[Quality of Glaucoma Care in the Greater Hamburg Area]. / Erfassung der Versorgungsqualität von Glaukompatienten im Großraum Hamburg.

Background There is insufficient data on the quality of health services and health-related quality of life of patients with glaucoma. The purpose of this study was to investigate the extent to which the health services for glaucoma patients in the Greater Hamburg area conform to the guidelines set by the German Ophthalmological Society (DOG). Materials and Methods 196 glaucoma patients were offered an interview-administered questionnaire during their inpatient diurnal IOP measurement. The quality of glaucoma care and examinations recommended by the DOG were analysed. The results of the questionnaire were correlated with glaucoma severity, according to the stage of visual field defects. The correlation to the type of glaucoma was also analysed. Results The frequency of visits to the ophthalmologist was 5.1 per year. Most patients reported quarterly medical consultations. The majority of patients reported short waiting periods, because appointments were made in advance. In 92 % of cases, an intraocular pressure measurement was performed with each medical consultation. Half of the patients stated that their intraocular pressure had been measured at different times of the day. The visual field was tested a mean of 0.9 times per year at the ophthalmology clinic, but 1.4 times per year in the outpatient area. Further measures for glaucoma diagnostic testing were carried out 0.8 times per year at the ophthalmology clinic, and 0.4 times per year in the outpatient area. For the majority of patients, there were no additional costs for outpatient glaucoma diagnostic testing. Only 4 % of patients had to pay more than 100 € per year for these services. Conclusions For the majority of glaucoma patients in the Greater Hamburg area, the glaucoma health services conform to the guidelines set by the German Ophthalmological Society. Intraocular pressure measurements were performed on almost all patients at the regular check-ups and visual fields were examined as recommended. However, for about one-fifth of the patients, regular procedures for optic nerve analysis do not take place. The date of the next appointment was arranged immediately, allowing close follow-up, with little or no additional costs for the majority of patients.

[The Limits of Selective Laser Trabeculoplasty in Glaucoma Therapy]. / Die Grenzen der selektiven Lasertrabekuloplastik zur Behandlung des Glaukoms.

Introduction: The aim of this study was to evaluate the efficacy of selective laser trabeculoplasty (SLT) in the University Eye Hospital Hamburg Eppendorf. Material and Methods: We conducted a retrospective analysis of 113 eyes of 113 consecutively treated patients who underwent SLT treatment between 03/2011 and 01/2014 and had a follow-up of at least 4 months. Results: Intraocular pressure was reduced by 1.08 mmHg (7 % reduction) on average. In 43.7 % of the treated eyes, additional medical or surgical glaucoma treatment was necessary within 12 months. Conclusion: SLT is not effective as monotherapy in pre-treated eyes with low target pressure.

[Diverse effectiveness of the trabectome for different types of glaucoma]. / Unterschiedliche Effekte der Trabektomoperation auf unterschiedliche Glaukomformen.

