in patients who are at risk for or suspected
of having glaucoma (see the image below).

Ocular hypertension study (OHTS). Percentage of patients who developed glaucoma during
this study, stratified by baseline intraocular pressure (IOP) and central corneal thickness
(CCT).
Visual field testing
Perform automated threshold testing (eg, Humphrey 24-2) to rule out any glaucomatous
visual field defects. A Humphrey visual field is shown below.

Humphrey visual field, right eye, showing patient with advanced glaucomatous field loss.
Notice both the arcuate extension from the blind spot (Bjerrum scotoma) and the loss nasally
(nasal step), which often occurs early in the disease process. Courtesy of M. Bruce Shields,
MD.
If the patient is unable to perform automated testing, Goldmann testing may be substituted.

Caveats about visual field analysis are outlined below (see also Other Tests).
New-onset glaucomatous defects are found most commonly as an early nasal step, temporal
wedge, or paracentral scotoma (more frequent superiorly); generalized depression related to
IOP level also can be found.
Swedish interactive thresholding algorithm (SITA)-based software algorithms may decrease
testing time and boost reliability, especially in older patients.
Short wavelength automated perimetry or blue-yellow perimetry (SWAP) may provide a
more sensitive method of detecting visual field deficits, especially in those previously labeled
as ocular hypertensive. If the Humphrey visual field testing results are normal, SWAP should
be considered to help detect visual field loss earlier. Recent studies suggest SWAP may detect
visual loss/progression up to 3-5 years earlier than conventional perimetry, as well as in 1242% of patients previously diagnosed with only OHT. Because the testing time may be
lengthened, it may be tiring for some patients. However, new SITA-SWAP algorithm
software may speed up the testing time and thus improve reliability.
Frequency doubling perimetry (also called frequency doubling technology or FDT, which is
enhanced with MATRIX software) is a newer technology that projects an alternating pattern
of gridlines onto a screen and stimulates specific neurons that may be damaged early in OHT
or POAG. As in SWAP, this may also be able to help detect nerve fiber layer loss at an earlier
stage in the glaucomatous disease process, thereby screening out more people who are
currently misdiagnosed as having OHT instead of early POAG. Current sensitivities and
specificities are continually improving, but continued baseline data is needed to determine in
what setting this newer technology will prove to be most useful.
Examination results must take into account that visual field defects may not be apparent until
over 40% loss of the nerve fiber layer has occurred. Therefore, the therapy should be based
on the overall clinical picture and not on visual field testing alone (see Treatment).
The pupil size should be documented at each testing session, as constriction can reduce
retinal sensitivity and mimic progressive field loss.
Risk factors, specifically for the development of glaucomatous field loss in OHT, have
recently been studied, and it was found that several presumed risk factors (ie, presence of

hypertension, diabetes, refractive error, race, family history of glaucoma, gender, smoking or
ethanol use, disc area) were not significant for prediction of eventual field loss.
Significant positive predictive factors for progressive field loss included higher IOP, older
age, presence of peripapillary atrophy, larger cup-to-disc ratio, smaller rim-disc area ratio,
and cup asymmetry. A study by De Moraes et al found some of the same risk factors for
visual field progression in treated glaucoma/POAG: female sex, African or Latin, exfoliation
syndrome, older age, cornea thinner and decreased CCT, peak IOP 1.13 mm Hg higher, disc
hemorrhage, and beta zone peripapillary atrophy.[8] Consequently, the relationship of risk
factors for OHT and POAG compared with that of actual field loss development is much
more complex than has been previously presumed.
The initial visual field baseline may need to be repeated at least twice on successive visits,
especially if initial testing shows low reliability indices. Newer glaucoma progression
analysis (GPA) software can help identify reliable perimetric baselines, and probability-based
analyses of subsequent fields can assist in determining if there is true progression over time
versus artifact. In follow-up, if a low risk of onset of glaucomatous damage is present, then
repeat testing may be performed once a year. If a high risk of impending glaucomatous
damage is present, then testing may be adjusted (as frequent as every 2 mo).
The rate of progression of visual field loss, as measured by mean deviation, is related to the
amount of visual field loss present at initial presentation; the rate is greater the more loss is
initially present.[9] A study by Nouri-Mahdavi et al suggests that accelerating the frequency of
visual field testing from annually to biannually increases the ability to detect progression of
glaucoma.[10]
Causes
The exact cause of elevated IOP in POAG is not certain, although the role of accumulating
mucopolysaccharides in the trabecular meshwork beams continues to be a focus of research.
In general, the physiologic chain of events that leads to glaucomatous optic nerve damage
from pressure or other secondary mechanisms is unknown, although various theories, as
described below, have been proposed.

The disease affects the individual axons of the optic nerve, which may die by apoptosis, also
known as programmed cell death.

There has been some laboratory data that shows glutamate may play a role in glaucomarelated apoptosis, via neurotransmitter excitatory toxicity. However, so far, a human subject
trial of the glutamate inhibitor (also referred to as an N-methyl D-aspartate [NMDA]
inhibitor), memantine, has been unsuccessful in meeting its endpoints. To date, it has not
been specifically approved by the US Food and Drug Administration (FDA) for the
treatment of glaucomatous optic neuropathy. It is available in the United States and is
approved for the treatment of other neurodegenerative diseases, such as certain types of
dementia.

As a whole, the subjects in the memantine trial did not show a significant difference in their
rates of progression whether on memantine or placebo. However, on further analysis of the
different study population subgroups, those subjects with severe glaucomatous vision loss
did possibly show a benefit on memantine. Future studies are needed to confirm,
characterize, and quantify this potential benefit.
Other various theories (see Pathophysiology) have been advanced to explain the possible
etiologic role of elevated IOP in glaucomatous optic neuropathy.

The mechanical compression theory suggests that elevated IOP causes a backward bowing
of the lamina cribrosa, kinking the axons as they exit through the lamina pores. This may
lead to focal ischemia, deprive the axons of neurotrophins, or interfere with axoplasmic
flow, triggering cell death.

The vascular theories propose that cell death is triggered by ischemia, whether induced by
elevated IOP or as a primary insult.

Other risk factors may play a role in the development of POAG, including a history of
migraine headaches (a condition associated with vasospasm), cardiovascular disease,
diabetes, systemic hypertension (leading to arteriosclerosis), and systemic hypotension
(leading to decreased perfusion).

Genetic theories propose that cell death is triggered by genetic predisposition. Following the
death of individual axons, substances may be released into the environment that causes a
secondary triggering of apoptosis in neighboring cells, including glutamate (a
neurotransmitter that may cause excitotoxicity), calcium, nitric oxide, and free radicals.

Glaucoma is not just a disease of IOP but rather a multifactorial optic neuropathy. However,
patients with OHT who have IOP outside of the statistically normal range should continue to
have periodic follow-up examinations, because they are always at risk for development of
glaucoma.

