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Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) are powerful in vitro models to study the mechanisms underlying cardiomyopathies and cardiotoxicity. Quantification of the contractile function in single hiPSC-CMs at high-throughput and over time is essential to disentangle how cellular mechanisms affect heart function. Here, we present CONTRAX, an open-access, versatile, and streamlined pipeline for quantitative tracking of the contractile dynamics of single hiPSC-CMs over time. Three software modules enable: parameter-based identification of single hiPSC-CMs; automated video acquisition of >200 cells/hour; and contractility measurements via traction force microscopy. We analyze >4,500 hiPSC-CMs over time in the same cells under orthogonal conditions of culture media and substrate stiffnesses; +/- drug treatment; +/- cardiac mutations. Using undirected clustering, we reveal converging maturation patterns, quantifiable drug response to Mavacamten and significant deficiencies in hiPSC-CMs with disease mutations. CONTRAX empowers researchers with a potent quantitative approach to develop cardiac therapies., (© 2024. The Author(s).)

A 68-year-old diabetic male with Fuchs endothelial corneal dystrophy cataract underwent combined DMEK and cataract surgery of the left eye. Post-operative course was complicated by a partial graft detachment on POD 3, treated with a re-bubbling procedure. The patient subsequently developed a corneal infiltrate, cultured by aqueous sample, that was found to be C. parapsilosis . Oral fluconazole and voriconazole, topical voriconazole 1%, and amphotericin B as well as intracameral and intrastromal voriconazole and amphotericin B were employed. By post-operative day 45, symptoms and signs of DMEK stromal C. parapsilosis keratitis had resolved, and a corneal scar remained. Best corrected visual acuity, at post-operative month 4, was 20/25-2 without correction. Post-DMEK fungal stromal keratitis is a rare post-operative complication. We present a case of C. parapsilosis DMEK stromal keratitis and describe diagnostic and therapeutic modalities that allowed for resolution of the infection, without explantation of the patient's graft, and preservation of visual acuity.

Aim: To review the efficacy and safety of two common postoperative regimens following Kahook Dual Blade goniotomy with phacoemulsification cataract extraction (KDB-CE)., Materials and Methods: This is a retrospective review of eyes undergoing KDB-CE from May 2016 to 2018 by a single surgeon. Almost 12-month follow-up data were assessed for two common postop regimens-treatment with (1) topical prednisolone acetate 1% with pilocarpine 1% (pred-pilo) or (2) difluprednate 0.05% postoperatively. Postoperative results were compared to each respective baseline intraocular pressure (IOP) levels., Results: There were 53 eyes in the difluprednate group and 25 eyes in the pred-pilo group. In the difluprednate group, the IOP decreased at postoperative day 1 (POD1) [16 ± 5 baseline vs 15 ± 5 POD1, mean ± standard deviation (SD) in mm Hg, and p = 0.321], but increased at postoperative week 1 (POW1) due to a 15% rate of IOP-spikes (19 ± 9, p = 0.099). The number of IOP-lowering drops decreased from baseline (2 ± 1 drops) to 1 ± 1 drops at POD1 ( p < 0.0001), and remained at 1 ± 1 drops through postoperative month 12 (POM12) ( p < 0.0001). In the pred-pilo group, there was a statistically significant decrease in mean IOP at POW1 (16 ± 4 POW1 vs 18 ± 6 baseline, p = 0.044), which persisted through POM6. The number of IOP-lowering drops was not statistically significantly lower from baseline at POM3 (2 ± 1 at POM3, p = 0.188). Spikes in IOP, corneal edema, and hyphema were the most common complications., Conclusion: Both postoperative regimens were effective following KDB-CE at reducing IOP at 12 months. The difluprednate group was likely to experience an IOP-spike at POW1 but used fewer IOP-lowering drops 12 months after KDB goniotomy. In the pred-pilo group, the number of IOP-lowering drops was equivalent to baseline levels at POM3. Aside from IOP spikes, there were similar complication rates observed between the two postoperative regimens. Due to demographic differences, it was not possible to compare relative IOP-lowering efficacy between the two postoperative regimens., Clinical Significance: It is efficacious and safe to use either postoperative regimen following KBD-CE. Postoperative trajectories may differ with respect to the postoperative regimen, but further randomized controlled trials are needed to compare various topical steroid medications for postoperative regimens following KDB-CE., How to Cite This Article: Birnbaum F, Wakil S, Vu DM, et al. Postoperative Management of Kahook Dual Blade Goniotomy with Phacoemulsification Cataract Extraction. J Curr Glaucoma Pract 2023;17(4):169-174., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2023; The Author(s).)

