REVIEW ARTICLE
Glaucoma Suspect: Diagnosis and Management
Robert T. Chang, MD, and Kuldev Singh, MD, MPH
Abstract: Glaucoma suspect is a diagnosis reserved for individuals who
do not definitively have glaucoma at the present time but have characteris-
tics suggesting that they are at high risk of developing the disease in the fu-
ture based on a variety of factors. This review provides a practical approach
to individuals classified as glaucoma suspects caused by one or more of the
following risk factors or indicators of disease: ocular hypertension, optic
nerve features suggestive of glaucoma, visual field abnormalities, and
other characteristics placing them at greater risk than the average popula-
tion. In addition to diagnostic considerations, this overview provides infor-
mation on therapeutic approaches to the glaucoma suspect.
Key Words: glaucoma suspect, diagnosis, therapy, review
(Asia Pac J Ophthalmol 2016;5: 3237)
G laucoma is a slowly progressive disease with characteristic
optic nerve abnormalities caused by accelerated retinal gan-
glion cell (RGC) loss and concomitant retinal nerve fiber layer
(RNFL) thinning. Normally, individuals have enough ganglion
cells to preserve vision for a lifetime, but in those with glaucoma,
the rate of RGC death may be too fast to allow visual function to
remain normal. The result is progressive peripheral and/or central
visual defects, which can, in some individuals, lead to complete
vision loss. Modern treatment slows the rate of vision loss, but
even treated individuals may still go blind depending on when
the disease is detected. Of note, the exact structure-function rela-
tionship for any given stage of glaucoma in a particular patient
is still not predictable. Eventually, in vivo imaging will aid in pro-
viding noninvasive neural cell counts, at which time a link be-
tween cellular pathophysiology and clinical manifestations will
be better characterized.1
Currently, glaucoma is the leading cause of irreversible
blindness worldwide. In 2013, an extensive meta-analysis of 50
population-based studies from around the world estimated the
global prevalence of open- and closed-angle glaucoma in individ-
uals aged 40 to 80 years to be 3.54% (95% confidence interval,
2.095.82) or about 64.3 million afflicted.2 This was similar to
the glaucoma prevalence estimate for 2010 projected by Quigley
and Broman3 in 2006. Therefore, although routine glaucoma
screening may be controversial from the perspective of the pri-
mary care provider, certainly identifying glaucoma is an important
task among vision care specialists. Glaucoma suspects are the key
group to identify and, in some cases, treat with intraocular pres-
sure (IOP)lowering therapy in an effort to prevent blindness. It
is more compelling to screen high-risk populations once every
12 months, including diabetics, individuals with a family history
of glaucoma, African Americans older than age 50, and Hispanic
Americans aged 65 years and older.4
From the Department of Ophthalmology, Byers Eye Institute at Stanford Uni-
versity School of Medicine, Palo Alto, CA.
Received for publication October 6, 2015; accepted November 17, 2015.
Robert Chang is a consultant at Allergan, Carl Zeiss Meditec, and Transcend
Medical. Kuldev Singh is a consultant at Alcon, Allergan, and Santen.
Reprints: Robert T. Chang, MD, Stanford Byers Eye Institute, 2452 Watson
Court, MC 5353, Palo Alto, CA 94303. E-mail: viroptic@gmail.com.
Copyright 2016 by Asia Pacific Academy of Ophthalmology
ISSN: 2162-0989
DOI: 10.1097/APO.0000000000000173
32 www.apjo.org Asia-Pacific Journal of Ophthalmology Volume 5, Number 1, January/February 2016
Copyright 2016 Asia Pacific Academy of Ophthalmology. Unauthorized reproduction of this article is prohibited.
RISK FACTORS
The term glaucoma encompasses many diseases, some of
which can be secondary to a variety of causes resulting in subcat-
egories such as neovascular, pseudoexfoliative, pigmentary, uveitic,
steroid induced, traumatic angle recession, postsurgical, and so on.
