# In Vivo Efficacy of Contact Lens Drug-Delivery Systems in Glaucoma Management. A Systematic Review
## 3 Results
### The Drug-S soaked CL  
The drug-soaked CL was the first method to be developed as a CL drug-delivery system, as described by [PERSON] and colleagues in 1960 [50]. The CL was soaked in a solution containing the drug to uptake it. Once applied, the CL released the drug over 60-90 min, as demonstrated by [PERSON] and colleagues' in vitro study (Figure 2) [31].  
[PERSON] successfully treated two patients affected by acute primary ACG with a CL soaked in pilocarpine 4% [32]. In both cases, IOP decreased in two hours (from 70 mmHg to 12 mmHg and from 72 mmHg to 36 mmHg) and symptoms resolved. However, details on the soaking method were not reported.  
[PERSON] et al. compared the pilocarpine penetration into monkeys' aqueous humour after installing topical eyedrops or applying a soaked CL [33]. A CL contained a drug dose of 400 \(\upmu\)g when soaked in 1% of pilocarpine solution for 2 min. Conversely, a pilocarpine eyedrop (0.1 mL) at 1% contained 1000 \(\upmu\)g of the drug, at 4%, 4000 \(\upmu\)g, and 8%, 8000 \(\upmu\)g. The soaked CL delivered the same pilocarpine amount in the aqueous as the 4% eydrops. Moreover, the CL achieved the highest aqueous drug concentration after two hours, even when compared to the instilled pilocarpine eyedrop at 8%. Finally, miosis in the eye treated with the soaked CL was more pronounced than in eyes treated with eyedrops even 24 h later. These authors concluded that the soaked CL enhanced the drug's penetration and prolonged the drug's effect [33].  
[PERSON] et al. treated 10 patients affected by ocular hypertension [34]. In particular, they soaked a CL in 0.5% pilocarpine for two minutes and obtained an IOP-lowering for the  
Figure 2: Drug diffusion through the polymeric matrix of a contact lens (CL).  
23 h of wearing (from 28 mmHg to 24 mmHg, 14.7%). Moreover, 24 h after treatment, an IOP reduction of 20% occurred after 30 min of wearing a soaked CL in 1% of pilocarppine and after 60 min with a CL soaked in 0.5% of pilocarppine [34].  
[PERSON] et al. treated 25 patients with acute primary ACG with a CL soaked in 1% of pilocarppine and 500 mg of intramuscular acetazolamide [35]. Results were retrospectively compared with 25 patients treated with topical pilocarppine 4% eyedrops instilled every minute for 5 min, then every 5 min for half an hour, and finally every 15 min for 90 min and 500 mg of intramuscular acetazolamide. The CL released 400 ug of pilocarppine, although the eyedrops instillation delivered about 40,000 ug. All patients well-tolerated lens wearing for two hours, and no one developed corneal abrasion. The CL drug delivery showed an increased efficacy compared to the eyedrop treatment, with a mean IOP-lowering of 54.8% compared to 49.7%, respectively [35]. In the following years, other studies confirmed the CL's therapeutic role in ACG and OAG when soaked with pilocarppine [36,51].  
The soaked CL was a straightforward drug-delivery system, although it had several limitations. The CL drug's affinity was a double-edged sword because when elevated, the CL poorly released the drug. Instead, if the affinity was low, the drug release immediately peaked after lens application. Moreover, to be available on the market, the soaked CL should be sterilised, altering the drug efficacy or release.  
Recently [PERSON] et al. evaluated the IOP-lowering effect of a CL soaked with timolol or brimonidine [31]. Three patients affected by OAG were enrolled. After three weeks of washout, patients wore, for 30 min a day for 21 days, a CL soaked with the same drug that they were already taking before the washout (one with brimonidine and two with timolol). The CL were loaded with 0.65 mg/mL timolol maleate, but no details were provided about the brimonidine tartrate-loaded CL. All patients showed IOP values similar to the ones with eyedrops, for all the periods. However, the CL released a drug quantity ten times inferior to the eyedrops [31].  
Latanoprost drug delivery with a soaked CL has also been recently investigated, although only an in vitro study has been conducted [52].