Corneal calcification and phosphates: do you need to prescribe phosphate free?

PURPOSE: Both superficial band keratopathy and deeper calcareous calcification have been linked to the presence of phosphate excipients in topical ophthalmic medicines. (1-3) The European Medicines Agency (EMA) has concluded that patients with ocular surface disease are at greatest risk. This potential side effect should be highlighted to both prescribers and patients. (4) We aimed to review the excipients of commonly prescribed ophthalmic medicines to prepare a list of phosphate-containing drugs and also to investigate where to find this information. METHODS: We reviewed 78 commonly used ophthalmic drops and ointments for the information about their excipients. We reviewed the information written on drug boxes, bottles, patient leaflets, and in the electronic Medicines Compendium (EMC), which contains up-to-date details of all medicines licensed for use in the United Kingdom. The British National Formulary (BNF) was also reviewed. RESULTS: We found 22 phosphate-containing, 13 unbuffered, and 43 ophthalmic drugs containing buffers other than phosphate based. Most displayed the list of their excipients on their boxes and in patient leaflets. This information was also available on the EMC website but not in the BNF. Despite the EMA recommendation, none of the phosphate-containing medicines mentions corneal calcification as a potential side effect. CONCLUSIONS: We present a reference list of phosphate-based ophthalmic drugs to be used with caution for patients with a compromised ocular surface. We found the EMC to be a reliable and easily accessible source of information about drug components. This information will also be included in the new editions of the BNF.

Progressive ulcerative keratitis related to the use of topical chlorhexidine gluconate (0.02%).

PURPOSE: To report a case of progressive ulcerative keratitis related to the use of topical chlorhexidine gluconate 0.02%. METHODS: A 45-year-old woman was treated for presumed Acanthamoeba keratitis with chlorhexidine gluconate 0.02% and propamidine 0.1% eyedrops. RESULTS: After using the chlorhexidine and propamidine eyedrops for 8 weeks, the patient developed a near total loss of the corneal epithelium and a progressive ulcerative keratitis, which eventually required penetrating keratoplasty. Histopathologic examination of the corneal button showed ulceration and loss of Bowman's membrane, massive loss of keratocytes with apparent apoptosis, and loss of the endothelial cells with inflammatory cells adherent to the remaining cells. These histopathologic findings are similar to those seen in Hibiclens keratopathy. Hibiclens contains chlorhexidine 4% with a detergent. No organisms were seen in sections stained with modified Ziehl-Neelsen, gram, Grocott, or periodic acid-Schiff, and immunohistochemistry showed no significant findings. CONCLUSION: We think that the topical use of chlorhexidine gluconate 0.02% may have resulted in a progressive ulcerative keratitis in our patient.