A 32-year-old male with surgically induced Horner’s syndrome in his right eye presented with mild hyperemia and irritation. He reported that his symptoms have persisted for several years. Additionally, a previous eye care provider “diagnosed” contact lens overwear, although that is a rather nonspecific term.

The patient reported dosing his right eye with Visine LR (McNeil-PPC) at least 20 times per day on top of his contact lens for the last decade to help control his Horner-induced ptosis. Upon examination of the right eye, we documented numerous deep-stromal opacities located across the entire cornea, as well as diffuse superficial punctate epithelial erosions. Remarkably, he had minimal hyperemia.

We diagnosed him with medicamentosa secondary to chronic topical dosing. We instructed him to discontinue Visine LR use. Additionally, to treat the underlying ptosis, we recommended either surgical intervention or use of a compounded, preservative-free formulation of oxymetazoline.

Medicamentosa may develop in patients who endure long-term exposure to certain topical medications or preservative agents. Photo: Andrew S. Gurwood, OD
What is Medicamentosa?
Medicamentosa is a chemical irritation or a delayed, cell-mediated hypersensitivity response of the ocular tissues to topically applied drugs or preservatives. It may take weeks, months or years for the symptoms of medicamentosa to appear. And, to further complicate the diagnosis, any documented symptoms may, in fact, be caused by unrelated complications––especially in the case of contact lens wearers, where there are other ocular surface irritants.

While there may be improvement of the underlying condition (e.g., ptosis), ancillary symptoms may develop over time, including irritation, grittiness, stinging, burning, photophobia, conjunctival hyperemia, lid swelling and blurred vision. Clinically apparent signs of medicamentosa include corneal or conjunctival staining, corneal edema, pseudodendrites and stromal infiltrates.

The differential diagnoses of medicamentosa include contact lens-related staining, viral keratoconjunctivitis, dry eye and rosacea.
Typically, medicamentosa is attributed to the preservative agent in an ophthalmic solution. However, in some instances the drug itself may cause unwanted effects on the eye that worsen with increased dosing.

In our patient’s case, Visine LR contains oxymetazoline (an alpha- 1 and partial alpha-2 agonist, which serves as a vascular decongestant and facilitates ptosis relief) and is preserved with benzalkonium chloride (BAK)––a known ocular irritant that causes corneal staining (see " Too Much of a Good Thing?" January 2011). In addition, however, oxymetazoline yields several side effects.

Agents Frequently Associated With Medicamentosa

  • Benzalkonium chloride
  • Brimonidine
  • Atropine
  • Neomycin
  • Acyclovir
  • Prostaglandin analogs
The entire class of topical vaso-constrictors (including oxymetazoline, naphazoline and tetrahydrozoline) has been shown to cause rebound hyperemia after discontinuation. Also, while commonly used by dry eye patients, these drugs can yield a significant decrease in tear volume and flow.1

There is at least one published study of corneal opacity development secondary to chronic vasoconstrictor dosing.2 In this report, the opacities partially resolved with drop discontinuation.

When medicamentosa is suspected, instruct the patient to discontinue the offending medication or switch to a preservative-free formulation. Keep in mind, however, that treatment of the underlying condition is still necessary.

1. Göbbels MJ, Achten C, Spitznas M. Effect of topically applied oxymetazoline on tear volume and tear flow in humans. Graefes Arch Clin Exp Ophthalmol. 1991;229(2):147-9.
2. Herman DC, Bartley GB. Corneal opacities secondary to topical naphazoline and antazoline (Albalon-A). Am J Ophth 1987 Jan 15;103(1):110-1.