Augenklinik Universitätsklinikum Würzburg

Previous attempts have shown the potential of T cells in immunotherapy of cancer. Here, we report on the clinical activity of a bispecific antibody construct called blinatumomab, which has the potential to engage all cytotoxic T cells in patients for lysis of cancer cells. Doses as low as 0.005 milligrams per square meter per day in non-Hodgkin's lymphoma patients led to an elimination of target cells in blood. Partial and complete tumor regressions were first observed at a dose level of 0.015 milligrams, and all seven patients treated at a dose level of 0.06 milligrams experienced a tumor regression. Blinatumomab also led to clearance of tumor cells from bone marrow and liver. T cell-engaging antibodies appear to have therapeutic potential for the treatment of malignant diseases.

CV Cardiovascular CYP Cytochrome P (CYP) Unfractionated heparin ULN Upper limit of normal VENTURE-AF Active-controlled multi-center study with blind-adjudication designed to evaluate the safety of uninterrupted Rivaroxaban and uninterrupted vitamin K antagonists in subjects undergoing catheter ablation for non-valvular Atrial Fibrillation VHD Valvular heart disease VKA Vitamin K antagonist VTE Venous thromboembolic event WOEST What is the Optimal antiplatelet and anticoagulant therapy in patients with oral anticoagulation and coronary stenting X-VeRT Explore the efficacy and safety of once daily oral rivaroxaban for the prevention of cardiovascular events in patients with non-valvular atrial fibrillation scheduled for cardioversion a SmPC: 110 mg BID if age > _80 years, concomitant verapamil (both based on pharmacokinetics/pharmacodynamics analyses; not studied in this setting). b Not specifically studied, follow-up data available up to 12 months in phase III trial. c SmPc: 20 mg QD in patients at high risk of recurrence. 2021 EHRA Practical Guide on the use of NOACs AF, atrial fibrillation; CrCl, creatinine clearance; INR, international normalized ratio; NOAC, non-vitamin K antagonist oral anticoagulant; NSAID, non-steroidal anti-inflammatory drug; TIA, transient ischaemic attack; VKA, vitamin K antagonist. For frequency of visits: see Figure 3.

Chimeric antigen receptor (CAR) T cells are a novel class of anti-cancer therapy in which autologous or allogeneic T cells are engineered to express a CAR targeting a membrane antigen. In Europe, tisagenlecleucel (Kymriah™) is approved for the treatment of refractory/relapsed acute lymphoblastic leukemia in children and young adults as well as relapsed/refractory diffuse large B-cell lymphoma, while axicabtagene ciloleucel (Yescarta™) is approved for the treatment of relapsed/refractory high-grade B-cell lymphoma and primary mediastinal B-cell lymphoma. Both agents are genetically engineered autologous T cells targeting CD19. These practical recommendations, prepared under the auspices of the European Society of Blood and Marrow Transplantation, relate to patient care and supply chain management under the following headings: patient eligibility, screening laboratory tests and imaging and work-up prior to leukapheresis, how to perform leukapheresis, bridging therapy, lymphodepleting conditioning, product receipt and thawing, infusion of CAR T cells, short-term complications including cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, antibiotic prophylaxis, medium-term complications including cytopenias and B-cell aplasia, nursing and psychological support for patients, long-term follow-up, post-authorization safety surveillance, and regulatory issues. These recommendations are not prescriptive and are intended as guidance in the use of this novel therapeutic class.

In human and experimental myocardial infarction (MI), cessation of blood supply leads to rapid necrosis of cardiac myocytes in the ischaemic heart. Immediately after injury, various intra- and intercellular pathways contribute to healing the myocardial wound in order to achieve tissue integrity and function. MI and the consequent loss of myocardium are the major aetiology for heart failure. Despite aggressive primary therapy, prognosis remains poor in patients with large infarction and severe left ventricular dysfunction. Thus, it would be highly desirable to improve healing of the cardiac wound to maintain structure and function of the heart. Healing in the heart occurs in overlapping phases. Herein, we review the inflammatory phase as a trigger of tissue formation.