PURPOSE: Ab interno trabeculotomy using the trabectome device is a intraocular pressure (IOP) decreasing operation by ablation of the trabecular meshwork and the inner wall of Schlemm's channel. This prospective study analyses the effectiveness of the trabectome operation in 122 patients. PATIENTS AND METHODS: The operation was conducted when topical medication was maxed out with the intraocular pressure (IOP) remaining above the desired target range. In addition to the evaluation of the whole study group further analysis concerned the effectiveness of the trabectome in different subclassifications of glaucoma. In some cases the procedure was combined with cataract surgery and subsequently the results were compared to the plain trabectome OP. The results were split into two groups: "complete success" (without postoperative medication) and "qualified success" (with medication). The evaluation was processed for the IOP levels ≤ 21 mmHg, ≤ 18 mmHg, ≤ 15 mmHg und ≤ 12 mmHg. Follow-up dates were 6 and 12 months after surgery. RESULTS: Baseline IOP was 20.15 ± 7.1 mmHg. After 6 months the average IOP of all patients was 16.53 ± 5.89 mmHg, after 12 months the IOP amounted to 15.6 ± 4.45 mmHg. At both follow-ups approximately 90 % of the "complete success" group exhibited an IOP ≤ 18 mmHg. Also at both follow-ups 75 % of the "qualified success" group achieved a range ≤ 18 mmHg - whereas 50 % gained an IOP ≤ 15 mmHg. In secondary glaucoma an IOP decrease of 36 % was achieved. In open-angle glaucomas and those with dysgenetic altered angles the operation evoked a pressure loss of ca. 20 %. The trabectome-only group as well as the group of combined surgery exhibited a significant lowering of IOP. This was accomplished by a significant reduction of eye drops. After surgery nearly half of all patients required none or 1 eye drop at most. CONCLUSION: The trabectome offers a safe and significant lowering of IOP for around 36 % and seems to be very effective in secondary glaucomas. In dysgenetic alterations and open-angle glaucoma a moderate lowering of IOP (ca. 20 %) may be expected. The amount of eye drops can be reduced for about 42 %. After surgery every second patient requires at most 1 eye drop. The technique can be combined with cataract surgery and permits a penetrating operation at a later date.

[Post-surgical treatment after non-penetrating glaucoma surgery: the goniopuncture]. / Nachbehandlung nach nicht penetrierender Glaukomchirurgie: die Goniopunktion.

Non-penetrating glaucoma surgery was primarily developed as an alternative to the widely applied trabeculectomy. Since the anterior chamber in non-penetrating surgery is not directly opened, common postoperative complications such as hypotony are rare. The most frequently applied technique in this group is the deep sclerectomy. After having prepared a superficial scleral flap a deeper scleral flap is performed and excised unroofing Schlemm's canal. The trabecular meshwork is then peeled leaving a residual trabeculodescemet membrane. As a consequence aqueous humour diffuses via the trabeculodescemet membrane under the scleral flap and subsequently under the conjunctiva. One of the reasons for a postoperatively high IOP is seen in the resistance of the residual trabculodescemet membrane. A solution to this problem lies in its puncture, the so-called goniopuncture. Goniopunctures are done in approximately 50 % of cases after deep sclerectomy and are also applied in cases of canaloplasty and viscocanaloplasty. Usually a 1064 nm Nd : YAG laser is used. A potential risk of iris incarceration is described. Two studies have shown that an equally IOP lowering effect can be achieved by treating the trabeculodescemet membrane with a frequency-doubled 532 nm Nd : YAG laser (SLT). No complications were detected in those cases. In conclusion, goniopuncture should be considered as the first line treatment for postoperative IOP increase in cases of non-penetrating glaucoma surgery. It should therefore be preferred to a (re)start of topical treatment.

[The relevance of diabetes for patients with glaucoma]. / Die Bedeutung des Diabetes mellitus für das Glaukom.

Although there are some hints for a correlation between diabetes and primary open angle glaucoma (POAG), it remains unclear in which way diabetes influences eye pressure (IOP) and glaucoma. Despite this, the main reason for neovascular glaucoma in diabetes is proven to be retinal ischaemia due to diabetic vessel damage. Primary open angle glaucoma is more frequent than neovascular glaucoma, but neovascular glaucoma is very aggressive and difficult to treat. The mainstay of the treatment is panretinal photo- or cryocoagulation. The next treatment options are cryodestructive procedures followed by filtering surgeries. In most cases a combination of treatments is necessary. In end-stage neovascular glaucoma sometimes enucleation is the only possible therapy when the IOP cannot be controlled or phthisis bulbi occurs.

[Long-term follow-up after deep sclerectomy]. / Langzeitverlauf nach tiefer Sklerektomie.

