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Medical Management of Glaucoma

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Title: Medical Management of Glaucoma

Author (s): Sean Collon, MS IV, Brock Alonzo, MD, Norman Zabriskie, MD

Date: 08/30/2018

Keywords/Main Subjects: Glaucoma medical agents

CORE Category: Glaucoma; Medical Management; Medical Agents

Diagnosis: N/A

Description of Case: N/A

Intraocular pressure lowering agents:

Drug Class Example Mechanism IOP Lowering Dosing Side Effects Notes
Prostaglandin F2a analogues Latanoprost (Xalatan)


Travoprost (Travatan)


Bimatoprost (Lumigan)


Tafluprost (Zioptan; preservative free)


Latanoprostene bunod (Vyzulta)

Increase outflow via uveoscleral pathway; decrease outflow resistance; mechanism unclear Latanaprost and Travoprost: 25-32%


Bimatoprost: 27-33%


Tafluprost: 27-31%





As a class, most potent

Once daily, usually in evening Ocular: Irritation, increased pigmentation of iris, lashes, and skin, hypertrichosis, prostaglandin associated periorbitopathy, loss of orbital fat over time


Often preferred as first line; highly effective at IOP lowering, with minimal systemic side effects.


Among preservative containing drops, side effects tend to be greatest with bimatoprost, and least with latanoprost.


Preservative free tafluprost may reduce irritation and ocular side effects and improve compliance in some patients.2

Systemic:  flu-like symptoms, myalgias and arthralgias, nasal congestion; generally very well tolerated
b-adrenergic antagonists Non-Selective: Timolol maleate (Timoptic;

Timoptic occudose = preservative free)


Timolol hemihydrate (Betimol)


Levobunolol (Betagan)




Carteolol HCl (partial alpha agonist)

Decrease aqueous production 20-30% 1-2 times daily




Once daily in morning; more effective in AM

Ocular: Blurring, irritation, punctate keratitis; metipranolol associated with uveitis Generally well tolerated from the perspective of ocular side effects.


History of asthma or other airway disease is a strong contraindication.


Suspect side effects of therapy in a patient with new onset depression, lethargy, or sexual dysfunction.


Carteolol may have less detrimental effect on lipid profile in some patients.3


Betaxolol may be slightly less likely to cause asthma or lung disease exacerbation, but still carries significant risk.4

Systemic: symptoms of b-blockade: heart block and bradycardia, decreased exercise tolerance, asthma and lung disease exacerbation, decreased symptoms of hypoglycemia in diabetes, depression, sexual dysfunction, lipid profile changes
Selective b 1:


Same 15-20% 2 times daily
a2-adrenergic agonists Apraclonidine HCl (Iopidine)


Brimonidine tartrate (Alphagan)

Decreases aqueous production, increases uveoscleral outflow to lesser extent 20-30% 2-3 times daily Ocular: Irritation, allergy, pruritis, dry eye As a class, most likely to cause ocular irritation.


High risk of apnea and CNS depression in infants with brimonidine. If CNS depression is a particular concern in any patient, apraclonidine does not cross blood-brain barrier and may be better choice.5,6

Systemic: Lethargy, hypotension, vasovagal attack, headache, dry mouth and nose, insomnia, anxiety; risk of apnea and CNS depression in infants with brimonidine, apraclonidine will not cross blood-brain barrier
Carbonic anhydrase inhibitors Oral:

Acetazolamide (Diamox)


Methazolamide (Neptazane)

Decreases aqueous production 15-20% Acetazolamide: 500-1000mg per day in 2-4 doses


Methazolamide: 25-50mg 2-3 times per day


IV Acetazolamide: 5-10mg/kg q6-8 hours

Ocular: None


Sulfa allergies are often cited as a contraindication to use of these drugs, but there is little structural overlap with antibiotic sulfa drugs, and thus most patients allergic to sulfa drugs will not be affected by carbonic anhydrase inhibitors. 7
Systemic: hypokalemia, poor tolerance of carbonated beverages, acidosis, paresthesias, blood dyscrasias, lethargy, nephrolithiasis, others




Dorzolamide (Trusopt)


Brinzolamide (Azopt)

Same Generally not as effective as oral acetazolamide 2 times daily (only FDA approved for 3 times daily) Ocular:  Induced myopia, blurred vision, stinging (less with Brinzolamide), allergic conjunctivitis, keratopathy Generally very safe, often used in infants and pregnant women.
Systemic: Less than with oral agents; bad taste in mouth
Parasympathomimetic agents Pilocarpine HCl


Echothiophate iodide (Phospholine iodide)

Miotics; increase trabecular outflow; ciliary muscles contract, put traction on scleral spur, open trabecular meshwork 15-25%



