Treatment of severe ocular-surface disorders with corneal epithelial stem-cell transplantation.
BACKGROUND
Conditions that destroy the limbal area of the peripheral cornea, such as the Stevens-Johnson syndrome, ocular pemphigoid, and chemical and thermal injuries, can deplete stem cells of the corneal epithelium. The result is scarring and opacification of the normally clear cornea. Standard corneal transplantation cannot treat this form of functional blindness.


METHODS
We performed and evaluated 70 transplantations of corneal epithelial stem cells from cadaveric eyes into 43 eyes of 39 patients with severe ocular-surface disorders and limbal dysfunction. Medical treatment had failed in all patients. The patients had a mean preoperative visual acuity of 0.004 (only being able to count the number of fingers presented by the examiner) in the affected eyes, which satisfies the criteria for legal blindness in most countries. In 28 eyes, we also performed standard corneal transplantation. Stem-cell transplantations were performed as many as four times on 1 eye if the initial results were not satisfactory; 19 eyes had multiple transplantations. Patients were followed for at least one year after transplantation.


RESULTS
A mean of 1163 days after stem-cell transplantation, 22 of the 43 eyes (51 percent) had corneal epithelialization; of the 22 eyes, 7 eyes had corneal stromal edema and 15 eyes had clear corneas. Mean visual acuity improved from 0.004 to 0.02 (vision sufficient to distinguish the largest symbol on the visual-acuity chart from a distance of 1 m) (P<0.001). The 15 eyes in which the cornea remained clear had a final mean visual acuity of 0.11 (the ability to distinguish the largest symbol from a distance of 5 m). Complications of the first transplantation included persistent defects in the corneal epithelium in 26 eyes, ocular hypertension in 16 eyes, and rejection of the corneal graft in 13 of 28 eyes. The epithelial defects eventually healed in all but two of the eyes.


CONCLUSIONS
Transplantation of corneal epithelial stem cells can restore useful vision in some patients with severe ocular-surface disorders.
Tsubota
K
K
Department of Ophthalmology, Tokyo Dental College, Chiba, Japan. kazuo@eyebank.or.jp
Satake
Y
Y
Kaido
M
M
Shinozaki
N
N
Shimmura
S
S
Bissen-Miyajima
H
H
Shimazaki
J
J
D000328:Adult; D017690:Cell Transplantation / Q000379:methods; D003316:Corneal Diseases / Q000601:surgery*; D016039:Corneal Transplantation; D019573:Epithelium, Corneal / Q000166:cytology* / Q000637:transplantation; D005131:Eye Injuries / Q000601:surgery; D005260:Female; D006084:Graft Rejection; D006801:Humans; D007165:Immunosuppression Therapy; D008297:Male; D008875:Middle Aged; D011182:Postoperative Care; D011183:Postoperative Complications; D033581:Stem Cell Transplantation; D017211:Treatment Failure; D014792:Visual Acuity