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Purpose: To report the long-term stability of paired arcuate corneal keratotomies (AKs) in patients with high regular postpenetrating keratoplasty astigmatism., Methods: Retrospective chart review of best-corrected visual acuity, refraction and keratometric values of 41 eyes with AK between 2003 and 2012., Results: Magnitude of median target induced astigmatism vector was 9.2 dioptres (Dpt). We reached a median magnitude of surgically induced astigmatism vector of 9.81 Dpt and a median magnitude of difference vector of 5.5 Dpt. In keratometry, we achieved a net median astigmatism reduction by 3.3 Dpt. The average correction index was 1.14, showing a slight overcorrection. Irregularity of keratometric astigmatism increased by 0.6 Dpt, and spherical equivalent changed by 1.75 Dpt. Monocular best spectacle corrected visual acuity increased from preoperatively 20/63 (0.5 logMAR) to 20/40 (0.3 logMAR) postoperatively. Median gain on the ETDRS chart was two lines. Long-term follow-up showed a median keratometric astigmatic increase by 0.3 Dpt per year., Conclusion: Arcuate corneal keratotomies is a safe and effective method to reduce high regular corneal astigmatism following penetrating keratoplasty but has limited predictability. The long-term follow-up shows an increase of keratometric astigmatism by 0.3 Dpt/year, equalizing the surgical effect after 10 years., (© 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: Astigmatism is a significant problem in penetrating keratoplasty. Lower astigmatism and better visual outcomes had been expected from laser-assisted penetrating keratoplasty, that is, from the top-hat, mushroom, or zig-zag cutting profiles. We report the long-term outcomes of 141 femtosecond laser-assisted penetrating keratoplasties retrospectively. We compare these outcomes with those of penetrating keratoplasty using the guided trephine system (GTS)., Methods: In all, 141 femtosecond laser-assisted penetrating keratoplasties had been performed in 119 patients. The results were compared with those of conventional keratoplasty (n = 1254; visual and refractive outcomes, graft rejections, and graft failure)., Results: Follow-up averaged 33 months. In eyes with keratoconus, the time to achieve a visual acuity of 10/20 (Snellen) was shorter in the mushroom than in the GTS group. However, there was no relevant long-term difference. Graft astigmatism was higher in the laser groups [keratometric astigmatism at the end of follow-up: -4.5 ± 4 (GTS), -5.8 ± 3.3 (top-hat), -5.9 ± 3.2 D (mushroom); P < 0.01]. In eyes with keratoconus, rates of graft rejection were highest in the mushroom group (55%). In the other groups, top-hat keratoplasty resulted in lower rates of rejection than GTS keratoplasty (31%)., Conclusions: There is no significant difference in the refractive and visual outcomes after femtosecond laser-assisted penetrating keratoplasty compared with GTS keratoplasty. The benefits from the use of the femtosecond laser may be limited and should be weighed against an increased risk of immune reactions, higher surgical complexity, and higher costs.

Background: Postoperative astigmatism following penetrating keratoplasty is a major problem after corneal transplantation. The main goal of new trephination techniques such as femtosecond laser or excimer-laser trephination is to improve refractive and visual outcomes. The femtosecond laser technique makes profiled corneal trephinations such as the top hat or mushroom profile possible. We present the postoperative outcome of femtosecond laser-assisted penetrating keratoplasties., Methods: We performed 123 femtosecond laser-assisted penetrating keratoplasties in 119 patients. The main outcome measures were intraoperative specifics, astigmatism, and irregularity in Orbscan corneal topography, as well as the occurrence of immune reactions and side-effects., Results: All sutures have been removed in 49 of these 123 eyes. Their mean follow-up was 13.9 ± 4.5 months. Time to complete suture removal (n = 49) was 12.0 ± 3.7 months in the mushroom group and 9.8 ± 2.1 months in the top hat group. Mean astigmatism in Orbscan topography was 6.4 ± 3.0 diopters in the mushroom and 5.8 ± 4.6 diopters in the top hat group (all sutures out)., Conclusions: Femtosecond laser-assisted penetrating keratoplasty is a safe surgical technique. Due to the steps in profiled trephinations, the wound area is larger and theoretically the wound healing is, thus, faster and more stable. Complete suture removal is possible at an earlier time point compared to conventional penetrating keratoplasty. However, refractive results are not superior to those following conventional trephination.