Other causes for optic neuropathy should be considered in all patients with apparent
normal-tension glaucoma, and appropriate lab or radiologic testing should be initiated if
history and/or physical findings are suggestive.

Patients who do not have elevated IOP but glaucomatous optic discs or visual fields may
have normal-tension glaucoma. It is a diagnosis of exclusion (after other causes for optic
neuropathy, such as temporal arteritis, have been investigated and ruled out).
Several secondary causes of glaucoma must be considered before diagnosing POAG. These
causes include the following (see also Differentials):

Exfoliation syndrome

Pigment dispersion syndrome (pigmentary glaucoma)

Lens-induced glaucoma

Ocular inflammatory diseases

Intraocular tumors

Raised episcleral venous pressure

Topical or systemic corticosteroid use

Syndromes (eg, Axenfeld-Rieger syndrome)

Differential Diagnoses

Fistula, Carotid Cavernous

Glaucoma, Angle Closure, Acute

Glaucoma, Angle Closure, Chronic

Glaucoma, Angle Recession

Glaucoma, Aphakic And Pseudophakic

Glaucoma, Drug-Induced

Glaucoma, Hyphema

Glaucoma, Intraocular Tumors

Glaucoma, Lens-Particle

Glaucoma, Low Tension

Glaucoma, Malignant

Glaucoma, Neovascular

Glaucoma, Phacolytic

Glaucoma, Phacomorphic

Glaucoma, Pigmentary

Glaucoma, Plateau Iris

Glaucoma, Primary Congenital

Glaucoma, Pseudoexfoliation

Glaucoma, Suspect, Adult

Glaucoma, Unilateral

Glaucoma, Uveitic

Ocular Ischemic Syndrome

Phacoanaphylaxis

Posner-Schlossman Syndrome

Sturge-Weber Syndrome

Synechia, Peripheral Anterior

Laboratory Studies
Patients suspected of having normal-tension glaucoma may need workup to rule out other
causes for optic neuropathy, including, but not limited to, CBC, erythrocyte sedimentation
rate (ESR), serology for syphilis (micro-hemagglutination-Treponema pallidum [MHA-TP],
not Venereal Disease Research Laboratory [VDRL] test), and if suggested by the pattern of
visual field loss, neuroimaging.
Progressive visual field loss in a patient with glaucoma is shown in the image below.

Example of progressive visual field loss over time (from top to bottom) in a patient with
glaucoma. Notice the early appearance of an inferior nasal step and arcuate loss, with
progressive enlargement and increasing density of the scotomata over time. Courtesy of M.
Bruce Shields, MD.
Some researchers have suggested an autoimmune etiology for some glaucomatous optic
neuropathies and have identified monoclonal gammopathies. Serum protein electrophoresis
can identify these rare individuals.
Imaging Studies
Fundus photography provides a permanent record of the appearance of the optic disc.
Photographs taken over a period of time may be compared to track the progression of
glaucoma.
The retinal nerve fiber layer sometimes can be imaged on high-contrast black and white film
using red-free techniques. This can allow identification of nerve fiber layer defects that are
characteristic of glaucomatous damage.
New techniques that use optical analysis of different physical properties of light can
document the status of the optic nerve and the thickness of the nerve fiber layer, and they can

be used to detect changes over time. The value of these technologies for diagnosing and
following glaucoma over time continues to be an active topic of discussion and investigation.
Modalities of the various technologies continue to be upgraded and enhanced, hopefully
increasing the accuracy and likelihood of detecting glaucomatous damage.
Confocal scanning laser ophthalmoscopy (eg, HRT III) can examine the optic disc and
peripapillary retina in 3 dimensions and provides quantitative information about the cup,
neuroretinal rim, and contour of the nerve fiber layer. Increased resolution and software
enhancements continue to improve this technology.
Scanning laser polarimetry (eg, GDX) measures the change in the polarization state of an
incident laser light passing through the naturally birefringent nerve fiber layer to provide
indirect estimates of peripapillary nerve fiber layer thickness. Improvements in neutralizing
corneal light polarization (as opposed to that of the nerve fiber layer) have helped to decrease
artifact in data obtained by this methodology.
Optical coherence tomography (eg, Stratus OCT) uses reflected light in a manner analogous
to the use of sound waves in ultrasonography to create computerized cross-sectional images
of the retina and optic disc, and it also gives quantitative information about the peripapillary
retinal nerve fiber layer thickness. Newer increased resolution and three-dimensional spectral
analysis hardware and software are also helping to propel this technology. Retinal nerve fiber
layer (RNFL) thickness maps generated by spectral-domain OCT can help detect the
progression of RNFL in glaucoma patients.[11]
For these technologies, continuing studies show good reproducibility over time for the same
instrument. However, significant variability and fluctuating correlation between instruments
is still noted, especially when compared with visual field testing results and other clinical
examination findings. Therefore, testing results for each modality should be clinically
confirmed by examination findings and other testing and not just singly used for clinical
decision-making.[12]
The combination of structural and functional measurements with standard automated
perimetry and optical coherence tomography performs better in estimating the rate of retinal
ganglion cell loss in glaucoma patients than either measure alone.[13]

Fluorescein angiography, ocular blood flow analysis via laser Doppler flowmetry, color
vision measurements, contrast sensitivity testing, and electrophysiological tests (eg, pattern
electroretinograms) are used currently as research tools in the evaluation and management of
patients with POAG. Routine clinical use is not advocated at this time.
Ultrasound biomicroscopy (UBM) may prove to be helpful in the future for obtaining a better
view of the angle, iris, and ciliary body structures to rule out anatomical pathology and
secondary causes of elevated IOP.
Other Tests
Other tonometric methods
Goldmann applanation tonometry is considered the criterion standard. However, Goldmann
applanation is dependent on corneal rigidity, curvature, thickness (measured by pachymetry),
and other biomechanical properties, so there is much room for error in patients with atypical
corneas or other eye conditions. Particularly, with the advent of refractive corneal procedures,
and the subsequent exponential increase of postsurgical eyes, the issue of tonometric
accuracy is becoming more and more paramount.
Studies now strongly suggest that applanation pressures vary significantly depending on
corneal thickness.

Some patients diagnosed with OHT actually may be normotensive when corrected for
increased corneal thickness.

Some supposed glaucoma suspects or patients with apparent low-tension glaucoma (with
normal range IOPs on applanation) can have abnormally thin corneas on pachymetry
(central corneal thickness measurements); therefore, their IOP measurements are
underestimated by applanation.

Pachymetry may play a role in determining a fudge factor by which to adjust each patient's
IOP measurement.

Pachymetry plays a role in the development of glaucoma in those with OHT (see
Morbidity/Mortality and the image below).

Ocular hypertension study (OHTS). Percentage of patients who developed glaucoma during
this study, stratified by baseline intraocular pressure (IOP) and central corneal thickness
(CCT).

Correction values according to corneal thickness are shown below.

Correction values according to corneal thickness.