Duchenne muscular dystrophy (DMD) is a severe muscle wasting disease caused by the lack of dystrophin. Heart failure, driven by cardiomyocyte death, fibrosis, and the development of dilated cardiomyopathy, is the leading cause of death in DMD patients. Current treatments decrease the mechanical load on the heart but do not address the root cause of dilated cardiomyopathy: cardiomyocyte death. Previously, we showed that telomere shortening is a hallmark of DMD cardiomyocytes. Here, we test whether prevention of telomere attrition is possible in cardiomyocytes differentiated from patient-derived induced pluripotent stem cells (iPSC-CMs) and if preventing telomere shortening impacts cardiomyocyte function. We observe reduced cell size, nuclear size, and sarcomere density in DMD iPSC-CMs compared with healthy isogenic controls. We find that expression of just one telomere-binding protein, telomeric repeat-binding factor 2 (TRF2), a core component of the shelterin complex, prevents telomere attrition and rescues deficiencies in cell size as well as sarcomere density. We employ a bioengineered platform to micropattern cardiomyocytes for calcium imaging and perform Southern blots of telomere restriction fragments, the gold standard for telomere length assessments. Importantly, preservation of telomere lengths in DMD cardiomyocytes improves their viability. These data provide evidence that preventing telomere attrition ameliorates deficits in cell morphology, activation of the DNA damage response, and premature cell death, suggesting that TRF2 is a key player in DMD-associated cardiac failure.

Duchenne muscular dystrophy (DMD) is a progressive genetic myopathy that leads to heart failure from dilated cardiomyopathy by early adulthood. Recent evidence suggests that tamoxifen, a selective estrogen receptor modulator widely used to treat breast cancer, ameliorates DMD cardiomyopathy. However, the mechanism of action of 4-hydroxytamoxifen, the active metabolite of tamoxifen, on cardiomyocyte function remains unclear. To examine the effects of chronic 4-hydroxytamoxifen treatment, we used state-of-the-art human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and a bioengineered platform to model DMD. We assessed the beating rate and beating velocity of iPSC-CMs in monolayers and as single cells on micropatterns that promote a physiological cardiomyocyte morphology. We found that 4-hydroxytamoxifen treatment of DMD iPSC-CMs decreased beating rate, increased beating velocity, and ameliorated calcium-handling deficits, leading to prolonged viability. Our study highlights the utility of a bioengineered iPSC-CM platform for drug testing and underscores the potential of repurposing tamoxifen as a therapy for DMD cardiomyopathy., (© 2022. The Author(s).)

