PURPOSE. Programmed cell death (apoptosis) is the controlled death of
cells that occurs with minimal collateral damage to surrounding cells
or tissue during development, homeostasis, and wound healing. The auth
ors hypothesize that keratocyte apoptosis is an initiating factor in t
he wound-healing response after refractive surgical procedures. To eva
luate the effects of different corneal manipulations, keratocyte apopt
osis was examined qualitatively and quantitatively after traditional e
pithelial scrape-photorefractive keratectomy. (PRK), transepithelial P
RK, removal of 3 cap of superficial cornea using a microkeratome, prod
uction of a flap of superficial cornea with a microkeratome, and laser
-assisted in situ keratomileusis (LASIK) compared with unwounded contr
ols in rabbit corneas. METHODS. Refractive surgical procedures or thei
r components were performed in rabbit eyes. Keratocyte apoptosis was m
onitored using the terminal deoxyribonucleotidyl transferase-mediated
dUTP-digoxigenin nick-end labeling assay to detect DNA fragmentation.
Cellular morphologic changes were evaluated by electron microscope exa
mination RESULTS. Keratocyte apoptosis was noted with each refractive
procedure or corneal manipulation and was variable from eye to eye wit
h each procedure. Transepithelial PRK was associated with the lowest l
evels of central corneal apoptosis, even if the stromal surface was sc
raped after the procedure. Keratocyte apoptosis is confined to the sup
erficial stroma extending to a depth of approximately 50 mu m to 75 mu
m after epithelial scrape-PRK and transepithelial PRK. Apoptosis was
noted in the beeper central corneal keratocytes located anteriorly and
posteriorly to the lamellar cut in LASIK. CONCLUSIONS. There are qual
itative and quantitative differences in keratocyte apoptosis between L
ASIK, epithelial scrape-PRK, and transepithelial PRK. Epithelial injur
y is an important factor modulating keratocyte apoptosis. The level an
d distribution of keratocyte apoptosis, along with subsequent repopula
tion by activated stromal keratocytes, are likely to be important dete
rminants of corneal wound healing associated with variability and regr
ession after PRK and LASIK. Transepithelial PRE; induces low levels of
keratocyte apoptosis, and, therefore, this approach may be useful for
treating higher levels of myopia and for retreatment after regression
.