Pluto's lower atmosphere and pressure evolution from ground-based stellar occultations, 1988-2016

Context. The tenuous nitrogen (N2) atmosphere on Pluto undergoes strong seasonal effects due to high obliquity and orbital eccentricity, and has recently (July 2015) been observed by the New Horizons spacecraft. Aims. The main goals of this study are (i) to construct a well calibrated record of the seasonal evolution of surface pressure on Pluto and (ii) to constrain the structure of the lower atmosphere using a central flash observed in 2015. Methods. Eleven stellar occultations by Pluto observed between 2002 and 2016 are used to retrieve atmospheric profiles (density, pressure, temperature) between altitude levels of ~5 and ~380 km (i.e. pressures from ~ 10 μbar to 10 nbar). Results. (i) Pressure has suffered a monotonic increase from 1988 to 2016, that is compared to a seasonal volatile transport model, from which tight constraints on a combination of albedo and emissivity of N2 ice are derived. (ii) A central flash observed on 2015 June 29 is consistent with New Horizons REX profiles, provided that (a) large diurnal temperature variations (not expected by current models) occur over Sputnik Planitia; and/or (b) hazes with tangential optical depth of ~0.3 are present at 4–7 km altitude levels; and/or (c) the nominal REX density values are overestimated by an implausibly large factor of ~20%; and/or (d) higher terrains block part of the flash in the Charon facing hemisphere

Absence of hypertensive retinopathy in a Turkish kindred with autosomal dominant hypertension and brachydactyly

BACKGROUND—A 60 member Turkish kindred with autosomal dominant hypertension, which cosegregates completely with brachydactyly and short stature, was studied. Affected people have severe hypertension and generally die of stroke by the age of 50. The hypertension closely resembles essential hypertension and, accordingly, the mechanisms of blood pressure elevation are unknown. The gene responsible was mapped to chromosome 12p.
METHODS—All 29 affected family members underwent a basic physical examination and funduscopy. Other than markedly elevated blood pressures and the residua of stroke in a few subjects, the apparent lack of end organ damage was striking, including the normal appearing fundi. Five affected individuals were studied in a clinical research unit study. All underwent a complete ophthalmological examination. Fluorescein angiograms were obtained in three subjects.
RESULTS—Systolic blood pressures ranged from 170 to 250 mm Hg, while diastolic blood pressures ranged from 100 to 150 mm Hg in affected individuals. In all affected subjects, the fundi were only minimally altered or clinically normal. All three fluorescein angiograms were normal. Despite severe hypertension since childhood the patients showed no signs of hypertensive retinopathy.
CONCLUSIONS—The absence of hypertensive retinopathy in this novel form of inherited hypertension is due to an altered structure of retinal arteriolar walls or some other protective mechanism. Since evidence of end organ damage is scarce in other organs as well, the protective mechanism appears to be generalised.

 Keywords: hypertension; retinopathy; genetics; fundus, fluorescein angiograph

Sphingosine kinase 2 modulates retinal neovascularization in the mouse model of oxygen-induced retinopathy

PURPOSE. Neovascularization is a major cause of blindness in various ocular diseases. Bioactive sphingosine 1-phosphate (S1P), synthesized by two sphingosine kinases (Sphk1, Sphk2), emerged as a key player in a multitude of cellular processes, including cell survival, proliferation, inflammation, migration, and angiogenesis. We investigated the role of Sphk2, S1P, and S1P receptors (S1PR) during retinal neovascularization using the oxygen-induced retinopathy mouse model (OIR). METHODS. Sphk2 overexpressing (tgSphk2) and Sphk2 knockout (Sphk2-/-) mice were used in the OIR model, exposed to 75% O2over 5 days from postnatal day (P)7 to 12 to initiate vessel regression. After returning to room air, these mice developed a marked neovascularization. Retinae recovered from untreated and treated eyes at P7, P12, P14, and P17 were used for lectin-stained retinal whole mounts, mass spectrometry, and quantitative real-time PCR. RESULTS. tgSphk2 mice showed higher retinal S1P concentrations, accelerated retinal angiogenesis, and increased neovascularization. Expression of S1PR, vascular endothelial growth factor α (VEGFα), and angiopoietin 1 and 2 was differentially regulated during the course of OIR in the different genotypes. Sphk2-/-displayed a markedly reduced retinal angiogenesis and neovascularization as well as decreased VEGFα and angiopoietin expression. CONCLUSIONS. Using genetic models of Sphk2 overexpression or deletion we demonstrate a strong impact of Sphk2/S1P on retinal vasculopathy and expression of vascular growth factors like VEGF and angiopoietin in the retina. Consequently, Sphk2, S1P, and S1PR may offer attractive novel therapeutic targets for ischemic retinopathies

Head-to-head comparison of ranibizumab PRN versus single-dose dexamethasone for branch retinal vein occlusion (COMRADE-B)

