Donor corneal tissue for transplantation is something that most US corneal specialists typically do not worry about, because our eye banking system here is the envy of the world. We have many well-regarded, well-established and well-managed organizations doing an incredible job of serving our communities. We can treat our patients with confidence, knowing that we can obtain high-quality donor corneal tissue, whenever and wherever we need it.

But what is the global situation, when it comes to donor cornea supply? How can corneal specialists make the best use of these resources? How can advances in technology change our diagnoses and practice patterns?

What We Know Today: Relevant Statistics
We as doctors (and scientists) tend to believe in data. A landmark study, published in 2016 in JAMA: Ophthalmology, surveyed the global landscape for corneal transplantation. Data collected from a 12-month period in 2012-13 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” – it’s where we source the oft-cited factoid that only one donor cornea is available worldwide for every 70 diseased eyes.

Not surprisingly, the US leads the world in corneal transplant rates at 199 patients per 1 million population, followed by Lebanon at 122 per million and Canada at 117 per million, while the median of the 116 transplanting countries was a mere 19 per million. In fact, our US cornea donor network is so strong, we are the world’s largest exporter of donor corneas (85% of total exports). It is also, the journal authors hypothesize, why US innovation regarding assistive devices and transplant tissue in the US is greater than in any other country: we have the resources, entrepreneurial mindset and the capacity to innovate.

Nevertheless, wait times for transplants and demand for donor corneas – even in developed countries – are surprisingly long. A 2019 survey, presented at the Canadian National Consensus Conference in February 2020, revealed that 30% of Canadian transplant surgeons estimate over 1-year wait times for non-urgent corneal transplants.

Which leads us to the questions of disease prevalence, diagnoses and physician practice patterns. The JAMA Ophthalmology survey indicated that approximately 12.7 million people worldwide have been diagnosed with corneal disease (of which 60% is 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 the age of 40 is prevalent for FECD, or approximately 6.5 million people. Yet The EBAA, in its 2021 report, cites fewer than 50,000 corneal transplants were performed in the US. This vast discrepancy – 6.5 million people in the US who are prevalent with disease vs. fewer than 50,000 people treated annually – is clearly not just about available supply of corneas.

How We Practice Medicine – and How that Changes Over Time

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

First, although it has generally excellent outcomes, endothelial keratoplasty is still invasive: our inclination is to perform surgery only when absolutely necessary. Fortunately, since endothelial disease is relatively slow to progress, patients have greater leeway to choose an optimal time to undergo this procedure. Further, innovations in endothelial keratoplasty have enabled use of thinner tissue used for less invasive procedures, first via DSAEK and now with DMEK. Accordingly, DMEK has grown in volume, due to shorter patient recovery times and excellent outcomes.

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

What’s Needed: More Research (and More Innovation)

I believe we are poised to experience another wave of innovations, but we need more research to fully grasp how best to leverage these discoveries, especially when it comes to diagnosis and treatment of corneal dystrophies. Recently, at the April 2022 ASCRS conference, the team from Aurion Biotech revealed key findings from a survey it sponsored, conducted by BMC Research.

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

The findings from this survey may help us to better understand frequency of CED diagnoses, but more work is needed to answer the ”then what happens?” questions. How long after initial diagnosis do patients wait for further treatment? When does the optometrist make a referral to an ophthalmologist? When does a patient, in consultation with their ophthalmologist, decide to opt for a procedure such as endothelial keratoplasty? If disease diagnosis is relatively common, why aren’t more ophthalmologists performing endothelial keratoplasties? Equally important, how will new innovations affect the current landscape of diagnosis and treatment decisions?

Many of us have read about the ground-breaking corneal endothelial cell therapy invented by Professor Shigeru Kinoshita and his colleagues at Kyoto Prefecture University of Medicine in Japan, in his articles published in New England Journal of Medicine and Ophthalmology Journal. Kinoshita and colleagues were able to get corneal endothelial cells to replicate in the lab – something these cells do not do in the body. Results from this cell therapy in patients were excellent – his studies show significant, lasting improvements in corneal edema and visual acuity.

Kinoshita’s innovations have profound implications for supply and demand: from a single donor, cells can be replicated to treat up to 100 eyes. In addition, the cell therapy procedure can be performed relatively quickly (~15-20 minutes), in an outpatient setting. Last year, this cell therapy was acquired by Aurion Biotech, and the company is investing in additional 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 the disease progression? Would we use this therapy in eyes undergoing a complex procedure such as a glaucoma procedure that have a risk of corneal failure? If this cell therapy can significantly expand the supply available for treatment, will that change the volumes of patients getting treated? What will clinicians and their patients require, in terms of proof points, to get comfortable in selecting this procedure?

Answers to all of these questions will help us to more effectively leverage the precious resources we have at our disposal. Because (of course), there is never enough corneal tissue to meet the needs of patients throughout the world. It’s our obligation as corneal specialists to do the best we can with what’s available to us and innovate to serve more patients worldwide.

Nicole Fram, MD

E: drfram@avceye.com

Dr. Nicole Fram is the managing partner of Advanced Vision Care and a clinical instructor of ophthalmology at the Stein Eye Institute, 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 the co-chief resident, followed by a fellowship in cornea and external disease at Francis I. Proctor Foundation, University of California, San Francisco (UCSF).

References

1 Note: unless otherwise footnoted, all statistics cited in this article come from the JAMA Ophthalmology Survey 2016 – https://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 12 April 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