Background: Diabetes mellitus is a risk factor for central retinal vein occlusion (CRVO); however, it is unclear whether certain commonly used medications among diabetics or glycemic control impact visual outcomes in diabetic eyes with CRVO., Purpose: To evaluate the effect of select systemic medications and glycemic control on presenting features, treatment burden, and outcomes in patients with diabetes who develop a central retinal vein occlusion (CRVO)., Methods: Retrospective longitudinal cohort study at a single tertiary academic referral center from 2009-2017 investigating eyes of patients being treated for diabetes mellitus at CRVO onset. Eyes with a prior history of anti-vascular endothelial growth factor (anti-VEGF) therapy or laser treatment within the year prior to CRVO onset were excluded. Main outcomes and measures were visual acuity (VA), central subfield thickness (CST), cystoid macular edema (CME), and number of intravitreal injections and laser treatment throughout follow-up., Results: We identified 138 eyes of 138 participants who were diabetic at CRVO onset. Of these, 49% had an ischemic CRVO. Median follow-up time was 25.5 months. Fifty-five eyes (40%) had a HbA1c within 6 months of CRVO presentation. HbA1c was positively correlated with both presenting CST ( p  = 0.04) and presence of CME ( p  < 0.01). In all 138 eyes, mean presenting VA was 20/246, and mean final VA was 20/364. Better-presenting VA was significantly associated with aspirin 325 mg use ( p  = 0.04). Lower CST at presentation was significantly associated with metformin use ( p  = 0.02). Sitagliptin use at CRVO onset was associated with a lower prevalence of CME at final follow-up ( p  < 0.01). Lower final CST was significantly associated with glipizide use at CRVO onset ( p  = 0.01). There were no significant associations between systemic medications or HbA1c and treatment burden or final VA ( p  > 0.05)., Conclusion: Although aspirin 325 mg, metformin, sitagliptin, and glipizide were associated with better-presenting VA, lower-presenting CST, lower prevalence of macular edema at final visit, and lower final CST, respectively, none of these systemic agents or glycemic control were associated with decreased treatment burden or improved visual outcomes in diabetics with CRVO., Competing Interests: Conflict of interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2022.)

Purpose: The purpose of this study was to investigate the effect of systemic antiplatelet agents and anticoagulants on the structural and functional outcomes of eyes with branch retinal vein occlusion (BRVO)., Methods: A retrospective longitudinal cohort study was performed on BRVO patients evaluated at a single tertiary care referral center between 2009 and 2017. Medical records were reviewed for antiplatelet agent and anticoagulant use including aspirin, clopidogrel, warfarin, rivaroxaban, apixaban, or dabigatran prior to BRVO onset. In addition, optical coherence tomography (OCT) parameters, clinical outcomes, and treatment patterns were also recorded., Results: A total of 354 BRVO eyes were identified with a mean follow-up time of 36 months. Antiplatelet or anticoagulant use was associated with presence of cystoid macular edema (CME) at presentation after controlling for potential confounding variables in a multivariate logistic regression. Multivariate regression also revealed an association between foveal hemorrhage at presentation and use of antiplatelet or anticoagulant medications. There were no significant differences in visual acuity or prevalence of CME at the final visit in those with antiplatelet/anticoagulant use compared to those not on these agents., Conclusion: Although the use of systemic antiplatelet or anticoagulant agents was associated with increased prevalence of CME and foveal hemorrhage at presentation of BRVO, the use of these medications was not associated with different visual or structural outcomes at the final visit., Competing Interests: Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: DSB is a consultant for Genentech and Verana Health. AST is a consultant for Alimera, Avesis, Bauch & Lomb, Genentech, Zeiss. SF receives patent royalties from Alcon. The other authors have no disclosures to report., (© The Author(s), 2021.)

Purpose: To compare the 18-month efficacy and safety of Kahook Dual Blade goniotomy (KDB) in combination with cataract surgery (combined group) or as a standalone procedure (standalone group)., Setting: Single surgeon practice., Design: Retrospective review study., Methods: A total of 116 eyes of 100 patients underwent KDB by a single well-experienced surgeon from May 2016 to 2018. A total of 93 eyes and 23 eyes were in the combined and standalone groups, respectively. Main outcome measures were reduction in intraocular pressure (IOP) and IOP-lowering medication and adverse events. Data were collected and analyzed using Welch t tests in R., Results: A total of 116 eyes of 100 patients were included in the analysis. Moderate or severe glaucoma was observed in 71% of eyes in the combined group compared with 83% in the standalone group. At baseline, mean IOP was 16.5 ± 5.0 mm Hg (n = 93) and 24.3 ± 9.1 mm Hg (n = 23) in the combined and standalone groups, respectively (P < .05). The IOP decreased in both groups at 12 months (14.1 ± 3.9 vs 16.9 ± 7.6, P = .24) and 18 months (14.4 ± 3.7 vs 16.7 ± 7.6, P = .5). There was a statistically significant difference in the number of drops between the combined and standalone groups at baseline (2.4 ± 1.2 vs 2.9 ± 1.0, P < .05) persisting at 12 months (1.3 ± 1.2 vs 2.6 ± 1.2, P < .05) and at 18 months (1.3 ± 1.2 vs 3.3 ± 1.2, P < .05). Complications included transient hyphemas (20 eyes [17%]) and IOP spike (20 eyes [17%]). Seven eyes required additional glaucoma surgery, 5 of which were in the standalone group., Conclusions: KDB was an effective and safe procedure for different glaucoma disease severities, whether combined with cataract surgery or as a standalone surgery. It is an alternative to consider prior to pursuing more invasive glaucoma surgeries.

