# Contact Lenses as Drug Delivery System for Glaucoma: A Review
## 1 Introduction
### Pharmacological Treatment  
IOP reduction is the only effective treatment to manage and prevent the development of glaucoma progression [5; 6]. Drugs can modify IOP by reducing the production of the aqueous humour from the ciliary processes, by increasing the rate of filtration of aqueous humour through the trabecular-meshwork or uveoscleral pathways or by the combination of both. They are included in five different groups: parasimpathomimetics such as pilocarpine, alpha2-agonists such as brimonidine, beta-blockers such as timolol, carbonic anhydrase inhibitors such as dorzolamide, and prostaglandlandins analogues such as latanoprost. Although all of them reduce IOP, none are exempt from side effects like blurred vision, tachycardia, or arrhythmia [33; 34]. These side effects are shown in Table 1.  
Many new compounds, apart from those already commercially available, have appeared, attempting to provide effective treatments to stop ocular hypertension and glaucoma progression [26]. One of the emerging group is melatonin and its analogues, which clearly present ocular hypotensive effects [35; 36; 37; 38] as well as potentially interesting neuroprotective actions which need to be confirmed [39; 40]. Melatonin is a neurohormone which is not only produced by the pineal gland but is also synthesized and released by some ocular structures such as the retina, ciliary body or the lens [41]. It is naturally present in the aqueous humor and is involved in the control of the aqueous humour dynamics [15]. In this sense, studies performed show that melatonin and its analogues can reduce IOP in normotensive and hypertensive conditions [42; 43], which has revealed the potential use of this compound and its analogues for the treatment of ocular hypertension and glaucoma [44]. Among other new potential substances to treat the elevation in IOP associated with glaucoma are nucleotides, which are seen to be interesting molecules since they could also modify the dynamic of aqueous humour [45]. Between these nucleotides, dinucleoside polyphosphates are a family of compounds formed by two nucleotides linked by a variable number of phosphates (from 2 to 7), which have revealed their key role in reducing IOP [46]. However, apart from the toxicity, the active compounds have per se, additional problems which can arise with topical antiglaucoma drugs when preservatives are added [47] or with the poor bioavailability they present. Because of this, there is a search for alternative sustained delivery approaches including nanoparticle-based topical formulations, bio adhesive matrix polymers, ocular inserts, surgical implanted drug reservoirs or contact lens-based delivery [48]. These sustained release methods may reduce the \begin{table}
\begin{tabular}{c c c c} \hline
**Glaucoma Medication** & **Name** & **Local Adverse Effects** & **Systemic Adverse Effects** \\ \hline Prostaglandin analogues & Latanoprost, brimatopost & Conjunctional hyperemia, lengthening of eyelashes, change of iris color, uveitis, macular edema, keratitis & Systemic effects related to headaches \\ \hline \(\alpha\)-adrenergic agonist & Brimonidine, apradonidine & Ocular irritation, Dry eyes, ocular allergy & Hypertension, irregular heart rate, bitter taste, dry mouth, renal or hepatic failure, respiratory arrest in young children \\ \hline \(\beta\)-adrenergic blockers & Timolol, levubonol, betaxololol & Ocular irritation, Dry eyes & Bradycardia, bronchospasm, depression, fatigue, respiratory effects \\ \hline Carbonic anhydrase inhibitors & Dorzolamide, brimzolamide, acetazolamide & Ocular irritation, Dry eyes, burning sensation with topical agents & Topical form: minimal systemic effects Oral form: paresthesia, nausea, diarrhea, loss of appetite and taste, lassitude, renal stones \\ \hline Cholinergic agonists & Pilocarpine, carbachol & Ocular irritation, induced myopia, decreased vision due to ciliary spasm & Ciliary spams carry headaches in young patients \\ \hline \end{tabular}
\end{table} 
Table 1: Common adverse effects associated to glaucoma drugs.