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T Reinhard

Publications and source records attributed to T Reinhard.

At least 37 records · Page 2Linked to original sources
PubMed2003

Individual analysis of expected time on the waiting list for HLA-matched corneal grafts.

OBJECTIVE: Recent studies report the beneficial effect of HLA matching for long-term prognosis of penetrating keratoplasty (kp). This improvement of prognosis, however, has to be weighed against the additional time on the waiting list due to the search for a HLA-compatible graft. Reliable estimation of this additional waiting period is a prerequisite for informed consent on the waiting policy. METHODS: A mathematical model based on survival analysis and HLA haplotype frequencies was used to estimate time on the waiting list for each of 1,400 HLA-typed patients registered at the Lions Cornea Bank NRW. Additionally, the waiting period of each patient was retrospectively determined. Both values were tested for correlation. This analysis was performed for acceptance of up to two mismatches on HLA-A, -B and -DR. RESULTS: When accepting two, one and zero mismatches, median predicted waiting period was 1 +/- 6, 7 +/- 49 and 17 +/- 159 months respectively. Median waiting period in retrospective simulation was 1 +/- 3, 5 +/- 9 and 15 +/- 14 months. Correlation of values from the predictive formula and simulation was statistically significant (p < 0.0001). CONCLUSION: Predicted time on the waiting list is a valuable tool for management of HLA matching in kp.

Cornea↗
PubMed2002

[Perforating keratoplasty with transplants from pseudophakic donors].

PURPOSE: Pseudophacia is considered to be a relative exclusion criterion for cornea donation. The aim of this retrospective study was to investigate the clinical outcome and prognosis of penetrating keratoplasty with grafts from pseudophacic donors. PATIENTS AND METHODS: From April 1996 to July 2000 16 patients received grafts from pseudophacic donors (group I). The control group (group II) comprised 26 patients with grafts from donors without a history of intraocular surgery. Graft survival, ratio of grafts without immune reactions and chronic endothelial cell loss were compared between both groups. RESULTS: During a follow-up of almost 1 year, no graft failures and no graft rejections were observed in group I. In group II 90% of the grafts remained clear and 91% of the grafts remained free of immune reactions in the same follow-up period (Kaplan-Meier estimation). The differences between the study groups were not statistically significant. Chronic endothelial cell loss was 0.86 +/- 0.82 cells per mm2 and day in group I and 1.4 +/- 1.8 cells per mm2 and day in group II. This difference was not statistically significant. CONCLUSION: Our clinical results reveal no reason to regard pseudophacia as a principal contraindication for cornea donation, provided a critical endothelial evaluation is carried out.

Aged↗
PubMed2002

[Possibilities and prospects of therapy and prevention of corneal dystrophies].

Therapeutic approaches in corneal dystrophies should aim at long-term avoidance of recurrences. At the moment, this goal can only be achieved by transplantation of healthy corneal cells. In dystrophies of keratocytes and/or endothelial cells this can be realized by conventional penetrating keratoplasty. In epithelial dystrophies, however, simultaneous transplantation of limbal stem cells is necessary. Optimal HLA-matching strategies and immunosuppressive medication are major means to prevent immunological destruction of these.

Corneal Dystrophies, Hereditary↗
PubMed2002

Predicting time on the waiting list for HLA matched corneal grafts.

Recent studies report the beneficial effect of HLA matching for the long-term prognosis of penetrating keratoplasty (KP). This improvement in prognosis, however, has to be weighed against the additional waiting time while a HLA compatible graft is found. Precise estimation of this additional waiting period is a prerequisite for informed consent on the waiting policy. A mathematical model based on survival analysis and HLA haplotype frequencies was used to estimate time on the waiting list for each of 1400 HLA typed patients registered at the Lions Cornea Bank North Rhine Westfalia (NRW). Additionally, the waiting period for each patient was retrospectively determined. Both values were tested for correlation. This analysis was performed for acceptance of up to two mismatches on HLA-A, -B and -DR. The median predicted waiting period was compatible with the median waiting period in retrospective simulation. Correlation of both entities was statistically significant also. Predicted time on the waiting list as derived from the patient's HLA genotype and a comprehensive database of HLA haplotype frequencies is thus a valuable tool for management of HLA-matching in KP.

Corneal Transplantation↗
PubMed2002

Organ-cultured corneal grafts from septic donors: a retrospective study.

