Glaucoma is a progressive disease that damages the optic nerve, frequently leading to irreversible vision loss. This damage is often associated with elevated Intraocular Pressure (IOP), the primary focus of most treatments. Conventional therapies, primarily eye drops, are effective but suffer from low bioavailability; less than five percent of the drug actually penetrates the eye’s internal structures. This poor absorption necessitates higher drug concentrations, which increases the risk of systemic side effects when excess medication drains into the bloodstream through the tear duct. New delivery methods, such as nasal sprays, are emerging as promising, non-invasive alternatives to bypass these issues.
Understanding Glaucoma and Treatment Risks
Traditional topical glaucoma medications carry significant risks due to their systemic absorption. When eye drops are administered, a large portion of the drug drains into the nasolacrimal duct and is absorbed into the general circulation, affecting organs outside the eye. This off-target effect is problematic with certain drug classes used to lower IOP.
Beta-blockers, for example, can lead to serious cardiovascular and respiratory issues in susceptible patients. Because they interfere with sympathetic nerve impulses, they may cause bronchospasm or slow the heart rate, leading to bradycardia or heart block. Alpha-adrenergic agonists also carry risks, including potential central nervous system effects such as lethargy, depression, and a high incidence of allergic reactions.
Patients must also be cautious with common over-the-counter nasal sprays, which are not designed for glaucoma treatment. Many nasal decongestants contain adrenergic ingredients that can cause the pupil to dilate. In individuals with narrow-angle glaucoma, this dilation can physically block the eye’s drainage angle, triggering acute angle-closure glaucoma. Furthermore, intranasal corticosteroid sprays, used for allergies, can occasionally cause a rise in IOP in certain patients, especially those with a history of steroid-related pressure elevation.
How Nasal Delivery Achieves Targeted IOP Reduction
The nasal route offers a unique physiological advantage for delivering medication directly to the eye and optic nerve, the main site of damage in glaucoma. This method leverages the anatomical proximity of the nasal cavity to the brain and ocular structures, utilizing the trigeminal and olfactory nerve pathways. Drugs are absorbed through the highly vascularized nasal mucosa and transported along these nerves, bypassing systemic circulation and the body’s natural barriers.
By using this “nose-to-brain” pathway, the therapeutic agent can reach the posterior segment of the eye more efficiently than traditional drops. This localized delivery minimizes drug concentration in the bloodstream, which is the primary cause of systemic side effects seen with eye drops. The nasal route is being explored for both IOP-lowering agents and neuroprotective compounds, which aim to shield optic nerve cells from damage.
One area of active research involves delivering drugs like ST266, a biologic derived from placental cells, which contains growth factors that offer neuroprotection. Preclinical studies show that when ST266 is administered intranasally, the highest concentrations are found specifically in the optic nerve tissue. This targeted approach ensures the medication is concentrated where it is needed most, potentially allowing for a lower overall dose and reducing systemic exposure.
Safety Profile and Current Status of Nasal Sprays
The development of nasal sprays specifically for glaucoma is still largely in the clinical trial phase, focusing on establishing both efficacy and a favorable safety profile. One investigational product, ST266, a neuroprotective agent, has completed Phase 1 open-label trials in glaucoma suspect patients. Preliminary safety results indicated that the intranasally delivered biologic was a safe treatment option, with no drug-related serious adverse events reported.
The safety of the delivery method must also be considered, particularly the potential for local nasal side effects. Patients may experience minor irritation, dryness, or mucosal changes related to the spray’s formulation, though these are typically localized and transient. This local irritation is generally less concerning than the systemic risks associated with traditional eye drops, such as cardiac or respiratory complications.
It is important to differentiate these emerging glaucoma treatments from common intranasal corticosteroid sprays used for allergies. While studies on certain steroid-based nasal sprays have shown no significant increase in IOP in patients with controlled glaucoma, the new glaucoma-specific nasal sprays are non-adrenergic and non-steroidal. Patients should discuss all emerging options with their ophthalmologist, understanding that a safe nasal spray offers targeted delivery with a significantly reduced systemic side effect burden compared to current topical medications.