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Thomas Reinhard

Publications and source records attributed to Thomas Reinhard.

34 records · Page 2Linked to original sources
PubMed2003

Synergistic antiherpetic effect of acyclovir and mycophenolate mofetil following keratoplasty in patients with herpetic eye disease: first results of a randomised pilot study.

PURPOSE: The main reasons for graft failure following penetrating keratoplasty in patients with herpetic eye disease are recurrence of herpetic disease and allograft rejection. In a randomised trial the effect of systemic acyclovir and mycophenolate mofetil (MMF) on these post-keratoplasty complications was evaluated. PATIENTS AND METHODS: Patients with typical clinical findings of recurrent herpetic keratitis were enrolled in this single-centre study after contraindications to systemic immunosuppression were ruled out. In a prospective randomised trial 30 patients were treated in three groups. In group A patients received acyclovir 200 mg five times/day for 3 weeks. In group B patients were treated with acyclovir 200 mg five times/day for 1 year, and patients in group C received acyclovir 200 mg five times/day in combination with MMF 1 g twice daily for 1 year. RESULTS: In group A 3 patients experienced seven herpes recurrences. One patient had a moderate and one further patient a severe allograft rejection. In group B three severe allograft rejections were observed. Herpes recurrences did not occur while receiving acyclovir prophylaxis, but only once after the prophylaxis had been stopped. In group C no herpes recurrence was observed, and only two mild allograft rejections occurred while being under combined acyclovir-MMF therapy. Another mild and one moderate allograft rejection were observed after cessation of MMF. CONCLUSIONS: These results demonstrate that systemic acyclovir protects the grafts from recurrences of herpetic disease as long as it is administered at efficient doses. Simultaneously administered mycophenolate mofetil does not trigger herpes recurrences and protects the graft from severe allograft rejections, but mild, less dangerous immune reactions may still occur while receiving MMF. The combination of systemic acyclovir and mycophenolate mofetil therefore is recommended for patients at high risk for herpes recurrence and allograft rejections.

Acyclovir↗
PubMed2003

Differential contribution of natural killer cells to corneal graft rejection in 3-week-old versus mature rats.

BACKGROUND: The aim of this study was to compare immunologic graft rejection in adult and 3-week-old immature recipients in the rat keratoplasty model. METHODS: Forty orthotopic penetrating keratoplasties were performed in four different donor-recipient combinations. Group 1 consisted of adult Fisher donors and adult Lewis recipients, group 2 consisted of adult Fisher donors and immature Lewis recipients, group 3 consisted of adult Lewis donors and recipients, and group 4 consisted of adult Lewis donors and immature Lewis recipients. An immunohistologic evaluation of the grafts was performed on day 14. RESULTS: Grafts in both allogeneic groups (groups 1 and 2) showed infiltration with CD4+ cells, CD8+ cells, natural killer (NK) cells, interleukin-2-receptor+ cells, macrophages, and intercellular adhesion molecule-1+ cells. The density of infiltrating CD4+, CD8+, interleukin-2-receptor+, and intercellular adhesion molecule-1+ cells in the graft stroma, however, was statistically significantly lower in the immature group (group 2) than in the adult group (group 1). The density of CD161+ NK cells, in contrast, was statistically significantly higher in the immature group than in the adult group. There were no or only a few infiltrating inflammatory cells in grafts of both syngeneic groups (groups 3 and 4). CONCLUSIONS: We were able to establish for the first time an animal model for keratoplasty in infants that showed that the mechanism of graft rejection in young recipients seems to be different from that in mature rats. In adult recipients, alloreactive T cells are the main mediators of rejection, whereas NK cells seem to play a more dominant role in immature recipients.

Age Factors↗
PubMed2003

[Systematic EDP-supported acquisition of follow-up data of keratoplasty patients--report on ten years' experience].

