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Premature closure is often described as a significant contributor to diagnostic error. Therefore, developing strategies to mitigate premature closure could reduce diagnostic errors and improve patient care. Here we propose the novel concept of pursuit of an “endpoint diagnosis” as a cognitive forcing strategy (CFS) for avoiding premature diagnostic closure. We define an “endpoint diagnosis” as an underlying causative explanation for a patient’s signs, symptoms, and laboratory and radiographic data that exhausts additional relevant diagnostic evaluation. We have observed four contexts in which the error of not pursuing an endpoint diagnosis most often occurs: (1) diagnoses that appear to result in the same treatment regardless of etiology, (2) cases that are particularly complex, (3) clinical scenarios that are vulnerable to systems errors, and (4) situations in which patients’ problems are attributed to uncontrolled underlying risk factors or an exacerbation of a known condition. Additionally, we address why we believe endpoint diagnoses are not universally pursued, delineate when this approach might be particularly useful, attempt to reconcile the potential conflict between accepting diagnostic ambiguity in certain instances and pursuing endpoint diagnoses, and outline possible concerns that might arise with using this CFS, including the possibility of lengthy evaluations resulting in overdiagnosis and overtreatment. Our overarching goal is for this CFS to help clinicians in their daily clinical practice as they seek to optimize their diagnostic skill and patient care.

Cardiac disease has emerged as a leading cause of mortality in Duchenne muscular dystrophy in the current era. This survey sought to identify the diagnostic and therapeutic approach to DMD among pediatric cardiologists in Advanced Cardiac Therapies Improving Outcomes Network. Pediatric cardiology providers within ACTION (a multi-center pediatric heart failure learning network) were surveyed regarding their approaches to cardiac care in DMD. Thirty-one providers from 23 centers responded. Cardiac MRI and Holter monitoring are routinely obtained, but the frequency of use and indications for ordering these tests varied widely. Angiotensin converting enzyme inhibitor and aldosterone antagonist are generally initiated prior to onset of systolic dysfunction, while the indications for initiating beta-blocker therapy vary more widely. Seventeen (55%) providers report their center has placed an implantable cardioverter defibrillator in at least 1 DMD patient, while 11 providers (35%) would not place an ICD for primary prevention in a DMD patient. Twenty-three providers (74%) would consider placement of a ventricular assist device (VAD) as destination therapy (n = 23, 74%) and three providers (10%) would consider a VAD only as bridge to transplant. Five providers (16%) would not consider VAD at their institution. Cardiac diagnostic and therapeutic approaches vary among ACTION centers, with notable variation present regarding the use of advanced therapies (ICD and VAD). The network is currently working to harmonize medical practices and optimize clinical care in an era of rapidly evolving outcomes and cardiac/skeletal muscle therapies.

Purpose: To quantify the differences in daily physical activity (PA) patterns, intensity-specific volumes, and PA bouts in youth with and without heart disease (HD). Methods: Seven-day PA was measured on children/adolescents with HD (n = 34; median age 12.4 y; 61.8% male; 70.6% single ventricle, 17.7% heart failure, and 11.8% pulmonary hypertension) and controls without HD (n = 22; median age 12.3 y; 59.1% male). Mean counts per minute were classified as sedentary, light, and moderate to vigorous PA (MVPA), and bouts of MVPA were calculated. PA was calculated separately for each hour of wear time from 8:00 to 22:00. Multilevel linear mixed modeling compared the outcomes, stratifying by group, time of day, and day part (presented as median percentage of valid wear time [interquartile range]). Results: Compared with the controls, the HD group had more light PA (33.9% [15%] vs 29.6% [9.5%]), less MVPA (1.7% [2.5%] vs 3.2% [3.3%]), and more sporadic bouts (97.4% [5.7%] vs 89.9% [9.2%]), but fewer short (2.0% [3.9%] vs 7.1% [5.7%]) and medium-to-long bouts (0.0% [1.9%] vs 1.6% [4.6%]) of MVPA. The HD group was less active in the late afternoon, between 15:00 and 17:00 (P Conclusion: Children/adolescents with HD exhibit differences in intensity-specific volumes, PA bouts, and daily PA patterns compared with controls.