Background and Objective: To compare outcomes in eyes with central retinal vein occlusion (CRVO) presenting with (group 1) or without (group 2) fovea-involving intraretinal hemorrhage (IRH)., Patients and Methods: Retrospective review of patients diagnosed with acute, treatment-naïve CRVO between January 2009 and July 2016., Results: One hundred fifteen (39.8%) of 289 CRVO eyes had fovea-involving IRH. At baseline, eyes in group 1 had significantly worse visual acuity (VA) (1.2 ± 0.10 logMAR vs. 0.9 ± 0.06 logMAR; P = .001) and greater central subfield thickness (CST) (610.4 μm ± 35.9 μm vs. 435.0 μm + 21.6 μm; P < .001) than eyes in group 2. Final visual outcomes were comparable between groups (1.24 ± 0.09 logMAR vs. 1.02 ± 0.08 logMAR; P = .08). Group 1 received a significantly greater number of intravitreal anti-vascular endothelial growth factor injections during the first year (7.80 ± 0.40 vs. 5.20 ± 0.40; P = .001)., Conclusions: Although treatment-naïve eyes with acute CRVO and fovea-involving IRH had worse VA and greater CST at presentation, the final VA was comparable to eyes without such a hemorrhage. Eyes with foveal IRH had a greater treatment burden in the first 12 months. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:752-759.]., (Copyright 2019, SLACK Incorporated.)

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.

Keratoconjunctivitis caused by adenoviruses (epidemic keratoconjunctivitis, EKC, ICD-10 B30.0+) is common, can be severe and may cause significant morbidity. In the early stages of adenoviral infections it is often difficult to differentiate the clinical presentation from other causes of a red eye. Because of its highly contagious nature that can rapidly lead to epidemic outbreaks, prompt viral identification and prevention of further spread are major challenges. Even today the diagnosis is still mainly clinical, with laboratory tests only rarely contributing. New diagnostic tests, such as the Rapid Pathogen Detector (RPS, Sarasota FL) AdenoPlus detection kit, that are practical, rapid and inexpensive to use in the general practice may obviate these problems. Because of its highly resistant properties to desiccation and highly developed escape mechanisms which protect the virus from the host's immune response, long-term problems often remain. Remnants of viral proteins often persist on the corneal surface of Bowman's layer for a long time and may lead to the formation of subepithelial infiltrates. No treatment other than symptomatic eye drops is available. The major sequelae are subepithelial infiltrates, which are difficult to treat. Cyclosporin A eye drops are a good option with a low risk profile. The use of topical steroids can possibly be disadvantageous but can be discussed at all stages of the disease. As nosocomial spread of adenoviruses is relatively common, preventive measures remain a major responsibility for ophthalmologists.

In order to prevent rejection of an allogeneic corneal transplant after perforating (high risk) keratoplasty, active agents from different classes of pharmacological substances are used, as with solid organ transplantation. In addition to glucocorticoids, antiproliferative agents, small molecule inhibitors and antibodies, those belonging to the group of macrolides with their many derivatives represent an interesting class of substances in this context. As a supplement to cyclosporin A (CSA) the most successful macrolide in transplantation medicine, animal experiments are currently being carried out to test newer macrolide derivatives, such as sanglifehrin A (SFA). This overview describes the classes of drugs and modes of action of currently administered standard medications in the clinical routine and new developments are presented.

