FDA Approved Indications
The American Academy of Ophthalmology published a practice guideline in 2016 which recommends periodic dilated eye exam in different age groups. 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. 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%. The lower concentration of 0.5% is preferable in adolescents since it produces less ocular discomfort with the same efficacy as the 1% solution.
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. 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.
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.
FDA Non-approved, off-label use
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. Another Parkinsonian symptoms in which tropicamide may have a role in alleviating is the characteristic tremor exhibited by Parkinson patients.
The mechanism for dilation:
The mechanism for cycloplegia:
The mechanism for reduction of sialorrhea:
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. In a recently published randomized clinical trial, researchers concluded that administration via an ophthalmic insert was safe and effective for use in neonates.
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. The use of anticholinergic drugs carries a small risk of central nervous system (CNS) disturbance, including psychotic reactions and behavioral problems. 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. 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. 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.
There are no recommended diagnostic exams for monitoring the use of tropicamide.
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. At times, only a partial reversal was observed. A study of 23 healthy subjects demonstrated that pilocarpine had an insignificant impact on returning pupil diameter to baseline. Seventeen percent of subjects reportedly had a reduction in visual acuity, indicating that the use of pilocarpine is not only futile but possibly detrimental. 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. The use of dapiprazole can cut recovery time in half compared to waiting for tropicamide to wear off on its own . 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 should wear sunglasses to mitigate light sensitivity.
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. Healthcare professionals should be informed to recognize better 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 the 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.
The use of tropicamide in the clinical setting requires an interprofessional 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]
|||Feder RS,Olsen TW,Prum BE Jr,Summers CG,Olson RJ,Williams RD,Musch DC, Comprehensive Adult Medical Eye Evaluation Preferred Practice Pattern(®) Guidelines. Ophthalmology. 2016 Jan; [PubMed PMID: 26581558]|
|||Mamalis N, Importance of pupil dilation for cataract surgery. Journal of cataract and refractive surgery. 2017 May; [PubMed PMID: 28602315]|
|||Grob SR,Gonzalez-Gonzalez LA,Daly MK, Management of mydriasis and pain in cataract and intraocular lens surgery: review of current medications and future directions. Clinical ophthalmology (Auckland, N.Z.). 2014; [PubMed PMID: 25061276]|
|||Hassler-Hurst J,Wadham C,Rayman G, A double-blind study comparing 0.5% and 1% tropicamide for annual retinal screening in diabetic adolescents. Diabetic medicine : a journal of the British Diabetic Association. 2004 May; [PubMed PMID: 15089787]|
|||Anderson HA,Bertrand KC,Manny RE,Hu YS,Fern KD, Comparison of two drug combinations for dilating dark irides. Optometry and vision science : official publication of the American Academy of Optometry. 2010 Feb; [PubMed PMID: 20035241]|
|||Siderov J,Nurse S, The mydriatic effect of multiple doses of tropicamide. Optometry and vision science : official publication of the American Academy of Optometry. 2005 Nov; [PubMed PMID: 16317370]|
|||Yazdani N,Sadeghi R,Momeni-Moghaddam H,Zarifmahmoudi L,Ehsaei A, Comparison of cyclopentolate versus tropicamide cycloplegia: A systematic review and meta-analysis. Journal of optometry. 2018 Jul - Sep; [PubMed PMID: 29132914]|
|||Lloret SP,Nano G,Carrosella A,Gamzu E,Merello M, A double-blind, placebo-controlled, randomized, crossover pilot study of the safety and efficacy of multiple doses of intra-oral tropicamide films for the short-term relief of sialorrhea symptoms in Parkinson's disease patients. Journal of the neurological sciences. 2011 Nov 15; [PubMed PMID: 21636098]|