Frailty is a multi-dimensional clinical syndrome that is associated with increased morbidity and mortality and decreased quality of life. Children/adolescents with heart disease (HD) perform significantly worse for each frailty domain compared to non-HD peers. Our study aimed to create a composite frailty score (CFS) that can be applied to children/adolescents with HD and evaluate associations between the CFS and outcomes. Children and adolescents (n = 30) with HD (73% single ventricle, 20% heart failure, 7% pulmonary hypertension) were recruited from 2016 to 2017 (baseline). Five frailty domains were assessed at baseline using measures validated for pediatrics: 1) Slowness: 6-minute walk test; 2) Weakness: handgrip strength; 3) Fatigue: PedsQL Multi-dimensional Fatigue Scale; 4) Body composition: triceps skinfold thickness; 5) Physical activity questionnaire. Frailty points per domain (range = 0–5) were assigned based on z-scores or raw questionnaire scores and summed to produce a CFS (0 = least frail; 25 = most frail). Nonparametric bootstrapping was used to identify correlations between CFS and cross-sectional change in outcomes over 2.2 ± 0.2 years. The mean CFS was 12.5 ± 3.5. In cross-sectional analyses of baseline data, correlations (|r|≥0.25) were observed between CFS and NYHA class, the number of ancillary specialists, total prescribed medications, heart failure medications/day, exercise test derived chronotropic index and percent predicted VO2peak, and between child and parent-proxy PEDsQL. At follow-up, CFS was correlated with an increase in the number of heart failure medications (r = 0.31). CFS was associated with cross-sectional outcomes in youth with heart disease. Longitudinal analyses were limited by small sample sizes due to loss to follow-up.

Children and adolescents with cardiac disease (CCD) have significant morbidity and lower quality of life. However, there are no broadly applicable tools similar to the frailty score as described in the elderly, to define functional phenotype in terms of physical capability and psychosocial wellbeing in CCD. The purpose of this study is to investigate the domains of the frailty in CCD. We prospectively recruited CCD (8–17.5 years old, 70% single ventricle, 27% heart failure, 12% pulmonary hypertension; NYHA classes I, II and III) and age and gender matched healthy controls (total n = 56; CCD n = 34, controls n = 22; age 12.6 ± 2.6 years; 39.3% female). We measured the five domains of frailty: slowness, weakness, exhaustion, body composition and physical activity using developmentally appropriate methods. Age and gender-based population norms were used to obtain Z scores and percentiles for each measurement. Two-tailed t-tests were used to compare the two groups. The CCD group performed significantly worse in all five domains of frailty compared to healthy controls. Slowness: 6-min walk test with Z score −3.9 ± 1.3 vs −1.4 ± 1.3, p

Background Fontan-associated liver disease (FALD) uniformly affects patients with long-term Fontan physiology. The effect of isolated heart transplant (HT) on the course of FALD post-HT is not well understood. Methods We evaluated serial liver imaging pre- and post-HT to assess liver changes over time in a single-center retrospective analysis of Fontan HT recipients who had pre- and ≥1-year post-HT liver imaging. Available patient demographic and clinical data were reviewed, including available liver biopsy results. Results Serial liver imaging was available in 19 patients with a median age at HT of 12 years (range 3-23), the median age from Fontan to HT of 5.7 years (range 0.8-16), and the median time from imaging to follow up of 27 months (range 12-136 months). Pre-HT liver imaging was classified as follows: normal (n=1), congested (n=9), fibrotic (n=7), and cirrhotic (n=2). The majority of transplanted patients (15/19) had improvement in their post-HT liver imaging, including 13 patients with initially abnormal imaging pre-HT having normal liver imaging at follow-up. One patient had persistent cirrhosis at 26-month follow-up, one patient had unchanged fibrosis at 18-month follow-up, and one patient progressed from fibrosis pre-HT to cirrhosis post-HT at 136 months. No patients had overt isolated liver failure during pre- or post-HT follow-up. Liver biopsy did not consistently correlate with imaging findings. Conclusions Post-HT liver imaging evaluation in Fontan patients reveals heterogeneous liver outcomes. These results not only provide evidence for the improvement of FALD post-HT but also show the need for serial liver imaging follow-up post-HT.