PURPOSE: To evaluate the quality of corneal grafts from donors, who have died from septic multi-organ failure and who are called septic donors in the following. METHODS: One hundred and eighty-two corneal grafts from septic donors were stored in organ culture for 10-14 days. Graft evaluation was performed according to the criteria of the European Eye Bank Association. Only donor corneas with cell density values above 2000 cells/mm(2) were transplanted. Ninety-one patients who received these transplanted corneas were examined retrospectively with special emphasis on endophthalmitis, graft failure and incidence of immune reactions. RESULTS: Ninety-one of 182 donor corneas (50%) from septic donors were discarded mainly due to endothelial damage (61; 67%). Only seven (8%) were discarded due to medium contamination. In contrast, 452 of 1261 donor corneas (36%) from non-septic donors during the same period were discarded, again mainly due to endothelial damage (264; 58%). In this group, 48 donor corneas (11%) were discarded due to medium contamination. No patient who had received a graft from a septic donor has experienced endophthalmitis. The rate of immune reactions and graft failure was in the same range when compared to a larger group who received grafts from non-septic donors. CONCLUSION: Our data reveal no contraindication against the use of corneal grafts derived from septic donors, critical graft assessment in organ culture provided.

Adolescent↗
PubMed2001

Topical treatment of acute adenoviral keratoconjunctivitis with 0.2% cidofovir and 1% cyclosporine: a controlled clinical pilot study.

OBJECTIVE: To evaluate the efficacy of 0.2% cidofovir eyedrops and 1% cyclosporine eyedrops administered 4 times daily (qid) to treat acute adenoviral keratoconjunctivitis. METHODS: A randomized, controlled, double-masked study was conducted on 39 patients with acute adenoviral keratoconjunctivitis of recent onset. Patients were divided into 4 treatment groups: (1) cidofovir qid, (2) cyclosporine qid, (3) cidofovir + cyclosporine qid, and (4) sodium chloride qid (control). The diagnosis was confirmed using adenoviral polymerase chain reaction from conjunctival swabs. Duration of treatment was 21 days. MAIN OUTCOME MEASURES: Severity of conjunctival hyperemia, conjunctival chemosis, superficial punctate keratitis during treatment, and presence and severity of corneal subepithelial infiltrates were evaluated using a clinical score. Duration until subjective improvement of symptoms was recorded. RESULTS: Subjective improvement of local symptoms was accelerated in the cyclosporine group. All other clinically relevant variables showed no statistically significant difference among the 4 treatment groups. Particularly, we did not find a difference in the frequency of corneal subepithelial infiltrates at the end of treatment. CONCLUSIONS: Use of cidofovir, cyclosporine, or both did not accelerate the improvement of clinical symptoms of acute adenoviral keratoconjunctivitis compared with the natural course of the infection as demonstrated by this pilot study. This might be because of the wide spectrum of the clinical course of the infection, low sensitivity to cidofovir, too low of a concentration of cidofovir, or early cessation of viral replication in the course of the infection. The effect of a higher concentration of topical cidofovir with and without cyclosporine requires investigation in a larger group of patients.

Acute Disease↗
PubMed2001

[Limbus transplantation for reconstruction of the ocular surface].

Proliferation of the corneal epithelium originates in undifferentiated, long-lived stem cells that are located in the basal limbal epithelium. Stem cells are important for corneal epithelial regeneration and wound healing. Depletion of stem cells due to accidents as well as malfunctions of stem cells due to inborn or inflammatory diseases result in limbal stem cell deficiency. Limbal deficiency is characterized by conjunctivalization of the cornea with vascularization and opacification. Partial limbal deficiency can be treated by removing ingrown conjunctival epithelium thus allowing normal limbal epithelium to repopulate the cornea. Unilateral limbus-derived stem cell disease requires either limbal autograft transplantation from the healthy partner eye or kerato-limbal allograft transplantation. Several modifications of the latter technique have been performed including large kerato-limbal lamellar grafts and central penetrating kerato-limbal allografts. All homologous procedures render a very high risk of immunological reactions that require long term systemic immunosuppression. The use of amniotic membrane, better pharmacological drugs for immunosuppression and improvements in the HLA-matching of limbal allografts as well as ex vivo expansion of corneal stem cells should allow for better reconstruction of the ocular surface in limbal deficiency.

Biological Dressings↗
PubMed2001

[Meeting the demand for quality and safety checked corneal transplants. The role of corneal banks and health care organizations in Germany].

Only cornea banks with organ culture techniques provide the substantial length of time often required by safety and quality controls of corneal transplants. In Germany the annual need would be 4,500 transplants per year, for which 7,500 donor corneas must be primarily taken into culture. Meeting total demand should theoretically be easy as only 3,800 corneal donors are needed from a total of 860,000 deceased per year. Since consent is given in up to 50% if approached properly, shortage in donor corneas should not pose a problem. However, shortage still is the major problem because most cornea banks are still in the initial phase. This is because of the lack of direct refinancing by health care organizations. These organizations must be required to meet their legal responsibilities in this area.

