Published: 6 December 2019


A drop in the eye has widespread ripples

Prescriber Update 40(4): 85–86
December 2019

Key Messages

  • Some eye drops can cause systemic adverse reactions.
  • Only a small proportion of each dose is retained in the eye.
  • Systemic absorption may be reduced by:
    • closing the eye and/or pressing a clean forefinger where the lower eyelid meets the nose
    • waiting at least 5–10 minutes between applying drops to the same eye.


The Centre for Adverse Reactions Monitoring (CARM) recently received the first report of a patient who developed confusion and psychosis approximately one week after starting treatment with prednisolone eye drops (CARM ID: 132498). The symptoms slowly resolved on stopping the prednisolone eye drops.

Where does the eye drop go?

Eye drops can cause systemic adverse reactions. It is estimated that only 5–10 percent of the active medicine included in an eye drop remains in the eye, and up to 80 percent may reach the general circulation. Because of poor bioavailability, the dose of the active ingredient in eye drops often needs to be comparatively high1.

How much remains in the eye depends on a variety of factors, such as the characteristics of the eye drop and administration technique. Infants, pregnant and nursing women and aged patients are particularly at risk for systemic adverse reactions from eye drops2.

Tears and eye drops drain through a small canal into the nose which is lined with nasal mucosa containing many blood vessels. Once in contact with the vascular nasal mucosa, relatively rapid absorption of the active ingredient into the bloodstream can occur avoiding the first passage through the liver1,3.

A second drop instilled immediately after the first results in an even higher proportion of active ingredient passing into the nasal mucosa1.

What do the data sheets say?

The New Zealand data sheets for prednisolone eye drops 1% solution state that, although systemic effects are extremely uncommon, there have been rare occurrences of systemic hypercorticoidism after use of topical steroids4,5.

Exogenous glucocorticoids such as prednisolone can lead to Cushing’s syndrome, which includes psychiatric disturbances.

Can systemic absorption be avoided?

Systemic absorption can be significantly reduced by:1,3,6

  • keeping the eyelid gently closed for 2–3 minutes after instilling drops
  • applying gentle pressure over the tear duct with a clean finger for 3 minutes after instillation
  • waiting at least 5–10 minutes between eye drops, if more than one drop is required.


  1. Labetoulle M, Frau E, Le Jeunne C. 2005. Systemic adverse effects of topical ocular treatments. Presse Med 34(8): 589–95.
  2. Vaajanen A, Vapaatalo H. 2017. A single drop in the eye – Effects on the whole body? Open Ophthalmol J 11: 305–14. DOI: 10.2174/1874364101711010305 (accessed 23 October 2019).
  3. Glaucoma Research Foundation. 2011. Eye Drop Techniques from Dr. Andrew Iwach 25 February 2011. URL: (accessed 18 October 2019).
  4. Allergan New Zealand Ltd. 2017. Pred Forte Eye drops, solution (Allergan) 1% New Zealand Data Sheet December 2017. URL: (accessed 18 October 2019).
  5. AFT Pharmaceuticals Ltd. 2018. Prednisolone Eye drops, solution (AFT) 1% New Zealand Data Sheet 20 November 2018. URL: (accessed 18 October 2019).
  6. Farkouh A, Frigo P, Czejka M. 2016. Systemic side effects of eye drops: a pharmacokinetic perspective. Clin Ophthalmol 10: 2433–41. DOI: 10.2147/OPTH.S118409 (accessed 18 October 2019).
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