INTRODUCTION: Evidence from a number of open-label, uncontrolled studies has suggested that rituximab may benefit patients with autoimmune diseases who are refractory to standard-of-care. The objective of this study was to evaluate the safety and clinical outcomes of rituximab in several standard-of-care-refractory autoimmune diseases (within rheumatology, nephrology, dermatology and neurology) other than rheumatoid arthritis or non-Hodgkin's lymphoma in a real-life clinical setting. METHODS: Patients who received rituximab having shown an inadequate response to standard-of-care had their safety and clinical outcomes data retrospectively analysed as part of the German Registry of Autoimmune Diseases. The main outcome measures were safety and clinical response, as judged at the discretion of the investigators. RESULTS: A total of 370 patients (299 patient-years) with various autoimmune diseases (23.0% with systemic lupus erythematosus, 15.7% antineutrophil cytoplasmic antibody-associated granulomatous vasculitides, 15.1% multiple sclerosis and 10.0% pemphigus) from 42 centres received a mean dose of 2,440 mg of rituximab over a median (range) of 194 (180 to 1,407) days. The overall rate of serious infections was 5.3 per 100 patient-years during rituximab therapy. Opportunistic infections were infrequent across the whole study population, and mostly occurred in patients with systemic lupus erythematosus. There were 11 deaths (3.0% of patients) after rituximab treatment (mean 11.6 months after first infusion, range 0.8 to 31.3 months), with most of the deaths caused by infections. Overall (n = 293), 13.3% of patients showed no response, 45.1% showed a partial response and 41.6% showed a complete response. Responses were also reflected by reduced use of glucocorticoids and various immunosuppressives during rituximab therapy and follow-up compared with before rituximab. Rituximab generally had a positive effect on patient well-being (physician's visual analogue scale; mean improvement from baseline of 12.1 mm). CONCLUSIONS: Data from this registry indicate that rituximab is a commonly employed, well-tolerated therapy with potential beneficial effects in standard of care-refractory autoimmune diseases, and support the results from other open-label, uncontrolled studies.

Information obtained at interview from 1,646 parasuicide patients in 14 regions in 13 European countries participating in the WHO/EURO Multicentre Study on Suicidal Behaviour was used to study self-reported intentions involved in parasuicide. Comparisons were made across cultures, genders, and age groups. Although some statistically significant differences were found, the effect sizes were very small. The main finding from this study is thus that parasuicide patients in different countries tend to indicate that similar types of intentions are involved in their acts of parasuicide, and that the intentions do not vary greatly with gender or age. The hypothesis that rates of suicide and parasuicide vary between regions with the frequency with which suicidal intention is indicated by the patients was also tested, but was supported only for women and in relation to national suicide rates. The findings from this study are likely to be generalizable to other settings and have implications for clinical practice.

Noncompaction of the ventricular myocardium (NVM) is the morphological hallmark of a rare familial or sporadic unclassified heart disease of heterogeneous origin. NVM results presumably from a congenital developmental error and has been traced back to single point mutations in various genes. The objective of this study was to determine the underlying genetic defect in a large German family suffering from NVM. Twenty four family members were clinically assessed using advanced imaging techniques. For molecular characterization, a genome-wide linkage analysis was undertaken and the disease locus was mapped to chromosome 14ptel-14q12. Subsequently, two genes of the disease interval, MYH6 and MYH7 (encoding the alpha- and beta-myosin heavy chain, respectively) were sequenced, leading to the identification of a previously unknown de novo missense mutation, c.842G>C, in the gene MYH7. The mutation affects a highly conserved amino acid in the myosin subfragment-1 (R281T). In silico simulations suggest that the mutation R281T prevents the formation of a salt bridge between residues R281 and D325, thereby destabilizing the myosin head. The mutation was exclusively present in morphologically affected family members. A few members of the family displayed NVM in combination with other heart defects, such as dislocation of the tricuspid valve (Ebstein's anomaly, EA) and atrial septal defect (ASD). A high degree of clinical variability was observed, ranging from the absence of symptoms in childhood to cardiac death in the third decade of life. The data presented in this report provide first evidence that a mutation in a sarcomeric protein can cause noncompaction of the ventricular myocardium.