BACKGROUND: Influencing factors on medium-term and long-term clear graft survival following penetrating keratoplasty are mostly basically known but their quantitative importance and interaction are far less well established. Due to abundance and complex interaction of influencing factors, comprehensive collection of pre- and postoperative data is imperative. Furthermore, application of stringent quality control as addressed in the German transplantation law established in 1997 is only possible if comprehensive data are available within a database system. METHODS: All data from corneas preserved at the Lions cornea bank NRW as well as donor and follow-up data are entered into a custom-relational database system. This system implements management of data concerning the waiting list, the donors, organ culture as well as surgical and follow-up data. In order to demonstrate analysis of these data, 5-year graft survival with respect to preoperative risk assessment is analysed. RESULTS: Data of 1710 donors and 3333 recipients have been entered into the system so far. Clear graft survival 5 years after normal risk keratoplasty is 85 %, whereas prognosis of high-risk cases is significantly worse (history of ocular herpes simplex virus keratitis: 80 %, increased risk of graft rejection as the only risk factor: 65 %, glaucoma: 45 %, limbal stem cell insufficiency: 30 %; p < 0.05; log-rank test). CONCLUSIONS: The database system has proved indispensable for documentation, quality control and research. The implementation of this system is possible at any cornea bank. A common relational database system for cornea banks would of the banks as well as multicentre keratoplasty studies.

Corneal Transplantation↗
PubMed2003

HLA class I and II matching improves prognosis in penetrating normal-risk keratoplasty.

BACKGROUND: HLA matching in penetrating keratoplasty is still neglected in most eye clinics. This is due to contradictory results of studies performed in the past. Different surgical techniques in multicenter studies, missing risk differentiation in high-risk situations and faulty HLA typing can be identified as the main reasons for these contradictory results. In this monocenter study, the value of HLA class I and II matching (A, B, DR loci) was examined in a homogenous group of 398 normal-risk keratoplasty patients using modern typing techniques. METHODS: Penetrating normal-risk keratoplasty was performed in two groups of patients (group I with 0-2, group II with 3-6 mismatches in the A/B/DR loci). Surgery was done by 3 experienced surgeons according to a standardized scheme. Also, postoperative therapy and controls were standardized. There were no statistically significant differences between the two study groups as regards number of AB0 or H-Y compatibilities, patient age, patient gender, ratio of previous intraocular surgery, ratio of triple procedures, indication for surgery, follow-up period, donor age, donor gender, post-mortem time of the graft and endothelial cell density of the graft at the end of organ culture. HLA typing was performed in a quality-controlled laboratory, serologically for HLA class I (A and B loci) and moleculargenetically for HLA class II (DR locus). RESULTS: Four years postoperatively, the ratio of clear and rejection-free graft survival was 91% in group I and 67% in group II (Kaplan-Meier estimation, log rank test, p = 0.03). Monovariate analysis in the Cox model gave no influence of solitary HLA class I or II matching, but only an influence of combined HLA class I and II matching (p = 0.03). CONCLUSIONS: In this monocenter study with proper typing techniques the beneficial effect of HLA class I plus II matching on clear and rejection-free graft survival could be demonstrated in a homogenous group of normal-risk keratoplasty patients.

Cornea↗
PubMed2002

Adjunctive intracameral application of corticosteroids in patients with endothelial immune reactions after penetrating keratoplasty: a pilot study.

This study was performed to gain first experiences with a new adjunctive measure in the treatment of endothelial immune reactions after penetrating keratoplasty, i.e., intracameral injections of corticosteroids. In eight penetrating keratoplasty patients with mild endothelial immune reactions (IM1), 10 patients with moderate endothelial immune reactions (IM2) and 10 patients with severe endothelial immune reactions (IM3) intracameral injections of corticosteroids were performed within 24 h after referral to the clinic, following informed consent. All patients (IM1-3) received basic therapy of steroid eye drops and subconjunctival steroid injections; patients in group IM3 also received oral steroids. In IM1 patients eight of eight grafts, in IM2 eight of 10 grafts and in IM3 five of 10 grafts remained clear during a mean follow-up of 9.9 (1-20), 10.7 (3-17) and 9.6 (1-20) months after intraocular intervention. Only one of the 28 patients developed a further immune reaction during follow-up. No complications of intracameral injection were observed. Intracameral steroid injections thus seem to be a safe and helpful therapeutic measure in the treatment of moderate and severe endothelial immune reactions after penetrating keratoplasty. Further investigations in controlled randomized trials are necessary.

