Therapeutic options - Canadian Ophthalmological Society

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Canadian Ophthalmological
Society
Evidence-based Clinical Practice
Guidelines for the Management of
Glaucoma in the Adult Eye
Therapeutic Options for
Lowering IOP
Therapeutic options
• Options for lowering IOP include:
– the use of topical or systemic medications,
– laser trabeculoplasty,
– surgery to improve outflow facility, and
– cyclodestructive laser to reduce aqueous
production.
Canadian Ophthalmological Society evidence-based clinical
practice guidelines for the management of glaucoma in the
adult eye. Can J Ophthalmol 2009;44(Suppl 1):S1S93.
Patient involvement in
decision to treat
Recommendation
Initiation of medical therapy should involve
discussion with the patient about the nature of the
disease, risks and benefits, and common side
effects. The patient, and their caregivers, should
be involved in the therapeutic decision-making
process [Consensus].
Canadian Ophthalmological Society evidence-based clinical
practice guidelines for the management of glaucoma in the
adult eye. Can J Ophthalmol 2009;44(Suppl 1):S1S93.
Medical management and
QOL considerations
Recommendation
In order to maximize patient QOL and adherence
to the treatment regimen, the clinician should strive
to utilize the minimum number of medications with
the minimum dosing frequency to achieve the
target IOP range [Consensus].
Canadian Ophthalmological Society evidence-based clinical
practice guidelines for the management of glaucoma in the
adult eye. Can J Ophthalmol 2009;44(Suppl 1):S1S93.
Uniocular therapeutic trials
Recommendation
A uniocular therapeutic trial could be considered to
evaluate the efficacy, as well as tolerability, of
newly initiated topical therapy. This would apply
particularly to individuals with bilateral disease in
whom baseline IOPs have been determined to be
symmetric [Consensus].
Canadian Ophthalmological Society evidence-based clinical
practice guidelines for the management of glaucoma in the
adult eye. Can J Ophthalmol 2009;44(Suppl 1):S1S93.
Documentation of
medical management
Recommendation
Monitoring of patients should include
documentation of the IOP (method and time
measured), patient confirmation of and frequency
of medications used, as well as the time of their
last medication administration [Consensus].
Canadian Ophthalmological Society evidence-based clinical
practice guidelines for the management of glaucoma in the
adult eye. Can J Ophthalmol 2009;44(Suppl 1):S1S93.
Optimizing patient adherence
• Adherence to therapy is fairly poor.1–3
• Minimizing the number of medications may
improve adherence.4
• There is no clear evidence linking reduced
adherence with more rapid VF deterioration.1
• However, educating patients about their
disease and treatment should ultimately:
– improve patient adherence, and
– reduce risk of significant progression.1
1.
2.
3.
4.
Olthoff CM, et al. Ophthalmology 2005;112:953–61.
Zhou Z, et al. Br J Ophthalmol 2004;88:1391–4.
Sleath B, et al. Ophthalmology 2006;113:431–6.
Patel SC, et al. Ophthalmic Surg 1995;26:233–6.
Canadian Ophthalmological Society evidence-based clinical
practice guidelines for the management of glaucoma in the
adult eye. Can J Ophthalmol 2009;44(Suppl 1):S1S93.
Glaucoma Medications
Used for Chronic Treatment
Alpha-2 adrenergic agonists
Generic name
Trade name
apraclonidine
0.5%, 1.0%
Iopidine
brimonidine 0.2%
Alphagan
Mechanism of
action
Decreases aqueous
production (prevents
severe elevation of
IOP following laser
procedures)
Decreases aqueous
production and
increases
brimonidine 0.15% uveoscleral outflow
Alphagan-P
(using Purite as
preservative)
Efficacy* and
dosing
Maximum effect
in 4–5 hours
Considerations
• High rate of allergy limits use
of apraclonidine for chronic
treatment
Duration of effect:
8–12 hours
For chronic use of brimonidine:
• Contraindications: Children,
Reduces IOP by
patients taking monoamine
20–30%
oxidase inhibitors
TID if mono• Side effects: Dry mouth, lid
therapy, BID if
retraction, allergy (more
adjunctive
common with apraclonidine),
therapy
conjunctival injection,
somnolence, fatigue,
Duration of effect:
headaches, hypotension
8–12 hours
• May be used with caution in
Reduces IOP by
pregnancy
20–30%
*Values reported are relative change (%) from baseline (peak to trough effect).
Canadian Ophthalmological Society evidence-based clinical
practice guidelines for the management of glaucoma in the
adult eye. Can J Ophthalmol 2009;44(Suppl 1):S1S93.
