Calibration of a portal imaging device for high-precision dosimetry: a Monte Carlo study

Today electronic portal imaging devices (EPID's) are used primarily to verify patient positioning. They have, however, also the potential as 2D-dosimeters and could be used as such for transit dosimetry or dose reconstruction. It has been proven that such devices, especially liquid filled ionization chambers, have a stable dose response relationship which can be described in terms of the physical properties of the EPID and the pulsed linac radiation. For absolute dosimetry however, an accurate method of calibration to an absolute dose is needed. In this work, we concentrate on calibration against dose in a homogeneous water phantom. Using a Monte Carlo model of the detector we calculated dose spread kernels in units of absolute dose per incident energy fluence and compared them to calculated dose spread kernels in water at different depths. The energy of the incident pencil beams varied between 0.5 and 18 MeV. At the depth of dose maximum in water for a 6 MV beam (1.5 cm) and for a 18 MV beam (3.0 cm) we observed large absolute differences between water and detector dose above an incident energy of 4 MeV but only small relative differences in the most frequent energy range of the beam energy spectra. It is shown that for a 6 MV beam the absolute reference dose measured at 1.5 cm water depth differs from the absolute detector dose by 3.8%. At depth 1.2 cm in water, however, the relative dose differences are almost constant between 2 and 6 MeV. The effects of changes in the energy spectrum of the beam on the dose responses in water and in the detector are also investigated. We show that differences larger than 2% can occur for different beam qualities of the incident photon beam behind water slabs of different thicknesses. It is therefore concluded that for high-precision dosimetry such effects have to be taken into account. Nevertheless, the precise information about the dose response of the detector provided in this Monte Carlo study forms the basis of extracting directly the basic radiometric quantities photon fluence and photon energy fluence from the detector's signal using a deconvolution algorithm. The results are therefore promising for future application in absolute transit dosimetry and absolute dose reconstruction.

Pharmacodynamics of antibiotics in the therapy of meningitis: infection model observations

Detailed studies of pharmacodynamic principles relevant to the therapy of bacterial meningitis are difficult to perform in man, while the rabbit model of bacterial meningitis has proved to be extremely valuable and has led to insights that appear relevant for the treatment of humans. Most importantly in the light of the restricted penetration of antibiotics into the CSF, animal studies have shown that in meningitis there is a dose-response curve between the CSF concentrations achieved by antibiotics and their bactericidal activity. This appears to be true for all classes of antibiotics thus far examined, including the beta-lactams, which do not show such a dose-response behaviour in other infections. Only CSF concentrations that exceed the MBC of the infecting organism by at least 10-30-fold achieve consistent and rapid bactericidal activity. Such rapid bactericidal activity is a requirement for successful therapy with beta-lactams and can be impaired with certain antibiotics by the specific conditions in infected CSF (protein content; acidic pH; slow-growing bacteria). However, rapid antibiotic killing of the infecting organisms may not be without adverse effects either. Some antibiotics, particularly beta-lactams lead to the brisk liberation of bacterial cell wall components (e.g. endotoxin, in the case of Gram-negative organisms) which have an inflammatory effect on the host and can lead to a temporary deterioration of the disease. Dexamethasone, when administered with the antibiotic, can prevent some of the adverse effects of rapid bacterial lysis.

Residence near power lines and mortality from neurodegenerative diseases: longitudinal study of the Swiss population

The relation between residential magnetic field exposure from power lines and mortality from neurodegenerative conditions was analyzed among 4.7 million persons of the Swiss National Cohort (linking mortality and census data), covering the period 2000-2005. Cox proportional hazard models were used to analyze the relation of living in the proximity of 220-380 kV power lines and the risk of death from neurodegenerative diseases, with adjustment for a range of potential confounders. Overall, the adjusted hazard ratio for Alzheimer's disease in persons living within 50 m of a 220-380 kV power line was 1.24 (95% confidence interval (CI): 0.80, 1.92) compared with persons who lived at a distance of 600 m or more. There was a dose-response relation with respect to years of residence in the immediate vicinity of power lines and Alzheimer's disease: Persons living at least 5 years within 50 m had an adjusted hazard ratio of 1.51 (95% CI: 0.91, 2.51), increasing to 1.78 (95% CI: 1.07, 2.96) with at least 10 years and to 2.00 (95% CI: 1.21, 3.33) with at least 15 years. The pattern was similar for senile dementia. There was little evidence for an increased risk of amyotrophic lateral sclerosis, Parkinson's disease, or multiple sclerosis.

