An Ophthalmologist’s Guide to Preservatives in Topical Medications, Part 2
By Marguerite McDonald, MD, FACS
Preservatives, of course, are necessary (and required) in ophthalmic solutions to prevent microbes from flourishing, potentially causing serious infection. But, preservatives are not without risks of their own.
For dry eye patients who use solutions regularly, it is particularly important to choose those that contain preservatives that are less likely to cause irritation.
Last month, we began a review of various preservatives used in ophthalmic solutions, and the mechanisms, benefits and drawbacks of each. In that edition, we discussed detergent agents. This month, we look at oxidative agents, which generally are small molecules that can pass through the microbial cell wall to enter the cell and disrupt internal enzymatic function.
SofZia. SofZia is a fairly recent advancement in the field of ophthalmic preservatives. When exposed to cations, such as those that are normally found in the tear film, SofZia is inactive. This is thought to induce less cytotoxicity to the ocular surface compared with more conventional preservatives.
The SofZia system effectively preserves the medicine while it is being stored; however, when the drug is applied to the eye, it breaks into harmless elements that are gentle on the ocular surface. For instance, it has been demonstrated that SofZia-preserved travoprost induces corneal and conjunctival changes similar to preservative-free artificial tears. Travoprost with SofZia also reduced amounts of conjunctival inflammation and corneal changes when compared with travoprost treated with BAK.
Stabilized Oxychloro Complex. Stabilized oxychloro complex (SOC) is an oxidative-type preservative that was introduced into topical ophthalmic medicines in the mid 1990s under the trade name Purite. One of its derivatives, sodium chlorite, has been used in water purification systems since the 1940s. Chemically, SOC is a mixture of chlorine dioxide, chlorite and chlorate. When exposed to light, SOC dissociates into oxygen, water, and sodium and chlorine-free radicals. The chlorine-free radicals are thought to inhibit microbial protein synthesis within cells by way of glutathione oxidation, leading to microbial cell death.
SOC is well tolerated by the ocular surface, and even at very low concentrations, the antimicrobial activity is broad and includes antibacterial, antifungal and antiviral effects. Purite has become a component of several types of artificial tear and antiglaucoma preparations.
Polyhexamethylene Biguanide. Polyhexamethylene biguanide (PHMB) was introduced as a component of pool cleansers, skin disinfectants, and urinary catheter flush solutions. More recently, it has been used in contact lens solutions. PHMB’s antimicrobial activity against Acanthamoeba and bacteria are well established. One huge advantage is that PHMB does not irritate human corneal cells; however, its antifungal activity is limited. PHMB works by integrating into bacterial cell walls, thereby disrupting the membrane. It also has been shown to lethally alter the transcription of bacterial DNA.
Sodium Perborate (GenAqua). GenAqua is a preservative composed of sodium perborate. Used in dental hygiene solutions since the 1950s, it is an oxidative preservative. Later it became one of the first oxidative-type preservatives used in ophthalmic solutions.
Sodium perborate works by altering protein synthesis within bacterial cells by oxidizing cell membranes and altering membrane-bound enzymes, which causes enzymatic inhibition. Upon exposure to water or an aqueous environment, it transforms into hydrogen peroxide, water and oxygen, a process exclusive to sodium perborate. The hydrogen peroxide generated by this reaction effectively kills microbes. The effective killing power of sodium perborate has been demonstrated on Aspergillus niger.
Marguerite McDonald, MD, FACS, with OCLI on Long Island, NY, is clinical professor of Ophthalmology at NYU Langone Medical Center, NY, and clinical professor of Ophthalmology at Tulane University Health Sciences Center, New Orleans, Louisiana.