Could It Be The Drops? Not-Too-Uncommon Complications from Glaucoma - PDF document

Could It Be The Drops? Not-Too-Uncommon Complications from Glaucoma Medications Cathy Sun, MD Assistant Professor of Ophthalmology, UCSF Glaucoma Update, 2019 Financial Disclosures No financial disclosures

Adverse Reactions  Main therapeutic agent - Allergic reaction - Adverse effect  Preservatives - Allergic reaction - Ocular surface disorders Prostaglandin Analogs Tafluprost (PF) Latanoprost Bimatoprost Travoprost, (0.01%, 0.03%) Travatan Z https://www.businesswire.com/news/home/20180913006149/en/Sun-Pharma-SPARC-Announce-FDA- Approval-XELPROS%E2%84%A2

Prostaglandin Analogs Adverse Effects  Conjunctival hyperemia (most common)  Eyelash growth  Hyperpigmentation of periocular skin  Prostaglandin-associated periorbitopathy, deepening of upper eyelid sulcus  Iris pigmentation (irreversible)  Reactivation of herpes infection  Cystoid macular edema - No definitive link with PGA since eye developing CME usually have Independent risk factors Inoue K. Managing adverse effects of glaucoma medications. Clinical ophthalmology (Auckland, NZ) 2014;8:903-13 . Inoue K, Shiokawa M, Higa R, et al. Adverse periocular reactions to five types of prostaglandin analogs. Eye. 2012;26(11):1465–1472 Lee AJ, McCluskey P. Clinical utility and differential effects of prostaglandin analogs in the management of raised intraocular pressure and ocular hypertension. Clinical ophthalmology (Auckland, NZ) 2010;4:741-64. Anterior Uveitis: PGA Control No difference in development of anterior uveitis Chang JH, McCluskey P, Missotten T, Ferrante P, Jalaludin B, Lightman S. Use of ocular hypotensive prostaglandin analogues in patients with uveitis: does their use increase anterior uveitis and cystoid macular oedema? British Journal of Ophthalmology 2008;92:916-921.

Cystoid Macular Edema: PGA Control No prior CME No active CME at treatment commencement No difference in development of CME Chang JH, McCluskey P, Missotten T, Ferrante P, Jalaludin B, Lightman S. Use of ocular hypotensive prostaglandin analogues in patients with uveitis: does their use increase anterior uveitis and cystoid macular oedema? British Journal of Ophthalmology 2008;92:916-921. Prostaglandin Analogs Practical Applications  Avoid unilateral use if possible given adverse cosmetic effects  Caution in patients with a history of herpes infection  In post-operative cataract patients, continue PGA and consider the concurrent use of an NSAID, especially in patients who underwent complex cataract surgery  If there is evidence of non-resolving post-operative CME, consider temporarily discontinuing PGA until resolution

Beta Blockers Carteolol Levobunolol Timolol Betaxolol (selective β-1  0.25% or 0.5% blocker)  Timolol Gel Forming Solution (qd)  Timolol PF Metipranolol Beta Blockers Adverse Effects  Topical: Corneal anesthesia  Systemic: - Bronchospasm - Bradycardia, hypotension, irregular pulse - CNS depression - Abrupt withdrawal can exacerbate hyperthyroidism symptoms - Can aggravate myasthenia gravis - Mask hypoglycemic symptoms in diabetics - Decrease HDL  No evidence this increases risk for cardiovascular disease https://www.aao.org/bcscsnippetdetail.aspx?id=9d937f6d-acc4-4510-8165-ff3de27dcafd

Beta Blockers Practical Applications  Try betaxolol or avoid BB if history of asthma or COPD - IOP lowering effect of betaxolol may be less than timolol  Dose daily in morning or try lower dose of 0.25%  Try Timolol GFS for daily dosing and fewer systemic side effects  Nasolacrimal occlusion or eyelid closure can decrease systemic absorption “Start low, go slow” Kumar H, Sudan R, Sethi HS, Sony P. Timolol maleate 0.5% versus timolol maleate in gel forming solution 0.5% (Timolol GFS) in open angle glaucoma in India. Preliminary safety and efficacy study. Indian journal of ophthalmology 2002;50:21-3. Zimmerman TJ, Kooner KS, Kandarakis AS, Ziegler LP. Improving the therapeutic index of topically applied ocular drugs. Archives of ophthalmology 1984;102:551-3. Carbonic Anhydrase Inhibitors Topical: Oral: Acetazolamide - Dorzolamide (solution) Methazolamide - Brinzolamide (suspension)

