Long-term Corneal Graft Survival Research Articles

Myeloid-derived suppressor cells promote allograft survival by suppressing regulatory T cell dysfunction in high-risk corneal transplantation

Highly inflamed and neovascularized corneal graft beds are known as high-risk (HR) environments for transplant survival. One of the primary factors leading to this rejection is reduction in the suppressive function of regulatory T cells (Treg). Our results show that myeloid-derived suppressor cells (MDSC) counteract interleukin-6–mediated Treg dysfunction by expressing interleukin-10. Additionally, MDSC maintain forkhead box P3 stability and their ability to suppress IFN-γ+ Th1 cells. Administering MDSC to HR corneal transplant recipients demonstrates prolonged graft survival via promotion of Treg while concurrently suppressing IFN-γ+ Th1 cells. Moreover, MDSC-mediated donor-specific immune tolerance leads to long-term corneal graft survival as evidenced by the higher survival rate or delayed survival of a second-party C57BL/7 (B6) graft compared to those of third-party C3H grafts observed in contralateral low-risk or HR corneal transplantation of BALB/c recipient mice, respectively. Our study provides compelling preliminary evidence demonstrating the effectiveness of MDSC in preventing Treg dysfunction, significantly improving graft survival in HR corneal transplantation, and showing promising potential for immune tolerance induction.

Survival of the fittest: phacoemulsification outcomes in four corneal transplants by Dr Ramon Castroviejo

AimTo evaluate and report the outcomes following phacoemulsification on four eyes, 45 years or more after corneal transplantation.MethodsA retrospective case series of four eyes in three patients (P1, P2, P3),...

Clinical Outcomes of Penetrating Keratoplasty and Descemet Stripping Automated Endothelial Keratoplasty in Asian Population with American Corneas.

To determine the comparative efficacy and safety of penetrating keratoplasty (PK) and Descemet stripping automated endothelial keratoplasty (DSAEK) in the Asian population receiving imported donor corneas, our single-center retrospective study provides analysis supporting the transition from PK to DSAEK in the Asian population using imported American donor corneas. We analyzed 259 patients with 241 and 57 cases of PK and DSAEK respectively during 2008 to 2017 using imported corneas at Chang Gung Memorial Hospital, Linkou, Taiwan. In terms of long-term graft survival analysis, there was no difference between PK and DSAEK (log-rank p = 0.386, HR = 0.920, 95% CI: [0.641–1.380]). However, Cox proportional regression analysis revealed that corneal survival rate of DSAEK group in the first 100 days after transplantation was inferior than that of PK group (log-rank p < 0.001, HR = 2.733, 95% CI: [1.501–4.977])]. Despite the inferior survival rate, there were significantly less neovascularization and Descemet membrane folds in the DSAEK group. Importantly, the non-complication rate of DSAEK was much higher than that of PK with significant difference (PK, 25.7% vs. DSAEK 42.0%, p = 0.022). Collectively, DSAEK is suggested as an alternative surgical modality in Asian patients using imported American donor corneas because of less complication, and no difference in long-term corneal graft survival rates between PK and DSAEK.

Long-term survival of full-thickness corneal xenografts from α1,3-galactosyltransferase gene-knockout miniature pigs in non-human primates.

We aimed to investigate (a) the long-term survival of corneal grafts from α1,3-galactosyltransferase gene-knockout miniature (GTKOm) pigs in non-human primates as a primary outcome and (b) the effect of anti-CD20 antibody on the survival of corneal grafts from GTKOm pigs as a secondary outcome. Nine rhesus macaques undergoing full-thickness corneal xenotransplantation using GTKOm pigs were systemically administered steroid, basiliximab, intravenous immunoglobulin, and tacrolimus with (CD20 group) or without (control group) anti-CD20 antibody. Graft survival was significantly longer (P = .008) in the CD20 group (>375, >187, >187, >83 days) than control group (165, 91, 72, 55, 37 days). When we compared the graft survival time between older (>7- month-old) and younger (≤7-month-old) aged donor recipients, there was no significant difference. Activated B cells were lower in the CD20 group than control group (P = .026). Aqueous humor complement C3a was increased in the control group at last examination (P = .043) and was higher than that in the CD20 group (P = .014). Anti-αGal IgG/M levels were unchanged in both groups. At last examination, anti-non-Gal IgG was increased in the control group alone (P = .013). The GTKOm pig corneal graft achieved long-term survival when combined with anti-CD20 antibody treatment. Inhibition of activated B cells and complement is imperative even when using GTKO pig corneas.