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.

Convention dictates that an axillary view be obtained when evaluating proximal humerus fractures (PHF). However, the axillary view is frequently omitted because of pain and technical considerations. Furthermore, its diagnostic utility is unclear in this setting.The purpose of this study was to (1) determine the rate of obtaining an adequate axillary X-ray and complete shoulder series at a level I trauma center, (2) understand the cost of ordering and attempting an axillary radiograph, and (3) determine if axillary radiographs influence the management of PHF.PHF treated between 2009 and 2011 that were ordered for an AP, scapular Y, and axillary view was identified. The types of radiographs actually obtained were recorded. The cost of obtaining three views and a single view of the shoulder with X-ray was determined. Lastly, three surgeons reviewed 42 PHF, both with and without an axillary view (AV), and treatment recommendations were compared.30% of PHF in this series had an adequate axillary view, and 14% received a complete trauma series. No factors could be identified that were associated with successfully obtaining an axillary view. Reviewers demonstrated substantial intraobserver reliability (κ = 0.759-0.808) regarding treatment recommendations for PHF with and without the axillary view. The addition of the AV had minimal influence on treatment recommendations.Considering that the axillary view for PHF is painful, labor-intensive, costly, and does not appear to provide additional diagnostic value, orthopedic surgeons can consider foregoing the use of the axillary view when evaluating and treating PHF, particularly if other advanced imaging is utilized.

Die durch Adenoviren ausgeloste Keratoconjunctivitis (epidemica, KCE; ICD-10 B30.0+) ist haufig, kann schwer verlaufen und verursacht eine erhebliche Morbiditat. In der Fruhphase ist es oft schwierig, allein aufgrund des klinischen Befundes die KCE von anderen Ursachen eines anderen „roten Auges“ zu unterscheiden. Aufgrund hoher Kontagiositat kann sich die Erkrankung rasch zu einem epidemischen Geschehen auswachsen. Daher bleibt eine rasche Virusidentifikation und Vermeidung weiterer Ausbreitung der Infektion eine wesentliche Herausforderung. Da es schwierig ist, kurzfristig den labortechnischen Erregernachweis zu fuhren, wird der Anfangsverdacht zunachst rein klinisch geausert. Neuentwicklungen wie Screeningtests sind von praktischer Bedeutung und konnen die Fruhdiagnose unterstutzen. Adenoviren sind klinisch problematisch, da sie eine hohe Resistenz gegenuber Umweltfaktoren aufweisen und hoch entwickelte „Escape-Mechanismen“ eine Persistenz des Virus auch uber lange Zeit an der Augenoberflache ermoglichen. Bestandteile der Virusproteine verbleiben haufig in der Hornhaut, vor allem in der Bowman-Schicht. Hier fuhren sie zu immunologischen Reaktionen und den typischen subepithelialen Infiltraten („Nummuli“). Die Behandlung der KCE beschrankt sich zurzeit auf symptomatische Oberflachenpflege. Das Hauptproblem, die Persistenz subepithelialer Infiltrate, ist schwierig anzugehen. Eine risikoarme Option ist die Anwendung von Ciclosporin-A-Augentropfen. Die Behandlung mit topischen Steroiden ist eher problematisch, kann jedoch in allen Krankheitsstadien diskutiert werden. Da die Verbreitung von Adenoviren oft nosokomial erfolgt, bleibt die Pravention der Infektion eine zentrale Verantwortung der Ophthalmologen.