Beta adrenergic antagonists
Generic name
Trade name
Selective beta-1
antagonist
betaxolol 0.25%
Betoptic S
Non-selective beta
antagonists
timolol† 0.25%, 0.5%
Timoptic
timolol gel-forming
solution 0.25%,
0.5%
Timoptic XE
levobunolol 0.25%,
0.5%
Betagan
Mechanism of
action
Decreases
aqueous
production
Efficacy* and
dosing
BID
Reduces IOP
by 20–23%
BID
Daily for
Timoptic XE
Reduces IOP
by 20–30%
BID
Reduces IOP
by 20–30%
*Values reported are relative change (%) from
baseline (peak to trough effect).
†Timolol may be used during lactation. Punctal
occlusion is recommended following drop instillation
to reduce systemic absorption, as timolol in particular
may appear in breast milk.
Considerations
• Better tolerated than non-selective agents,
but not as effective
• Relative side effects and contraindications
same as non-selective agents
• Additive to most IOP-lowering agents
• Side effects: Exacerbates obstructive
pulmonary diseases such as asthma, slows
heart rate and lowers BP. May mask
symptoms of hypoglycemia in patients with
diabetes on insulin or insulin secretagogues
• Best-tolerated class from ocular standpoint,
some dry eye symptoms
• Absolute contraindications: Patients with
asthma, COPD, sinus bradycardia, or
greater than first-degree heart block.
Precaution: Not recommended in patients
with life-threatening depression
• May be used with caution in pregnancy.
Fetal heart monitoring for bradycardia and
arrhythmia may be indicated periodically
Canadian Ophthalmological Society evidence-based clinical
practice guidelines for the management of glaucoma in the
adult eye. Can J Ophthalmol 2009;44(Suppl 1):S1S93.
Carbonic anhydrase
inhibitors — systemic
Generic name
Trade name
acetazolamide
methazolamide
Mechanism of
action
Decreases
aqueous
formation
Efficacy* and
dosing
Acetazolamide:
125–250 mg PO
QID
Considerations
• Indicated when topical medication
is not effective
• May lead to hypokalemia
• Contraindications: When sodium
Methazolamide:
and potassium blood levels are
25–50 mg PO TID
depressed, as in kidney or liver
disease; in sickle cell anemia
Reduces IOP by
• Side effects: Parasthesia,
25–35%
gastrointestinal symptoms,
depression, decreased libido,
kidney stones, blood dyscrasias,
metabolic acidosis, electrolyte
• Imbalance
• Precautions: Allergy to
sulfonamides, pregnancy
(teratogenic effects reported), and
nursing mothers
*Values reported are relative change (%) from baseline (peak to trough effect).
Canadian Ophthalmological Society evidence-based clinical
practice guidelines for the management of glaucoma in the
adult eye. Can J Ophthalmol 2009;44(Suppl 1):S1S93.
Carbonic anhydrase
inhibitors — topical
Generic name
Trade name
brinzolamide 1%
Azopt
dorzolamide† 2%
Trusopt
Mechanism of
action
Decreases
aqueous
Formation
Efficacy* and
dosing
Azopt: BID
Reduces IOP by
15–22%
Considerations
• Side effects: Ocular burning and
discomfort
• Precautions: May increase
corneal edema with low
Trusopt:
endothelial cell count and (or)
Monotherapy: TID
corneal endothelial dysfunction
Adjunctive to
(e.g., Fuchs dystrophy).
topical beta
Combined oral and topical
blockers: BID
carbonic anhydrase inhibitors not
Reduces IOP by
recommended in this patient
15–22%
population
• Not well studied in pregnancy,
and should probably be avoided
due to concerns with oral agents
and teratogenicity
*Values reported are relative change (%) from baseline (peak to trough effect).
†Dorzolamide may be used during lactation. Punctal occlusion is recommended following drop
instillation to reduce systemic absorption, as timolol in particular may appear in breast milk.
Canadian Ophthalmological Society evidence-based clinical
practice guidelines for the management of glaucoma in the
adult eye. Can J Ophthalmol 2009;44(Suppl 1):S1S93.
