Issue: May 10, 2020
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Disclosures: The sources report no relevant financial disclosures.
May 05, 2020
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Sight restoration foundation will help improve outcomes for severe ocular surface disease

Issue: May 10, 2020
Source/Disclosures
Disclosures: The sources report no relevant financial disclosures.
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The newly formed Holland Foundation for Sight Restoration will begin funding positions and providing corneal specialists with the tools they need to integrate a treatment protocol for severe ocular surface failure into future centers of excellence across the country.

The foundation is intended to provide surgical education for corneal specialists and funding for additional practice positions to ensure successful rehabilitation for patients affected by severe ocular surface disease.

For the more than 100,000 patients across the country who have lost vision due to thermal/chemical injury, genetic ocular surface failure or systemic disease, the process to rehabilitate vision is complex and costly, OSN Cornea/External Disease Board Member Edward J. Holland, MD, director of cornea at Cincinnati Eye Institute, said.

Edward J. Holland
Edward J. Holland, MD, uses a stringent postoperative immunosuppression regimen on par with treatment protocols for kidney transplantations to reduce the risk for graft rejection.
Source: Edward J. Holland, MD

“We have created a foundation to raise money for ophthalmologists to fund necessary positions at their practice and to break down the roadblocks we see challenging treatment for these patients at other institutions,” Holland said.

A difficult disorder to treat

The conjunctiva, limbal stem cells and cornea are typically affected in severe ocular surface impairment. These patients are not eligible for standard corneal transplantation due to conjunctival and limbal stem cell injury and need ocular surface stem cell transplantation and subsequent corneal transplantation to regain functional vision, Holland said.

The protocols in place at Cincinnati Eye Institute/University of Cincinnati are used at practices outside of Cincinnati but on a much smaller scale, if at all, Robert J. Dempsey, chairman of the board for the Holland Foundation for Sight Restoration, said.

“We have the opportunity with Dr. Holland and his protocols, and a select group of doctors across the country who utilize them, to really make a difference and give the gift of sight to these patients,” Dempsey said. “I challenged [Holland] to make a difference, so we developed a team, a board of directors and started a foundation that will take this ball and run with it.”

The foundation has secured 501(c)(3) designation to accept donations in order to establish six initial centers of excellence across the country with corneal specialists who currently use Holland’s surgical protocols but may not have the resources to do it on a large scale.

Funds for training

The centers of excellence will receive training from the foundation to teach which ocular surface transplantation procedure is indicated for each patient, such as Holland’s technique, the “Cincinnati procedure,” using a combined conjunctival limbal allograft and keratolimbal allograft in patients with the most severe ocular surface failure.

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As graft rejection is the main cause of failure, Holland uses a stringent postoperative immunosuppression regimen on par with treatment protocols for kidney transplantations to reduce the risk for rejection. Oral immunosuppressive medications are administered as determined preoperatively by the University of Cincinnati renal transplant team and are individualized for each patient based on preoperative factors such as the cause of ocular surface failure, amount of inflammation, age and level of immunologic match of the donor.

Holland’s surgical protocols for this difficult-to-treat group of patients result in “impressive” outcomes, Dempsey said.

A 2017 publication in American Journal of Ophthalmology reviewed Holland’s long-term outcomes of various ocular surface stem cell allograft transplantations, including living-related conjunctival limbal allograft, keratolimbal allograft and the Cincinnati procedure, in patients with total ocular surface failure. There were 165 eyes of 110 patients with 5 years or more of follow-up. A 72.7% success rate in maintaining the ocular surface was achieved. Additionally, 62.1% maintained a significant improvement in their vision over this long-term period.

The patients with the most severe disease (conjunctival and limbal deficiency) have the worst prognosis and are treated with the Cincinnati procedure. In the original publication of this technique, Biber and colleagues reported on the outcomes of this surgery, all performed by Holland, in 24 eyes of 19 patients with severe ocular surface disease and conjunctival deficiency. In 21 eyes, preoperative best corrected visual acuity was 20/400 or worse; postoperatively, 17 of 24 eyes achieved 20/125 or better.

In another series of 11 eyes of 11 patients operated by Holland, Chan and colleagues described a modified Cincinnati procedure that used autograft in patients with unilateral ocular injury caused by chemical and/or thermal accident. Preoperatively, BCVA was 20/400 or worse in all eyes. At mean follow-up of 35.8 months, 73% of eyes had BCVA of 20/80 or better, and the ocular surface was stable in 82% of eyes.