Purpose: The femtosecond laser is a new option for cutting corneal tissue at high precision. The "top-hat" profile has an overlapping graft-host interface at the edge because of a larger inner trephination diameter. This may enhance graft fixation, thus improving the outcome and accelerating rehabilitation after penetrating keratoplasty., Methods: Femtosecond laser top-hat keratoplasties with overlaps of 0 and 3 mm between inner and outer trephination diameters were performed in vitro. After trephination, the excised corneal buttons were readapted by different suturing profiles. Pressure in the artificial anterior chamber was then raised until we observed wound leakage and ultimately wound prolapse., Results: Better wound stability was found in conjunction with all profiled trephinations. When using 4 interrupted sutures, wound leakage occurred at a median of 13.0 cm H2O (mean, 12.3 cm H2O) and "zero overlap," at 19.0 cm H2O (mean, 20.8 cm H2O) and 1-mm overlap, at 32.0 cm H2O (mean, 32.8 cm H2O) and 2-mm overlap, and at 48.5 cm H2O (mean, 49.4 cm H2O) and 3-mm overlap. Comparing zero overlap with the mean values of 1- to 3-mm overlaps, wound leakage happened at 13.0 (mean, 12.3) versus 32.0 (mean, 34.3) cm H2O with 4 interrupted sutures, at 57.5 (mean, 58.3) versus 61.0 (mean, 70.8) cm H2O with 8 interrupted sutures, at 31.5 (mean, 32.0) versus >97.0 (mean, 75.5) cm H2O with 1 running and 4 interrupted sutures, and at 34.0 (mean, 32.3) versus 80.0 (mean, 69.9) cm H2O with 1 running suture. The analysis of variance revealed a statistically significant increase in wound stability for all overlaps independently from the size of the overlap., Conclusions: Femtosecond laser-assisted profiles with even small overlaps for penetrating keratoplasty may make fewer sutures and earlier suture removal possible because of better wound stability, contributing to earlier visual recovery and helping to prevent wound rupture after trauma. However, further study is required to identify the optimum profile including the various technical parameters.

Objective: To present the technique and report the results of up to 36 months after allogenic central penetrating limbo-keratoplasty in conjunction with conjunctivoplasty, mitomycin C (MMC), and amniotic membrane (AM) transplantation in patients with bilateral limbal stem cell deficiency (LSCD)., Design: Retrospective, consecutive subject cohort study., Participants: Case records of 20 eyes from 20 patients who presented with bilateral LSCD due to aniridia, chemical/thermal burn, cicatrizing pemphigoid, and chronic ocular surface inflammation and who were treated at the University Eye Hospital, Freiburg., Methods: All eyes were treated with central limbo-keratoplasty in conjunction with conjunctivoplasty, MMC, and AM. There were 20 human leukocyte antigen-typed allolimbal transplants from cadaveric donors. All patients received systemic immunosuppression with mycophenolate mofetil or cyclosporine A., Main Outcome Measures: Surgical success was measured by the duration for which a healthy corneal epithelium was maintained. Visual success was measured by an improvement in visual acuity (VA) in the eye during follow-up and directly correlated with central clear graft survival., Results: The follow-up period was up to 34 months (mean, 20 months; median, 22.4 months). Mean VA, measured in decimal fractions, increased from 0.029 (∼20/400; median, 0.005; first quartile 0.005; third quartile 0.005) before surgery to 0.281 (20/70; median, 0.2; first quartile 0.04; third quartile 0.55) after surgery. Healthy corneal epithelium showing survival of limbal stem cells was observed in 14 eyes (70%) during complete follow-up., Conclusions: Penetrating limbo-keratoplasty with conjunctivoplasty, MMC, and AM transplantation is a promising new surgical technique for improving vision and conjunctivalization in patients with severe bilateral LSCD necessitating allogenic transplants., (Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

