Penetrating keratoplasty in children under 3 years old with congenital corneal opacities

AIM: To evaluate the graft rejection and visual outcomes after penetrating keratoplasty (PK) in the presence of various congenital corneal opacities in children. METHODS: In this retrospective cohort study, children who underwent PK were then followed for 5y. The patient's medical records were collected from June 2014 until June 2019 and analyzed in December 2019. All patients were children under three years old with congenital corneal opacities with or without microcornea who came to a pediatric ophthalmologist and underwent PK in Jakarta Eye Center (JEC). Beforehand, all children have participated in a thorough evaluation for PK. In the case of severe microcornea was not advised to undergo surgery. The visual outcomes and graft survival rate were described in percentages. The graft survival plot was presented with Kaplan-Meier, while the visual acuity was analyzed using the Wilcoxon signed ranks test. RESULTS: Sixteen eyes from eleven patients (seven girls and four boys) underwent PK. The graft survival rate of the first 6, 12, and 18 mo later of keratoplasty was 100%, 83.3%, and 66.7%, respectively. The overall mean survival time is 22mo (standard error 2.419), and no significant difference between the patients underwent PK before and after 36mo of their age (P=0.52). The graft failure was 50%, and post-surgery complications included cataract 43.7%, band keratopathy 12.5%, and scleromalasia 6.25%. Wilcoxon test analysis of visual acuity post keratoplasty was not statistically significant (P=0.34), while overall showed 44% improvements of visual outcome for 5y of follow-up. With a good survival at one year up to 22mo (83.3%), the visual acuity could be achieved (63%), and showed improvements (44%) during follow-up. CONCLUSION: The complications are frequent for pediatric PK. Thus, corneal surgery on infants requires careful case selection, adequate pre-operative evaluation, skilled surgery (optical correction), very close cooperation family–physician, intensive post-operation care, and amblyopia management in the future.

Possible association between viral infection and poor survival of the corneal graft after penetrating keratoplasty in patients with congenital corneal opacity: a cohort study

BackgroundCongenital corneal opacity (CCO) is a rare disorder. Penetrating keratoplasty (PK) is the main surgical option for CCO, but many factors affect graft survival. Therefore, this study aimed to perform a virological examination of CCO specimens after PK to explore the relationship between virological factors and graft survival after PK.MethodsThis prospective study included consecutive patients (<6 months of age) diagnosed with CCO and treated with PK at Beijing Tongren Hospital from August 2017 to January 2018. Next-generation sequencing was used to detect viral DNA in the CCO specimens. The survival of the primary graft was analysed using the Kaplan-Meier method.ResultsOverall, 24 eyes of 24 infants were treated with PK during the study period. The mean age at surgery was 4.8±1.1 months. Epstein-Barr virus DNA was detected in two specimens, varicella-zoster virus DNA in one specimen, herpes simplex virus DNA in three specimens and cytomegalovirus DNA in one specimen. In the virus-positive group, only one (14.3%) graft remained clear during follow-up. In contrast, in the virus-negative group (n=17), 13 (76.5%) grafts were still clear at the last follow-up. The mean survival of the grafts in the virus-positive group was significantly shorter than in the virus-negative group (11.0±9.8 months vs 27.1±7.7, p<0.001).ConclusionThe presence of viral DNA in CCO specimens might be associated with poor graft survival after PK.

The Effect of Locally Delivered Apocynin on Fat Graft Survival in an Experimental Rat Animal Model

Objectives: We aimed to investigate the efficacy of locally delivered apocynin on fat graft survival in an experimental autologous fat grafting (AFG) model created in rats. Methods: Twenty-one Wistar albino male rats were included in this study. The 0.647 g mean weight grafts were harvested from the inguinal region and transferred to the nape of every rat. The subjects were randomly separated into three groups. Saline, dimethyl sulfoxide (DMSO) and apocynin, a dose of 20 mg/kg, solutions were applied once a day for 2 weeks. After 3 months, the rats were sacrificed. The evaluation of physical measurements (weight and volume) and survival rates of the grafts for volume (SRV) and weight (SRW), the viable cell count (VC) with the MTT assay, and histopathological parameters were done. Results: All biophysical parameters were found to be significantly higher in the apocynin group compared to other groups (p < .05). In the MTT test, the saline group was normalized to 100%. According to this, DMSO and apocynin groups’ means were 106% and 163%, respectively. The VC was significantly higher in the apocynin group than the other groups (p < .05). The VC was significantly higher in the DMSO group than in the saline group (p < .05). No significant difference was found in other comparisons performed according to biophysical and histopathological parameters (p > .05). Conclusion: The locally delivered apocynin decreases fat graft volume loss in an experimental AFG model. Consequently, apocynin can be used as an effective substance to increase graft survival.

