Pupil responses derived from outer and inner retinal photoreception are normal in patients with hereditary optic neuropathy.

We compared the pupil responses originating from outer versus inner retinal photoreception between patients with isolated hereditary optic neuropathy (HON, n = 8) and healthy controls (n = 8). Three different testing protocols were used. For the first two protocols, a response function of the maximal pupil contraction versus stimulus light intensity was generated and the intensity at which half of the maximal pupil contraction, the half-max intensity, was determined. For the third protocol, the pupil size after light offset, the re-dilation rate and re-dilation amplitude were calculated to assess the post-light stimulus response. Patients with HON had bilateral, symmetric optic atrophy and significant reduction of visual acuity and visual field compared to controls. There were no significant mean differences in the response curve and pupil response parameters that reflect mainly rod, cone or melanopsin activity between patients and controls. In patients, there was a significant correlation between the half-max intensity of the red light sequence and visual field loss. In conclusion, pupil responses derived from outer or inner retinal photoreception in HON patients having mild-to moderate visual dysfunction are not quantitatively different from age-matched controls. However, an association between the degree of visual field loss and the half-max intensity of the cone response suggests that more advanced stages of disease may lead to impaired pupil light reflexes.

In conditions of limited chromophore supply rods entrap 11-cis-retinal leading to loss of cone function and cell death.

RPE65 is a retinoid isomerase required for the production of 11-cis-retinal, the chromophore of both cone and rod visual pigments. We recently established an R91W knock-in mouse strain as homologous animal model for patients afflicted by this mutation in RPE65. These mice have impaired vision and can only synthesize minute amounts of 11-cis-retinal. Here, we investigated the consequences of this chromophore insufficiency on cone function and pathophysiology. We found that the R91W mutation caused cone opsin mislocalization and progressive geographic cone atrophy. Remnant visual function was mostly mediated by rods. Ablation of rod opsin corrected the localization of cone opsin and improved cone retinal function. Thus, our analyses indicate that under conditions of limited chromophore supply rods and cones compete for 11-cis-retinal that derives from regeneration pathway(s) which are reliant on RPE65. Due to their higher number and the instability of cone opsin, rods are privileged under this condition while cones suffer chromophore deficiency and degenerate. These findings reinforce the notion that in patients any effective gene therapy with RPE65 needs to target the cone-rich macula directly to locally restore the cones' chromophore supply outside the reach of rods.

Effect of Noncondensable Gases on Circulation of Primary Coolant in Nuclear Power Plants in Abnormal Situations

The present study focuses on two effects of the presence of a noncondensable gas on the thermal-hydraulic behavior of thecoolant of the primary circuit of a nuclear reactor in the VVER-440 geometry inabnormal situations. First, steam condensation with the presence of air was studied in the horizontal tubes of the steam generator (SG) of the PACTEL test facility. The French thermal-hydraulic CATHARE code was used to study the heat transfer between the primary and secondary side in conditions derived from preliminary experiments performed by VTT using PACTEL. In natural circulation and single-phase vapor conditions, the injection of a volume of air, equivalent to the totalvolume of the primary side of the SG at the entrance of the hot collector, did not stop the heat transfer from the primary to the secondary side. The calculated results indicate that air is located in the second half-length (from the mid-length of the tubes to the cold collector) in all the tubes of the steam generator The hot collector remained full of steam during the transient. Secondly, the potential release of the nitrogen gas dissolved in the water of the accumulators of the emergency core coolant system of the Loviisa nuclear power plant (NPP) was investigated. The author implemented a model of the dissolution and release ofnitrogen gas in the CATHARE code; the model created by the CATHARE developers. In collaboration with VTT, an analytical experiment was performed with some components of PACTEL to determine, in particular, the value of the release time constant of the nitrogen gas in the depressurization conditions representative of the small and intermediate break transients postulated for the Loviisa NPP. Such transients, with simplified operating procedures, were calculated using the modified CATHARE code for various values of the release time constant used in the dissolution and release model. For the small breaks, nitrogen gas is trapped in thecollectors of the SGs in rather large proportions. There, the levels oscillate until the actuation of the low-pressure injection pumps (LPIS) that refill the primary circuit. In the case of the intermediate breaks, most of the nitrogen gas is expelled at the break and almost no nitrogen gas is trapped in the SGs. In comparison with the cases calculated without taking into account the release of nitrogen gas, the start of the LPIS is delayed by between 1 and 1.75 h. Applicability of the obtained results to the real safety conditions must take into accountthe real operating procedures used in the nuclear power plant.