Radiation metabolomics. 1. Identification of minimally invasive urine biomarkers for gamma-radiation exposure in mice

Gamma-radiation exposure has both short- and long-term adverse health effects. The threat of modern terrorism places human populations at risk for radiological exposures, yet current medical countermeasures to radiation exposure are limited. Here we describe metabolomics for gamma-radiation biodosimetry in a mouse model. Mice were gamma-irradiated at doses of 0, 3 and 8 Gy (2.57 Gy/min), and urine samples collected over the first 24 h after exposure were analyzed by ultra-performance liquid chromatography-time-of-flight mass spectrometry (UPLC-TOFMS). Multivariate data were analyzed by orthogonal partial least squares (OPLS). Both 3- and 8-Gy exposures yielded distinct urine metabolomic phenotypes. The top 22 ions for 3 and 8 Gy were analyzed further, including tandem mass spectrometric comparison with authentic standards, revealing that N-hexanoylglycine and beta-thymidine are urinary biomarkers of exposure to 3 and 8 Gy, 3-hydroxy-2-methylbenzoic acid 3-O-sulfate is elevated in urine of mice exposed to 3 but not 8 Gy, and taurine is elevated after 8 but not 3 Gy. Gene Expression Dynamics Inspector (GEDI) self-organizing maps showed clear dose-response relationships for subsets of the urine metabolome. This approach is useful for identifying mice exposed to gamma radiation and for developing metabolomic strategies for noninvasive radiation biodosimetry in humans.

Oral melatonin reduces blood coagulation activity: a placebo-controlled study in healthy young men

Melatonin has previously been suggested to affect hemostatic function but studies on the issue are scant. We hypothesized that, in humans, oral administration of melatonin is associated with decreased plasma levels of procoagulant hemostatic measures compared with placebo medication and that plasma melatonin concentration shows an inverse association with procoagulant measures. Forty-six healthy men (mean age 25 +/- 4 yr) were randomized, single-blinded, to either 3 mg of oral melatonin (n = 25) or placebo medication (n = 21). One hour thereafter, levels of melatonin, fibrinogen, and D-dimer as well as activities of coagulation factor VII (FVII:C) and VIII (FVIII:C) were measured in plasma. Multivariate analysis of covariance and regression analysis controlled for age, body mass index, mean arterial blood pressure, heart rate, and norepinephrine plasma level. Subjects on melatonin had significantly lower mean levels of FVIII:C (81%, 95% CI 71-92 versus 103%, 95% CI 90-119; P = 0.018) and of fibrinogen (1.92 g/L, 95% CI 1.76-2.08 versus 2.26 g/L, 95% CI 2.09-2.43; P = 0.007) than those on placebo explaining 14 and 17% of the respective variance. In all subjects, increased plasma melatonin concentration independently predicted lower levels of FVIII:C (P = 0.037) and fibrinogen (P = 0.022) explaining 9 and 11% of the respective variance. Melatonin medication and plasma concentration were not significantly associated with FVII:C and D-dimer levels. A single dose of oral melatonin was associated with lower plasma levels of procoagulant factors 60 min later. There might be a dose-response relationship between the plasma concentration of melatonin and coagulation activity.

Serum metabolomics reveals irreversible inhibition of fatty acid beta-oxidation through the suppression of PPARalpha activation as a contributing mechanism of acetaminophen-induced hepatotoxicity