Other technology
Other technologies for measuring intraocular pressure continue to be studied to determine if
they are more accurate than Goldmann tonometry. To date, none have been able to surpass it
in accuracy for all patients; however, in the future, they may be useful for those who have
abnormal pachymetry or other corneal properties. Their role is yet to be finalized. [14,
17]

Two examples of new technology are described below.

15, 16,

The Ocular Response AnalyzerTM from Reichert[18] uses a rapid air impulse and an electrooptical system to record two applanation pressure measurements; one measurement is while
the cornea is moving inward, and the other measurement is as the cornea returns. Because of
its biomechanical properties, the cornea resists the dynamic air puff, thereby causing delays
in the inward and outward applanation events and resulting in two different pressure values.
See the image below.

Intraocular pressure measurements. Adapted from Reichert Ophthalmic Instruments, Ocular

Response Analyzer, How does it work Web page.
The average of these two pressure values provides a repeatable, Goldmann-correlated IOP
measurement. The difference between these two values is referred to as corneal hysteresis,
which is a measurement of the corneal tissue properties that is a result of viscous damping in
the corneal tissue. Low corneal hysteresis demonstrates that the cornea is less capable of
absorbing (damping) the energy of the air pulse. Clinical data from several studies show a
universal reduction in post-LASIK corneal hysteresis.
Some experts hypothesize that this is not primarily a function of corneal thinning, but rather a
result of weakening of the tissue structure related to creation of the flap. Decreased corneal
hysteresis may also play a role in indicating the presence or onset of other corneal tissue
disorders.

The PASCAL Dynamic Contour TonometerTM is a digital contact tonometer that directly
measures IOP continuously based on a numeric output of IOP and ocular pulse amplitude
(OPA). Unlike applanation tonometry, which is influenced by corneal thickness and other
characteristics of the cornea, the PASCAL Dynamic Contour Tonometer TM provides a direct
measurement of IOP, independent of interindividual variations in corneal properties and
biomechanics, and also measures pulsatile pressure fluctuations caused by the change in
ocular blood flow during systole versus diastole.[1, 18]
In cases of increased corneal or scleral rigidity (ie, S/P keratoplasty, scleral buckle), the
newer methods, as described above, as well as other alternatives, such as pneumotonometry
or Tono-Pen, may also be more accurate than applanation methods.
Other tests
Other tests of historical and research interest include the following:

Tonography, which has been used to help determine trabecular outflow facility, is primarily
a research tool used in testing pharmacologic agents.

Provocative testing (eg, water-drinking test) was used in the past to try to differentiate who
would develop early open-angle glaucoma. This test was of no aid in distinguishing those
patients who would develop visual field defects from those who would not develop them.
Patients whose visual field defects seem to progress in a manner uncharacteristic of glaucoma
should have a workup for other causes of visual loss.
Medical Care
Major drug classes for medical treatment of POAG include the following: alpha-agonists,
beta-blockers, carbonic anhydrase inhibitors, miotic agents, and prostaglandin analogs.
Basic science research continues on other possible pharmacologic sites of action, including
nitric oxide and cannabinoid pathways, although no topical product has been evaluated in US
FDA trials of yet.
Medical marijuana is not indicated for glaucoma treatment, as marijuana lowers IOP
minimally and its duration of action is very short. In the future, topical derivatives that affect

cannabinoid M receptors governing aqueous dynamics may be effective, but this is still under
early investigation.
The other drug classes mentioned above have much more documented duration of action and
efficacy without the systemic cannabinoid adverse effects. Furthermore, other options to treat
ocular pain from end-stage glaucoma have arisen (eg, trans-scleral or endoscopic
cyclophotocoagulation, absolute alcohol [ethanol] or chlorpromazine retrobulbar injections),
which directly and more effectively alleviate the problem than in the past when marijuana
was used for eye pain from end-stage glaucoma.
Legal justification of glaucoma as an indication for systemic medical marijuana use is
scientifically and medically improper, as well as unethical; education of the public and
legislators is needed on this subject.
Some physicians incorrectly treat all elevated IOPs over 21 mm Hg with the above topical
medications. Other physicians do not treat unless evidence of optic nerve damage exists,
although nerve fiber layer loss of up to 40% may occur before visual field defects occur, so
do not treat based on visual field testing alone. Most physicians select and treat those patients
thought to be at greatest risk for POAG damage and/or progression (most common approach).
See History for a list of risk factors for glaucomatous field loss.
In any case, the goal of treatment is reduction of the pressure before it causes progressive loss
of vision. Considering the high average monthly cost of glaucoma medication, along with the
possible risks of adverse effects or toxic reactions from drugs, inconvenience of use, and
incidence of noncompliance, a strong reason not to treat indiscriminately exists.
Several questions should be asked when considering treatment, to include the following: Is
the elevated pressure significant? Will this patient develop visual loss if left untreated? Is the
treatment worth the risk of adverse effects of the medications?
One should consider treatment more strongly if the patient reliability or the consequences of
missing field loss is an issue (eg, poor reliability on visual field examination, 1-eyed patient,
poor availability for follow-up care, younger patient, patient whose optic nerve is difficult to
visualize, history of vascular occlusion).

Treatment is highly recommended if signs of damage consistent with glaucomatous optic

neuropathy (eg, disc hemorrhage; visible nerve fiber layer defects; notching or vertical
ovalization of the cup; asymmetric cupping, especially if >0.7) are observed.
Progressive cupping, even in the absence of visual field loss, can be glaucoma and should be
treated as such, although systemic and neurologic workup/correlation for other disorders,
including possible neuroimaging studies, should be considered, particularly if there are other
nonophthalmologic symptoms. Otherwise, it depends on the assessment of risk factors and
benefit of therapy to the patient, as to whether therapy should be initiated.
Discussion with the patient about the pros and cons of treatment versus observation should be
completed. Individualization of therapy is the key; an ideal pressure in one patient may cause
glaucomatous damage in another patient. Risk factors, systemic conditions, life expectancy of
the patient, quality of life issues, and the patient's desire for therapy should be weighed when
considering treatment.
Due to the high risk of optic nerve damage, most ophthalmologists treat if pressures are
consistently above 28-30 mm Hg. If treatment is based on a high IOP only, then it should be
ensured that the risks of treatment do not exceed the risk of the disease. Other reasons to treat
include such symptoms as halos, blurred vision, or pain, or recent elevation of IOP, with
continuing elevation on successive visits.
Initiation of a monocular trial (see Medication) may be useful in helping to decide whether or
not to treat (ie, if the medication is effective in achieving good pressure reduction without
adverse effects, which may argue in favor of treatment, instead of just observation).
Considering all of the above, no consensus exists on what is the appropriate medical
treatment for preventing or delaying the damage due to POAG when a patient has only
elevated IOP and no other signs of POAG. To date, no one has been able to define
conclusively which subgroups will develop damage if left untreated, as opposed to those who
will not sustain damage even if not treated.
The question of medical therapy versus observation in patients with solely elevated IOP is
being addressed in the OHTS, an ongoing multicenter randomized clinical trial.