The femtosecond laser technique allows completely new trephination procedures in penetrating and lamellar keratoplasty. With femtosecond laser-assisted penetrating keratoplasty it is possible to perform profiled trephination, such as top hat and mushroom profiles. Thus, it is easier to get a watertight wound closure intraoperatively and due to the larger wound surface wound healing is faster and allows early complete suture removal. In lamellar keratoplasty the femtosecond laser enables the surgeon to cut to any depth in the corneas resulting in thin corneal donor buttons, e.g. for DSAEK. In this manuscript an overview is given of the state of the art and of the perspectives of femtosecond laser keratoplasty.

Purpose: Postoperative astigmatism after penetrating keratoplasty is a major problem in corneal transplantation. The purpose of this prospective randomized study was to evaluate the efficacy and safety of an intrastromal corneal ring after penetrating keratoplasty., Methods: Twenty patients were included, 10 of whom received an intracorneal ring (group 1) and 10 who did not (group 2, control group). Astigmatism in Orbscan corneal topography, occurrence of immune reactions, and occurrence of side effects were this study's main outcome criteria., Results: Mean follow-up time was 27.6 ± 5.3 months. Mean astigmatism (Orbscan) was 4.4 diopters in group 1 and 4.4 diopters in group 2 (P = 0.695). Spontaneous suture rupture occurred in 5 patients with corneal ring but in none of those in the control group. We observed 3 immune reactions in 3 patients with corneal ring, whereas group 2 experienced no rejection (P < 0.05). Endothelial cell loss was 15.1% in the group with the ring and 8.7% in the control group. That difference was not statistically significant (P = 0.146)., Conclusions: The use of the intrastromal corneal ring after penetrating keratoplasty caused no reduction in postoperative astigmatism. However, its use was statistically significantly associated with adverse events.

Purpose: Penetrating keratoplasty can restore vision in corneal blindness. However, immunologic rejection threatens graft survival. Matching donors at swine leukocyte antigen (SLA)-class II convey allo-specific tolerance in a large animal kidney-transplantation model despite mismatches at SLA-class I. The same matching pattern seems to account for the blood transfusion effect in kidney transplantation. Relying on the molecular basis of HLAMatchmaker eplets, we assessed whether this finding would also apply to keratoplasty, and if it would enhance the benefit from matching human leukocyte antigen (HLA)-class I alone., Methods: We retrospectively selected two independent cohorts comprising 586 and 975 penetrating keratoplasties. Our computations revealed a quantitative tolerogenicity factor analogous to the animal model. The number of mismatched HLA-class I eplets functioned as a factor for conventional histocompatibility. In the first cohort, we empirically determined the thresholds with the highest predictive power on graft rejection for both factors, and confirmed those thresholds in the second cohort. We applied Cox proportional hazards regression for these analyses., Results: The thresholds with highest predictive power revealed 220 eplets(2) for the tolerance factor and 10 eplets for HLA-class I histocompatibility. The respective hazards ratios were 2.22 (p=0.04) versus 3.63 (p<0.01) in the first cohort and 2.09 (p<0.01) versus 1.51 (p=0.02) in the second, confirmatory cohort. The threshold factors proved to be additive in predicting immune reactions in both cohorts, (hazard ratios 2.66 in cohort 1 versus 1.70; p<0.01 in cohort 2)., Conclusions: Operational tolerance may be inducible by balanced matching of HLA-class I and II HLAMatchmaker eplets. Furthermore, such tolerance is additive to histocompatibility at HLA-class I.

