Florian Birnbaum

Long-term graft survival in penetrating keratoplasty: the biexponential model of chronic endothelial cell loss revisited.

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.

FTY720 prolongs clear corneal allograft survival with a differential effect on different lymphocyte populations.

Background: FTY720 is a potent immunomodulator with unique effects on lymphocyte homing and has recently proved to be safe and effective in renal transplantation in man. The authors investigated the potency of FTY720 in inhibiting allograft rejection in the rat model of orthotopic allogeneic penetrating keratoplasty. Methods: Penetrating keratoplasties were performed using Fisher rats as donors and Lewis rats as recipients or donors: group 1 (n = 10), allogeneic control; group 2 (n = 10), Lewis/Lewis syngeneic control; group 3 (n = 9), mycophenolate mofetile (MMF) 40 mg/kg; group 4 (n = 10), FTY720 1.2 mg/kg; group 5 (n = 8), FTY720 0.3 mg/kg. Four animals from each group were sacrificed for immunohistological evaluation on day 14. Medication in the therapy groups was given for 18 days. Results: The mean (SD) rejection free graft survival time was 11.3 (0.8) days for the allogeneic control (group 1), 24.6 (2.5) days for group 3 (MMF), 44.5 (5.7) days for group 4 (FTY720 1.2 mg/kg), and 35.3 (5.7) days for group 5 (FTY720 0.3 mg/kg) (p<0.05). The allogeneic control showed a dense infiltration with CD4+, CD8+, CD161+ (NK-cells), CD25+ (IL2 receptor), and macrophages. In the therapy groups the density of infiltrating CD4+, CD8+, CD161+ (NK-cells), and CD25+ (IL2 receptor) cells was notably reduced compared with the allogeneic control (p<0.05). In group 5 however, the reduction of infiltration by CD4+ cells was higher than the reduction of infiltration by CD8+ (p<0.05) and CD161+ (NK) cells. Discussion: Oral immunosuppression with FTY720 significantly prolongs corneal allograft survival in this transplant model. The results suggest that FTY720 has a different effect on certain lymphocyte populations. CD4+ cells seem to be more affected than CD8+ cells and NK-cells.

Endothelial cell loss after autologous rotational keratoplasty

PurposeTo 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.MethodsFor 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).ResultsAfter 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%.ConclusionsThe 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.

An open prospective pilot study on the use of rapamycin after penetrating high-risk keratoplasty.

Background. The purpose of this study was to prove efficacy and safety of systemic immunosuppression with rapamycin following penetrating high-risk keratoplasty. Rapamycin has shown its immunosuppressive potential in the rat keratoplasty model and is a component of several immunosuppressive protocols after solid organ transplantation. In this pilot study, we compared the efficacy and safety of rapamycin and mycophenolate mofetil (MMF). Methods. Ten patients (group 1) undergoing high-risk keratoplasty were included in this study, receiving rapamycin as postoperative immunoprophylaxis. Rapamycin was administered orally once daily (blood trough level 4–10 ng/ml) for 6 months. Thereafter, it was tapered over 2 weeks. The control group (group 2) consisted of 24 patients who received 1000 mg MMF twice daily for 6 months. All of the patients received postoperative medication with fluocortolone 1 mg/kg/day (tapered over 3 weeks) and prednisolone acetate eyedrops 5 times per day (tapered over 5 months). Results. Mean follow-up of all patients (n=34) was 739 days. No immune reaction was observed in groups 1 and 2 during the first 6 months under immunosuppression. Two immune reactions occurred in group 1, and five in group 2 within a 2-year follow-up. All of the immune reactions were reversible. The side effects observed in both groups were mostly reversible. Conclusions. Rapamycin and mycophenolate mofetil seem to be similarly efficacious in preventing immune reactions after high-risk keratoplasty, as long as they are administered. However, we observed a broad spectrum of side effects from rapamycin.

Allogenic limbo-keratoplasty with conjunctivoplasty, mitomycin C, and amniotic membrane for bilateral limbal stem cell deficiency.

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.

Toxic Anterior Segment Syndrome Following Penetrating Keratoplasty

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.

Systemic immunosuppressives after penetrating keratoplasty

ZusammenfassungDie immunologische Abstoßungsreaktion ist der wichtigste Grund für ein Transplantatversagen nach Hornhauttransplantation. Ohne systemische Immunsuppression kommt es in einer Hochrisikosituation in über 50% der Fälle zu einer Eintrübung des Transplantats innerhalb des ersten postoperativen Jahres. Die klonale Expansion von alloreaktiven Lymphozyten findet in lymphoiden Organen statt. Da topische Steroide die sekundären lymphatischen Gewebe nicht erreichen und auch systemische Steroide nicht ausreichend die klonale Expansion von aktivierten T-Zellen unterdrücken, ist der Einsatz von systemischen Immunsuppressiva unumgänglich, um ein klares Transplantatüberleben zu erreichen. Es ist allerdings besonders nach Hochrisikokeratoplastik, einer nicht lebensrettenden Transplantation wichtig, die Vor- und Nachteile einer immunsuppressiven Therapie abzuwägen.AbstractImmunologic 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.

Systemische Immunsuppressiva nach perforierender Keratoplastik

ZusammenfassungDie immunologische Abstoßungsreaktion ist der wichtigste Grund für ein Transplantatversagen nach Hornhauttransplantation. Ohne systemische Immunsuppression kommt es in einer Hochrisikosituation in über 50% der Fälle zu einer Eintrübung des Transplantats innerhalb des ersten postoperativen Jahres. Die klonale Expansion von alloreaktiven Lymphozyten findet in lymphoiden Organen statt. Da topische Steroide die sekundären lymphatischen Gewebe nicht erreichen und auch systemische Steroide nicht ausreichend die klonale Expansion von aktivierten T-Zellen unterdrücken, ist der Einsatz von systemischen Immunsuppressiva unumgänglich, um ein klares Transplantatüberleben zu erreichen. Es ist allerdings besonders nach Hochrisikokeratoplastik, einer nicht lebensrettenden Transplantation wichtig, die Vor- und Nachteile einer immunsuppressiven Therapie abzuwägen.AbstractImmunologic 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.

The intrastromal corneal ring in penetrating keratoplasty-long-term results of a prospective randomized study.

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 studys 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.

Successful treatment of cystoid macular edema with valdecoxib

PURPOSE: To evaluate the safety and efficacy of the COX‐2 inhibitor valdecoxib in treating macular edema after cataract surgery. SETTING: University Eye Clinic, Freiburg, Germany and Reis Medical Institution, Liechtenstein. METHODS: The COX‐2 inhibitor valdecoxib (Bextra) was administered systemically to patients with significant visual loss resulting from macular edema in a prospective clinical trial. RESULTS: Ten patients were enrolled. Valdecoxib was tolerated well and led to a significant visual improvement within 10 days of therapy in all patients. CONCLUSION: The fast and persistent control of macular edema with valdecoxib warrants further investigation.