# In Vivo Efficacy of Contact Lens Drug-Delivery Systems in Glaucoma Management. A Systematic Review
## 4 Discussion
### Barriers to Widespread Use in Clinical Practice  
Today, no CL drug-delivery system is available on the market because different issues prevent its widespread use [50]. In particular, the drug-soaked CL and the CL with vitamin E have limited drug loading capability. The drug-soaked CL also cannot release a drug for an extended period at a constant rate. Moreover, extended CL wear is related to several ocular complications, classifiable into infectious and non-infectious [72].  
The infectious side effect related to CL wear is mainly microbial keratitis. The CL wearer has an 80-times increased risk of developing it compared to healthy people, and visual acuity decreases in 10-15% of CL wearers after microbial keratitis resolution [73; 74]. Principal pathogens are _Pseudomonas_ ssp., _Acanthamoeba_, and _Candidia_ spp., although the causative organism varies according to the region [72]. Traumatic or incorrect lens insertion or removal may cause a corneal abrasion, that needs strict control to prevent microbial keratitis development [72].  
Chronic hypoxia belongs to the non-infectious group and leads to ocular and limbal erythema, microcystic and stromal oedema, vascularisation, epithelial thinning, endothelial polymegethism, and pleomorphism [75; 76; 77]. However, these adverse events are usually reversible once CL wear is discontinued [78]. Other non-infectious complications related to extended CL wear are a peripheral corneal ulcer, single or multiple corneal infiltrates without anterior chamber reaction, conjunctivl hyperaemia, and papillary conjunctivitis [72].  
CL wearing is also a risk factor for dry-eye disease [79]. The exact responsible mechanism remains unclear. Maybe the CL blocks meibomian gland ducts with desquamated epithelial cells aggregates, due to mechanical trauma after each blinking [72]. Once the external lipid layer is altered, the tear film became unstable, and the vicious circle of dry eye is set. Other suggested mechanisms are inflammation and chronic hypoxia [80].  
Corneal warpage is another crucial complication due to extended CL wear. It is defined as topographic corneal alterations that affect refraction and are distinguished by other ectasic disorders [81; 82].  
Another significant limitation is that people not accustomed to wearing a CL may hesitate to adopt this therapeutic solution, even if wearing it for a day allows an IOP-lowering lasting a week [39]. Main concerns could be the impact on vision quality in patients without refractive errors, cosmetic appearance, difficulties in day-to-day activities, and inconveniences rendered in daily life.  
Likely, CL drug-delivery systems may overcome issues related to prescription refill or white-coat adherence (instilling the therapy just five to seven days before the visit). Nevertheless, some patients may not be able to wear a CL autonomously, as for eyedrops. In particular, 11.3-60.6% of patients cannot instil eyedrops correctly, and 6.8-37.3% of patients miss the eye when instilling the eyedrops [12]. The main risk factors are older age, severe visual field defect, lower educational level, and comorbidities such as arthritis [12]. In these cases, even with a CL drug-delivery system, a caregiver's presence is still necessary. However, this technology may reduce the burden on relatives or health-care providers because the CL can be changed just every fifteen or thirteen days.  
Finally, CL drug-delivery system manufacturing increases the number of synthesis and processing steps or requires long periods until the drug-loaded CL is usable, with a not negligible economic burden [83].