Despite the strong interest in the NK cell-mediated immunity toward malignant cells and viruses, there is a relative lack of data on the interplay between NK cells and filamentous fungi, especially Aspergillus fumigatus, which is the major cause of invasive aspergillosis. By studying the in vitro interaction between human NK cells and A. fumigatus, we found only germinated morphologies to be highly immunogenic, able to induce a Th1-like response, and capable of upregulating cytokines such as IFN-γ and TNF-α. Moreover, priming NK cells with human rIL-2 and stimulating NK cells by direct NK cell-pathogen contact were essential to induce damage against A. fumigatus. However, the most interesting finding was that NK cells did not mediate anti-Aspergillus cytotoxicity through degranulation of their cytotoxic proteins (perforin, granzymes, granulysine), but via an alternative mechanism involving soluble factor(s). To our knowledge, our study is the first to demonstrate that IFN-γ, released by NK cells, directly damages A. fumigatus, attributing new properties to both human NK cells and IFN-γ and suggesting them as possible therapeutic tools against IA.

BACKGROUND: Chronic alcoholism in humans is associated with the development of hyperhomocysteinemia, the mechanism of which remains unclear. Among the causes of hyperhomocysteinemia is depletion of folate, vitamin B12, or vitamin B6. Population-based studies indicate that folate is the strongest vitamin determinant of hyperhomocysteinemia and, in most settings, folate supplementation effectively lowers elevated homocysteine levels. However, it is not clear whether folate deficiency is the cause of alcohol-related hyperhomocysteinemia. METHODS: In the present study, 10 male Sprague Dawley rats were fed ethanol-containing Lieber-DeCarli diets with 13 mg of folic acid per kilogram of diet. This represents a folate intake more than 20 times the basal requirement. Ethanol represented 36% of total energy, which yielded a concentration of 6.2% (vol/vol). The same number of rats were pair-fed with isocaloric control diets that contained an identical level of folate in which ethanol was entirely replaced by maltodextrin. RESULTS: At the end of 4 weeks, alcohol-fed rats did not show any significant reduction in plasma or hepatic folate concentrations, plasma pyridoxal-5'-phosphate concentration, or plasma vitamin B12 concentration. On the other hand, alcohol-fed rats were significantly hyperhomocysteinemic (17.24 +/- 4.63 micromol/liter,p < 0.01) compared to the nonalcohol group (10.73 +/- 2.76 micromol/liter). Alcohol-fed rats also had a significantly lower hepatic S-adenosylmethionine and higher hepatic S-adenosylhomocysteine levels. CONCLUSIONS: Chronic alcohol consumption produces hyperhomocysteinemia by a mechanism that is related to interference with one-carbon metabolism, and not through vitamin depletion.

OBJECTIVE: The aim of the study was to examine the relationship between suicide attempts and major public holidays in Europe. METHOD: The analysis was based on data on 24 388 suicide attempts by persons aged 15 years or older in the period 1989-1996. Data from 13 centres (representing 11 countries) participating in the WHO/EURO Multicentre Study on Parasuicide were analysed. The analysis of the fluctuation of suicide attempts around public holidays was based on the daily number of suicide attempts for each centre. For each day in the period under examination a mean number of suicide attempts (mu) was calculated. The analysis was based on the assumption that the data followed a Poisson distribution. The observed number of daily suicide attempts was compared with the expected number of attempts. A multiplicative model for the expected number in each centre was developed. RESULTS: Before Christmas there were fewer suicide attempts than expected, and after Christmas there were approximately 40% more attempts than expected. In addition, more attempts than expected were registered on New Year's Day. In countries where people have the day off work on Whit Monday there were significantly fewer attempts during the 3 days before, but where Whit Monday is a normal working day significantly fewer attempts occurred on the Monday to Wednesday after Whit Sunday. CONCLUSION: There appears to be a transposition of a significant number of suicide attempts from before (and during) a major public holiday until after it. The division of holidays into non-working and working days showed that a 'holiday effect' could only be found around major public holidays, particularly Christmas, Easter and Whitsun. These findings support the theory of the 'broken-promise effect' for major public holidays.

