Smarter delivery systems for retinal disease treatments could reduce how often patients need injections.

Delivering drugs to the back of the eye has long frustrated ophthalmologists. Even when medications are injected directly into the eye, much of the drug fails to reach the retina, the main target for many treatments.

To tackle this issue, researchers at Ghent University have developed a method to actively guide drugs to the back of the eye. Their approach could be particularly valuable for diseases affecting the retina, including age-related macular degeneration and diabetic retinopathy, where precise drug delivery is essential.

Navigating the eye’s natural barrier

The challenge lies in the eye’s internal structure. The vitreous humor, which fills the space between the lens and retina, is a gel-like network of collagen and biomolecules that helps maintain the eye’s shape and protect it from damage. Medications intended for the retina must first navigate this dense barrier.

“The diffusion of drug molecules within the vitreous humor is slow, heterogeneous, and hard to predict, making it difficult for the drug to reach its target at the back of the eye,” explains Léa Guerassimoff, a postdoctoral researcher in the Laboratory of General Biochemistry and Physical Pharmacy at Ghent University.

Even when delivered directly into the vitreous, drugs are often cleared relatively quickly and may require repeated injections to maintain their effect, adding to the risks. “These frequent intravitreal injections increase the risk of complications, including infections, retinal damage, and inflammation,” Guerassimoff says.

Guerassimoff and her colleagues combined nanoparticles—tiny particles that can be used as drug carriers—with indocyanine green, a dye ophthalmologists routinely use to visualize eye tissue. When a laser is aimed into the vitreous and pulsed in bursts lasting a few nanoseconds, the dye absorbs the energy and generates localized heating, setting the surrounding vitreous in motion and helping steer the nanoparticles toward the illuminated region.

Without dye staining or laser treatment, the nanoparticles—made of polystyrene and not loaded with drugs—moved randomly within a confined area.

“Our approach demonstrates, for the first time, the directed transport of drug cargos within the vitreous humor,” Guerassimoff says.

A surprising physical mechanism

How the nanoparticles move toward the laser-targeted region surprised the researchers. They initially expected thermophoresis—a force that pushes individual particles along temperature gradients—to dominate. Although thermophoresis contributes to some extent, they found that the key mechanism is the movement of the vitreous itself, known as thermal convection. The laser-induced heating creates tiny circulating currents in the vitreous that carry the nanoparticles along.

This insight could reshape how such systems are designed.

“Designing active delivery approaches in the vitreous humor should focus on controlling or leveraging these convective flows,” Guerassimoff says.

Toward more precise, personalized treatments

The team also showed that the process can be tuned. Increasing dye concentration or laser intensity strengthens the effect, while particle size influences how easily particles move through the vitreous.

At the same time, the study highlights aging as an important biological variable. Over time, the vitreous humor partially liquefies, forming pockets of liquid that change how particles move. “This significantly alters the behavior of drug molecules following intravitreal injection,” Guerassimoff explains.

The nanoparticles moved more freely in aged, liquefied vitreous and responded differently to laser guidance, raising the possibility of tailoring treatments to individual patients.

“Such patient-specific variations must be considered in routine clinical practice,” Guerassimoff notes.

From proof of concept to clinical potential

If translated into practice, the drug-delivery technique could reshape how retinal diseases are treated. A patient might receive an injection containing drug-loaded nanoparticles and dye, followed by targeted laser application to guide the medication to the retina. “This combination of injection and laser irradiation could improve drug localization, enhance therapeutic efficacy, and potentially reduce the need for repeated injections,” Guerassimoff says.

For now, the work remains at an early stage. The experiments were conducted in controlled laboratory settings using vitreous extracted from bovine eyes, and further safety studies will be needed before testing the method in patients.

Still, the pairing of two established tools in ophthalmology—an approved dye and clinically relevant laser wavelengths—means the approach is already aligned with clinical practice, which could help facilitate its eventual adoption.

Reference: Léa Guerassimoff et al., Photothermal Transport for Guiding Nanoparticles Through the Vitreous Humor. Advanced Science (2025), DOI: 10.1002/advs.202516534

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