Aim: To present a novel interpretation of the biexponential nature of chronic endothelial cell loss after penetrating keratoplasty (PK). We hypothesize that the fast component of endothelial cell loss reflects the endothelial cells of graft origin. The slow component might just reflect cell loss of the recipient endothelium. We investigate herein whether this hypothesis is in line with long-term survival in bullous keratopathy (BK: almost no endothelium in the recipient bed) and keratoconus (KK: recipient bed with plenty of endothelium)., Methods: We reviewed endothelial graft failures in PK for BK (n = 88) and KK (n = 87). Patients with immune reactions or a history of glaucoma were excluded. We built a statistical model to predict graft failures from biexponential endothelial cell loss and compared this data to the actual outcomes., Results: After 15 years, the incidence of late endothelial failures was 8% in KK and 33% in BK. The 95% confidence intervals of the simulated outcomes corresponded completely to the actual outcomes during follow-up., Conclusions: Our novel interpretation of the biexponential model is in line with long-term data of PK for BK and KK. Our findings highlight the importance of the recipient bed endothelial reservoir on the long-term prognosis in PK.

Background: Penetrating keratoplasty in infants has a very poor outcome compared to adults. It is of intrinsic interest to gain insight into the still unknown immunological mechanisms of graft failure because any form of uncorrected corneal opacity leads to amblyopia., Methods: Allogeneic keratoplasty was performed between Lewis and Fisher rats. The recipients' ages were 10 and 3 weeks, respectively. All experiments were controlled syngeneically. Survival rates were calculated and cellular infiltrates analysed histologically., Results: Median graft survival times were 15 days in old recipients and 9 days in young recipients (p<0.01). There were fewer infiltrating cells in the younger rats than in the older ones on the day of rejection. Despite the fact that T cells dominated there were significantly more NK cells in young recipients at all time points after transplantation when compared to old recipients., Conclusions: An animal model has been established that shows similar rejection kinetics as in children, that is corneal graft failure occurs sooner in young rats. Already little infiltration was sufficient to reject a corneal allograft. The dominance of infiltrating NK cells and the vigorous rejection process suggest an involvement of the innate immune system in this process.

Since 2001 the femtosecond laser has primarily been used in refractive surgery, e. g., for lasik, implantation of intracorneal ring segments or antiastigmatic corneal incisions. However, the femtosecond laser is more and more used for therapeutic reasons in corneal surgery. In this context it is used for profiled trephinations in penetrating keratoplasty where various profiles of the cutting edge can be designed (e. g., top-hat profile, mushroom profile, zig-zag profile). The potential advantages of these profiles include improved graft adaptation, better and more stable wound healing leading to earlier suture removal and eventually prolonged graft survival. However, none of these potential advantages has been demonstrated by reliable study results until now. First clinical experiences show that much earlier suture removal is possible without significant complications. However, with sutures in there seems to be no advantage of the femtosecond laser compared to mechanically guided trephination systems regarding visual acuity and postoperative astigmatism. Besides penetrating profiles, the femtosecond laser also allows for lamellar cuts. As deep anterior lamellar keratoplasty can only be supported by the femtosecond laser, it is mostly used for posterior lamellar grafts in this context. However, first clinical results using the femtosecond laser for DSAEK (descemet stripping automated endothelial keratoplasty) are poorer than those using microkeratome-prepared lamellar grafts for DSAEK., (Georg Thieme Verlag KG Stuttgart, New York.)

Penetrating keratoplasties due to herpetic corneal scars are more often performed compared to persisting Varicella zoster virus infections, which are quite seldom. Penetrating keratoplasties in herpetic corneas are risk keratoplasties due to the vascularisation and the risk of recurrent virus replication. The prognosis in these corneal transplantations has been improved in recent years due to better postoperative medical treatment with virustatics and systemic immunosuppression. Indications for and treatment following penetrating keratoplasty in herpetic eyes are the topics of this review.

The femtosecond laser technique allows completely new trephination methods in penetrating keratoplasty with profiles in the graft and the host cornea. The most common so-called profiled trephinations are the top hat and mushroom profiles. Due to the profile it is easier to get a watertight wound closure intraoperatively and due to the larger wound surface the wound healing is faster and more stable. This will possibly allow an earlier suture removal with final visual rehabilitation. First clinical results show that femtosecond laser-assisted penetrating keratoplasty is a safe surgical procedure. The long term results after complete suture removal will show whether the astigmatism results are better than those of conventional trephination techniques.

