W. John Armitage

Influence of donor and histocompatibility factors on corneal graft outcome.

The Corneal Transplant Follow-up Study has followed 2311 penetrating keratoplasties for up to 450 days after transplant. A total of 207 failures were observed, including 65 classical rejections and 35 endothelial decompensations. At 12 months, graft survival was 89%, and survival free from rejection was 87%. For surviving grafts, risk of failure reduced from 4.8% in the first 75 days and stabilized after 5 months at 1.2% in each 75-day interval. Risk of rejection initially followed a similar pattern, but then increased after 12 months. Multifactorial analyses accounted for differences in recipient characteristics and interrelationships of donor factors. Donor age, sex, cause of death, and method of corneal storage were not found to influence significantly either time to graft failure or time to first rejection. Grafts in prospectively tissue-typed donor-recipient pairs were generally considered before surgery to be at increased risk of either graft failure or rejection. With due allowance, increasing risk of rejection was associated with increasing numbers of mismatches at HLA-A and HLA-B broad antigens. The opposite was true at HLA-DR broad antigens, where increased risk of rejection was observed with no mismatches.

Impact of obstetric factors on cord blood donation for transplantation

Recent reports have shown that low nucleated cell dose significantly decreases survival after cord blood transplantation. Prior to starting clinical cord blood banking we investigated the impact of obstetric factors on cell dose and volume of cord blood donations. Cord blood was obtained from 114 normal full‐term deliveries. Mean volume collected was 93.5 ml, mean total nucleated cell count (TNC) was 13.1 × 108. Statistical analysis was by backwards stepwise regression. Significant factors affecting nucleated cell yield were volume of blood collected (P < 0.001), length of gestation (P < 0.0001), time from delivery of the infant to cord clamping (P = 0.018) and total length of labour (P = 0.002). In clinical cord blood banking we have successfully used these findings for pre‐collection assessment of placentae. Out of 476 cord blood donations subsequently collected for banking, only 29 (6.1%) have been discarded due to low volume. The mean TNC of the 409 banked units following volume reduction was 10.1 × 108. Despite careful optimization of collection, processing and storage techniques, cell dose still limits cord blood transplantation to smaller recipients.

The Clinical Time-Course of Experimental Autoimmune Uveoretinitis Using Topical Endoscopic Fundal Imaging with Histologic and Cellular Infiltrate Correlation

PURPOSE EAU is an established preclinical model for assessment of immunotherapeutic efficacy toward translation of therapy for posterior uveitis. Reliable screening of clinical features that correlate with underlying retinal changes and damage has not been possible to date. This study was undertaken to describe, validate, and correlate topical endoscopic fundus imaging (TEFI) with histologic features of murine experimental autoimmune uveoretinitis (EAU), with the intent of generating a rapid noninvasive panretinal assessment of ocular inflammation. METHODS EAU was induced in B10.RIII mice by immunization with the peptide RBP-3(161-180). The clinical disease course (days 0-63) was monitored and documented using TEFI. Disease severity and pathology were confirmed at various time points by histologic assessment. The composition of the cell infiltrate was also examined and enumerated by flow cytometry. RESULTS TEFI demonstrated the hallmark features of EAU, paralleling many of the clinical features of human uveitis, and closely aligned with underlying histologic changes, the severity of which correlated significantly with the number of infiltrating retinal leukocytes. Leukocytic infiltration occurred before manifestation of clinical disease and clinically fulminant disease, as well as cell infiltrate, resolved faster than histologic scores. During the resolution phase, neither the clinical appearance nor number of infiltrating retinal leukocytes returned to predisease levels. CONCLUSIONS In EAU, there is a strong correlation between histologic severity and the number of infiltrating leukocytes into the retina. TEFI enhances the monitoring of clinical disease in a rapid and noninvasive fashion. Full assessment of preclinical immunotherapeutic efficacy requires the use of all three parameters: TEFI, histologic assessment, and flow cytometric analysis of retinal infiltrate.

