Benzalkonium chloride corneal toxicity post-cataract surgery

Two patients with presumed benzalkonium chloride (BAK) corneal toxicity after routine cataract surgery are presented. Patient 1 had corneal stroma and Descemet’s membrane folds. Patient 2 had moderate superficial punctate epithelial erosions (SPEE). They were on Chlorsig, Maxidex, and Acular eye drops tds postoperatively. The corneas of these two patients improved when BAK was removed or minimized from the postoperative eye drop regimen. Two vials of 1 ml dexamethasone 4mg/ml for injection were added to Chlorsig 10 ml bottle to substitute for Maxidex eye drops. BAK toxicity should be suspected when the cornea is not as clear as expected postoperatively. A practical way to eliminate BAK from postoperative eye drops is described, and would be useful until pharmaceuticals mass-produce BAK-free steroid eye drops economically.

Two vials of 1 ml Dexamethasone 4mg/ml for injection were added to a Chlorsig 10 ml bottle, and Acular tds was replaced with Ilevro (nepafenac, Alcon) once daily. At 2.5 weeks, there was no significant improvement in corneal appearance. As Ilevro contained BAK, Ilvero was stopped and replaced with Indomethacin 25 mg daily orally. He continued with Chlorsig-Dexamethasone tds. At 6 weeks, he mentioned that he had noticed improvement after a week on the new regimen, and VA was 6/9 with much improvement of corneal stroma and Descemet's membrane folds, ECC of 2882/mm 2 , and CCT of 594 microns.
When he underwent right cataract phacoemulsification and PCIOL, he was prescribed Chlorsig-Dexamethasone tds and Indomethacin 25 mg orally daily. There was no corneal problem. VA was 6/9 on day one and at one month.

Patient 2
A 65-year-old female underwent routine right cataract phacoemulsification and PCIOL (Alcon SN 60WF). She has a past history of dry eye controlled with tear supplements. On day 1 postoperative, VA was 6/9 with myopic correction. At 1-week postoperative, VA was 6/12 corrected and IOP was 16 mmHg bilaterally. She had extensive SPEE fluorescein staining of the cornea, with no significant corneal stroma or Descemet's folds (Fig. 3). She was on Chlorsig, Maxidex, and Acular drops tds. She was changed to Chlorsig-Dexamethasone tds and Acular once daily. At 5 weeks, SPEE improved and VA was 6/9 with myopic correction. When she underwent left cataract phacoemulsification and PCIOL, she was on Chlorsig-Dexamethasone tds and Acular once daily. There was no corneal problem and VA was 6/9 on day one and at one month postoperative.

Discussion
BAK toxicity usually presents as corneal SPEE. 1,2 Corneal edema 3 with corneal stroma and Descemet's folds is uncommon. Mechanisms proposed include damage to corneal epithelial cells by disruption of cell tight junctions and toxicity to the corneal endothelium. 1,2,4 BAK causing mitochondrial dysfunction may play a part in the corneal changes. 5 Maxidex and Acular contain BAK, and when BAK is instilled six times a day, corneal toxicity is more likely to occur in a shorter time frame. Chlorsig contains polymercuric acetate as preservative. When BAK was eliminated or reduced from the eye drop regimen, the cornea of these two patients did not have any significant corneal stroma, Descemet's folds, or SPEE.
BAK allergy is less common, and the conjunctiva and eyelid skin are inflamed and itchy. Maxidex eye drops contain BAK, and when used, the dexamethasone steroid often masks the conjunctival inflammation, whereby only the eyelid and lid margin develop inflammation and redness.
Hence, BAK toxicity should be suspected when the cornea is not as clear as expected postoperatively. A practical way to eliminate BAK from postoperative eye drops is described, and would be useful until BAK-free steroid eye drops are easily available and affordable.