Background: The purpose of this prospective, randomised, multicentre study was to prove the efficacy and safety of mycophenolate mofetil (MMF) in preventing graft rejection and in improving clear graft survival following high-risk keratoplasty., Methods: In all, 98 of 140 scheduled patients were included in this study (57 MMF, 41 control). Recruitment was stopped prematurely due to a statistically significant result. The patients in the MMF group received MMF orally 2 x 1 g daily for 6 months. All of the patients received fluocortolone 1 mg/kg/day tapered over 3 weeks and topical prednisolone acetate 5 x /day tapered over 5 months. Main criteria were immune reaction-free and clear graft survival, and the occurrence of side effects., Results: The mean follow-up time was 34.9+/-16.3 (mean+/-SD) months. Eleven patients withdrew from the study (nine patients due to protocol deviation, two because of side effects). Six reversible and two irreversible graft rejections occurred in the MMF group, and five reversible and seven irreversible rejections in the control group. The Kaplan-Meier analysis revealed an immune reaction-free graft survival after the mean follow-up time of 83% in the MMF group and 64.5% in the control group (P=0.044). Graft failure occurred in 10 MMF-treated patients (two due to rejection) and in nine patients in the control group (seven due to rejection). A total of 36 of 57 MMF-treated patients experienced mostly reversible adverse events., Conclusions: Systemic immunosuppression with MMF over 6 months is relatively well tolerated and improves rejection-free graft survival following high-risk keratoplasty statistically significant, even in the long run.

Objectives: To describe an outbreak of toxic anterior segment syndrome (TASS) following penetrating keratoplasty (PK) and to examine its possible causes., Methods: Owing to a series of TASS following PK between June 6, 2007, and October 2, 2007, we reviewed the records of all patients who had undergone PK during that time. In addition to routine microbial tests on organ culture media, we looked for specific pathogens and endotoxins in all of the materials used for organ culture or PK. Furthermore, we analyzed all of the perioperative products and instrument processing., Results: Of the 94 patients who underwent PK, we observed 24 cases of postoperative sterile keratitis. Causal research revealed that the accumulation of cleaning substances or heat-stable endotoxins on the surface of the routinely used guided trephine system was most likely responsible for the TASS., Conclusions: To our knowledge, this is the first report on TASS following PK. Suboptimal reprocessing of surgical instruments may be an important cause of TASS as in this series the TASS-like symptoms resolved after modified instrument-cleaning procedures. The standardization of protocols for processing reusable trephine systems might prevent outbreaks of TASS following PK.

Background: The purpose of the study was to evaluate the efficacy and safety of Krumeichs' intrastromal corneal ring following penetrating keratoplasty. Postoperative astigmatism and occurrence of complications were the main criteria of this study., Material and Methods: A total of 20 patients were included in this prospectively randomized study (10 patients with and 10 patients without corneal ring). Follow-up examinations were performed 6 weeks, 4, 12, and 18 months postoperatively, including best corrected visual acuity and Orbscan corneal topography., Results: The mean follow-up time is currently 18.9+/-2.8 months. The mean astigmatism (Orbscan) is 3.9 D in the group with ring and 4.0 D in the group without a ring. Spontaneous suture rupture occurred in five patients with corneal ring., Conclusions: The use of the intrastromal corneal ring following penetrating keratoplasty caused no reduction of postoperative astigmatism. The reason for the spontaneous suture ruptures is unclear.

We present the case of a 45-year-old patient with severe atopic disease and keratoconus who suffered from corneal melting following cross-linking and deep anterior lamellar keratoplasty (DALK) due to subclinical infection with Herpes simplex virus (HSV). Penetrating keratoplasty and intensive antiviral and immunosuppressive medical treatment were necessary to control the infection. The case demonstrates the difficulties in the treatment of keratoconus in patients with severe atopic disease.