Clinical and Surgical Factors Influencing Corneal Graft Survival, Visual Acuity, and Astigmatism

Purpose: To quantify clinical and operative factors that influence corneal graft outcome. Methods: A multifactorial analysis was done on 2242 corneal grafts registered by the United Kingdom Transplant Service from July 1987, to June 1991. Results: There was an increased risk of graft failure in patients with preoperative diffuse and other noncentral stromal edema, less-common eye diseases, small trephine size, difference in donor and recipient sizes greater than 0.25 mm, and use of mixed continuous and interrupted sutures. Visual acuity 3 months after surgery was poorer in patients who had glaucoma and low visual acuity preoperatively, small trephine size, and combined vitreous surgery. Use of interrupted sutures resulted in higher astigmatism at 3 months. Conclusions: After allowing for the effects of recipient factors, surgical factors significantly affected corneal graft outcome. No factors that showed significant benefits for graft survival also adversely affected visual performance. Details of medical history, clinical condition, and surgical method failed to predict more than a small proportion of observed variability in visual performance of functioning grafts.

The suitability of corneas stored by organ culture for penetrating keratoplasty and influence of donor and recipient factors on 5-year graft survival.

PURPOSE To determine the impact of donor factors on the suitability of corneas stored by organ culture for penetrating keratoplasty (PK) and the influence of donor and recipient factors on 5-year survival of first PK. METHODS Logistic regression analyses were carried out to determine the influence of donor factors on, respectively, the risk of microbial contamination during organ culture, the suitability of corneas for PK (endothelial cell density ≥ 2200 cells/mm(2)), and the quality of corneas (endothelial cell density ≥ 2500 cells/mm(2)). Only one cornea, randomly selected, from each donor was included in these analyses. A Cox regression analysis was used to determine the influence of donor and recipient factors on 5-year PK survival. RESULTS Risk of contamination (n = 8317): Causes of donor death including infection, respiratory disease, and cancer all increased the risk of contamination during organ culture (P < 0.0001). Suitability for PK and endothelial quality (n = 7107): Donor age (P < 0.0001) and storage time in organ culture (P < 0.0001) were the principal factors affecting suitability and quality. Death to enucleation and enucleation to processing times had little influence. Corneas from organ donors were more likely to be suitable for PK (P = 0.0003). Five-year graft survival (n = 3014): Graft survival was dominated by the indication for PK (P < 0.0001). Allograft rejection was also a major risk factor for failure (P < 0.0001). The only donor factor affecting survival was sex (P = 0.008). CONCLUSIONS Donor age and storage time but not postmortem times influenced the suitability of corneas for PK. The indication for PK and other recipient factors were the main predictors of graft failure.

Transplantation of ocular tissue from a donor with sporadic Creutzfeldt–Jakob disease

Background:  One definite, one probable and several possible transmissions of sporadic Creutzfeldt–Jakob disease (sCJD) have followed corneal transplantation. We report an incident in the UK in 1997 in which both corneas and scleras from a donor, subsequently confirmed to have had sCJD, were transplanted. The final clinical outcome for two surviving recipients is still not yet known.

Cryopreservation of cornea: a low cooling rate improves functional survival of endothelium after freezing and thawing.

AIM To investigate the influence of low cooling rates on endothelial function and morphology of corneas frozen with propane-1,2-diol (PROH). METHODS Rabbit corneas, mounted on support rings, were exposed to 1.4mol/l (10% v/v) PROH, seeded to initiate freezing, and cooled at 0.2 or 1 degrees C/min to -80 degrees C. Corneas were frozen immersed in liquid or suspended in air. After being held overnight in liquid nitrogen, corneas were warmed at 1 or 20 degrees C/min. After stepwise removal of the cryoprotectant, the ability of the endothelium actively to control corneal hydration was monitored during normothermic perfusion. Morphology was assessed after staining with trypan blue and alizarin red S, and by specular microscopy during perfusion. RESULTS Functional survival was achieved only after slow cooling (0.2 degrees C/min) with the cornea immersed in the cryoprotectant medium, and rapid warming (20 degrees C/min). These conditions also gave the best morphology after freezing and thawing. CONCLUSION Cooling rates lower than those typically applied to cornea improved functional survival of the endothelium. This result is in accord with previous observations showing the benefit of low cooling rates for cell monolayers [CryoLetters 17 (1996) 213-218].