BACKGROUND: The aim of this study was to evaluate the long-term outcome of deep sclerectomy (DS) with a follow-up of up to 8 years. PATIENTS AND METHODS: All patients who underwent a deep sclerectomy between February 2004 and October 2005 and who attended a follow-up visit between August 2009 and October 2011 were included in this study. RESULTS: This study evaluated 74 eyes of 65 patients with a mean postoperative follow-up of 76.28 ± 10.6 (53.65-92.02) months. Preoperative IOP was 18.37 ± 6.36 mmHg, postoperative IOP at the last follow-up was 12.85 ± 3.5 mmHg, corresponding a 30 % reduction. The number of IOP-lowering eye drops was reduced from 2.36 ± 1.24 to 1.66 ± 1.21 after more than 6 years (p < 0.05). The visual fields showed a mean deviation of - 9.16 ± 8.48 dB initially and - 9.43 ± 8.07 dB at the last follow-up (p > 0.05). Complete success (IOP ≤ 15 mmHg without eye drops or additional surgery) was achieved in 5 % of patients. Qualified success (IOP ≤ 15 mmHg with eye drops or additional surgery) was achieved in 81 %. 53 % (n = 39) underwent cyclophotocoagulation and 20 % (n = 15) needed revision surgery during the follow-up period. CONCLUSION: DS is an effective long-term IOP-lowering procedure leading to visual field stabilisation.

European proficiency study with control serum for the tumor marker CA 19-9 measured on different test systems.

BACKGROUND: Reliable and precise CA 19-9 testing is required for the long-term follow-up of patients with pancreatic carcinoma during therapy. The aim of this longitudinal proficiency study was to evaluate the comparability, linearity, and precision of CA 19-9 determinations performed in different laboratories using currently available test systems under routine conditions. METHODS: During the one year study period, 15 laboratories applied 7 different tests and included a liquid BIOREF control serum with pancreatic carcinoma derived CA 19-9 in their routine testing and quality control procedures. The results were collected centrally and evaluated statistically. RESULTS: The comparability of CA 19-9 results is limited especially when different tests are used, albeit, some tests show a good correlation: The CA 19-9 values obtained by different laboratories using different test systems vary up to a factor of 2. The precision of CA 19-9 determinations was acceptable in most laboratories with coefficients of variation ranging between very low 3.2% and high 17.8%. The imprecision was slightly increased when automatic dilution procedures of the analysers were used. CONCLUSIONS: The comparability of CA 19-9 test results must be improved. The precision is acceptable in most cases. In order to monitor key performance parameters, every laboratory should participate in external quality assessment schemes and should perform a routine internal quality control with a control serum independent from the test kit manufacturer.

Chromosomal deletion complexes in mice by radiation of embryonic stem cells.

Chromosomal deletions ("deficiencies') are powerful tools in the genetic analysis of complex genomes. They have been exploited extensively in Drosophila melanogaster, an organism in which deficiencies can be efficiently induced and selected. Spontaneous deletions in humans have facilitated the dissection of phenotypes in contiguous gene syndromes and led to the positional cloning of critical genes. In mice, deletion complexes created by whole animal irradiation experiments have enabled a systematic characterization of functional units along defined chromosomal regions. However, classical mutagenesis in mice is logistically impractical for generating deletion sets on a genome-wide scale. Here, we report a high-throughput method for generating radiation-induced deletion complexes at defined regions in the genome using ES cells. Dozens of deletions of up to several centiMorgans, encompassing a specific locus, can be created in a single experiment and transmitted through the germline. The ability to rapidly create deletion complexes along chromosomes will facilitate systematic functional analyses of the mammalian genome.

Suppression of natural lens fluorescence in fundus autofluorescence measurements: review of hardware solutions.

