mycophenolic-acid and Corneal-Diseases

To describe the clinical features and course of 2 patients with autoimmune diseases and their experience with the Boston keratoprosthesis. To draw on general medical literature to try to better understand recurrent complications.. Retrospective review of 2 patients treated with Boston keratoprostheses. The clinical histories, examinations, and other diagnostics were reviewed. A literature review was performed.. The first patient presented with end-stage ocular disease secondary to toxic epidermal necrolysis (TENS). The second patient presented with end-stage ocular disease secondary to mucous membrane pemphigoid (MMP). Both patients underwent treatment with the Boston keratoprosthesis. Both patients suffered numerous corneal melts requiring multiple repeat implantations.. Patients with corneal blindness secondary to autoimmune disease often fare poorly with available surgical treatments. Study of existing literature on prosthetic device complications in autoimmune diseases may help uncover common mechanisms of tissue destruction to establish perioperative immunomodulatory regimens targeted to specific underlying diseases.

Topics: Adult; Alternaria; Anti-Inflammatory Agents; Antibodies, Monoclonal; Autoimmune Diseases; Blindness; Corneal Diseases; Female; Humans; Infliximab; Male; Middle Aged; Mycophenolic Acid; Mycoses; Pemphigoid, Benign Mucous Membrane; Prednisolone; Prostheses and Implants; Prosthesis Implantation; Stevens-Johnson Syndrome; Treatment Outcome; Visual Acuity

To describe the clinical outcome of allogenic simple limbal epithelial transplantation (alloSLET) utilising tissue from cadaveric donor eyes after failed re-epithelialisation of the corneal surface.. Medical records of 14 eyes from 14 patients treated for persistent corneal epithelial defects with alloSLET were reviewed. The primary outcome measure was complete epithelialisation of the corneal surface. Secondary outcome measures were best corrected visual acuity (BCVA) and postoperative side effects due to surgery or medical therapy.. Of the 14 eyes, 7 received alloSLET only and 7 alloSLET together with penetrating keratoplasty (PK). Thirteen (92.9%) of 14 eyes had an epithelialised corneal surface 3 and 6 months after surgery and 10 (71.4%) of 14 eyes displayed an epithelialised corneal surface 12 months after surgery. In both subgroups, alloSLET only and alloSLET with PK, respectively, 5 (71.4%) of 7 eyes had a stable corneal epithelium 12 months after surgery, respectively. Postoperatively, BCVA improved markedly in the whole patient collective. However, the increase was not significant when looking at the two individual subgroups. One patient lost his bandage contact lens several times within the first postoperative month and had a partial detachment of the amniotic membrane. The ocular surface of this patient failed to epithelialise. In three patients, limbal donor pieces translocated to the centre of the cornea, which possibly prolonged the improvement of BCVA.. AlloSLET appears to be an effective treatment option in eyes with non-healing corneal epithelial defects when autologous limbal tissue is not available.

Topics: Adult; Aged; Aged, 80 and over; Allografts; Cadaver; Corneal Diseases; Epithelium, Corneal; Female; Humans; Immunosuppressive Agents; Limbus Corneae; Male; Middle Aged; Mycophenolic Acid; Prednisolone; Re-Epithelialization; Retrospective Studies; Tissue Donors; Treatment Outcome; Visual Acuity

To describe the outcomes of allograft ocular surface stem cell transplantation (OSST) and the complication profile of systemic immunosuppression (SI) in pediatric patients with limbal stem cell deficiency.. This was a retrospective interventional case series from a single tertiary referral institution of 20 eyes from 13 patients who 1) underwent allograft OSST surgery, 2) were 18 years or less at time of OSST, and 3) received SI with 4) a minimum of 12-months follow-up. The main outcome measures were ocular surface stability, visual acuity, and SI adverse events.. The mean age of patients was 15.1 ± 3.2 years (range 9-18 years). The mean follow-up was 5.6 ± 5.0 years after OSST. At the last follow-up, 15 eyes (75%) had a stable ocular surface, 1 eye (5%) developed partial failure, and 4 eyes (20%) developed total surface failure. Preoperative mean logarithm of the minimum angle of resolution visual acuity 1.5 improved to 1.1 at the last follow-up (P = 0.1); when 4 eyes of 3 nonadherent patients were excluded, the results were more pronounced and statistically significant (1.5 improved to 1.0, P = 0.002). SI was tolerated well by all patients with minimal adverse events.. OSST provides a stable ocular surface and is a successful treatment option for pediatric patients with limbal stem cell deficiency. SI is well-tolerated with a minimal complication profile.

