Glaucoma is one of the leading causes of irreversible blindness in the world and the latest figures show that around 80 million people are affected and 11 million patients are already blind in both eyes due to glaucomatous optic neuropathy.
Elevated intraocular pressure (IOP) is still identified as a major risk factor for the onset and progression of glaucoma and international guidelines recommend, as a first therapeutic approach, to reduce and control it through appropriate hypotensive drug therapy, both topical and systemic.
Topical therapy with hypotensive eye drops generally constitutes the first line of treatment, but poses significant problems of patient adherence, as the medication must be taken every day in chronic therapy and sometimes more than one eye drop must be used. Older patients often have difficulty correctly instilling the drops and some of the eye drops are often dispersed on the cheeks. It is estimated that more than 80% of patients do not use hypotensive eye drops according to prescription and this poor therapeutic adherence is among the causes of worse visual outcomes. In addition, there are important anatomical barriers in the eye that can lead to suboptimal levels of drug concentration in the target tissues. Add to this the fact that administration in eye drops is characterised by a 'pulsating' pattern with concentration peaks close to administration and lower levels prior to subsequent dosing, which can result in poorer IOP control and an increased risk of adverse effects.
The Italian study, 'Drug Delivery Systems for Glaucoma: A Narrative Review", published in Pharmaceuticals, took stock of sustained-release systems under development, which could avoid some of the problems of hypotensive eye drops therapy. In fact, a sustained-release system is associated with a more constant lowering of IOP over time, a lower total dosage, and a lower risk of systemic side effects. Not to be overlooked is the advantage of not needing to be reminded of daily dosing, with a probable reduction in the risk of treatment non-adherence.
The sustained-release systems for the treatment of glaucoma and ocular hypertension, currently in clinical or pre-clinical development, illustrated in this review are:.
- Systems with release through the tear duct
- Delivery systems through the conjunctival fornix
- Medicated contact lenses
- Drug delivery systems in the periocular area
- Intracameral drug delivery systems
At the beginning of 2025, a preclinical study was also published in the Journal of Advanced Material, "Colloid-Forming Prodrug-Hydrogel Composite Prolongs Lower Intraocular Pressure in Rodent Eyes after Subconjunctival Injection" in which researchers from the Institute of Biomedical Engineering and Chemical Engineering at the University of Toronto developed a new method to significantly extend the duration of antiglaucomatous treatment. By exploiting the drug's colloidal aggregates - which were previously considered a problem in drug development - they have developed a technology for extended release of the anti-glaucomatous drug into the eye.
A subconjunctival injection was used as the route of administration, containing a modified version of a drug commonly used in glaucoma therapy: timolol, which can be converted from the soluble form to a colloidal aggregate form to be injected into the subconjunctival space. A single intravitreal administration produces hypotensive effects for 7 weeks, instead of the standard 6 hours for conventional eye drops: about 200 times longer.
If similar results prove reproducible in humans, the risk of systemic side effects, such as bradycardia, would be minimised because the drug's circulating concentrations would remain low. In parallel, the need for daily instillations of the eye drops would be reduced, improving patient compliance.
From research laboratories to clinical practice: this, then, is the path that could mark a real turning point in glaucoma therapy, thus meeting an important and still unmet need in ophthalmology.
On the subject of glaucoma, we also propose:
- Blood pressure and glaucoma - Oculist Italiano
- Oestrogen and glaucoma - Oculist Italiano
- Glaucoma: the frontiers of research - Oculista Italiano
- Fea AM, Vallino V, Cossu M, Marica V, Novarese C, Reibaldi M, Petrillo F. Drug Delivery Systems for Glaucoma: A Narrative Review. Pharmaceuticals (Basel). 2024 Sep 2;17(9):1163. doi: 10.3390/ph17091163. PMID: 39338326; PMCID: PMC11435076.
- Dang M, Slaughter KV, Cui H, et al. Colloid-Forming Prodrug-Hydrogel Composite Prolongs Lower Intraocular Pressure in Rodent Eyes after Subconjunctival Injection. Adv Mater. 2025 Jan 6:e2419306. doi: 10.1002/adma.202419306
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