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BackgroundThe ability to quantify an immune response after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential. This study assessed the clinical utility of the quantitative Roche Elecsys® Anti-SARS-CoV-2 S assay (ACOV2S) using samples from the 2019-nCoV vaccine (mRNA-1273) phase 1 trial (NCT04283461).MethodsSamples from 30 healthy participants, aged 18–55 years, who received two injections with mRNA-1273 at a dose of 25 μg (n=15) or 100 μg (n=15), were collected at Days 1 (first vaccination), 15, 29 (second vaccination), 43 and 57. ACOV2S results (shown in U/mL – equivalent to BAU/mL per the first WHO international standard) were compared with results from ELISAs specific to antibodies against the Spike protein (S-2P) and the receptor binding domain (RBD) as well as neutralization tests including nanoluciferase (nLUC80), live-virus (PRNT80), and a pseudovirus neutralizing antibody assay (PsVNA50).ResultsRBD-specific antibodies were already detectable by ACOV2S at the first time point of assessment (d15 after first vaccination), with seroconversion before in all but 2 participants (25 μg dose group); all had seroconverted by Day 29. Across all post-baseline visits, geometric mean concentration of antibody levels were 3.27–7.48-fold higher in the 100 μg compared with the 25 μg dose group. ACOV2S measurements were highly correlated with those from RBD ELISA (Pearson’s r=0.938; p80 r=0.933; PsVNA50, r=0.771; PRNT80, r=0.672; all p≤0.0001).ConclusionThe Elecsys Anti-SARS-CoV-2 S assay (ACOV2S) can be regarded as a highly valuable method to assess and quantify the presence of RBD-directed antibodies against SARS-CoV-2 following vaccination, and may indicate the presence of neutralizing antibodies. As a fully automated and standardized method, ACOV2S could qualify as the method of choice for consistent quantification of vaccine-induced humoral response.

Objectives. To investigate the frequency of anti-infliximab antibodies in patients with RA and the associations with adverse drug reactions and treatment failure. Methods. Based on the DANBIO registry, patients with RA who initiated treatment with infliximab at Hvidovre Hospital between 2000 and 2008 and had available serum samples were identified. The patients were followed for 52 weeks. Anti-infliximab antibodies were determined prior to infusion at baseline and during follow-up (weeks 2, 6, 14 and 52 or at withdrawal) using the IMPACT indirect assay (Roche Diagnostics) and merged with clinical data prospectively registered in the DANBIO registry. Results. A total of 218 patients with RA were included (80% females, median age 56 years, disease duration 10 years, 65% RF positive, median DAS28 = 5.0). During the 52-week follow-up, 28 patients (13%) withdrew due to adverse events and 50 (23%) due to treatment failure. Antibodies were detected in 118 patients (54%) during follow-up. Patients with detectable anti-infliximab antibodies after 6 weeks had an increased risk of adverse drug reactions [hazard ratio (HR) = 5.06, 95% CI 2.36, 10.84; P < 0.0001] compared with patients without anti-infliximab antibodies. Similar results were observed in patients with anti-infliximab antibodies after 14 weeks (HR = 3.30, 95% CI 1.56, 6.99; P = 0.0009). Patients with detectable anti-infliximab antibodies during the 52-week follow-up were less likely to achieve sustained minimal disease activity and remission. Conclusion. Early anti-infliximab antibody formation increased the risk of adverse drug reactions, including infusion reactions. Anti-infliximab antibody formation during the 52-week follow-up decreased the likelihood of minimal disease activity and remission in patients with RA treated in routine care.

To identify differences in extracellular matrix contents between idiopathic epiretinal membranes (IEM) of cellophane macular reflex (CMRM) or preretinal macular fibrosis (PMFM) type.

The purpose of this study was to characterise an ex-vivo adult porcine retina-retinal pigment epithelium (RPE) perfusion organ culture model. Fresh porcine full-thickness retina-RPE-choroid tissue samples were clamped into tissue carriers and mounted in two-compartment containers. The retinal and choroidal sides were continuously perfused with culture medium. pO(2), [Na(+)], [K(+)], [Cl(-)], [glucose], [lactate], and pH were measured in the medium. Tissue samples were examined after 24h, 4, 7, and 10 days in culture. The morphology of the retina and the RPE was examined by light and electron microscopy (LM, EM). The retinal cellular integrity was further examined by immunohistochemistry (Ki 67, GFAP, rhodopsin, synaptophysin, syntaxin, NF 200, TUNEL-test). Fresh porcine full-thickness retina-RPE-choroid tissue samples and tissue samples in static organ culture served as controls. LM, EM, and immunohistochemistry showed intact retinal and RPE cytoarchitecture kept in perfusion culture. Photoreceptor outer segments showed first signs of degeneration after 24h, significant signs of apoptosis and necrosis appeared in the retina after 4 days in perfusion culture. Control tissue samples kept in static culture showed disintegration of the retinal cytoarchitecture after 4 days in culture. The data show that adult porcine retina-RPE tissue can be maintained morphologically intact in perfusion organ culture for at least 10 days. Although first signs of degeneration set in after 24h the structural preservation of the tissue in perfusion organ culture is superior to that in static culture. The perfusion culture model of the retina refines organotypic in vitro test systems and may help to reduce the number of necessary animal experiments in retina and RPE research. It offers new perspectives for the safety testing of substances designed for intraocular application.