PURPOSE: To clarify the theoretical background of the rigid contact lens overrefraction (CLO) method to determine corneal power after corneal refractive surgery. SETTING: University Eye Clinic, University of Würzburg, Würzburg, Germany. METHODS: Using paraxial geometrical optics, the measurement situation for the contact lens method was analyzed and the definitions of corneal refractive power were reviewed. Based on the theoretical Gullstrand eye, model eyes were constructed, representing 1 emmetropic and 2 myopic eyes (primary refraction -5.21 diopters [D] and -10.25 D, respectively) before and after photorefractive keratectomy and laser in situ keratomileusis. In these eyes, the application of the CLO was mathematically simulated using Gaussian thick-lens optics and commercial ray-tracing software. RESULTS: The CLO method measured neither the equivalent (total) power nor the vertex (back) power of the cornea but rather the quantity 336/R(1C) (R(1C) = anterior corneal radius). Based on these results and the Gullstrand eye, new formulas are proposed to derive the equivalent power and vertex power of the cornea by the CLO method. CONCLUSIONS: Depending on whether intraocular lens calculation formulas are based on equivalent (total) corneal power or vertex corneal power, the respective new formulas for the CLO method should be applied in patients after corneal refractive surgery. An increase in prediction accuracy of the refractive outcome is expected.

The creatine kinase (CK) system is involved in the rapid transport of high-energy phosphates from the mitochondria to the sites of maximal energy requirements such as myofibrils and sarcolemmal ion pumps. Hearts of mice with a combined knockout of cytosolic M-CK and mitochondrial CK (M/Mito-CK(-/-)) show unchanged basal left ventricular (LV) performance but reduced myocardial high-energy phosphate concentrations. Moreover, skeletal muscle from M/Mito-CK(-/-) mice demonstrates altered Ca2+ homeostasis. Our hypothesis was that in CK-deficient hearts, a cardiac phenotype can be unmasked during acute stress conditions and that susceptibility to ischemia-reperfusion injury is increased because of altered Ca2+ homeostasis. We simultaneously studied LV performance and myocardial Ca2+ metabolism in isolated, perfused hearts of M/Mito-CK(-/-) (n = 6) and wild-type (WT, n = 8) mice during baseline, 20 min of no-flow ischemia, and recovery. Whereas LV performance was not different during baseline conditions, LV contracture during ischemia developed significantly earlier (408 +/- 72 vs. 678 +/- 54 s) and to a greater extent (50 +/- 2 vs. 36 +/- 3 mmHg) in M/Mito-CK(-/-) mice. During reperfusion, recovery of diastolic function was impaired (LV end-diastolic pressure: 22 +/- 3 vs. 10 +/- 2 mmHg), whereas recovery of systolic performance was delayed, in M/Mito-CK(-/-) mice. In parallel, Ca2+ transients were similar during baseline conditions; however, M/Mito-CK(-/-) mice showed a greater increase in diastolic Ca2+ concentration ([Ca2+]) during ischemia (237 +/- 54% vs. 167 +/- 25% of basal [Ca2+]) compared with WT mice. In conclusion, CK-deficient hearts show an increased susceptibility of LV performance and Ca2+ homeostasis to ischemic injury, associated with a blunted postischemic recovery. This demonstrates a key function of an intact CK system for maintenance of Ca2+ homeostasis and LV mechanics under metabolic stress conditions.

