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Treating Patients Presenting With Advanced

Glaucoma
Should We Reconsider Current Practice?
Anthony J King; Richard E Stead; Alan P Rotchford
Br J Ophthalmol. 2011;95(9):1185-1192.

Abstract and Introduction

Abstract

The management of patients presenting with advanced glaucoma presents a challenge to glaucoma clinicians.
Presentation with advanced visual field loss is an important risk factor for progression to blindness in the affected
eye(s) during the patients' lifetime. Maximising intraocular pressure (IOP) control in such situations is likely to minimise
the risk of further visual field deterioration thus either preventing or slowing progression to blindness. Currently most
patients presenting with advanced disease in the UK are managed on an escalating regime of medical treatment.
Should this fail glaucoma surgery is usually employed to further lower IOP. Although glaucoma surgery is generally a
safe and successful intervention it carries a small risk of severe visual loss and is considered by many clinicians as an
intervention only to be used following failure of medical treatment. Recently however the National Institute for Clinical
Excellence has suggested in its clinical guidelines for management of ocular hypertension and glaucoma that primary
surgery should be offered to patients presenting with advanced glaucomatous visual field loss. This is contrary to the
practice of most UK ophthalmologists. In this review the current available evidence underlying the management of
presentation with advanced disease is examined.

Introduction

Glaucoma is a potentially blinding condition and the second most common cause of visual impairment registration in
the UK. Patients most at risk of blindness during their lifetime are those who present with advanced disease. This
distinction is recognised in the recently published National Institute for Health and Clinical Excellence (NICE)
guidelines in which the suggested management approaches for patients presenting with advanced and early disease
differ.[1] The principle difference is the recommendation that primary surgical intervention should be offered to patients
with advanced disease. This review examines the evidence supporting this recommendation.

Background and Epidemiology

The WHO estimates that in 2010, 4.5 million people are blind due to glaucoma1a, accounting for 12.3% of global
blindness. A substantial increase is predicted over the next few years.[2] These figures are almost certainly an
underestimate because of the way in which causes of blindness in patients with more than one pathology are assigned
in prevalence surveys, and because most blindness surveys do not consider subjects functionally blind due to severely
restricted visual field.

In the UK and other similar populations, glaucoma is estimated to be present in about 2% of the population over the
age of 40 years, increasing with age[3–7] and affecting as many 10% of those in their 80s. It is the second commonest
cause for registration as visually impaired in the UK, accounting for 11.6% of registrations over the age of 65 years,[8]
although, again, this is likely to be underestimate.[9]

Between 10% and 39% of patients with glaucoma present with advanced disease in at least one eye in the UK.[10–15]
In the most recent study, more than a third of patients presenting had severe disease in at least one eye at
presentation.[10] Those most at risk include the socially disadvantaged with no family history of glaucoma, those with
high intraocular pressure (IOP) and those who do not attend an optometrist regularly.[10 16 17]

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Advanced Glaucoma at Presentation—A Risk Factor for Blindness

Presentation with advanced visual field loss increases the risk of further progression and blindness[11 13 18–21] Grant
and Burke[11] found that eyes with a visual field defect at the beginning of treatment were more likely to progress to
blindness than eyes in which treatment was started when there was no field loss. Odberg[18] noted in a cohort of
patients with advanced glaucoma 70% of the affected eyes had progressed after a mean of 7.6 years despite
treatment. Wilson et al[20] found that initial field loss was the strongest determinant of the rate of further field loss. The
rate of deterioration was 11.7 times faster in eyes with more advanced field loss at presentation.

