Radiation-Induced DNA Damage in Uveal Melanoma Is Influenced by Dose Delivery and Chromosome 3 Status.

Purpose: The purpose of this study was to analyze the extent of DNA breaks in primary uveal melanoma (UM) with regard to radiotherapy dose delivery (single-dose versus fractionated) and monosomy 3 status. Methods: A total of 54 patients with UM were included. Stereotactic radiotherapy (SRT) was performed in 23 patients, with 8 undergoing single-dose SRT (sdSRT) treatment and 15 receiving fractionated SRT (fSRT). DNA breaks in the enucleated or endoresected tumors were visualized by a TUNEL assay and quantified by measuring the TUNEL-positive area. Protein expression was analyzed by immunohistochemistry. Co-detection of chromosome 3 with proteins was performed by immuno-fluorescent in situ hybridization. Results: The amount of DNA breaks in the total irradiated group was increased by 2.7-fold (P < 0.001) compared to non-irradiated tissue. Tumors treated with fSRT were affected more severely, showing 2.1-fold more DNA damage (P = 0.007) compared to the cases after single (high) dose irradiation (sdSRT). Monosomy 3 tumors showed less DNA breaks compared to disomy 3 samples (P = 0.004). The presence of metastases after radiotherapy correlated with monosomy 3 and less DNA breaks compared to patients with non-metastatic cancer in the combined group with fSRT and sdSRT (P < 0.05). Conclusions: Fractionated irradiation led to more DNA damage than single-dose treatment in primary UM. As tumors with monosomy 3 showed less DNA breaks than those with disomy 3, this may indicate that they are less radiosensitive, which may influence the efficacy of irradiation.

A COMPARATIVE ANALYSIS OF TRAUMATIC RETINAL DETACHMENT AFTER OPEN AND CLOSED GLOBE INJURIES IN CHILDREN.

PURPOSE: Pediatric traumatic retinal detachment (RD) resulting from open globe injuries (OGIs) or closed globe injuries (CGIs) presents unique challenges due to complexity often resulting in lifelong sequelae. This study compares pediatric traumatic RD outcomes and prognostic factors following OGI and CGI. METHODS: A retrospective analysis reviewed 47 cases of pediatric traumatic RD in children (age <18 years), who underwent RD surgery between 2002 and 2021. Among them, 25 cases were caused by CGI and 22 cases by OGI. Demographics, RD characteristics, surgical procedures, and anatomical and functional results were assessed. Predictive factors for visual outcomes were investigated. RESULTS: In the CGI group, mean (±SD) age was 11 years ± 4 years, and 10 years ± 5 years in the OGI group. Closed globe injury traumatic RD had significantly better preoperative (CGI: logarithm of the minimum angle of resolution 1.39 ± 0.19 (mean ± standard error); OGI: logarithm of the minimum angle of resolution 2.12 ± 0.20) and follow-up (CGI: logarithm of the minimum angle of resolution 0.94 ± 0.19; OGI: logarithm of the minimum angle of resolution 1.85 ± 0.20) best-corrected visual acuity (BCVA) ( P < 0.05). Initial BCVA improvement was observed in CGI only. In multivariable analysis, prognostic factors for favorable BCVA outcomes included higher preoperative BCVA, older age, and absence of proliferative vitreoretinopathy ( P < 0.05). CONCLUSION: Visual prognosis for pediatric traumatic RD remains limited, favoring CGI cases compared with OGI. Baseline BCVA emerged as a major determinant of final visual acuity. Tailored management approaches can optimize treatment results.

The time course of spontaneous closure of idiopathic full-thickness macular holes.

