Dilating agents, which are frequently used for retinal examination and refraction, are a class composed of sympathomimetics and parasympatholytics. These agents have potentially severe systemic side effects, as listed in Table 1 , to which premature infants are especially sensitive. All mydriatics work more effectively in those with lighter irides, which may necessitate higher doses for dark-eyed patients.
Phenylephrine hydrochloride (AK-Dilate®, Akorn, Someret, NJ; Mydfrin®, Alcon, Ft. Worth, TX) is often used in conjunction with parasympatholytics to produce maximal dilation of the pupil for examination of the peripheral retina or prior to intraocular surgery. Phenylephrine may cause hypertension and tachycardia and should be used with caution in children, especially those with hyperthyroidism or tachyarrhythmias. One case was reported of acute gastric dilatation in a preterm infant after two drops each of cyclopentolate 0.5% and phenylephrine 2.5%, and paralytic ileus. Delaying feeding until after the ocular examination minimizes gastrointestinal side effects. Some preparations may contain sulfites, which cause allergic reactions in susceptible individuals. Systemic effects are rare with preparations of 2.5% or less. The 10% solution should be avoided in children as significant reactions can occur. In one study of preterm infants, a significant increase of blood pressure and heart rate peak values was observed within 7-10 minutes after use of a combination of 0.5% cyclopentolate and 0.5% tropicamide but did not occur after use of a combination of 2.5% phenylephrine and 0.5% tropicamide. The phenylephrine-tropicamide combination also gave superior mydriasis.
In another study, two doses of phenylephrine 2.5% plus 1% tropicamide resulted in a 20% increase in mean blood pressure of infants weighing less than 1,600 g, with three of 12 infants having a greater than 50% increase in mean blood pressure. Microdrops (5.6 µl) were compared to standard drops (35.4 µl) of cyclopentolate, phenylephrine, and tropicamide in one study. There was no significant difference in pupillary diameter between groups, but mean blood pressure increased significantly in infants given standard drops.
Phenylephrine-induced hypertension may be relieved by administration of an alpha-adrenergic blocking agent (e.g., phentolamine). The pupillary dilation caused by phenylephrine and tropicamide can be reversed with dapiprazole hydrocloride (Rev-Eyes™, Storz Ophthalmic, a division of Bausch & Lomb, Rochester, NY) Dapiprazole induces miosis via relaxation of the radial muscle of the iris. It may also partially reverse paralysis of accommodation (Lexi-Comp™ Online, accessed April 10, 2005).
Cycloplegic agents are para-sympatholytics that cause both mydriasis and cycloplegia. These medications are indicated for retinal examination and refraction in infants and young children, the treatment of amblyopia, postoperative cycloplegia, and prevention of synechiae and pain management due to ciliary spasm in uveitis. Atropine is necessary to achieve adequate cycloplegia in some children. The usual dosage for cycloplegic refraction in children is one drop of 0.5% atropine solution bilaterally twice daily or one centimeter of a 1% ointment into the conjunctival sac once daily for 1-3 days prior to examination. One study demonstrated that an accurate assessment of refraction was possible with a single dose of atropine 90 minutes prior to examination, which produced a cycloplegic effect within 0.5 diopters (D) of that achieved with 3-day atropinization. Atropine is also useful as a treatment for amblyopia, and the usual dosage is 1% once daily or twice weekly in the sound eye. Long-acting cycloplegic agents, such as scopolamine 0.25% (Isopto® hyoscine, Alcon, Ft. Worth, TX), administered two to four times daily, or atropine 0.25%/0.5%/1%, given twice daily, are also utilized for treatment of ciliary spasm and to prevent posterior synechiae in uveitis. The average duration of action for scopolamine is 4-7 days, compared to 1-2 weeks for atropine.
The general signs and symptoms of anticholinergic toxicity include dryness of mouth and skin, fever, delirium, tachycardia, and death in the debilitated patient. Infants are more susceptible to the toxic effects of atropine, which may occur with as little as one drop of a 0.5% solution bilaterally. Some patients are particularly susceptible to toxicity, including those with Down syndrome, lightly pigmented individuals, and brain-damaged patients. The history of toxic effects of ocular atropine in children does include several reported deaths in medical literature published prior to 1951; no such reports are found in current published literature. An online drug index reported that four deaths due to topical atropine in patients 10 months to 3 years of age involved total estimated ophthalmic doses of 1.6, 2, 4, and 18 mg given once or over 1-2 days ( www.rxlist.com , accessed April 10, 2005). If accidentally ingested, emesis should be induced or gastric lavage performed with 4% tannic acid. If an infant or child shows evidence of severe anticholinergic toxicity, physostigmine 0.05% should be injected intravenously (0.02 mg/kg) every 5 minutes as needed, up to a maximum of 2 mg.
Cyclopentolate has a duration of action of 6-24 hours and is ideal for refraction in children. It is typically given once or twice (with a 5-minute inter val between doses) and a cycloplegic refraction is done 30-40 minutes later. Approximately 0.5-0.75 D of hypermetropia may be undetected compared to refraction after atropine. The adverse systemic effects of cyclopentolate are dose related and include behavioral changes, seizures, and gastrointestinal disturbances, including necrotizing enterocolitis in infants. Six drops of 0.5% cyclopentolate have been reported to have systemic effects on premature infants. There are some reports that cyclopentolate may increase cellular infiltration in the anterior chamber, leading some clinicians to avoid using this agent in patients who have uveitis.
Tropicamide produces incomplete cycloplegia and has a duration of action of 2-6 hours. The use of a combination of lignocaine and tropicamide has been reported to potentiate mydriasis in dark eyes, possibly due to increased intraocular penetration via a mechanism of corneal microepithelial damage and reduced tearing. In a double-masked, placebo-controlled, randomized clinical study, 60 dark brown eyes (patients aged 5-60 years of age) were randomized to administration of either one drop of 4% lignocaine or placebo 3 minutes before administration of 1% tropicamide. The study eyes demonstrated significantly increased pupillary diameters in patients receiving lignocaine (3.62 ± 0.75 mm) as compared to controls (90% of study eyes attained 6-mm size versus 67% of control eyes [P = 0.016]). The time required for 50% of the eyes to reach this 6-mm size was also much faster in the study group (median time = 23.3 minutes) when compared with the control group (30.0 minutes; P = 0.005).
The combination of cyclopentolate hydrochloride 0.2% and phenylephrine hydochloride 1% (Cyclomydril®, Alcon, Ft. Worth, TX) delivers lower concentrations than separate instillations of commercially available cyclopentolate 1% and phenylephrinine 2.5%, making it desirable for mydriasis prior to examining premature infants. In one study of 30 low birth weight infants, Cyclomydril® did not produce any increase in mean blood pressure. In another study, one drop of a combination of 1.3% cyclopentolate, 0.167% tropicamide, and 1.6% phenylephrine gave effective cycloplegia in dark irides with no side effects in 25 children, offering the advantages of rapid onset, short duration, and single dose.
Compr Ophthalmol Update. 2005;6(2):85-101. © 2005 Comprehensive Ophthalmology Update, LLC
Cite this: Ophthalmic Medications in Pediatric Patients - Medscape - Mar 01, 2005.