The OHTS is a multicenter, prospective, randomized, controlled, clinical trial studying over
1600 subjects to evaluate the safety and efficacy of medical treatment in preventing or
delaying onset of visual field loss and/or optic nerve damage in patients with OHT who are
at moderate risk for developing POAG.

Their medical therapy goal for the treated group is stepped therapy to reduce IOP by at least
20% from the average baseline IOP with its treated absolute value of 24 mm Hg or less.

So far, their results show a 10% risk over 5 years of developing glaucoma in those patients
with baseline IOP of 24-31 mm Hg. This risk was reduced to 5% with medical therapy.

The OHTS has also revealed the importance of pachymetry as a diagnostic tool as well as in
the workup.
Several sources agree on this initial goal of 20-25% reduction, while some specialists feel
that more absolute numbers of less than 15 should be the goal of treatment. Keep in mind that
the IOP goal must be set independently for each patient, depending on the risk factors, as an
IOP level for one person with minimal risk factors may be far too high for a patient with
multiple risk factors for sustaining glaucomatous damage.
Other regimens have been suggested, as follows: for minimal risk factors, consider lowering
IOP by 20-30%; if moderate number of risk factors are present, lower by 30-40%; and in
cases of numerous risk factors with markedly elevated pressures, reduction in the 40-60%
range may need to be achieved to prevent neuronal loss.
If the patient is older than 65 years, consider treatment to keep IOP 25 mm Hg or less,
secondary to 3% risk of vascular occlusion in OHT patients.
In any case, the target IOP should be reevaluated periodically, and regular review of IOP
trends should be performed to determine whether the patient is consistently maintaining that
goal.
Below is a suggested time guideline for therapy and follow-up based on initial IOP level.
Adjust frequency of follow-up testing as needed based on the number of risk factors and
clinical picture.

IOP 28 mm Hg or greater: Patients should be treated (see Medication), with follow-up care
in 1 month to assess if treatment is effective and no adverse effects are present. If the goal is
reached, then follow-up care should be performed every 3-4 months.

IOP 26-27 mm Hg: Follow-up care should be performed in 2-3 weeks to recheck pressure.
If IOP is still within 3 mm Hg of the initial reading, then follow-up should be continued
every 3-4 months with visual field and dilated optic nerve evaluation at least once a year. If
IOP is lower, then a longer time should be considered between the pressure checks, making
sure to recheck IOP at different times of the day on subsequent appointments.

IOP 22-25 mm Hg: Follow-up care should be performed 2-3 months later for recheck of
IOP at different times of the day (ie, 8 am, 11 am, 1 pm, 4 pm). If it is still within 3 mm Hg
of the initial reading at the second visit, then follow-up at 6 months with Humphrey visual
field testing and dilated optic nerve evaluation, repeating it at least yearly.
Other caveats concerning follow-up care are as follows:

If a new visual field defect becomes apparent on testing, confirmation with repeat (possibly
multiple) examinations during future office visits should be performed, before using it as a
basis for the treatment of presumed progression of POAG.

Gonioscopy should be performed at least once every 1-2 years if a significant increase in
IOP occurs, or if miotic therapy is instituted.

Optic disc photos should be repeated after the initial examination if a change in disc
appearance is noted (or every 1-2 years if available).
o

Technologic and financial barriers, as well as increasing lack of trained

ophthalmic staff, are making optic disc photos more difficult to obtain in many practices.

Whether nerve fiber layer imaging technologies (instead of recurring, serial

optic disc photos) are sufficient for mainstream nontertiary ophthalmology practices is still
under debate.

Retinal tomography, ocular coherence tomography, and/or laser polarimetry should be

measured at baseline and then every 1-2 years. Results should be correlated with visual field
results, IOP measurements, and examination findings.
Surgical Care

Surgery is indicated when glaucomatous optic neuropathy worsens (or is expected to worsen)
at any given level of IOP and the patient is on maximum tolerated medical therapy (MTMT).
MTMT varies considerably between individuals, and it may consist of medicines from 1 or
several classes (including a beta-adrenergic antagonist, a prostaglandin agent, an alphaagonist, and a topical carbonic anhydrase inhibitor). Some patients are observed to progress
simply because compliance with the medical regimen becomes too difficult because of the
following: high drug costs, inability to remember the schedule of multiple medications,
inability to instill them in the eyes properly secondary to arthritis or other incapacitation
(especially common among elderly patients or those with other chronic systemic conditions),
or intolerable ocular and systemic adverse effects.
A brief mention of surgical options is listed below. Detailed information on surgical
procedures, indications, and postoperative care is beyond the scope of this chapter.
Argon laser trabeculoplasty

Argon laser trabeculoplasty (ALT) uses a laser beam focused through a goniolens to treat at
the border between anterior and posterior trabecular meshwork. A full treatment consists of
100 spots placed over the entire 360 degrees of the trabecular meshwork. This may be
divided between 2 sessions consisting of 50 spots over 180 degrees.

Aqueous outflow improves after the procedure.

The specific mechanism of this improved outflow is unknown, but one hypothesis is upregulation of trabecular endothelial cells.

IOP reduction obtained is usually in the 7-10 mm Hg range, and it may last up to 3-5 years
following ALT.

A study by Heijl et al studied patients with low IOP levels before ALT. The study found that
IOP before ALT significantly influenced the IOP reduction produced by ALT, in that a much
larger decrease was observed in eyes with higher IOP before ALT. [19]

Unfortunately, the decrease in IOP is not usually permanent. Approximately 10% of treated
patients will return to pretreatment IOP for each year following treatment.

Complications include a brief, but potentially significant, increase in IOP after the procedure
(therefore, alpha-agonists often are used either preoperatively or postoperatively for

prophylaxis of this occurrence); transient iritis or corneal opacities; peripheral anterior

synechiae; and hyphema.

ALT usually is pursued after MTMT has been reached, but it may be performed sooner in the
treatment algorithm if pseudoexfoliation or pigmentary glaucoma is present, or if the patient
is of black ethnicity, because laser therapy may be most effective in these individuals.
Selective laser trabeculoplasty

Selective laser trabeculoplasty (SLT) uses a Q-switched 532 Nd:YAG laser to selectively
target pigmented cells of the trabecular meshwork in a nonthermal manner, increasing fluid
outflow and thereby lowering IOP.

The 3-nanosecond high-energy specific wavelength of light used induces the same cell
replacement mechanism as traditional ALT but without the destructive burning and
obliteration of structural support tissue in the meshwork. The short pulse of the laser does not
allow time for heat to spread to other cells. SLT delivers just enough energy to the trabecular
meshwork to target specific melanin-rich cells, without incurring collateral thermal damage
and scarring to adjacent nonpigmented trabecular meshwork cells and underlying trabecular
beams. When treated with SLT, a primarily biologic response is induced in the trabecular
meshwork that involves the release of cytokines that trigger macrophage recruitment as well
as other changes leading to IOP reduction.