Topics: Adolescent; Allografts; Child; Corneal Diseases; Drug Combinations; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Limbus Corneae; Male; Mycophenolic Acid; Retrospective Studies; Stem Cell Transplantation; Stem Cells; Tacrolimus; Treatment Outcome; Visual Acuity

To report a case of local transmission of invasive lobular carcinoma from a donor to a recipient in a keratolimbal allograft after cessation of systemic immunosuppressive therapy.. This is a case report including the clinicopathologic findings. Sections of the donor breast tumor and recipient conjunctival lesions were stained with hematoxylin and eosin. Immunohistochemical studies were performed using pancytokeratin, CK7, CK20, CAM 5.2, CD138, TTF1, estrogen receptor, progesterone receptor, GATA-3, GCDFP-15, and mammaglobin. Polymerase chain reaction-based DNA profiling of tumor cells was performed.. Histopathologic examination revealed an infiltrate of atypical cells with large hyperchromatic nuclei consistent with carcinoma. Immunohistochemical analysis showed pancytokeratin, CK7, CAM 5.2, GATA-3, and estrogen receptor positivity and progesterone receptor absence, consistent with the previously determined phenotype of the donor's breast carcinoma. Results of polymerase chain reaction analysis were also consistent with the donor's tumor. After reduced dosing of tacrolimus and mycophenolate mofetil, 2 limbal tumors occurred in the recipient. The immunosuppressive treatment had been stopped completely before the appearance of the third lesion. The recipient had no history of malignancy, and she had routine screenings for breast cancer.. We report a case of donor-derived breast carcinoma in a keratolimbal allograft recipient. The grafted tissue harbored donor-derived tumor cells for more than 4 years after surgery even after systemic immunosuppression was discontinued. Although no similar reports of tumor transfer could be found in the literature, this case suggests the need for increased stringency in donor selection and heightened surveillance for such tumor transmission.

Topics: Aged; Allografts; Biomarkers; Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Lobular; Conjunctival Neoplasms; Corneal Diseases; DNA Fingerprinting; Female; GATA3 Transcription Factor; Humans; Immunohistochemistry; Immunosuppressive Agents; Keratin-7; Keratins; Limbus Corneae; Mycophenolic Acid; Polymerase Chain Reaction; Receptors, Estrogen; Stem Cell Transplantation; Tacrolimus; Tissue Donors

To report a case of probable donor-derived cytomegalovirus (CMV) infection after keratolimbal allograft (KLAL) transplantation.. Observational case report.. A 41-year-old man with a history of aniridic keratopathy and limbal stem cell deficiency underwent KLAL in his right eye. Preoperatively, he was negative for CMV IgG and IgM. Postoperatively, he was maintained on tacrolimus and mycophenolate mofetil for systemic immunosuppression; he was also on prophylactic valganciclovir (for CMV) and trimethoprim/sulfamethoxazole (for pneumocystis pneumonia) for 1 month. Approximately 5 weeks postoperatively, he developed a nonproductive cough, rhinorrhea, and dyspnea. His condition did not improve with oral azithromycin or levofloxacin. He developed worsening symptoms over the next 2 weeks despite therapy. The serum CMV polymerase chain reaction was positive, and he was readministered valganciclovir with subsequent resolution of symptoms.. We present the first case of CMV disease in a seronegative patient who received a presumed CMV-seropositive donor KLAL. Similar to solid organ transplantation, prophylactic and therapeutic management of CMV infection is necessary in the setting of systemic immunosuppression.