Mikelberg et al[19] found that when scotoma mass was small the rate of visual field loss was slow, but when large,
rapid linear progression of visual field loss occurred. Oliver found that unilateral blindness more than doubled the risk
of blindness.[22]

Current Treatment Options

Reducing IOP is currently the only effective treatment for glaucoma.[23–26] The Advanced Glaucoma Intervention
Study (AGIS) demonstrated that the extent of IOP-lowering was related to the progression of visual fields over an 8-
year period, showing that progression was least when IOPs were Hg at all follow-up visits. maintained below 18
mm[27]

Primary treatment may involve a medical, laser or surgical intervention. Currently most ophthalmologists treat patients
medically starting with topical drop monotherapy followed by escalating drop therapy until maximum tolerated therapy
is achieved. In patients who continue to progress or in whom target IOP is not achieved, clinicians may opt for surgical
intervention, most frequently trabeculectomy, which may or may not be preceded by laser therapy[23–26 28–35]

Should we Change Current Practice?

A recent systematic review[23] comparing primary medical versus surgical treatment for open angle glaucoma (OAG)
identified four studies that were considered relevant ( and ). Despite methodological weaknesses and although the
treatments compared are not currently standard clinical practice,[24 36–38] the authors concluded that "in more severe
open-angle glaucoma there is some evidence, from three trials[36–38] that medication was associated with more
progressive visual field loss Hg less intraocular pressure lowering than surgery. and 6 to 9 mm In the longer-term[36 37]
the risk of failure of the randomised treatment was greater with medication than trabeculectomy (OR 3.90, 95% CI
1.60 to 9.53; HR 7.27, 95% CI 2.23 to 25.71)." The authors concluded that surgery lowers IOP more than medication;
however, none of these trials specifically addressed the management of patients presenting with advanced glaucoma
and the authors recommended that further randomised controlled trials of current medical treatments compared with
modern glaucoma surgery are required in people with advanced OAG.[23]

Table 1. Summary of randomised controlled trials comparing medical versus surgical treatment of glaucoma—study
design and baseline characteristics

Outcomes Disease
Study Inclusion criteria Exclusion criteria Interventions
measured severity

1. POAG, PXF or
pigmentary in
one or both eyes;
1. Cumulative
2. One of three lifetime use of
combinations of eye drops for
qualifying glaucoma >14

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Goldman days; Surgery:

Progressive VF
applanation IOP trabeculectomy
loss: Humphrey
>Hg, 20 mm 2. Any eye drops (with or without 5-
24-2 perimetry,
Humphrey visual for glaucoma in fluorouracil at the
with a scoring
field changes and 3 weeks prior to surgeon's
method designed
optic disc baseline visit 1 discretion) within
for the study,
findings: (washout from 14 days of
recorded every 3
≤14 days randomisation, if
months.
a. IOP >Hg, permitted); failure then ALT
HRQOL:
24-2 with then sequence of
3. CIGTS score measured using
three medications, then
>16.0 either disease specific
contiguous repeat
eye; and generic
points on trabeculectomy Hg) IOP
measures = (1)
the total with antifibrotic (mm
4. Other ocular symptom and
deviation agents, then medicine
disease that health problem
20 mm repeat group 27.6
might affect IOP check
plot at medications. (5.5)
readings, list, (2) Visual
<2% level Criteria for surgery
assessment of Activities
and GHT intervention failure group 27.4
visual function, Questionnaire, (3)
outside had to be met (5.7)
visual field Glaucoma Health
normal each time that a VA score
testing and/or Perceptions Index
and optic further treatment (logMAR)
facility of (4) Sickness
discs step was initiated. medicine
aqueous Impact
compatible Medical: group 85.6
CIGTS24 outflow; Profile, (5) CES-
with sequence of (5.9)
N=607 D, (6) Health
glaucoma. medications, surgery
5. Proliferative Perceptions
usually beginning group 85.8
b. IOP >Hg diabetic Index.
with topical beta- (5.5)
and 24-2 retinopathy, IOP: GAT
blocker followed VF score
with at diabetic macular recorded three
by an alternative (CIGTS
least two oedema or non- monthly.
single topical scale)
contiguous proliferative VA: ETDRS.
agent, dual, triple medicine
points in diabetic Incidence of
then alternative group 4.6
the same retinopathy with cataract surgery.
topical and or oral (4.2)
26 mm more than ten Treatment
medications. If surgery
hemi-field microaneurysms crossover after
further treatment group 5.0
on total by clinical count intervention
required, the next (4.3)
deviation at baseline; failure.
treatment step
probability Adverse events:
6. Undergone was ALT followed
plot at mortality (overall
ophthalmic by trabeculectomy
<2% level deaths but not by
laser, refractive, (with or without 5-
and GON. intervention
conjunctival or fluorouracil at the
group); surgical
intraocular surgeon's
c. IOP >Hg complications
surgery in either discretion), repeat
with GON, reported but for all
eye; medication, repeat
not eyes (ie, including
trabeculectomy
required to the other eye not
7. Likely to require with antifibrotic
have included in the
cataract surgery agents, repeat
visual field trial).
within a year of medication
changes;
randomisation;
27 mm