PURPOSE: Spontaneous closure of idiopathic full-thickness macular holes (iFTMH) has been reported regularly. However, little is known about its probability and timeline. METHODS: In this retrospective study all consecutive patients who presented between August 2008 and August 2019 were screened for the presence of a macular hole and only iFTMHs were included. The primary outcome measure was the spontaneous closure of the iFTMH. RESULTS: Of 1256 eyes with macular holes, 338 fulfilled the inclusion criteria. Spontaneous closure of the iFTMH was detected in 31 eyes (9.2%) with a median time of 44 days after diagnosis. Eyes exhibiting spontaneous closure demonstrated a higher baseline best-corrected visual-acuity (BCVA) and smaller iFTMH diameter (p < 0.0001 and p < 0.0001, respectively). The mean BCVA improved from 0.4 logMAR (SD ± 0.21) to 0.29 logMAR (SD ± 0.20) after spontaneous closure (p = 0.031). The iFTMH diameter was positively correlated with the time to spontaneous closure (Pearson-r = 0.37, p = 0.0377). Spontaneously closed iFTMHs reopened in 16% (n = 5) of cases, with a median of 136 days after closure. A logistic regression model showed the hole diameter was associated with spontaneous closure (odds-Ratio 0.97, 95%CI [0.96, 0.98]). The Kaplan-Meier-Curve revealed that approximately 25% of small-iFTMH (n = 124) and 55% of iFTMH with a diameter < 150µm (n = 48) closed spontaneously within two months. CONCLUSION: The established gold-standard for the treatment of iFTMHs is macular surgery. However, the potential for spontaneous closure of small iFTMHs must be acknowledged. Therefore, if surgical treatment is delayed in individual cases, close observation is recommended.

[Surgical therapy and pathogen detection in endogenous endophthalmitis : Analysis of data from five German eye hospitals]. / Operative Therapie und Keimnachweis bei endogener Endophthalmitis : Datenauswertung aus 5 Augenkliniken.

BACKGROUND: Endogenous endophthalmitis results from hematogenous spread of bacterial or fungal infection in severely diseased patients. Specific systemic and intraocular therapy is required. The basis for this treatment is causal pathogen detection in blood culture or vitreous sample. However, functional results are limited. OBJECTIVE: The current article provides practical hints for surgical therapy and pathogen detection in patients with endogenous endophthalmitis. METHODS: A retrospective analysis of anonymous data of 68 male and female patients from 2018-2023 from five ophthalmology clinics in Germany was performed. RESULTS: Mean age of affected patients was 71.4 years (31-96 years). Surgical therapy included pars plana vitrectomy (ppV) and intravitreal injection (IVOM). In 44 of 68 patients (65%), 1-3 surgeries were performed, 4-6 surgeries were required in 14/68 (21%) of patients, and 10 or more surgeries were required in 4/68 patients (6%). Pathogen detection was possible in 34% of vitreous specimens and in 11% of anterior chamber samples. Mean initial visual acuity was logMAR 1.5. After treatment and a mean follow-up of 2.5 months, mean visual acuity was logMAR 1.3. Preanalytical methods for specimen collection like the Freiburg endophthalmitis set to optimize pathogen detection are presented. CONCLUSION: Severe inflammatory intraocular reactions in endogenous endophthalmitis necessitate a combination of ppV and repeated IVOM. In addition to providing a vitreous sample, ppV also serves to remove inflammatory fibrin membranes. Early pars plana vitrectomy with specific antibiotic or antifungal therapy should be sought in addition to the focus search and systemic therapy.

Introducing a customized low-cost macular buckle.

PURPOSE: To demonstrate a novel surgical technique that is a low-cost alternative to commercial implants for macular buckling in high myopia. METHODS: A silicon encircling band serves as the anchor. A second silicon circling band is employed, with a 10mm silicon strip to widen the posterior scleral indentation. This band is inserted posteriorly the lateral and inferior rectus muscles and pushed behind the globe, orienting it in a superior-temporal to inferio-nasal position with the silicone strip directly under the macula. For better visualization, the placement of the macular buckle is done under the microscope. RESULTS: The placement of the macular buckle led to reattachment of the central retina in treated patients during long-term follow-up. This technique eliminates the need for detaching a rectus muscle. Visual acuity remained stable throughout the follow-up period. CONCLUSION: This customized macular buckle technique can improve the anatomical outcome in patients with central retinal detachment due to high myopia.

Incidence of central retinal artery occlusion peaks in winter season.