To describe optical coherence tomography (OCT) findings in patients with juxtafoveal retinal telangiectasis (JRT). Fourteen consecutive patients (28 eyes) with JRT (12 patients with JRT type II, one with JRT type I and one with JRT type III) were examined using fluorescein angiography (FA) and OCT. Despite prominent leakage in FA, macular oedema was absent in all 26 eyes with type II JRT. In contrast to that, in patients with type I and type III JRT, cystoid macular oedema was evident. In 14 of 28 eyes (all with type II JRT), a single foveal cyst was found in OCT. It varied significantly in size and was associated with visual acuity decrease. An intraretinal hyperreflective lesion was seen in eight of 28 eyes and flattening of the fovea in three eyes. Foveal cyst, absent macular oedema, intraretinal hyperreflective lesions and foveal flattening were the most common OCT findings in patients with JRT type II. These may represent progressive loss of retinal tissue, possibly due to Muller cells degeneration, and provide additional diagnostic criteria for JRT.

To carry out a prospective investigation of the functional and morphological outcome of idiopathic epiretinal membrane (IEM) surgery with or without the assistance of indocyanine green (ICG) in a randomised controlled clinical trial. Sixty patients who underwent vitrectomy with removal of IEM combined with cataract surgery were randomly allocated to two groups: 27 patients were operated on with ICG 0.1% in glucose 5%, 33 patients without ICG. Functional outcome was assessed 3-4 months postoperatively with improvement of best-corrected visual acuity (BCVA), Amsler grid test, and automated and kinetic perimetry. Postoperative residual or recurrent IEM was assessed with bio-microscopy, and macular oedema with optical coherence tomography (OCT). Improvement in BCVA was the main outcome measure. BCVA improved in 49 patients, remained unchanged in five and decreased in five. Improvement in BCVA and reduction of macular oedema were statistically significant within both groups (P

During excimer laser photoablation keratocyte cell death is induced in the retroablation area. Afterwards this area is repopulated by keratocyte mitosis and migration from the adjacent stroma. The aim of this study was to investigate keratocyte density in the retroablation area and in the posterior stroma during the first year after LASEK for the correction of myopia.In a prospective study LASEK surgery was performed in 17 eyes of 10 consecutive patients for the correction of myopia (-2.25 D to -9.0 D, mean -5.0 D). Confocal microscopy (Nidek Confoscan 2) was performed before surgery and 1 month, 3 months, 6 months and 12 months after LASEK. Keratocyte density was assessed in the anterior retroablation area at depths of 5 mum and 25 mum and in the posterior stroma at distances of 5 mum and 100 mum from the corneal endothelium and compared with the corresponding area before surgery.Keratocyte density was statistically significant reduced in the retroablation area at all timepoints after LASEK. At a depth of 5 mum, cell densities were decreased by 64%, 47%, 43%, and 28% at 1 month, 3 months, 6 months and 12 months after LASEK compared with preoperative values. At a depth of 25 mum, cell densities were decreased by 51%, 32%, 28%, and 18% at 1 month, 3 months, 6 months and 12 months after LASEK compared with preoperative values. In the posterior stroma no significant change in keratocyte density was observed at any time after LASEK.Keratocyte density in the anterior retroablation area recovers during the first year after LASEK for the correction of myopia, but does not go back to preoperative values.

Histologisch entspricht die Sekundarkatarakt („posterior capsule opacification“ [PCO]) regenerativem Gewebe aus transformierten Linsenepithelzellen („lens epithelial cells“ [LEC]) und Extrazellularmatrix. In dieser Studie wurde der Einfluss ionisierender Strahlen auf proliferierende LEC in vitro untersucht. Jeweils vier bzw. 14 Linsen aus Schweinebulbi wurden mit Elektronen der Energie 6 MeV mit je 8, 10, 12 und 20 Gy bestrahlt. 1–2 h nach Radiatio wurde der Linsenkern durch Kapsulorrhexis und Hydrodissektion aus der Linsenkapsel extrahiert. Nach Fixation der Linsenkapsel in einer speziellen Halterung wurde taglich die Proliferation residueller LEC bei zwolffacher Vergroserung untersucht und photographisch dokumentiert. Der Versuch galt als beendet, wenn die Linsenkapsel durch konfluierende Zellproliferate vollstandig getrubt war. Eine Radiatio mit Elektronen verzogert signifikant die Entwicklung einer PCO im Dosisbereich von 8–12 Gy in vitro. Ab 20 Gy induziert sie eine vollstandige Inhibition der PCO. Zur Inhibition einer PCO in vitro ist eine Einzeldosis von mindestens 20 Gy erforderlich. Das hier angewandte Modell erlaubt eine optimale Untersuchung der PCO-Genese unter verschiedenen auseren Einflussen und eignet sich gut fur radiobiologische Fragestellungen.