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3. Best corrected 8. Current or

EDTRS >70 expected use of
(Snellen corticosteroids.
equivalent 20/40
in each eye).

Progressive visual
field loss: Lister
manual perimetry.
Outcome
measured as
mean score
difference
Surgery: modified between
Scheie's intervention
1. Hg on two 1. Previous
procedure with groups.
occasions IOP glaucoma
sector iridectomy IOP: GAT
≥23 mm surgery Hg; Mean
Medical: VA: Snellen acuity
Moorfields baseline
pilocarpine 2%, (expressed as
GT 2. Visual field loss 2. Black race IOP 25 mm
guanethidine, percentage eg,
196838 compatible with Disease
3. Other epinephrine. 6/6=100%,
N=43 glaucoma severity: not
ophthalmic Timolol 6/60=10%). Long-
defined
3. Glaucomatous abnormalities of incorporated term outcome
cupping importance 1979. Surgery if measured as
adequate control score difference.
not achieved Need for
additional
medicine or
surgery due to
intervention
failure only
reported for
medical group.

66/107°
Progressive field
(62%) had
loss: fields
severe
Surgery: measured using
glaucoma
trabeculectomy. Tubingen manual
defined by
Subsequent perimetry.
investigators
medical therapy Classified into five
as field
introduced as stages of loss*.
stage 2–5.
1. All of: clinically Significant
Field stage
indicated. change defined
2. previously 1 (n=41)
Medical: up to as at least one full
undiagnosed Hg Mean
three different stage of
case of POAG or IOP 32.23
topical or systemic classification from
open angle mm
ocular diagnosis.
glaucoma with Field stage
hypotensive IOP: GAT
PXF 2 (n=12)
Glasgow agents. If max Progressive optic
Hg Mean
medical treatment disc damage:

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trial37 48 3. Untreated IOP Not specified insufficient to change in vertical IOP 40.5
N=116 >Hg (GAT) on control IOP or cup to disc ratio of mm
two occasions 26 prevent field loss >±0.1. Field stage
mm then VA: Snellen. 3 (n=17)
trabeculectomy Adverse events: Hg Mean
4. Visual field performed. mortality; severe IOP 38.24
defects Treatments irreversible mm
characteristic of include miotics, reduction of Field stage
glaucoma beta blockers, vision: onset of 4 (n=30)
guanethidine, cataract. Hg Mean
epinephrine or No fixed criteria IOP 37.54
systemic carbonic for intervention mm
anhydrase failure; treating Field stage
inhibitors ophthalmologist's 5 (n=7)
clinical Hg Mean
judgement. IOP 40.43
mm

