Eye drops for cataracts

Medical researchers may have found a way to treat cataracts with eye drops instead of surgery, the long-sought Holy Grail for lens biologists.

When light enters the eye, a structure called the lens helps to focus it onto the light-sensitive retina in the back of the eye. In order to do this, the lens needs to be completely transparent. Put simply, a cataract is a lens that became opaque.

Unlike most other cells in the body that produce thousands of different types of proteins, cells in the lens produce only a few different types of proteins called crystallins. These crystallin proteins pack together in a specific way to form the lens’ transparent structure¹. A cataract forms when crystallins aggregate, or clump together, to make the lens opaque². Often, cataracts only appear in elderly patients.

In the US, it’s easy to dismiss cataracts as a relatively trivial problem because they’re so easy to treat here. Before cataracts significantly impair vision, patients can get a routine, relatively simple surgery performed to have them removed. In place of the original lens in the eye, surgeons implant an artificial lens, called an intraocular lens, or IOL³. After surgery, the problem is effectively fixed for the rest of their lives.

Cataract removal unfortunately isn’t an option for many patients in underdeveloped nations. According to the World Health Organization (WHO), cataracts account for ~48% of cases involving significant visual impairment⁴. Cataract patients in the underdeveloped parts of the world eventually lose their vision because IOL implant surgery isn’t widely available.

In addition to the elderly, cataracts can develop early in childhood or as the result of an injury to the eye. Childhood cataracts are known as congenital cataracts and are usually the result of some sort of genetic disease.

Unlike in adults, IOL implantation in children isn’t as straightforward because of complications surrounding the surgery in young patients. Early surgical intervention is critical to prevent problems with eye growth and visual cortex development in the brain, but the surgery itself also can cause problems in children. Even when a surgeon successfully removes a cataract in a child, there is a significant risk of amblyopia (lazy eye), glaucoma, severe inflammation, and retinal detachment (when the light-sensitive retina rips away from the back of the eye)³.

Because surgery isn’t a great option for children and is unavailable to many patients in poorer parts of the world, lens biologists have worked for decades towards a better treatment option. Eye drops, like the one proposed by a group of researchers recently, may be that better option. The researchers conducting the study stumbled upon the treatment when they were looking at some families with a history of congenital cataracts.

When they were looking at these families to try to gain some understanding about how cataracts form, they found these families had mutations in the LSS gene that codes for a protein known as lanosterol synthase. This protein is critical for the production of lanosterol, a molecule derived from cholesterol that is common in the lens².

Because lanosterol is abundant in the lens and these people had problems making the molecule, the researchers conducting the study delivering lanosterol by eye drop could fix the cataract. When they tried the eye drops in rabbit lenses, the cataracts dissolved in a matter of hours².

Excited by these results, the researchers decided to test the same eye drops in older dogs. Dogs, like humans, can have either congenital cataracts or develop them with age⁵. Also, like humans in underdeveloped parts of the world, dogs aren’t normally treated for cataracts by surgery, either because of cost or because veterinary ophthalmologists aren’t common. When the researchers tried the lanosterol eye drops in elderly dogs with cataracts, the dogs’ cataracts also improved².

In many ways, it’s hard to overstate how important this study is. Although most people with cataracts don’t have mutations in the LSS gene or have problems with lanosterol synthesis, the fact these eye drops helped aging dogs suggests the eye drops may also work in aging humans.

Because of the time it takes to get FDA approval to start clinical trials and enroll patients, we probably won’t know whether they work in humans for years. That being said, the researchers conducting this study did a fantastic job. I am very encouraged by this study and hope this will lead to a better, more widely available treatment for an incredibly common cause of blindness.

Correction: This post originally reported lanosterol eye drops were administered to engineered mice. In fact, the drops were administered to rabbits.

References

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2666974/pdf/nihms84083.pdf

http://www.nature.com/nature/journal/v523/n7562/full/nature14650.html

http://www.ncbi.nlm.nih.gov/pubmed/23224414

http://www.who.int/blindness/causes/en/

https://www.aspca.org/pet-care/dog-care/cataracts