UPFRONT

Out of the Box

Peter K. Kaiser, MD

In many aspects of ophthalmology, we have a dosing problem. Glaucoma patients have to remember to take their drops several times a day. Retina patients need to succumb to monthly injections for many diseases, and may have worse outcomes when they do not do this. Developing better ways to fix this problem is the cornerstone of several start-up companies.

“Thinking outside the box” is what these companies have to do to solve the problem of sustained release. Some are developing reservoir-type implants by which the drug is slowly released from a refillable implant. This is the easiest solution because, in general, the drug does not need to be reformulated and only the device needs to be designed.

Approval is also straightforward because one must only prove the safety of the device itself (as well as in the case of a catastrophic failure), but the drug itself has already been tested. Other companies are looking at different polymers that will slowly release drugs over time. But the truly innovative companies are looking at even longer-term delivery through ideas that many of us have not even heard of.

In this issue, we explore some of the innovative ways that electrical current can be used to advance our field. Many readers will recognize the field of iontophoresis, in which an electrical field is used to pass a drug into the eye, but few will know about electroporation, in which an electrical current is used to change the configuration of cell membranes to allow direct injection of DNA/RNA into cells — gene therapy without a virus.

Other companies are looking at the idea of using stem cells to produce the trophic factors necessary for retinal survival. Interestingly, both ideas target the ciliary body instead of the retina for their action. These are excellent examples of researchers thinking way outside the box, and they illustrate how far we will go to treat retinal disease.

The commonly used quote is related to the nine-dot topographical puzzle shown above, in which the only way to connect the dots with four straight, continuous lines is to draw lines outside the dots themselves. In other words, look beyond the perceived, unspecified boundaries imposed by the dots. Thankfully, many researchers are doing exactly that.