Researchers from Japan treated bullous keratopathy with an injection of cultured human corneal endothelial cells (CECs) supplemented with a rho-associated protein kinase (ROCK) inhibitor.
Study design
This non-randomized prospective study enrolled 11 patients with corneal edema secondary to Fuchs endothelial dystrophy or pseudophakic bullous keratopathy. The patients had no detectable endothelial cells on specular microscopy, a central corneal thickness greater than 630 μm and frank epithelial edema.
The CECs were cultured from a donor cornea and injected into the anterior chamber with a silicone cannula. Ten patients received approximately 1x106 cells, while the remaining patient received 5x106 cells. The injection medium contained the ROCK-selective inhibitor, Y-27632.
After the procedure, patients were placed in a prone position for 3 hours and maintained on topical corticosteroids as an anti-rejection prophylaxis.
Outcomes
At 24 weeks post-injection, all patients had an endothelial cell count (ECC) above 500 cells/mm2, meeting the primary endpoint of the study. The mean ECC at 24 weeks was 1,924 cells/mm2 (range 947–2,833 cells/mm2). Pachymetry decreased to less than 630 μm in 10 of 11 eyes, with a mean value of 549 μm.
Two years later, all 11 eyes showed clear corneas. The mean ECC was 1,534 cells/mm2. Ten eyes had a pachymetry value lower than 600 μm.
No patients experienced anterior uveitis or rejection. One patient experienced elevated IOP (27 mm Hg) and underwent trabeculotomy.
Limitations
Though the outcomes are promising, this small study raises questions: Do the extra cells enter systemic circulation, potentially causing future harm? Are the injected cells responsible for the development of glaucoma? The glaucoma time-course is consistent with steroid-induced disease, and the authors note abnormal trabecular meshwork findings. Further evaluation and longer follow-up are needed to address these concerns.
Clinical significance
This is an exciting study with a promising new technique for treating endothelial cell loss and resulting bullous keratopathy. Though the idea is in its infancy, the cornea community will be following further developments with enthusiasm.