Is it possible that tens of thousands of babies have had eye operations that inadvertently destroyed their natural ability to heal, leaving many of them blind, when a minor surgical tweak could have cured them?
That is one implication of a study published Wednesday in the journal Nature.
Standard cataract surgery destroys the eye’s own stem cells, scientists in the United States and China reported. But a procedure they devised would not only preserve the cells but also awaken them from a biological slumber.
In lab animals as well as in 12 babies born with cataracts, the minimally invasive technique triggered the eye’s own stem cells to rebuild a complete, healthy, clear-as-glass lens. It is the first time researchers have regenerated a functional mammalian eye.
Dr. Ali Djalilian, an ophthalmologist at the Illinois Eye and Ear Infirmary who was not involved in the study, called the results “interesting and worth studying” further. But he cautioned that eight months — the latest time for which the paper reported data — is too short to show definitively that the experimental procedure is safe and effective, including whether the new lenses have the flexibility to see near and far.
Still, “the fact that they didn’t find serious complications over eight months is remarkable,” he said. “I was pleasantly surprised.”
Cataracts make the lens of the eye cloudy, impairing vision enough to cause blindness. Although cataracts are better known as consequences of aging, they also occur in 1 in every 3,000 newborns, or about 1,200 American babies each year, mostly due to genetic mutations.
The standard treatment for congenital cataracts is surgery to remove the clouded lens and implant an artificial one. Surgical techniques do not have to be rigorously tested, let alone win approval from health regulators such as the Food and Drug Administration; they can spread through the profession once a few pioneers vouch for them.
In the case of congenital cataracts, the operation — starting with a large incision — often causes complications, including inflammation, glare, and calcification, with the result that many of the children need glasses or additional surgery. Some even develop glaucoma.
The procedure also destroys what are called lens epithelial stem cells, which self-renew — that is, they make more of both themselves and specialized lens cells.
For their study, scientists led by Dr. Kang Zhang of Sun Yat-sen University of China and the University of California, San Diego, first tested how well lenses of infant macaques and rabbits could regenerate. They removed the lenses of the animals’ eyes using a new, minimally invasive surgery they developed which preserved the lens stem cells. After seven weeks and five months, respectively, the rabbits and monkeys had beautiful double-convex lenses just like nature’s, the product of their lens stem cells.
The scientists then launched a clinical trial at the Zhongshan Ophthalmic Center, the largest eye hospital in China, involving 12 infants and toddlers who had been born with cataracts in both eyes. Using the technique they had tested on the lab animals, the scientists found that all 24 eyes developed clear, healthy lenses within three months of the novel surgery. By eight months, the lenses were just like natural ones.
“We have continued following these children and most of them [continue] to have good vision and a functional lens,” Zhang said.
In contrast, the 25 children who received the standard surgery in both cataract-ridden eyes had an 11-times higher complication rate, including swelling in 15 eyes (versus two in the eyes that had the new operation) and inflammation in 37 (versus four).
Crucially, 42 of the eyes that underwent the standard operation required additional surgery; none of the eyes that had the new procedure did. And the transparency of the lenses that got the new surgery was 20-times better than with the standard-of-care treatment.
However, outside experts question whether that was a fair comparison. Dr. Deborah VanderVeen, a pediatric cataract surgeon at Boston Children’s Hospital, cautioned that the outcomes for the control group in the study were worse than what she and other top surgeons get in their infant patients, and echoed the concern that the reported follow-up time was not long enough to conclude that the new lenses would not become cloudy.
Still, she said, “the nice thing about this paper is that it shows the lens material can regenerate into a convex shape” — just like the natural lens.
The findings, if validated in additional patients, not only offer a better surgical procedure: If natural stem cells can indeed be coaxed into creating a new lens, it means that the standard treatment has, unbeknownst to anyone, prevented that regenerative process.
Although this study was in children, the scientists found lens stem cells in adults, too. Those cells proliferated particularly well after the lens was injured, suggesting the new surgical procedure could induce healthy, clear lenses to regrow in the eyes of elderly cataract patients.
“We plan to expand our study into older patients who undergo cataract surgery and hope to restore both their distance and reading vision via lens regeneration,” Zhang said.
Another strategy could be to build new eye parts in the lab. To that end, scientists in Japan and Wales reported in a related Nature paper out Wednesday on a new way of growing what is essentially a two-dimensional eye-in-a-dish.
They started with human induced pluripotent stem cells — basically, cells that started out as adult cells but were time-traveled back to an embryonic state. Treated with biochemicals, a tiny fraction of these cells matured into cells of the cornea, lens, retina, and other eye structures, all forming a flat disc with different cell types arrayed in concentric rings.
When the scientists, led by Dr. Kohji Nishida of Osaka University, grew some of the cells into sheets of cornea cells and transplanted them into the eyes of blind rabbits, the animals’ vision was restored.
The expense of cell therapies makes it unlikely that the technique, should it work in people, would be economically feasible, cautioned Julie Daniels, a stem cell expert at the University College London Institute of Ophthalmology who authored a commentary on the two Nature papers.
But if the tweaked cataract operation lives up to the initial promise, it could transform surgery for infants and the elderly alike.