Parasympathomimetics
(cholinergic agents)
Generic name
Trade name
pilocarpine
1%, 2%, 4%
Isopto Carpine
pilocarpine gel 4%
Pilopine HS
carbachol
1.5%, 3%
Isopto Carbachol
Mechanism of
action
Increases facility
of outflow
of aqueous
through
conventional
trabecular
outflow pathway
Efficacy* and
dosing
Pilocarpine
lowers IOP in
1 hour and lasts
6–7 hours
Pilocarpine: QID
Pilopine HS: HS
Carbachol: TID
Reduces IOP by
15–25%
Considerations
• Contraindications: Uveitis-related
and neovascular glaucoma,
aqueous misdirection syndrome
• Side effects: Miosis, myopia with
accommodative spasm, brow
ache, retinal detachment,
intestinal cramps, bronchospasm
• Precautions: Axial myopia, history
of rhegmatogenous retinal
detachment, or peripheral retinal
disease predisposing to retinal
detachment
• May be used with caution in
pregnancy
*Values reported are relative change (%) from baseline (peak to trough effect).
Canadian Ophthalmological Society evidence-based clinical
practice guidelines for the management of glaucoma in the
adult eye. Can J Ophthalmol 2009;44(Suppl 1):S1S93.
Prostaglandin derivatives
Generic name
Trade name
bimatoprost 0.03%
Lumigan
Mechanism
of action
Increases
uveoscleral
outflow
latanoprost 0.005% Bimatoprost
may also
Xalatan
increase
travoprost 0.004%
trabecular
Travatan
outflow
Efficacy* and
dosing
Dosing once daily
IOP lowering starts
2–4 hours after
administration
Maximum IOPlowering often takes
3–5 weeks from start
of treatment
Reduces IOP:
latanoprost 28–31%
travoprost 29–31%
bimatoprost 28–33%
Considerations
• Side effects: Iris colour changes,
conjunctival hyperemia, burning,
stinging, foreign-body sensation,
eyelash change (length, thickness,
color; reversible after cessation),
cystoid macular edema in aphakia
and pseudophakia, possible
reactivation of herpes keratitis,
possible anterior uveitis
• Should be avoided in pregnancy, as
prostaglandin F2-alpha can cause
uterine contraction and influence
fetal circulation
*Values reported are relative change (%) from baseline (peak to trough effect).
Canadian Ophthalmological Society evidence-based clinical
practice guidelines for the management of glaucoma in the
adult eye. Can J Ophthalmol 2009;44(Suppl 1):S1S93.
Surgical therapy
• It is important for the surgeon to discuss all
treatment options, as well as the risks and
benefits of surgery.
• Minimize postoperative complications and
optimize patient outcomes by:
– preoperative evaluation of the patient by the
surgeon, and
– frequent postoperative visits (particularly within the
first postoperative 12–48 hours) and over the
ensuing weeks.
Canadian Ophthalmological Society evidence-based clinical
practice guidelines for the management of glaucoma in the
adult eye. Can J Ophthalmol 2009;44(Suppl 1):S1S93.
Glaucoma surgery — patient
expectations and acceptance
Recommendation
Preoperative discussion with the patient is paramount
when planning glaucoma surgery. It is important for the
patient to be well informed about the intent of the
surgery, with particular emphasis on the fact that the
surgery is being done in an attempt to preserve visual
function and not to improve vision. Success can only
be achieved when the desired surgical outcome is in
alignment with the patient’s realistic expectations
[Consensus].
Canadian Ophthalmological Society evidence-based clinical
practice guidelines for the management of glaucoma in the
adult eye. Can J Ophthalmol 2009;44(Suppl 1):S1S93.
Laser trabeculoplasty
• Laser trabeculoplasty is an effective means of
lowering IOP in open-angle glaucoma.
• It is most often employed as adjunctive therapy
in the treatment of glaucoma, which may help
achieve target IOP in patients above target on:
– maximally tolerated medical therapy, or
– one or a few medications without having to add
additional medications.
Canadian Ophthalmological Society evidence-based clinical
practice guidelines for the management of glaucoma in the
adult eye. Can J Ophthalmol 2009;44(Suppl 1):S1S93.
Laser trabeculoplasty (cont’d)
• Laser trabeculoplasty will lower IOP significantly
in approximately 75% of patients.1
• Treatment effect will be lost in approximately
10% of successfully treated individuals per year
over a 5-year period.2–5
1. Glaucoma Laser Trial Research Group. Am J Ophthalmol
1995;120:718–31.
2. Spaeth GL, et al. Arch Ophthalmol 1992;110:491–4.
3. Schwartz AL, et al. Arch Ophthalmol 1985;103:1482–4.
4. Krupin T, et al. Ophthalmology 1986;93:811–6.
5. Shingleton BJ, et al. Ophthalmology 1993;100:1324–9.
Canadian Ophthalmological Society evidence-based clinical
practice guidelines for the management of glaucoma in the
adult eye. Can J Ophthalmol 2009;44(Suppl 1):S1S93.