Purpose: Central serous chorioretinopathy (CSC) affects mostly young and middle-aged adults. Typically, a serous retinal detachment occurs with a focal leakage point in fluorescein angiography. Fundus autofluorescence (AF) is related to the lipofuscin within the retinal pigment epithelium (RPE). As CSC is thought to be associated with RPE disorders, AF measurements might be able to detect distinct changes within the RPE level. The purpose of this study was to compare AF patterns in acute and chronic-recurrent CSC and to evaluate the potential value of AF as a non-invasive monitoring tool. Methods: From 85 patients diagnosed with CSC (mean age 43 years), AF images were retrospectively evaluated and compared with angiographic and ophthalmoscopic findings. Fluorescein angiography and AF measurements were performed using a Heidelberg retina angiograph. Autofluorescence was excited at a wavelength of 488 nm and detected above 500 nm. Results: Acute CSC as determined by an acute decrease in visual acuity (VA) within the last 6 weeks, focal point leakage and neurosensory retinal detachment was diagnosed in 39 patients. In 36 of those patients (92%), a significantly decreased AF at the leakage point (72%) and/or decreased AF in the area of neurosensory detachment (77%) were observed. Regarding chronic-recurrent CSC as determined by a decrease in VA for longer than 6 weeks and mottled hyperfluorescent appearance in angiography, abnormalities in AF were observed in 44/46 patients (96%). In those patients, decreased or mottled AF was observed at the leakage point itself (76%), whereas significantly increased AF was seen in the area of residual neurosensory retinal detachment (85%). Conclusions: In acute CSC, decreased AF is presumably due to a blockage caused by oedema, whereas in chronic-recurrent forms, irregular and increased AF is observed, possibly reflecting reactive RPE changes secondary to RPE defects and neurosensory detachment. If these findings could be systematically underlined by prospective clinical studies, AF might be an interesting non-invasive tool for monitoring RPE changes in CSC and for performing differential diagnosis.

Non-invasive imaging of the retinal pigment epithelium (RPE) using autofluorescence became recently available with the introduction of confocal laser scanning ophthalmoscopes. Fundus autofluorescence is usually excited at a wavelength of 488nm and the emitted light is detected above 500nm. This intrinsic autofluorescence was shown to derive from the lipofuscin accumulating within the RPE either with age or also due to different hereditary or degenerative diseases of the macula as e.g. age-related macular degeneration. Since a variety of macular diseases correlate with distinct RPE changes, specific patterns of autofluoresce nce could be evaluated within the recent years for diagnostic and prognostic reasons in those RPE-related diseases. Moreover autofluorescence can also be regarded as a monitoring tool after therapeutic applications as macular surgery or laser treatment. Other new applications try to determine macular pigment density using autofluorescence or use it to evaluate oxygen-dependent cell metabolism. This review summarizes the recent findings of autofluoresce nt patterns in specific diseases and therapeutic approaches and emphasizes on the tremendous potential of this novel imaging method.

Perfluorocarbon liquids (PFCLs) and heavy fluorocarbon liquids (HFCLs) are being increasingly used as soft tools during vitreoretinal surgery. However, since long-term intraocular tolerance is still unsatisfactory, at present complete removal at the end of surgery is recommended. With the aim to improve long-term intraocular compatibility and to enlarge the spectrum of clinical applications, modified HFCLs have been developed. HFCL-oligomers with a higher viscosity represent the latest perspective. All three groups of fluorocarbon liquids will be compared with respect to their physical and chemical properties, experimental and clinical results, and prospects for clinical applications. Common features of PFCLs, HFCLs and HFCL-oligomers are biological inertness, specific gravity higher than water, immiscibility with water or blood, and a high gas binding capacity. In PFCLs such as decalin, octane, or phenanthrene, all carbon atoms of the carbon backbone are completely fluorinated. In experimental and clinical use, emulsification, vascular changes and structural alterations of the retina have been described. By only partial replacement of hydrogen atoms by fluorine, the specific gravity of HFCLs is reduced, whereas lipophilic properties increase. Thus HFCLs are potential solvents for intraocular silicone oil remnants. However, after long-term application, side-effects are similar to those observed with PFCLs. Substances of this group, such as F6H6, F6H8, O44, and O62 are used intraoperatively and are currently being investigated for clinical long-term application. With the aim to avoid emulsification and to improve intraocular tolerance, we have developed HFCL-oligomers consisting of 2–4 HFCL molecules with increased viscosity. The oligomers were tolerated well in rabbit eyes for up to 4 months. In contrast to PFCLs or monomers, they did not emulsify nor show vascular alterations. ERGs returned to normal after removal of the oligomer from the eye. Histology of the retina showed mild alterations. Conclusion: according to physical properties, experimental intraocular compatibility and stability against emulsification, HFCL-oligomers are promising candidates for improved long-term tamponade of the lower retina. At present, indications for an application in human eyes have to be determined in clinical trials.

Background: In adolescents and adults, an association between obesity and asthma was found in females. Does this sex-specific association already exist in young children? Methods: Questionnaire data on 9357 5- and 6-year-old German children were collected in 1997 in two rural regions in Bavaria. The diagnosis of asthma, hay fever, and eczema was ascertained with the ISAAC core and other validated questions. Overweight was defined by a BMI of >90th and ≤97th percentile and obesity by a BMI of >97th percentile. Results: The lifetime prevalence of doctor's diagnosed asthma in girls was 3.5% (95% CI 2.9–4.1%) for normal weight, 5.8% (95% CI 3.2–8.4%) for overweight, and 10.3% (95% CI 5.3–15.2%) for obesity, whereas no relation to weight was found in boys. Hay fever and eczema were unrelated to weight in girls and boys. The adjusted odds ratio for asthma in girls was 2.12 (95% CI 1.22–3.68) for overweight and 2.33 (95% CI 1.13–4.82) for obesity. Conclusions: A sex-specific association with doctor's diagnosed asthma was also observed in girls at school entry. Since this association was confined to doctor's diagnosed asthma in the absence of other atopic conditions, and no association with other atopic manifestations was found, we hypothesize that this association is related to factors other than atopic sensitization.

