Doctors who transplant corneas have always thought of the vision-saving surgery as gender-neutral, but a new study in the U.K. has found that female patients do better if they get their new corneas from other women rather than men.

The study of more than 18,000 patients in the U.K. found that female transplant recipients were more likely to have successful transplants if they got a woman’s cornea—but there was no gender difference in failure rates for men receiving women’s tissue. With one corneal disease, called Fuchs endothelial dystrophy, women’s transplants were 40 percent less likely to fail if they received another woman’s cornea instead of a man’s, according to the study published Thursday in the American Journal of Transplantation.

Christopher J. Rapuano, who heads the cornea service at the Wills Eye Hospital in Philadelphia and was not involved in the research, says he was surprised to see gender turn up as such a significant factor. “It seems like something that we would have known about before,” he says.

The cornea is the front part of the eye that gives it its curvature and two thirds of its refracting power. Injury, infection or disease can damage the cornea, limiting vision and potentially leading to blindness. Surgeons perform about 45,000 to 50,000 corneal transplants a year in the U.S.

Proteins called human leukocyte antigen (HLA) help the body identify which cells belong to it and which are foreign. In solid organs transplants, which involve a lot of blood vessels, HLA matching is beneficial. In contrast, HLA matching is not generally undertaken for corneal transplants as the cornea has no blood vessels and HLA matching has not been shown to be beneficial, explains Stephen Kaye, the study's senior author. As such, in the U.S., Australia as well as in the United Kingdom, HLA matching is not done for corneal transplants, Kaye notes. In other words, he says, the gender effect reported was not related to HLA matching.

Previous research has not indicated the need to separate transplants by gender. “In Australia, we do not see—have never seen—an influence of gender matching or mismatching on corneal graft outcome,” Keryn Williams, scientific director of the Australian Corneal Graft Registry who was not involved in the research, wrote in an e-mail. Williams speculated that the results could be at least partly due to the fact that donors and patients in the U.K. are matched differently than they are in many other parts of the world.

Kaye says the vast majority of patients he studied were not HLA matched. The gender effect was strongest in patients with certain diseases, such as Fuchs endothelial dystrophy, he says—but less evident in other higher-risk conditions. Patients in the U.K. may have different outcomes from those in the U.S. because of procedural differences, says Kaye, a professor of opthamology at The Royal Liverpool University. In the U.S. tissue is stored under different conditions than in the U.K., and post-mortem times in the U.S. are much shorter, he says.*

The amount of tissue transplanted may also make a difference in rejection rates, Rapuano says. Most patients only need to replace the crucial back layer of cells, which account for 10 to 20 percent of the cornea, he explains. Transplanting fewer cells may mean a lower chance of rejection—and gender would therefore matter less to the outcome, Rapuano adds, noting that more than half of all corneal transplants in the U.S. are partial.

Gender has not been widely considered significant in the success of transplanting solid organs such as the heart, kidney or lungs. But there are questions about the importance of gender “scattered in the transplant literature,” according to David Klassen, chief medical officer of the United Network for Organ Sharing, a nonprofit organization that handles solid organ procurement in the U.S. and manages the organ transplant waiting list under contract with the government. “Overall, gender mismatch doesn’t really have a major impact on solid organ transplantation,” says Klassen, who was not involved in the new study. Gender does sometimes make a difference, however, when it affects the size of the donated organ, he says. A small woman would have trouble accommodating lungs donated by a large man, and a large man would have trouble getting enough oxygen if he were to receive the heart of a small woman.

Reza Dana, a corneal transplant surgeon who works at Massachusetts Eye and Ear hospital in Boston and was not involved in the research, says the new study does give him pause about the practice of transplanting a man’s cornea into a woman. Before doctors start changing their procedures, however, Dana would like to see a larger, prospective trial to provide more evidence that gender matching is warranted. “The problem is that changing the patterns of how tissue banks manage tissues is a major undertaking which will carry costs. Of course, having excess rejections or graft failures also carries costs,” says Dana, also a professor and senior scientist at Harvard Medical School.

Rapuano says he doubts most transplant programs would have the luxury of turning down organs based on gender without conclusive evidence that it makes a significant difference. “If you say male tissue can only go to males, you’re really limiting what tissue can be used for females—you’re decreasing their donor population by half,” he says.

But Williams said the new study is a reminder of unexpected roles that gender may play in health—and of the importance of such research. “If you don't measure outcomes in prospective, longitudinal cohort studies, you may never know whether you are doing the best you can for a population of patients,” she wrote via e-mail. “The data from the British registry has potential to significantly improve outcomes for corneal graft recipients in Britain, if not necessarily elsewhere. If you don't measure it, you won't know.”

*Editor's Note (7/15/16): This paragraph was added after posting to update the story with the perspective of the study's senior author.