Tolerogenic Delivery of a Hybrid Insulin Peptide Markedly Prolongs Islet Graft Survival in the Non-Obese Diabetic (NOD) Mouse

The induction of antigen (Ag)-specific tolerance and replacement of islet β-cells are major ongoing goals for the treatment of Type 1 Diabetes (T1D). Our group previously showed that a hybrid insulin peptide (2.5HIP) is a critical autoantigen for diabetogenic CD4⁺ T cells in the non-obese diabetic (NOD) mouse model. In this study, we investigated whether induction of Ag-specific tolerance using 2.5HIP-coupled tolerogenic nanoparticles (NPs) could protect diabetic NOD mice from disease recurrence upon syngeneic islet transplantation. Islet graft survival was significantly prolonged in mice treated with 2.5HIP NPs, but not NPs containing the insulin B chain peptide 9-23. Protection in 2.5HIP NP-treated mice was attributed both to the simultaneous induction of anergy in 2.5HIP-specific effector T cells and to the expansion of Foxp3+ regulatory T cells specific for the same antigen. Notably, our results indicate that effector function of graft-infiltrating CD4⁺ and CD8⁺ T cells specific for other β-cell epitopes was significantly impaired, suggesting a novel mechanism of therapeutically induced linked suppression. This work establishes that tolerance induction with a hybrid insulin peptide can delay recurrent autoimmunity in NOD mice, which could inform the development of an Ag-specific therapy for T1D.

Tolerogenic Delivery of a Hybrid Insulin Peptide Markedly Prolongs Islet Graft Survival in the Non-Obese Diabetic (NOD) Mouse

The induction of antigen (Ag)-specific tolerance and replacement of islet β-cells are major ongoing goals for the treatment of Type 1 Diabetes (T1D). Our group previously showed that a hybrid insulin peptide (2.5HIP) is a critical autoantigen for diabetogenic CD4⁺ T cells in the non-obese diabetic (NOD) mouse model. In this study, we investigated whether induction of Ag-specific tolerance using 2.5HIP-coupled tolerogenic nanoparticles (NPs) could protect diabetic NOD mice from disease recurrence upon syngeneic islet transplantation. Islet graft survival was significantly prolonged in mice treated with 2.5HIP NPs, but not NPs containing the insulin B chain peptide 9-23. Protection in 2.5HIP NP-treated mice was attributed both to the simultaneous induction of anergy in 2.5HIP-specific effector T cells and to the expansion of Foxp3+ regulatory T cells specific for the same antigen. Notably, our results indicate that effector function of graft-infiltrating CD4⁺ and CD8⁺ T cells specific for other β-cell epitopes was significantly impaired, suggesting a novel mechanism of therapeutically induced linked suppression. This work establishes that tolerance induction with a hybrid insulin peptide can delay recurrent autoimmunity in NOD mice, which could inform the development of an Ag-specific therapy for T1D.

Tolerogenic Delivery of a Hybrid Insulin Peptide Markedly Prolongs Islet Graft Survival in the Non-Obese Diabetic (NOD) Mouse

The induction of antigen (Ag)-specific tolerance and replacement of islet β-cells are major ongoing goals for the treatment of Type 1 Diabetes (T1D). Our group previously showed that a hybrid insulin peptide (2.5HIP) is a critical autoantigen for diabetogenic CD4+ T cells in the non-obese diabetic (NOD) mouse model. In this study, we investigated whether induction of Ag-specific tolerance using 2.5HIP-coupled tolerogenic nanoparticles (NPs) could protect diabetic NOD mice from disease recurrence upon syngeneic islet transplantation. Islet graft survival was significantly prolonged in mice treated with 2.5HIP NPs, but not NPs containing the insulin B chain peptide 9-23. Protection in 2.5HIP NP-treated mice was attributed both to the simultaneous induction of anergy in 2.5HIP-specific effector T cells and to the expansion of Foxp3+ regulatory T cells specific for the same antigen. Notably, our results indicate that effector function of graft-infiltrating CD4+ and CD8+ T cells specific for other β-cell epitopes was significantly impaired, suggesting a novel mechanism of therapeutically induced linked suppression. This work establishes that tolerance induction with a hybrid insulin peptide can delay recurrent autoimmunity in NOD mice, which could inform the development of an Ag-specific therapy for T1D.