Metabolic bioactivation, glutathione depletion, and covalent binding are the early hallmark events after acetaminophen (APAP) overdose. However, the subsequent metabolic consequences contributing to APAP-induced hepatic necrosis and apoptosis have not been fully elucidated. In this study, serum metabolomes of control and APAP-treated wild-type and Cyp2e1-null mice were examined by liquid chromatography-mass spectrometry (LC-MS) and multivariate data analysis. A dose-response study showed that the accumulation of long-chain acylcarnitines in serum contributes to the separation of wild-type mice undergoing APAP-induced hepatotoxicity from other mouse groups in a multivariate model. This observation, in conjunction with the increase of triglycerides and free fatty acids in the serum of APAP-treated wild-type mice, suggested that APAP treatment can disrupt fatty acid beta-oxidation. A time-course study further indicated that both wild-type and Cyp2e1-null mice had their serum acylcarnitine levels markedly elevated within the early hours of APAP treatment. While remaining high in wild-type mice, serum acylcarnitine levels gradually returned to normal in Cyp2e1-null mice at the end of the 24 h treatment. Distinct from serum aminotransferase activity and hepatic glutathione levels, the pattern of serum acylcarnitine accumulation suggested that acylcarnitines can function as complementary biomarkers for monitoring the APAP-induced hepatotoxicity. An essential role for peroxisome proliferator-activated receptor alpha (PPARalpha) in the regulation of serum acylcarnitine levels was established by comparing the metabolomic responses of wild-type and Ppara-null mice to a fasting challenge. The upregulation of PPARalpha activity following APAP treatment was transient in wild-type mice but was much more prolonged in Cyp2e1-null mice. Overall, serum metabolomics of APAP-induced hepatotoxicity revealed that the CYP2E1-mediated metabolic activation and oxidative stress following APAP treatment can cause irreversible inhibition of fatty acid oxidation, potentially through suppression of PPARalpha-regulated pathways.

Unanticipated structural and functional properties of delta-subunit-containing GABAA receptors

GABA(A) receptors mediate inhibitory neurotransmission in the mammalian brain via synaptic and extrasynaptic receptors. The delta (delta)-subunit-containing receptors are expressed exclusively extra-synaptically and mediate tonic inhibition. In the present study, we were interested in determining the architecture of receptors containing the delta-subunit. To investigate this, we predefined the subunit arrangement by concatenation. We prepared five dual and three triple concatenated subunit constructs. These concatenated dual and triple constructs were used to predefine nine different GABA(A) receptor pentamers. These pentamers composed of alpha(1)-, beta(3)-, and delta-subunits were expressed in Xenopus oocytes and maximal currents elicited in response to 1 mm GABA were determined in the presence and absence of THDOC (3alpha, 21-dihydroxy-5alpha-pregnane-20-one). beta(3)-alpha(1)-delta/alpha(1)-beta(3) and beta(3)-alpha(1)-delta/beta(3)-alpha(1) resulted in the expression of large currents in response to GABA. Interestingly, the presence of the neurosteroid THDOC uncovered alpha(1)-beta(3)-alpha(1)/beta(3)-delta receptors, additionally. The functional receptors were characterized in detail using the agonist GABA, THDOC, Zn(2+), and ethanol and their properties were compared with those of non-concatenated alpha(1)beta(3) and alpha(1)beta(3)delta receptors. Each concatenated receptor isoform displayed a specific set of properties, but none of them responded to 30 mm ethanol. We conclude from the investigated receptors that delta can assume multiple positions in the receptor pentamer. The GABA dose-response properties of alpha(1)-beta(3)-alpha(1)/beta(3)-delta and beta(3)-alpha(1)-delta/alpha(1)-beta(3) match most closely the properties of non-concatenated alpha(1)beta(3)delta receptors. Furthermore, we show that the delta-subunit can contribute to the formation of an agonist site in alpha(1)-beta(3)-alpha(1)/beta(3)-delta receptors.

Anaemia may add information to standardised disease activity assessment to predict radiographic damage in rheumatoid arthritis: a prospective cohort study

OBJECTIVE: Anaemia in rheumatoid arthritis (RA) is prototypical of the chronic disease type and is often neglected in clinical practice. We studied anaemia in relation to disease activity, medications and radiographic progression. METHODS: Data were collected between 1996 and 2007 over a mean follow-up of 2.2 years. Anaemia was defined according to WHO (♀ haemoglobin<12 g/dl, ♂: haemoglobin<13 g/dl), or alternative criteria. Anaemia prevalence was studied in relation to disease parameters and pharmacological therapy. Radiographic progression was analysed in 9731 radiograph sets from 2681 patients in crude longitudinal regression models and after adjusting for potential confounding factors, including the clinical disease activity score with the 28-joint count for tender and swollen joints and erythrocyte sedimentation rate (DAS28ESR) or the clinical disease activity index (cDAI), synthetic antirheumatic drugs and antitumour necrosis factor (TNF) therapy. RESULTS: Anaemia prevalence decreased from more than 24% in years before 2001 to 15% in 2007. Erosions progressed significantly faster in patients with anaemia (p<0.001). Adjusted models showed these effects independently of clinical disease activity and other indicators of disease severity. Radiographic damage progression rates were increasing with severity of anaemia, suggesting a 'dose-response effect'. The effect of anaemia on damage progression was maintained in subgroups of patients treated with TNF blockade or corticosteroids, and without non-selective nonsteroidal anti-inflammatory drugs (NSAIDs). CONCLUSIONS: Anaemia in RA appears to capture disease processes that remain unmeasured by established disease activity measures in patients with or without TNF blockade, and may help to identify patients with more rapid erosive disease.