The laser beam bypasses surrounding tissue leaving it undamaged by light. Unlike ALT, SLT
can be repeated several times. Whereas patients treated with ALT can receive only 2
treatments in their lifetime, patients treated with SLT can receive 2 treatments a year.

SLT requires a specially designed laser, as follows:

A short pulse to allow for thermal relaxation

Precise wavelength for optimal melanin absorption

Sufficient energy to heat melanin to the point that it releases cytokines

Sufficient spot size to ensure full coverage at the trabecular meshwork

Trabeculectomy

Trabeculectomy surgery usually is performed after MTMT and ALT have failed to control
IOP adequately. If IOP is so high that ALT and SLT are likely to be ineffective in reaching
target IOP, then proceeding from MTMT to penetrating surgery may be indicated.

A superficial flap of sclera is dissected anteriorly to the trabecular meshwork, and a section of
trabecular meshwork is removed underneath the flap.

This alternate outflow pathway is created to increase passage of aqueous from the anterior
chamber to the subconjunctival space, creating a filtering bleb and, thereby, lowering IOP.

Either releasable sutures or laser suture-lysis may be used to control aqueous drainage and
corresponding IOP postoperative. Alternatively, to maximize surgical success, antimetabolites
(eg, 5-fluorouracil, mitomycin C) may be applied during or after surgery to decrease
fibroblast proliferation and scar formation.

Risks

and complications

of filtering

surgery include

the following: hypotony,

blebitis/endophthalmitis, hyphema, suprachoroidal hemorrhage or effusions, encapsulation of

the bleb with resultant transient IOP elevation, loss of 1 or more lines of visual acuity, and
increased risk of cataract formation.

With the risk of severe complications from trabeculectomy and the need for frequent
postoperative follow-up care (ie, usually weekly for 2 months, initially), some patients with
transportation, financial, or long-distance issues concerning postoperative follow-up care may
be better served by tube shunt surgery instead. See the Tube versus Trabeculectomy Study
below.

Vision loss may be a serious complication after trabeculectomy, with severe and ongoing
unexplained loss ("snuff-out") experienced by as many as 2% of patients. Attendant risk
factors such as split fixation on visual fields prior to surgery, preoperative number of
quadrants with split fixation, and postoperative choroidal effusions with eventual resolution
are possible. [20]
Drainage implant (ie, seton/tube/shunt) surgery

Generally, this procedure is performed after multiple attempts at successful trabeculectomy

have failed.

A tube is placed in the anterior chamber to shunt aqueous to an equatorial reservoir, and then
posteriorly to be absorbed in the subconjunctival space.

Types of implants include Molteno, Baerveldt, Ahmed, and Krupin.

Most shunts function by allowing passive drainage of aqueous from the anterior chamber.

The Molteno implant consists of a silicone drainage tube, which is connected to 1 or 2

acrylic plates that are sutured to the sclera.

The Baerveldt implant is available with larger plates with increased reservoir size. The
seton (tube) connected to the reservoir usually is tied off with an absorbable suture,
allowing flow to initiate 4-6 weeks postoperative once some conjunctival wound
remodeling has taken place, thereby reducing the risk of immediate postoperative hypotony.

The Ahmed and Krupin implants have 1-way valves, which are designed to maintain
pressure above 8 mm Hg. These implants may reduce the risk of hypotony, a complication
of nonvalved shunts in the early postoperative period.

Because of less numerous postoperative visits, tube shunts may be indicated as primary
surgery when patients are unable to come as frequently for follow-up care (because of
transportation, financial, or long-distance issues). This can be a particular concern in rural
areas that cover large distances.

A valved shunt may also be indicated as primary surgery if a patient has a strenuous job or
other activities that require strenuous exertion. Severe exertion may cause a significant
Valsalva maneuver, significantly increasing venous pressure postoperatively, which could
result in a delayed suprachoroidal hemorrhage and possible severe loss of vision.

The Tube versus Trabeculectomy Study has been undertaken to see if glaucoma tube shunt
surgery may actually be a viable first-line alternative to (or even surpass) trabeculectomy
surgery. Some training programs have removed trabeculectomy training from their residency
program curricula, with only fellows performing trabeculectomy (not a general trend).

One-year data have shown nonvalved tube shunt surgery was more likely to maintain IOP
control and to avoid persistent hypotony or reoperation for glaucoma than trabeculectomy at
1 year, although both procedures produced similar IOP reduction.

Less supplemental medical therapy has been needed so far in the trabeculectomy group.

The incidence of postoperative complications at 1 year was higher in the trabeculectomy

group.

Serious complications resulting in reoperation and/or vision loss occurred with similar
frequency in both groups at 1 year.
Ciliary body ablation

Postoperative pain and inflammation are common complaints. Loss of 1 or more lines of
visual acuity has been reported. Phthisis is a concern after this procedure, although it has not
been reported as of yet after the diode laser method of cycloablation.

This procedure is indicated as a last resort for patients who have failed medical management
and other surgeries or for those patients who have limited visual potential (often 20/200 or
less).

By destroying a portion of the nonpigmented ciliary epithelium, aqueous humor production is

limited.

The ciliary body epithelium can be destroyed by cyclocryotherapy, diathermy, ultrasound,

transscleral Nd:YAG or diode laser (known as cyclophotocoagulation), or a newer endoscopic
laser (EndoOptiks, Inc). [21]
Several of the newer surgical procedures are promising, but many ideas have been tried
before and few have stood the test of time. Generally, the less complications, the less
effective in lowering IOP. There is the possibility that visual loss can be better prevented,
with fewer complications, and treatment can be tailored to the individual patient. If simple,
safe procedures become available, surgery could be performed earlier in the disease process
and adherence to medications could become less problematic.
The ideal glaucoma procedure would use the healthy portions of the outflow system and
bypass the diseased portions; control IOP without infection and other risks of a thin-walled
bleb; reduce the risk of hypotony during the perioperative period, with less postoperative care
management and complications, as compared with trabeculectomy and setons; and provide
adequate IOP control for the life of the patient.
Many innovative glaucoma surgical techniques and devices are on the horizon. Interest in this
new frontier is because of the lack of an existing, ideal glaucoma procedure despite decades
of research. Many devices are not yet approved by the FDA for use in the United States.
Newer techniques

Deep sclerectomy/viscocanalostomy/with or without collagen implant This is probably not

as effective as trabeculectomy and is technically more difficult, but it is associated with less
complications.

