The Cornea Donor Study was designed to determine the effect of donor age on penetrating keratoplasty (PK) outcomes. While donor age had no effect on five-year graft survival, a slight association between increasing donor age and greater post-PK corneal endothelial cell loss was detected in an ancillary study, the Specular Microscopy Ancillary Study. It also confirmed substantial cell loss in successful grafts at five years irrespective of donor age. This evaluation of the two studies looked at whether other donor, recipient and operative factors affect endothelial cell loss during the first five years after PK. They found that larger donor graft size, younger donor age, and female donor were associated with higher ECD.
Subjects included 567 study participants who underwent PK for a moderate-risk condition, principally Fuchs dystrophy or pseudophakic or aphakic corneal edema. Larger grafts (P < .001), younger donor age (P < .001), and female donor (P = .004) were significantly associated with higher endothelial cell density (ECD) during follow-up. Method of tissue retrieval, donor cause of death, history of diabetes, and time from death to preservation or to surgery were not significantly associated with changes in ECD.
The age association was most evident with corneas from donors younger than 40 years. Among grafts that survived five years postoperatively, those from donors younger than 40 experienced 62 percent cell loss, compared with a 75 percent loss among grafts from donors between ages 70 and 76.
Median endothelial cell loss at five years was 68 percent for grafts larger than 8 to 9 mm in diameter, 75 percent for grafts 7 mm to smaller than 8 mm in diameter, and 74 percent for grafts 8 mm in diameter. Grafts from female donors showed a 67 percent cell loss compared with a 72 percent cell loss in male donor grafts.
A longitudinal multivariate analysis found female donor was significantly associated with higher ECD during the course of follow-up (P=.004), but this association was not significant at five years in grafts that had not failed. Receptors for both male and female hormones have been shown to be present in the epithelium, keratocytes, and, most relevantly, the endothelium of the human cornea, which raises the possibility that these hormones may play a biological role in corneal function. While some studies have reported an effect of these hormones on lacrimal and meibomian gland function and corneal thickness, none have reported effects on corneal endothelial viability. One study suggested a differential effect of the sex hormones on cellular apoptosis. Further in vitro, ex vivo, and clinical studies are warranted to determine whether hormones, particularly estrogen, play a role in endothelial survival following keratoplasty.
The authors note that while endothelial cell loss may be a proxy measure for later graft failure, this relationship is not straightforward. Cornea Donor Study data showed that an ECD less than 1700 cells/mm2 at six months was associated with a graft failure rate of 13 percent at five years, while an ECD of 2500 cells/mm2 or greater at six months was associated with a 2 percent failure rate at five years. On the other hand, 14 percent of clear grafts had an ECD less than 500 cells/mm2 at five years. Thus, further observation is warranted to determine how the observed decrease in ECD at five years affects the graft success rate over a longer period.