Investigation of the inhibitory effects of the benzodiazepine derivative, 5-BDBD on P2X4 purinergic receptors by two complementary methods

BACKGROUND/AIMS ATP-gated P2X4 purinergic receptors (P2X4Rs) are cation channels with important roles in diverse cell types. To date, lack of specific inhibitors has hampered investigations on P2X4Rs. Recently, the benzodiazepine derivative, 5-BDBD has been proposed to selectively inhibit P2X4Rs. However, limited evidences are currently available on its inhibitory properties. Thus, we aimed to characterize the inhibitory effects of 5-BDBD on recombinant human P2X4Rs. METHODS We investigated ATP-induced intracellular Ca(2+) signals and whole cell ion currents in HEK 293 cells that were either transiently or stably transfected with hP2X4Rs. RESULTS Our data show that ATP (< 1 μM) stimulates P2X4R-mediated Ca(2+) influx while endogenously expressed P2Y receptors are not activated to any significant extent. Both 5-BDBD and TNP-ATP inhibit ATP-induced Ca(2+) signals and inward ion currents in a concentration-dependent manner. Application of two different concentrations of 5-BDBD causes a rightward shift in ATP dose-response curve. Since the magnitude of maximal stimulation does not change, these data suggest that 5-BDBD may competitively inhibit the P2X4Rs. CONCLUSIONS Our results demonstrate that application of submicromolar ATP concentrations allows reliable assessment of recombinant P2XR functions in HEK 293 cells. Furthermore, 5-BDBD and TNP-ATP have similar inhibitory potencies on the P2X4Rs although their mechanisms of actions are different.

Influence of Gestational Age and Parental Education on Executive Functions of Children Born Very Preterm

Background: Children born very preterm (<32 weeks’ gestational age; VPT) and/or very low birth weight (<1500 g; VLBW) are at high risk of deficits in executive functions, namely inhibition, working memory, and shifting. Both, gestational age and socioeconomic factors, such as parental education, are known to influence executive functions, with children born at lower gestational age and with lower educated parents displaying worse executive skills. This study aimed to investigate if maternal and paternal education moderated the relationship between gestational age and executive functions in VPT/VLBW children aged 8-12 years. It was hypothesised that the disadvantageous effect of low gestational age could be buffered more easily in families with higher educational background. Methods: Sixty VPT/VLBW children born in the cohort of 1998-2003 were recruited. All children completed executive function tasks (inhibition, working memory, and shifting). Results: There was a significant dose-response-relationship between gestational age and inhibition, with children being born at earlier gestational age showing worse inhibition. However, neither maternal nor paternal education moderated the relationship between gestational age and executive functions significantly. Conclusion: children than parental education. The disadvantageous effect of low gestational age was equal in children with higher and lower educated parents. However, the impact of gestational age and parental education on executive functions may differ depending on the socioeconomic spectrum of the study sample.

Nano Aerosol Chamber for In-Vitro Toxicity (NACIVT) studies.

Abstract Inhalation of ambient air particles or engineered nanoparticles (NP) handled as powders, dispersions or sprays in industrial processes and contained in consumer products pose a potential and largely unknown risk for incidental exposure. For efficient, economical and ethically sound evaluation of health hazards by inhaled nanomaterials, animal-free and realistic in vitro test systems are desirable. The new Nano Aerosol Chamber for in-vitro Toxicity studies (NACIVT) has been developed and fully characterized regarding its performance. NACIVT features a computer-controlled temperature and humidity conditioning, preventing cellular stress during exposure and allowing long-term exposures. Airborne NP are deposited out of a continuous air stream simultaneously on up to 24 cell cultures on Transwell® inserts, allowing high-throughput screening. In NACIVT, polystyrene as well as silver particles were deposited uniformly and efficiently on all 24 Transwell® inserts. Particle-cell interaction studies confirmed that deposited particles reach the cell surface and can be taken up by cells. As demonstrated in control experiments, there was no evidence for any adverse effects on human bronchial epithelial cells (BEAS-2B) due to the exposure treatment in NACIVT. The new, fully integrated and transportable deposition chamber NACIVT provides a promising tool for reliable, acute and sub-acute dose-response studies of (nano)particles in air-exposed tissues cultured at the air-liquid interface.

