Influence of baseline diabetic retinopathy status on initial anatomical response of intravitreal ranibizumab therapy for diabetic macular oedema.

PurposeIntraocular vascular endothelial growth factor (VEGF) levels increases with the severity of diabetic retinopathy. Response of diabetic macular oedema (DMO) to ranibizumab is driven by VEGF suppression. We hypothesised that the initial reduction of central macular thickness by ranibizumab should be maximum in severe diabetic retinopathy until the levels of VEGF decreases to the levels observed in eyes with mild retinopathy.MethodsConsecutive patients with centre-involving DMO (central subfield thickness (CSFT)>300 µm) who had three consecutive monthly ranibizumab injections followed by as needed therapy were included. Retinopathy status was graded as mild non-proliferative diabetic retinopathy (NPDR) (G1), moderate to severe NPDR with no prior panretinal photocoagulation (G2), and treated PDR (G3).ResultsTwo hundred and thirty-nine eyes from 204 patients with a mean age of 64.9 years were included. The distribution was 31.4 G1, 32.2 G2, and 36.4% G3. Mean baseline CSFT for all eyes was 458.5±110.8 µm. Baseline CSFT for G1, G2, and G3, respectively, were 437.6±90.9, 472.3±109.8, and 464.7±124.9 µm (P=0.2155). Mean change in CSFT after three consecutive injections was 128.5±116.6 µm. The mean changes were 95.8±101.4 µm for G1, 137.2±112.9 µm for G2, and 148.9±126.9 µm for G3. The changes in CSFT between groups adjusted for baseline CSFT were statistically significant (P=0.0473). At 6 and 12 months after a mean of 4.5 and 7.7 injections, the changes between groups were no longer significant, P=0.4783 and P=0.8271, respectively.ConclusionsThe initial anatomical response of DMO with intravitreal ranibizumab injections was maximum in eyes with treated PDR, suggesting that the higher the VEGF levels, the better the response with ranibizumab.

A randomized clinical trial comparing fixed vs pro-re-nata dosing of Ozurdex in refractory diabetic macular oedema (OZDRY study).

OBJECTIVE: To compare the clinical effectiveness and safety of 5-monthly fixed dosing vs pro-re-nata (PRN) Ozurdex treatment in patients with refractory diabetic macular oedema (DMO). DESIGN: Prospective, multicentre, randomized active-controlled non-inferiority clinical trial. PARTICIPANTS: Participants were 100 patients who attended Medical Retina Clinics for management of centre-involving refractory DMO. INTERVENTIONS: Participants were randomized 1 : 1 to either 5-monthly fixed dosing or optical coherence tomography (OCT)-guided PRN regimen of Ozurdex therapy for DMO. Data were collected on best-corrected visual acuity (BCVA), patient-reported outcome measures (PROM), macular thickness and morphology, diabetic retinopathy status, number of injections and adverse events from baseline for a period of 12 months.Main outcome measuresThe primary outcome was the difference between arms in change in BCVA from baseline to 12 months. The prespecified non-inferiority margin was five ETDRS letters. Key secondary outcomes included change in PROM scores, change in macular thickness, change in retinopathy and macular morphology, and safety profile. RESULTS: The mean change in BCVA was +1.48 (SD 14.8) in the fixed arm vs -0.17 (SD 13.1) in the PRN arm, with adjusted effect estimate +0.97, 90% confidence interval (-4.01, +5.95), P=0.02 (per protocol analysis). The conclusions of the ITT analysis were primarily supportive, -0.34 (-5.49, 4.81) P=0.07, but sensitive to an alternative assumption on missing data, +0.28 (-4.72, 5.27) P=0.04. CONCLUSIONS: The mean change in BCVA with 5-monthly fixed dosing of Ozurdex was non-inferior to OCT-guided PRN Ozurdex therapy for refractory DMO based on a per protocol analysis.

Early postnatal development of rat brain: in vivo diffusion tensor imaging.

Perinatal hypoxia is a major cause of neurodevelopmental deficits. Neuronal migration patterns are particularly sensitive to perinatal hypoxia/ischemia and are associated with the clinical deficits. The rat model of hypoxia/ischemia at P7 mimics that of perinatal injury in humans. Before assessing the effects of postnatal injury on brain development, it is essential to determine the normal developmental trajectories of various brain structures in individual animals. In vivo longitudinal diffusion tensor imaging (DTI) was performed from postnatal day 0 (P0) to P56 on Wistar rats. The DTI metrics, mean diffusivity (MD), fractional anisotropy (FA), axial (lambdal) and radial (lambdat) diffusivities, were determined for four gray matter and eight white matter structures. The FA of the cortical plate and the body of corpus callosum decreased significantly during the first 3 weeks after birth. The decrease in the cortical plate's FA value was associated mainly with an increase in lambdat. The initial decrease in FA of corpus callosum was associated with a significant decrease in lambdal. The FA of corpus callosum increased during the rest of the observational period, which was mainly associated with a decrease in lambdat. The FA of gray matter structures, hippocampus, caudate putamen, and cortical mantle did not show significant changes between P0 and P56. In contrast, the majority of white matter structures showed significant changes between P0 and P56. These temporal changes in the DTI metrics were related to the neuronal and axonal pruning and myelination that are known to occur in the developing brain.

Adsorption of Cholera and Heat-Labile Escherichia coli Enterotoxins by Various Adsorbents: an In Vitro Study.

A variety of common inorganic adsorbents representing aluminas, zeolites, phyllosilicate clays, silica, and carbon were compared for their abilities to adsorb cholera toxin (CT) and heat-labile (LT) Escherichia coli enterotoxin. An appropriate assay system for the enterotoxins was developed using the Y-1 mouse-adrenal-tumor cell line, End points were determined by counting the number of rounded (cytotonic) cells at the relevant dilution. The adsorption varied between 177.0 × 106 and 109.6 × 102 CYTU (cytotonic titer unit) for CT with charcoal and boehmite respectively, and between 60.7 × 104 and 180.4 × 101 CYTU for LT with charcoal and boehmite respectively. Several of the other materials adsorbed CT and LT well, particularly attapulgite and sodium bentonite. The tightness of CT and LT binding to sodium bentonite and charcoal was determined by washing the adsorbent-enterotoxin pellets. Both toxins were strongly adsorbed, with dissociation of only 46.3 × 10° CYTU (<0.01 %) of the bound CT from sodium bentonite and 18.0× 101 CYTU (0.06%) of the bound LT from charcoal. The clay and charcoal pellets were assayed for their cytotonicity. Most of the activity of the adsorbed enterotoxins was lost: 93.1 and 89.6% for CT with sodium bentonite and charcoal, respectively, and 93.8 and 85.9% for LT with sodium bentonite and charcoal, respectively. The effect of dietary protein (casein) in enterotoxin adsorption by clay was also investigated. One percent casein (when adsorbed to sodium bentonite clay) completely blocked the adsorption of CT. When this protein-clay complex was treated with enzymes present in pancreatin, the digestive effect on the casein was sufficient to permit the adsorption of 137.6 × 101 CYTU of CT, although most of the blocking effect of casein remained. Further in vitro studies are needed to model the stomach, pancreatic, and intestinal digestive systems for determining if dietary proteins can block CT adsorption by clay in vivo. These results extend and support previously published data, obtained experimentally in rabbit and rat intestinal loops and from studies of children suffering spontaneous diarrhea, on the beneficial role of clays and other inorganic adsorbents in controlling enterotoxin activity.