Background: Until now cyclosporin A (CSA) and mycophenolate mofetil (MMF) are the only available systemic immunosuppressants for patients undergoing risk keratoplasty. Basiliximab is a chimeric monoclonal interleukin 2-receptor antibody, which inhibits T-cell proliferation. Basiliximab is approved for the treatment in patients after kidney transplantation. The aim of this study was to prove the efficacy and safety of Basiliximab after penetrating risk keratoplasty., Patients and Methods: 20 patients undergoing risk keratoplasty received as postoperative medication fluocortolon 1 mg/kg/d (tapered off within three weeks) and prednisolone acetate eye-drops 5x/d (tapered off within five months). In addition, 10 patients received 20 mg basiliximab immediately following surgery and four days postoperatively. 10 patients in the control group received oral CSA adapted to the blood-trough level (120-150 ng/mL) for six months., Results: After a mean follow-up time of 477 +/- 263 days 4 patients of the basiliximab group showed corneal immune reactions (2 irreversible), while no side effects were observed. In the CSA group 2 immune reactions occurred (1 irreversible). In 2 CSA-treated patients the CSA administration had to be stopped due to side effects., Conclusions: Basiliximab has a lower efficacy in preventing immune reactions after risk keratoplasty than CSA. However, the side effect profile of basiliximab is more favourable than that of CSA.

Purpose: Aim of this study was to prove the efficacy and safety of the new malononitrilamide immunosuppressive FK778 in prolonging clear graft survival following allogeneic orthotopic keratoplasty in rats., Methods: Sixty-seven penetrating keratoplasties were performed using Fisher and Lewis rats as donors and recipients, respectively: group 1 (n=11), allogeneic control without therapy; group 2 (n=12), syngeneic control; group 3 (n=11), mycophenolate mofetil (MMF) 40 mg/kg bodyweight; group 4 (n=12), FK778 5 mg/kg bodyweight; group 5 (n=12), FK778 10 mg/kg bodyweight; and group 6 (n=9), FK778 20 mg/kg bodyweight. Four animals in each group were killed for immunohistological evaluation on day 14. Therapy was administered orally for 18 days. The grafts were evaluated every three days by means of a scoring system including opacity, oedema, and vascularization. Time to rejection was analysed with the Kaplan-Meier survival analysis and compared with the log-rank test. The densities of infiltrating immune cells were compared statistically using the non-parametric Mann-Whitney test., Results: Mean rejection-free graft survival was 11.4 days in group 1 (allogeneic control), 100 days (total follow-up time) in group 2 (syngeneic control), 24.0 days in group 3 (MMF 40 mg/kg), 15.7 days in group 4 (FK778 5 mg/kg), 19.1 days in group 5 (FK778 10 mg/kg), and 25.4 days in group 6 (FK778 20 mg/kg) (P<0.005)., Conclusions: Systemic immunosuppression with FK778 prolongs graft survival in the rat keratoplasty model. FK778's efficacy is comparable with that of MMF in preventing immunologic graft rejection.

Background: Long-term application of topical steroids following penetrating keratoplasty is disadvantageous due to side effects (steroid response, cataract, surface disorders). In this study we investigated the efficacy of topical pimecrolimus regarding clear graft survival following allogeneic orthotopic keratoplasty in rats., Methods: A total of 46 penetrating keratoplasties were performed using Fisher rats (allogeneic groups) and Lewis rats (syngeneic group) as donors and Lewis rats as recipients: group 1 (n = 11), allogeneic control without therapy; group 2 (n = 12), syngeneic control; group 3 (n = 11), mycophenolate mofetil (MMF) 40 mg/kg body weight; group 4 (n = 12), pimecrolimus 1% ointment twice daily. Four animals of each group were sacrificed for immunohistological evaluation on day 14. Therapy was administered for 18 days. The grafts were evaluated once every 3 days regarding opacity, oedema and vascularisation. Graft rejection was defined as total graft opacity., Results: Mean rejection-free graft survival was 11.4 days in group 1 (allogeneic control), 100 days (total follow-up time) in group 2 (syngeneic control), 24.0 days in group 3 (MMF 40 mg/kg) and 11.6 days in group 4 (topical pimecrolimus). The immunohistological evaluation showed no statistically significant difference in cell infiltration of the grafts comparing groups 1 and 4., Conclusions: Topical immunosuppression with pimecrolimus does not prolong graft survival in the allogeneic keratoplasty rat model.