Abstract Purpose: A novel, selective, next-generation transforming growth factor beta (TGFβ) receptor type-1 small molecule inhibitor, LY3200882, demonstrated promising preclinical data. This first-in-human trial evaluated safety, tolerability, recommended phase II dose (RP2D), pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of LY3200882 as monotherapy or with other anticancer agents in patients with advanced cancer. Patients and Methods: This phase I multicenter study of oral LY3200882 (NCT02937272) comprised dose escalation, monotherapy expansion in grade 4 glioma, and combination therapy in solid tumors (LY3200882 and PD-L1 inhibitor LY3300054), pancreatic cancer (LY3200882, gemcitabine, and nab-paclitaxel), and head and neck squamous cell cancer (LY3200882, cisplatin, and radiation). Results: Overall, 139 patients with advanced cancer were treated. The majority (93.5%) of patients experienced ≥1 treatment-emergent adverse events (TEAE), with 39.6% LY3200882-related. Grade 3 LY3200882-related toxicities were only observed in combination therapy arms. One patient in the pancreatic cancer arm experienced cardiovascular toxicity. The LY3200882 monotherapy RP2Ds were established in two schedules: 50 mg twice a day 2-weeks-on/2-weeks-off and 35 mg twice a day 3-weeks-on/1-week-off. Four patients with grade 4 glioma had durable Revised Assessment in Neuro Oncology (RANO) partial responses (PR) with LY3200882 monotherapy (n = 3) or LY3200882-LY3300054 combination therapy (n = 1). In treatment-naïve patients with advanced pancreatic cancer, 6 of 12 patients achieved Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 PR and 3 of 12 patients demonstrated stable disease, for an overall 75% disease-control rate with the combination of LY3200882, gemcitabine, and nab-paclitaxel. Conclusions: LY3200882 as monotherapy and combination therapy was safe and well tolerated with preliminary antitumor activity observed in pancreatic cancer. Further studies to evaluate the efficacy of LY3200882 with gemcitabine and nab-paclitaxel in advanced pancreatic cancer are warranted.

Multiple myeloma (MM) is incurable, so there is a significant unmet need for effective therapy for patients with relapsed or refractory disease. This situation has not changed despite the recent approval of the anti-CD38 antibody daratumumab, one of the most potent agents in MM treatment. The efficiency of daratumumab might be improved by combining it with synergistic anti-MM agents. We therefore investigated the potential of the histone deacetylase (HDAC) inhibitor ricolinostat to up-regulate CD38 on MM cells, thereby enhancing the performance of CD38-specific therapies. Using quantitative reverse transcription polymerase chain reaction and flow cytometry, we observed that ricolinostat significantly increases CD38 RNA levels and CD38 surface expression on MM cells. Super-resolution microscopy imaging of MM cells by direct stochastic optical reconstruction microscopy confirmed this rise with molecular resolution and revealed homogeneous distribution of CD38 molecules on the cell membrane. Particularly important is that combining ricolinostat with daratumumab induced enhanced lysis of MM cells. We also evaluated next-generation HDAC6 inhibitors (ACY-241, WT-161) and observed similar increase of CD38 levels suggesting that the upregulation of CD38 expression on MM cells by HDAC6 inhibitors is a class effect. This proof-of-concept illustrates the potential benefit of combining HDAC6 inhibitors and CD38-directed immunotherapy for MM treatment.

