Ocular drug delivery is the process of transporting medications to specific parts of the eye. The primary goal is to ensure a medication can exert its therapeutic effect on the target tissue while reducing potential side effects. This is necessary because the eye is a well-protected organ, making it difficult for drugs to reach the areas where they are needed.
The Eye’s Natural Defenses
The eye has several defenses that complicate drug delivery. The tear film, a thin fluid layer on the eye’s surface, lubricates the eye but also quickly flushes away medications. The eye holds only about 25 microliters of fluid, so excess from an eye drop spills out immediately. The remainder is washed into the tear drainage system within minutes, limiting the time for the drug to be absorbed.
The cornea acts as a structural barrier to drugs entering the front of the eye. It is composed of multiple layers of tightly packed cells that are difficult for most drug molecules to penetrate. Its outer layer, the epithelium, repels water-soluble molecules, while the inner layer, the endothelium, repels fat-soluble ones. A drug must have a mix of both properties to navigate this tissue.
For drugs needing to reach the back of the eye, the blood-retinal barrier is another obstacle. Similar to the blood-brain barrier, this selective gateway controls which substances pass from the bloodstream into the retinal tissue. This barrier consists of tightly joined cells lining the retinal blood vessels, preventing toxins from entering. This protection also blocks most oral or intravenous medications from reaching the retina in sufficient concentrations.
Topical Drug Administration
Topical administration, applying medication directly to the eye’s surface, is the most common treatment method. This includes formulations like eye drops, gels, and ointments. These are used for diseases affecting the anterior part of the eye, such as glaucoma, dry eye, and conjunctivitis. Direct application is convenient and targets the affected area without systemic exposure.
Gels and ointments offer an advantage over eye drops as their thicker consistency allows them to remain on the eye’s surface longer, improving drug absorption. However, these formulations can cause temporary blurred vision. The choice between these options depends on the condition, dosing frequency, and patient preference.
Despite their widespread use, topical delivery methods are inefficient. Due to the eye’s natural defenses, less than 5% of the administered drug is absorbed. The rest is washed away or drained into the systemic circulation, where it can cause side effects. This low bioavailability means high drug concentrations are needed in the formulation to be effective.
Intraocular Drug Administration
For diseases affecting the back of the eye, clinicians use intraocular administration to overcome topical delivery limitations. This method involves injecting medication directly into the eyeball, bypassing surface barriers. The most common form is the intravitreal injection, delivering a drug into the vitreous humor. This approach ensures a concentrated dose reaches the retina.
Intravitreal injections are a standard treatment for retinal diseases like wet age-related macular degeneration (AMD), diabetic retinopathy, and retinal vein occlusion. The drugs administered, such as anti-VEGF agents, stop the growth of abnormal blood vessels that damage the retina. This direct delivery is more effective for these conditions than topical or oral medications.
While effective, intravitreal injections have challenges. Patients require repeated injections, which can be a treatment burden. The procedure is safe but carries a small risk of complications, including:
- Infection
- Inflammation
- Retinal detachment
- Increased pressure inside the eye
Researchers are exploring ways to reduce injection frequency without compromising therapeutic benefit.
Sustained-Release Drug Systems
To address the challenges of frequent dosing, researchers developed sustained-release drug systems. These technologies deliver a continuous supply of medication over an extended period, from weeks to years. This improves treatment outcomes by ensuring consistent drug levels and reducing the burden on patients. These systems represent a shift in managing chronic eye diseases.
One example is the ocular implant, a tiny device placed inside the eye during a minor surgical procedure. Implants can be non-biodegradable, requiring surgical removal, or biodegradable, dissolving on their own. These devices release medication for months or years, offering a long-term solution for conditions like chronic uveitis and diabetic macular edema.
Another approach involves ocular inserts, placed on the eye’s surface or in the tear duct. These flexible devices slowly release medication over days or weeks, providing a more consistent dose than eye drops. A more recent innovation is the drug-eluting contact lens, which combines vision correction with drug delivery. The lens material is infused with medication that gradually releases into the tear film, offering a convenient option for treating surface conditions.