Pilocarpine: 2-4 times daily, usually 4 times daily


Echothiopentate: 1-2 times daily, usually 2 times daily

Ocular: Posterior synechiae, intense miosis, keratitis, cataract, retinal detachment, angle closure, epiphora, induced myopia Consider echothiophate in patients with a complicated anterior segment, e.g. aphakia, PK, ACIOL, etc., with inadequate pressure control. In certain patients it can be the sole effective drug.8
Systemic: increased salivation, increased gastric secretion, abdominal cramps
Rho kinase inhibitors Netarsudil (Rhopressa) Increases trabecular outflow, decreases episcleral venous pressure9 Reduces IOP by ~5.5-6 mmHg regardless of baseline IOP10 FDA approved for once daily, more efficacious when used twice daily in studies Ocular: conjunctival hyperemia and hemorrhage, corneal deposits (verticillata), blurry vision, epiphora, pruritis, punctate keratitis, eyelid erythema, conjunctival edema, foreign body sensation Though not as effective at IOP reduction as other classes, may have benefit in patients with lower baseline IOP (IOP reduction less dependent on baseline IOP than other classes), and as an adjunct to other drugs, as mechanism of action (increases trabecular outflow rather than uveoscleral) is different from the most commonly used classes.10
Systemic: None achieving statistical significance in recent studies10
Hyperosmotic agents Mannitol 20% (parenteral)

Glycerol 50% (oral)

Creates osmotic gradient, dehydrates vitreous Mannitol: 0.5-2.0 g/kg

Glycerol: 1-1.5 g/kg

Ocular: IOP rebound, aqueous flare  
Systemic: urinary retention, headache, nausea, vomiting, diarrhea, electrolyte disturbances, cardiac complications, contraindicated in renal failure

In addition, several combination drugs are available, including:

All combination drugs offer IOP lowering greater than with monotherapy with either individually, while allowing patients to use fewer drops. Side effect profiles remain the same as for individual drugs.


 Medeiros FA et al. Comparison of Latanoprostene Bunod 0.024% and Timolol Maleate 0.5% in Open-Angle Glaucoma or Ocular Hypertension: The LUNAR Study. American Journal of Ophthalmology. Volume 168, 250-259.

  1. Liu Y, Mao W. Tafluprost once daily for treatment of elevated intraocular pressure in patients with open-angle glaucoma. Clinical Ophthalmology (Auckland, NZ). 2013;7:7-14. doi:10.2147/OPTH.S30951.
  2. Stewart WC et al. Effects of carteolol and timolol on plasma lipid profiles in older women with ocular hypertension or primary open-angle glaucoma. American Journal of Ophthalmology , Volume 127 , Issue 2 , 142 – 147
  3. Morales DR, Dreischulte T, Lipworth BJ, Donnan PT, Jackson C, Guthrie B. Respiratory effect of beta‐blocker eye drops in asthma: population‐based study and meta‐analysis of clinical trials. British Journal of Clinical Pharmacology. 2016;82(3):814-822. doi:10.1111/bcp.13006.
  4. Envedi LB, Freedman SF. Safety and efficacy of brimonidine in children with glaucoma. J AAPOS. 2001 Oct; 5(5): 281-284.
  5. Wright TM, Freedman SF. Exposure to topical apraclonidine in children with glaucoma. Journal of Glaucoma: 2009 June; 18(5): 395-398.
  6. Guedes GB1, Karan A, Mayer HR, Shields MB. Evaluation of adverse events in self-reported sulfa-allergic patients using topical carbonic anhydrase inhibitors. J Ocul Pharmacol Ther.2013 Jun;29(5):456-61. doi: 10.1089/jop.2012.0123. Epub 2013 Feb 27.
  7. Geyer O, Levinger E, Segev E. Echothiophate iodide for uncontrolled glaucoma in aphakia and pseudophakia . Investigations in Ophthalmology and Visual Sciences. 2004;45(13):2091.
  8. Kazemi A, McLaren JW, Kopczynski CC, Heah TG, Novack GD, Sit AJ. The Effects of Netarsudil Ophthalmic Solution on Aqueous Humor Dynamics in a Randomized Study in Humans. Journal of Ocular Pharmacology and Therapeutics. 2018;34(5):380-386. doi:10.1089/jop.2017.0138.
  9. Serle JB et al. Two Phase 3 Clinical Trials Comparing the Safety and Efficacy of Netarsudil to Timolol in Patients With Elevated Intraocular Pressure: Rho Kinase Elevated IOP Treatment Trial 1 and 2 (ROCKET-1 and ROCKET-2). American Journal of Ophthalmology. Volume 168, 116-127.
  10. Girkin CA. 2016-2017 Basic Clinical Science Course, Section 10, Glaucoma. San Francisco, CA: American Academy of Ophthalmology, 2017. Web. 17 Aug 2018.
  11. Zabriskie NA. Medical Management of Glaucoma. [Classroom Presentation]. 16 Aug 2018.

Faculty Approval by: Griffin Jardine, MD

Copyright statement: Sean Collon, ©2018. For further information regarding the rights to this collection, please visit:

Identifier: Moran_CORE_25543