Worldwide, 7.7 million people suffer visual impairment or blindness due to glaucoma, with that number projected to grow as populations age (World Health Organization, 2021). Glaucoma is an extensively studied condition for which there are known effective treatments to mitigate the risk of vision loss. Among these, the most common first-line treatment is topical medications that the patient instills in the affected eye(s).

Treatment with topical eye drops requires lifelong adherence to treatment. Adherence to treatment is defined as using 80% or more of doses prescribed (Achilleos et al, 2021). Studies have shown that approximately 26.5% of glaucoma patients are non-adherent, though the true percentage may be significantly higher (Achilleos et al, 2021).

Failure to adhere to treatment increases the risk of progression of visual field loss (Shu et al, 2021).

Novel drug delivery systems have the potential to improve adherence to and efficacy of glaucoma treatment. This month, we will assess the role of medication-eluting contact lenses (CLs) in the treatment of glaucoma.

A Look at Efficacy

While medication-eluting CLs have not been used in human patients to date, in vivo animal studies have been completed to evaluate the efficacy of the delivery method.

In 2016, Ciolino and colleagues studied the effect of latanoprost-eluting CLs on intraocular pressure (IOP) in a monkey model with induced unilateral glaucoma. Two concentrations of latanoprost were used: low dose and high dose. The CLs were worn for one week of continuous wear. IOP measurements were compared for low dose, high dose, daily 0.005% latanoprost drops without CL delivery system, and no treatment.

Both CL doses reduced IOP statistically significantly compared to untreated baseline. There was no statistically significant difference between the low and high doses.

At several points, the high-dose CL reduced IOP greater than latanoprost drops. This was an unexpected result, as once daily 0.005% latanoprost has been established as the optimal dosing schedule, and increased doses of latanoprost drops have not been found to produce greater IOP reduction. The authors concluded that latanoprost-eluting CLs are at least as effective as daily topical ophthalmic latanoprost, and may be more effective than the drops.

Jung and colleagues (2013) studied the effect of timolol-releasing silicone CLs in beagle dogs using an extended-wear lens over a one-month time period. The nanoparticles in the CL delivered timolol at therapeutic doses for about a month, and a positive reduction in IOP was found in the beagle model.

Another study in spontaneously glaucomatous beagles used CLs soaked in timolol and found that IOP was reduced comparably to topical timolol. This study also provides evidence that CLs increase bioavailability of a drug, as results remained comparable in CLs that had one-third the concentration of timolol (Peng et al, 2012).

The ability of a CL to elute latanoprost was also studied in the rabbit model. Rabbit eyes do not demonstrate IOP reduction with latanoprost. Rather than monitoring IOP, absorption of latanoprost was measured based on concentration of the drug in the aqueous humor. The concentration was found to be greater in the latanoprost-eluting CL group compared to the control receiving latanoprost drops during the 28 days of CL wear (Ciolino et al, 2014).

Advantages and Challenges

Topical eye drops drain rapidly from the surface of the eye, requiring a high concentration to achieve effect. Less than 5% of the drug typically becomes bioavailable with traditional drops. CLs can increase the bioavailability of the drug to an estimated 50% (Kompella et al, 2021).

Sustained release of medications can reduce the fluctuations in IOP, reduce the burden of adherence to a dosing regimen and the likelihood of missed doses, and improve quality of life. However, there are challenges with ensuring safe, sustained release of the medication.

The most conventional method of preparing a CL to elute medication is by soaking the CL in the medication before applying it to the eye. The method has some downsides. Most glaucoma medications are water soluble and tend to elute rapidly from hydrogel lenses. Storing CLs in solution also increases the potential for the medication to leach out of the lens.

In the aforementioned study that measured aqueous humor concentrations of latanoprost in the rabbit model, the first day of CL wear was found to produce a burst of latanoprost that exceeded the maximum concentration provided with topical treatment, consistent with an initial rapid elution of the medication from the CL (Ciolino et al, 2014). Fortunately, after the initial burst, the concentration reached a steady state for the remaining days of the 28-day trial (Ciolino et al, 2014). The lens used in this trial used a drug-polymer film.

In addition to polymeric films, other techniques are being studied to stabilize the medication and maintain consistent sustained release. These include, but are not limited to, microemulsion-laden gels, Vitamin E transport barriers, nanodiamond-nanogel with enzyme-triggered release, and temperature-sensitive release (Singh et al, 2020). More research is needed to determine the most efficacious method of loading the CL.

Potential drawbacks to medication-eluting lenses include the need for continuous CL wear. All the known hazards associated with soft CL wear exist with medication-eluting lenses, including the risk of painful and potentially vision-threatening conditions such as microbial keratitis (Fleiszig et al, 2020). Barriers to CL wear may prevent patients from being able to utilize medication-eluting CLs, including patient comfort with application and removal, compliance with CL care and hygiene, and ocular surface disease (Gurnani and Kaur, 2022).

Further in vivo studies are needed to determine whether the risks associated with all soft contact lens wear vary from baseline for CLs that elute medications. The decreased concentration of drug needed to achieve therapeutic effect may reduce the risk of common side effects of topical ophthalmic glaucoma medications (Peng et al, 2012). Furthermore, without excess medication spilling over the eyelids and draining into the nasolacrimal duct, irritant responses such as contact dermatitis and blepharitis may be less likely to occur (Ciolino et al, 2014).

The in vivo studies completed by Ciolino and colleagues (2014 and 2016) both monitored for complications in the animal model. In the rabbit model, none of the eyes demonstrated any signs of discomfort (Ciolino et al, 2014). In the monkey model, some signs of ocular discomfort were observed, including mild mucus discharge, hyperemia, and punctate corneal staining. One monkey developed a corneal ulcer, treated with ofloxacin. However, the rate of adverse effect from contact lens wear has been shown to be higher in the breed of monkeys used in the study compared to that in humans (Ciolino et al, 2016).

In Vivo Human Studies

Thus far, there have been very limited in vivo studies in human patients for this medication delivery system, and even fewer studies specific to glaucoma treatment. In most of the human studies that have been completed, the lens was prepared by simply soaking it in the medication and demonstrated rapid, uncontrolled elution of the drug. The majority of these studies were completed in the 1970s (Rykowska, 2021). Now that preparation techniques have shown improvement in both in vitro and animal in vivo studies, it remains to be seen whether these effects are consistent in human subjects.

One study utilized a soft CL soaked for four hours in 4% pilocarpine (Ruben and Watkins, 1975). The lens released an initial burst of pilocarpine, though there was some sustained effect, and patients’ IOPs were successfully controlled over a period of 20 months in limited patient studies. Another study used CLs that had been passively soaked in timolol or brimonidine (Schultz, 2009). Only three volunteer patients took part in this study. They wore the treated CLs for 30 minutes each day for a period of two weeks. IOP was found to be equivalent to results achieved with topical instillation.

Concluding Remarks

Medication-eluting CLs have the potential to improve adherence to treatment and reduce the burden on patients to maintain a lifelong dosing regimen. If medication loading techniques are improved and if successes in animal models are repeatable in human patients, this delivery method could lead to predictable, sustained IOP reduction without the risks associated with surgical procedures. Keeping IOP under stable control can reduce glaucomatous progression and maintain patients’ quality of life by preventing permanent vision loss.

Further study is needed in this field before medication-eluting CLs are available for clinical use, but initial studies suggest the IOP reduction to be at least equivalent to traditional topical ophthalmic treatment. CLS

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