To compare radiographic and clinical outcomes of supination external rotation type IV equivalent (SER IV E) ankle fractures (AO/OTA classification 44-B2.1) treated with transsyndesmotic screw fixation with those treated with deltoid and posterior inferior tibiofibular ligament (PITFL) repair.Case series and single-surgeon retrospective analysis of a prospective database.Academic level I trauma center.Forty-five SER IV E ankle fractures fulfilled all inclusion/exclusion criteria with at least 12 months of radiographic follow-up.Deltoid and PITFL repair in addition to lateral malleolus fixation compared with transsyndesmotic screw fixation.Syndesmotic reduction compared with contralateral extremity on a postoperative computed tomography scan and maintenance of reduction based on final postoperative radiographs [medial clear space (MCS) and tibiofibular clear space (TCS)].There was no significant difference in mean postoperative TCS, MCS, or change in TCS or MCS between the cohorts. The anatomic treatment group had significantly better postoperative syndesmotic reduction compared with the transsyndesmotic cohort (7.4% vs. 33.3%; P = 0.02). Fourteen patients in the transsyndesmotic screw cohort underwent removal compared with 3 patients in the anatomic cohort who required secondary procedures. The transsyndesmotic screw cohort had statistically significant better mean dorsiflexion of ankle (mean 20 vs. 17 degrees; P = 0.02).This comparison of treatment strategies for SER IV E ankle fractures has shown an improvement in immediate postoperative syndesmotic reduction and the elimination of reoperation for removal of transsyndesmotic screws in patients treated with PITFL repair. Previous research has shown a good correlation between functional outcomes and syndesmotic reduction; however, further investigation into the functional outcomes of these patients is necessary to determine the future clinical impact of this anatomic fixation strategy.Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Background— Intravenous inotropic therapy can be used to support children awaiting heart transplantation. Although use of this therapy is discouraged in adults because of poor outcomes, its use in children, particularly outpatient, has had limited evaluation. We aimed to evaluate the safety and efficacy of this practice. Methods and Results— A retrospective analysis of an intent to treat protocol was completed on United Network for Organ Sharing status 1A patients discharged on inotropic therapy from 1999 until 2012. Intravenous inotropic therapy was initiated for cardiac symptoms not amenable to oral therapy. Patients who were not status 1A or required >1 inotrope were excluded. Efficacy was analyzed by time to first event: transplantation; readmission until transplantation; improvement leading to inotrope withdrawal; or death. Safety included analysis of infection rates, line malfunctions, temporary hospitalization, neurological events, and arrhythmias. One hundred six patients met inclusion criteria. The mean age was 10.1±6.4 years, 47% of patients had congenital heart disease, and 80% of these patients had single ventricle physiology. In patients without congenital heart disease, 53% had dilated cardiomyopathy, 91% of patients received milrinone, 85% of patients underwent transplantation, 8% of patients successfully weaned from support as outpatients, whereas 6% died. Fifty percent of patients were readmitted before transplantation or weaning from support, of which 64% required only 1 readmission. The majority of readmissions were for heart failure. Conclusions— Outpatient intravenous inotropic therapy can be safely used as a bridge to transplantation in pediatric patients. A minority of patients can discontinue inotropic therapy because of clinical improvement.

Viral infections can affect the pediatric heart in a multitude of ways. The two most common viral cardiac processes are myocarditis and pericarditis. Numerous viruses have been implicated in these disease states. In addition to direct viral effects on the myocardium and pericardium, inflammatory mediators also play a role in these conditions. A high index of suspicion, thorough history and physical examination, along with directed laboratory testing, electrocardiography and echocardiography are necessary for the diagnosis and management of myocarditis and pericarditis. Occasionally, more advanced studies such as magnetic resonance imaging (MRI) and endomyocardial biopsy may be useful. Finally, human immunodeficiency virus (HIV) can have a number of cardiac related effects. Children with HIV, require routine cardiac monitoring and counseling.

