FDA Approved Indications

• Intended for diagnostic purposes: to achieve mydriasis

The American Academy of Ophthalmology published a practice guideline in 2016 which recommends periodic dilated eye exam in different age groups.[1] Achieving a clinically effective pupil diameter of 6mm is essential for viewing structures in the posterior segment. The most common indication for a comprehensive exam with pupillary dilation is screening for diabetic retinopathy, in which the nondilated exam gives the correct classification for presence or stage of diabetic retinopathy in only  50% cases. Dilation is also necessary for specific intraocular procedures such as cataract surgery to reduce intraoperative complications and for better exposure of the cataract during surgery.[2] Pupillary dilation is also necessary for retinal surgery and investigations of the posterior segment. The use of mydriatic agents such as tropicamide has, therefore, become ubiquitous in all optical settings. Tropicamide comes in two formulations, 0.5%, and 1.0%.[3] The lower concentration of 0.5% is preferable in adolescents since it produces less ocular discomfort with the same efficacy as the 1% solution.[4]

Conversely, the higher concentration is typically used in adults and challenging to dilate patients such as those who have pigmented eyes. Tropicamide binds with pigment and therefore, may take longer to act on darker irises.[5] Interestingly, one pilot study that evaluated the use of multiple drops of tropicamide concluded that a single drop of 0.5% is not inferior to two drops of 0.5% in pigmented eyes.[6]

• Intended for diagnostic purposes: cycloplegia

Eyecare specialists are interested in accommodation paralysis, also known as cycloplegia, when determining a patient's refractive error. Cycloplegic agents inactivate the ciliary muscle, so the patient is unable to influence the refractive measurement. Accurate evaluation is necessary before LASIK surgery, for example. In a 2017 meta-analysis, the more popular cycloplegic drug of choice, cyclopentolate, was compared to tropicamide. The research concluded that tropicamide is a viable alternative.[7]

FDA Non-approved, off-label use 

• Parkinson Disease

The properties of anticholinergics can counter the imbalanced dopaminergic to cholinergic activity in neurological disorders such as Parkinson's disease. One randomized, pilot study observed the safety and efficacy of tropicamide's ability to reduce sialorrhea in neurodegenerative diseases. Tropicamide was given orally as a dissolving film. Although the small sample size limited the power, a significant decrease in perceived symptoms on the visual analog scale and saliva volume measured with cotton balls occurred.[8] Another Parkinsonian symptoms in which tropicamide may have a role in alleviating is the characteristic tremor exhibited by Parkinson patients.

The mechanism for dilation:

• As a parasympathetic antagonist, tropicamide exerts its dilatory effects by acting on the pupillary sphincter muscle to cause its relaxation.[9]  Like other anticholinergic agents, tropicamide inhibits the parasympathetic drive, allowing the sympathetic actions to dominate.[10]  As the radial muscles of iris (dilator pupillae), which are innervated by the sympathetic nervous system, are unaffected, they contract and cause the pupil to dilate. Its optimal effect occurs 25 to 30 minutes post-administration.[11] Typically, mydriasis reverses within 4 to 8 hours. However, it may take 24 hours for the mydriatic effect to wear off in some individuals. Weaker strength may cause mydriasis with little cycloplegia.

The mechanism for cycloplegia:

• Accommodation becomes hindered when tropicamide blocks the muscarinic receptors of the ciliary body. Its cycloplegic effect can last anywhere from 4 to 10 hours, with the onset of action occurring within 20 to 30 minutes.[12]

The mechanism for reduction of sialorrhea: 

• Inhibition of the muscarinic acetylcholine receptors on salivary glands is responsible for decreasing hypersalivation in Parkinson patients.[8][13] Its potential therapeutic utility is because it is relatively selective for M4 receptors. Researchers have seen promising results in abolishing drug-induced tremulous jaw movement in rodent models.[14] Future studies will have to determine if the tremorolytic effects can be clinically useful and extended to man.

Administration requires the removal of contact lenses. This topical ophthalmic solution is instilled into the eye in droplet form. The lacrimal sac should be compressed with the fingertip for 2 to 3 minutes after administration to reduce systemic absorption and systemic adverse effects. The tip of the dropper should not touch any surface as it might contaminate the drug. In a child, ensure that the drug does not get to their mouth. Hands require washing after instilling the drop. The individual should avoid driving and should not engage in potentially hazardous activities during pupillary dilation. After pupillary dilation, sensitivity to light may occur, and sunglasses may be necessary.

An infrequently used option is by way of spray application. Several studies have shown that using tropicamide in its vaporized form is just as effective in achieving increased pupil diameter, but with less patient-reported discomfort.[15][16][17] In a recently published randomized clinical trial, researchers concluded that administration via an ophthalmic insert was safe and effective for use in neonates.[18]

Along with the active ingredient (tropicamide), there are multiple inactive ingredients in the drop. These include- benzalkonium chloride (preservative), purified water, edetate disodium dihydrate, and boric acid. Hydrochloric acid and/or sodium hydroxide are used to adjust pH to 4.0 to 5.8. 

For refraction, one drop of tropicamide 1% is put in each eye 5 minutes apart. For examination of the fundus, 0.5% strength is an option.

Tropicamide may be used to dilate pupils in acute anterior uveitis, and one drop every 5 to 10 minutes should dilate the pupil optimally.

Ocular adverse events include transient stinging, photophobia, superficial punctate keratitis, blurred vision, and a rise in intraocular pressure.

Potential anticholinergic effects include dry mouth, increased heart rate, and headache. Young children and the elderly are most susceptible to these side effects. Fortunately, due to its low affinity for muscarinic receptors, tropicamide rarely causes the systemic effects listed above.[19] The use of anticholinergic drugs carries a small risk of central nervous system (CNS) disturbance, including psychotic reactions and behavioral problems.[20] Serious adverse events, especially vasomotor and cardiorespiratory collapse, behavioral changes, and psychotic reactions, have been reported rarely in children with the use of anticholinergic drugs. The medicine should remain out of the reach of children.

Other side effects include nausea, vomiting, pallor, allergic reactions, and muscular rigidity.

Precipitating angle closure in primary open-angle glaucoma patients, as well as the potential increase in intraocular pressure after mydriasis is a frequent concern to many ophthalmologists.[21] However, multiple studies that involved high-risk groups demonstrated that the incidence is relatively low, and the risk of underdiagnosing vision-threatening diseases should take priority.[22] The importance of getting a clear view of the fundus should not be undermined. Nonetheless, clinicians should be careful to monitor and educate at-risk patients regarding what symptoms to look out for, such as headache and eye pain. 

Tropicamide is a category C drug in pregnancy, and it is not known whether this drug is excreted in human milk. 

Hypersensitivity to any active/inactive ingredient constitutes a contraindication for its use. There have been no studies on tropicamide use during breastfeeding, but nursing mothers can reduce the amount that reaches the lactiferous ducts by applying pressure to the tear duct for 1 minute and wiping away any excess solution.[23]