Purpose: To flatten pigment epithelial detachments (PED) cue to age-related macular degeneration in an attempt to visualize the underlying choroidal neovascularization by fluorescein angiography (FA) and reveal a treatment target. Methods: Nine patients with PED received intravitreal gas injections via the pars plana and postured face down. Fluorescein angiograms were obtained before and after gas injection. In two patients, retinal scotopic sensitivity was also measured. Results: Eight patients demonstrated change in the shape and size of the PED following gas injection. Four patients showed a better delineation of underlying structures on FA. Three patients had focal laser treatment to the newly visible choroidal neovascular complex, but this was successful in only one patient with flattening of the PED. Conclusion: Pigment epithelial detachments can be modified by intravitreal gas injection in some patients, but this treatment did not have a major impact on overall outcome or management.

Purpose: To ascertain whether the use of the polymerase chain reaction (PCR) technique leads to more rapid diagnosis of infectious endophthalmitis after cataract surgery. Setting: University Eye Clinic Regensburg, Germany. Methods: The aqueous humor and vitreous of 16 eyes with infectious endophthalmitis (10 acute, 6 delayed) were evaluated by microscopy, diagnostic culture, and PCR to detect the infectious agent. Results: Microscopy of the vitreous was positive in 3 eyes and the culture media results were positive in 7 eyes, all with acute endophthalmitis. Significantly fewer positive results were obtained in the aqueous humor. Using PCR, an infectious agent was detected in the aqueous humor of all 16 eyes and in the vitreous of 14. The vitreous sample was negative in 2 eyes with delayed endophthalmitis. Conclusions: Detection of the infectious agent was more successful using PCR than using conventional microbiological tests, especially in the diagnosis of delayed endophthalmitis where the pathogen was detected in the aqueous humor in all eyes.

There are presently several concepts to restore vision in blind or highly visually handicapped persons by implanting electronic devices into the eye in order to partially restore vision. Here, the approach to replace retinal photoreceptors by a subretinally implanted microphotodiode array (MPDA) is summarized. A survey is given on the present state of the development of MPDAs, the possibility of in vitro and in vivo tests as well as first results on biocompatibility and histology. Additionally, electrophysiological recordings in rabbits and rats are presented which have received such subretinal implants.

AIM OF THE STUDY The aim of this study was to determine whether capsulotomy size influences visual performance. PATIENTS AND METHODS Twenty eyes were included in this study and were divided into two groups: 10 eyes had small central capsulotomies without dilating the pupil, and 10 eyes had large capsulotomies through dilated pupils. We measured both, visual acuity and glare due to forward light scatter using a computer system. RESULTS Following treatment both groups had equally significant (< 0.001) improvements in visual acuity. However, a significant (p < 0.001) improvement of glare due to forward light scatter was only observed in the eyes with a large size capsulotomy. CONCLUSIONS Our study showed that measurements of forward light scatter are more sensitive than visual acuity testing in demonstrating loss of visual performance in patients with media opacities. It is recommended that pupils are dilated prior to Nd:YAG capsulotomy if forward light scatter from capsule remnants and the subsequent glare disability are to be minimised.

To compare the efficacy of pars plana vitrectomy (ppV) with intravitreal injection of recombinant tissue plasminogen activator (rtPA) and gas versus ppV with subretinal injection of rtPA and intravitreal injection of gas.Nonrandomized, retrospective, interventional, comparative consecutive series including 47 patients with submacular hemorrhage. Eighteen patients were treated with ppV, intravitreal injection of rtPA and 20% SF6 gas [group A: mean age 78 years, mean duration of symptoms 6.6 days, 15 age-related macular degeneration (AMD), three retinal arterial macroaneurysm (RAMA)]. Twenty-nine patients were treated with ppV, subretinal injection of rtPA and intravitreal injection of SF6 gas (group B: mean age 75 years, mean duration of symptoms 5.9 days, 26 AMD, two RAMA, one blunt ocular trauma). The main outcome measure was complete displacement of submacular hemorrhage from the fovea.Complete displacement of submacular hemorrhage was achieved in less patients in group A (22%) than in group B (55%) (p = 0.025). In group A, mean best-corrected visual acuity (BCVA) change was logMAR -0.14, standard deviation (SD) = 0.64, and in group B logMAR -0.32, SD = 0.68 without statistically significant difference between the two groups (p = 0.2, Mann-Whitney test). Complications (retinal detachment, vitreous hemorrhage, and recurrence of submacular hemorrhage) were more frequent in group B than in group A.ppV with subretinal injection of rtPA and intravitreal injection of gas was more effective than ppV with intravitreal injection of rtPA and gas in terms of complete displacement of submacular hemorrhage; however, it may be associated with a higher rate of postoperative complications. Functional improvement in the majority of patients suggests the absence of direct retinal toxicity of subretinally applied rtPA.