Precision of the Retinal Tomograph as a Screening Device.

Purpose: To assess the diagnostic accuracy of the Heidelberg Retinal Tomograph 3 (HRT3) as a screening device in comparison with the reference standard of Octopus standard automated perimetry results (SAP) combined with clinical findings. Methods: All patients underwent screening examinations and investigations within a single day. Abnormal screening results were classified as follows: The HRT3: Either "borderline" or "outside normal limits" using the global Moorfields classification (MFC); SAP and clinical exam: A mean defect > 2.4 dB or "outside normal limits" clear text analysis of SAP; and one of the following i) IOP > 21 mmHg, ii) Van Herrick < ¼, iii) cup disc ratio > 0.55, iv) optic nerve head abnormality, v) narrow iridocorneal angle or vi) evidence of peripheral anterior synechiae on gonioscopy. Results: The mean age of the participants was 59.9 years (± 14.8 [21, 91]). Twenty-three subjects (16 %) were classified as abnormal on SAP and clinical exam. The HRT3 classification had a sensitivity of 30 % (95 % CI [16 %, 51 %]) with associated specificity of 58 % (95 % CI [49 %, 66 %]). Of the sixty subjects classified as borderline or outside normal limits with the HRT MFC global result, seven subjects were also abnormal according to SAP and clinical exam. Conclusion: The results suggest that the HRT3 may not be suitable as a sole screening device; however, further investigation is necessary.

Recurrent Macular Edema in Central Retinal Vein Occlusion Treated with Intravitreal Ranibizumab using a Modified Treat and Extend Regimen.

Background: The aim of this study was to evaluate the stability over time of the individually defined interval of intravitreal ranibizumab injection (IVR) for the treatment of recurrent macular edema (ME) in central retinal vein occlusion (CRVO). Patients and Methods: A case series of treatment naïve patients followed in the Jules Gonin Eye Hospital for macular edema due to central retinal vein occlusion is presented. Patients were treated monthly with IVR until complete absence of fluid on qualitative SD-OCT with a minimum of 5 monthly IVR. Thereafter, they were followed according to a modified treat and extend regimen (mTER). Results: Twelve eyes (12 patients) with ME due to CRVO were included. The mean follow-up period was 31.3 months. Analysis showed that best corrected visual acuity (BCVA), central macular thickness and qualitative spectral domain optical coherence tomography (SD-OCT) showed comparable results under monthly interval, after titration of an individualized interval and when performed in a series. 78 % of treating intervals were within ± 2 weeks of the first individually adjusted interval. The mean first defined interval was 4.3 weeks and the mean interval over time was 5.5 weeks (p = 0.003). There was a trend towards longer interval over time. Conclusion: The adjusted interval of retreatment of patients with ME due to CRVO showed a high stability with a trend toward longer duration over time. An mTER regimen seems to be valuable to follow patients with ME with good stabilization of VA.

The year in cardiology 2014: peripheral circulation.

In 2014, the debate on the indication of revascularization in case of asymptomatic carotid disease continued, while another one regarding the use of surgery vs. stenting addressed some new issues regarding the long-term cardiac risk of these patients. Renal arteries interventions trials were disappointing, as neither renal denervation nor renal artery stenting was found associated with better blood pressure management or outcome. In contrast, in lower-extremities artery disease, the endovascular techniques represent in 2014 major alternatives to surgery, even in distal arteries, with new insights regarding the interest of drug-eluting balloons. Regarding the aorta, the ESC published its first guidelines document on the entire vessel, emphasizing on the role of every cardiologist for screening abdominal aorta aneurysm during echocardiography. Among vascular wall biomarkers, the aorta stiffness is of increasing interest with new data and meta-analysis confirming its ability to stratify risk, whereas carotid intima-media thickness showed poor performances in terms of reclassifying patients into risk categories beyond risk scores. Regarding the veins, new data suggest the interest of D-dimers and residual venous thrombosis to help the decision of anti-coagulation prolongation or discontinuation after the initial period of treatment for deep vein thrombosis.

