Drug delivery systems in glaucoma - Current innovations and future perspectives.

Glaucoma is the leading cause of irreversible visual loss worldwide, and as yet, there is no cure. The only evidence-based treatment to slow progression is by lowering intraocular pressure (IOP). Despite the development of new topical medications to reduce IOP, the major limitation of eyedrops lies in human and anatomical factors, namely patient compliance and poor bioavailability, making current medical glaucoma treatment ineffective. In this manuscript, we summarise the limitations of traditional topical anti-glaucoma therapy and study current drug delivery systems to lower IOP, with focus on the only two that have made FDA-approval- Durysta and iDose TR. We highlight their limitations and discuss real-world economic challenges that make it prohibitively difficult for these drug delivery systems to be more widely adopted in daily practice. In this perspective, we also introduce gene therapy as a novel therapeutic option to target downstream pathways of IOP regulation, neuroprotection of the optic nerve, and reducing mitochondrial stress to delay the progression of glaucoma. We discuss promising results of gene therapy for glaucoma treatment in in vivo animal models as well. We also explore the concept of novel nanoparticle-based drug delivery systems, which have the advantage of being highly modifiable and customisable, able to incorporate large amounts of cargo while maintaining a high transfection efficacy, and at a fraction of the cost. Lastly, we propose that nanomedicine, in conjunction with gene therapy, offers a promising solution to the aforementioned challenges of current glaucoma therapy, and can herald a new era of sustained glaucoma treatment.