Carbonic Anhydrase Inhibitors Adverse Effects  Topical: - Burning, irritation with instillation. Dorzolamide is acidic with pH 5.5-5.9 - Blurry vision, whitish deposit with brinzolamide - Caution in patients with corneal endothelial disorders Systemic  - Bitter taste - Increased risk of kidney stone - Dysesthesia of fingers, around lips - Frequent urination - Anorexia, weight reduction - Metabolic acidosis - Aplastic anemia (rare) Carlsen J, Durcan J, Zabriskie N, Swartz M, Crandall A. Nephrolithiasis with dorzolamide. Archives of ophthalmology 1999;117:1087-8 Inoue K. Managing adverse effects of glaucoma medications. Clinical ophthalmology (Auckland, NZ) 2014;8:903-13 Konowal A, Morrison JC, Brown SV, et al. Irreversible corneal decompensation in patients treated with topical dorzolamide. American journal of ophthalmology 1999;127:403-6. Cross-reactivity with sulfa? No If you have a sulfa antibiotic allergy, you’re just as likely to have an allergy to penicillin as you are to sulfa non- antibiotics. Patients with sulfa antibiotic allergies have a general predisposition to allergic reactions. Strom BL, Schinnar R, Apter AJ, et al. Absence of cross-reactivity between sulfonamide antibiotics and sulfonamide nonantibiotics. The New England journal of medicine 2003;349:1628-35. http://glaucomatoday.com/2016/06/revisiting-risk/

Carbonic Anhydrase Inhibitors Practical Applications  If unable to tolerate dorzolamide due to burning/irritation, try brinzolamide  Caution in patients with corneal endothelial disorders and avoid in patients with corneal edema  If prior allergy to sulfonamide antibiotic, be aware there is a higher risk of allergy to oral CAIs - Ask about reaction (mild vs life threatening) - Does not preclude use of an oral CAI if it’s medically necessary - Be cautious and consider monitoring in clinic with first-time use Selective Alpha-2 Agonists Apraclonidine Brimonidine - 0.025% (Lumify) - OTC - 0.1%, 0.15%, 0.2% - Brimonidine-Purite

Selective Alpha-2 Agonists Adverse Effects  Topical: - Ocular hyperemia - Vasoconstriction at low doses (0.025%) - Allergic conjunctivitis - Periocular contact dermatitis - Anterior uveitis  Systemic: - Drowsiness, apnea, hypotension, bradycardia  Contraindicated in kids <2yr  Caution in all kids  Can also effect elderly - Dry mouth - Caution with anti-depressants Cantor LB. Brimonidine in the treatment of glaucoma and ocular hypertension. Therapeutics and clinical risk management 2006;2:337-46 Katz LJ. Twelve-month evaluation of brimonidine-purite versus brimonidine in patients with glaucoma or ocular hypertension. Journal of glaucoma 2002;11:119-26 Butler P, Mannschreck M, Lin S, Hwang I, Alvarado J. Clinical experience with the long-term use of 1% apraclonidine. Incidence of allergic reactions. Archives of ophthalmology 1995;113:293-6. Selective Alpha-2 Agonists Practical Applications  Dose brimonidine BID. May have better compliance  If adverse reactions, try: - Lower concentrations - Brimonidine-Purite  Avoid in young kids  Contraindicated in kids <2yr  Caution if on oral anti-depressants (TCA, MAOI) due to effect on metabolism  Ask if they’re using any red eye drops - Safety study did not report any somnolence in kids >5yo on Lumify Walters TR. Development and use of brimonidine in treating acute and chronic elevations of intraocular pressure: a review of safety, efficacy, dose response, and dosing studies. Surv Ophthalmol 1996;41 Suppl 1:S19-26 https://reference.medscape.com/drug/alphagan-p-qoliana-brimonidine-343594#5

Miotics/Parasympathomimetics Echothiophate iodide (0.125%) Pilocarpine (1%, 2%, 4%) Miotics/Parasympathomimetics Adverse Effects  Topical: - Miosis, decreased night vision - Induced myopia - Decreased accommodation, accommodative spasm - Risk of retina tears and detachments - Cataract - Uveitis - Induced angle closure - Iris cyst formation (echothiophate)  Systemic: - Brow ache, headache - Increase in parasympathetic activity (e.g. GI symptoms) - Prolonged paralysis with succinylcholine (echothiophate) Kini MM, Dahl AA, Roberts CR, Lehwalder LW, Grant WM. Echothiophate, pilocarpine, and open-angle glaucoma. Archives of ophthalmology 1973;89:190-2.

Miotics/Parasympathomimetics Practical Applications  Usually last line therapy - Adverse effects - Frequent dosing for pilocarpine, though echothiophate is dosed qd  Bridging until surgery in patients who are on maximum tolerated medications with OAG  Longer term therapy in patients who are on maximum tolerated medications and poor surgical candidate  Avoid in young patients, risk of RD, uveitics, risk of angle closure  Can be “objective evidence of noncompliance” Take Home Messages  Determine Cause - Preservatives - Allergic reaction - Known adverse effect of drug  Start low, go slow - Lower concentration - Less frequent dosing  Timolol qd  Brimonidine BID - Combination drops  Nasolacrimal occlusion and eyelid closure can decrease systemic adverse effects  Consider SLT or surgery

Thank You!  Mentors at UCSF and Bascom Palmer  Sarah Wellik, MD  Elizabeth Hodapp, MD  Peter Chang, MD