Advances in Therapeutic Contact Lenses for the Management of Different Ocular Conditions

“

TL;DR

This review examines the use of contact lenses as drug delivery systems to improve ocular bioavailability, which is typically only 1–5% with eye drops. Various materials and fabrication methods, including silicone hydrogels, molecular imprinting, and vitamin E barriers, have been developed to achieve sustained drug release for conditions like glaucoma and keratoconus. The clinical significance lies in the potential for enhanced patient compliance and more effective treatment of chronic ocular surface diseases.

Full summary

4,462 CHARS

**Background:** Topical eye drops, the most common ophthalmic formulation (over 90% of all formulations), suffer from low bioavailability (1–5% in target tissue, less than 0.5% for hydrophilic molecules) due to rapid drainage and clearance. This necessitates frequent administration, leading to poor patient compliance, especially in chronic conditions like glaucoma and dry eye disease. Therapeutic contact lenses (TCLs) have emerged as a promising platform to overcome these limitations by providing sustained drug release, improving bioavailability, and enhancing therapeutic outcomes. The concept originated with Otto Wichterle and Drahoslav Lim's 1965 patent on poly(2-hydroxyethyl methacrylate) (PHEMA) lenses for drug diffusion.

**Methods:** This is a narrative review that synthesizes the literature on TCLs, covering material design, fabrication methods, drug loading strategies, and applications for various ocular conditions. The review discusses hard (rigid gas-permeable) and soft (hydrogel and silicone hydrogel) contact lens materials. Key materials include HEMA, N-vinyl pyrrolidone (NVP), silicone-based polymers (e.g., TRIS, PDMS), and various copolymers. Fabrication methods include lathe-cutting, spin-casting, cast-molding, and additive manufacturing (3D printing). Drug loading strategies are categorized into: (1) soaking method, (2) incorporation of functional molecules (e.g., ion components, cyclodextrins), (3) molecular imprinting, (4) supercritical fluid method, and (5) colloidal nanoparticles (including liposomes, micelles, and polymeric nanoparticles). The review also explores the use of vitamin E as a diffusion barrier to extend drug release.

**Key Results:** The review highlights several key findings from the literature: - Silicone hydrogel lenses allow oxygen permeability sufficient for up to 29 days of wear, compared to HEMA-based lenses suitable for at most weekly wear. - Contact lenses can achieve a minimum corneal bioavailability of 50% under ideal conditions, with predictions placing it between 50 and 70%. - Vitamin E barriers in ACUVUE TruEye® lenses extended the release of timolol and dorzolamide to about 2 days, achieving superior intraocular pressure reduction with about 6-fold lower drug loading compared to eye drops. - HEMA/cetalkonium chloride lenses extended dexamethasone release to 50 hours with good wettability and low protein adsorption. - Cyclodextrin-based lenses (HEMA γ-cyclodextrins) sustained miconazole delivery for over 14 days and completely prevented Candida albicans biofilm formation. - Molecularly imprinted MAA/MAm hydrogels achieved atropine release for up to 72 hours. - Valacyclovir-imprinted hydrogels (MAA/HEMA/EGDMA) showed sustained release for 10 hours with significant corneal accumulation. - Prednisolone-loaded PLGA nanoparticles in HEMA/MAA/EGDMA lenses released 10.8% of encapsulated drug over 24 hours with minimal changes in lens properties. - Pluronic® F-68/gatifloxacin-loaded lenses (DMA/siloxane/NVP/EGDMA/HEMA) exhibited excellent optical transmittance, swelling, and sustained drug release. - The review notes that keratoconus, with a prevalence of 1.38 per 1000 individuals, has not been addressed by TCLs in the literature, but proposes a potential approach using gas-permeable lenses with riboflavin for controlled release and UVA light for collagen cross-linking.

**Clinical Implications:** TCLs represent a significant advancement in ophthalmic drug delivery, offering improved bioavailability, reduced dosing frequency, and enhanced patient compliance for chronic ocular surface diseases. The integration of vitamin E barriers, cyclodextrins, molecular imprinting, and nanoparticle systems has shown promise in achieving sustained release for various drugs, including antibiotics, anti-glaucoma agents, and anti-inflammatory drugs. However, challenges remain, including the need to maintain lens transparency, water content, oxygen permeability, and mechanical properties while ensuring effective drug loading and release. The review also highlights the potential for TCLs in keratoconus management through riboflavin delivery for collagen cross-linking, though this remains a hypothesis. Future directions include the development of smart contact lenses for real-time monitoring and on-demand drug delivery, as well as the need for further research to address commercialization hurdles, including clinical trial costs and manufacturing requirements.