The Cincinnati team now follows more than 500 patients on oral immunosuppression.

The average corneal surgeon without a team can’t follow these challenging patients — it’s too much for them to do alone,” Holland said.

Importance of coordination

To manage and organize the stringent postoperative immunosuppression needs of his patients, Holland employs a transplant coordinator. Transplant recipients require constant postoperative monitoring and mandatory examinations, with strict adherence to immunosuppressive therapy.

“The coordinator manages all of the immunosuppression protocols and follows all of the labs for our patients,” Holland said. The foundation is structured to provide funding for transplant coordinators for up to 3 years for each established center of excellence.

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Holland’s coordinator, Elizabeth M. Kinosz, LPN, works closely with hundreds of transplant patients to coordinate follow-up appointments, answer questions, coordinate lab appointments, and track immunosuppression medications and adherence.

The transplant coordinator is also the liaison among the patient, the surgeon and the nephrology team.

“Our patients on immunosuppression medications get labs very frequently, so we monitor them constantly and make sure their primary care provider is aware of their results. We’re constantly evaluating for abnormal results. We monitor each patient’s adherence to their immunosuppression and medication protocols. This is essential,” Kinosz said.

Patients are referred to the clinic from all over the world, so constant evaluation and monitoring of their status and compliance are crucial to their overall treatment. It is impossible for cornea specialists to track and monitor hundreds of patients, which makes the coordinator a key cog in the necessary protocols for success, Kinosz said.

Nephrologists help with immunosuppression

In addition to providing funding for transplant coordinators, the Holland Foundation for Sight Restoration will identify interested regional nephrologists for centers of excellence to aid in the immunosuppression aspect of treatment, Holland said.

“What we have seen on the referrals we get for failed ocular surface transplants is that those patients have had low-dosing immunosuppression for a short period of time. That doesn’t work. It doesn’t work for organ transplantation, and it doesn’t work for ocular surface stem cell transplant,” Holland said.

The Cincinnati program works closely with Amit Govil, MD, a nephrologist at the University of Cincinnati’s College of Medicine, and David Hooper, MD, a nephrologist at Cincinnati Children’s Hospital, to stay up to date on immunosuppression therapies, drugs, protocols and techniques for transplant procedures.

“The real breakthroughs in immunosuppression and in the field of immunosuppression come from nephrology. The kidney was the first major organ ever to be transplanted; it is the most common transplanted organ, more so than hearts, lungs or livers,” Holland said.

Robert J. Dempsey
Robert J. Dempsey

The average nephrologist working in kidney transplantation completes a fellowship in nephrology and a second fellowship in the management of organ transplantation and immunosuppression. Finding a nephrologist to work closely with each center of excellence is a key strategy, Holland said.

“We’ve seen what happens when programs use oncologists, rheumatologists or internists to help manage immunosuppression. Usually they give patients low-dose, anti-inflammatory medications, but those are not the same medications used specifically for organ transplant patients, and that’s what we need,” Holland said.

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Nationwide, patients are referred to the Cincinnati Eye Institute for the transplant procedure.

“Ed has been somewhat on his own in Cincinnati, really focusing on severe ocular surface disease patients. He dedicates a tremendous portion of his craft to treating extremely difficult-to-treat patients,” Dempsey said. “He has developed a comprehensive network of nephrologists and trained his own transplant coordinator to help him manage patients referred to him from around the country and the world.”

Funding is crucial

Dempsey and Holland put together a board of directors to set the bylaws of the foundation, create the infrastructure of the group and begin the process of creating a 501(c)(3). With the 501(c)(3) now in place, organizations and individuals can make tax-deductible donations to the foundation.

“The creation of the 501(c)(3) gives us the ability to engage high net worth donors and industry partners to accept donations,” Dempsey said.

The donations will help initially fund centers of excellence for six physicians: Winston Chamberlain, MD, Albert Cheung, MD, Ali Djalilian, MD, Marjan Farid, MD, Nicole R. Fram, MD, and Christopher E. Starr, MD.

There has been a long-standing unmet need of treating patients with stem cell deficiency, and “Dr. Holland’s program has taken an interest in this subgroup of people who are so desperately in need,” according to Fram, of Advanced Vision Care in Los Angeles.

