Effect of Graft Attachment Status and Intraocular Pressure on Descemet Stripping Automated Endothelial Keratoplasty Outcomes in the Cornea Preservation Time Study.

PURPOSE: To examine the association of donor, recipient, and operative factors on graft dislocation after Descemet stripping automated endothelial keratoplasty (DSAEK) in the Cornea Preservation Time Study (CPTS) as well as the effects of graft dislocation and elevated IOP on graft success and endothelial cell density (ECD) 3 years postoperatively. DESIGN: Cohort study within a multi-center, double-masked, randomized clinical trial. METHODS: 1090 individuals (1330 study eyes), median age 70 years, undergoing DSAEK for Fuchs endothelial corneal dystrophy (94% of eyes) or pseudophakic or aphakic corneal edema (6% of eyes). Recipient eyes receiving donor corneal tissue randomized by preservation time (PT) of 0-7 days (N = 675) or 8-14 days (N = 655) were monitored for early or late graft failure through 3 years. Donor, recipient, operative, and postoperative parameters were recorded including graft dislocation (GD), partial detachment, and pre- and post-operative IOP. Pre- and postoperative central donor ECD were determined by a central image analysis reading center. Proportional hazards, mixed effects, and logistic regression models estimated risk ratios and (99% confidence intervals). RESULTS: Three independent predictive factors for GD were identified: a history of donor diabetes (odds ratio [OR]: 2.29 [1.30, 4.02]), increased pre-lamellar dissection central corneal thickness (OR: 1.13 [1.01, 1.27] per 25µ increase), and operative complications (OR: 2.97 [1.24, 7.11]). Among 104 (8%) eyes with GD, 30 (28.9%) developed primary donor or early failure and 5 (4.8%) developed late failure vs. 15 (1.2%; P < .001) and 29 (2.4%; P = .04), respectively, of 1226 eyes without GD. 24 (2%) of 1330 study eyes had early acutely elevated postoperative IOP that was associated with a higher risk of graft failure through 3 years (hazard ratio: 3.42 [1.01, 11.53]), but not with a lower mean 3-year ECD (mean difference 61 (-479, 601) cells/mm2, P = .77). History of elevated postoperative IOP beyond 1 month was not significantly associated with 3-year graft success or ECD. CONCLUSIONS: Donor diabetes, increased donor corneal thickness, and intraoperative complications were associated with an increased risk of GD. Early acutely elevated postoperative IOP and GD significantly increased the risk for graft failure following DSAEK.

Spontaneous and inheritable R555Q mutation in the TGFBI/BIGH3 gene in two unrelated families exhibiting Bowman's layer corneal dystrophy.

PURPOSE: Bowman's layer corneal dystrophies (CDBs) include 2 distinct types: CDB1, or Reis-Bücklers (RBCD), and CDB2, or Thiel-Behnke (TBCD). We studied the genetic basis of 2 cases of apparent spontaneous CDB mutations and attempted to determine if these are sporadic and inheritable mutations. DESIGN: Retrospective molecular genetic study and case report. PARTICIPANTS: Twelve patients were recruited from 2 unrelated families for this study, including 2 affected individuals from one family (family A) and 1 affected individual from another (family B). METHODS: Slit-lamp examination was performed for each patient to determine the disease phenotype. Histological analysis of affected cornea specimens was used for identification of pathogenic corneal opacities in 2 affected patients from family A. MAIN OUTCOME MEASURES: Genomic DNA was isolated from the blood samples and used for mutation screening of the TGFBI/BIGH3 gene. Sixteen polymorphic DNA markers from 9 different chromosomes were used to establish the maternity and paternity of the 2 probands. RESULTS: The 2 families were confirmed to be unrelated. The age onset of ocular symptoms was <2 years for all 3 affected patients. Clinical diagnoses of CDB1 (RBCD) and CDB2 (TBCD) were made for probands A and B, respectively. The affected corneas showed epithelial haze with diffuse, irregular, patchy opacities in a honeycomb and geographic pattern. Subepithelial plaques, increased trichome staining of anterior stroma, and irregular Bowman's layer were observed. An R555Q mutation was found in TGFBI/BIGH3 in the 2 probands but not in their parents. The son of proband A was also affected and apparently inherited his disease allele from his father. CONCLUSION: The R555Q mutation occurred spontaneously and independently in the 2 unrelated CDB families and was confirmed to be transmitted to the next generation in 1 of the 2 families. These findings strongly support the notion that a genetic diagnosis should be determined for CDB and other dystrophies associated with mutations in TGFBI/BIGH3. The discovery of a spontaneous mutation should alert clinicians to be aware of the existence of genetic alterations for their patients without apparent family history of the disease.