IOP: GAT with

daytime phasing
carried out on
each patient
annually
Surgery: Cairn's Visual fields:
type Friedmann Surgery
1. IOP of at least 24 trabeculectomy analyser (Mark 1). group (n 57)
mm Medical: Two years after Hg Mean
pilocarpine, and/or commencement IOP 34±5.4
2. Cup:disc ratio a of the trial a mm
greater than 0.6, sympathomimetic, Humphrey Stage of
and/or notching, and/or timolol, as perimeter was glaucoma
and/or pallor of the initial therapy, used in addition. Early 17
neuroretinal rim increasing to a A field score of Mid 16
max-tolerated the number of Late 24
3. Glaucomatous medical therapy Medicine
spots missed was
field loss using which could, in group (n56)
calculated at each
the Friedmann individual cases Hg Mean
visit for the
field analyser require three IOP 35±7.9
relative and
Moorfields (Mark 1). Minimal topical absolute spots mm
PTT36 acceptable defect Not specified medications and a missed, giving Stage of
N=168 was loss of at carbonic two numeric glaucoma
least three anhydrase Early 16
values for each
adjacent spots at inhibitor Mid 10
eye at each visit.
intensities 0.4 Laser: two Late 30
Disease staged to
Log units greater treatments argon Laser group
the degree of field
than threshold up laser (n 55)
loss at
to a maximum trabeculoplasty Hg Mean
presentation into
intensity and/or consisting of 50 IOP 35±8.7
early (field score
one absolute burns over 180° of mm
<2 absolute
defect the anterior Stage of
defects), middle
trabecular (field score of 2- glaucoma
4. Open drainage

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angle. meshwork, 12 absolute Early 13

separated by an defects) and late Mid 10
interval of 2 (>12 absolute Late 32
weeks. defects).
Optic discs:
photographed
annually
VA: Snellen

ALT, argon laser trabeculoplasty; CES-D, Centre for Epidemiological Studies – Depression Score; CIGTS,
Collaborative Initial Glaucoma Treatment Study; ETDRS, Early Treatment Diabetic Retinopathy Study; GAT, Goldman
applanation tonometry; GON, glaucomatous optic neuropathy; GT, glaucoma trial; HRQOL, health-related quality of
life; IOP, intraocular pressure; logMAR, logarithm of the minimum angle of resolution; POAG, primary open angle
glaucoma; PXF, pseudoexfoliation; VA, visual acuity.
*Glasgow 1988 staging system. Stage 1: early relative defects (to 1.0/10asb Tubingen; equivalent to 1–2e Goldmann)
in arcuate area or nasal step. Stage 2: absolute defects (to 1.0/00asb Tubingen; equivalent to 1–4e Goldmann)
outside 10° of fixation in all quadrants. Stage 3: as stage 2 but encroaching between 5° and 10° from fixation in 1 to 4
quadrants. Stage 4: as stage 2 but within 5° of fixation in 1 to 3 quadrants. Stage 5: as stage 2 but within 5° of fixation
in all quadrants. Excludes four participants who dropped out in the first year and five participants who died.

Table 2. Summary of randomised controlled trials comparing medical versus surgical treatment of glaucoma—
outcomes

Main outcomes

Study IOP control VF progression VA loss HRQOL

Generic
measures—no
statistically
significant
difference
No difference
between the
two treatment
groups for the
total score of
the VAQ.
Approx. 5%
Medically more
treated dysfunction on
patients had the VAQ acuity
Lower IOP found in the primary surgery half the risk subscale
cohort. Difference between groups Hg No difference in VF outcomes of a VA loss demonstrated
CIGTS24 in favour of reduced with time. At 5 between the two groups when of at least 0.3 in the primary
N=607 years the difference was 1.9 mm effect of cataract factored into logMAR surgery cohort.
surgery but this difference was not analysis compared The CIGTS
statistically significant with Symptom
surgically Impact
treated Glaucoma
cohort Scale revealed

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patients
undergoing
primary
trabeculectomy
reported more
symptoms on
the total score
and on the
local eye
symptom
subscale.

No difference
Patients treated medically
Moorfields Hg at long-term follow-up) Initial surgery between
had significantly more
GT associated with greater reduction in IOP groups. Both
increase in VF score Not assessed
196838 compared with medication (approx. 6 groups
(progression) compared with
N=43 mm demonstrated
surgery.
VA reduction.