“What I am most excited about is that hopefully more people are going to take an interest in this challenging patient population. There will be more accessible care, and it will be based on the Holland protocol, which has probably had the highest success rate in the world,” Fram said.

The funding and potential for additional research may help improve the protocols in this underserved area of ophthalmology and increase the availability of stem cell transplantation procedures, Fram said.

“We can’t do anything without stem cells. It’s a huge area of neglect in our field,” she said.

Additional employees reduce burden

The additional people power allotted to practices, however, will have the biggest impact for surgeons. Fram said her practice cares for nearly 200 postoperative patients a month overall, and in this high-risk cohort, identifying problems before they become serious is key.

Marjan Farid
Marjan Farid

A transplant coordinator, the paired nephrologist and primary care physicians can monitor these patients for follow-up on any systemic issues, she said.

“Patients get the best care when their doctors are communicating. You can’t have an abstract person just reading labs in an office in this patient population. A patient undergoing stem cell transplantation on immunosuppression requires meticulous observation and care due to the comorbidities associated with immunosuppressive therapy,” she said.

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Most clinics are busy, and “there are things that can fall through the cracks,” Fram said, but with this particular patient population, there is zero tolerance. “This group needs systemic treatment to be followed up every 3 to 6 weeks at the start of their postoperative period and then every 6 to 8 weeks to monitor for complications with their immunosuppression therapies. Having the people power to care for these patients is by far the biggest practical hurdle,” she said.

Treating more patients nationally

Farid, an OSN Cornea/External Disease Board Member, said with the additional support from the foundation she will likely be able to treat up to 10 times more patients than she handles in a year.

Presently, Farid is one of the few surgeons on the West Coast who performs limbal stem cell transplants with the Cincinnati protocol, but her resources are limited. When her center of excellence gets off the ground, Farid said she hopes to be able to take a portion of the patient load Cincinnati Eye cannot handle.

“Currently Ed and I coordinate with patients, but this will really help us kick off our treatment of a larger number of patients. This will help so many who otherwise would not have much hope for the restoration of their vision,” she said.

The additional manpower will help provide the resources needed for Farid to expand services and handle referrals from across the country.

The transplant coordinator will help manage the higher volume of patients coming into Farid’s practice, but the close relationship with an educated and involved nephrologist will ensure the types of outcomes Holland achieves.

“To bring in his nephrology team to train our nephrology team would be ideal. They are much more willing to listen to someone in their own specialty than to listen to an ophthalmologist,” she said.

Most surgeons attempting these procedures usually do not use the correct cocktail of immunosuppression drugs or administer the drugs for an appropriate amount of time. This is where the nephrologist and ophthalmic surgeon can collaborate and base treatments on the most up-to-date protocols for immunosuppression, Farid said.

“Previously ocular surface transplantation would have a high failure rate due to poor immunosuppression protocols. Many would only use cyclosporine or prednisone only, but a correct combination of immunosuppression therapies similar to those used for renal transplantation is required,” she said.

The centers of excellence should in theory take the burden off Holland’s team to treat this entire subgroup of patients. Holland’s system and protocol work, so it is only a matter of expanding it throughout the country to serve this hard-to-treat population, Farid said.

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“Ed is a giant in our field, and he’s helped so many people in a way that no other corneal surgeon has in terms of this particular niche of severe ocular surface disease where there really is no other hope for them,” she said.

Future expansion of centers

When the foundation begins accepting donations, Holland said other potential centers of excellence will be identified, and then plans to fund positions and educate surgeons on his protocols will begin.

Patients from across the country are referred to Holland for surgery. Having additional locations where this underserved group can be treated with the same protocols and can expect the same surgical outcomes is the ultimate goal of the foundation, Holland said.

“We have to follow all of our patients. While there are a lot of great corneal specialists across the country, if they’re not doing ocular surface transplantation, they don’t know what to look for. We simply cannot complete this surgery and send the patients home. We’d love to have more corneal surgeons become involved and use our protocols,” Holland said. – by Robert Linnehan

To learn more about the Holland Foundation for Sight Restoration, visit www.HollandFoundationforSight.org or www.linkedin.com/company/holland foundationforsight/ or email Robert Dempsey at robertdempsey@comcast.net.

Disclosures: The sources report no relevant financial disclosures.

Click here to read the point/counter, "What is the best method to manage limbal stem cell deficiency?"