Adrenal Cortex Hormones↗
PubMed2002

Soluble Fas ligand and transforming growth factor beta2 in the aqueous humor of patients with endothelial immune reactions after penetrating keratoplasty.

BACKGROUND: Excellent long-term prognosis of penetrating corneal grafts has been explained by the immunological privilege of the cornea and the anterior chamber. In animal models the secretion of transforming growth factor beta(2) (TGF-beta(2)) into the anterior chamber and the expression of the Fas ligand on corneal endothelial cells were identified as important for the integrity of the immunological privilege. OBJECTIVE: To determine the TGF-beta(2) and soluble Fas ligand (sFasL) levels in the aqueous humor of patients after penetrating keratoplasty (PK) who have and who do not have immune reactions. METHODS: Anterior chamber puncture was performed in 13 patients who had a cataract without PK (group 1), in 31 patients after PK who did not have immune reactions (group 2), and in 12 patients after PK newly diagnosed as having endothelial immune reactions (group 3). Total TGF-beta(2) and sFasL were determined via enzyme-linked immunosorbent assay. RESULTS: Transforming growth factor beta(2) was detected in all patients, irrespective of the underlying condition; there was no difference in TGF-beta(2) levels between the different groups (P =.89, analysis of variance). None of the patients in group 1, 11 of 31 patients in group 2, and 8 of 12 patients in group 3 had detectable sFasL concentrations (P =.002, chi(2) test). Soluble Fas ligand averaged (mean [SD]) 20.8 (31.1) pg/mL in group 2, and 38.1 (33.2) pg/mL (P<.01, analysis of variance) in group 3. CONCLUSIONS: It appears that total TGF-beta(2) is maintained at high steady-state levels, while the level of sFasL is up-regulated in patients who underwent PK, particularily in the advent of graft rejection.

Aged↗
PubMed2002

The effects of cidofovir 1% with and without cyclosporin a 1% as a topical treatment of acute adenoviral keratoconjunctivitis: a controlled clinical pilot study.

OBJECTIVE: To evaluate the efficacy of cidofovir 1% eyedrops with and without cyclosporin A 1% eyedrops as a treatment of acute adenoviral keratoconjunctivitis (AKC). DESIGN: Randomized, controlled trial. PARTICIPANTS: Thirty-four patients with acute adenoviral keratoconjunctivitis of recent onset. METHODS: Patients were divided into 4 treatment groups: 1) cidofovir four times daily, 2) cidofovir 10 times daily, 3) cidofovir four times daily and cyclosporin A four times daily, and 4) sodium chloride four times daily (control). The diagnosis was confirmed by adenoviral polymerase chain reaction from conjunctival swabs. Duration of treatment was 21 days. MAIN OUTCOME MEASURES: Severity of conjunctival injection, conjunctival chemosis, punctate epithelial keratitis during the course of treatment, and presence and severity of corneal subepithelial infiltrates were evaluated by a clinical score. Duration until subjective improvement of symptoms was recorded. RESULTS: The frequency of severe corneal opacities was lower with cidofovir (P = 0.048). Cidofovir was toxic locally to the skin of the eyelids and the conjunctiva in a dose-dependent manner. Symptoms of local toxicity were clinically similar to the signs of the initial viral inflammation. They first appeared 8 to 12 days after beginning of treatment and completely subsided 7 to 28 days after discontinuation of cidofovir. The outcome measures of local inflammation did not differ between the four treatment groups. Cyclosporin A did not alter the course of the infection. CONCLUSIONS: Cidofovir lowers the frequency of severe corneal opacities, but its clinical use 4 to 10 times daily at a 1% concentration is limited by local toxicity. Further clinical studies to find an efficacious yet tolerable dosage regimen of cidofovir, possibly using an improved pharmaceutical preparation, are required.