A compact and portable deposition chamber to study nanoparticles in air-exposed tissue

BACKGROUND Epidemiological studies show that elevated levels of particulate matter in ambient air are highly correlated with respiratory and cardiovascular diseases. Atmospheric particles originate from a large number of sources and have a highly complex and variable composition. An assessment of their potential health risks and the identification of the most toxic particle sources would require a large number of investigations. Due to ethical and economic reasons, it is desirable to reduce the number of in vivo studies and to develop suitable in vitro systems for the investigation of cell-particle interactions. METHODS We present the design of a new particle deposition chamber in which aerosol particles are deposited onto cell cultures out of a continuous air flow. The chamber allows for a simultaneous exposure of 12 cell cultures. RESULTS Physiological conditions within the deposition chamber can be sustained constantly at 36-37°C and 90-95% relative humidity. Particle deposition within the chamber and especially on the cell cultures was determined in detail, showing that during a deposition time of 2 hr 8.4% (24% relative standard deviation) of particles with a mean diameter of 50 nm [mass median diameter of 100 nm (geometric standard deviation 1.7)] are deposited on the cell cultures, which is equal to 24-34% of all charged particles. The average well-to-well variability of particles deposited simultaneously in the 12 cell cultures during an experiment is 15.6% (24.7% relative standard deviation). CONCLUSIONS This particle deposition chamber is a new in vitro system to investigate realistic cell-particle interactions at physiological conditions, minimizing stress on the cell cultures other than from deposited particles. A detailed knowledge of particle deposition characteristics on the cell cultures allows evaluating reliable dose-response relationships. The compact and portable design of the deposition chamber allows for measurements at any particle sources of interest.

Apoptosis of hippocampal neurons in organotypic slice culture models: direct effect of bacteria revisited

Neurons of the hippocampal dentate gyrus selectively undergo programmed cell death in patients suffering from bacterial meningitis and in experimental models of pneumococcal meningitis in infant rats. In the present study, a membrane-based organotypic slice culture system of rat hippocampus was used to test whether this selective vulnerability of neurons of the dentate gyrus could be reproduced in vitro. Apoptosis was assessed by nuclear morphology (condensed and fragmented nuclei), by immunochemistry for active caspase-3 and deltaC-APP, and by proteolytic caspase-3 activity. Co-incubation of the cultures with live pneumococci did not induce neuronal apoptosis unless cultures were kept in partially nutrient-deprived medium. Complete nutrient deprivation alone and staurosporine independently induced significant apoptosis, the latter in a dose-response way. In all experimental settings, apoptosis occurred preferentially in the dentate gyrus. Our data demonstrate that factors released by pneumococci per se failed to induce significant apoptosis in vitro. Thus, these factors appear to contribute to a multifactorial pathway, which ultimately leads to neuronal apoptosis in bacterial meningitis.