360-degree suture canaloplasty (iScience) This is a useful alternative in infants (with

congenital glaucoma or juvenile glaucoma) to trabeculotomy. In adults, suture under tension
left in the Schlemm canal to further open the trabecular meshwork (similar mechanism to
miotics).
New devices

ExPress shunt (Optonol)

Erosion problems if used without scleral flap

Now mainly used underneath trabeculectomy flap to better regulate flow through
sclerostomy

Easy to learn, appears effective, and otherwise has low complication rate

Awaiting long-term trials

May be especially useful for the ophthalmologist who only occasionally does glaucoma
surgery

iStent (Glaukos)

Shunt device from the anterior chamber into the Schlemm canal

Internal placement approach

May need multiple devices placed

Still undergoing continuing research

Eyepass

Shunt device from the anterior chamber into the Schlemm canal

External placement approach

Inactive technology

Poor long-term IOP control

Solx gold suprachoroidal space microshunt (OccuLogix)

Shunts fluid from the anterior chamber into the suprachoroidal space via gold
microchannels

External placement approach

Possibly titratable effect with titanium-sapphire laser to modify microchannel size

Needs further published series data

Trabectome (NeoMedix)

FDA approved

Ablates all of the trabecular meshwork for 90 degrees to 180 degrees via electrocautery and
aspiration of the internal wall of the Schlemm canal

Similar idea to goniotomy but prevents rescarring of the Schlemm canal edges, as all tissue
is removed

May have a place between trabeculoplasty and anterior filtering operations

Safer than trabeculectomy or tube shunt but may be less effective

Needs more long-term data on complication rate and persistence of effect

Consultations
Neuro-ophthalmology consultation may have a role in those patients who are experiencing
progressive visual loss that does not appear to follow a typical glaucomatous pattern or if
there are systemic symptoms or complaints.
Activity
Some studies show that a moderate amount of exercise can decrease IOP in both POAG
patients and normal individuals. Whether it results in actual long-term IOP control and
prevention of visual loss has yet to be determined.
Medication Summary
Current medical therapy is limited toward lowering IOP. A rational approach to choosing
antiglaucoma medications should minimize the number of medications and the probability of
significant adverse effects. The ideal drug for treatment of POAG should have the following
characteristics: (1) effectively lower IOP, (2) no adverse effects or systemic exacerbation of
disease, and (3) inexpensive with once-a-day dosing. However, because no medicine
possesses all of the above, these qualities must be prioritized based on the patient's individual
needs and risks; then, therapy should be chosen accordingly.
Once a medicine has been initiated, close follow-up care should be performed to assess its
effect. Initial follow-up care should be performed 3-4 weeks after the beginning of therapy.
IOP should be rechecked at the drug's peak and trough times to see if the target IOP has been

reached and is maintained throughout the day. Look for signs of allergy (eg, hyperemia, skin
rash, follicular reaction). Inform the patient of systemic adverse effects and symptoms that
may occur. Treatment should be continued if a therapeutic trial has shown effective lowering
of IOP without adverse effects. Reevaluation should be performed 2-4 months later
depending on the clinical picture.
A monocular therapeutic trial should be considered when first initiating the medical therapy,
as the other eye's IOP can be used as a baseline control to gauge effect of a medication
(particularly useful in patients with a widely fluctuating diurnal curve). A difference of more
than 4 mm Hg between the 2 eyes posttreatment is strongly suggestive of a clinical effect.
However, some agents (especially beta-blockers) may have crossover effects on the other eye
even with monocular treatment, so clinical correlation must be kept in mind. If monocular
therapy is found to be effective, then initiation of binocular therapy may be considered.
Some medications (eg, latanoprost, brimonidine) may have an effect that plateaus at 6-8
weeks in certain patients; keep this effect in mind when scheduling further follow-up
examinations. Other patients will be nonresponders to some therapies. If this occurs, the
medication should be discontinued and a new drug initiated. While discontinuing or changing
therapies, keep in mind that many drugs have a wash-out period of up to 2-4 weeks
(especially beta-blockers), during which they may still have some IOP-lowering effect or
residual systemic response.
If one medication is not adequate in reaching the target pressure, a second medication should
be chosen that has a different mechanism of action, so that the 2 drug therapies will have an
additive effect. (Usually, no additive effect is seen if 2 medications from the same drug class
are used.)
A specific plan of pharmacotherapy should be administered only after the possible effects of
the systemic medications that a patient is taking (eg, beta-blockers, calcium channel blockers,
ACE inhibitors) have been taken into consideration.
Before mention of particular medications currently used in most practices, note that as the
mechanisms of axonal death by apoptosis are becoming better understood, therapies are being
developed to protect nerve fibers from undergoing injury and death by several possible
theoretical mechanisms. This halting of processes that is believed to contribute to ganglion

cell death in glaucoma has been termed neuroprotection, and several new pharmaceuticals are
being developed that hopefully will work in this manner. Agents currently under investigation
as neuroprotective include glutamate receptor blockers, calcium channel blockers, inhibitors
of nitric oxide synthase, free radical scavengers, and drugs to increase blood flow to the optic
nerve.
See Ocular Hypertension and AAO monograph #13 for further in-depth descriptions of
particular drugs.
Beta-adrenergic blockers
Class Summary
Topical beta-adrenergic receptor antagonists decrease aqueous humor production by the
ciliary body. Adverse effects are due to systemic absorption of the drug, decreased cardiac
output, and bronchoconstriction. In susceptible patients, this may cause bronchospasm,
bradycardia, heart block, or hypotension. The patient's pulse rate and blood pressure also
should be monitored if symptoms emerge after initiation of treatment. Patients may be
instructed to perform punctal occlusion after administering the drops to reduce systemic
absorption. Depression or anxiety may be experienced in some patients, and sexual
dysfunction may be initiated or exacerbated. Ocular adverse effects may include blurred
vision, eye ache, and corneal anesthesia.
Levobunolol 0.25%, 0.5% (Betagan)
Nonselective beta-adrenergic blocking agents that lower IOP by reducing aqueous humor
production.
Timolol maleate/hemihydrate (Timoptic 0.25%, 0.5%; Timoptic XE, Betimol
0.25%, Istalol)
Nonselective agents that may reduce elevated and normal IOP, with or without glaucoma, by
reducing production of aqueous humor.
The brands Timoptic XE and Istalol are both administered qd. However, Timoptic XE is a
gel-forming solution, while Istalol is an aqueous solution.

Carteolol ophthalmic (Cartrol, Ocupress)

Blocks beta1- and beta2-receptors and has mild intrinsic sympathomimetic activity (ISA),
with possibly fewer cardiac and lipid profile adverse effects.
Betaxolol ophthalmic (Betoptic-S)
Beta1-selective adrenergic antagonist, with possibly less pulmonary effects than nonselective
agents. IOP-lowering effect is slightly less than nonselective beta-blockers.
Metipranolol hydrochloride (OptiPranolol)
Beta-adrenergic blocker that has little or no intrinsic sympathomimetic effects and membrane
stabilizing activity. Has little local anesthetic activity. Reduces intraocular pressure by
reducing production of aqueous humor.
Adrenergic agonists
Class Summary
Alpha2-adrenergic agonists work by decreasing aqueous production. Systemic adverse effects
include dry mouth, fatigue, and drowsiness. Ocular adverse effects include allergic
(follicular) conjunctivitis and contact dermatitis.
Of this class, the alpha2-selective agonist, brimonidine, is used most commonly to treat
POAG. Apraclonidine also is alpha2-selective but is believed to have more of an allergic
potential; therefore, it is used less commonly as a long-term medication.
Brimonidine (Alphagan-P 0.2%, 0.15%, 0.1%)
Lowering of IOP of up to 27% reported. Bid dosing used initially, especially if in
combination with other classes of agents. Tid dosing used most often in single-agent therapy
that does not adequately control IOP with bid dosing. A moderate risk of allergic response to

this drug exists. Caution should be used in individuals who have developed an allergy to
Iopidine.
The brand Alphagan-P contains the preservative Purite and has been shown to be much better
tolerated than its counterpart Alphagan or generic brimonidine.

