Tropicamide

Article Author:
Diana Hong
Article Editor:
Koushik Tripathy
Updated:
7/30/2019 4:31:27 PM
PubMed Link:
Tropicamide

Indications

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 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 difficult 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.

Mechanism of Action

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 is 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. Promising results have been demonstrated 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

Contact lenses should be removed before administration. 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 children, ensure that the drug does not get to their mouth. Hands require washing after instillation of 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, administration via an ophthalmic insert was concluded to be 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 may be used to dilate the pupil optimally.

Adverse Effects

Ocular adverse events include transient stinging, photophobia, superficial punctate keratitis, blurred vision, and 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] Use of anticholinergic drugs carries the 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 reaction 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 disease should take priority.[22] The importance of getting a clear view of the fundus should not be undermined. Nonetheless, care should be taken to monitor and educate at-risk patients of 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. 

Contraindications

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]

Monitoring

There are no recommended diagnostic exams for monitoring the use of tropicamide.

Toxicity

Although tropicamide is a short-acting drug, and frequency of associated adverse events are rare, there are certain instances when reversal of mydriasis is necessary, including decreasing the risk of angle closure glaucoma, improving blurry vision, and decreasing recovery time for patient comfort. Presumably, a cholinergic agent like pilocarpine should be able to undo the effects of an anticholinergic drug. However, several studies have reported conflicting pupillary response.[24][25][22][26] At times, only a partial reversal was observed.[27] A study of 23 healthy subjects demonstrated that pilocarpine had an insignificant impact on returning pupil diameter to baseline. Seventeen percent of subjects were reported to have a reduction in visual acuity, indicating that the use of pilocarpine is not only futile but possibly detrimental.[25] For these reasons, its use after tropicamide-induced dilation has not gained wide acceptance. Alternatively, an adrenergic block agent, such as dapiprazole or moxisylyte, can be used. This class of drug exerts its effect by causing relaxation of the dilator muscle.[27] Use of dapiprazole can cut recovery time in half compared to waiting for tropicamide to wear off on its own [28]. Unfortunately, FDA has removed dapiprazole off the market for reasons unrelated to safety and efficacy. Currently, there are no approved methods of reversing tropicamide-induced mydriasis and patients are still advised to wear sunglasses to mitigate light sensitivity.

Enhancing Healthcare Team Outcomes

Intravenous injection of tropicamide and other eye-drops is a non-clinical use that has been on the rise in polydrug abusers. A recently published review describes factors such as low cost, easy access, and enhancement of heroin effects as reasons for its misuse.[29] Healthcare professionals should be informed to better recognize high-risk populations of drug users and patients with psychiatric disorders.

There is limited information on interprofessional communication and tropicamide as the absence of associated adverse events is well established. Nonetheless, coordinated care between healthcare team including the pharmacist, optician, nurse practitioner, and the ophthalmologist ensures better outcomes. Suggestions for improvement include proper medication documentation and routine patient education.

Use of tropicamide in the clinical setting requires an interdisciplinary approach including physicians, specialists, specialty trained nurses, and the pharmacist, operating in a team structure that leads to optimal patient results and minimizes adverse events. [Level V]


References

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