Canadian Ophthalmological Society

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):S1S93.

Patient involvement indecision to treat

RecommendationInitiation 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].



Medical management andQOL considerations

RecommendationIn 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].



Uniocular therapeutic trials

RecommendationA 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].



Documentation ofmedical management

RecommendationMonitoring 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].



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. Olthoff CM, et al. Ophthalmology 2005;112:953–61.2. Zhou Z, et al. Br J Ophthalmol 2004;88:1391–4.3. Sleath B, et al. Ophthalmology 2006;113:431–6.4. Patel SC, et al. Ophthalmic Surg 1995;26:233–6.



Glaucoma Medications Used for Chronic Treatment

Alpha-2 adrenergic agonistsGeneric nameTrade name

Mechanism of action

Efficacy* and dosing

Considerations

apraclonidine 0.5%, 1.0%Iopidine

Decreases aqueous production (prevents severe elevation of IOP following laser procedures)

Maximum effect in 4–5 hours

Duration of effect: 8–12 hours

Reduces IOP by 20–30%

• High rate of allergy limits use of apraclonidine for chronic treatment

For chronic use of brimonidine:• Contraindications: Children,

patients taking monoamine oxidase inhibitors

• Side effects: Dry mouth, lid retraction, allergy (more common with apraclonidine), conjunctival injection, somnolence, fatigue, headaches, hypotension

• May be used with caution in pregnancy

brimonidine 0.2%Alphagan

brimonidine 0.15%Alphagan-P(using Purite as preservative)

Decreases aqueousproduction and increases uveoscleral outflow

TID if mono-therapy, BID if adjunctive therapy

Duration of effect: 8–12 hoursReduces IOP by 20–30%

*Values reported are relative change (%) from baseline (peak to trough effect).



Beta adrenergic antagonistsGeneric nameTrade name

Mechanism of action


Considerations

Selective beta-1antagonistbetaxolol 0.25%Betoptic S

Decreases aqueousproduction

BID


• Better tolerated than non-selective agents, but not as effective

• Relative side effects and contraindications same as non-selective agents

Non-selective beta antagonists

timolol† 0.25%, 0.5%Timoptic

timolol gel-formingsolution 0.25%, 0.5%Timoptic XE

BIDDaily for Timoptic XE


• 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

levobunolol 0.25%, 0.5%Betagan

BID


*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.



Carbonic anhydraseinhibitors — systemic

Generic nameTrade name

Mechanism of action


Considerations

acetazolamidemethazolamide

Decreases aqueousformation

Acetazolamide:125–250 mg PO QID

Methazolamide:25–50 mg PO TID


• Indicated when topical medication is not effective

• May lead to hypokalemia• Contraindications: When sodium

and potassium blood levels are depressed, as in kidney or liver disease; in sickle cell anemia

• Side effects: Parasthesia, gastrointestinal symptoms, depression, decreased libido, kidney stones, blood dyscrasias, metabolic acidosis, electrolyte

• Imbalance• Precautions: Allergy to

sulfonamides, pregnancy (teratogenic effects reported), and nursing mothers




Carbonic anhydraseinhibitors — topical


Mechanism of action


Considerations

brinzolamide 1%Azopt

Decreases aqueousFormation

Azopt: BIDReduces IOP by 15–22%

Trusopt:Monotherapy: TIDAdjunctive to topical beta blockers: BIDReduces IOP by 15–22%

• Side effects: Ocular burning and discomfort

• Precautions: May increase corneal edema with low endothelial cell count and (or) corneal endothelial dysfunction (e.g., Fuchs dystrophy). Combined oral and topical carbonic anhydrase inhibitors not recommended in this patient population

• Not well studied in pregnancy, and should probably be avoided due to concerns with oral agents and teratogenicity

dorzolamide† 2%Trusopt

*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.



Parasympathomimetics(cholinergic agents)


Mechanism of action


Considerations

pilocarpine 1%, 2%, 4%Isopto Carpine

pilocarpine gel 4%Pilopine HS

Increases facility of outflowof aqueous throughconventional trabecularoutflow pathway

Pilocarpine lowers IOP in1 hour and lasts6–7 hours

Pilocarpine: QID

Pilopine HS: HS

Carbachol: TID


• 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

carbachol1.5%, 3%Isopto Carbachol




Prostaglandin derivatives


Mechanism of action


Considerations

bimatoprost 0.03%Lumigan

Increases uveoscleraloutflow

Bimatoprost may alsoincrease trabecularoutflow

Dosing once daily

IOP lowering starts 2–4 hours after administration

Maximum IOP- lowering often takes 3–5 weeks from start of treatment

Reduces IOP:latanoprost 28–31%travoprost 29–31%bimatoprost 28–33%

• 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

latanoprost 0.005%Xalatan

travoprost 0.004%Travatan




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.



Glaucoma surgery — patient expectations and acceptance

RecommendationPreoperative 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].



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.



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.



Laser angle surgery— considerations

RecommendationLaser 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.



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.



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.



Success rate oftrabeculectomy (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.



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.

1. Carassa RG, et al. Ophthalmology 2003;110:882–7.2. 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.



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.



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

1. Pastor SA, et al. Ophthalmology 2001;108:2130–8.



Cataract and Glaucoma

Advantages and disadvantages of single andcombined cataract and glaucoma procedures

Procedure Advantages Disadvantages Phacoemulsification alone

• Quick procedure with more rapid visual recovery

• Improved vision, which benefits QOL

• May lower IOP a small amount in some patients

• 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

Trabeculectomyalone

• Quicker than combined procedure

• May achieve superior long-term IOP lowering than combined procedure or cataract alone

• Will not improve vision• May cause or worsen

cataract



Procedure Advantages Disadvantages Combined procedure • 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

• 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



Advantages and disadvantages of single andcombined cataract and glaucoma procedures

Cataract and glaucoma — cataract surgery with early glaucoma

RecommendationA 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.



Cataract and glaucoma — combined glaucoma and cataract surgery

Recommendation•A visually significant cataract in the presence of moderate to advanced glaucoma, with a pre-operative IOP within or near the target range, should be treated with combined phacoemulsification/IOL implantation and trabeculectomy [Level 31].

1. Friedman DS, et al. Ophthalmology2002;109:1902–15.



Cataract and glaucoma — glaucoma surgery followed by cataract surgery

RecommendationWhen 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 intra-operative complications such as suprachoroidal hemorrhage [Consensus].



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).



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