Other categories include congenital, primary open-angle (POAG),
and primary angle-closure (PACG), all of which are generally as-
sociated with higher than average IOP as the primary risk factor.
Thus, the term glaucoma suspects may be any of these types
(predisease), but generally, individuals are labeled glaucoma sus-
pects when they have at least 1 clinical feature of the disease, in-
cluding an elevated IOP, a suspicious optic nerve appearance
commonly referred to as cupping, a repeatable visual field ab-
normality consistent with optic nerve damage, or a strong family
history of glaucomatous disease. From the Baltimore Eye Survey,
age-adjusted associations of POAG with a family history of glau-
coma were 3.69 times higher in siblings and 2.17 times higher in
parents relative to those with no family history of disease.5 How-
ever, the genetic inheritance of glaucoma has not been simple to
elucidate and is multifactorial. It has been difficult to find a single
biomarker for glaucoma. Other risk factors derived from large
prospective cohort studies include increased age, ethnicity, se-
lected medication, myopia, and a thin cornea.6 Finally, some
specific risk factors may be associated with normal- or low-
tension glaucoma, such as migraine headaches, disc hemorrhages,
vascular dysregulation, and sleep apnea.7,8 But the hallmark sign
separating true pathology from a glaucoma suspect, regardless
of IOP, is progressive glaucomatous visual field loss distinct
from neurologic field defects or nonprogressive defects that can
mimic glaucoma.
Elevated IOP is a well-known strong risk factor for glau-
coma, yet not all individuals with high pressure develop glau-
coma. The Barbados Eye Studies revealed in more than 9 years of
follow-up that, although persons of African origin with a baseline
IOP more than 25 mm Hg had a 13-fold relative risk of developing
POAG, most cases arose with a lower baseline IOP.9 Because many
individuals with glaucoma may not always have a high IOP and
the majority with a higher-than-average IOP do not develop glau-
coma, relying on IOP to diagnose glaucoma is not advisable. Two
landmark 5-year clinical trials were undertaken to determine the
benefit of treating ocular hypertensive glaucoma suspects: the Oc-
ular Hypertension Treatment Study (OHTS)10 completed in 2002
and the European Glaucoma Prevention Study (EGPS).11 The for-
mer study included 1636 participants with IOP between 24 and
32 mm Hg, with 9.5% of untreated subjects converting to POAG
across 5 years versus only 4.4% of treated subjects. Its other break-
through finding was that a thinner central corneal thickness (CCT)
was an independent risk factor for developing glaucoma. The same
study also found that a thicker CCT was protective, but there is no
validated linear correlation correction formula for IOP and CCT,
as corneal biomechanics can also affect IOP readings gathered in-
directly through the cornea. By combining the longitudinal data
from the OHTS and EGPS, a validated glaucoma progression risk
calculator was created using the inputs of age, IOP, CCT, vertical
cup-to-disc (C/D) ratio, and pattern standard deviation of visual
field test (http://ohts.wustl.edu/risk/calculator.html).12 Unfortunately,
the risk factors in the calculator are essentially not modifiable ex-
cept IOP, the vertical C/D ratio is very subjective and, along with
Asia-Pacific Journal of Ophthalmology Volume 5, Number 1, January/February 2016
the pattern standard deviation, is used to define the diseaseall
points that make the calculator a bit less useful. Nonetheless,
when the point system estimates greater than 15% chance of con-
version to glaucoma in the next 5 years, the prediction model pro-
vides evidence of when to initiate therapy selectively instead of
treating every case of high IOP automatically.