At the latest follow-up (mean

Surgery Hg compared with associated No difference
4.6 years), 47% (27/57) of
with a lower mean IOP at 1 year (15 between
Glasgow medically treated patients
mm Hg in the medical cohort). 32% of groups in
trial37 48 progressed by at least one Not assessed
the medical cohort underwent 20.8 mm loss of at
N=116 stage of VF severity
trabeculectomy by the end of year 1 least 2 lines
compared with 26% (13/50) in
increasing to 58% at year 4. Snellen
the surgery group. OR 2.56.

Friedman analysis
Surgery associated with significantly
demonstrated patients treated
reduced IOP at 5 years compared with
successfully in the medical
Hg respectively; Hg and 18.5 mm
arm had a significantly
medical treatment (14.1 mm No significant
greater increase in VF score
Moorfields p<0.0001).Trabeculectomy associated difference in
from baseline than patients
PTT36 with less diurnal variation with Hg and mean acuity Not assessed
treated successfully by
N=168 fewer peaks and troughs. Maximum scores over a
primary trabeculectomy. No
mean phasing IOP was 15.5 mm Hg, 5-year period
significant correlation
Hg and 15.9 mm Hg compared with
between stage (ie, starting
22.1 mm minimum mean IOP was 13.1
field score) and subsequent
mm respectively, for medical treatment.
change in field score.

CIGTS, Collaborative Initial Glaucoma Treatment Study; GT, glaucoma trial; HRQOL, health-related quality of life; IOP,
intraocular pressure; logMAR, logarithm of the minimum angle of resolution; PPT, primary treatment trial; VA, visual
acuity; VAQ, visual activities questionnaire; VF, visual field.

The advanced glaucoma intervention study (AGIS) did not specifically address the management of patients with
advanced visual field loss alone, but also included patients on maximum medical therapy with less severe visual field
defects. In addition, it did not compare medical versus surgical treatment options but rather different sequences of
laser and trabeculectomy interventions.[39] Similarly the Collaborative Initial Glaucoma Treatment Study (CIGTS),
while addressing the effects of primary medical and surgical treatment in newly diagnosed patients with glaucoma,
consisted of patients presenting with predominantly early disease (CIGTS score 4.6±4.2).[24] A recent update from
CIGTS suggests that patients presenting with more advanced disease have a better outcome with primary surgery by
demonstrating that patients with more advanced disease at presentation (mean deviation (MD) <−10 db) had slower
visual field progression if their primary intervention was surgical rather than medical.[40]

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NICE has recently produced guidance for the management of glaucoma for England and Wales.[1] NICE recommends
that patients presenting with advanced glaucoma should be offered primary surgery; however, they acknowledge that
the current evidence-base supporting this recommendation is of poor quality.

Evidence for Better Outcomes for Surgical or Medical Treatments

IOP Outcomes

Several large prospective studies[25 27 41–45] have shown that lower mean IOP reduces the risk of glaucoma Hg of
progression. It is estimated that each additional mm post-intervention IOP elevation increases the risk of glaucoma
progression by 12–19%.[45 46]

Odberg[18] in his retrospective cohort of patients with advanced glaucoma noted that lower IOPs were generally
achieved with surgical intervention.

Jay and colleagues[37 47 48] randomly allocated newly diagnosed patients with glaucoma to either conventional
therapy (drops followed by surgery if uncontrolled) or primary trabeculectomy. After 1 year they found a difference in
mean IOP between the groups with that in the medical group at Hg. Hg and in the surgery group at 15.0 mm 20.8 mm

Migdal et al[36] in the Moorfields Primary Treatment Trial (PTT) found the mean IOP was significantly better in the
surgery group at 6 months and Hg for surgery versus Hg and 14.1 mm 5 years (13.4 mm Hg for medical treatment at
Hg and 18.5 mm 20.6 mm 6 months and 5 years, respectively).