Background: The hyperplantarflexion variant ankle fracture is composed of a posterior tibial lip fracture with posterolateral and posteromedial fracture fragments separated by a vertical fracture line. This infrequently reported injury pattern often includes an associated “spur sign” or double cortical density at the inferomedial tibial metaphysis. The objective of this study was to quantitatively establish the association of the ankle fracture spur sign with the hyperplantarflexion variant ankle fracture. Methods: Our clinical database of operative ankle fractures was retrospectively reviewed for the incidence of hyperplantarflexion variant and nonvariant ankle fractures as determined by assessment of injury radiographs, preoperative advanced imaging, and intraoperative observation. Injury radiographs were then evaluated for the presence of the spur sign, and association between the spur sign and variant fractures was analyzed. Results: The incidence of the hyperplantarflexion variant fracture among all ankle fractures was 6.7% (43/640). The spur sign was present in 79% (34/43) of variant fractures and absent in all nonvariant fractures, conferring a specificity of 100% in identifying variant fractures. Positive predictive value and negative predictive value were 100% and 99%, respectively. Conclusion: The ankle fracture spur sign was pathognomonic for the hyperplantarflexion variant ankle fracture. It is important to identify variant fractures preoperatively as patient positioning, operative approach, and fixation construct of variant fractures often differ from those employed for osteosynthesis of nonvariant fractures. Identification of the spur sign should prompt acquisition of advanced imaging to formulate an appropriate operative plan to address the variant fracture pattern. Level of Evidence: Level III, retrospective comparative study.

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.

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. 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. 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. 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.

Purpose: The accuracy of Goldmann applanation tonometry (GAT) has been shown to depend on several biomechanical properties of the cornea. Newer tonometry devices (e.g., the Dynamic Contour Tonometer PASCAL? [DCT] and the Tono-Pen? XL [TP]) have been designed to accurately measure intraocular pressure (IOP) independent of corneal thickness (CCT) and pathology. This study investigates the influence of corneal pathologies on the accuracy of these IOP measuring devices, and compares this accuracy to that of direct intracameral IOP measurement. Methods: 8 eyes of 8 patients suffering from corneal pathologies scheduled for penetrating keratoplasty, and 10 eyes of 10 patients scheduled for cataract surgery (control group) were examined. Before surgery, the anterior chamber was cannulated at the temporal corneal limbus. In a closed system, the intraocular pressure (IOP) was directly set to 10, 20, and 30 mmHg with a manometric water column. Intraocular pressure measurements taken by GAT, DCT, and TP were compared to intracameral measurements obtained by a precision reference pressure sensor. Results: Control group: All three methods showed good agreement with the intracameral readings (mean deviation of all three devices, -0.9 mmHg). Group with corneal pathologies: The TP yielded the most exact IOP values in the group with corneal pathologies when taking all diagnoses into account. The mean deviations from the intracameral IOP measurements were -0.9 mmHg ± 3.2 mmHg (mean ± SD) for TP, -2.9 mmHg ± 3.3 mmHg for GAT, and -5.0 mmHg ± 7.9 mmHg for DCT. For bullous keratopathy, the most exact IOP readings were obtained by the TP (mean deviation -0.2 mmHg ± 3.5 mmHg). The TP and GAT devices underestimated IOP in the patients with Fuchs’ endothelial dystrophy; all 3 devices underestimated adjusted IOP after keratoplasty. DCT showed the greatest deviations from adjusted IOP in the case of non-herpetic scars. In the control group, none of the devices showed a statistically relevant dependency on CCT. Nevertheless, in the group with corneal pathologies, only TP showed no dependency on CCT. Conclusion: Our results suggest that the Tono-Pen XL? is the most accurate measurement device to determine IOP in patients with corneal pathologies, especially in patients suffering from corneal edema (bullous keratopathy). GAT yielded surprisingly exact IOP values in patients suffering from irregular corneal surface. DCT showed a high degree of deviation from the adjusted IOP, and should not be used to determine IOP in corneas with the disorders listed here.