Besides increased IOP, the other most common reason for
suspected glaucoma is cupping or an enlarged C/D ratio visual-
ized on routine funduscopic examination. The distinction between
physiologic cupping and pathologic cupping is not always easy,
and accurate classification can be quite subjective even among ex-
perts.13 Pathological optic disc cupping is most often caused by
glaucoma but may also be seen with several less common neuro-
ophthalmic conditions. Typically, glaucomatous cupping may in-
volve disc excavation with neuroretinal rim loss, focal notching,
bayoneting or nasalization of blood vessels as the rim thins, baring
of the lamina cribrosa (laminar dots), beta zone peripapillary atro-
phy, splinter hemorrhages, and enlarging RNFL defects. Tradi-
tional teaching states that a healthy neuroretinal rim tends to
have the thickest nerve fiber layer inferiorly, then superiorly, then
nasally, and then temporally (ISNT rule). However, disc excava-
tion has also been described in those with optic nerve hypoplasia,
optic nerve head drusen, morning glory syndrome, septo-optic
dysplasia, optic nerve compression, traumatic optic neuropathy,
anterior ischemic optic neuropathy or systemic shock (low perfu-
sion), radiation optic neuropathy, Leber hereditary optic neuropa-
thy, and dominant optic atrophy.14 Thus, these conditions should
be ruled out in cases with a large C/D ratio.
High myopia has long been known to be associated with
glaucoma. The Blue Mountains Eye Study15 found a 2- to 3-fold
increase in glaucoma prevalence related to myopia, and this was
confirmed by multiple subsequent studies even after incorporat-
ing axial length and adjusting for cataract. The challenge is that
anomalous optic nerves with RNFL bundle defects may be con-
fused with the appearance of a glaucomatous optic nerve, partic-
ularly in cases with high myopia, nerve tilt or oblique insertion,
staphyloma, coloboma, optic pit, and large peripapillary atrophy.
Many of these diagnostic dilemmas may or may not be seen con-
comitantly with high IOP, and oftentimes assessing carefully for
glaucomatous visual field progression is the primary method of
teasing out a glaucoma diagnosis in the setting of an anomalous-
appearing uninterpretable optic nerve.
Physiologic cupping is typically characterized by bilaterally
round, symmetrically enlarged optic cups without focal RNFL
thinning. The disc area may or may not be larger than average,
but clinicians are more suspicious of glaucoma with large optic
disc areas, particularly when greater than 3.0 mm.2 However, a
large intact cup within a large disc often represents physiologic
cupping, as the same normal amount of annular neuroretinal rim
is spread over a larger area. Also, superotemporal and inferotemporal
RNFL bundles tend to vary in location and converge more tempo-
rally with increasing myopia, which, although appearing abnormal,
may be normal for a given individual.16 Individuals of African de-
scent have a higher prevalence of open-angle glaucoma relative
to whites, but they also may have larger disc areas, so it is impor-
tant to measure the disc size in all glaucoma suspects to aid in
distinguishing physiologic cupping.17 Lastly, 2 other strong risk
factors frequently mentioned in association with glaucoma in in-
dividuals with average IOPs are reduced ocular perfusion pres-
sure18 and disc hemorrhages (originally Drance hemorrhages),19
but these typical flame-shaped hemorrhages can also occur near
the disc edge in association with other conditions such as posterior
vitreous detachment, optic disc drusen, vascular occlusive retinal
diseases, nonglaucomatous optic neuropathy, and systemic condi-
tions such as diabetes, hypertension, leukemia, and lupus.20
2016 Asia Pacific Academy of Ophthalmology
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Glaucoma Suspect
DIAGNOSIS
Among all glaucoma types, POAG is classified as a neurode-
generative disease, and POAG suspects display a constellation of
risk factors or clinical findings that indicate a pretest probability
of disease. Primary open-angle glaucoma suspects have open an-
gles and subjective structural optic disc or nerve fiber layer
changes. Primary angle-closure glaucoma subjects have variable
amounts of closed angle, and the current nomenclature divides
the closed-angle group into primary angle-closure suspect (PACS),
primary angle closure (PAC), and PACG. The PAC designation re-
fers to closed angle with peripheral anterior synechiae and/or ele-
vated IOP but no structural nerve damage, whereas PACG has
definite nerve damage. In PACS, then, a shallow peripheral angle
with iridotrabecular contact in at least 3 quadrants is seen without
peripheral anterior synechiae but with otherwise normal IOP and
optic nerve. Glaucoma can be divided into preperimetric and
perimetric disease based on the absence or presence of reproducible
glaucomatous visual field defects. Generally, glaucoma suspects
have converted to true glaucoma once classic field defects, includ-
ing arcuate bundle defect, nasal step, paracentral scotoma, and alti-
tudinal defect, appear and are not attributable to any other optic
neuropathies. An initial glaucoma evaluation includes a history
and physical examination and a comprehensive adult medical eye
evaluation, including IOP measurement, CCT, gonioscopy, anterior
and posterior segment evaluation with optic nerve head imaging,
and perimetry testing.21,22 Oftentimes, a diagnosis of an open- or
closed-angle glaucoma suspect is made on a single visit, but serial
follow-up testing moves the suspicion level either higher or lower.
