Cell therapy may be on the horizon for corneal endothelial disease
Click Here to Manage Email Alerts
It is estimated that in the U.S. alone, 4% of the population older than 40 years old has Fuchs’ endothelial corneal dystrophy, one of the leading types of corneal endothelial disease.
Despite the prevalence of Fuchs’ endothelial corneal dystrophy in millions of people, each year fewer than 70,000 patients worldwide undergo endothelial keratoplasty procedures. While endothelial keratoplasty is effective in treating corneal endothelial disease, these are complex procedures that require access to corneal tissue, skilled corneal surgeons and an onerous recovery for patients. Globally, there are many more patients in need than tissue and surgeons to serve them; for every 70 diseased eyes, there is only one donor cornea available.
I have recently had the opportunity to participate in an exploratory clinical trial of a new technique in which injections of human cultured corneal endothelial cells (CECs) are used to treat patients with corneal endothelial disease. What is most exciting about this approach is that mature cultured CECs from a single donor cornea can be used to treat many patients.
This CEC therapy has been in development by Shigeru Kinoshita, MD, PhD, at the Kyoto Prefectural University of Medicine in Japan over the past 25 years. After extensive laboratory work, he treated the first patient in 2013 and published 2-year and 5-year results for the first 11 eyes treated. Preoperatively, each of these 11 eyes was severely compromised. Cell therapy resulted in a rapid decrease in corneal thickness within 4 weeks, with gradually refined deturgescence of the cornea over time. At 5 years, mean central corneal thickness (CCT) was less than 630 µm, and best corrected visual acuity was 20/40 or better in 10 of the 11 eyes (91%).
Exploratory trial
In 2020, Aurion Biotech acquired the intellectual property and initiated further development of this cell therapy, beginning with the IOTA trial in El Salvador. To date, I have been part of the surgical team that has treated 50 eyes of 45 patients with CECs produced from just two donor corneas.
The genius of Kinoshita’s invention lies in both the production of CECs in vitro and in the cell therapy procedure itself. The CECs are separated from the Descemet’s membrane of a healthy donor cornea, placed into culture and expanded over multiple passages spanning a number of weeks. At present, Aurion has successfully produced enough cells to treat 100 eyes from a single donor. Importantly, these are fully differentiated CECs, not stem cells, so they do not need to “learn” to acquire the properties of CECs. The viability of the CECs is promising thus far, with cells that were cultured in Japan able to be imported to El Salvador for the procedures.
The cell therapy procedure itself occurs in three steps. The surgeon makes an incision into the anterior chamber to mechanically remove the patient’s diseased endothelium from the cornea undergoing treatment. Cultured cells in a proprietary suspension that includes a Rho kinase inhibitor are preloaded into a syringe for injection into the anterior chamber. After the injection, the patient is placed facedown, in a prone position, for 3 hours to help the cells settle into place and form a monolayer. Within days, vision begins to improve, and most patients show significant improvements in CCT and BCVA at 3 months postoperatively.
The patients treated in the IOTA trial had some of the worst corneal endothelial disease I have ever seen. When I returned for the 6- and 12-month examinations, their improvements were startling (Figure 1). Patients who had been previously functionally blind and required daily living assistance at the preoperative appointment returned for follow-up exams able to see and move more independently through their environments. They told us they were able to care for themselves, see their family members for the first time in years and even work again.
Source: Elizabeth Yeu, MD
Advantages of cell therapy
Corneal endothelial cell therapy has the potential to provide significant advantages compared with endothelial keratoplasty. The technique is relatively straightforward to learn and can be performed by comprehensive anterior segment surgeons. Unlike endothelial keratoplasty, the area treated is not limited by graft size. A cell therapy injection can restore the entire corneal endothelium, from limbus to limbus, for patients who have diffuse pseudophakic corneal edema from multiple prior surgeries, for example. Equally important, Kinoshita’s early work indicates that this treatment is durable; his first patients continue to exhibit healthy corneas more than 7 years after their cell therapy procedures.
After personally witnessing the early results in the IOTA trial, I believe we are entering an era in which ophthalmologists will be able to help patients with corneal endothelial disease in a way that was previously unimaginable. This research has already changed my understanding of the anatomy and nuances of the corneal endothelium; I believe it will eventually change much of what we know about corneal disease and open the door for further developments in regenerative medicine.
- References:
- Fuchs endothelial dystrophy. https://medlineplus.gov/genetics/condition/fuchs-endothelial-dystrophy/#frequency. Updated Aug. 18, 2020. Accessed March 10, 2022.
- Gain P, et al. JAMA Ophthalmol. 2016;doi:10.1001/jamaophthalmol.2015.4776.
- Kinoshita S, et al. N Engl J Med. 2018;doi:10.1056/NEJMoa1712770.
- Numa K, et al. Ophthalmology. 2021;doi:10.1016/j.ophtha.2020.09.002.
- For more information:
- Elizabeth Yeu, MD, can be reached at Virginia Eye Consultants, 241 Corporate Blvd., Norfolk, VA 23502; email: eyeu@cvphealth.com.
Collapse
Read more about
Click Here to Manage Email Alerts