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

▶
could it be the drops
SMART_READER_LITE
LIVE PREVIEW

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

Oct 03, 2023 209 likes •377 views

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

slide-1
SLIDE 1

Could It Be The Drops?

Cathy Sun, MD Assistant Professor of Ophthalmology, UCSF Glaucoma Update, 2019

Not-Too-Uncommon Complications from Glaucoma Medications

Financial Disclosures

No financial disclosures

slide-2
SLIDE 2

Adverse Reactions

  • Main therapeutic agent
  • Allergic reaction
  • Adverse effect
  • Preservatives
  • Allergic reaction
  • Ocular surface disorders

Prostaglandin Analogs

Latanoprost

https://www.businesswire.com/news/home/20180913006149/en/Sun-Pharma-SPARC-Announce-FDA- Approval-XELPROS%E2%84%A2

Bimatoprost (0.01%, 0.03%) Travoprost, Travatan Z Tafluprost (PF)

slide-3
SLIDE 3

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

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.

No difference in development of anterior uveitis

slide-4
SLIDE 4

Cystoid Macular Edema: PGA Control No prior CME No active CME at treatment commencement

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.

No difference in development of CME

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

slide-5
SLIDE 5

Beta Blockers

Timolol

  • 0.25% or 0.5%
  • Timolol Gel

Forming Solution (qd)

  • Timolol PF

Betaxolol (selective β-1 blocker) Levobunolol Carteolol 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

slide-6
SLIDE 6

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

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

  • phthalmology 1984;102:551-3.

“Start low, go slow”

Carbonic Anhydrase Inhibitors

Topical:

  • Dorzolamide (solution)
  • Brinzolamide (suspension)

Oral: Acetazolamide Methazolamide

slide-7
SLIDE 7

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?

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/

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.

No

slide-8
SLIDE 8

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

Brimonidine

  • 0.025% (Lumify) - OTC
  • 0.1%, 0.15%, 0.2%
  • Brimonidine-Purite

Apraclonidine

slide-9
SLIDE 9

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

  • phthalmology 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
  • n 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

slide-10
SLIDE 10

Miotics/Parasympathomimetics

Pilocarpine (1%, 2%, 4%) Echothiophate iodide (0.125%)

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.

slide-11
SLIDE 11

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
slide-12
SLIDE 12

Thank You!

  • Mentors at UCSF and Bascom Palmer
  • Sarah Wellik, MD
  • Elizabeth Hodapp, MD
  • Peter Chang, MD
slide-13
SLIDE 13

Latanoprostene bunod

  • MOA: Prostaglandin analog + Nitric Oxide donor
  • Adverse effects:
  • Prostaglandin analog adverse effects
  • In JUPITER study:
  • Conjunctival hyperemia (17.7%)
  • Eyelash growth (16.2%)
  • Eye irritation (11.5%)
  • Eye pain (10%)

Kawase K, Vittitow JL, Weinreb RN, Araie M. Long-term Safety and Efficacy of Latanoprostene Bunod 0.024% in Japanese Subjects with Open-Angle Glaucoma or Ocular Hypertension: The JUPITER Study. Advances in therapy 2016;33:1612-27.

Rho kinase (ROCK) Inhibitors

Netarsudil 0.02% Netarsudil 0.02% + Latanoprost Ripasudil (available in Japan)

slide-14
SLIDE 14

ROCK Inhibitors

Adverse Effects

  • Conjunctival hyperemia (50%)
  • Starts early <24 hours
  • Lead to discontinuation of drug in 12% of patients in ROCKET-2

(1 year phase 3 study comparing netarsudil to timolol)

  • Corneal verticillata (26%)
  • Resolves after stopping drop
  • Conjunctival hemorrhage (20%)
  • Instillation site pain
  • Blurred vision
  • Pruritus
  • Increased tearing
  • Eyelid erythema

Kahook MY, Serle JB, Mah FS, et al. Long-term Safety and Ocular Hypotensive Efficacy Evaluation of Netarsudil Ophthalmic Solution: Rho Kinase Elevated IOP Treatment Trial (ROCKET-2). American journal of ophthalmology 2019;200:130-137

ROCK Inhibitors

Practical Applications:

  • Warn patients about red eyes
  • Common
  • Resolve if drop is stopped
  • Mention corneal verticillata
  • Not visually significant
  • Resolves if drop is stopped
slide-15
SLIDE 15

Any role for pilocarpine after angle surgery?

Mean IOP

Esfandiari H, Hassanpour K, Yaseri M, Loewen NA. Extended pharmacological miosis is superfluous after glaucoma angle surgery: A retrospective study. F1000Research 2018;7:178.

No difference after trabectome in eyes treated with & without pilocarpine No difference in eyes treated with & without pilocarpine No difference in time to resolution of hyphema in eyes with/without Pilocarpine

Toxicity from Preservatives?

  • Try alternative preservatives:
  • Travatan Z (sofZia)
  • Alphagan P (Purite)
  • Xelpros
  • Try preservative free versions:
  • Tafluprost
  • Timoptic in Ocudose
  • Cosopt PF
  • Try oral antihypertensives:
  • Acetazolamide or Methazolamide
  • SLT
  • Surgery