Cardiomyopathies represent an uncommon but serious cause of heart disease in the pediatric population and can be categorized as dilated, hypertrophic, restrictive and left ventricular non-compaction. Each of these subtypes has multiple potential genetic etiologies in addition to possible non-genetic causes. Many patients with cardiomyopathies can benefit from transplantation, although there is not insignificant morbidity and mortality for those patients. Outcomes both prior to and following transplantation depend on the underlying etiology, the amount of support needed prior to transplantation and the illness severity of the patient prior to transplantation. Mechanical circulatory support is frequently used to bridge patients to transplantation, and newer technologies are currently in development.

Obstructive sleep apnea (OSA) is a common pediatric breathing disorder, affecting 1-5% of all children. Pulmonary hypertension (PH), a severe complication of OSA, is associated with significant morbidity and mortality. Despite this important relationship between OSA and PH, there is sparse literature addressing this subject in children. This review will examine the putative relationship between OSA and PH, synthesize the available literature in children, and suggest a reasonable approach, despite limited data, for clinicians. We conclude that available evidence suggests many children with OSA have evidence of PH (estimates ranging from 0% to 85%) and vice versa (estimates ranging from 6% to 24%). Furthermore, previous studies demonstrate that treatment of the OSA, either with surgery or non-invasive ventilation, ameliorates pulmonary artery pressures to the extent of cure in a substantial number of cases. Future studies are required to better delineate the true co-occurrence of these diseases and help predict which patients are at greater risk for this serious complication. Clinicians who maintain a healthy vigilance for this important interaction of disease states will likely recognize opportunities to intervene and improve prognoses in these patients.

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).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).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); P0.01]. 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%).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.

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. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Acute myocarditis may lead to left ventricular dysfunction and subsequent need for cardiac transplantation. We describe a 15-month-old child who presented with right heart failure of unclear cause. Echocardiography showed normal left ventricular function; however, right ventricular function was markedly reduced. The patient required extracorporeal membrane oxygenation followed by placement of a right-sided Berlin EXCOR ventricular assist device. There was little recovery, and the child underwent cardiac transplantation. Subsequent pathologic examination revealed lymphocytic myocarditis. We believe this is the first use of an isolated right ventricular assist device as a bridge to heart transplantation.

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.

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.

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.

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.

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.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.Median graft survival times were 15 days in old recipients and 9 days in young recipients (p0.01). 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.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.

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.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.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.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.

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.

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.

Ziel dieser Studie war der Nachweis der Sicherheit und Effektivitat des intrastromalen Hornhautringes nach Krumeich bei perforierender Keratoplastik. Das Hauptzielkriterium war der postoperative Astigmatismus. Es wurden insgesamt 20 Patienten in diese Studie eingeschlossen (randomisiert 10 Patienten mit Ring; 10 Patienten ohne Ring). Bei den Nachkontrollen wurde neben Bestimmung des bestkorrigierten Visus jeweils eine Orbscan-Hornhaut-Topographie durchgefuhrt. Die mittlere Nachbeobachtungszeit betragt derzeit 18,9±2,8 Monate. Der mittlere Astigmatismus (im Orbscan) betragt 3,9 dpt in der Gruppe mit Hornhautring und 4,0 dpt in der Gruppe ohne Ring. Bei 5 Patienten mit Hornhautring kam es zu spontanen Fadenrupturen. In dieser Studie zeigte die Verwendung des intrastromalen Hornhautringes mit teilweise noch liegenden fortlaufenden Nahten keine Minderung des postoperativen Astigmatismus. Die Ursache fur die spontanen Fadenrupturen ist unklar.