INTRAOCULAR PRESSURE
Intraocular pressure is an important part of every glaucoma
suspect evaluation because there is an exponential increase in
glaucoma risk with a progressively higher IOP. Whereas the nor-
mal pressure range for a white population is 15 to 16 mm Hg with
a standard deviation of 3 mm Hg, up to 61% of patients with
POAG have a single screening IOP less than 21 mm Hg, making
abnormal IOP as a diagnostic criterion less than optimal.23 Fur-
thermore, it can be difficult to obtain accurate noninvasive read-
ings, as isolated office visit measurements do not reflect the full
range of IOP changes during a 24-hour period. To complicate
matters further, the long-standing gold standard method for
checking IOP is the Goldmann applanation tonometer (GAT),
which has known flaws in terms of estimating the true manometric
pressure of the eye because GAT is an indirect measurement
through the cornea. For example, a history of refractive surgery
can alter corneal biomechanics and corneal thickness, resulting
in falsely low IOP readings. Also, the GAT reference standard as-
sumes a specific CCT, which varies widely in all populations. At
present, there is no proven formula to adjust IOP for CCT. How-
ever, most of the evidence-based clinical trials have used GAT
IOP as an outcome measure, and thus it is difficult to interpret
the relevance of newer methods such as noncontact tonometry, dy-
namic contour tonometry, rebound tonometry, or ocular response
analyzer. All noninvasive tonometers have their own limitations,
especially if used to obtain a single isolated value of a physiologic
parameter that is quite variable with every heartbeat and eye
movement.24 External and internal 24-hour IOP-monitoring de-
vices are under study to record peak IOP as well as short- and
long-term IOP fluctuation, and it remains unclear whether IOP
fluctuation also plays an independent role in glaucoma progres-
sion.25 Knowing how IOP behaves in low-pressure glaucoma
and while on various glaucoma therapies would be interesting as
well. The most exciting potential of 24-hour IOP devices is the
possibility that circadian IOP patterns may predict future
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Chang and Singh Asia-Pacific Journal of Ophthalmology Volume 5, Number 1, January/February 2016
glaucoma progression, and such devices may be able to help ob-
tain such clinically useful information.26,27 There is 1 specific sit-
uation when IOP is used to make the diagnosis of glaucoma, and
that is when it is not possible to visualize the optic nerve and field
testing is impossible. Then, if the visual acuity is diminished and
the IOP is elevated, a diagnosis may be assumed.
FUNDUS EXAMINATION
A stereoscopic view of the optic nerve through a dilated pupil
when feasible is the preferred examination technique. There is ev-
idence that glaucomatous changes can be detected at the level
of the optic nerve head and RNFL before any findings on tests
such as standard automated perimetry (SAP).2830 In regions of
the world where perimeters, fundus cameras, and optical coher-
ence tomography (OCT) machines are easily accessible, baseline
testing is performed to support or refute a glaucoma diagnosis
and to document findings for future comparison. This is critical
to glaucoma suspect monitoring and follow-up, as glaucoma pro-
gression can be slowed but is currently not curable or reversible,
and thus it is ideal to identify rapid progressors early. Color stereo-
photography has long been the accepted method for documenting
optic nerve head appearance, especially as the technology required
to perform such tests is unlikely to be outdated over time and
sometimes glaucoma takes years to develop. Precision medi-
cine emphasizes customized therapy to each individuals rate
of disease development, and serial high-resolution OCT is a
rapidly emerging area for individualized early detection of
change.31 Repeat automated structural testing at a very high re-
producibility allows each individual to have his or her own
normative data or change from baseline rather than relying
on population norms.