BACKGROUND: Ocular trauma has significant impact on the patient's future quality of life. Progress in the treatment of ocular trauma may ameliorate the outcome, but preventive measures are more effective. However, prevention of ocular trauma can only be effective when the current epidemiology of ocular trauma is known. Therefore, we have now collected data on ocular trauma over nearly 20 years. This paper provides an overview on the development of open globe injuries in the past 20 years. PATIENTS: The records of 1026 patients with open globe injuries who were primarily treated at the Universities of Freiburg and Würzburg between January 1, 1981 and December 31, 1999, were sufficiently analyzed. The following parameters were evaluated: age, extent of injury, sex, cause. and activity at the time of injury. RESULTS: After correction for demographic distribution, the risk for open globe injury was highest for young adults and lowest for seniors. In recent years, the risk for severe eye injury is more equally distributed and is increasing for old people. We noted decreasing injuries at work and during traffic accidents, especially for young female front-seat passengers. On the other hand, we observed an increasing proportion of domestic eye injuries related to hobby activities. With increasing age we noted more posterior segment injuries. 9 % of all open globe injuries occurred among seniors (> 65 years old), but 41 % of all ruptures occurred in this age group. Preceding cataract surgery was identified as a risk factor. 38 % of injured persons in this age group had already had intraocular surgery. After the introduction of small incision techniques at the beginning of the 1990 s, the frequency of globe ruptures began to decrease again. 3.6 % of the injured eyes developed an endophthalmitis, in agricultural injuries the rate of endophthalmitis was 12 %. CONCLUSION: There is a relative constant incidence of 3.0 open globe injuries per 100,000 population. The circumstances of the injuries underwent major changes within the period of these observations.

AIM: To investigate whether diagnostic data from implanted cardiac resynchronization therapy defibrillators (CRT-Ds) retrieved automatically at 24 h intervals via a Home Monitoring function can enable dynamic prediction of cardiovascular hospitalization and death. METHODS AND RESULTS: Three hundred and seventy-seven heart failure patients received CRT-Ds with Home Monitoring option. Data on all deaths and hospitalizations due to cardiovascular reasons and Home Monitoring data were collected prospectively during 1-year follow-up to develop a predictive algorithm with a predefined specificity of 99.5%. Seven parameters were included in the algorithm: mean heart rate over 24 h, heart rate at rest, patient activity, frequency of ventricular extrasystoles, atrial-atrial intervals (heart rate variability), right ventricular pacing impedance, and painless shock impedance. The algorithm was developed using a 25-day monitoring window ending 3 days before hospitalization or death. While the retrospective sensitivities of the individual parameters ranged from 23.6 to 50.0%, the combination of all parameters was 65.4% sensitive in detecting cardiovascular hospitalizations and deaths with 99.5% specificity (corresponding to 1.83 false-positive detections per patient-year of follow-up). The estimated relative risk of an event was 7.15-fold higher after a positive predictor finding than after a negative predictor finding. CONCLUSION: We developed an automated algorithm for dynamic prediction of cardiovascular events in patients treated with CRT-D devices capable of daily transmission of their diagnostic data via Home Monitoring. This tool may increase patients' quality of life and reduce morbidity, mortality, and health economic burden, it now warrants prospective studies. ClinicalTrials.gov NCT00376116.

BACKGROUND: The clinical utility of modern hybrid imaging modalities for detecting recurrent bone or soft tissue sarcoma remains to be determined. In this report, the authors present a clinical study on the diagnostic accuracy and incremental value of integrated (18) F-fluorodeoxyglucose positron emission tomography/computed tomography ((18) F-FDG PET/CT) in patients with a history of sarcoma who have clinically suspected disease recurrence. METHODS: Forty-three patients who had a history of bone or soft tissue sarcoma and had documented complete remission underwent (18) F-FDG PET/CT. Image analysis was performed independently for (18) F-FDG PET (n = 43) and for contrast-enhanced spiral CT (CE-CT) (n = 30) by 2 separate readers, whereas combined (18) F-FDG PET/CT (n = 43) images were analyzed in consensus by both readers. Imaging findings were rated on a 5-point scale and finally were reported as malignant, benign, or equivocal. Imaging findings were validated either by histopathology (n = 24) or by clinical follow-up (n = 19). RESULTS: (18) F-FDG PET/CT had greater sensitivity and specificity compared with CE-CT alone (94% and 92% vs 78% and 67%, respectively), resulting in significantly greater accuracy (93% vs 73%; P = .03). (18) F-FDG PET/CT was particularly superior regarding detection of local recurrence or soft tissue lesions (sensitivity and specificity: 83% and 100% vs 50% and 100%, respectively) or bone metastases (100% and 100% vs 85% and 88%, respectively). CONCLUSIONS: (18) F-FDG PET/CT had greater diagnostic accuracy in the detection of recurrent bone or soft tissue sarcoma compared with CE-CT alone. The detection of local recurrence was the most evident advantage of (18) F-FDG PET/CT over CE-CT. Cancer 2013. © 2012 American Cancer Society.