The Outcomes of Primary Pediatric Keratoplasty in Singapore

To evaluate the long-term corneal graft survival and risk factors for graft failure in pediatric eyes. Retrospective, interventional consecutive case series. Unilateral eyes of 105 patients aged 16 years and below were included from the Singapore Corneal Transplant Study between April 4, 1991 and April 4, 2011. Corneal graft survival was calculated using Kaplan-Meier survival analysis, and survival distributions were compared using log-rank test. Mean recipient age was 8.38 ± 5.63 years (range 0.18-15.92 years). Mean follow-up time was 34.16 ± 39.10months. Main diagnoses were corneal scar (22.9%), limbal dermoid (21.9%), anterior segment dysgenesis (15.2%), and keratoconus (14.3%). Forty-four eyes (41.9%) underwent penetrating keratoplasty (PK), 37 (35.2%) underwent anterior lamellar keratoplasty (ALK), 22 (21.0%) underwent lamellar corneal patch graft, and 2 (1.9%) underwent Descemet stripping automated endothelial keratoplasty (DSAEK). Kaplan-Meier survival rates for PK were 92.8% at 1 year, 88.9% at 2-4 years, and 80.9% at 5-16 years; survival rates for ALK were 88.0% at 1 year and 84.3% at 2-7 years; survival rates for corneal patch graft were 100% at 1-3 years and 90% at 4-10 years; these were not statistically significant (P= .362). Deep corneal vascularization (P= .012), preexisting active inflammation (P= .023), preexisting glaucoma drainage device (P= .023), and preexisting ocular surface disease (P= .037) were associated with reduced graft survival in a univariate analysis. We report good long-term graft survival following pediatric keratoplasty for various indications. Lamellar keratoplasty, when indicated, should be the procedure of choice in high-risk keratoplasties.

A Novel Cyclosporine A Drug-Delivery System for Prevention of Human Corneal Rejection after High-risk Keratoplasty: A Clinical Study

To evaluate the efficacy of a novel cyclosporine A (CsA) drug-delivery system (DDS) in the anterior chamber for suppressing the occurrence of rejection and improving the survival of corneal allografts after high-risk keratoplasty. Single-center, noncomparative case series. Ninety-two eyes of 92 patients with corneal blindness who required corneal transplantation at Shandong Eye Institute from May 2003 to June 2011. The CsA DDS was implanted into the anterior chamber during high-risk keratoplasty, and subsequent therapeutic effects were evaluated. Occurrence and reversal of graft rejection within 12 months after surgery, long-term survival of corneal grafts (>12 months), biodegradation of the CsA DDS, endothelial cell density by noncontact specular microscopy, and iris status by ultrasound biomicroscopy (UBM). At 6 months, the transplantation was scored as success in 81 eyes (88.0%), partial success in 7 eyes (7.6%), and failure in 4 eyes (4.3%). The mean graft survival time was 36.1 ± 17.7 months (range, 12.3-61.6 months). The carrier of the CsA DDS, polylactide-co-glycolide-co-caprolactone, biodegraded completely at 7.6 ± 4.3 months (range, 5-13 months). The density of endothelial cells was 2154 ± 230 cells/mm(2) (range, 2067-2319 cells/mm(2)) immediately after surgery and 2079 ± 156 cells/mm(2) (range, 1950-2254 cells/mm(2); P > 0.05) at 6 months. No edema of corneal stroma and iris was observed by UBM. The CsA DDS implanted in the anterior chamber seems to be effective for the prophylaxis of immune rejection after high-risk keratoplasty without toxicity to the cornea and the iris of patients. It can decrease the rejection episode and prolong the survival time of allografts. The anterior chamber may be a promising drug-delivery target for treatment or prevention of endothelial graft rejection after corneal transplantation.

Descemet's Stripping Endothelial Keratoplasty: Long-term Graft Survival and Risk Factors for Failure in Eyes with Preexisting Glaucoma