The Collaborative Initial Glaucoma Treatment Study (CIGTS) showed that mean IOP was on average Hg lower in the
surgery group during a 4-year follow-up 3 mm period.

Several authors have found significantly less diurnal IOP fluctuation, less marked peak IOP values and a lower mean
diurnal IOP value in surgically treated patients.[39 49 50] Shaarawy et al[51] have concluded that these observations
constitute a definite advantage of surgery over medical treatment. This is supported by the work of Asrani et al[52] who
measured diurnal IOP fluctuation using home tonometry and concluded that diurnal fluctuations contributed to visual
field progression.

Visual Acuity Outcomes

Neither the Glasgow,[37 47 48] Moorfields PTT[36] or CIGTS[24] studies found any significant difference in the mean
loss of visual acuity (VA) between the conventional treatment and surgery groups. The Glasgow study did note that six
patients in the conventional group lost central fixation during the follow-up compared with none in the surgery group,
whereas in the CIGTS[24] there was an initial reduction in VA in the surgery group that took 4 years to equalise with the
medically treated group.

However, none of these studies was specifically looking at these outcomes in patients with advanced glaucoma.

Visual Field Outcomes

Both the Glasgow[37 47 48] and Moorfields PTT[36] studies found more visual field deterioration in the patient groups
treated with primary medical treatment.

CIGTS found no overall difference in visual field progression between groups; however, a recent CIGTS[40] report
identifies an interaction between treatment group and baseline visual field loss, indicating that subjects who presented
with more advanced visual field loss showed better visual field control over time when treated with initial surgery
versus initial medications. At 7 years after treatment initiation in patients who had an MD of −10 dB or worse at
baseline, those treated surgically had on average a 1.03 dB better MD than those treated medically (p=0.01). No such
effect was seen in subjects with mild visual field loss at presentation (−2 dB or better). Although such subgroup

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analysis needs treating with caution, this supports previous observations made by Odberg.[18]

In addition to the better outcomes demonstrated by several studies it is important to acknowledge that prolonged
attempts at medical management of glaucoma can result in further progression,[53] an even more important
consideration when considered in the context of subjects who already have advanced disease.

Treatment Crossover
In both the Glasgow[37 47 48] and Moorfields PTT,[36] treatment crossover was much more likely from medical to
surgical groups than vice versa. The Glasgow study found that at 1 year after enrolment 32% of the medical group had
had surgery and by 4 years this had risen to 53%. However, for patients with more advanced visual field loss and
significantly elevated IOP despite treatment the operation rate was 58% at 1 year and 75% at 3 years. In contrast only
15% of the eyes treated in the surgery group required additional medical treatment. The participants treated with
conventional medical therapy were four times more likely to have failed compared with trabeculectomy participants.[23]

In the Moorfields PTT,[36] over a 5-year follow-up period, initial medical treatment was less Hg or less than primary
likely to achieve an IOP 22 mm trabeculectomy did, and required crossover to one or other of the alternative treatment
arms (HR 7.3).[23]

In CIGTS[24] no statistically significant crossover difference was demonstrated between the groups.[23] However in the
CIGTS protocol argon laser trabeculoplasty (ALT) was an intermediate treatment step before crossing over to the
alternative treatment. Participants treated initially with medications were significantly more likely to need ALT at 1 year
(OR 2.4) and 4 years (OR 1.5) compared with primary trabeculectomy.[23] There was no subgroup analysis for those
presenting with more advanced disease.

Safety
Surgery-related Complications

One of the primary concerns when considering trabeculectomy is the potential of a sight-threatening complication.
While complications are a risk, modern glaucoma surgery techniques as developed by Khaw and colleagues[54–59]
have greatly reduced the risk of both intra- and postoperative complications.

The UK national trabeculectomy surgery survey,[60] which reported outcomes of more than 1200 trabeculectomies,
reported early complications in 578 cases (46.6%) and late complications in 512 cases (42.3%).