Contains fulltext : 70028.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To test if a combination of biomarkers can increase the classification power of autoantibodies to cyclic citrullinated peptides (anti-CCP) in the diagnosis of rheumatoid arthritis (RA) depending on the diagnostic situation. METHODS: Biomarkers were subject to three inclusion/exclusion criteria (discrimination between RA patients and healthy blood donors, ability to identify anti-CCP-negative RA patients, specificity in a panel with major non-rheumatological diseases) before univariate ranking and multivariate analysis was carried out using a modelling panel (n = 906). To enable the evaluation of the classification power in different diagnostic settings the disease controls (n = 542) were weighted according to the admission rates in rheumatology clinics modelling a clinic panel or according to the relative prevalences of musculoskeletal disorders in the general population seen by general practitioners modelling a GP panel. RESULT: Out of 131 biomarkers considered originally, we evaluated 32 biomarkers in this study, of which only seven passed the three inclusion/exclusion criteria and were combined by multivariate analysis using four different mathematical models. In the modelled clinic panel, anti-CCP was the lead marker with a sensitivity of 75.8% and a specificity of 94.0%. Due to the lack in specificity of the markers other than anti-CCP in this diagnostic setting, any gain in sensitivity by any marker combination is off-set by a corresponding loss in specificity. In the modelled GP panel, the best marker combination of anti-CCP and interleukin (IL)-6 resulted in a sensitivity gain of 7.6% (85.9% vs. 78.3%) at a minor loss in specificity of 1.6% (90.3% vs. 91.9%) compared with anti-CCP as the best single marker. CONCLUSION: Depending on the composition of the sample panel, anti-CCP alone or anti-CCP in combination with IL-6 has the highest classification power for the diagnosis of established RA.

Silicone oil injection in conjunction with pars plana vitrectomy was carried out by five surgeons in 415 consecutive patients using the same surgical equipment, the same surgical techniques and the same highly purified silicone oil (viscosity, 5000 mPa.s). Indications for silicone oil injection after vitrectomy included advanced stages of proliferative vitreoretinopathy following rhegmatogenous retinal detachment (49%), severe proliferative diabetic retinopathy (38%), and proliferative vitreoretinopathy following retinal detachment due to ocular trauma (13%). Postoperative complications were noted in a 6- to 30-month follow-up period. Cataractous changes of varying degree were seen in all phakic eyes. Silicone oil entered the anterior chamber in 6% of all phakic and pseudophakic eyes. Subretinal silicone oil was noted in 4%. Other complications associated with the use of intravitreal silicone oil included biomicroscopically visible silicone oil emulsification (0.7%), keratopathy (5.5%), glaucoma (6%), closure of the inferior iridectomy (6%), and reproliferation of epiretinal and subretinal fibrous membranes (40%). We anticipate that the physico-chemical characteristics of the highly purified silicone oil (viscosity, 5000 mPa.s) and the routine performance of an inferior iridectomy in all aphakic eyes had a positive impact on the low incidence of silicone-oil-related complications such as emulsification, keratopathy and secondary glaucoma.

Background Loa Loa is a chronic parasitemic disease which is endemic in the tropical rain forests of Western Africa. Vector of this disease is a mangrove fly with the name Chrysops. Besides the eye worm and skin affections a systemic infection with microfilariae is common. Patient A West African tourist from Bangibe showed up at the university eye clinic. His complaints were a red eye and a mobile subconjunctival tumor (Fig. 1) that showed vermiform movements. The worm was transparent and 4-5 cm in length. After topical anaesthesia and the attempt to paralyze the worm (1) with Pilocarpine 2% it vanished. Two days later the patient showed up in the morning for the planned blood test. No worm was visible at that time but at noontime the blood test was carried out and at that time the worm was visible in the nasal conjunctiva. This time the worm was removed without delay under topical anaesthesia. The worm was fixed with a forceps through the conjunctiva which was opened for 0.5 cm. The worm was grasped with a second forceps and drawn out under massive vermiform movement. Systemic therapy was recommended with Hetrazan (Diethylcarbamazine) using Corticosteroides and Antihistamine to minimize allergic side effects by the therapy due to the systemic microfilariae blood load. Eosinophilia was 8%. Conclusions A subconjuctival Loa Loa worm can be removed under topical anaesthesia by fixing it with a forceps through the conjunctiva and opening it and grasping the worm with a second forceps. According to our experience the paralyzation with Pilocarpine cannot be realized. Careful systemic therapy avoiding reported allergic side effects with Hetrazan which is not available in Germany is necessary.

Purpose To investigate the complication profile and the long-term functional outcome of combined pars plana vitrectomy and scleral-fixated sutured posterior chamber lens (PC IOL) implantation. Design Retrospective, consecutive, interventional case series. Methods The records of 63 patients (mean age, 67.5 years) were reviewed retrospectively (follow-up, 12 to 132 months; mean, 43.5 months). The underlying ocular pathologic features; the intraoperative, early (within two weeks after surgery), and late complications (more than two weeks after surgery); final best-corrected visual acuity (BCVA); and the refractive outcome were recorded. Results Fifty-nine of 63 procedures (93.7%) were performed without complications. Intraoperative complications included vitreous hemorrhage (n = 2), a retinal tear (n = 1), and a rupture of the iris base (n = 1). Early complications included transient raise of intraocular pressure (IOP; n=19), transient vitreous hemorrhage (n = 2), scleral tunnel insufficiency (n = 5), pupillary capture of intraocular lens [IOL] (n = 6), persistent vitreous (n = 3), and choroidal hemorrhage (n = 1). Late complications occurred in 12 patients: rhegmatogenous retinal detachment (n = 4), proliferative vitreoretinopathy retinal detachment secondary to the underlying ocular pathologic features (n = 2), choroidal hemorrhage (n = 1), macular pucker (n = 1), and IOL dislocation (n = 4), including two cases of suture break. Mean BCVA in logarithm of the minimum angle of resolution units improved significantly from 1.025 (standard deviation [SD], 0.654) to 0.766 (SD, 0.750; P = .03). Mean cylindric equivalent significantly changed from 0.92 diopters (D; SD, 1.075) to 1.76 D (SD, 1.344; P = .005). Conclusions The surgical procedures were performed safely in approximately 94% of patients. Most postoperative complications were minor: significant ones occurred in approximately 20%, whereas suture breaks were observed rarely. The only moderate long-term functional improvement in this case series was mainly determined by the underlying ocular pathologic features.