Apraclonidine 0.5%, 1% (Iopidine)

Reduces IOP whether or not accompanied by glaucoma. Selective alpha-adrenergic agonist
without significant local anesthetic activity. Has minimal cardiovascular effect.
Less-selective sympathomimetics
Class Summary
These less-selective adrenergic drugs increase outflow of aqueous humor through the
trabecular meshwork and possibly through the uveoscleral outflow pathway, probably by a
beta2-agonist action. Up to one third of patients will not respond to these drugs.
Less-selective adrenergics, such as epinephrine and dipivefrin, also can have a significantly
higher allergic component and other substantial adverse effects, such as exacerbation of
hypertension, angina, palpitations, or cystoid macular edema (CME). These less-selective
agents are used infrequently.
Dipivefrin (AKPro, Propine)
Prodrug converted to epinephrine in eye by enzymatic hydrolysis. Appears to act by
decreasing aqueous production and enhancing outflow facility. Has same therapeutic effect as
epinephrine with fewer local and systemic adverse effects. May be used as an initial therapy
or as an adjunct with other antiglaucoma agents for the control of IOP.
Epinephrine (Epifrin)

Lowers IOP by increasing outflow and reducing production of aqueous humor. Used as
adjunct to miotic or beta-blocker therapy. Combination of miotic and sympathomimetic will
have additive effects in lowering IOP.
Dipivefrin is converted to epinephrine in eye by enzymatic hydrolysis. Appears to act by
decreasing aqueous production and enhancing outflow facility. Has same therapeutic effect as
epinephrine with fewer local and systemic adverse effects. May be used as an initial therapy
or as an adjunct with other antiglaucoma agents for the control of IOP.
Memantine (Namenda, Axura)
Indicated for moderate-to-severe Alzheimer disease; failed initial phase III trial endpoints for
glaucoma indication, although subgroup analysis shows possible efficacy for patients with
severe visual loss from glaucoma; possible neuroprotective systemic treatment of glaucoma,
although as of now, this is a non-FDA approved off-label use of the drug. N-methyl-Daspartate (NMDA) antagonist. NMDA receptor stimulation in the CNS by glutamate (an
excitatory amino acid) is hypothesized to contribute to Alzheimer symptoms, as well as
apoptosis (programmed cell death) and neuronal degeneration.
Carbonic anhydrase inhibitors
Class Summary
Reduce secretion of aqueous humor by inhibiting carbonic anhydrase (CA) in the ciliary
body. In acute angle-closure glaucoma, administer systemically; apply topically in patients
with open-angle glaucoma. These drugs are less effective, and their duration of action is
shorter than many other classes of drugs. Adverse effects are relatively rare but include
superficial punctate keratitis, acidosis, paresthesias, anorexia, nausea, depression, dysgeusia,
and lassitude.
Oral agents, such as acetazolamide and methazolamide, primarily are used only for the
treatment of refractory POAG and secondary glaucomas because they have increased
systemic adverse effects. However, oral CAIs can have a slightly greater effect than topical
CAI medications and are appropriate to use in certain clinical situations. The mechanism of
IOP reduction is similar to other CAIs, being accomplished by reduction of bicarbonate
accumulation in the posterior chamber, with a resultant decrease in sodium and associated

fluid movement linked to the bicarbonate ion. An additional IOP-lowering effect exists by the
creation of a relative metabolic acidosis.
Dorzolamide (Trusopt)
More commonly used concomitantly with other topical ophthalmic drug products to lower
IOP. If more than one ophthalmic drug is being used, administer drugs at least 10 min apart.
Either drug reversibly inhibits CA, reducing hydrogen ion secretion at renal tubule, and
increases renal excretion of sodium, potassium bicarbonate, and water to decrease production
of aqueous humor.
Brinzolamide (Azopt)
Catalyzes reversible reaction involving hydration of carbon dioxide and dehydration of
carbonic acid. May use concomitantly with other topical ophthalmic drug products to lower
IOP.
May cause less ocular discomfort on instillation, secondary to a buffered pH, but can still
cause foreign body sensation.
If more than one topical ophthalmic drug being used, administer drugs at least 10 min apart.
Acetazolamide (Diamox)
Reduces rate of aqueous humor formation by direct inhibition of enzyme carbonic anhydrase
(CA) on secretory ciliary epithelium, causing in turn a reduction in intraocular pressure
(IOP). More than 90% of CA must be inhibited before IOP reduction can occur. May reduce
IOP by 40-60%. Effects are seen in about an hour, they peak in 4 h, and trough in about 12 h.
Derived chemically from sulfa drugs. If one form is not well tolerated, another form may be
better or lower dose of the drug may better tolerated.
Used for adjunctive treatment of chronic simple (open-angle) glaucoma and secondary
glaucoma and preoperatively in acute angle-closure glaucoma when delay of surgery desired
to lower IOP
Methazolamide (Neptazane)

Reduces aqueous humor formation by inhibiting enzyme carbonic anhydrase, which results
in decreased IOP.
Antiglaucoma, Combos
Class Summary
Combination solution may further decrease aqueous humor secretion compared to each
solution used as monotherapy, while improving compliance.
Timolol/brimonidine (Combigan)
Brimonidine is a selective alpha2 adrenergic receptor agonist and timolol is a nonselective
beta-adrenergic receptor inhibitor. Each of these agents decrease elevated IOP, whether or not
associated with glaucoma.
Timolol/dorzolamide (Cosopt)
Dorzolamide is a carbonic anhydrase inhibitor that decreases aqueous humor secretion,
causing a decrease in IOP. This agent presumably slows bicarbonate ion formation with
subsequent reduction in sodium and fluid transport. Timolol is a nonselective beta-adrenergic
receptor blocker that decreases IOP by decreasing aqueous humor secretion.
Both agents administered together bid may result in additional IOP reduction compared with
either component administered alone, but reduction is not as much as when dorzolamide tid
and timolol bid are administered concomitantly.
Brinzolamide/brimonidine (Simbrinza)
This combination product contains the carbonic anhydrase inhibitor brinzolamide and the
alpha2 adrenergic receptor agonist brimonidine. It is indicated for reduction of elevated
intraocular pressure in patients with primary open-angle glaucoma.
Prostaglandin analogs
Class Summary

