Extraocular, periocular, and intraocular routes for sustained drug delivery for glaucoma

Although once daily anti-glaucoma drug therapy is a current clinical reality, most therapies require multiple dosing and there is an unmet need to develop convenient, safe, and effective sustained release drug delivery systems for long-term treatment to improve patient adherence and outcomes. One of the first sustained release drug delivery systems was approved for the reduction of intraocular pressure in glaucoma patients. It is a polymeric reservoir-type insert delivery system, Ocusert™, placed under the eyelid and on the ocular surface for zero-order drug release over one week. The insert, marketed in two strengths, released pilocarpine on the eye surface. While many clinicians appreciated this drug product, it was eventually discontinued. No similar sustained release non-invasive drug delivery system has made it to the market to date for treating glaucoma. Drug delivery systems under development include punctal plugs, ring-type systems, contact lenses, implants, microspheres, nanospheres, gels, and other depot systems placed in the extraocular, periocular, or intraocular regions including intracameral, supraciliary, and intravitreal spaces. This article discusses the advantages and disadvantages of the various routes of administration and delivery systems for sustained glaucoma therapy. It also provides the reader with some examples and discussion of drug delivery systems that could potentially be applied for glaucoma treatment. Interestingly, one intracamerally injected implant, Durysta™, was approved recently for sustained intraocular pressure reduction. However, long-term acceptance of such devices has yet to be established. The ultimate success of the delivery system will depend on efficacy relative to eye drop dosing, safety, reimbursement options, and patient acceptance. Cautious development efforts are warranted considering prior failed approaches for sustained glaucoma drug delivery. Neuroprotective approaches for glaucoma therapy including cell, gene, protein, and drug-combination therapies, mostly administered intravitreally, are also rapidly progressing towards assessment in humans.