Introduction: Stroke incidence exhibits seasonal trends, with the highest occurrences observed during winter. This study investigates the incidence of central retinal artery occlusion (CRAO), a stroke equivalent of the retina, and explores its monthly and seasonal variations, as well as potential associations with weather and ambient air pollutants. Methods: A retrospective search of medical records spanning 15 years (January 2008-December 2022) was conducted at the University Eye Hospital Tübingen, Germany, focusing on diagnosed cases of CRAO. Incidences were evaluated on a monthly and seasonal basis (winter, spring, summer, fall). Weather data (temperature, precipitation, atmospheric pressure) and concentrations of ambient air pollutants [fine particulate matter (PM2.5), coarse particulate matter (PM10), nitrogen dioxide (NO2), and ozone (O3)], were analyzed for a potential association with CRAO incidence. Results: Out of 432 patients diagnosed with CRAO between 2008 and 2022, significantly varying incidences were observed monthly (p = 0.025) and seasonally (p = 0.008). The highest rates were recorded in February and winter, with the lowest rates in June and summer. Concentrations of NO2, PM2.5 and lower ambient air temperature (average, minimum, maximum) showed significant correlations with CRAO incidence. Discussion: This comprehensive 15-year analysis reveals a pronounced winter peak in CRAO incidence, with the lowest occurrences in summer. Potential associations between CRAO incidence and ambient air pollutants and temperature underscore the importance of considering seasonal trends and call for further investigations to elucidate contributing factors, potentially leading to targeted preventive strategies and public health interventions.

Fall-related ocular trauma in patients over 90 years in tertiary ophthalmic center in Germany: 90-TOSG Report 1.

PURPOSE: To investigate the clinical characteristics of fall-related ocular trauma in patients over 90 years of age. METHODS: Retrospective, medical record reviews. Patients over the age of 90 years treated in a tertiary center with fall-related ocular trauma were included in the study. RESULTS: Fifty consecutive patients (fifty eyes) were analyzed. The mean age was 93.6 ± 1.8 years and 41 patients (82%) were female. The most common site of the injuries was orbital fracture (18 patients, 36%), accompanied with open globe rupture (OGR) in three patients, and globe contusion in two patients. Seventeen patients (34%) presented with OGR. Ocular trauma score in those patients was category 1 in 10 patients (58.8%) and category 2 in the others. Conjunctival hemorrhage and/or periocular contusion was seen in 14 patients (28%) and globe contusion in six patients (12%). At the presentation, the mean best corrected visual acuity (BCVA) was 2.82 ± 0.24 logMAR in patients with OGR and 1.98 ± 0.81 logMAR in six patients with globe contusion. Three of the patients with OGR had a final vision of 20/200 or better whereas the remaining patients had hand movements or less. The most common risk factors were female gender (82%) and use of antihypertensive drugs (46%). CONCLUSION: Patients with OGR had a poor visual outcome despite the early treatment. It is important to raise public awareness about of the poor prognosis of ocular injuries due to falls in the elderly population in order to establish preventive measures.

A Case Study from the Past: "The RGC-5 vs. the 661W Cell Line: Similarities, Differences and Contradictions-Are They Really the Same?"

In the pursuit of identifying the underlying pathways of ocular diseases, the use of cell lines such as (retinal ganglion cell-5) RGC-5 and 661W became a valuable tool, including pathologies like retinal degeneration and glaucoma. In 2001, the establishment of the RGC-5 cell line marked a significant breakthrough in glaucoma research. Over time, however, concerns arose about the true nature of RGC-5 cells, with conflicting findings in the literature regarding their identity as retinal ganglion cells or photoreceptor-like cells. This study aimed to address the controversy surrounding the RGC-5 cell line's origin and properties by comparing it with the 661W cell line, a known cone photoreceptor model. Both cell lines were differentiated according to two prior published redifferentiation protocols under the same conditions using 500 nM of trichostatin A (TSA) and investigated for their morphological and neuronal marker properties. The results demonstrated that both cell lines are murine, and they exhibited distinct morphological and neuronal marker properties. Notably, the RGC-5 cells showed higher expression of the neuronal marker ß-III tubulin and increased Thy-1-mRNA compared with the 661W cells, providing evidence of their different properties. The findings emphasize the importance of verifying the authenticity of cell lines used in ocular research and highlight the risks of contamination and altered cell properties.

Long-term outcomes of autologous platelet treatment for optic disc pit maculopathy.