PURPOSE: To report a case of bilateral acute posterior multifocal placoid pigment epitheliopathy (APMPPE) evaluated by optical coherence tomography (OCT), fundus autofluorescence (AF) and microperimetry, both in the acute phase and after resolution of symptoms. METHODS: Complete ophthalmological evaluation, including fluorescein angiography, OCT, AF, and microperimetry upon presentation and 1 month later, after lesions have subsided. An attempt to correlate the findings on presentation and changes after resolution is performed using the results of these new investigational techniques. RESULTS: APMPPE showed hyperreflectance in OCT at the level of the outer retinal layers, without increase in retinal thickness. AF revealed early decreased fluorescence due to a masking effect, and later reveals increased fluorescence after resolution of OCT findings. Function is disturbed at the lesion sites, as shown by microperimetry, and later returns to near normal values on microperimetry. CONCLUSION: APMPPE shows outer retinal layers changes on OCT, which resolve totally after subsidence of the acute phase. AF shows areas of increased fluorescence after resolution, with near normal return of function on microperimetry.

AIM: To investigate macular function and morphology after surgical removal of idiopathic epiretinal membrane (IEM) with and without assistance of indocyanine green (ICG). METHODS: A retrospective study as a consecutive case series, of 39 patients with IEM. 39 patients, 23 female, 16 male, mean age 67 years, underwent standard three port pars plana vitrectomy with removal of epiretinal membrane. Two groups of patients were consecutively operated: in 20 patients ICG 0.1% in glucose 5% was used to stain the epiretinal membrane. 19 patients underwent the identical procedure but without use of ICG. Postoperative follow up was 1-92 months (mean 15.5 months). Functional outcome was assessed with subjective improvement, best corrected visual acuity (BCVA), Amsler grid test, 10 degrees and 30 degrees automated perimetry (Heidelberg visual field analyser) (HFA), and Goldmann kinetic perimetry. Macular morphology was assessed with stereoscopic biomicroscopy and optical coherence tomography (OCT). The main outcome measures were macular function as determined by BCVA, presence of visual field defects, and metamorphopsia as determined by Amsler grid test, macular morphology as determined by slit lamp biomicroscopy, and OCT. RESULTS: BCVA improved in 28 patients, remained unchanged in eight patients, and decreased in three patients. Improvement of BCVA was statistically significant in both groups (p = 0.003). Mean BCVA in patients operated with ICG improved from 0.33 preoperatively to 0.53 postoperatively. Mean BCVA in patients operated without ICG improved from 0.32 preoperatively to 0.54 postoperatively. Reduction of macular oedema as measured by OCT was statistically significant in both groups (p

Schlottmann K, Fuchs-Koelwel B, Demmler-Hackenberg M, Gabel V-P, Scholmerich J he evaluation of symptomatic or incidentally diagnosed ophthalmic tumors usually is performed using funduscopy and Aand B-mode sonography. Additional techniques are Doppler modes [1], fluorescence or indocyanine green angiography [2], CT [3], and MR tomography [4]. Aand B-mode sonography allows the measurement of tumor depth and size [5], and A-mode and Doppler sonography estimates tumor vascularization and perfusion [6]. Histologic data indicate the importance of tumor vascularization as a determinant of the biologic behavior and the response to radiation therapy of choroidal melanoma. Hence, the analysis of tumor perfusion is crucial to discriminate solid from liquid or degenerative lesions and for the evaluation of response of choroidal melanoma to radiation therapy [7]. Uveal melanoma vascularity also is correlated to its metastatic potential [8]. A new sonographic technique, contrast harmonic imaging, uses IV-administered gasfilled microbubbles that remain intravascular after IV injection [9]. The nonlinear harmonic backscatter signals from such resonating microbubbles now can be visualized continuously at very low transmit power (low mechanical index). We have adapted contrast harmonic imaging at a low mechanical index using the sonographic contrast agent BR1 and a high-frequency transducer to analyze perfusion of ophthalmic tumors. In this feasibility study, we show the analysis of perfusion of choroidal tumors is possible on contrast harmonic imaging, even when other sonographic techniques fail to detect tumor perfusion.

Young patients with vitreous, retinal and subvitreal haemorrhages without neovascularisation or prior trauma are a diagnostic challenge for the physician. In this case report, a patient is presented who developed unilateral, spontaneous, subvitreal, retinal and subretinal haemorrhages and was diagnosed with von Willebrand's disease.A 33-year-old Caucasian woman presented at our clinic with unilateral subvitreal, retinal and subretinal haemorrhages. The haemorrhages occurred spontaneously without prior trauma, and the patient had no history of prior bleeding complications. Analysis of the coagulation-fibrinolysis system and von Willebrand multimer analysis led to the diagnosis von Willebrand's disease type I.Spontaneous subvitreal, retinal and subretinal haemorrhages may be associated with coagulation disorders. Especially in young patients, von Willebrand's disease should be considered as a possible cause.