Corneal Transplantation↗
PubMed2001

[Immunology-related chronic progressive cicatricial conjunctival diseases: diagnosis, therapy and prognosis].

PURPOSE: We reviewed the records of patients with chronic cicatricial disease of the conjunctiva for differences in prognosis between clinical and histopathological subgroups of the disease and in therapeutic options. PATIENTS: In 30 patients (58 eyes) with an average age of 69 years (52-86) chronic cicatricial disease of the conjunctiva was diagnosed clinically. Only in 22/30 patients conjunctival biopsies could be performed. The correlation of histopathological and immunohistochemical diagnoses with clinical course under systemic immunosuppression was studied. RESULTS: 15/22 biopsies led to a classification into different subgroups. Under systemic immunosuppression disease ceased to progress for a mean time of 15 months in 13 of 15 patients with positive biopsies and in 9 of 15 without classification. The results after cyclosporine A therapy (4 of 5 patients stabilized after a mean of 27.5 months) and mycophenolate mofetil (8 of 11 patients stabilized at a mean of 7.8 months) were better than those after therapy with dapsone, azathioprine and cyclophosphamide. CONCLUSIONS: Histopathological and immunohistochemical examinations led to a classification in two-thirds of the patients with clinical aspects of chronic cicatricial disease of the conjunctiva. There was no correlation between different histopathological subgroups, success of therapy and prognosis of the disease. There is little hope in using new systemic immunosuppression such as cyclosporine A and mycophenolate mofetil.

Aged↗
PubMed2001

RAD, a new immunosuppressive macrolide in murine corneal transplantation.

BACKGROUND: RAD is a novel macrolide immunosuppressant with effects on growth factor signalling. We investigated the potency of RAD in inhibiting allograft rejection in the rat model of orthotopic allogeneic penetrating keratoplasty. METHODS: Fifty-four allogeneic orthotopic penetrating keratoplasties were performed using Fisher rats as donors and Lewis rats as recipients. The animals were divided into five groups: syngeneic control, allogeneic control, RAD 1.5 mg/kg bw per day, RAD 2.5 mg/kg bw per day, cyclosporin A (CSA) 10 mg/kg bw per day. Medication started on the day of operation and continued daily for the duration of 18 days. Each animal was examined by slit-lamp microscopy every 3rd day. For immunohistological evaluation rats were killed on day 14. Immunohistology was performed using monoclonal mouse anti-rat antibodies against CD4, CD8, CD25, CD45 and CD54. RESULTS: The average transplant survival time in the allogeneic combination was 12.3 days (+/- 0.3). Therapy with RAD 1.5 mg/kg and 2.5 mg/kg led to a statistically significant prolongation of transplant survival to 32.3 days (+/- 11.3, P<0.05) and 37.7 days (+/- 12.5), respectively. This efficacy was similar to that of CSA 10 mg/kg (39.7 +/- 12.5 days). There was a statistically significant reduction in the number of CD4+, CD8+ as well as CD45+ cells in both the RAD- and the CSA-treated animals compared with the allogeneic control. CONCLUSIONS: The results show that oral immunosuppression with RAD significantly prolongs corneal allograft survival. Further investigation of RAD in preclinical and clinical high-risk keratoplasty is warranted.

Administration, Oral↗
PubMed2001

Systemic mycophenolate mofetil in comparison with systemic cyclosporin A in high-risk keratoplasty patients: 3 years' results of a randomized prospective clinical trial.

BACKGROUND: With the use of systemic cyclosporin A (CsA), graft prognosis after high-risk penetrating keratoplasty has improved considerably. However, the application of CsA is limited owing to a variety of severe side effects. In this prospectively randomized study mycophenolate mofetil (MMF), a safe and efficient immunosuppressive medication after renal transplantation, was compared with CsA after high-risk penetrating keratoplasty. METHODS: Twenty-nine high-risk keratoplasty patients were treated with MMF 2x 1 g daily; another 27 patients received CsA, aiming at blood trough levels of 120-150 ng/ml. Systemic immunosuppression was scheduled for 6 months. In both groups oral corticosteroids (fluocortolone 1 mg/kg) were administered for 3 weeks postoperatively. RESULTS: During the first year after operation, no graft failure was recorded. Two years postoperatively 92%/82% and 3 years postoperatively 74%/69% of grafts were clear in the MMF and CsA group, respectively (Kaplan Meier P=0.33, logrank test). In total, two graft failures were recorded in the MMF group and four in the CsA group. Three years postoperatively 53% of the grafts were rejection-free in the MMF group and 73% in the CsA group (Kaplan Meier P=0.46, log-rank test). Eight endothelial immune reactions were observed in the MMF group (three under systemic immunosuppression/five thereafter; six mild/two severe) and five in the CsA group (three under systemic immunosuppression/two thereafter; three mild/two severe). Side effects occurred in six patients under MMF and 11 under CsA. CONCLUSIONS: Concerning efficacy, no statistically significant difference between systemic MMF and systemic CsA administered for 6 months after high-risk penetrating keratoplasty could be shown. Systemic MMF was proven to be at least as safe as CsA. The main mechanism in improving graft survival is a shift from severe to milder endothelial immune reactions, as already demonstrated for CsA. Thus, MMF may become an alternative to CsA for immunosuppression after penetrating high-risk keratoplasty. About 2 years postoperatively, pharmacologically induced relative immunological tolerance slowly decreases. Therefore, long-term administration of systemic MMF should be evaluated in further studies.