VISUAL FIELDS
Perimetry has long been the mainstay test for managing glau-
coma suspects and detecting glaucoma deterioration because it is
the main visual outcome measure. The preferred technique is au-
tomated static achromatic threshold perimetry, commonly with the
central 24- or 30-degree program.32 Both trend and event analyses
are used for establishing change within a series of visual field
tests. Because fields can be highly subjective based on patient
cooperation, repeat confirmatory visual field examinations are
strongly recommended. On average, 3 fields are needed in 1 year
to detect an overall change in mean deviation of 4 dB over 2 years
in a patient with average visual field variability.33 One way to
think about fields in glaucoma suspects is to realize that they
can help differentiate between rapid and slow progressors, which
can affect the choice of therapeutic intervention. With FORUM
image management software (Carl Zeiss Meditec, Dublin, Calif ),
clinicians can easily see the Visual Field Index plotted over time
and look at the Glaucoma Progression Analysis for localized event
changes simultaneously with Visual Field Index trend analysis. In
the OHTS trial, when the 2 study end points of visual field pro-
gression or optic disc change were compared, both were found
to be important, as either could be the first to demonstrate the ini-
tial evidence of glaucomatous damage.34
If identifying preperimetric glaucoma using progression on
OCT accurately predicts perimetric vision loss, then it makes
sense to initiate or increase therapy sooner instead of waiting for
confirmatory visual field changes. If a clinician only has access
to 1 abnormal field, however, then repeat examinations are needed,
as the question is whether the field is stable or still worsening.
Some glaucoma suspects may have normal fields and abnor-
mal OCTs, and still others may have normal fields and nor-
mal OCTs but elevated IOPs. Given these different glaucoma
34 www.apjo.org
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suspect situations, clinicians need to assimilate multiple inputs
of age, vision, IOP, nerve status, and visual field reserve to slow
further vision loss until restorative therapies become available
in the future.
OPTICAL COHERENCE TOMOGRAPHY
Optical coherence tomography, currently spectral-domain
OCT (SD-OCT), is a powerful, rapidly evolving, computer-based
imaging tool that complements fundus photography. Using good-
quality images without artifacts, OCT provides quantitative infor-
mation about the RNFL, optic nerve head, and ganglion cell layer
with high reproducibility. Numerous studies have demonstrated
the sensitivity and specificity of OCT to distinguish between nor-
mal and glaucomatous eyes with an area under the receiver oper-
ating characteristic curve value of approximately 0.9 (best with
more advanced glaucoma).35 The RNFL thickness is the primary
parameter of interest, although the ganglion cell layer with inner
plexiform layer and the ganglion cell complex (ganglion cell com-
plex = ganglion cell layer with inner plexiform layer + RNFL) of-
fer additional information. One reason to obtain both macular and
optic nerve cube scans is that macular thickness maps can be es-
pecially useful in high myopes when the RNFL appears abnormal
because of tilted discs. Event and trend analyses are applied to
OCT parameters just as they are for visual fields; however, some
unresolved issues are whether all eyes have a linear rate of struc-
tural loss, if age-related loss varies as a function of baseline
RNFL, and how to accommodate old data when there are so many
different machines with nonshareable data.35,36 With Cirrus
SD-OCT (Carl Zeiss Meditec), clinicians have the RNFL thick-
ness and deviation maps to view localized event changes com-
bined with the Guided Progression Analysis trend analysis tool.
As SD-OCT is highly reproducible with a resolution of approxi-
mately 5 m, the trend analysis is a powerful way to align each im-
age using blood vessel registration and compare the same spot
every time to detect subtle changes in early disease when all the
scans are of good quality and similar signal strength. One down-
side of OCT is that glaucoma tends to progress slowly through
the years (and sometimes, the technology changes faster than
the disease).