Clinical outcome of repeat penetrating keratoplasty.

Purpose: To compare the clinical outcome of regrafts with first grafts. Methods: Two-year outcome data were obtained from the Swedish Cornea Transplant Register for patients undergoing penetrating keratoplasty between 2001 and 2008. Only data from the 3 centers with follow-up return rates >75% were included. The survival and visual outcome of regrafts with the original diagnoses of keratoconus, Fuchs endothelial dystrophy (FED), or bullous keratopathy (BK) were compared with first grafts for the same diagnoses by univariate and logistic regression methods. Results: For keratoconus, the failure rate increased 3-fold in regrafts compared with first grafts (ie, 17% vs. 6%; P = 0.002) and doubled in FED regrafts (33% vs. 15%; P = 0.001). In BK, the failure rate was already high in first grafts, and the increase in failure of regrafts was minimal (P = 0.9). Visual acuity was also worse in regrafts compared with first grafts, mainly in the keratoconus and FED patients. In the keratoconus group, visual acuity with preferred correction was ≥0.5 in 69% of first grafts compared with only 55% in regrafts (P = 001). In FED, 52% of first grafts but only 19% of regrafts achieved visual acuity ≥0.5 (P = 0.001). The visual outcome of regrafts in BK was poor but little different from first grafts where fewer than 20% achieved visual acuity ≥0.5. Conclusions: This analysis confirmed the poorer survival of regrafts where the original indication was keratoconus or FED. In addition, visual outcome was also worse than in the first grafts. However, the outcomes of regrafts in BK were similar to first grafts.

Outcomes of Same-Sizing versus Oversizing Donor Trephines in Keratoconic Patients Undergoing First Penetrating Keratoplasty

PURPOSE To investigate whether use of same-size donor and recipient trephines reduced myopia after penetrating keratoplasty for keratoconus. DESIGN Retrospective cohort study. PARTICIPANTS Eight hundred seventy-eight first grafts for keratoconus were reported to UK Transplant between April 1999 and December 2003. There were 234 and 644 grafts in the same-size and oversize donor trephine groups, respectively. At 1 year, mean spherical equivalent (SE) data were available for 116 eyes (50%) and 295 eyes (46%) in the same-size and oversize groups. At 2 years, mean SE data were available for 64 eyes (27%) and 148 eyes (23%) in the same-size and oversize groups. METHODS Logistic regression and univariate analysis of follow-up data submitted to UK Transplant. MAIN OUTCOME MEASURES At 1 and 2 years postoperatively, mean SE, magnitude of the cylindrical component of the refraction, postoperative uncorrected visual acuity (VA), postoperative best-corrected VA, and postoperative complications were recorded. RESULTS The mean SEs for the same-size and oversize donor trephine groups, respectively, were -1.45 diopters (D) and -1.41 D at 1 year (P = 0.6) and -1.74 D and -2.19 D at 2 years postoperatively (P = 0.3). Although there were no differences in graft survival between the groups at 1 and 2 years, there was a higher incidence of postoperative wound leaks in the same-size group (P = 0.03). CONCLUSION Use of same-size donor and recipient trephines did not reduce myopia and was associated with an increased risk of postoperative complications.

Corneal oedema after cataract surgery: predisposing factors and corneal graft outcome

Purpose:  Pseudophakic bullous keratopathy (PBK) is one of the main indications for corneal transplantation. Graft survival and visual outcome in this group are often poorer than for other indications. The aim of this study was to find risk factors for developing corneal oedema after cataract surgery and factors that influence the subsequent survival of the graft and the visual outcome.