Laser angle surgery
— considerations
Recommendation
Laser angle surgery for glaucoma should
incorporate the following [Consensus]:
– preoperative evaluation by the treating surgeon,
– postoperative evaluation by the surgeon including IOP
measurement within 2 hours after the laser treatment, and
– IOP measurement up to 4–6 weeks later to determine
treatment effect.
Canadian Ophthalmological Society evidence-based clinical
practice guidelines for the management of glaucoma in the
adult eye. Can J Ophthalmol 2009;44(Suppl 1):S1S93.
Trabeculectomy
• Trabeculectomy provides an alternative route of
egress for aqueous humour.
• It is the most widely practiced surgical method for
lowering IOP.
• It is generally employed when other methods of
lowering IOP have been unsuccessful
• Trabeculectomy may also be employed as a means of
reducing or eliminating the use of medications for
patients in whom:
– medications are poorly tolerated, or
– medications are significantly reducing QOL.
Canadian Ophthalmological Society evidence-based clinical
practice guidelines for the management of glaucoma in the
adult eye. Can J Ophthalmol 2009;44(Suppl 1):S1S93.
Success rate of trabeculectomy
• The success rate of trabeculectomy varies and
is somewhat race dependent.
• The success rate is reduced:
– in eyes with previous surgical conjunctival
manipulation, and
– in eyes with inflammation.
Canadian Ophthalmological Society evidence-based clinical
practice guidelines for the management of glaucoma in the
adult eye. Can J Ophthalmol 2009;44(Suppl 1):S1S93.
Success rate of
trabeculectomy (cont’d)
• The success rate of trabeculectomy is improved:
– in glaucoma filtering surgery with postoperative topical
corticosteroids,1
– with perioperative locally applied antimetabolites,
particularly in eyes at risk for failure. However, they may
also increase the risk of postoperative complications,
including:
•
•
•
•
wound leak,2
hypotony,3
suprachoroidal hemorrhage, and
bleb-related endophthalmitis.4
1. Araujo SV, et al. Ophthalmology 1995;102:1753–9.
2. Greenfield DS, et al. Arch Ophthalmol 1998;116:443–7.
3. Zacharia PT, et al. Am J Ophthalmol 1993;116:314–26.
4. Jampel HD, et al. Arch Ophthalmol 2001;119:1001–8.
Canadian Ophthalmological Society evidence-based clinical
practice guidelines for the management of glaucoma in the
adult eye. Can J Ophthalmol 2009;44(Suppl 1):S1S93.
Nonpenetrating filtration surgery
• Nonpenetrating filtration surgery includes viscocanalostomy
and nonpenetrating deep sclerectomy.
• Proposed advantages of these procedures include a potential
lower rate of bleb-related complications and hypotony.
• In the hands of most surgeons, probably does not lower IOP
to the same degree as trabeculectomy.1,2
• Trabeculectomy is likely a better choice, particularly for
patients in whom a low target IOP is desired.
• More studies on this technique should further clarify its role.
Canadian Ophthalmological Society evidence-based clinical
practice guidelines for the management of glaucoma in the
1. Carassa RG, et al. Ophthalmology 2003;110:882–7.
adult eye. Can J Ophthalmol 2009;44(Suppl 1):S1S93.
2. El Sayyad F, et al. Ophthalmology 2000;107:1671–4.
Tube shunts
• Several different tube shunt designs exist.
• Few studies have compared one implant with another,
and there are no clear long-term advantages of one
implant over another.1,2
• The Trabeculectomy Versus Tube study3 has given
impetus to considering tube shunt surgery earlier in the
treatment algorithm, particularly following failure of a
single previous mitomycin trabeculectomy.
• Further studies with longer follow-up in this area are
needed.
1. Hong CH, et al. Surv Ophthalmol 2005;50:48–60.
2. Minckler DS, et al. Cochrane Database Syst Rev
2006;2:CD004918.
3. Gedde SG, et al. Am J Ophthalmol 2007;143:9–22.
Canadian Ophthalmological Society evidence-based clinical
practice guidelines for the management of glaucoma in the
adult eye. Can J Ophthalmol 2009;44(Suppl 1):S1S93.
Cyclodestructive surgery
• Cyclodestructive surgery is usually performed
with the use of a contact trans-scleral laser
delivery system.
• It is largely reserved for patients with poor vision
in the operative eye in whom:
– other surgical interventions have failed, and
– there are few other options for obtaining IOP control.
• It is generally easy to perform in the office or
clinic setting.
Canadian Ophthalmological Society evidence-based clinical
practice guidelines for the management of glaucoma in the
adult eye. Can J Ophthalmol 2009;44(Suppl 1):S1S93.