Die haufigste Ursache fur die Eintrubung eines Transplantats nach perforierender Keratoplastik ist die Abstosungsreaktion. Die endotheliale Immunreaktion ist die haufigste und zugleich fur das Transplantat gefahrlichste Form der Abstosung, da sie das Transplantatendothel zerstoren und damit zum Transplantatversagen fuhren kann. Die Therapie der „akuten“ endothelialen Abstosungsreaktion besteht in der lokalen und ggf. systemischen Gabe von Steroiden. Die intrakamerale Applikation von Kortikosteroiden mittels Vorderkammerspulung zur Therapie der schweren endothelialen Abstosung nach perforierender Keratoplastik ist eine zusatzliche Masnahme, welche besonders schnell die Immunreaktion stoppen kann. Die Durchfuhrung dieser Masnahme wird bei allen mittelschweren und schweren endothelialen Abstosungsreaktionen empfohlen.

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.

Die immunologische Abstosungsreaktion ist der wichtigste Grund fur ein Transplantatversagen nach Hornhauttransplantation. Ohne systemische Immunsuppression kommt es in einer Hochrisikosituation in uber 50% der Falle zu einer Eintrubung des Transplantats innerhalb des ersten postoperativen Jahres. Die klonale Expansion von alloreaktiven Lymphozyten findet in lymphoiden Organen statt. Da topische Steroide die sekundaren lymphatischen Gewebe nicht erreichen und auch systemische Steroide nicht ausreichend die klonale Expansion von aktivierten T-Zellen unterdrucken, ist der Einsatz von systemischen Immunsuppressiva unumganglich, um ein klares Transplantatuberleben zu erreichen. Es ist allerdings besonders nach Hochrisikokeratoplastik, einer nicht lebensrettenden Transplantation wichtig, die Vor- und Nachteile einer immunsuppressiven Therapie abzuwagen.

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.

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.

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.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.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) (p0.05). 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 (p0.05). In group 5 however, the reduction of infiltration by CD4+ cells was higher than the reduction of infiltration by CD8+ (p0.05) and CD161+ (NK) cells.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.

Die autologe Rotationskeratoplastik stellt bei zentralen Hornhautnarben eine therapeutische Option zur Visusrehabilitation dar. Ihr groser Vorteil gegenuber allogenen Verfahren ist das Ausbleiben von Immunreaktionen. In dieser retrospektiven Analyse sollen langfristige Ergebnisse prasentiert werden. Seit 1988 wurde bei 19 Patienten eine Autorotationskeratoplastik durchgefuhrt. Die Trepangrose variierte von 7,0–9,0 mm. Die mittlere Nachbeobachtungszeit betrug 7,1±4,6 Jahre. 16 von 19 Transplantaten waren innerhalb der Nachbeobachtungszeit zentral klar geblieben. Mit Brillenkorrektur war ein Visusanstieg von 0,25 (±0,16) praoperativ auf 0,34 (±0,27) postoperativ und mit harter Kontaktlinse postoperativ auf 0,43 (±0,3) erreichbar. Der mittlere postoperative Astigmatismus lag bei 6,41 dpt (±3,87). Nur wenige postoperative Transplantatkomplikationen wurden beobachtet. Insbesondere in Situationen mit hohem Risiko fur Immunreaktionen (beispielsweise im Sauglingsalter) kann die autologe Rotationskeratoplastik daher als Alternative zu allogenen Operationsverfahren empfohlen werden.