Advantages and Limitations of Clinical Scores for Donation After Circulatory Death Liver Transplantation

Background: Scoring systems have been proposed to select donation after circulatory death (DCD) donors and recipients for liver transplantation (LT). We hypothesized that complex scoring systems derived in large datasets might not predict outcomes locally.Methods: Based on 1-year DCD-LT graft survival predictors in multivariate logistic regression models, we designed, validated, and compared a simple index using the University of California, San Francisco (UCSF) cohort (n = 136) and a universal-comprehensive (UC)-DCD score using the United Network for Organ Sharing (UNOS) cohort (n = 5,792) to previously published DCD scoring systems.Results: The total warm ischemia time (WIT)-index included donor WIT (dWIT) and hepatectomy time (dHep). The UC-DCD score included dWIT, dHep, recipient on mechanical ventilation, transjugular-intrahepatic-portosystemic-shunt, cause of liver disease, model for end-stage liver disease, body mass index, donor/recipient age, and cold ischemia time. In the UNOS cohort, the UC-score outperformed all previously published scores in predicting DCD-LT graft survival (AUC: 0.635 vs. ≤0.562). In the UCSF cohort, the total WIT index successfully stratified survival and biliary complications, whereas other scores did not.Conclusion: DCD risk scores generated in large cohorts provide general guidance for safe recipient/donor selection, but they must be tailored based on non-/partially-modifiable local circumstances to expand DCD utilization.

Everolimus Reduces Cancer Incidence and Improves Patient and Graft Survival Rates after Kidney Transplantation: A Multi-Center Study

Kidney transplantation can prevent renal failure and associated complications in patients with end-stage renal disease. Despite the good quality of life, de novo cancers after kidney transplantation are a major complication impacting survival and there is an urgent need to establish immunosuppressive protocols to prevent de novo cancers. We conducted a multi-center retrospective study of 2002 patients who underwent kidney transplantation between 1965 and 2020 to examine patient and graft survival rates and cumulative cancer incidence in the following groups categorized based on specific induction immunosuppressive therapies: group 1, antiproliferative agents and steroids; group 2, calcineurin inhibitors (CNIs), antiproliferative agents and steroids; group 3, CNIs, mycophenolate mofetil, and steroids; and group 4, mammalian target of rapamycin inhibitors including everolimus, CNIs, mycophenolate mofetil, and steroids. The patient and graft survival rates were significantly higher in groups 3 and 4. The cumulative cancer incidence rate significantly increased with the use of more potent immunosuppressants, and the time to develop cancer was shorter. Only one patient in group 4 developed de novo cancer. Potent immunosuppressants might improve graft survival rate while inducing de novo cancer after kidney transplantation. Our data also suggest that everolimus might suppress cancer development after kidney transplantation.

Corneal graft survival analysis after penetrating keratoplasty in a retrospective cohort study

Purpose. To assess the results of penetrating keratoplasty and identify the risk factors for the graft disease (GD) development. Material and methods. Data of 582 patients after corneal transplantation performed in the period since 2011 to 2019 for keratoconus (41%), as well for corneal leucorrhoea and dystrophies (59%), aggravated by concomitant pathology, the so-called high-risk keratoplasty (HRK) were analyzed in a retrospective cohort study. We estimated the functional results and incidence of GD. The calculation of the t-criterion; cross-tabulation method; Kaplan–Meier survival analysis and multivariate analysis were applied. Results. As a result of penetrating keratoplasty, the BCVA (best corrected visual acuity) in patients with keratoconus increased by 20%; in patients with HRK – by 8%. In the general group the graft survival rate was 72%, while the 8-year successful graft engraftment in patients with keratoconus comprised 91%, with HRK – 60%. A significant relationship of the GD development with preoperative diagnosis and rekeratoplasty was determined. The risk of GD incidence was minimal in patients under 30 years of age and maximum in patients aged from 50 to 70 years. Survival rates for corneal transplants were better in men than in women. Conclusion. Penetrating keratoplasty in patients with keratoconus provides a good functional result with a minimal risk of GD development. With penetrating keratoplasty in high-risk patients, the effectiveness of surgical interventions is significantly lower (by ~30%). Key words: keratoconus, penetrating keratoplasty, corneal transplantation, survival analysis