Eye drops research progresses

Posted: Tuesday 16 October 2018

Age-related macular degeneration (AMD) is the leading cause of sight loss in the UK. There is no treatment for the “dry” form, and all the existing treatments for the “wet” form involve delivering a specially designed antibody to the retina.

It’s hard to get enough of the drug into the retina using tablets or injections into a vein, so the best technique at the moment involves injecting a small volume of a drug directly into the middle of the eyeball. The drug then stays inside the eye and works away on the retina over a period of weeks, before it is broken down by the human body.

This treatment is effective, but giving repeated injections, sometimes for many years, means patients have to make multiple clinic appointments. Each injection also has a small potential risk of sight-threatening complications.

The ideal treatment would be something that patients could take themselves with a minimum of effort. If wet AMD could be treated with eye drops instead of injections, not only would patients be happier, but the NHS would save a lot of time and resources. So it’s no wonder that this is a “holy grail” of AMD research at the moment.

In 2018’s Spotlight magazine, we described work at the University of Birmingham using cell-penetrating peptides to “drag” an anti-VEGF drug to the back of the eye. This could mean that eye drops replace injections as a treatment for wet AMD, but at the time of going to press the drops had been tested only on rats.

Now researchers have reported encouraging results in experiments with rabbit and pig eyes, which are more similar to human eyes, and plan to start clinical trials on humans as early as spring 2019.

How do eye drops work?

For a molecule from an eye drop to cross the front of the eye (the cornea), it needs to overcome its most important barrier, the surface epithelium. Fat-soluble molecules move through the epithelium more easily than water-soluble ones.

Other eye conditions, such as glaucoma, are already treated with eye drops – in this case, a surfactant is added to the eye drop to help the drug penetrate better. But to treat glaucoma, drops only need to cross the cornea to reach their target. For AMD treatments targeting the retina, the drug has further to travel, and must withstand attack from enzymes in the eye that want to break it down. All of this makes it harder to get a large enough dose of the drug to where it’s needed.

The future

Some promising research has used nanoparticles to deliver larger drug molecules to the back of the eye. Attaching the drug to a nanoparticle can make it more fat-soluble, protect it from degradation from enzymes and increase the uptake of the drug into human cells. A number of nanoparticles with a variety of complex structures and distinctive building blocks have been tried. However, a viable solution is likely to take many years to be tested and approved.

Even though replacing injections with eye drops would be very popular with patients, the drops would still need to be taken regularly, which may be an even greater challenge. This area nevertheless remains an encouraging avenue for research.

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