Fluorescence lifetime imaging ophthalmoscopy (FLIO), a technique for investigating metabolic changes in the eye ground, can reveal the first signs of diseases related to metabolism. The fluorescence of the natural lens overlies the fundus fluorescence. Although the influence of natural lens fluorescence can be somewhat decreased with mathematical models, excluding this influence during the measurement by using hardware enables more exact estimation of the fundus fluorescence. Here, we analyze four 1-photon excitation hardware solutions to suppress the influence of natural lens fluorescence: aperture stop separation, confocal scanning laser ophthalmoscopy, combined confocal scanning laser ophthalmoscopy and aperture stop separation, and dual point confocal scanning laser ophthalmoscopy. The effect of each principle is demonstrated in examples. The best suppression is provided by the dual point principle, realized with a confocal scanning laser ophthalmoscope. In this case, in addition to the fluorescence of the whole eye, the fluorescence of the anterior part of the eye is detected from a non-excited spot of the fundus. The intensity and time-resolved fluorescence spectral data of the fundus are derived through the subtraction of the simultaneously measured fluorescence of the excited and non-excited spots. Advantages of future 2-photon fluorescence excitation are also discussed. This study provides the first quantitative evaluation of hardware principles to suppress the fluorescence of the natural lens during measurements of fundus autofluorescence.

Alpha-1-Fetoprotein (AFP): international proficiency study with different test systems.

BACKGROUND: The present proficiency study aimed to elucidate the comparability and reliability of test systems for the determination of AFP concentrations. METHODS: 25 laboratories using 8 different commercial test systems used liquid BIOREF-AFP control serum in their routine internal quality control over a period of one year. For statistical analysis the results were collected centrally. RESULTS: The statistical analysis of the test results revealed considerable variation for the different laboratories. The deviations of the mean values of different laboratories from the overall mean value varied between 0.1 and 26.1%, and for most of the laboratories the deviation was round about 10%. The precision of measured values in the individual laboratories was in most cases acceptable: Nevertheless, the coefficients of variation of the individual laboratories ranged from 13 to 16.1%. CONCLUSIONS: In conclusion, this study indicates that AFP results vary between different laboratories albeit an international standard for AFP is available. Therefore, every laboratory should participate in external ring studies and should use a quality control serum independent of the test kit manufacturer for the internal quality control.

Comparison of algorithms to suppress artifacts from the natural lens in fluorescence lifetime imaging ophthalmoscopy (FLIO).

Fluorescence lifetime imaging ophthalmoscopy (FLIO) has developed as a new diagnostic tool in ophthalmology. FLIO measurements are taken from 30° retinal fields in two spectral channels (short spectral channel (SSC): 498-560 nm, long spectral channel (LSC): 560-720 nm). Because of the layered structure of the eye, the detected signal is an interaction of the fluorescence decay of the anterior part and of the fundus. By comparing FLIO measurements before and after cataract surgery, the impact of the natural lens was proven, despite the application of a confocal laser scanning (cSLO) technique. The goal of this work was to determine the best algorithmic solution to isolate the sole fundus fluorescence lifetime from the measured signal, suppressing artifacts from the natural lens. Three principles based on a tri-exponential model were investigated: a tailfit, a layer-based approach with a temporally shifted component, and the inclusion of a separately measured fluorescence decay of the natural lens. The mean fluorescence lifetime τm,12 is calculated using only the shortest and the intermediate exponential component. τm,all is calculated using all three exponential components. The results of tri-exponential tailfit after cataract surgery were considered as a reference, because the implanted artificial lens can be assumed as non-fluorescent. In SSC, the best accordance of τm,all of the reference was determined with τm,12 of the tailfit before surgery. If high-quality natural lens measurements are available, the correspondence of τm,12 is best with τm,all of the reference. In LSC, there is a good accordance for all models between τm,12 before and after surgery. To study the pure fundus fluorescence decay in eyes with natural lenses, we advise to utilize fluorescence lifetime τm,12 of a triple-exponential tailfit, as it corresponds well with the mean fluorescence lifetime τm,all of eyes with fluorescence-less artificial intraocular lenses.

Correlations and incipient antiferromagnetic order within the linear Mn chains of metallic Ti4MnBi2.