Topics: Adult; Allografts; Antiviral Agents; Corneal Diseases; Cytomegalovirus Infections; Drug Therapy, Combination; Eye Infections, Viral; Ganciclovir; Humans; Limbus Corneae; Male; Mycophenolic Acid; Stem Cell Transplantation; Tacrolimus; Tissue Donors; Valganciclovir

In this study, we aimed to evaluate the efficacy and safety of systemic immunosuppression with mycophenolate mofetil (MMF) to prevent corneal graft rejection after high-risk penetrating keratoplasty.. One hundred and ninety-six consecutive patients who underwent high-risk penetrating keratoplasty defined as the presence of deep vascularization in more than two quadrants, keratouveitis, emergency keratoplasties, and retransplantations were enrolled in the study. Ninety-eight prospectively followed up patients were treated with MMF [with dose adjustment based on mycophenolic acid (MPA) serum concentration], and 98 patients were in the non-MMF-treated retrospectively assessed control group.. During a mean of 24 months of observation, immune reactions occurred in eight cases (8 %) and graft rejection with subsequent graft failure occurred in three cases (3 %) in the MMF group. In the control group, graft rejection occurred in 76 cases (78 %) and failure due to graft rejection occurred in 30 cases (31 %). Kaplan-Meier analysis demonstrated that 93 % of the grafts in the MMF-treated group and 47 % in the control group showed no immune rejection (p < 0.01, log-rank test) after a year. Cox regression analysis proved that MMF treatment decreased the risk of graft rejection 11 times (RR = 11, 95.0 % CI 4.8-25, p < 0.0001). Among 98 MMF-treated patients, 13 had gastric discomfort, three developed leucopenia, and two had anemia that resolved after MMF dose reduction.. MMF treatment after high risk penetrating keratoplasty is safe and reduces the incidence of immune graft rejection and graft failure. Side effects were rare and reversible in all but one case.

Topics: Adult; Aged; Aged, 80 and over; Corneal Diseases; Female; Follow-Up Studies; Graft Rejection; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Keratoplasty, Penetrating; Male; Middle Aged; Mycophenolic Acid; Prospective Studies; Retrospective Studies; Risk Factors; Young Adult

To report postoperative complications of keratolimbal allograft (KLAL) transplantation in patients with bilateral total limbal stem cell deficiency.. In this retrospective observational case series, medical charts of 45 patients with at least 6 months of follow-up were reviewed. The main outcome measure was postoperative complications including graft-related issues (thickness, position, and alignment) and immunologic rejection.. Sixty-six KLALs were performed on 45 eyes. The mean follow-up period was 26.1 ± 11.8 months (range, 6-48 months). Primary failure occurred in 5 eyes primarily as a result of ocular surface exposure and severe dry eyes. Graft-related complications included misalignment (4 eyes), buttonhole (4), inner-edge tear (4), inadvertent limbal trephination (2), and thick KLAL (2). Postoperatively, regional thinning of the graft was observed in 8 KLALs as a result of exposure, regional ischemia, and after epithelial rejection. Acute rejection was diagnosed 16 times in 8 eyes, whereas chronic rejection was observed in 24 eyes. At last follow-up, 12 cases (26.6%) had failed because of recurrent acute rejection (4), chronic rejection (5), refractory herpetic keratitis (1), exposure (1), and refractory papillomavirus keratitis (1).. KLAL may be complicated by several adverse events. The most important complications are immunologic rejections, chronic ocular surface exposure, and graft-related complications.

Topics: Adolescent; Adult; Cell Transplantation; Child; Corneal Diseases; Drug Therapy, Combination; Epithelium, Corneal; Female; Graft Rejection; Humans; Immunosuppressive Agents; Limbus Corneae; Male; Middle Aged; Mycophenolic Acid; Postoperative Complications; Retrospective Studies; Stem Cell Transplantation; Tacrolimus; Tissue Donors; Transplantation, Homologous; Young Adult

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).. Retrospective, consecutive subject cohort study.. 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.. 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.. 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.. 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.. 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.

Topics: Adult; Alkylating Agents; Amnion; Conjunctiva; Corneal Diseases; Cyclosporine; Female; Follow-Up Studies; Graft Survival; Humans; Immunosuppressive Agents; Keratoplasty, Penetrating; Limbus Corneae; Male; Middle Aged; Mitomycin; Mycophenolic Acid; Retrospective Studies; Stem Cells; Transplantation, Homologous; Visual Acuity