Percutaneous Transfemoral Placement of a New Flexible Stent-Graft Into the Thoracic Aorta Followed by a Percutaneous Suture-Mediated Closure of the Access Site - Initial Experience. Purpose: To evaluate the transfemoral placement of a new, flexible stent-graft into the thoracic aorta and the suture-mediated closure of the femoral access. Patients and Methods: Five patients were treated endovascularly with a stent-graft for an aneurysm (n = 3) or acute dissection (n = 2) of f the thoracic aorta via a femoral 24 F sheath. The femoral access site was closed with two suture-mediated closure devices after placement of the stent-graft. Results: The aneurysm or the false lumen was excluded from perfusion by the placement of the stent-graft in all patients. Hemostasis at the femoral access site was successful in all patients with the percutaneous suture device. A minor stenosis of the femoral artery was found angiographically in four patients after suture-mediated closure. Besides a reversible renal failure due to the medically induced hypotension for the treatment of an acutely ruptured aneurysm, no complications resulted from the stent-graft placement or the percutaneous suture. Conclusion: The percutaneous transfemoral placement of stent-grafts in the thoracic aorta using a suture-mediated closure of the access site is technically feasible. Long-term results of the technique have to be awaited.

Die Einfuhrung des Femtosekundenlasers ermoglichte vollig neue Trepanationstechniken bei der perforierenden Keratoplastik mit Stufen in Transplantat und Wirtshornhaut. Die gebrauchlichsten der sog. profilierten Trepanationen sind das Top-hat- und das Mushroom-Profil. Durch die Stufen wird eine bessere Abdichtbarkeit intraoperativ erreicht und durch die grosere Wundflache eine zugigere und stabilere Wundheilung. Dies ermoglicht moglicherweise eine schnellere Fadenentfernung und endgultige Visusrehabilitation. Die ersten klinischen Ergebnisse zeigen, dass es sich um eine sichere Operationsmethode handelt. Ob die Astigmatismusergebnisse besser sind als mit herkommlichen Trepanationsmethoden, werden die Langzeitergebnisse nach kompletter Fadenentfernung zeigen.

Die Keratokonjunktivitis epidemica ist eine haufige Infektionskrankheit der Augenoberflache, die durch Adenoviren verursacht wird. Die Keratitis nummularis ist die chronische Verlaufsform. Cyclosporin A ist ein Kalzineurininhibitor, der in der Augenheilkunde seit etwa 15 Jahren in der Lokaltherapie chronischer Entzundungszustande der Augenoberflache eingesetzt wird. Fur die Behandlung der Keratitis nummularis hat sich dieses Medikament seit den 90er Jahren des letzten Jahrhunderts bewahrt. Die Indikation zur Behandlung mit Cyclosporin-A-Augentropfen sollte gestellt werden, wenn sich bei nummulibedingter Visusminderung innerhalb von 6 Wochen nach der akuten Entzundung keine Tendenz zur spontanen Besserung zeigt.

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.

A rare neurodevelopmental disorder in the Old Order Mennonite population called PMSE (polyhydramnios, megalencephaly, and symptomatic epilepsy syndrome; also called Pretzel syndrome) is characterized by infantile-onset epilepsy, neurocognitive delay, craniofacial dysmorphism, and histopathological evidence of heterotopic neurons in subcortical white matter and subependymal regions. PMSE is caused by a homozygous deletion of exons 9 to 13 of the LYK5/STRADA gene, which encodes the pseudokinase STRADA, an upstream inhibitor of mammalian target of rapamycin complex 1 (mTORC1). We show that disrupted pathfinding in migrating mouse neural progenitor cells in vitro caused by STRADA depletion is prevented by mTORC1 inhibition with rapamycin or inhibition of its downstream effector p70 S6 kinase (p70S6K) with the drug PF-4708671 (p70S6Ki). We demonstrate that rapamycin can rescue aberrant cortical lamination and heterotopia associated with STRADA depletion in the mouse cerebral cortex. Constitutive mTORC1 signaling and a migration defect observed in fibroblasts from patients with PMSE were also prevented by mTORC1 inhibition. On the basis of these preclinical findings, we treated five PMSE patients with sirolimus (rapamycin) without complication and observed a reduction in seizure frequency and an improvement in receptive language. Our findings demonstrate a mechanistic link between STRADA loss and mTORC1 hyperactivity in PMSE, and suggest that mTORC1 inhibition may be a potential treatment for PMSE as well as other mTOR-associated neurodevelopmental disorders.