Acute Disease↗
PubMed2002

Chronic endophthalmitis mimicking an endothelial immune reaction after penetrating keratoplasty.

We describe a patient with chronic inflammation after combined penetrating keratoplasty and cataract surgery. This condition has been considered an unusual endothelial immune reaction. Cytopathological examination of the aqueous humor showed abundant neutrophil granulocytes, a few macrophages, and sparse lymphocytes. The predominance of neutrophil granulocytes but no macrophages or lymphocytes, as found in cases of an endothelial immune reaction, was interpreted as evidence of chronic endophthalmitis. Cytopathological evaluation of aqueous humor can be a helpful tool for differentiating between an endothelial immune reaction and chronic endophthalmitis after combined PKP and cataract surgery.

Antibody Formation↗
PubMed2002

[Topical Fk506 in inflammatory corneal and conjunctival diseases. A pilot study].

BACKGROUND: Topical corticosteroids are the only effective measure in serious inflammatory corneal and conjunctival diseases. Although results obtained with topical cyclosporin A are encuraging it is not effective in all patients. The mode of action of Fk506 is similar to that of cyclosporin A, i.e. it exerts an inhibitory effect on transcription of interleukin 2 in T lymphocytes. The immunosuppressive potential of Fk506, however, is much larger. Furthermore, it penetrates more easily into cornea and conjunctiva. To find out whether the theoretical advantages of topical Fk506 can be translated into clinical practice, a selected group of patients refractory to conventional therapy was treated in this pilot study. PATIENTS AND METHODS: Fk506 0.06 % was administered initially three times daily in 15 patients with atopic blepharokeratoconjunctivitis, Mooren's ulcer, ocular pemphigoid, Thygeson's superficial punctate keratitis, nummular adenoviral keratitis, graft-versus-host reaction of the conjunctiva and steroid response glaucoma after penetrating keratoplasty. RESULTS: Within a follow-up of 26 +/- 15 weeks improvement was recorded in 5/15 patients and stabilization in 5/15 patients. In two patients progression of the disease was noted (one patient with progression of ocular pemphigoid, another patient with suspected automutilation). Premature withdrawal the drug was judged to be necessary in two patients with ocular surface disorders and in one patient with non-compliance. CONCLUSIONS: Topical Fk506 seems to be a promising new immunosuppressive drug for patients with atopic blepharokeratoconjunctivitis, Thygeson's superficial punctate keratitis and nummular adenoviral keratitis. Exact efficacy in these and other corneal and conjunctival inflammatory diseases has to be determined in randomised clinical studies. Before these studies may start the risk of side-effects must be reduced via an improvement of the drops.

Adult↗
PubMed2002

[Chronic endothelial cell loss of the graft after penetrating keratoplasty: influence of endothelial cell migration from graft to host].