Background: As the desire for spectacle independence following cataract surgery grows, so does interest in the implantation of multifocal intraocular lenses. However, glare phenomena, reduced intermediate vision and loss of image quality are known problems associated with this new generation of lenses. We compared the functional results achieved by the implantation of the diffractive-refractive Acri.LISA 366D lenses to those achieved from implanting monofocal Acri.Smart 46LC lenses., Methods: In a retrospective data analysis we followed ten patients who received bifocal intraocular lenses (Acri.LISA 366D) and ten patients who received monofocal intraocular lenses (Acri.Smart 46LC). Lenses were always implanted in both eyes. In each group we assessed visual acuity and contrast sensitivity with the Freiburg Vison Test (FrACT) at multiple distances ranging from 0.5 to 5 m. Additionally, we assessed near vision with the Birkhaeuser charts. We also evaluated photopic phenomena and patient satisfaction using a standardised questionnaire. One patient in the Acri.LISA group and six patients in the control group missed the recommended follow-up visits., Results: We found good uncorrected distance and near visual acuity. Only three of nine patients wore glasses occasionally. Although their contrast sensitivity decreased by a factor of two compared to the control group, patients did not complain about visual disturbances. Patient satisfaction was predominantly high following Acri.LISA 366D implantation., Conclusions: With the Acri.LISA 366D, patients demonstrate excellent near and distance vision, albeit with reduced contrast sensitivity. Acri Lisa is a viable option in patients that do not want to depend on spectacles.

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.)

A 57-year-old male patient with Marfan syndrome presented at our clinic with a whitish gelatinous corneal tumour in the right eye. The initial examination revealed pronounced corneal oedema, bullous keratopathy, as well as an iris-fixed anterior chamber lens implanted 7 years previously. After the tumour was removed, the anterior chamber lens was explanted and keratoplasty was explanted and a two stage keratoplasty was performed. Histological analysis of the tumour and the cornea revealed vimentin and a number of smooth muscle actin (SMA)-positive tumour cells. The cornea below the tumour displayed a partially absent Bowman's layer and extensive pannus tissue. The characteristics of the corneal tumour and the subjacent cornea as described above are typical of secondary corneal myxoma. The influence of Marfan syndrome, a systemic connective tissue disorder present in the patient, on the etiopathogenesis of the corneal myxoma could not be fully determined.

Helicobacter pylori (H. pylori) is a gram-negative, spiral-shaped bacterium that infects more than half of the world's population and is a major cause of gastric adenocarcinoma. The mechanisms that link H. pylori infection to gastric carcinogenesis are not well understood. In the present study, we report that the Raf-kinase inhibitor protein (RKIP) has a role in the induction of apoptosis by H. pylori in gastric epithelial cells. Western blot and luciferase transcription reporter assays demonstrate that the pathogenicity island of H. pylori rapidly phosphorylates RKIP, which then localizes to the nucleus where it activates its own transcription and induces apoptosis. Forced overexpression of RKIP enhances apoptosis in H. pylori-infected cells, whereas RKIP RNA inhibition suppresses the induction of apoptosis by H. pylori infection. While inducing the phosphorylation of RKIP, H. pylori simultaneously targets non-phosphorylated RKIP for proteasome-mediated degradation. The increase in RKIP transcription and phosphorylation is abrogated by mutating RKIP serine 153 to valine, demonstrating that regulation of RKIP activity by H. pylori is dependent upon RKIP's S153 residue. In addition, H. pylori infection increases the expression of Snail, a transcriptional repressor of RKIP. Our results suggest that H. pylori utilizes a tumor suppressor protein, RKIP, to promote apoptosis in gastric cancer cells.

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.