Several subsequent large randomised surgical intervention series have since reported much more encouraging
results. Singh et al[61] compared the safety and efficacy of 5-fluorouracil (5-FU) and mitomycin C (MMC)
trabeculectomies in primary glaucoma and found very low complication rates with the use of either antimetabolite after
1 year of follow-up. No episodes of endophthalmitis or blebitis were reported.

CIGTS[24] reported complications from all surgeries including fellow eye procedures (n=525). Intra-operative
complications included intra-operative bleeding in the anterior chamber (7.1%) and conjunctival buttonhole (1.0%).
During the first postoperative month, the most frequent complications were shallow or flat anterior chamber (14.2%),
encapsulated bleb (11.9%), ptosis (11.9%), serous choroidal detachment (11.3%), and anterior chamber bleeding or
hyphaema (10.5%). The CIGTS Data and Safety Monitoring Committee did not identify any safety issues of concern.

Wong et al[62] reported no cases of endophthalmitis, hypotonous maculopathy, retinal detachment or blindness
following surgery in either group in the Singapore 5-Fluorouracil Trabeculectomy Study after 3 years of follow-up. They
reported a choroidal effusion rate of 6.8% that resolved without any residual visual consequences.

Cataract Formation

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Patients undergoing glaucoma surgery are at an increased risk for the development and progression of cataract.[63]
CIGTS[24] reported that initial surgical treatment resulted in the development of more cataracts requiring removal than
initial medical treatment. The crude proportion of cataract extraction in the surgery group (17.3%), unadjusted for
variable follow-up, was almost three times greater than the proportion in the medicine group (6.2%) (p<0.0001). AGIS
demonstrated a 78% increased risk of either developing cataract or undergoing cataract surgery in eyes that had
undergone trabeculectomy surgery.[64] Interestingly, evidence suggests that topical glaucoma treatment also
accelerates cataract formation.[44 65] A recent Cochrane review[23] summarised the incidence of cataract from three
trials[24 36 48] to be in the order of 14% in surgically treated eyes compared with 6% of medically treated eyes.

The Singapore 5-Fluorouracil Trabeculectomy Study[62] reported the number of patients who underwent cataract
surgery was comparable in both 5-FU (50%) and placebo groups (54%). No complications (intra-operative or
postoperative) were encountered with the cataract surgeries. Furthermore, there was no significant effect of cataract
surgery on IOP failure between the operated and unoperated patients at 3 years follow-up, although this remains an
area of controversy.[66 67]

Health-related Quality of Life Outcomes From Glaucoma Interventions

Only CIGTS has evaluated quality of life between medical and surgical treatment of glaucoma. CIGTS[68] found no
specific difference at 4 years follow-up for generic measures. For vision-specific measures it found no difference for
the overall visual scores; however, those who underwent surgery had a slightly worse visual acuity subscale
assessment at several time-points and complained of more visual dysfunction, such as visual blurring or difficulty with
bright lights, and local eye symptoms, such as foreign body sensation, ocular pain, etc. These differences between the
groups peaked at 12 months and disappeared over the subsequent years. Despite the suggestion of more problems
related to primary surgery, patients' satisfaction for their treatment (rated as moderately or very successful) was similar
for both groups from about 12 months following initiation of treatment.

It is important, however, to remember that this was a group of patients with early visual field loss and that this may not
be applicable to patients with more advanced disease in whom visual symptoms are likely to be more pronounced.

Economic Considerations
The severity of glaucoma affects the cost of treatment.[69] Economic analysis comparing primary surgery against
primary medical treatment for glaucoma is limited[40] and does not exist for patients presenting with advanced
glaucoma. The Glasgow study suggested no material difference in the costs of treatment between medical and
surgical treatment arms;[70] however, the average inpatient stay was 7.6 days. It is likely that the cost of surgical
intervention would be significantly lower today.[70] Burr et al.[23] addressed this by applying current NHS costings to
the Glasgow data, including a single day inpatient stay for those undergoing surgery. This analysis suggested that the
primary surgery approach would be less expensive (£1404 for initial medical therapy against £1130 for initial surgery
treatment). It is likely that the surgery cost would be even lower now as most trabeculectomy surgery is performed as
a day case procedure. However, these shorter inpatient savings may be mitigated by more intensive postoperative
follow-up and intervention[71] and thus these figures may not be applicable to modern practice.