BACKGROUND: Chronic endothelial cell loss of the graft is common after penetrating keratoplasty. Some kind of subclinical immunological reaction that is not visible at the slitlamp has been suspected as main cause for this phenomenon. Furthermore, migration of graft endothelial cells towards the host cornea has been discussed to add to this loss in special cases. In this study, 3 homogenous patient groups with similar risk of immunological reactions were examined. Main difference between these groups was the potential of graft endothelial cells to migrate towards the host cornea. PATIENTS AND METHODS: Patients with keratoconus without cataract surgery (group I with little migration potential, n = 273), patients with Fuchs endothelial dystrophy without/with cataract surgery (groups IIa/IIb with moderate migration potential, n = 89/n = 165) and patients with bullous keratopathy after cataract surgery (group III with potentially large migration tendency, n = 188) were included in the study. All patients had a first keratoplasty. Patients with glaucoma or further intraocular procedures after keratoplasty were excluded from the study. Clear graft survival and ratio of grafts without immune reactions were estimated according to Kaplan and Meier. Endothelial analysis concerned only patients without immune reactions and with at least 3 postoperative endothelial cell density values of the graft center (76 patients in I, 18 patients in IIa, 41 patients in IIb and 23 patients in III). RESULTS: Mean relative loss of endothelial cells per year was 14.0 +/- 19.0 % in group I, 17.0 +/- 19.1 % in group IIa, 20.8 +/- 18.2 % in group IIb and 29.4 +/- 17.6 % in group III (ANOVA, p < 0.01). Five years postoperatively in group I 99 %, in group IIa 98 %, in group IIb 93 % and in group III 69 % of the grafts were centrally clear (log rank test, p < 0.001). In the same period in group I 88 %, in group IIa 86 %, in group IIb 83 % and in group III 81 % of the grafts were free of immune reactions (log rank test, p < 0.05). Reasons for irreversible graft failure were immune reactions (0 in group I; 0 in group IIa; 1 in group IIb; 9 in group III, ), surface disorders (1 in group I; 0 in IIa; 1 in group IIb; 3 in group III) and endothelial failure (0 in group I; 1 in group IIa; 5 in group IIb; 6 in group III) (chi square test, p < 0.01). CONCLUSIONS: In patients with bullous keratopathy endothelial cell loss via migration seems to add significantly to the general chronic loss which is suspected to be immunological. Peripheral migration of endothelial cells, therefore, most probably contributes to limited prognosis of patients with bullous keratopathy in terms of clear graft survival. In consequence, corneal grafts for bullous keratopathy should be as large as immunologically tolerable, and endothelial cell density should be as high as possible in order to counteract this special endothelial loss factor.

Adult↗
PubMed2002

[Epithelial damage of corneal grafts after prolonged storage in dextran-containing organ culture medium - a prospective study].

BACKGROUND: High-molecular dextran added to organ culture medium is used for deswelling of corneal grafts before surgery. As we had the impression to have more often epithelial desquamation if storage time in dextran-containing medium was longer than 1 day, we investigated this problem in a pilot study. METHODS: We examined prospectively the effect of the storage period on the graft epithelium one day after penetrating keratoplasty in 137 corneal grafts which were stored in dextran-containing storage medium (dextran T500 6 %). 88 corneal grafts were stored for 1 - 2 days (12 - 48 hours) and 49 corneal grafts were stored for 3 - 4 days (60 - 96 hours). Before deswelling, all 137 grafts had been stored 10 - 14 days in dextran-free organ culture medium. Postoperative epithelial defects observed 1 day after surgery were classified as margin and central erosions of the graft. RESULTS: With a storage period in dextran-containing organ culture medium of 1 - 2 days statistically significantly less epithelial defects were observed in comparison to a longer storage period of 3 - 4 days (33 % vs. 57 %, p = 0,005). We found a statistically high significant correlation between storage time in dextran-containing organ culture medium and central erosions (p = 0,001), whereas margin erosions were observed after 1 - 2 days as well as after 3-4 days (p = 0,2). CONCLUSION: Our data show that early postoperative epithelial stability of corneal grafts depends on the storage period in dextran-containing organ culture medium.

Corneal Diseases↗
PubMed2002

Immune cells in the anterior chamber of patients with immune reactions after penetrating keratoplasty.

