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 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):S1S93. 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):S1S93. 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):S1S93. 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):S1S93. 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):S1S93. 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):S1S93. 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):S1S93. 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):S1S93. 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):S1S93. 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):S1S93. 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):S1S93. 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):S1S93. 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):S1S93. 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):S1S93. 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):S1S93. 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):S1S93. 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):S1S93. 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):S1S93. 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):S1S93. 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):S1S93. 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):S1S93. 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):S1S93. 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):S1S93. 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):S1S93. 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):S1S93. 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):S1S93. 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):S1S93. 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):S1S93. 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):S1S93.