Cyclodestructive surgery (cont’d)
• However, cyclodestructive surgery can be
associated with:
– significant perioperative discomfort and inflammation,
– postoperative hypotony,
– significant visual acuity reduction of ≥2 lines in a
substantial number of patients after treatment, or
– frank phthisis bulbi.1
• Further study through large RCTs is needed to
establish efficacy, precise indications and use in
the glaucoma population.1
Canadian Ophthalmological Society evidence-based clinical
practice guidelines for the management of glaucoma in the
adult eye. Can J Ophthalmol 2009;44(Suppl 1):S1S93.
1. Pastor SA, et al. Ophthalmology 2001;108:2130–8.
Cataract and Glaucoma
Advantages and disadvantages of single and
combined cataract and glaucoma procedures
Procedure
Phacoemulsification
alone
Advantages
• Quick procedure with
more rapid visual
recovery
• Improved vision, which
benefits QOL
• May lower IOP a small
amount in some
patients
Trabeculectomy
alone
•
•
Disadvantages
• Postoperative IOP spike is a
potential risk, particularly in
patients with advanced VF
loss
• Not regarded as a
consistent or powerful
means of lowering IOP
• IOP should be watched
closely in both the early
postoperative period and
later
Quicker than combined • Will not improve vision
procedure
• May cause or worsen
May achieve superior
cataract
long-term IOP lowering
than combined
procedure or cataract
alone
Canadian Ophthalmological Society evidence-based clinical
practice guidelines for the management of glaucoma in the
adult eye. Can J Ophthalmol 2009;44(Suppl 1):S1S93.
Advantages and disadvantages of single and
combined cataract and glaucoma procedures
Procedure
Combined procedure
Advantages
• Minimizes anesthetic
risk by combining 2
procedures in 1
• Convenience to patient
with 1 trip to operating
room rather than 2
• Cost savings
• May blunt potentially
damaging
postoperative IOP
spikes in patients with
advanced VF loss
• Opportunity to improve
IOP control and
improve vision at the
same time with
enhanced QOL
Disadvantages
• May not be as effective at
long-term IOP control as
trabeculectomy alone
• Increased risk of
complications with 2
procedures rather than 1
• Slower visual recovery than
doing cataract alone
Canadian Ophthalmological Society evidence-based clinical
practice guidelines for the management of glaucoma in the
adult eye. Can J Ophthalmol 2009;44(Suppl 1):S1S93.
Cataract and glaucoma —
cataract surgery with early glaucoma
Recommendation
A visually significant cataract in the presence of
early glaucoma, controlled with 1 or 2 medications
and (or) laser trabeculoplasty, should be treated
with phacoemulsification/IOL implantation alone
[Level 21].
1. Friedman DS, et al. Ophthalmology
2002;109:1902–15.
Canadian Ophthalmological Society evidence-based clinical
practice guidelines for the management of glaucoma in the
adult eye. Can J Ophthalmol 2009;44(Suppl 1):S1S93.
Cataract and glaucoma —
combined glaucoma and cataract surgery
Recommendation
• A visually significant cataract in the presence of
moderate to advanced glaucoma, with a preoperative IOP within or near the target range,
should be treated with combined
phacoemulsification/IOL implantation and
trabeculectomy [Level 31].
1. Friedman DS, et al. Ophthalmology
2002;109:1902–15.
Canadian Ophthalmological Society evidence-based clinical
practice guidelines for the management of glaucoma in the
adult eye. Can J Ophthalmol 2009;44(Suppl 1):S1S93.
Cataract and glaucoma — glaucoma
surgery followed by cataract surgery
Recommendation
When a visually significant cataract is present in
an eye with an uncontrolled pre-operative IOP,
consideration should be given to performing a
trabeculectomy first, following by
phacoemulsification/IOL implantation several
months later, in order to mitigate the risk of intraoperative complications such as suprachoroidal
hemorrhage [Consensus].
Canadian Ophthalmological Society evidence-based clinical
practice guidelines for the management of glaucoma in the
adult eye. Can J Ophthalmol 2009;44(Suppl 1):S1S93.
Cataract and glaucoma
• Cataract surgery in the glaucoma patient may
involve challenges specific to the glaucoma
patient, including:
–
–
–
–
small pupils,
posterior synechiae,
abnormally shallow or deep anterior chambers, and
weakened zonules (especially in patients with PXF
syndrome/glaucoma).
Canadian Ophthalmological Society evidence-based clinical
practice guidelines for the management of glaucoma in the
adult eye. Can J Ophthalmol 2009;44(Suppl 1):S1S93.
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