To describe the systemic immunosuppression protocol used at the Cincinnati Eye Institute and University of Cincinnati, and to evaluate the success, tolerability, and side effects of systemic immunosuppression in patients undergoing ocular surface stem cell transplantation (OSST).. Retrospective study of all patients who had OSST from 1997 to 2007 and received follow-up for systemic immunosuppression at the Cincinnati Eye Institute. Patients were analyzed for demographics, systemic immunosuppression exposure, ocular surface stability, efficacy, and toxicity variables.. A total of 225 eyes from 136 patients with a mean age of 43.6 years (range, 8.9-80.6 years) underwent OSST with systemic immunosuppression. The most common systemic immunosuppression regimen consisted of tacrolimus, mycophenolate mofetil, and a short course (1-3 months) of prednisone (102/136 patients, 75%). Prophylactic valganciclovir and trimethoprim/sulfamethoxazole (dapsone if sulfa allergy was present) were also used. Mean duration of immunosuppression was 42.1 months (range, 3.6-128 months) and mean follow-up time after OSST was 53.9 months (range, 3.6-147.3 months). At the patients' final follow-up visit, 105/136 patients (77.2%) had a stable ocular surface. There were 3 severe adverse events in 2 patients (1.5%) and 21 minor adverse events in 19 patients (14.0%). Of the 21 patients with adverse events, 10 (47.6%) had systemic comorbidities at initial presentation.. The prevention of graft rejection with the use of systemic immunosuppression after OSST is crucial and should be approached with the same rigor as in solid organ transplantation. With appropriate long-term monitoring by the cornea specialist and transplant physician, the risk of irreversible toxicity at current dosages of systemic immunosuppression in this population is minimal.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Corneal Diseases; Drug Therapy, Combination; Epithelium, Corneal; Female; Follow-Up Studies; Graft Rejection; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Limbus Corneae; Male; Middle Aged; Mycophenolic Acid; Prednisone; Retrospective Studies; Stem Cell Transplantation; Tacrolimus; Time Factors; Young Adult

To determine the long-term outcomes of keratolimbal allograft (KLAL).. Scores of such risks as infrequent blinking, blink-related microtrauma, conjunctival inflammation, elevated intraocular pressure, dry eye, symblepharon, lagophthalmos, and previous KLAL or penetrating keratoplasty (PKP) failure were calculated and recorded before, during, and after KLAL. Prolonged oral mycophenolate mofetil and tacrolimus and short-term prednisone and acyclovir were administered in 12 eyes (10 consecutive patients) with total limbal stem cell deficiency after KLAL. Ten eyes underwent subsequent PKP.. More corrective measures were required in eyes with higher risk scores. During a follow-up of 61.2 months (standard deviation [SD], 18.2; range, 36-91 months) after KLAL, postoperative epithelial breakdown due to exposure occurred late in the period after PKP and remained a primary risk. Mean daily doses of 1.4 g of mycophenolate mofetil and 1.6 mg of tacrolimus were administered for 52.7 months (SD, 22.5; range, 23-91 months) with few adverse effects and reached trough levels of 1.6 microg/mL (SD, 0.6 microg/mL) and 4.5 ng/mL (SD, 2 ng/mL), respectively. Keratolimbal allograft and PKP rejection was noted in 2 and 3 eyes, respectively, though there was a reversal in 1 eye in each group, yielding final KLAL and PKP survivals in 10 and 8 eyes, respectively, and ambulatory visual acuity of up to 20/20 in 10 eyes for 67.2% of the entire follow-up period.. Correction of ocular surface deficits combined with an immunosuppressive regimen further improves the long-term outcome of KLAL in eyes with total limbal stem cell deficiency.

Topics: Adult; Aged; Amnion; Combined Modality Therapy; Corneal Diseases; Drug Therapy, Combination; Epithelial Cells; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Limbus Corneae; Male; Middle Aged; Mycophenolic Acid; Risk Factors; Stem Cell Transplantation; Stem Cells; Suture Techniques; Tacrolimus; Transplantation, Homologous; Treatment Outcome

