Not enough corneas: fact or fiction?

Donor corneal tissue for transplantation is something most American cornea specialists don’t usually worry about, because our eye bank system here is the envy of the world. We have many reputable, well-established and well-managed organizations that do incredible work serving our communities. We can treat our patients with confidence knowing that we can obtain high quality donor corneal tissue when and where we need it.

But what is the overall situation, with regard to the supply of donor cornea? How can cornea specialists make the most of these resources? How can technological advances change our diagnoses and practice habits?

What we know today: relevant statistics
As doctors (and scientists), we tend to believe in data. A landmark study, published in 2016 in JAMA: Ophthalmology, studied the global corneal transplant landscape. Data collected over a 12-month period in 2012-2013 was obtained from 742 eye banks and analyzed approximately 185,000 corneal transplants in 116 countries. Although this is the most recent and definitive survey of its kind, it is not “new news” – this is where we find the oft-quoted factoid that a single cornea donor eye is available worldwide for 70 diseased eyes.

Not surprisingly, the United States leads the world in corneal transplant rates with 199 patients per million population, followed by Lebanon at 122 per million and Canada at 117 per million, while the median of 116 transplant countries was only 19 per million. In fact, our cornea donor network in the United States is so strong that we are the world’s largest exporter of donor corneas (85% of total exports). It is also, the review authors hypothesize, why American innovation in assistive devices and tissue grafting in the United States is greater than in any other country: we have the resources, the entrepreneurship and the ability to innovate.

Nevertheless, waiting times for transplants and the demand for donor corneas – even in developed countries – are surprisingly long. A 2019 survey, presented at the Canadian National Consensus Conference in February 2020, found that 30% of Canadian transplant surgeons estimate wait times for elective corneal transplants to be over a year.

Which brings us to questions of disease prevalence, diagnostics, and physician practice habits. The JAMA Ophthalmology A survey indicated that approximately 12.7 million people worldwide have been diagnosed with corneal disease (60% of which are Fuchs endothelial corneal dystrophy, or FECD) and are awaiting a transplant. Another oft-cited NIH/NLM study suggests that 4% of the US population over age 40 is prevalent for FECD, or about 6.5 million people. Yet the EBAA, in its 2021 report, cites fewer than 50,000 corneal transplants performed in the United States. This vast gap – 6.5 million people in the United States who are prevalent with the disease versus less than 50,000 people treated each year – is clearly not just about the available supply of corneas.

How we practice medicine – and how it changes over time

Why is it that even in the United States, where we know we have an adequate supply of corneal tissue, we treat only a small subset of patients with corneal disease? I believe there are several reasons for the current state of practice.

First of all, although it generally has excellent results, endothelial keratoplasty remains invasive: our tendency is to operate only when absolutely necessary. Fortunately, because endothelial disease progresses relatively slowly, patients have greater latitude in choosing an optimal time to undergo this procedure. Additionally, innovations in endothelial keratoplasty have enabled the use of thinner tissue used for less invasive procedures, first via DSAEK and now with DMEK. As a result, DMEK has grown in volume, due to shorter recovery times for patients and excellent results.

However, many corneal specialists consider DMEK to be a more laborious, complex and time-consuming procedure – perhaps another reason for the relatively small annual volume increases. Whatever the reasons for the current state of the practice, it seems that EDC is a category with plenty of room for growth – and more treatment innovations.

What is needed: more research (and more innovation)

I think we’re about to see another wave of innovation, but we need more research to really understand how best to take advantage of these discoveries, especially when it comes to diagnosing and treating corneal dystrophies. Recently, at the April 2022 ASCRS conference, the Aurion Biotech team revealed key findings from a survey they sponsored and conducted by BMC Research.

Of the 1,500 survey respondents (mix of optometrists, ophthalmologists and cataract specialists), more than 60% indicated that they frequently diagnose patients with corneal endothelial disease (CED) (at least 1 to 2 patients per month, and as frequently as 1-2 per week). Nearly half of those who frequently diagnose CEDs are optometrists.

The results of this survey can help us better understand frequency of CED diagnoses, but there is still work to be done to answer the question “so what is going on?” questions. How long after the initial diagnosis do patients wait for further treatment? When does the optometrist refer to an ophthalmologist? When does a patient, in consultation with his ophthalmologist, decide to opt for an intervention such as endothelial keratoplasty? If diagnosis of the disease is relatively common, why aren’t more ophthalmologists performing endothelial keratoplasty? Equally important, how will new innovations affect the current landscape of diagnostic and treatment decisions?

Many of us have heard of the revolutionary corneal endothelial cell therapy invented by Professor Shigeru Kinoshita and his colleagues at Kyoto Prefectural Medical University in Japan, in his articles published in New England Journal of Medicine and Journal of Ophthalmology. Kinoshita and his colleagues were able to reproduce corneal endothelial cells in the laboratory, which these cells do not do in the body. The results of this cell therapy in patients have been excellent – his studies show significant and lasting improvements in corneal edema and visual acuity.

Kinoshita’s innovations have profound supply and demand implications: from a single donor, cells can be replicated to treat up to 100 eyes. Additionally, the cell therapy procedure can be performed relatively quickly (~15-20 minutes), on an outpatient basis. Last year, this cell therapy was acquired by Aurion Biotech, and the company is investing in further clinical development.

If corneal endothelial cell therapy proves to be a viable option for certain corneal endothelial diseases, would ophthalmologists and their patients opt for this procedure, perhaps even earlier in disease progression? Would we use this therapy in eyes undergoing a complex procedure such as a glaucoma procedure that are at risk for corneal insufficiency? If this cell therapy can significantly increase the supply available for treatment, will this change the number of patients treated? What will clinicians and their patients need, in terms of evidence points, to feel comfortable choosing this procedure?

The answers to all of these questions will help us use the precious resources we have more efficiently. Because (of course) there is never enough corneal tissue to meet the needs of patients around the world. As corneal specialists, we have an obligation to do the best we can with what is available to us and to innovate to serve more patients around the world.

Nicole Fram, MD

Email: [email protected]

Dr. Nicole Fram is Managing Partner of Advanced Vision Care and Clinical Instructor in Ophthalmology at the Stein Eye Institute at the University of California, Los Angeles (UCLA). She is a member of the Medical Advisory Board of Aurion Biotech and CorneaGen. She completed her residency at the prestigious Wills Eye Hospital and served as Co-Chief Resident, followed by a fellowship in Cornea and External Diseases at the Francis I. Proctor Foundation, University of California, San Francisco (UCSF) .

References

1 Note: unless otherwise stated, all statistics quoted in this article come from the JAMA Ophthalmology Survey 2016https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2474372

2 https://bmcproc.biomedcentral.com/articles/10.1186/s12919-021-00215-6

3 https://medlineplus.gov/genetics/condition/fuchs-endothelial-dystrophy/#frequency

4 EBAA: 2021 Eye Banking Statistical Report, Figure 3, p. 3

5 EBAA: 2021 Eye Banking Statistical Report, Table 5, p. 8

6 Kunst, Greg, Aurion Biotech Eyecelerator presentation April 12, 2022

7 https://aurionbiotech.com/wp-content/uploads/2021/04/NEJMoa1712770.pdf

8 https://aurionbiotech.com/wp-content/uploads/2021/04/AAO-Journal-Article.pdf

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