# In Vivo Efficacy of Contact Lens Drug-Delivery Systems in Glaucoma Management. A Systematic Review
## 4 Discussion  
Recently, [PERSON] et al. detailed technical aspects of a CL drug-delivery system in glaucoma, highlighting the increased drug bioavailability [21]. Simultaneously, administering a lower drug dose, adverse events' frequency and severity were reduced [21]. In particular, only 20% of the drug dose was required to produce a similar therapeutic effect with CL drug-delivery systems compared to the dose needed with eyedrops delivery systems [65].  
Our review illustrated the in vivo findings of CL drug-delivery system, focusing on IOP-lowering and assessment versus eyedrops. Therefore, these data provided a scaffold to analyse the potential impact of CL drug-delivery systems in managing glaucomatous patients.  
During recent years, multiple attempts to improve patient cooperation, such as educational brochures, pamphlets, and fact sheets have been developed [66]. Video and Web-based patient educational tools were designed to encourage patient adherence and stimulate dialogue with the clinician. Also, reminders and recall systems were developed to avoid missed appointments or skipped drugs [66]. Nevertheless, the adherence issue is still unresolved, and there is still much to do.  
The development of minimally invasive glaucoma surgery allows surgery to be performed earlier than before [67]. In particular, these techniques are currently adopted in selected glaucoma patients with early or moderate disease, usually associated with phacoemulsification [4; 68]. However, patients consider surgery a last-chance treatment and still prefer non-invasive treatment, such as alternative drug-delivery systems [69].  
To increase adherence, preservative-free topical drugs have also been developed. Long-term therapy has usually caused topical toxic effects such as discomfort during instillation, foreign body sensation, burning, and ocular inflammation signs [10]. These side effects reduced patients' cooperation; consequently, the European Medicines Agency (EMA) in 2009 provided crucial recommendations for preservative-free topical drug development [70]. Even with the massive development in preservative-free eyedrop delivery systems in recent years, this technology has remained expensive. It also does not resolve other obstacles limiting patients' adherence, such as incorrect drop instillation, skipped instillation, and poor doctor-patient communication.  
For these reasons, alternative systems for drug delivery in ophthalmology are currently under development, such as nanoparticles, punctal plugs, and CL-eluting glaucoma medications.  
A recent survey of 199 glaucomatous patients investigated the acceptance of drug-delivery systems [69]. The CL showed the second-lowest acceptance rate (31%) compared to triple combination eyedrops (85%), eye spray (54%), periocular ring inserts (43%), injectable subconjunctival drug inserts (32%), and injectable anterior chamber implants (30%). Moreover, patients with greater disease severity and prior incisional glaucoma surgery were more likely to pursue alternatives to traditional eyedrops [69].  
Another survey of 150 glaucomatous patients compared the drug-eluting CL, ring inserts, punctal plugs, and sub-conjunctival injections as an alternative to eyedrops [71]. In this study, the CL acceptance rate of these drug-delivery systems was higher than ring inserts (36% more) or sub-conjunctival injections (32% more). However, alternative drug-delivery systems would be accepted if surgery was avoided or they were more effective than eyedrops [71].  
However, multiple obstacles limit their adoption in current practice.