Adolescent↗
PubMed2001

Testing of corneoscleral discs and their culture media of seropositive donors for hepatitis B and C virus genomes.

UNLABELLED: The prevalence of donors seropositive for hepatitis B virus (HBV) surface antigen (HBsAg) or hepatitis C virus (HCV) antibody (anti-HCV) in western countries is estimated to be 0.5%-1%. There have been only two cases, however, published so far, where hepatitis B was suspected to have been transmitted by penetrating keratoplasty [4]. Concerning HCV, no suspected transmission by keratoplasty has been reported so far. This is also true for the time before serological screening for infectious diseases became mandatory for corneal donors. In the Lions Cornea Bank North Rhine Westfalia, 4.7% (HBV) and 3.2% (HCV) respectively of the corneas of the years 1995 to 1999 were discarded due to a "non-negative serology". In about 50% of these cases the screening test (ELISA) generated no valid signal and, therefore, a "questionable positivity" was assumed. Since in Germany corneal graft shortage still is a limiting factor for penetrating keratoplasty, this study was to evaluate the detectability of HBV-DNA and HCV-RNA in the serum samples, organ culture media and corneas of donors tested seropositive for HBsAg or anti-HCV in an attempt to obtain information as to the potential infectivity of this donor material. In this study, 29 corneas of 17 donors seropositive by ELISA for HBsAg and 27 corneas of 14 donors seropositive by ELISA for anti-HCV were evaluated. The organ culture media and the sera were screened for the presence of HBV-DNA or HCV-RNA by PCR. The corneoscleral discs were divided into a central trephinate (7 mm) and the corneoscleral rim. Concerning HBV-DNA both tissues were examined separately by polymerase chain reaction (PCR). In the case of HCV-RNA, a further, more sensitive nucleotide amplification method (NAT), the transcription mediated amplification (TMA), was used to test media, central corneas and cornealscleral rims. The media were additionally tested by PCR. Viral nucleic acid was detected in the sera from 6 of 17 HBsAg positive donors and from 6 of 14 anti-HCV positive donors. Viral genomes could not be detected in the organ culture media nor in the central corneas or corneoscleral rims by PCR at a detection limit of 1000 and 100 copies/ml. Concerning HCV-RNA, two media were positive in the TMA with 50-100 copies/ml. CONCLUSION: according to our results, the risk of transmitting hepatitis B or C virus by penetrating keratoplasty appears to be low: although hepatitis C virus RNA could be detected in 2 media (from two donors) out of 27 with a low concentration of virus copies between 50-100/ml. It remains open whether such a low virus particle number may cause infection in the recipient.

Adolescent↗
PubMed2001

Herpes simplex virus infection in the media of donor corneas during organ culture: frequency and consequences.

BACKGROUND AND PURPOSE: According to polymerase chain reaction (PCR) studies 2-38% of organ culture donor corneas may contain herpes simplex virus (HSV) DNA, but there are only 6 reported instances of proven virus replication in a corneoscleral disc. Moreover there are only 6 patients reported in whom primary graft failure and extensive post-operative epithelial defects were probably caused by a herpetic infection of the corneal graft. Recently we observed virus replication in a donor cornea with subsequent complete endothelial necrosis in our cornea bank. The aim of this study was to investigate the possible correlation between herpetic donor cornea infection and endothelial necrosis in organ culture. METHODS: To evaluate the frequency of HSV as a reason for endothelial necrosis in organ culture we tested the media of 199 donor corneas discarded due to an altered endothelium in the years 1997 to 1999 by PCR for HSV. As a negative control group we screened the media of 117 transplanted corneas using PCR. RESULTS: In the control group we had only negative PCR results, in contrast to the corneas with severe or complete endothelial necrosis where HSV DNA was detected in 12 media of the corneas of 9 donors. Virus could be cultivated out of 7 media. CONCLUSIONS: (1) HSV replication is a common cause of severe endothelial necrosis in organ culture corneas. (2) Replication of the virus during organ culture comes close to a virus cultivation using the corneoscleral disc as a cell culture. (3) We consider the danger of transplanting active HSV to be very small if critical assessment of the graft prior to surgery is carried out.