The German 'SubRet' consortium has fabricated various types of microphotodiode arrays, the photovoltaic response of which will induce a retina response after implantation in the subretinal space. Ultrathin and flexible devices have been designed as well as CMOS-based chips with different pixel sizes and electrode configurations. From in-vitro electrostimulation studies, it becomes clear that a purely photovoltaic mode of operation will not be feasible, but an additional energy input by near-infrared radiation or radio frequency power transmission needs to be incorporated. Implantation experiments on pigs and rabbits prove the biocompatibility, general function and local stability of the implants. The inner retina architecture is well preserved, and literally no glia proliferation is found from long-term monitoring and histological examination. In conclusion, the subretinal approach is very promising and our results are encouraging, although major obstacles cannot be excluded concerning the application in human.

Background. Heavy tamponades for pathologies in the lower part of the retina are a new development, and different tamponades have recently come into clinical use: semifluorinated alkanes (F6H6, F6H8) and their oligomers (OL62HV). Method. Nine patients had been operated on using F6H8 (n=5) and by OL62HV (n=4). In all cases the reasons for using the tamponades were complicated retinal detachments in the lower part. In three cases the use was primary and in six cases tamponades were used after reoperations. In all cases the endotamponade was removed within 6 weeks. Fluorescein angiography (FLA) was performed in the F6H8 group. Results. In the F6H8 group dispersion developed in two of the three aphacic patients. In two out of five cases soft epiretinal membranes and cellular material could be found between the substance and the lower periphery. In two membranes examined by light microscopy, cystic cells and amorphous material could be found. In one case (PDRP, aphacic) cyclophotocoagulation had to be performed because of persistent elevated IOP. FLA was unremarkable. In the OL62HV group, severe recurrent PVR reaction occurred in the lower periphery (2/4) and unusual precipitates were observed (4/4). In one case, after a normal postoperative period (VA 0.05 after 5 days) an extensive cellular reaction on the complete surface of the tamponade occurred. After 5 weeks VA was no light perception. During removal of the oligomer unusual adherent cellular components were found on the surface of the retina. The retina appeared necrotic, showed constricted retinal vessels and there was optic atrophy. Histologically, fluffy epiretinal material and a lens capsule obtained from one eye filled with OL62HV resembled the appearance with F6H8. Conclusion. Heavy endotamponades on the basis of semifluorinated alkanes can lead to an unusual biological reaction and need further investigation before clinical use.

Introduction: Retinal detachment after macular hole surgery is a rare complication, usually occurring because of small, peripheral holes. We present a patient with a high bullous exudative retinal detachment following pars plana vitrectomy. Case report: A healthy 69-year-old patient presented with a macular hole stage III of the left eye. Corrected visual acuity was 20/200. Pars plana vitrectomy was performed without peeling of the internal limiting membrane or an epiretinal membrane, a few drops of platelet concentrate were instilled onto the hole, and the bulbus was filled subtotally with a non-expanding SF6/air mixture. On the 3rd postoperative day a small retinal detachment of the inferior half of the retina was noticed that increased over the next 3 days until it reached the inferior vascular arcade. During the following 3 days a spontaneous remission occurred with complete reattachment of the retina. Six weeks after operation the retina was completely reattached, the macular hole was closed, and the visual acuity was 20/200 with a slight cataract. Conclusion: Retinal detachments after macular hole surgery are not always of rhegmatogenous nature but may also be exudative and related to an inflammatory reaction caused by adjuvants. When a retinal detachment occurs immediately after macular hole surgery without detectable holes it may be advisable to wait for some days before reoperation.

Data from a case-control study in Lower Saxony, Germany, were used to assess whether the risk for childhood cancer may be reduced by bacille Calmette-Guérin (BCG) vaccination in the neonatal period. There were 420 newly diagnosed childhood cancer cases from the German cancer registry and 613 controls eligible for this study. A mailed questionnaire was completed during a telephone interview with parents. Details on the perinatal history were abstracted from the birth charts by nurses blinded to the children's case-control status. Complete information was available for 259 cases and for 323 controls. A total of 85% of the controls had been BCG vaccinated in the newborn period. The adjusted odds ratios for BCG vaccination were 0.90 (95% confidence interval; 0.51-1.61) for leukemia and 0.61 (95% confidence interval; 0.25-1.50) for other cancers. Based on these data the probability of a 50% or more reduction of more reduction of the cancer risk by BCG vaccination in the newborn period is small. The statistical power of this study, however, was not high enough to rule out a smaller, still relevant reduction in cancer risk.