To evaluate long-term corneal graft survival and risk factors for graft failure after Descemet's stripping endothelial keratoplasty (DSEK) in eyes with preexisting glaucoma. Retrospective case control study. A total of 835 DSEK cases performed by a single surgeon between December 2003 and August 2007 were reviewed. Only the first treated eye of each patient with at least 1 year follow-up was included, resulting in 453 cases; 342 had no prior glaucoma (C), 65 had medically managed preexisting glaucoma (G), and 46 had prior glaucoma surgery (GS). Corneal graft failure was defined as persistent corneal edema resulting in irreversible loss of optical clarity. Corneal graft survival in the 3 groups was calculated using Kaplan-Meier survival analysis. Nine potential risk factors for graft failure were evaluated by Cox proportional hazards univariate and multivariate analysis. These methods took length of follow-up into consideration. Corneal graft survival and risk factors influencing long-term corneal endothelial failure. The 1-, 2-, 3-, 4-, and 5-year graft survival was 99%, 99%, 97%, 97%, and 96%, respectively, in group C; 100%, 98%, 98%, 96%, and 90%, respectively, in group G; and 96%, 91%, 84%, 69%, and 48%, respectively, in group GS (P < 0.001). In the GS group, the 5-year survival rate for eyes with a glaucoma drainage device (GDD) and those with trabeculectomy only was 25% and 59%, respectively. Indication for DSEK, surgically managed glaucoma, type and number of prior glaucoma surgeries, and occurrence of a rejection episode were the significant risk factors for graft survival in univariate analysis. Several factors were correlated; in a multivariate model, prior glaucoma surgery (P < 0.0001) and a prior rejection episode (0.0023) were the significant risk factors for corneal endothelial failure. Patients with medically managed glaucoma had significantly better 5-year graft survival than those with surgically managed glaucoma. A prior glaucoma shunt or trabeculectomy significantly increased the risk of DSEK endothelial failure.

Effect of αGal on corneal xenotransplantation in a mouse model

It has been reported that hyperacute rejection (HAR) does not occur after pig-to-nonhuman corneal xenotransplantation. However, considering that immune privilege is already disrupted in most human corneal recipients, and the expression of αGal can be gradually reduced after pig-to-rat corneal transplantation, the long-term survival of corneal grafts from wild-type pigs cannot be guaranteed. Accordingly, we aimed to investigate the effect of αGal on the change in anti-Gal antibodies, using sensitized α1,3-galactosyltransferase gene-knockout (GTKO) mice recipients. C57BL/6 (B6) and GTKO mice were divided into 5 groups and underwent orthotopically full thickness cormeal transplantation as follows (n=4 for each group): (1) group 1: B6 to B6; (2) group 2: fresh porcine posterior corneal lamella to B6; (3) fresh porcine posterior corneal lamella to GTKO; (4) group 4: decellularized porcine posterior corneal lamella to GTKO, and (5) group 5: B6 to GTKO. Before transplantation, all GTKO recipients were sensitized using intraperitoneal injections of rabbit blood cells. Median survival times (MST) for the corneal grafts of the different groups were compared and plasma concentrations of IgG/IgM anti-Gal antibodies were evaluated at 1 week, 2 weeks and 3 weeks post-transplantation. There were no differences in MSTs between groups. Although there was no HAR of fresh porcine posterior corneal grafts even in sensitized GTKO recipients, αGal expression was induced in the transplanted fresh porcine corneal grafts and plasma concentration of IgG anti-Gal antibody was gradually increased in fresh porcine cornea-grafted GTKO recipients. On the contrary, αGal expression did not increase in the grafts and plasma concentration of anti-Gal antibodies did not change after transplantation using decellularized porcine corneas. Our findings suggest that αGal may affect the long-term survival of porcine corneal xenografts via antibody-mediated rejection, although αGal does not have an effect on acute rejection and decellularized porcine corneas may enable the long-term survival of porcine corneal xenografts.

Postoperative Risk Factors Influencing Corneal Graft Survival in the Singapore Corneal Transplant Study

To determine postoperative risk factors that influence long-term corneal graft survival. Prospective cohort study. Nine-hundred one consecutive penetrating keratoplasty procedures for optical, therapeutic, or tectonic indications from the Singapore Corneal Transplant Study. Univariate and multivariate analysis was performed for postoperative risk factors; Cox proportional hazards regression with a time-dependent covariate was used for preoperative, intraoperative, donor, and postoperative risk factors in a combined model. Raised intraocular pressure (20.7%) was the most common complication, followed by rejection (18.2%), whereas glaucoma surgery (7.9%) and repeat grafting (7.3%) were the most common procedures after penetrating keratoplasty. The primary graft failure rate was 1.4%, and late failure was seen in 9.4% of eyes. In the combined regression model, rejection (hazard ratio [HR], 3.4; P = .00), microbial keratitis (HR, 3.6; P = .00), endophthalmitis (HR, 7.7; P = .00), primary disease recurrence (HR, 73.9; P = .00), wound dehiscence (HR, 2.8; P = .02), lid surgery (HR, 2.3; P = .02), glaucoma surgery (HR, 2.46; P = .02), and repeat grafting (HR, 3.2; P = .00) were the significant postoperative failure predictors; the significant preoperative and intraoperative factors identified were female gender, graft size of less than 7 mm and more than 9 mm, primary diagnosis, preoperative inflammation, and preexisting perforation. Postoperative complications and operative procedures after grafting have an adverse effect on graft survival.

