β-Adrenergic antagonists

Topical β-adrenergic antagonists, or β-blocker agents, must be used with caution in children. The systemic absorption of these agents is considerable—even with topical application—and can cause bronchospasm, bradycardia, and hypotension in susceptible children. β-Blockers should thus be avoided in children with asthma or significant cardiac disease. To decrease the risk of bronchospasm, the clinician may consider administering the cardioselective β-blocker betaxolol. The risk of adverse effects can also be diminished with occlusion of the nasolacrimal drainage system for 2 to 5 minutes after administration and use of the lowest effective dose (eg, timolol 0.25% or levobunolol 0.25% as opposed to 0.5%), particularly for young children. The clinician should teach parents how to occlude the nasolacrimal drainage system for administration at home. Patients with lighter irides may respond as well to timolol 0.25% or levobunolol 0.25% as they do to 0.5% of the same medication.

Carbonic anhydrase inhibitors

Topical use of dorzolamide or brinzolamide has a minimal risk of systemic adverse effects and is an excellent first-line therapy. Systemic CAIs (acetazolamide and methazolamide) provide slightly more IOP lowering than the topical preparations but are associated with numerous systemic adverse effects, including anorexia, diarrhea, weight loss, paresthesia, hypokalemia, risk of sickle cell crisis in patients with sickle cell anemia, and metabolic acidosis, which can affect bone growth. Children using other diuretics are particularly at risk for these adverse effects. Because of the risk of these adverse effects and of rare but life-threatening reactions such as Stevens-Johnson syndrome and aplastic anemia, systemic CAIs are reserved for patients at great risk of vision loss due to highly elevated IOP. The pediatric dosage of oral acetazolamide is 10–20 mg/kg/day.

α-Adrenergic agonists

The α2-adrenergic agonist brimonidine, which crosses the blood–brain barrier, may have significant effects on the central nervous system, including apnea, hypotension, bradycardia, hypotonia, hypothermia, and somnolence. Infants and young children are particularly susceptible to brimonidine’s adverse effects; thus α2-adrenergic agonists are contraindicated in children younger than 2 years. Although brimonidine is FDA approved for use in children over the age of 2, there is some debate about the age at which children can safely use this drug. In general, it should be used with caution in children up to the teenage years. The lowest dose possible should be used and punctal occlusion employed to minimize systemic absorption.

The α2-adrenergic agonist apraclonidine is better tolerated systemically in children, but the risk of follicular conjunctivitis increases with long-term use. Apraclonidine also acts as a vasoconstrictor and can be used to minimize bleeding during surgery.

Prostaglandin analogues

Prostaglandin analogues have minimal systemic side effects and are dosed once daily. They have been shown to effectively lower IOP in JOAG. Older children respond better to prostaglandin analogues than younger children and infants. These drugs have been shown to be well tolerated and effective in patients with uveitis; however, in some cases, they may cause or exacerbate uveitis.

Cholinergic agonists

Cholinergic agonists are seldom used for long-term glaucoma therapy, particularly in phakic eyes due to induced myopia. Echothiophate (Phospholine Iodide) is highly effective in many patients with aphakic glaucoma and can be dosed once daily; however, its use in children is associated with the development of iris cysts. Use of echothiophate also results in breakdown of the blood–aqueous barrier; therefore, it must be discontinued well in advance of any surgical procedure to prevent postsurgical inflammation. Cholinergic agents can be used intraoperatively to induce miosis, which facilitates angle surgery. They are sometimes used for a limited period of time after angle surgery to prevent peripheral anterior synechiae formation.

Rho kinase inhibitors

There are no published reports on the use of Rho kinase inhibitors in pediatric patients.

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• Coppens G, Stalmans I, Zeyen T, Casteels I. The safety and efficacy of glaucoma medications in the pediatric population. J Pediatr Ophthalmol Strabismus. 2009;46(1):12–18.

• Maeda-Chubachi T, Chi-Burris K, Simons BD, et al; A6111137 Study Group. Comparison of latanoprost and timolol in pediatric glaucoma: a phase 3, 12-week, randomized, double-masked multicenter study. Ophthalmology. 2011;118(10):2014–2021.

Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.