1. Canadian Ophthalmological Society Evidence-based Clinical Practice Guidelines for the Management of Glaucoma in the Adult Eye

2. Therapeutic Options for Lowering IOP

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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. 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.

9. Glaucoma Medications Used for Chronic Treatment

10. Alpha-2 adrenergic agonists Generic name Trade 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 aqueous production and increases uveoscleral outflow TID if mono- therapy, BID if adjunctive therapy Duration of effect: 8–12 hours Reduces IOP by 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.

11. Beta adrenergic antagonists Generic name Trade name Mechanism of action Efficacy* and dosing Considerations Selective beta-1 antagonist betaxolol 0.25% Betoptic S Decreases aqueous production BID Reduces IOP by 20–23% 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-forming solution 0.25%, 0.5% Timoptic XE BID Daily for Timoptic XE Reduces IOP by 20–30% 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 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. 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.

12. Carbonic anhydrase inhibitors — systemic Generic name Trade name Mechanism of action Efficacy* and dosing Considerations acetazolamide methazolamide Decreases aqueous formation Acetazolamide: 125–250 mg PO QID Methazolamide: 25–50 mg PO TID Reduces IOP by 25–35% 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 *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.

13. Carbonic anhydrase inhibitors — topical Generic name Trade name Mechanism of action Efficacy* and dosing Considerations brinzolamide 1% Azopt Decreases aqueous Formation Azopt: BID Reduces IOP by 15–22% Trusopt: Monotherapy: TID Adjunctive to topical beta blockers: BID Reduces 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. 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.

14. Parasympathomimetics (cholinergic agents) Generic name Trade name Mechanism of action Efficacy* and dosing Considerations pilocarpine 1%, 2%, 4% Isopto Carpine pilocarpine gel 4% Pilopine HS Increases facility of outflow of aqueous through conventional trabecular outflow pathway Pilocarpine lowers IOP in 1 hour and lasts 6–7 hours Pilocarpine: QID Pilopine HS: HS Carbachol: TID Reduces IOP by 15–25% 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 carbachol 1.5%, 3% Isopto Carbachol *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.

15. Prostaglandin derivatives Generic name Trade name Mechanism of action Efficacy* and dosing Considerations bimatoprost 0.03% Lumigan Increases uveoscleral outflow Bimatoprost may also increase trabecular outflow 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 *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.

16. 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.

17. 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.

18. 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.

19. 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.

20. 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.

21. 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.

22. 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.

23. 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.

24. 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. 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.

25. 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 study 3 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.

26. 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.

27. 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. 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.

28. Cataract and Glaucoma

29. Advantages and disadvantages of single and combined cataract and glaucoma procedures ProcedureAdvantagesDisadvantages 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 Trabeculectomy alone 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 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.

30. ProcedureAdvantagesDisadvantages 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 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

31. 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 2 1 ]. 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.

32. 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 3 1 ]. 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.

33. 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 intra- operative 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.

34. 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.