A recent longitudinal study estimating the diagnostic accu-
racy and lead time of OCT detection of glaucoma before the
development of field defects found that the receiver operating
characteristic curve areas were 0.87, 0.77, and 0.65 at 0, 4, and
8 years before visual field loss, respectively. At 95% specificity,
up to 35% of eyes had abnormal average RNFL thickness 4 years
before the development of visual field loss, demonstrating the
powerful use of OCT in glaucoma suspects to detect glaucoma be-
fore fields.37 In advanced glaucoma, checking OCT is less useful
because there is no RNFL left to measure, only residual glial and
blood vessels. In those cases, serial visual field testing is more
useful. In an important study to determine the RNFL thickness
at which visual field damage becomes detectable, Wollstein et al38
found that the mean SD-OCT RNFL thickness threshold for visual
field loss was 75.3 m (95% confidence interval, 68.981.8) in
their study population of 74 normal and 40 glaucoma subjects.
Thus, one of the main strengths of OCT in glaucoma suspects
is that a normal RNFL scan reveals with a high likelihood that
glaucoma is not present. Serial OCT RNFL typically detects con-
version to glaucoma in one of 3 ways: 1) expansion of RNFL de-
fect, 2) development of new defect, or 3) deepening of existing
defect.39 The defects are most commonly located at the infero-
temporal meridian and should be studied carefully on the RNFL
thickness maps. Any suspected new change should be assessed
in terms of consistency with other clinical features.
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Asia-Pacific Journal of Ophthalmology Volume 5, Number 1, January/February 2016
PROMISING GLAUCOMA TESTING MODALITIES
Because glaucoma pathogenesis begins at the ganglion cell
level, an ideal imaging technique to diagnose and monitor glau-
coma would quantify RGCs noninvasively with high specificity
and sensitivity in vivo. Such a test would optimally label the un-
healthy cells before inevitable apoptosis occurs, opening the door-
way to neuroprotection or other regenerative therapies. Current
cellular markers under study in vivo are fluorescent labels, includ-
ing CapQ and Annexin-A5.40 However, these probes are used
mostly in animal models and are just starting to be used in phase
I trials. The difference between the proportion of apoptotic cells
in healthy eyes compared with glaucomatous eyes is not yet clear.
As glaucoma is not limited to the loss of RGCs but also ex-
tends to the posterior visual pathway, there is a potential to use
advanced morphological and functional magnetic resonance tech-
niques to detect glaucomatous optic neuropathy. Whereas most of
the techniques (morphometry, diffusion tensor imaging, arterial
spin labeling, and functional connectivity) can only detect qualita-
tive changes in advanced glaucoma, diffusion tensor imaging has
demonstrated some promise in identifying early glaucoma. In pa-
tients with glaucoma, diffusion tensor imaging identified an in-
crease in mean diffusivity and a decrease in fractional anisotropy
more evident at the proximal site of the optic nerve. This suggests
that studying the entire optic pathway in glaucoma with magnetic
resonance may yield a new imaging biomarker.41
Perimetry has used different stimulus size, color (blue on yel-
low short wavelength automated perimetry), and contrast gratings
(achromatic vertical sine wave grating of low spatial frequency at
a high temporal frequency = frequency doubling technology) all
in an attempt to identify earlier glaucoma damage. An emerging
technology called microperimetry uses stimuli projected di-
rectly onto the retina, with accurate test-retest of the same retinal
point made possible by high-speed tracking of the fundus image.
The difference between SAP and microperimetry is that the retinal
sensitivities for SAP are an average of various points located
within a fixation area as large as 5 degrees in diameter, whereas
for microperimetry, the retinal sensitivities are located within an
area as small as 0.5 degrees, a feat accomplished by using real-
time tracking to compensate for any microfixation changes.42
One caveat is that the stimulus intensity of the microperimeters
does not directly compare with SAP. The main advantage of
microperimetry, then, is monitoring retinal sensitivity changes in
the same spot across time using the same instrument. Current re-
search on microperimetry in glaucoma has focused on evaluating
macular sensitivity changes in advanced glaucoma,43 but more re-
search is needed before treatment decisions can be based on
microperimetry results.