PURPOSE: Optic disc pits (ODPs) are rare congenital cavitary abnormalities of the optic nerve head, which can lead to serous macular detachments. The aim of this study was to evaluate the long-term efficacy of pars plana vitrectomy (PPV) combined with autologous platelet concentrate (APC) for the treatment of optic disc pit maculopathy (ODP-M). METHODS: A retrospective analysis was performed on eleven eyes of ten patients with ODP-M, who received PPV combined with APC. Nine eyes operated primary, four of which had a repeat surgery also with injection of APC and two eyes underwent a rescue surgery, after they have been operated in another eye center without APC. Morphological and functional results were the main outcome parameters, determined by optical coherence tomography (OCT) and best-corrected visual acuity (BCVA), respectively. RESULTS: The mean duration of visual loss before surgery was 4.7 ± 3.89 months (range 0-12 months). The mean BCVA increased significantly from 0.82 ± 0.33 logMAR (range 0.4-1.3) preoperatively to 0.51 ± 0.36 logMAR (range 0-1.2) at the last examination (p = 0.0022). A significant morphological improvement was also noticed with decrease of the mean foveal thickness from 935.82 ± 248.48 µm (range 559-1400 µm) preoperatively to 226.45 ± 76.09 µm (range 110-344 µm) at the final examination (p < 0.0001). The patients were followed-up for a mean 65.36 ± 48.81 months (range 1-144 months). Two eyes developed postoperatively a retinal detachment. Cataract surgery was performed in 5 eyes during the follow-up period. CONCLUSION: Our study demonstrated that PPV with APC can improve functional and morphological outcomes, both as a primary and a rescue therapy, without any recurrence over a long follow-up period. To the best of our knowledge, this was the longest observation period regarding the use of APC in treatment of ODP-M.

Pitfalls of predicting age-related traits by polygenic risk scores.

Polygenic risk scores (PRS) are a method increasingly used to capture the combined effect of genome-wide significant variants and those which individually do not show genome-wide significant association but are likely to contribute to the risk of developing diseases. However, their practical use incurs complications and inconsistencies that so far limit their clinical applicability. The aims of the present review are to discuss the PRS for age-related diseases and to highlight pitfalls and limitations of PRS prediction accuracy due to ageing and mortality effects. We argue that the PRS is widely used but the individual's PRS values differ substantially depending on the number of genetic variants included, the discovery GWAS and the method employed to generate them. Moreover, for neurodegenerative disorders, although an individual's genetics do not change with age, the actual score depends on the age of the sample used in the discovery GWAS and is likely to reflect the individual's disease risk at this particular age. Improvement of PRS prediction accuracy for neurodegenerative disorders will come from two sides, both the precision of clinical diagnoses, and a careful attention to the age distribution in the underlying samples and validation of the prediction in longitudinal studies.

Two Methods for the Isolation and Cultivation of Porcine Primary Corneal Cells.

In ophthalmic research, there is a strong need for in vitro corneal cell models. Here, we describe different protocols for the cultivation of primary corneal cells that were isolated from porcine eyes. This primary cell culture can be used to test new therapeutic options for corneal diseases, such as dry eye disease, traumatic injuries, or corneal infections, and to study limbal epithelial stem cell (LESC) expansion. Two different isolation methods were performed: the outgrowth and the collagenase method. To perform the outgrowth protocol, small explants of the corneal limbus were generated and incubated in culture flasks in an incubator for 4-5 weeks. Regarding the collagenase method, to extract corneal cells, porcine corneas were removed, cut into small pieces, and incubated with collagenase. After incubation and centrifugation, the cells were seeded in 6- or 12-well plates and incubated in an incubator for 2-3 weeks. The differences between corneal cell cultivation with fetal bovine serum (FBS) and without it are also discussed. Therefore, the main advantages of the outgrowth method are that it requires fewer porcine eyes, and it takes less time to be performed compared to the collagenase method. On the other hand, with the collagenase method, mature cells are obtained earlier, at about 2 to 3 weeks.

What does heritability of Alzheimer's disease represent?