Purpose: Penetrating keratoplasty has a very poor outcome compared with adults if performed in the first years of life. Rejection in these young patients occurs even in the absence of known immunological risk factors. Recently, a baby rat model was introduced and an essential contribution of natural killer (NK) cells during allograft rejection was suggested. To analyze this, NK cells were depleted in baby rats before keratoplasty., Methods: Allogeneic keratoplasty was performed between Lewis and Fisher rats. The recipient's ages were 10 and 3 weeks, respectively. NK cells were depleted by an intraperitoneal injection of a monoclonal antibody. All experiments were controlled by the injection of isotypic control antibodies and syngeneically. Survival rates were calculated and cellular infiltrates were analyzed histologically., Results: NK cell depletion did delay median graft survival times in a statistically significantly way compared with the control animals (p<0.01). At median rejection time points, macrophages, CD4(+) T cells and CD25(+) leukocytes infiltrated to a greater extent in the depleted recipients. No significant changes in the cell numbers of infiltrating CD8(+) T cells were observed., Conclusions: We conclude that NK cells play a role during allograft rejection in baby rats, but their effect is replaceable. A greater infiltration of macrophages and CD4(+) T cells suggests that they might compensate for the missing NK cells' response in this experimental setting. Our results represent another step toward understanding the complex mechanisms of an accelerated corneal graft rejection in infant recipients.

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.

Keratoconjunctivitis is a common infectious disease of the eye surface, which is caused by adenovirus. The chronic form is keratitis nummularis. Cyclosporin A is a calcineurin inhibitor which has been used in ophthalmology for approximately 15 years for local therapy of chronic inflammation of the eye surface. Since the 1990s this medication has proven effective for the treatment of keratitis nummularis. The indications for treatment with cyclosporin A eyedrops are given when a reduction in vision due to keratitis nummularis has not shown any improvement within 6 weeks after acute inflammation.

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.

Background: Immunological graft rejection is the main reason for graft failure following corneal transplantation despite the use of topical and systemic steroids. As steroids are associated with side effects, alternative therapeutic strategies are needed., Patients and Methods: In this clinical trial patients undergoing corneal transplantation have been prospectively randomised to receive either prednisolone acetate 1 % eye drops 5 x /day, tapering off by one drop every month (n = 20), or to receive FK 506 eye drops 3 x /day for six months (n = 20). Patients in both groups received additionally systemic steroids for three weeks (fluocortolon 1 mg/kg body weight). Primary endpoints were the number of immune reactions and the clear graft survival, the secondary endpoint was the number of side effects., Results: Three immune reactions in the steroid group and one immune reaction in the FK 506 group were seen within the follow-up time of three years. No irreversible graft rejections occurred in either group. Eight patients in the FK 506 group concluded the study early due to local side effects., Conclusions: In this long-term follow-up the use of FK 506 eye drops following corneal transplantation resulted in a lower number of immune reactions when compared to topical steroids. With a change in the galenic formulation FK 506 might be a powerful therapeutic option for preventing immunological graft rejection.

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.

In some cases topical antimicrobial treatment of microbial keratitis or corneal ulcers remains unsuccessful, with increasing infiltration of the corneal stroma. In this situation the steam cautery procedure developed by Karl Wessely in 1911 can lead to rapid healing of the inflammatory process, avoiding further corneal surgery. In this article we describe the steam cautery technique and discuss its indications for microbial keratitis.

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.

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.

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.

Two patients had uneventful phacoemulsification. After initial improvement, vision deteriorated because of cystoid macular edema (CME). In 1 patient, treatment with systemic nonsteroidal antiinflammatory drugs showed significant improvement in visual acuity but had to be discontinued because of side effects and a relapse of the disease. In the other patient, this therapy was not sufficient. Both patients were given valdecoxib, a cyclooxygenase-2 inhibitor. The new therapy was tolerated well and led to significant and stable improvement in visual acuity in both patients. To our knowledge, this is the first report of using a cyclooxygenase-2 inhibitor in the treatment of clinically significant CME.

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.