Systemic Side Effects of Atropine Eye Drops

As there are systemic side effects of atropine eye drops, they could be contraindicated in young patients with some conditions, syndromes, and medications. Atropine, known to eye care professionals for its mydriatic and cycloplegic effects and efficacy to slow the progression of myopia, is also a systemic medication used in cardiovascular management.¹ Originally derived from Belladonna,² it is an antimuscarinic agent (or muscarinic antagonist), which means it inhibits postganglionic (end-of-nerve) muscarinic receptors. When used systemically, this affects the parasympathetic system, and increases cardiac output - increases heart rate and conduction.¹ It is mainly used in the treatment of people with bradycardia³ (when your heart rate is too slow), but as it affects the parasympathetic system it is sometimes used to decrease salivation in patients whom are intubated.¹

Acetylcholine is involved in the developing retina, and when atropine is given as an eye drop it blocks the action of acetylcholine at the muscarinic receptors which is postulated to be a mechanism by which atropine can slow eye growth and myopia progression^.4

Atropine's ocular side effects are well known. In myopia control studies, some have reported 100% of patients on 1% atropine experience photophobia,⁵ which reduces to 22% at 0.5% and 7% at 0.25%.⁶ Despite the mydriatic side effects which could increase intraocular pressure, there have been no reports of atropine inducing ocular hypertension in children.⁷ Lower concentrations appear to have fewer side effects, and with correct spectacle management such as photochromatic and bifocal or  progressive spectacle lenses, the studies report that most patients can find stronger concentrations tolerable when they are utilized.⁸

If atropine passes through the puncta to the nasolacrimal duct and is absorbed through the nasal mucosa it has the potential to cause systemic side effects. These can include mouth and eye dryness,⁸ delirium or restlessness,^4,8 tachycardia⁸ (rapid and weak pulse) and flushed skin and face.^8,9

A suggested mnemonic for remembering the systemic activity and side effects of atropine is "hot as a hare, red as a beet, dry as a bone, blind as a bat, mad as a hatter."⁸ More significant cases of systemic atropine poisoning can cause drowsiness, central nervous depression, circulatory collapse with respiratory failure and death.⁸ Whilst atropine-related deaths are rare, due to the high metabolic excretion rate, a dose of as little 10mg can be fatal: or the oral ingestion of 20 drops of a 1% atropine solution.⁸ A case of this occurring in America⁸ highlights that whilst the safety profile of the eye drop is good, medication should be stored safely, properly and far out of the reach of children.

When considering the systemic toxicity effects of atropine as an eye drop, poisoning via the eye is likely impossible. A 0.1% solution of atropine contains 0.5mg per drop, and to achieve the potential lethal dose from the eye drop for children 20 drops would be required to be absorbed simultaneously through the conjunctiva, which is not anatomically or physiologically possible for the eye's limited capacity to hold eye drop volume.¹⁰ Atropine is also quickly metabolised, between 2-5 hours - it's likely that achieving systemic toxicity through an ocular preparation would be difficult.¹⁰ There have been reported fatalities, though, following the use of ocular topical 1% atropine in small children with the congenital cardiac condition Patent Ductus Arteriosus (PDA) and other cardiac co-morbidities.⁸

Anticholinergic medications have been associated with decreased cognitive function, but there is only a correlation between long term, high dose, systemic use,⁴ and further studies about the potential later life impacts of long term atropine dosing should be studied. It is presumed that with proper punctal occlusion and safe medicine storage, this would be unlikely in a child treated long term in the low concentrations prescribed for myopia control.

Allergic reactions to the atropine drops can not only be ocular but periocular, and occur with more frequency as the concentration of atropine increases.¹¹ Symptoms may include lid oedema, itching and madarosis (loss of eyelashes).¹¹ Any of these symptoms should lead to ceasing of atropine and appropriate management of the allergy.

So who is not suitable for atropine use? Firstly, many clinical manuals and suggest that atropine drops should be avoided in patients with down syndrome, due to concerns regarding excessive mydriatic and cycloplegic effects and potential system toxicity.^10,12 However other studies refute this, suggesting that reduced accommodative ability is part of the clinical syndrome,⁸ and concerns are unfounded.^8,10,13

The majority of reported systemic complications from atropine have occurred from children with pre-existing heart conditions, such a congenital rubella syndrome and developmental delays.^8,14 If your patient has a congenital syndrome or a heart condition, caution should be exercised in regards to topical atropine prescription. Caution should also be taken in patients with a history of asthma, or other lung disease as systemic dosing of atropine can cause thickening of the mucous in the lungs and drying in the airways.² Also exercise caution when patients are taking other medications that may have anticholingeric or antimuscarinic effects to avoid increased side effects - this includes some medicines used to treat depression and some antihistamines¹⁵ but this is by no means an exhaustive list.  Communication and co-management with the patient's healthcare team is essential to discuss risk/benefits - strict instruction and close supervision of patients in a risk category is a must.¹⁴

One way of reducing potential side effects is by instilling the drops in a way that reduces risk of atropine passing through the puncta with eventual systemic absorption. Ensure clean hands and that the bottle top does not touch the eye. Instruct parents to retract the lower lid of the child and place the drop in the "pouch" formed while the child looks up. Place a single drop and instruct the patient to close their eye immediately. Place a finger gently but firmly on the nasal corner of the closed eye and hold for about two minutes. By doing this technique or the very similar DOT technique (Don't Open Eyes), systemic absorption is reduced.¹⁵

If your childhood myopic patient does not have any of the potential contraindications listed above, the use of low dose atropine should be safe for the majority.^8,9,14,16 As with all medications, careful monitoring of the patient for tolerance, compliance and side effects and ongoing follow up is a must.

• Atropine – wonder or weak treatment?
• When to prescribe Atropine for myopia control
• Complex Atropine Cases
• Complications in atropine compounding
• The Latest and Greatest Research on Atropine

• Which atropine dosage should I prescribe for myopia control?

• Atropine eye drops and ocular allergy - what's the cause?

1. Atropine, engaging with science and responsible practice with Professor Karla Zadnik from Ohio State University, USA.

2. More on atropine 0.01% treatment for myopia management with Professor Mark Bullimore from the University of Houston, Texas USA.

3. Atropine 0.01% for myopia management with Professor James Loughman from Technological University Dublin, and the Centre for Eye Research Ireland.