Background: The pathogenesis of central serous chorioretinopathy is poorly understood. It is believed to be due to dysfunction of the retinal pigment epithelium and/or choroid and has been associated with elevated levels of epinephrine and administration of corticosteroids. Epinephrine and corticosteroids have previously been shown to induce apoptosis (programmed cell death) in various types of cells. The objective of this study was to investigate whether these agents can induce apoptosis in cultured retinal pigment epithelium cells. This may help elucidate the pathogenesis of central serous chorioretinopathy. Methods: Third-passage porcine retinal pigment epithelium cells were grown to confluence and incubated for 1–7 days in culture medium containing epinephrine (102–109 pg/ml) or a corticosteroid, dexamethasone (4–4×104 ng/ml). The cultures were evaluated for apoptosis by phase-contrast microscopy and in situ terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. Results: Epinephrine (7×107– 109 pg/ml) induced apoptosis in a dose- and time-dependent manner. Exposure to lower concentrations of epinephrine (102–6×107 pg/ml) and all tested levels of dexamethasone did not result in apoptosis. Conclusion: Retinal pigment epithelium cells may undergo apoptosis following exposure to elevated levels of epinephrine. These findings suggest a possible pathophysiologic mechanism for the development of central serous chorioretinopathy.

Objective To assess the impact of breast feeding on the risk of obesity and risk of being overweight in children at the time of entry to school. Design Cross sectional survey Setting Bavaria, southern Germany. Methods Routine data were collected on the height and weight of 134 577 children participating in the obligatory health examination at the time of school entry in Bavaria. In a subsample of 13 345 children, early feeding, diet, and lifestyle factors were assessed using responses to a questionnaire completed by parents. Subjects 9357 children aged 5 and 6 who had German nationality.

PURPOSE This study evaluated the outcome of severely injured eyes treated with early primary vitrectomy with silicone oil filling. METHODS A total of 435 eye injuries, which required surgical intervention, were reviewed retrospectively. In 13 eyes (3%) pars plana vitrectomy and silicone oil filling were performed as primary surgical repair. Silicone oil filling was restricted to cases with laceration of the retina larger than 4 disc diameters (nine eyes), primary retinal detachment larger than two quadrants (two eyes) and/or persistent intrasurgical hemorrhage (12 eyes). All patients underwent surgery within 24 hours. RESULTS After a mean follow-up period of 28.7 months (range, 9-70 months), 11 eyes achieved a visual acuity ranging from 20/25 to 20/200. Silicone oil was removed in 11 of 13 eyes after 5.8 +/- 4.6 months. Recurrent proliferative vitreoretinopathy developed in two eyes. CONCLUSIONS Silicone oil tamponade after early primary pars plana vitrectomy may be an alternative for primary repair after trauma, especially in severely injured eyes with retinal lacerations larger than 4 disc diameters, persistent intrasurgical bleeding, and/or primary retinal detachments.

Purpose The perception of 11 persons blinded by hereditary retinal degeneration elicited by a subretinally implanted 16-electrode array used for light-independent direct stimulation of the retina is described. This device is part of the Tubingen retina implant, which also employs a light-sensitive, multiphotodiode array (MPDA). The ability to reliably recognize complex spatial percepts was investigated. Methods Eleven blind volunteers received implants and participated in standardized psychophysical tests investigating the size and shape of perceptions elicited by single-electrode activation, multiple-electrode activation, and activation of compound patterns such as simplified letters. Results Visual percepts were elicited reliably in 8 of 11 patients. On single-electrode activation, percepts were generally described as round spots of light of distinguishable localization in the visual field. On activation of a pattern of electrodes, percepts matched that pattern when electrodes were activated sequentially. Patterns such as horizontal or vertical bars were identified reliably; the most recent participant was able to recognize simplified letters presented on the 16-electrode array. The smallest distance between sites of concurrent retinal stimulation still yielding discernible spots of light was assessed to be 280 μm, corresponding to a logMAR of 1.78. Conclusions Subretinal electric stimulation can yield reliable, predictable percepts. Patterned perception is feasible, enabling blind persons to recognize shapes and discriminate different letters. Stimulation paradigms must be optimized, to further increase spatial resolution, demanding a better understanding of physical and biological effects of single versus repetitive stimulation (ClinicalTrials.gov number, NCT00515814).

PURPOSE. To assess retinal toxicity of indocyanine green (ICG) in a porcine ex vivo perfusion organ culture model, and to measure intraretinal penetration of ICG applied to the retinal surface. METHODS. The retinal surface of fresh porcine retinal tissue was exposed to ICG 0.1% and 1% dissolved in glucose 5% for 1 and 30 minutes with and without concomitant illumination. Specimens were then kept in perfusion organ culture for 24 hours before examination by light microscopy and the TUNEL technique. Tissue samples treated with DNAse served as positive controls, and samples exposed to saline served as negative controls. Fluorescence microscopy was used to localize ICG at 1 minute, 60 minutes, 2 hours, and 3 hours after a 1-minute exposure of the retinal surface to ICG 1%. RESULTS. No increase in TUNEL-positive cells was observed after exposure to ICG 0.1% for 1 minute. Moderate apoptosis was found after 1-minute exposure to ICG 1% and 30-minute exposure to ICG 0.1%, and severe apoptosis was found after 30-minute exposure to ICG 1%. Concomitant application of light did not influence the degree of apoptosis. No signs of cell necrosis were found. After 1-minute exposure of the retinal surface, ICG 1% gradually penetrated the entire retina. CONCLUSIONS. ICG induced apoptosis but not necrosis in all nuclear retinal layers in a dose-dependent manner. Brief exposure to ICG 0.1% for 1 minute and illumination for 3 minutes simulated the intraoperative use of ICG. No retinal apoptosis or necrosis was observed. ICG briefly applied to the retinal surface gradually penetrated the entire retina. (Invest Ophthalmol