Discussion
With the limited evidence available, surgery appears to offer better IOP and visual field outcomes than medical
treatment for advanced glaucoma; however, there is a continued reluctance among ophthalmologists to advocate this
as primary treatment. This is understandable for patients with early glaucoma but less so in those with advanced
disease, who are more likely to go blind as a result of disease progression. There are several other arguments
supporting the primary surgery approach. A large proportion of patients started on medical treatment will be non-
adherent to their medication[72–80] and are therefore likely to progress. These non-adherent patients are likely to be
tried on multiple different medical options and have frequent outpatient follow-up visits to monitor their IOP before a

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decision to operate is made. Some patients will not respond adequately despite adherence to the currently available
medication or will be intolerant or allergic to them. Attempts at medical control of IOP in these patients would result in a
delay in successful IOP reduction and may result in further visual field progression.[53] Multiple outpatient visits have
economic implications and exposure of the eye to multiple drop therapies for prolonged period may affect the success
of subsequent surgery.[81–84] The risk of non-adherence and its consequent disease progression and resource
implications would be reduced with primary surgery.

However, surgical intervention is associated with risk and in the worst instance catastrophic loss of vision due to either
early or late complications. Despite glaucoma surgery becoming safer there is a reluctance with the current limited
evidence base on the part of both clinicians and patients to expose patients to this risk. Indeed, a recent survey of
consultants' opinions in the UK has suggested that the main reason for not advocating primary surgery is the concern
regarding surgical complications; interestingly, however, a large proportion indicated that they would be willing to
change their practice should evidence support primary surgery.[85]

There is a suggestion of marginally more quality of life problems in those undergoing primary surgery in the CIGTS
study, but equal numbers of patients from both groups were satisfied with their treatment. Patients in the Moorfields
PTT who had bilateral glaucoma and who were randomised to the surgery group uniformly requested they have
surgery to the unoperated eye[86] Indeed, patients themselves are less concerned with the mode of treatment they are
exposed to and more concerned about the effectiveness of that treatment in prevention of visual loss.[87]

The effect of severe glaucoma and blindness on patients' quality of life is profound,[88] placing a burden on society and
healthcare resources.[89–91] It is possible that there is no lifetime solution currently available to manage patients
presenting with advanced glaucoma as the results of both medical[92–94] and surgical[95–97] intervention diminish with
time. However, establishing which of the options is likely to lead to more prolonged visual stability and better quality of
life will direct clinicians to the best way to initiate primary therapy.

Recently published guidance from NICE[1] has recommended primary surgical intervention for patients presenting with
advanced disease. The evidence supporting this recommendation is limited and often inferred, as there are currently
no studies comparing modern medical against modern surgical interventions in patients presenting with advanced
disease. The best way to address this issue would be a randomised trial comparing primary surgery against the
currently used scaled approach to medical treatment in patients presenting with advanced disease. A future study
should be adequately powered to answer the questions of visual field progression, intervention safety, health-related
quality of life measurements, and to allow a health economic evaluation. This information would put us in a better
position to offer evidence-based advice to patients and healthcare services.

With the current available evidence there is no reason for clinicians to adopt the approach suggested by NICE of
primary surgical intervention. Clinicians should continue to manage patients according to their current practice until
more decisive evidence becomes available.

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Competing interests
None declared.

Provenance and peer review

Not commissioned; externally peer reviewed.

Br J Ophthalmol. 2011;95(9):1185-1192. © 2011 BMJ Publishing Group

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