We report measurements on Ti4MnBi2, where a crystal structure involving linear chains of Mn ions suggests one-dimensional magnetic character. The electrical resistivity is metallic, consistent with the results of electronic-structure calculations that find a robust Fermi surface albeit with moderate electronic correlations. A Curie-Weiss fit to the magnetic susceptibility suggests that the Mn moments are in the low-spin S = 1/2 configuration. Neutron diffraction measurements detect weak antiferromagnetic order within the Mn chains, with further evidence for the small staggered moment coming from the entropy associated with the ordering peak in the specific heat as well as from the results of spin-polarized electronic-structure calculations. The antiferromagnetic moments are apparently associated with the d x 2 - y 2 and d xy orbitals of Mn while the remaining Mn orbitals are delocalized and nonmagnetic. Strong quantum fluctuations, possibly related to an electronic instability that forms the Mn moment or to the one-dimensional character of Ti4MnBi2, nearly overcome magnetic order.

Precision and long-term stability of different estradiol immunoassays assessed in a multi-center quality control study.

BACKGROUND: Because of the vast range of physiological relevant estradiol concentrations the requirements to be met by an estradiol assay are high. In the present study the performance of various commercially available estradiol assays was evaluated with regard to imprecision and long-term stability. METHODS: Precision and long-term stability of 7 commercially available estradiol immunoassays were assessed in a multi-centre quality control study based on the repeated measurement of liquid BIOREF estradiol control sera by 18 laboratories during a 14-month study period. RESULTS: The mean estradiol concentrations determined in 594 runs performed for each control level were 71 pg/ml, 349 pg/ml and 676 pg/ml. A high variation was found for the method specific mean values calculated from all results measured with the same method, which ranged between 32 - 90 pg/ml, 187 - 392 pg/ml and 373 - 790 pg/ml, resulting in a similar high inter-laboratory variation with coefficients of variation (CVs) of 25.0%, 16.7% and 17.5%. In contrast, the intra-laboratory variation of estradiol values as well as the variation of values measured with the same method were found to be considerably lower with coefficients of variation < 10% for most laboratories and methods; only the low control level was measured with CV values > 10% by the majority of laboratories and methods. For none of the laboratories a tendency was observed in the results from beginning to end of the 14 month study period indicating a high uniformity in assay production and a good long-term stability of the control material used. CONCLUSIONS: The present data demonstrate that also with the currently available estradiol immunoassays the comparability of results measured with different methods is limited. With most assays very low estradiol concentrations, as observed in postmenopausal women, can be determined only with a precision which is not adequate for clinical assessment.

ES cells do not activate p53-dependent stress responses and undergo p53-independent apoptosis in response to DNA damage.

BACKGROUND: Embryonic stem (ES) cells can contribute precursors to all adult cell lineages. Consequently, damage to ES cell genomes may cause serious developmental malfunctions. In somatic cells, cell-cycle checkpoints limit DNA damage by preventing DNA replication under conditions that may produce chromosomal aberrations. The tumor suppressor p53 is involved in such checkpoint controls and is also required to avoid a high rate of embryonic malformations. We characterized the cell-cycle and DNA-damage responses of ES cells to elucidate the mechanisms that prevent accumulation or transmission of damaged genomes during development. RESULTS: ES cells derived from wild-type mice did not undergo cell-cycle arrest in response to DNA damage or nucleotide depletion, although they synthesized abundant quantities of p53. The p53 protein in ES cells was cytoplasmic and translocated inefficiently to the nucleus upon nucleotide depletion. Expression of high levels of active p53 from an adenovirus vector could not trigger cell cycle arrest. Instead, ES cells that sustained DNA damage underwent p53-independent apoptosis. The antimetabolite-induced p53-dependent arrest response was restored in ES cells upon differentiation. CONCLUSIONS: Cell-cycle regulatory pathways in early embryos differ significantly from those in differentiated somatic cells. In undifferentiated ES cells, p53 checkpoint pathways are compromised by factors that affect the nuclear localization of p53 and by the loss of downstream factors that are necessary to induce cell-cycle arrest. A p53-independent programmed cell death pathway is effectively employed to prevent cells with damaged genomes from contributing to the developing organism. The p53-mediated checkpoint controls become important when differentiation occurs.