INTRODUCTION: Both late-onset Alzheimer's disease (AD) and ageing have a strong genetic component. In each case, many associated variants have been discovered, but how much missing heritability remains to be discovered is debated. Variability in the estimation of SNP-based heritability could explain the differences in reported heritability. METHODS: We compute heritability in five large independent cohorts (N = 7,396, 1,566, 803, 12,528 and 3,963) to determine whether a consensus for the AD heritability estimate can be reached. These cohorts vary by sample size, age of cases and controls and phenotype definition. We compute heritability a) for all SNPs, b) excluding APOE region, c) excluding both APOE and genome-wide association study hit regions, and d) SNPs overlapping a microglia gene-set. RESULTS: SNP-based heritability of late onset Alzheimer's disease is between 38 and 66% when age and genetic disease architecture are correctly accounted for. The heritability estimates decrease by 12% [SD = 8%] on average when the APOE region is excluded and an additional 1% [SD = 3%] when genome-wide significant regions were removed. A microglia gene-set explains 69-84% of our estimates of SNP-based heritability using only 3% of total SNPs in all cohorts. CONCLUSION: The heritability of neurodegenerative disorders cannot be represented as a single number, because it is dependent on the ages of cases and controls. Genome-wide association studies pick up a large proportion of total AD heritability when age and genetic architecture are correctly accounted for. Around 13% of SNP-based heritability can be explained by known genetic loci and the remaining heritability likely resides around microglial related genes.

CLOUDING OF INTRAOCULAR SILICONE OIL IN THE ABSENCE OF EMULSIFICATION.

PURPOSE: To describe intraocular clouding of silicone oil in the absence of emulsification. METHODS: Retrospective observational case series of patients who received silicone oil injections and developed silicone oil discoloration without emulsification after pars plana vitrectomy. Clinical examinations and physicochemical analyses were performed to find out the common cause for the opaque oil. RESULTS: Thirteen patients developed silicone oil discoloration after pars plana vitrectomy. It could be traced down that all patients had received silicone oil from one respective production batch. The silicone oil was removed as soon as possible after the changes were detected (range, 8-16 weeks). Gas chromatography flame ionization detector, size exclusion chromatography, and high-performance liquid chromatography analysis showed the absence of low-molecular-weight compounds in the opaque lot. Thermogravimetric analysis revealed the opaque lot was more temperature stable. During the follow-ups, no obvious retinal toxicity could be observed and best-recorded visual acuity improved considerably in 12 patients and was only limited by the underlying retinal pathologic conditions. CONCLUSION: This is the first report on opacification of intraocular silicone oil without emulsification. This discoloration of silicone oil may disturb vision and prevent proper fundus examination; however, it seems to be a nontoxic phenomenon without serious long-term consequences.

Legal obligation in the general population: face mask influence on endophthalmitis after intravitreal injection.

PURPOSE: To investigate whether compulsory face masking in public life changes the incidence or pattern of post-injection endophthalmitis (PIE). PATIENTS AND METHODS: All injections of bevacizumab, ranibizumab, aflibercept, dexamethasone or triamcinolone between 01/01/2015 and 12/31/2021 at the University Eye Clinic of Tuebingen were included in this retrospective analysis. The injection procedure itself was unchanged since 2015 and included the use of a sterile drape covering the head up to the shoulders which prevents airflow toward the eye. Furthermore, all staff wore a face mask and gloves at all times. The two study periods were defined by the introduction of a compulsory face masking rule in public life (01/01/2015 until 04/27/2020 vs. 04/28/2020 until 12/31/2021). RESULTS: A total of 83,543 injections were performed in the tertiary eye clinic, associated with a total of 20 PIE (0.024%, 1/4177 injections). Of these, thirteen PIE were documented during the pre-pandemic period (0.021%, 1/4773 injections) and seven PIE during the pandemic period (0.033%, 1/3071 injections). No significant difference in PIE risk was observed (p = 0.49), and there was no case of oral flora associated PIE. CONCLUSION: Although some potential confounders (wearing time, skin flora) could not be considered, there was no clear signal that the introduction of compulsory face masking in public life did alter the risk for PIE in our patient population. Three and six months after PIE, no difference in visual acuity was detectable between the two study periods.

Development of retinal atrophy after subretinal gene therapy with voretigene neparvovec.