Graft Failure After Penetrating Keratoplasty in Eyes With Ahmed Valves

To determine incidence and risk factors for graft failure following penetrating keratoplasty (PK) in eyes with Ahmed valves (AV). Retrospective, observational cohort study. Patients who underwent PK after AV implantation (both performed at our institution through 2004) were studied. Intervals to graft failure (defined as either dysfunction [stromal thickening with retention of clarity] or decompensation [central microcystic edema or loss of clarity]) were analyzed using Kaplan-Meier technique. Risk factors for graft failure were analyzed using Cox proportional hazard models. Included were 77 eyes (77 patients; first procedure 1993). Following PK, 40 eyes (52%) required increased numbers of glaucoma medications; 10 eyes (13%) required additional glaucoma drainage device(s). Graft failure at 1, 2, and 3 years was 42.4% (95% confidence interval: 32.0%-54.6%), 57.1% (45.6%-69.1%), and 59.1% (47.5%-71.2%), respectively. Prior PK (HR 2.38, P = .006) and stromal vessels (HR 2.90, P = .0005) were associated with increased risk of graft failure. Use of glaucoma medications (HR 0.27, P = .009) and evidence of lower intraocular pressures (IOP) during follow-up (excluding hypotony; HR 0.92, P = .010) were associated with reduced risk of graft failure. Endothelial rejection episodes were observed in 13 eyes (17%); however, rejection was not a risk factor for graft failure (P = .98). Long-term survival of corneal grafts is poor in eyes with AV. The majority of graft failures are associated with progressive loss of endothelial function, without observed immunologic rejection. Despite the presence of an AV, escalation in glaucoma therapy often follows PK; graft failure may be related to poor IOP control.

Baseline Donor Characteristics in the Cornea Donor Study

The Cornea Donor Study (CDS) is an ongoing study that is being conducted to determine whether donor age is related to long-term corneal graft survival. Characteristics of the donor population have been evaluated with respect to donor age, endothelial cell density, and death to preservation interval. Within the context of a prospective, double-masked, controlled trial, 1101 donor corneas were assigned without regard to donor age. Slit-lamp characteristics of the donor corneas showed little variation with donor age, except for the presence of corneal arcus. As death to preservation time decreased, fewer epithelial abnormalities and a lower frequency of stromal edema and Descemet folds were observed. There was little change in the mean of the endothelial cell density with donor age beyond age 60, despite variation. With respect to donor age, there was little difference in either the slit-lamp characteristics or endothelial cell density of the donor corneas. Fewer epithelial abnormalities were observed with shorter death to preservation time.

An evaluation of image quality and accuracy of eye bank measurement of donor cornea endothelial cell density in the Specular Microscopy Ancillary Study

The Specular Microscopy Ancillary Study was designed to examine donor corneal endothelial specular image quality, compare the central endothelial cell density determined by eye banks with the endothelial cell density determined by a central specular microscopy reading center, and evaluate donor factors that may have an impact on specular image quality and endothelial cell density accuracy. Nonrandomized comparative trial. Endothelial specular images of donor corneas assigned in the Cornea Donor Study. Certified readers assessed donor image quality (analyzable from fair to excellent vs. unanalyzable) and determined the central endothelial cell density. Independent adjudication was performed if there was a difference in the quality of grading or if the endothelial cell density varied by > or =5.0% between readers. Average reading center-determined endothelial cell density was compared with the endothelial cell density determined by each eye bank. Evaluation of image quality and accuracy of endothelial cell density. Of 688 donor endothelial images submitted by 23 eye banks, 663 (96%) were analyzable (excellent, 40 [6%]; good, 302 [44%]; fair, 321 [47%]), and 25 (4%) were unanalyzable by reading center standards. In situ retrieval and greater epithelial exposure correlated with a higher image quality grading. The eye bank-determined endothelial cell density of 434 of the 663 (65%) analyzable images were within 10% of the endothelial cell density determined by the reading center, whereas 185 (28%) were more than 10% higher and 44 (7%) were more than 10% lower. Greater variation in endothelial cell density between the eye banks and the reading center was observed with shorter time of death to preservation, presence of an epithelial defect, folds in Descemet's membrane, lower image quality, and the use of fixed-frame or center method endothelial cell density analysis. Overall, donor endothelial specular image quality and accuracy of endothelial cell density determination were good. However, the data suggest that factors that may affect image quality and contribute to variation in interpretation of the endothelial cell density should be addressed, because the donor endothelial cell density is an important parameter for assessing long-term corneal graft survival.