Immune reaction is the main cause for graft failure following penetrating keratoplasty. Endothelial immune reaction is the most frequent and most dangerous subtype of rejection because destruction of the graft endothelium can lead to graft failure. "Acute" endothelial rejection is treated by administration of topical and systemic steroids. Intracameral application of corticosteroids by means of an anterior chamber flush is an adjunctive measure that can stop the immune reaction immediately. This measure is thus recommended in all intermediate and severe endothelial rejections.

Topical steroids are routinely used in the postoperative treatment following penetrating keratoplasty. Due to the known side effects such as steroid-response glaucoma, cataract, and surface disorders, a broader armamentarium of topical immunomodulating drugs with comparable efficacy, better tolerance and less side effects is desirable. Cyclosporine A and FK506 eye drops are a promising alternative. A new approach involves subconjunctival drug delivering implants and locally applied antiangiogenic substances, which still have to be tested in clinical studies.

Immunologic rejection is the main cause of corneal graft failure. If corneal transplantation is performed in a high-risk situation without the use of systemic immunosuppression, corneal graft failure has to be expected in over 50% of patients within the first postoperative year. The clonal expansion of graft-specific lymphocytes occurs in lymphoid tissues. As topical steroids do not reach the secondary lymphoid organs, and even systemic steroids do not interfere sufficiently with the clonal expansion of activated T cells, it is essential to administer systemic immunosuppressives in order to achieve clear graft survival. As corneal transplantation is not a life-saving procedure, the profile of side-effects is a central issue when choosing an immunosuppressive medication.

Background: Graft-prognosis after penetrating high-risk keratoplasty has improved considerably with the use of systemic immunosuppressive medications. In this retrospective investigation we analyzed the long-term results of 417 high-risk keratoplasties with systemic immunosuppression (cyclosporine A [CsA] or mycophenolate mofetil [MMF])., Methods: A total of 417 high-risk keratoplasties with postoperative systemic immunosuppression were evaluated retrospectively: CsA has been given in 252 keratoplasties since 1987, aiming at blood trough levels of 120 to 150 ng/mL. Systemic MMF at a daily dose of 2 x 1 g was administered in 149 surgical procedures. After 16 high-risk keratoplasties, combined systemic immunosuppression with CsA and MMF was administered. Systemic immunosuppression was scheduled for 6 to 12 months. All patients received fluocortolone 1 mg/kg body weight per day, tapered over 3 weeks, and topical prednisolone acetate 1%, tapered over 5 months., Results: Rejection-free graft survival after 1 year was 75% in the CsA group and 89% in the MMF group; 60% of the grafts in the CsA group and 72% of the grafts in the MMF group were rejection-free 3 years postoperatively (Kaplan-Meier log-rank test P=0.03). Clear graft survival after 1 and 3 years was 92% and 77% (CsA) and 96% and 87% (MMF), respectively. The MMF-treated patients showed fewer side effects than the CsA-treated patients. The side effects attributable to both drugs were reversible., Conclusions: We found a statistically significant, stronger effect of MMF compared with CsA in preventing immune reactions after high-risk keratoplasty, despite a shorter MMF administration compared with CsA. Both systemic immunosuppressants were shown to have comparable potency regarding clear graft survival and were well tolerated.

Purpose: To investigate whether it may be possible to ascertain the influence of immunological factors on chronic endothelial cell loss by comparing chronic endothelial cell loss after autologous rotational penetrating keratoplasty and after homologous penetrating keratoplasty., Methods: For six patients who had undergone autologous rotational penetrating keratoplasty the relative annual loss of endothelial cells was calculated by means of an exponential regression analysis. The findings were compared with those in a homogeneous historical control group (53 patients undergoing homologous penetrating keratoplasty for keratoconus)., Results: After autologous rotational keratoplasty relative annual loss of endothelial cells was 1.1%+/-2.6% (mean +/- standard deviation). Relative annual loss of endothelial cells in the control-group was 16.7%+/-20.8%., Conclusions: The results of the study lead to the assumption that immunological influences might be the main cause for chronic endothelial cell loss after homologous penetrating keratoplasty.