BACKGROUND/AIMS: Voretigene neparvovec (VN) is the first and only subretinal gene therapy approved by the Food and Drug Administration and European Medicines Agency. Real-world application has started in 2018 in patients with vision impairment due to biallelic retinal pigment epithelium (RPE) 65 mutation-associated inherited retinal degenerations. Herein, we evaluated the development of retinal atrophy within in a single-centre patient cohort treated with VN. METHODS: 13 eyes of eight patients treated with VN were retrospectively analysed for areas of retinal atrophy over a period of 6-24 months following surgery. Ultrawide field images were used to measure the area of atrophy. Fundus autofluorescence imaging is presented as an instrument for early detection of signs of retinal atrophy in these patients. RESULTS: Atrophic changes beyond the retinotomy site were observed in all eyes. Areas of atrophy developed within the area of detachment (bleb) in all eight patients and outside the bleb in three patients. Changes in autofluorescence preceded the development of retinal atrophy and were already evident 2 weeks after surgery in the majority of patients. The areas of atrophy increase with time and progression continued over year 1. Functional outcomes remained stable (VA, FST, visual field). CONCLUSION: Subretinal injection of VN can lead to RPE atrophy with consequent photoreceptor loss in and outside of the bleb area. Fundus autofluorescence is an important tool to monitor atrophic changes in patients after gene therapy. Interestingly, while areas of atrophy also included central areas, the functional benefits of the treatment did not appear to be affected and remained stable.

Pupillotonia after endolaser retinopexy during vitrectomy for retinal detachment: a prospective cohort study comparing circumferential and focal retinopexy.

PURPOSE: To determine differences in postoperative pupil diameter in eyes that undergo pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD) with endolaser retinopexy (ELR), comparing 360° vs focal ELR. METHODS: Patients with uncomplicated RRD who underwent PPV were prospectively analysed regarding the postoperative pupil diameter difference (PDD) between the affected eye and the partner eye. Group 1 underwent 360° ELR and group 2 received focal ELR. Postoperative vision and complications, including redetachment rate, macular oedema and epiretinal membrane formation, were also compared. RESULTS: A total of 72 patients, 42 in group 1 and 30 in group 2, were analysed. PDD, as observed at 6 weeks, was significantly greater than the preoperative values in both groups 1 and 2. It increased by a mean of 1±1.11 mm in group 1 and by 0.5±0.78 in group 2. This initial increase in PDD receded over time, but remained statistically significant in both groups, even at 6 months. The top 20% of patients with the largest PDD change comprised 13 out of 15 eyes from group 1, which was a statistically significant overrepresentation (p=0.0435). CONCLUSIONS: Moderate pupillotonia was induced post-ELR in vitrectomy and correlated to the extent of ELR. The pupillotonia effect of ELR was significantly less marked in pseudophakic eyes.

DMEK outcome after one year - Results from a large multicenter study in Germany.

PURPOSE: Descemet membrane endothelial keratoplasty (DMEK) accounts for >50% of all corneal transplants in Germany. So far, no data from such a large multicenter study have been published. METHODS: This retrospective study included 3200 DMEKs at seven departments performed for Fuchs endothelial corneal dystrophy (FECD) or bullous keratopathy (BK). We evaluated best corrected visual acuity (BCVA, logMAR), endothelial cell density (ECD, cells/mm2 ), minimal corneal thickness (CT, µm), rebubbling-, primary transplant failure- and immune reaction-rate. Changes over time were evaluated by linear mixed models for repeated measures and correlation with case number by center by weighted linear regression. RESULTS: For patients without vision-limiting comorbidities (74% of all analysed eyes, n = 2270), mean BCVA improved from 0.6 ± 0.4 logMAR to 0.2 ± 0.2 logMAR 6 months (p < 0.001, n = 1441) and 0.1 ± 0.2 logMAR 12 months (p = 0.001, n = 1402) postoperatively. BK- had a worse BCVA compared to FECD-patients (0.3 ± 0.5 vs. 0.1 ± 0.2 logMAR [p < 0.001] at 1 year). ECD declined from 2465 ± 259 cells/mm2 (n = 2876 preoperatively) to 1587 ± 433 cells/mm2 after 12 months (p < 0.001, n = 1237). Mean rebubbling rate was 0.4 ± 0.7/eye. 784 eyes (25%) received at least one rebubbling. More rebubblings correlated with a lower ECD, a worse BCVA, a higher CT, and higher transplant failure and rejection rates (p < 0.001, p = 0.013 for BCVA at 12 months). A single rebubbling did not influence the BCVA (p = 0.785). Graft failure rate was 3% (n = 67), rejection rate 1.5% (n = 48). CONCLUSION: Descemet membrane endothelial keratoplasty increases visual acuity with low transplant failure- and rejection-rates. FECD has a better outcome than BK. Since a quarter of all patients need a rebubbling, this should be included in the informed consent. Remarkably, one rebubbling has no influence on the outcome.