Another exciting area for monitoring the glaucoma suspect is
telemedicine, or teleglaucoma. Information technology has been
rapidly improving, and the related regulatory, legal, and financial
issues are starting to diminish. Teleglaucoma-friendly technology
is now more common, including digitized IOP readings, disc pho-
tographs, OCT, and SAP. In remote glaucoma management, the
outcome of interest is the number of false-negatives or missed
cases who are losing vision.44 So far, single test diagnostic screen-
ing is still of limited value even in high-risk groups. In the Northern
Alberta remote teleglaucoma program, a collaborative care ap-
proach was taken between optometrists locally and ophthalmolo-
gists remotely. Of the 247 patients followed, 27% were referred
for in-person glaucoma evaluation, 69% managed by their refer-
ring optometrist, and 48% required repeat teleconsultation.45 Al-
though cost savings may be achieved, teleglaucoma is still in its
early stages and seems to be best suited for areas with poor access
to ophthalmic care.
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Glaucoma Suspect
MANAGEMENT
The management of glaucoma suspects, particularly the sub-
category who have a high IOP, has been largely influenced by the
OHTS and EGPS trials. The primary goal of glaucoma therapy is
to slow visual deterioration such that the patient experiences no
symptoms from the disease during the course of his or her life-
time. Intraocular pressure is the only modifiable parameter in
glaucoma, and the decision to treat with medicines, laser, or sur-
gery can be complex. Clinicians should take into account various
disease risk factors, prognosis, and patient wishes in addition to
risks, side effects, expense, and compliance to long-term treat-
ment. Individualized risk assessment is important and should take
into account age, life expectancy, and quality of life.22,23,46 Two
sometimes difficult decisions regarding glaucoma suspects in-
clude deciding when to treat and, if so, with which therapy. For
a slowly progressive disease, observation is always a choice. All
treatment decisions involve a risk/benefit analysis pitting the nat-
ural history of the disease against the likely outcome with a given
therapy. A decision to treat may arise when testing confirms pro-
gression, when eye pressure is at a level where damage is very
likely to occur, or when the risk factors are overwhelmingly in fa-
vor of needing therapy to preserve vision.
MEDICATIONS
In the developed world, unless contraindicated, eye drops are
most commonly the first intervention to lower IOP. The choice of
medication is often affected by insurance plan coverage, but the
first-line agent for glaucoma suspects is typically a prostaglandin
analog (PGA). These medications are generally the most effective,
but eye drops need to be checked for a therapeutic response. Be-
cause medicine only works when it is taken, adherence is maxi-
mized by selecting the medication with the least side effects and
the easiest dosing interval. After a partial but insufficient response
to a PGA, occasionally an intraclass switch is used or advance-
ment to laser trabeculoplasty47,48 is considered, with selective la-
ser trabeculoplasty (SLT) sometimes being a first-line therapy.49
Alternatively, other topical glaucoma medication classes, includ-
ing alpha2-agonists, beta-blockers, carbonic anhydrase inhibitors,
or fixed-combination ocular hypotensive agents, may be consid-
ered as adjuncts to prostaglandins. Most of the time, with each ad-
ditional medicine given, the IOP-lowering effect is diminished
compared with monotherapy. Factors influencing selection in-
clude efficacy, cost, side effects, dosing frequency, and the effect
on the diurnal IOP curve.50 A meta-analysis of 10 studies looking
at the additive effect of the above 3 medication classes when com-
bined with PGAs revealed a statistically similar reduction in mean
diurnal IOP ranging from approximately 2.3 to 3.0 mm Hg.51 As a
reference comparison, initial monotherapy with PGAs was found
to lower IOP by 8 to 8.6 mm Hg from an elevated baseline in the
XLT study.52 One other reason for considering PGAs as first-line
therapy is that these agents have been shown to lower nocturnal
IOP better than other classes. Unfortunately, because glaucoma