How to prevent venous cannula orifice obstruction during extracorporeal circulation.

Venous cannula orifice obstruction is an underestimated problem during augmented cardiopulmonary bypass (CPB), which can potentially be reduced with redesigned, virtually wall-less cannula designs versus traditional percutaneous control venous cannulas. A bench model, allowing for simulation of the vena cava with various affluent orifices, venous collapse and a worst case scenario with regard to cannula position, was developed. Flow (Q) was measured sequentially for right atrial + hepatic + renal + iliac drainage scenarios, using a centrifugal pump and an experimental bench set-up (afterload 60 mmHg). At 1500, 2000 and 2500 RPM and atrial position, the Q values were 3.4, 6.03 and 8.01 versus 0.77*, 0.43* and 0.58* l/min: p<0.05* for wall-less and the Biomedicus(®) cannula, respectively. The corresponding pressure values were -15.18, -31.62 and -74.53 versus -46.0*, -119.94* and -228.13* mmHg. At the hepatic position, the Q values were 3.34, 6.67 and 9.26 versus 2.3*, 0.42* and 0.18* l/min; and the pressure values were -10.32, -20.25 and -42.83 versus -23.35*, -119.09* and -239.38* mmHg. At the renal position, the Q values were 3.43, 6.56 and 8.64 versus 2.48*, 0.41* and 0.22* l/min and the pressure values were -9.64, -20.98 and -63.41 versus -20.87 -127.68* and -239* mmHg, respectively. At the iliac position, the Q values were 3.43, 6.01 and 9.25 versus 1.62*, 0.55* and 0.58* l/min; the pressure values were -9.36, -33.57 and -44.18 versus -30.6*, -120.27* and -228* mmHg, respectivly. Our experimental evaluation demonstrates that the redesigned, virtually wall-less cannulas, allowing for direct venous drainage at practically all intra-venous orifices, outperform the commercially available control cannula, with superior flow at reduced suction levels for all scenarios tested.

Strokes in the anterior circulation: comparison between bridging and intravenous thrombolysis.

BACKGROUND AND PURPOSE: To compare safety and efficacy of bridging approach with intravenous (IV) thrombolysis in patients with acute anterior strokes and proximal occlusions. PATIENTS AND METHODS: Consecutive patients with ischemic anterior strokes admitted within a 4 h 30 min window in two different centers were included. The first center performed IV therapy (alteplase 0.6 mg/kg) during 30 min and, in absence of clinical improvement, mechanical thrombectomy with flow restoration using a Solitaire stent (StS); the second carried out IV thrombolysis (alteplase 0.9 mg/kg) alone. Only T, M1 or M2 occlusions present on CT angiography were considered. Endpoints were clinical outcome and mortality at 3 months. RESULTS: There were 63 patients in the bridging and 163 in the IV group. No significant differences regarding baseline characteristics were observed. At 3 months, 46% (n = 29) of the patients treated in the combined and 23% (n = 38) of those treated in the IV group had a modified Rankin scale (mRS) of 0-1 (P < 0.001). A statistical significant difference was observed for all sites of occlusion. In a logistic regression model, National Institute of Health Stroke Scale (NIHSS) and bridging therapy were independent predictors of good outcome (respectively, P = 0.001 and P = 0.0018). Symptomatic hemorrhage was documented in 6.3% vs 3.7% in the bridging and in the IV group, respectively (P = 0.32). There was no difference in mortality. CONCLUSIONS: Our results suggest that patients treated with a bridging approach were more likely to have minimal or no deficit at all at 3 months as compared to the IV treated group.