Increase uveoscleral outflow of aqueous. One mechanism of action may be through induction
of metalloproteinases in the ciliary body, which breakdown the extracellular matrix, thereby
reducing resistance to outflow through the uveoscleral pathway. Can be used in conjunction
with beta-blockers, alpha-agonists, or topical CAIs. Many patients respond well to these
agents; other patients do not respond at all. Adverse effects include conjunctival hyperemia,
iris pigmentation, CME, and uveitis.
Latanoprost 0.005% (Xalatan)
Decreases IOP by increasing outflow of aqueous humor through uveoscleral pathways.
Bimatoprost (Lumigan)
Prostaglandin agonist that selectively mimics effects of naturally occurring substances,
prostamides. Exact mechanism of action unknown but believed to reduce IOP by increasing
outflow of aqueous humor through trabecular meshwork and uveoscleral routes. Used to
reduce IOP in open-angle glaucoma or ocular hypertension.
Travoprost ophthamic solution (Travatan)
Prostaglandin F2-alpha analog and selective FP prostanoid receptor agonist. Exact
mechanism of action unknown but believed to reduce IOP by increasing uveoscleral outflow.
Unoprostone (Rescula)
Prostaglandin F2-alpha analog and selective FP prostanoid receptor agonist. Exact
mechanism of action unknown but believed to reduce IOP by increasing uveoscleral outflow.
Tafluprost (Zioptan)
Tafluprost is a preservative-free, topical, ophthalmic prostaglandin analog indicated for
elevated IOP associated with open-angle glaucoma or ocular hypertension. The exact
mechanism by which it reduces IOP is unknown, but it is thought to increase uveoscleral
outflow.
Miotic agents (parasympathomimetics)

Class Summary
Miotics work by contraction of the ciliary muscle, tightening the trabecular meshwork and
allowing increased outflow of aqueous through traditional pathways. Miosis results from
action of these drugs on the pupillary sphincter. Adverse effects include brow ache, induced
myopia, and decreased vision in low light. These agents are used less commonly today since
the advent of newer drugs with fewer adverse effects.
Pilocarpine is one of the more commonly used agents in this class. Less frequently used
miotics include phospholine iodide (0.03%, 0.06%, 0.125%, 0.25% qd/bid) and carbachol
(0.75%, 1.5%, 3% tid/qid).
Pilocarpine ophthalmic (Pilocar, Pilagan, Pilogel, Ocusert)
A naturally occurring alkaloid, pilocarpine mimics the muscarinic effects of acetylcholine at
postganglionic parasympathetic nerves. Directly stimulates cholinergic receptors in the eye,
decreasing resistance to aqueous humor outflow.
Instillation frequency and concentration are determined by patient's response. Individuals
with heavily pigmented irides may require higher strengths.
If other glaucoma medication also is being used, at bedtime, use gtt at least 5 min before gel.
Patients may be maintained on pilocarpine as long as IOP is controlled and no deterioration in
visual fields occurs.
May use alone or in combination with other miotics, beta-adrenergic blocking agents,
epinephrine, CAIs, or hyperosmotic agents to decrease IOP. Use with prostaglandin analogs
can have a small additive effect.
Hyperosmotic agents

Class Summary

These agents are used infrequently, most commonly to reduce extremely elevated IOP in
acute situations of angle-closure or certain secondary glaucomas, or selectively as a
preoperative measure before intraocular surgery.
Osmotics lower IOP by increasing the osmotic gradient between the blood and ocular fluids,
resulting in loss of water from the eye (especially the vitreous) into the hyperosmotic blood
plasma, with concomitant lowering of IOP, but an increase in intravascular volume.
Therefore, care should be used in any patient with cardiac, renal, or hepatic abnormalities.
Systemic adverse effects include nausea, vomiting, headache, increased thirst, chills, fever,
confusion or disorientation, electrolyte imbalances, and urinary retention.
Isosorbide dinitrate (Ismotic)

In the eyes, may create an osmotic gradient between plasma and ocular fluids and induce
diuresis by elevating osmolarity of glomerular filtrate. Effects may, in turn, inhibit tubular
reabsorption of water. Treatment is preferred when less risk of nausea and vomiting than that
posed by other oral hyperosmotic agents desired. Palatability best if poured over ice before
ingestion. May use in patients with diabetes.
Mannitol (Osmitrol, Resectisol)
Reduces elevated IOP when the pressure cannot be lowered by other means.
Initially assess for adequate renal function in adults by administering a test dose of 200
mg/kg, given IV over 3-5 min. Should produce a urine flow of at least 30-50 mL/h of urine
over 2-3 h.
In children, assess for adequate renal function by administering a test dose of 200 mg/kg,
given IV over 3-5 min. Should produce a urine flow of at least 1 mL/h over 1-3 h.
The 20% w/v solution most commonly is used IV. Alternatively, concentrations of 10%, 15%,
or 25% may be used.

Glycerin (Ophthalgan, Osmoglyn)

Used in glaucoma to interrupt acute attacks. Oral osmotic agent for reducing IOP. Able to
increase tonicity of blood until finally metabolized and eliminated by the kidneys. Maximum
reduction of IOP usually occurs 1 h after glycerin administration. Effect usually lasts
approximately 5 h.
Used for diagnostics. Facilitates ophthalmoscopic and gonioscopic examination in acute
glaucoma. Used only for topical application to cornea. By virtue of osmotic action (attraction
of water through the semipermeable corneal epithelium), promptly reduces edema and causes
clearing of corneal haze. Action is transient and therefore used primarily for diagnostic
purposes.
Further Outpatient Care
Depending on the amount of optic nerve damage and level of IOP control, POAG patients
may need to be seen from every 2 months to yearly, even sooner if a marked lack of IOP
control is present. Follow-up studies/examinations should be performed as detailed under
Treatment.
Glaucoma still should be a concern in people with elevated IOP in the presence of normal
discs and visual fields or in people who have normal IOP with suspicious-looking discs and
fields. These patients should be observed closely, because they are at an increased risk for
development of glaucomatous damage. SWAP visual field testing may also play a role,
because it may help detect visual field defects earlier in these otherwise healthy patients.
Prognosis
Prognosis is generally good for patients with POAG. With careful follow-up care and
compliance with therapy, the vast majority of patients with POAG retain useful vision
throughout their lifetime.
Patient Education

Patient education is essential for successful treatment of glaucoma. The patient who
understands the chronic, potentially progressive nature of glaucoma is more likely to comply
with therapy. Numerous handouts are available to patients, including the following:

"Understanding and Living with Glaucoma: A Reference Guide for People with Glaucoma
and Their Families," Glaucoma Research Foundation, 1-800-826-6693.

"Glaucoma Patient Resource: Living More Comfortably with Glaucoma," Prevent

Blindness America, 1-800-331-2020.

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