Oligodendrocytes are the myelinating glia of the central nervous system and ensure rapid saltatory conduction. Shortage or loss of these cells leads to severe malfunctions as observed in human leukodystrophies and multiple sclerosis, and their replenishment by reprogramming or cell conversion strategies is an important research aim. Using a transgenic approach we increased levels of the transcription factor Sox10 throughout the mouse embryo and thereby prompted Fabp7-positive glial cells in dorsal root ganglia of the peripheral nervous system to convert into cells with oligodendrocyte characteristics including myelin gene expression. These rarely studied and poorly characterized satellite glia did not go through a classic oligodendrocyte precursor cell stage. Instead, Sox10 directly induced key elements of the regulatory network of differentiating oligodendrocytes, including Olig2, Olig1, Nkx2.2 and Myrf. An upstream enhancer mediated the direct induction of the Olig2 gene. Unlike Sox10, Olig2 was not capable of generating oligodendrocyte-like cells in dorsal root ganglia. Our findings provide proof-of-concept that Sox10 can convert conducive cells into oligodendrocyte-like cells in vivo and delineates options for future therapeutic strategies.

The risk associated with silicone oil removal after complex vitreoretinal surgery is unclear. Therefore, a cohort of 87 consecutive cases of silicone oil removal were analyzed. Eyes with attached retina before silicone oil removal with a follow-up of at least 5 months were included into the study. Forty-eight eyes had severe proliferative diabetic retinopathy; 39 eyes had complex proliferative vitreoretinopathy or giant retinal tears after trauma. Additional clinical features included the presence of a secondary cataract or secondary glaucoma in some eyes. The rate of postoperative complications was different in the two groups: 75% of proliferative diabetic retinopathy patients remained attached; of proliferative vitreoretinopathy patients, only 48.5% remained stable. Whereas success was independent of the duration of intraocular silicone oil tamponade in proliferative diabetic retinopathy, removal of silicone oil was more successful in cases of proliferative vitreoretinopathy in which there was a longer period of silicone oil tamponade. Complications occurring usually were severe and led to a loss of visual acuity. The removal of silicone oil from eyes with secondary glaucoma resulted in an improvement in 68% of patients. The rate of vitreoretinal complications after silicone oil removal, even in cases with a clinically stable-appearing retina, is rather high. Silicone oil removal therefore has to be considered a procedure posing new and ill-defined risks, especially if the indications for the use of silicone oil as an internal tamponade are rather strict. Exact criteria for the timing and safe removal of silicone oil in these complex vitreoretinal disorders still need to be defined.

AIMS: To assess the involvement of the recently identified human homogentisate 1,2-dioxygenase gene (HGO) in alkaptonuria (AKU) in two unrelated patients with ochronosis of the conjunctiva, sclera, and cornea. METHODS: A mutation screen of the entire coding region of the HGO gene was performed using single stranded conformational analysis after polymerase chain reaction with oligonucleotide primers flanking all 14 exons of the HGO gene. Fragments showing aberrant mobility were directly sequenced. RESULTS: Two homozygous missense mutations, L25P and M368V, were identified, each of which leads to the replacement of a highly conserved amino acid in the HGO protein. CONCLUSIONS: The authors describe a novel mutation, L25P, in the German population and bring to 18 the total number of known HGO mutations.