Purpose: To compare the efficacy and safety of ranibizumab 0.5 mg versus dexamethasone 0.7 mg according to their European labels in macular oedema secondary to branch retinal vein occlusion (BRVO) in a 6-month, phase IIIb, randomized trial. Methods: Patients received eithermonthly ranibizumabfor 3 months followed byPro re nata (PRN) treatment (n = 126) or a sustained-release dexamethasone implant followedbyPRNshaminjections (n = 118).Mainoutcomesweremeanaveragechange in best-corrected visual acuity(BCVA)frombaseline tomonth1throughmonth6,mean changes inBCVAand foveal centre point thickness (FCPT), and adverse events (AEs). Results: There was no difference in BCVA gains between the treatments prior to month 3. Best-corrected visual acuity (BCVA) gain with dexamethasone declined thereafter. From month 3 to month 6, mean BCVA change from baseline was significantly higher with ranibizumab than with dexamethasone [raw means (standard deviation):+16.2 ( 11) letters versus+9.3 ( 10.1) letters].Atmonth 6, the difference in BCVA gains from baseline was +17.3 letters in the ranibizumab versus +9.2 letters in the dexamethasone group. Patients in the ranibizumab group received a mean of 2.94 loading injections and 1.74 PRN retreatment injections, while those in the dexamethasone group received a single loading injection. Elevated intraocular pressure (IOP) and AEs were more frequent with dexamethasone than ranibizumab treatment. Conclusion: Ranibizumab PRN resulted in greater visual acuity (VA) gains in macular oedema following BRVO compared with single-dose dexamethasone over a 6-month study period, observed from month 3, when administered according to their European label. In clinical practice, retreatment with dexamethasone may be required prior to this point

Head-to-head comparison of ranibizumab PRN versus single-dose dexamethasone for branch retinal vein occlusion (COMRADE-B)

Purpose: To compare the efficacy and safety of ranibizumab 0.5 mg versus dexamethasone 0.7 mg according to their European labels in macular oedema secondary to branch retinal vein occlusion (BRVO) in a 6-month, phase IIIb, randomized trial. Methods: Patients received eithermonthly ranibizumabfor 3 months followed byPro re nata (PRN) treatment (n = 126) or a sustained-release dexamethasone implant followedbyPRNshaminjections (n = 118).Mainoutcomesweremeanaveragechange in best-corrected visual acuity(BCVA)frombaseline tomonth1throughmonth6,mean changes inBCVAand foveal centre point thickness (FCPT), and adverse events (AEs). Results: There was no difference in BCVA gains between the treatments prior to month 3. Best-corrected visual acuity (BCVA) gain with dexamethasone declined thereafter. From month 3 to month 6, mean BCVA change from baseline was significantly higher with ranibizumab than with dexamethasone [raw means (standard deviation):+16.2 ( 11) letters versus+9.3 ( 10.1) letters].Atmonth 6, the difference in BCVA gains from baseline was +17.3 letters in the ranibizumab versus +9.2 letters in the dexamethasone group. Patients in the ranibizumab group received a mean of 2.94 loading injections and 1.74 PRN retreatment injections, while those in the dexamethasone group received a single loading injection. Elevated intraocular pressure (IOP) and AEs were more frequent with dexamethasone than ranibizumab treatment. Conclusion: Ranibizumab PRN resulted in greater visual acuity (VA) gains in macular oedema following BRVO compared with single-dose dexamethasone over a 6-month study period, observed from month 3, when administered according to their European label. In clinical practice, retreatment with dexamethasone may be required prior to this point

Factors predicting normal visual acuity following anatomically successful macular hole surgery

Purpose: To assess the incidence of normal vision following anatomically successful macular hole surgery and associated clinical variables. Methods: Multicentre, retrospective chart review. Preoperative, intraoperative and postoperative clinical data were extracted from electronic medical records from seven European vitreoretinal units. Inclusion criteria were as follows: eyes undergoing primary vitrectomy for idiopathic full-thickness macular hole from January 2015 to January 2018; postoperative macular hole closure confirmed by spectral domain optical coherence tomography (OCT); preoperative pseudophakia or phakic eyes receiving combined cataract surgery; one-year follow-up. The primary outcome was \u2018normal vision\u2019 defined as a final best-corrected visual acuity (BCVA) 65 20/25. Univariate, multivariate and decision-tree analyses were conducted to evaluate the clinical variables associated with \u2018normal vision\u2019. Odds ratios (OR) and confidence intervals (CIs) were calculated. Results: Of 327 eligible cases, 91 (27.8%) achieved \u2018normal vision\u2019 at 1 year. Multivariate analysis identified variables significantly associated with \u2018normal vision\u2019: shorter symptom duration (odds ratio [OR]=1.05; 95% confidence interval [CI]:1.02-1.09; p = 0.002), smaller preoperative OCT minimum linear diameter (OR per 100-micron increase = 1.65; 95%CI:1.31-2.08; p < 0.001) and better mean preoperative BCVA (OR = 15.13; 95%CI: 3.59-63.65; p < 0.001). The decision-tree analysis found that the most significant variable associated with \u2018normal vision\u2019 was symptom duration. \u2018Normal vision\u2019 was achieved in 70.6% of eyes operated within one week from symptom onset and in 45% of eyes with symptom duration between 1 and 3 weeks. Conclusions: These findings suggested urgent surgery is justified for small macular holes of short duration