|||Park JH,Lee YC,Lee SY, The comparison of mydriatic effect between two drugs of different mechanism. Korean journal of ophthalmology : KJO. 2009 Mar; [PubMed PMID: 19337478]|
|||Smith SA,Smith SE, Evidence for a neuropathic aetiology in the small pupil of diabetes mellitus. The British journal of ophthalmology. 1983 Feb; [PubMed PMID: 6821679]|
|||Pukrushpan P,Tulvatana W,Kulvichit K, Intraocular pressure change following application of 1% tropicamide for diagnostic mydriasis. Acta ophthalmologica Scandinavica. 2006 Apr; [PubMed PMID: 16637852]|
|||Hofmeister EM,Kaupp SE,Schallhorn SC, Comparison of tropicamide and cyclopentolate for cycloplegic refractions in myopic adult refractive surgery patients. Journal of cataract and refractive surgery. 2005 Apr; [PubMed PMID: 15899444]|
|||Nakamura T,Matsui M,Uchida K,Futatsugi A,Kusakawa S,Matsumoto N,Nakamura K,Manabe T,Taketo MM,Mikoshiba K, M(3) muscarinic acetylcholine receptor plays a critical role in parasympathetic control of salivation in mice. The Journal of physiology. 2004 Jul 15; [PubMed PMID: 15146045]|
|||Betz AJ,McLaughlin PJ,Burgos M,Weber SM,Salamone JD, The muscarinic receptor antagonist tropicamide suppresses tremulous jaw movements in a rodent model of parkinsonian tremor: possible role of M4 receptors. Psychopharmacology. 2007 Oct; [PubMed PMID: 17594079]|
|||Portes AJ,Barbosa AC,de Mello GL,Lopes MA,Cavalcanti RS, Tropicamide 1% mydriatic effect: comparison between spray in closed eyes and eye drops in open eyes. Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics. 2012 Dec; [PubMed PMID: 22775152]|
|||Akman A,Aydin P, Comparison of mydriatic efficacy of spray application and drop instillation of tropicamide 1%. Eye (London, England). 1999 Oct; [PubMed PMID: 10696320]|
|||Wong CY,Fan DS,Yu CB,Lam DS, Topical mydriatic and cycloplegic spray for Chinese children. Journal of pediatric ophthalmology and strabismus. 2003 Nov-Dec; [PubMed PMID: 14655983]|
|||Bremond-Gignac D,Jacqz-Aigrain E,Abdoul H,Daruich A,Beresniak A,Baud O,Alberti C, Ophthalmic Insert versus Eye Drops for Mydriasis in Neonates: A Randomized Clinical Trial. Neonatology. 2019; [PubMed PMID: 30481790]|
|||Vuori ML,Kaila T,Iisalo E,Saari KM, Systemic absorption and anticholinergic activity of topically applied tropicamide. Journal of ocular pharmacology. 1994 Summer; [PubMed PMID: 8083562]|
|||van Minderhout HM,Joosse MV,Grootendorst DC,Schalij-Delfos NE, Adverse reactions following routine anticholinergic eye drops in a paediatric population: an observational cohort study. BMJ open. 2015 Dec 23; [PubMed PMID: 26700273]|
|||Lavanya R,Baskaran M,Kumar RS,Wong HT,Chew PT,Foster PJ,Friedman DS,Aung T, Risk of acute angle closure and changes in intraocular pressure after pupillary dilation in Asian subjects with narrow angles. Ophthalmology. 2012 Mar; [PubMed PMID: 22118999]|
|||Pandit RJ,Taylor R, Mydriasis and glaucoma: exploding the myth. A systematic review. Diabetic medicine : a journal of the British Diabetic Association. 2000 Oct; [PubMed PMID: 11110501]|
|||Tropicamide 2006; [PubMed PMID: 30000733]|
|||Anastasi LM,Ogle KN,Kearns TP, Effect of pilocarpine in counteracting mydriasis. Archives of ophthalmology (Chicago, Ill. : 1960). 1968 Jun; [PubMed PMID: 5652262]|
|||Nelson ME,Orton HP, Counteracting the effects of mydriatics. Does it benefit the patient? Archives of ophthalmology (Chicago, Ill. : 1960). 1987 Apr; [PubMed PMID: 3566601]|
|||Mapstone R, Dilating dangerous pupils. The British journal of ophthalmology. 1977 Aug; [PubMed PMID: 143952]|
|||Doughty MJ,Lyle WM, A review of the clinical pharmacokinetics of pilocarpine, moxisylyte (thymoxamine), and dapiprazole in the reversal of diagnostic pupillary dilation. Optometry and vision science : official publication of the American Academy of Optometry. 1992 May; [PubMed PMID: 1350669]|
|||Molinari JF,Johnson ME,Carter J, Dapiprazole clinical efficiency for counteracting tropicamide 1%. Optometry and vision science : official publication of the American Academy of Optometry. 1994 May; [PubMed PMID: 7915025]|
|||Bersani FS,Imperatori C,Prilutskaya M,Kuliev R,Corazza O, Injecting eye-drops: a mini-review on the non-clinical use of tropicamide. Human psychopharmacology. 2015 Jul; [PubMed PMID: 26216560]|