Adult↗
PubMed2001

[Highly active antiviral and immunosuppressive combination therapy with acyclovir and mycophenolate mofetil following keratoplasty in patients with herpetic eye disease].

BACKGROUND: Herpes simplex virus (HSV) infection is the most common cause of corneal blindness in developed countries. Penetrating keratoplasty is the only therapeutic option for visual rehabilitation in patients with severely scarred corneas. Recurrence of the underlying disease and allograft rejection (AR) are the common causes of graft failure. Systemic immuno-suppression with cyclosporin A is contraindicated due to the risk of HSV recurrence. The potent immunosuppressive properties of mycophenolate mofetil (MMF) have already been shown clinically. By reducing the intracellular guanosid-pool MMF inhibits the proliferation of lymphocytes. As these quanosin-nucleosides also act as competing substrates to acyclovir at the viral DNA-polymerase, a synergistic effect of MMF and acyclovir might be expected. The aim of this study was to evalute the efficacy and safety of a double-drug regimen with MMF and acyclovir in the prevention of acute allograft rejection and HSV recurrence following corneal transplantation. METHODS: Patients following penetrating keratoplasty due to herpetic eye disease have been treated with MMF 1 g twice dialy and acyclovir 5 x 200 mg/day for one year. Primary efficacy variables have been the number of acute AR and recurrence of herpetic disease per patient and time. The number of adverse events has been documented for safety analysis. RESULTS: Fifteen patients have been enrolled. The average follow up period was 9.1 (+/- 5.2) months. No graft opacifications have been seen. With two AR and no recurrence of herpetic disease the efficacy ofthis therapeutic regimen was supperior compared with historical control groups. CONCLUSION: In this first study on the efficacy and safety of a double drum regimen with acyclovir and MMF for the control of acute corneal AR and HSV-recurrenct following keratoplasty in patients with herpetic eye disease, the combination therapy has been shown to be a safe and highly efficient protocol for graft protection.

Acyclovir↗
PubMed2001

[Regression analysis of idiopathic endothelial cell loss after perforating normal risk keratoplasty: basic principles for long-term analysis of endothelial risk factors in a retrospective clinical study].

BACKGROUND: For the characterisation of influencing factors on chronic endothelial cell loss after penetrating keratoplasty by means of multivariate statistics, a mathematical description of the course of the individual postoperative endothelial cell density is a prerequisite. This mathematical description should result in a standardized index value describing course and amount of the postoperative endothelial cell loss over time in a canonical way. The slopes of the linear regression lines for each individual scatter plot of a) the endothelial cell density values plotted against the respective postoperative time directly (linear regression), and b) after logarithmic transformation (exponential regression) are evaluated, respectively. PATIENTS AND METHODS: 58 patients after normal-risk keratoplasty (26x keratokonus, 22x Fuchs-dystrophy and 10 cases of corneal decompensation after cataract surgery) with 5 or more postoperatively acquired endothelial density values and without any episodes of graft rejection were included in this study. Mean follow up was 2.9 +/- 1.1 years. The postoperative endothelial cell density values were plotted against the respective time for each patient individually. The coefficients of variation (R2) derived from the linear and the exponential regression models were calculated for each of these scatter plots. The pairs of R2 values (linear vs. exponential) were compared statistically. A dependence of the difference of linear and exponential R2-values on the ophthalmologic diagnosis was tested as well. RESULTS: The linear model is able to declare 83% the total variance of the course of the endothelial cell density. The exponential model even declares 86%. This small difference was statistically significant. Since both methods of regression describe the course of the cell density well, intra/and extrapolation of missing endothelial values is possible with both models. No dependence of the difference of linear and exponential R2-values on the ophthalmologic diagnosis could be demonstrated. CONCLUSIONS: Both, the intuitively understandable slope of the linear regression line and the constant of decay of the exponential regression curve, are suitable for describing the amount of the postoperative loss of endothelial cells after normal-risk keratoplasty independent of the ophthalmologic diagnosis. Both can thus be used as target variable in forthcoming statistical analyses for chronic endothelial cell loss.

Adult↗