A new digitised screen test for strabismus measurement.

PURPOSE: Our study presents a digitised tangent screen test for ocular motility analysis according to the Harms and Hess tests (measurement of the squint angle in all fields of vision). This test uses an image beamer to display the tangent screen, a position sensor to measure the patient's head orientation, and a distance sensor to measure the fixation distance. Digital measurement of head orientation allows for a test procedure that eliminates the conventional requirement for a light pointer in the patient's hand. Thus, the digital screen test is presented, and the uncertainty of the measurement system is evaluated. METHODS: A mathematical relationship was given between the measured squint angles, as well as the angle of diagnostic gaze direction, and the influence quantities on their measurement uncertainty. The individual uncertainties resulted from deviations in the measured values by the position and distance sensors, the calibration of the projection image of the beamer in length units, and the finite image resolution of the beamer. The individual standard uncertainties of the influence quantities were determined. The combined standard measurement uncertainties of the squint and gaze direction angles were given based on the model equation of the error propagation law at the tangent table according to Harms at a test distance of 2.5 m. The patient's uncertainty contribution to the mobility analysis was not considered. RESULTS: The combined standard uncertainty of the measurement system (coverage factor k = 2 for 95% confidence level) for the squint angle is ≤ 0.43° for the angle of diagnostic gaze direction ≤ 3.13° at the test distance of 2.5 m. The individual standard uncertainties of the influence quantities on the angles are (k = 1): 1.55°/1.01° (horizontal/vertical angle of the position sensor), 0.19° (distance sensor), 0.06° (calibration of the projection image of the beamer), and 0.02° (image resolution of the beamer). The maximum valid test distance of the digital screen test is 3.8 m. CONCLUSION: The digital screen test is compact and can be used at different locations. Compared to the traditional test, the time required for examination via the digitised test is less; additionally, its documentation is simplified. The measurement uncertainty of the diagnostic gaze direction angle is dominated by the sensor drift of the position sensor in the horizontal direction (yaw angle) and is due to the sensor technology. However, this drift error does not affect the squint angle measurement result nor its measurement uncertainty because the measurement principle used here is based on the congruence between the position cross and the fixation object and the confusion principle and compensates for the drift error. The measurement uncertainties of the determined measurement system are the lower limits of the uncertainties in the clinical use of the digital screen test if there are no effects due to significant patient deviations.

Modelling of Lemna minor L. growth as influenced by nutrient supply, supplemental light, CO2 and harvest intervals for a continuous indoor cultivation.

Given the proper conditions, Lemna spp. rapidly produce a high amount of valuable biomass which is considered as an alternative source for feed and food. For a continuous and long-term indoor production under controlled conditions, environmental and harvest parameters have to be optimized to suppress algal growth and constantly yield a high-quality product. Experimentally assessing the effect of a larger number of parameters on the growth rate ri is impossible due to the theoretically high number of parameter combinations. Thus, a SIMILE® - based model has been developed. This enables production parameters to be assessed individually for its effect on the growth rate r i by a differential equation. Start values for numerical integration were taken from measured data and analytical solutions of the differential growth equation. At 400 ppm CO2, the regrowth rate ri in an optimized laboratory set-up amounted to 216 g FM·m-2d-1, harvesting one third of the biomass at intervals of 5 days. In up-scaled set-ups, lower regrowth rates ri of about 173 g FM·m-2d-1 (Kalkar) and 190 g FM·m-2d-1 (Berlin) were obtained, because temperature and light conditions were below optimum. At 3,500 ppm CO2, the regrowth rate ri in laboratory set-up increased to 323 g FM·m-2d-1 by shortening the harvest interval to three days. Maximum growth rates ri were obtained with an NH4 +/NO3 - ratio of 1/9 at 1.14 mM total N concentration. The results indicate how to optimize culture conditions and harvest intervals. Model runs closely match the experimental data taken from the three different approaches and thus confirm the validity of the model.