PURPOSE: Lymphocytes, monocytes, and macrophages are the predominating immune cells in graft rejection after keratoplasty in animal models. This study focuses on the isolation of immune cells from the anterior chamber of patients with slight, moderate, and severe endothelial immune reactions after penetrating keratoplasty. METHODS: Anterior chamber puncture was performed in five patients with cataract without inflammation and without penetrating keratoplasty (C1), in three patients undergoing penetrating keratoplasty without immune reactions (C2), in four patients undergoing penetrating keratoplasty after complete resolution of endothelial immune reactions (C3), in seven patients undergoing penetrating keratoplasty with slight endothelial immune reactions (IMI), in 10 patients undergoing penetrating keratoplasty with moderate endothelial immune reactions (IM2), and in eight patients undergoing penetrating keratoplasty with severe endothelial immune reactions (IM3). In each patient, approximately 0.1 mL of aqueous humor was examined. Cells in suspension were directly centrifuged on glass slides using a Cytospin centrifuge, stained, and evaluated under the light microscope. RESULTS: Groups C1, C2, and C3 did not contain cells. Immune cells were identified in three of seven patients in IM1, in eight of 10 patients in IM2, and in eight of eight patients in IM3. Predominating cells were macrophages and monocytes followed by lymphocytes. Regarding all patients in IMI, IM2, and IM3, a statistically significant correlation between detected cells and patient age, period between penetrating keratoplasty and anterior chamber puncture, or period between first symptoms and anterior chamber puncture could not be revealed. Granulocytes were found statistically significantly less often in patients with high-risk indications, in patients with a history of immune reactions and under immunosuppression. Lymphocytes were found statistically significantly less often in patients with a history of immune reactions. CONCLUSIONS: The probability to isolate immune cells from the anterior chamber of patients undergoing penetrating keratoplasty correlates with the severity of the endothelial immune reactions. This study is a first step to evaluate how detailed immunologic findings from animal keratoplasty models fit to clinical reality in patients undergoing keratoplasty. In the next step, cells found in the aqueous humor of patients with endothelial immune reactions should be further characterized directly (determination of molecules on the surface of the cells) or indirectly (determination of cytokine levels in the aqueous humor).

Adult↗
PubMed2002

Synergism of RAD and cyclosporin A in prevention of acute rat corneal allograft rejection.

PURPOSE: The novel immunosuppressant RAD, 40-0-(2-hydroxy-ethyl)-rapamycin, has synergistic effects with cyclosporin A. The aim of this study was to evaluate the combined effect of RAD and cyclosporin A in the prevention of acute allograft rejection after murine corneal transplantation. METHODS: Fisher donor corneas were implanted into Lewis recipients. Postoperative evaluation included slit-lamp biomicroscopy and immunohistology. Treatment groups were comprised of rats treated orally with RAD 2.5 mg/kg/day, cyclosporin A 10 mg/kg/day, RAD 1.5 mg/kg/day plus cyclosporin A 5 mg/kg/day. RESULTS: Therapy with RAD 2.5 mg/kg and cyclosporin A 10 mg/kg led to a statistically significant and comparable prolongation of transplant survival. However. combination therapy was significantly superior. There was a significant reduction in the number of infiltrating cells in the animals treated with RAD and cyclosporin A. CONCLUSIONS: This is the first study on the efficacy of a double drug regimen with RAD and cyclosporin A for the control of acute corneal allograft rejection. Combination therapy resulted in superior graft survival.

Acute Disease↗
PubMed2002

Influencing factors on chronic endothelial cell loss characterised in a homogeneous group of patients.

BACKGROUND/AIM: Advanced donor age, long death to excision time interval, and factors related to organ culture can trigger unfavourable intracellular processes in the graft endothelium and contribute to chronic endothelial cell loss after penetrating keratoplasty. The aim of this study was to investigate factors influencing chronic endothelial cell loss in a homogeneous group of patients. METHODS: 177 patients after first normal risk keratoplasties for keratoconus were retrospectively selected from the quality control database of our clinic. For 71 of them at least four central endothelial cell density values were documented in follow up. From these patients, only those 53 without any further intraocular procedures, without glaucoma, and without graft rejection were considered. A scatter plot of logarithmised endothelial cell density values against postoperative time was drawn for each patient. The slope of the regression line then equals the constant of decay in central endothelial cell density. The influence of donor age and storage time in organ culture on this index value of cell loss was investigated by means of linear regression analysis. RESULTS: Mean loss of central endothelial cell density was 16.7% per year. Regression analysis revealed a statistically significant negative linear effect of both postmortem time (beta = -0.324; p = 0.014) and donor age (beta = -0.282; p = 0.036) and a trend for storage time in organ culture (beta = -0.195; p = 0.142) in a combined linear regression model. CONCLUSION: Increased postmortem time and advanced donor age exert a significant negative effect on chronic endothelial cell loss. Storage time in organ culture seems to be third influencing factor. These negative influences may be reduced by compensating advanced donor age with minimised postmortem and storage time.

Age Factors↗