suspects are asymptomatic, adherence to medication can be poor,
as demonstrated in 1 electronic dosing aid study where nearly
45% of patients took fewer than 75% of their prescribed doses.53
LASER TRABECULOPLASTY
Laser therapy such as SLT may benefit high-risk glaucoma
suspects as either a primary therapy choice over medicines or as
an adjunctive therapy.4749 Selective laser trabeculoplasty is as
effective as argon laser trabeculoplasty or a single ocular hypoten-
sive agent in reducing IOP in glaucoma and ocular hyperten-
sion.54 The treatment effect is not equal among all individuals
and also decreases over time, but the procedure is repeatable.55
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Chang and Singh Asia-Pacific Journal of Ophthalmology Volume 5, Number 1, January/February 2016
Adverse effects are minimal, such as postlaser intraocular inflam-
mation or transient IOP spikes, which generally resolve quickly. A
few isolated cases of transient corneal stromal edema have been
reported.56 The major advantages of laser trabeculoplasty over
medications for glaucoma suspects are not having to worry about
compliance, avoiding drop toxicity, and convenience. Positive cost
savings have been modeled for SLT as a primary therapy.57 Given
some patient reluctance to having a procedure performed initially,
it is important to present medicine and laser trabeculoplasty
equally to avoid bias among newly diagnosed patients. Even
though PGAs are associated with a generally safe side effect pro-
file, some individuals have concerns about the iris color and other
periocular cosmetic changes, and these patients may be ideal can-
didates for SLT. One study published a 5-year follow-up of SLT
versus medications in 58 Chinese eyes with POAG or ocular hy-
pertension, and SLT showed a similar reduction in IOP compared
with medical therapy alone.58 Thus, SLT use is associated with
short-term evidence and some long-term data supporting its use
as a first-line therapy for glaucoma suspects.49
CATARACT SURGERY
Surgery is generally not a first-line therapy for glaucoma sus-
pects, but there is mounting evidence that cataract surgery alone
lowers IOP. If glaucoma suspects are taking eye drops and are go-
ing to have a cataract removed, then there is also an opportunity to
combine cataract surgery with minimally invasive glaucoma sur-
gery with strong safety profiles to control IOP without medica-
tion. Such an approach is controversial in individuals for whom
a glaucoma diagnosis has not been confirmed. There seem to be
some promising minimally invasive glaucoma surgery choices
on the horizon that are performed in combination with cataract
surgery.59 In addition, cataract removal can improve imaging of
the optic nerve and assist in the interpretation of perimetric testing.
One other benefit of cataract surgery before filtering surgery is
that it can be advantageous to have already removed the lens both
for technical reasons and for trabeculectomy failure rates after
phacoemulsification.60 However, the emphasis here is not to con-
vey cataract surgery as a treatment for glaucoma suspects, as there
is no current evidence to support this, but to acknowledge the
trend of IOP reduction in some patients.
Multiple retrospective studies suggest that cataract extraction
produces a significant and sustained IOP reduction in individuals
with open-angle glaucoma, ocular hypertension, and angle-closure
glaucoma. For ocular hypertensives, analysis of the OHTS fellow
eye data revealed that postoperative IOP after cataract surgery had
a significant mean decrease of 16.5% for at least 3 years.61 In a re-
cent study from India, clear lens extraction led to a significant re-
duction in IOP from 27 to 13 mm Hg at 12 months in 44 eyes
with PACG and persistently raised IOP after laser peripheral
iridotomy.62 Although that scenario is still controversial, symp-
tomatic cataracts affecting daily life are indicated for removal and
may lower IOP in those with narrow angles, hyperopia, and thick
anteriorly vaulted lenses.63
In summary, the diagnosis and management of the glaucoma
suspect continue to evolve and are aided by advances in technol-
ogy that allow us to confirm the disease earlier, follow progression
more accurately, and treat with better therapeutic options.
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