Commentary
Article
Weighing the benefits and trade-offs of preserved versus preservative-free glaucoma treatments is key to optimizing long-term patient care.
Preservative-related toxicity is an important factor in the lifelong management of patients with glaucoma. (Image credit: AdobeStock/RFBSIP)
The rise in ocular surface disease (OSD) among patients with glaucoma is a pressing issue that cannot be overlooked. As ophthalmologists, we must prioritize ocular health and mitigating OSD over our patients’ lifetime, not just manage their glaucoma.
Although glaucoma is not typically considered a disease of the ocular surface, literature suggests that 30% to 70% of patients with glaucoma also suffer from OSD, a stark contrast to the 5% to 30% among similarly aged adults without glaucoma.3,4,6 This is not just a minor inconvenience. OSD is also linked to a higher rate of failure in subconjunctival glaucoma surgery.1,2,7
A combination of risk factors—including increasing age, genetics, sex, and systemic comorbidities—may play a role in the increasing prevalence. In some patients, OSD could be a preexisting condition, exacerbated by topical treatments. Yet, there are a multitude of studies that show OSD manifesting after initiation of first-line topical glaucoma therapies in up to 59% of patients.4,7 Use of laser trabeculoplasty as first-line treatment helps mitigate this, but most patients ultimately require topical therapy. The number of antiglaucoma medications, administrations per day, and treatment duration are also key predictors of significant OSD and severity of glaucoma.1,2,6
Preservatives have long been used in ophthalmic medications to provide antimicrobial activity to maintain sterility.4-6,8 This is a double-edged sword; while effective against pathogens, there is mounting evidence of serious, deleterious effects on the ocular surface associated with long-term use.1-8
Benzalkonium chloride (BAK), once marketed as a disinfectant, is present in 70% of ophthalmic formulations.6,8 Despite the extensive documentation of cytotoxic effects and association with increases in OSD, BAK is still the most widely used preservative in glaucoma treatments.1-8
Several studies have linked higher BAK concentrations in glaucoma treatments and cumulative exposure to greater ocular surface toxicity and damage. Infiltration into the eye and accumulation in deep ocular structures such as the trabecular meshwork (TM) ultimately led totear film instability, loss of goblet cells, disruption of the corneal epithelium barrier, and damage to deeper ocular tissue.1,2,5-7
Patients using preserved medications frequently report pain, burning, stinging, ocular dryness, and itching that are exacerbated by unstable tear film irritation, and overall worse scores on the Ocular Surface Disease Index.1-7 These side effects are of clinical importance considering effectiveness of treatment depends on adherence. So, it is not surprising that nonadherence has been reported in up to 60% of patients with glaucoma with treatment-related side effects or among patients using preservative-containing drops.4,7
Although most available generic glaucoma treatments contain BAK as a preservative, preservative-free formulations are becoming more widely available. These formulations have demonstrated less cytotoxicity than their BAK-preserved versions.6,7 Clinical studies and real-world observational studies have shown decreased signs and symptoms of OSD and increased adherence to treatment without compromising IOP control.4,6,7
With equally effective and readily available preservative-free alternatives, the question remains: why are we still prescribing treatments with molecules originally marketed as disinfectants?6,8
As with many interventions, the challenge is insurance coverage and cost to the patient. Generic drops are inexpensive, but we need to balance this with the long-term effect on the ocular surface. The prior authorization burden to clinical practices to obtain preservative-free drops can be onerous, but the more we request them, the more payers will recognize the need to allow access to these compounds. Our overarching goal is to protect our patients’ vision by using the minimum number of medications required to reach the target IOP range.
Choosing preservative-free glaucoma treatments over preserved formulations is a solution within reach. These formulations can reduce OSD symptoms, promote better adherence to treatment without compromising efficacy, and decrease risk of surgery by preserving the ocular surface and TM. It is up to us to ensure that our patients are informed of their options. It is up to us to protect their vision with the utmost care and consideration for their ocular surface health.
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