[A comparison between absorbable and non-resorbable scleral implants in deep sclerectomy (T-Flux and SK-Gel)]. / Vergleich von resorbierbaren und nichtresorbierbaren skleralen Implantaten bei tiefer Sklerektomie (SK-Gel und T-Flux).

BACKGROUND: The intraocular pressure (IOP) lowering effects of deep sclerectomy (partially combined with phacoemulsification) with different scleral implants (T-Flux- or SK-Gel) were investigated. PATIENTS AND METHODS: In a retrospective study, 72 patients with medically uncontrollable glaucoma underwent non-penetrating deep sclerectomy. Of these, 54 patients received T-Flux implants and 18 SK-Gel implants. Examinations were carried out shortly before and after surgery, as well as after 12 months. RESULTS: Prior to surgery IOP was 18.4+/-5.5 mmHg (n=72) and 12 months after surgery it was 13.1+/-3.8 mmHg (n=65). The number of antiglaucomatous eyedrops used prior to surgery was 2.3+/-1.3 (n=72) and 12 months after surgery 0.2+/-0.6 mmHg (n=65). Secondary IOP-lowering surgery after 12 months was carried out on 15.3% of the operated eyes, and consecutive goniopunctures after 12 months were 25%. No significant differences were found between the two groups. CONCLUSIONS: The short- and mid-term IOP lowering effects in deep sclerectomy with scleral implants were quite satisfying no matter which implant was used. There was no difference in deep sclerectomy whether or not combined with cataract surgery.

[Central arterial occlusion after blunt force ocular injury : Case report]. / Zentralarterienverschluss nach stumpfem Bulbustrauma : Eine Fallvorstellung.

A healthy young male patient suffered a nearly complete loss of vision after a minor ocular injury. We describe a rare case of central arterial occlusion after blunt force trauma. After rheological therapy the visual acuity increased from perception of hand movement to 1/20, 1 month after the injury. Central artery occlusion is a rare but severe complication after blunt force ocular trauma that should be considered when patients suffer severe posttraumatic loss of vision.

[Toric add-on intraocular lenses for correction of high astigmatism after pseudophakic keratoplasty]. / Torische AddOn-Intraokularlinsen zur Korrektur hoher Astigmatismen nach pseudophaker Keratoplastik.

Perforating keratoplasty shows good morphological results with a clear cornea; however, a limiting factor is often the resulting astigmatism, which cannot be corrected with either glasses or contact lenses (CL) in up to 20% of the patients. We retrospectively investigated 15 patients after pseudophakic perforating keratoplasty, who received implantation of toric add-on intraocular lenses (IOL) to correct astigmatism. The mean preoperative astigmatism of 6.5 diopter (dpt) could be reduced to a mean postoperative value of 1.0 dpt. The mean visual acuity could be improved from a preoperative value of sc <0.05 (cc 0.6) to a postoperative value of sc 0.4 (cc 0.63). There were no complications except for one case of a lens extension tear. Based on our good experiences we now provide toric add-on IOL to all patients with pseudophakic perforating keratoplasty when this cannot be corrected or only insufficiently corrected by conservative methods.

Transmission at autonomic neuroeffector junctions.

For organs innervated by the autonomic nervous system, it is generally held that neuroeffector transmission is achieved by varicosities releasing transmitters some distance from the membranes of target cells. Transmitters are thought to diffuse through the extracellular space and interact with post-junctional receptors that are widely distributed over the cell membranes. This article presents an alternative view, suggesting that transmission can occur at organized neuroeffector contacts, that transmitters interact with restricted pools of specialized junctional receptors, and that many receptors on target cells are not involved in neuroeffector transmission.