Emergency penetrating keratoplasty is said to have a poorer outcome than conventional keratoplasty. We performed a retrospective analysis of 272 cases of emergency keratoplasty to evaluate this hypothesis.. We analysed 272 cases of emergency keratoplasty and compared the results with a control group of 1,257 scheduled normal-risk keratoplasties and 407 scheduled high-risk keratoplasties. Kaplan-Meier estimations were performed to estimate the percentage of clear graft survival and development of immune reactions. Indications for emergency keratoplasty were microbial diseases (n=109, acanthamoeba, bacteria, fungi), herpes simplex virus infections (n=83), ulcers due to immunological diseases (n=63), and 17 cases of ulcers of unknown origin.. Within 1,500 postoperative days, grafts following emergency keratoplasty suffered statistically significantly more graft failures (clear graft survival, 67.9 vs. 86.9%, P<0.01) and immune reactions (grafts free from immune reactions, 62.8 vs. 78.6%, P<0.01) than grafts following scheduled, normal-risk keratoplasty. There was no statistically significant difference between emergency and scheduled high-risk keratoplasties (clear graft survival, 67.9 vs. 70.2%, and grafts free from immune reactions, 62.8 vs. 66.8%). For emergency keratoplasties, systemic immunosuppression (with cyclosporin A and/or mycophenolatmophetil) had a statistically significant positive effect on clear graft survival (77.4 vs. 63.5%, P=0.01), but not on the development of immune reactions (62.8 vs. 62.3%). A sub-group analysis showed that the effect on clear graft survival was mainly an effect on the underlying systemic immunological disease that had lead to emergency keratoplasty.. This retrospective analysis revealed that clear graft survival is limited following emergency keratoplasty. As in high-risk situations, systemic immunosuppression may be the key to improving prognosis following emergency keratoplasty in the long run.

Topics: Adult; Aged; Aged, 80 and over; Cornea; Corneal Diseases; Cryopreservation; Cyclosporine; Emergency Treatment; Graft Rejection; Graft Survival; Humans; Immune System; Immune Tolerance; Immunosuppressive Agents; Keratoplasty, Penetrating; Middle Aged; Mycophenolic Acid; Organ Culture Techniques; Organ Preservation; Prognosis; Retrospective Studies

The purpose of our study was to compare the effectiveness of immunosuppressive drugs on the prevention of allograft rejection in a murine model of low-risk and high-risk keratoplasty. The therapy included FK 506 (tacrolimus; 0.2 mg/kg), mycophenolate mofetil (30 mg/kg), aminoguanidine (0.1 g/kg), and combination of FK506 + mycophenolate mofetil or FK506 + aminoguanidine. The results obtained from the Gray's survival model stratified according to the type of subjects suggest that a major rejection risk reduction was achieved using FK506; good results also were obtained for mycophenolate mofetil. Although the point estimates of both the survival and relative risk of rejection suggest a deferred effect of the combination FK506 + mycophenolate mofetil, this finding did not prove statistically significant.

Topics: Animals; Corneal Diseases; Corneal Transplantation; Disease Models, Animal; Drug Combinations; Female; Graft Rejection; Graft Survival; Guanidines; Immunosuppressive Agents; Male; Mice; Mycophenolic Acid; Risk Factors; Tacrolimus; Transplantation, Homologous

To determine the prognosis of allogeneic penetrating limbo-keratoplasty in patients with total limbal stem cell deficiency and to find out if donor limbal stem cells survive in the long run.. Noncomparative prospective case series.. Forty-eight patients with total limbal stem cell deficiency.. Allogeneic penetrating limbo-keratoplasty. All patients received systemic cyclosporin A and/or mycophenolate mofetil in the postoperative course. Thirteen patients received grafts with 0 to 1 HLA mismatches in the HLA-A, HLA-B, and HLA-DR loci; 13 patients received grafts with 2 to 6 mismatches; and 22 patients received untyped grafts.. Long-term clear graft survival and survival of donor limbal stem cells.. Five years postoperatively, 65% of the grafts with 0 to 1 mismatches, 41% of the grafts with 2 to 6 mismatches, and 14% of the untyped grafts were clear centrally (estimation according to Kaplan-Meier log rank test, P = 0.03). Immunogenetic analysis of epithelial cells from the surface of the graft could be performed successfully in 7 of 9 patients and revealed donor DNA in the epithelium of 5 of these 7 patients up to 56 months postoperatively.. Long-term survival of donor epithelium could be demonstrated immunogenetically in patients undergoing allogeneic penetrating limbo-keratoplasty. Human leukocyte antigen-matched grafts seem to deliver better results than untyped grafts. Progress with matching and immunosuppressive strategies may further improve current results.

Topics: Adult; Cell Survival; Corneal Diseases; Cyclosporine; Female; Follow-Up Studies; Graft Survival; Histocompatibility Testing; Humans; Immunogenetics; Immunosuppressive Agents; Keratoplasty, Penetrating; Limbus Corneae; Male; Middle Aged; Mycophenolic Acid; Prognosis; Prospective Studies; Stem Cell Transplantation; Stem Cells; Transplantation, Homologous