Aluminum toxicity in a tropical montane forest ecosystem in southern Ecuador

Aluminum phytotoxicity frequently occurs in acid soils (pH < 5.5) and was therefore discussed to affect ecosystem functioning of tropical montane forests. The susceptibility to Al toxicity depends on the sensitivity of the plant species and the Al speciation in soil solution, which can vary highly depending e.g., on pH, ionic strength, and dissolved organic matter. An acidification of the ecosystem and periodic base metal deposition from Saharan dust may control plant available Al concentrations in the soil solutions of tropical montane rainforests in south Ecuador. The overall objective of my study was to assess a potential Al phytotoxicity in the tropical montane forests in south Ecuador. For this purpose, I exposed three native Al non-accumulating tree species (Cedrela odorata L., Heliocarpus americanus L., and Tabebuia chrysantha (Jacq.) G. Nicholson) to increased Al concentrations (0 – 2400 μM Al) in a hydroponic experiment, I established dose-response curves to estimate the sensitivity of the tree species to increased Al concentrations, and I investigated the mechanisms behind the observed effects induced by elevated Al concentrations. Furthermore, the response of Al concentrations and the speciation in soil solution to Ca amendment in the study area were determined. In a final step, I assessed all major Al fluxes, drivers of Al concentrations in ecosystem solutions, and indicators of Al toxicity in the tropical montane rainforest in Ecuador in order to test for indications of Al toxicity. In the hydroponic experiment, a 10 % reduction in aboveground biomass production occurred at 126 to 376 μM Al (EC10 values), probably attributable to decreased Mg concentrations in leaves and reduced potosynthesis. At 300 μM Al, increased root biomass production of T. chrysantha was observed. Phosphorus concentrations in roots of C. odorata and T. chrysantha were significantly highest in the treatment with 300 μM Al and correlated significantly with root biomass, being a likely reason for stimulated root biomass production. The degree of organic complexation of Al in the organic layer leachate, which is central to plant nutrition because of the high root density, and soil solution from the study area was very high (mean > 99 %). The resulting low free Al concentrations are not likely to affect plant growth, although the concentrations of potentially toxic Al3+ increased with soil depth due to higher total Al and lower dissolved organic matter concentrations in soil solutions. The Ca additions caused an increase of Al in the organic layer leachate, probably because Al3+ was exchanged against the added Ca2+ ions while pH remained constant. The free ion molar ratios of Ca2+:Al3+ (mean ratio ca. 400) were far above the threshold (≤ 1) for Al toxicity, because of a much higher degree of organo-complexation of Al than Ca. High Al fluxes in litterfall (8.8 – 14.2 kg ha−1 yr−1) indicate a high Al circulation through the ecosystem. The Al concentrations in the organic layer leachate were driven by the acidification of the ecosystem and increased significantly between 1999 and 2008. However, the Ca:Al molar ratios in organic layer leachate and all aboveground ecosystem solutions were above the threshold for Al toxicity. Except for two Al accumulating and one non-accumulating tree species, the Ca:Al molar ratios in tree leaves from the study area were above the Al toxicity threshold of 12.5. I conclude that toxic effects in the hydroponic experiment occurred at Al concentrations far above those in native organic layer leachate, shoot biomass production was likely inhibited by reduced Mg uptake, impairing photosynthesis, and the stimulation of root growth at low Al concentrations can be possibly attributed to improved P uptake. Dissolved organic matter in soil solutions detoxifies Al in acidic tropical forest soils and a wide distribution of Al accumulating tree species and high Al fluxes in the ecosystem do not necessarily imply a general Al phytotoxicity.

Treatment of exudative age-related macular degeneration with a designed ankyrin repeat protein that binds vascular endothelial growth factor: a phase I/II study

PURPOSE To evaluate the safety, tolerability and bioactivity of ascending doses of MP0112, a designed ankyrin repeat protein (DARPin) that binds with high affinity to vascular endothelial growth factor-A (VEGF-A), in treatment-naive patients with exudative age-related macular degeneration (AMD). DESIGN Phase I/II, open-label, multicenter, dose-escalation study. METHODS Patients were to receive a single intravitreal injection of MP0112 at doses ranging from 0.04 to 3.6 mg and be monitored for 16 weeks for safety, efficacy, pharmacokinetics, and dose response. RESULTS Altogether, 32 patients received a single injection of MP0112. The maximum tolerated dose was 1.0 mg because of a case of endophthalmitis in the 2.0 mg cohort. Drug-related adverse events were reported by 13 (41%) of 32 patients; they included ocular inflammation in 11 patients (7 mild, 4 moderate in severity). Visual acuity scores were stable or improved compared with baseline for ≥4 weeks following injection; both retinal thickness and fluorescein angiography leakage decreased in a dose-dependent manner. Rescue therapy was administered to 20 (91%) of 22 patients who received 0.04-0.4 mg MP0112 compared with 4 of 10 (40%) patients who received 1.0 or 2.0 mg. Of patients in the higher-dose cohorts who did not require rescue treatment, 83% (5/6) maintained reductions in central retinal thickness through week 16. CONCLUSIONS A single injection of 1.0 or 2.0 mg MP0112 resulted in mean decreases in retinal thickness and leakage area despite ocular inflammation. Larger-scale studies are warranted to confirm these observations.