March 2020

CORNEA

Research Highlight
Role of lymphatic vessels in failed corneal transplants


by Maxine Lipner Senior Contributing Writer


When performing corneal procedures such as PKP, DALK, DSAEK, and DMEK, lymphatic vessels may play a role in graft failure.
Source: Neeru Gupta, MD

“The fact that we consistently found lymphatic vessels in all of the failed grafts in which we detected neovascularization suggests that they play some role in corneal transplant failure and that they need attention.”
—Neeru Gupta, MD

While neovascularization is a leading cause for graft failure, it does not appear to be the sole factor, according to Neeru Gupta, MD. A study indicates that lymphatic vessels are also found when there is graft failure in patients.1
“In every case of graft failure in which there were abnormal blood vessels, we also found lymphatic vessels,” Dr. Gupta said.
In launching the study, investigators hoped their work might help eliminate the need for future repeat grafts, hypothesizing that the lymphatic system might be involved, Dr. Gupta explained.
“The eye has traditionally been thought to be devoid of lymphatic vessels,” she said. While much time has been spent trying to tackle corneal neovascularization in an attempt to forestall graft failure, graft survival hadn’t changed much in 30 years.

Testing for lymphatics

Unlike traditional blood vessels, lymph is a clear fluid, making it difficult to detect. While it is part of nearly all organs, it is not supposed to be in the cornea.
“Our hypothesis was: If we haven’t seen any changes, given our current therapeutic approach, maybe there are abnormal lymphatics as part of the process in corneal graft failure,” Dr. Gupta said.
Systematically, investigators conducted tests on the graft failures, which included not only the usual immunohistochemistry but also testing for messenger RNA associated with lymphatics. With this testing, they were able to identify these lymphatic vessels in all nine of the failed grafts they examined, Dr. Gupta reported. Abnormal blood vessels were easily identified in all.
“The lymphatic vessels were distinct and separate,” she said. “The fact that we consistently found lymphatic vessels in all of the failed grafts in which we detected neovascularization suggests that they play some role in corneal transplant failure and that they need attention.”

Multipronged approach

To help curtail graft failure, drugs that target lymphatics are needed, Dr. Gupta said.
“We may need to hone in on specific targets to get rid of these lymphatic vessels as part of the process,” she explained, adding that these are part of the afferent pathway of the immune system and a vehicle for inflammatory infiltrates. While traditionally practitioners have stringently treated those experiencing graft rejection with a panoply of topical corticosteroids, immunosuppressive agents, cyclosporine, and other agents, it hasn’t been sufficient, given that the graft failure rate has not gone down in decades, Dr. Gupta said.
She would like to see such treatment used in conjunction with traditional therapy.
“We can continue to offer patients steroids, hitting the inflammatory component, to try to get those blood vessels to regress. But wouldn’t it be great to add something to the mix that was anti-lymphatic so that we could make sure that we were also hitting the immune system arm and able to salvage the cornea that way?” Dr. Gupta said.
Down the line, it may be possible to use an in vivo imaging system to detect those who have lymphatic vessels and treat them accordingly.
“It’s highly reasonable that with sophisticated imaging tools such as OCT or some other technology to look at the cornea microscopically, we might be able to say, ‘This patient has lymphatics, and based on this, we are going to prescribe drug A + B + C, or A + B instead of just A,’” Dr. Gupta said.
She views the study as bringing to light a new aspect of graft rejection.
“I think the takeaway is just because you can’t see them, doesn’t mean they’re not there,” Dr. Gupta said. “We need to turn our attention with full force to the lymphatics to understand their role and to advance the field. If we can easily pick them up in the clinic and target these as part of preventing graft failure, it would be a way to advance the field and personalize care.”
This would ultimately reduce the burden of graft failure on the donor tissue supply, which is an issue worldwide, she concluded.

About the doctor

Neeru Gupta, MD
Professor and Dorothy Pitts Chair
Departments of Ophthalmology & Vision Sciences
Laboratory Medicine and Pathobiology
St. Michael’s Hospital
University of Toronto
Toronto, Canada

Contact

Gupta: guptan@smh.ca

Reference

1. Diamond MA, et al. Lymphatic vessels identified in failed corneal transplants with neovascularisation. Br J Ophthalmol. 2019;103:421–427.

Relevant disclosures

Gupta
: None

Role of lymphatic vessels in failed corneal transplants Role of lymphatic vessels in failed corneal transplants
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