Pegaptanib sodium treatment in neovascular age-related macular degeneration: clinical experience in Germany

Nikolaus Feucht, Huebner Matthias, Chris P Lohmann, Mathias MaierAugenklinik rechts der Isar, Technical University Munich, GermanyBackground: The VEGF Inhibition Study In Ocular Neovascularisation (VISION) reported the efficacy of intravitreal (ITV) vascular endothelial growth factor (VEGF) inhibition with pegaptanib sodium (Macugen®) for the treatment of neovascular age-related macular degeneration (AMD). This paper reports clinical experience with pegaptanib sodium for the treatment of occult or minimally classic choroidal neovascularization (CNV) due to AMD.Material and methods: The study included 50 eyes (in 49 patients) with either occult CNV or minimally classic CNV secondary to neovascular AMD who were not eligible for photodynamic therapy (PDT). Study data were analyzed retrospectively. During the 6-month study, patients were administered an average 2.74 injections of 0.3 mg ITV pegaptanib sodium. Angiography and optical coherence tomography (OCT) examinations were carried out and intraocular pressure (IOP) and visual acuity (VA) were measured at baseline, at 3 months and at 6 months. An eye examination was performed and VA was measured the 2 days following treatment and then again at weeks 4–6, and at 3 and 6 months. OCT, VA, and IOP were also assessed at 1 month.Results: ITV pegaptanib sodium was well tolerated and no treatment complications arose. Mean VA was measured as: 0.37 ± 0.24 at baseline; 0.37 ± 0.25 at 1 month; 0.37 ± 0.25 at 3 months and 0.40 ± 0.26 at 6 months. VA was stabilized in approximately 90% of eyes treated with pegaptanib sodium. OCT examination showed a minimal change in central retinal thickness (CRT) during the course of the study, from 251.19 µm at baseline to 251.63 µm at 6 months. No elevation in IOP was measured during treatment at 4–6 months in patients receiving pegaptanib sodium.Conclusions: ITV therapy with pegaptanib sodium for occult and minimally classic CNV secondary to neovascular AMD offered good efficacy with a favorable adverse events profile. The majority of patients showed stabilization in all assessed parameters. In clinical practice, careful consideration should be given to the use of nonselective VEGF inhibition in patients with a high cardiovascular risk profile or in those with a history of thromboembolic events.Keywords: Intravitreal (ITV) injection, age-related macular degeneration (AMD), choroidal neovascularization (CNV), anti-VEGF therapy, pegaptanib sodiu

Fluorescence lifetime imaging microscopy (FLIM) to demonstrate the nuclear binding of flavanols and (--epigallocatechin gallate

The use of light microscopy and DMACA staining strongly suggested that plant and animal cell nuclei act as sinks for flavanols [1, 2]. Detailed uv-vis spectroscopic titration experiments indicated that histone proteins are the likely binding sites in the nucleus [2]. Here we report the development of a multi-photon excitation microscopy technique combined with fluorescent lifetime measurements of flavanols. Using this technique, (+) catechin, (-) epicatechin and (-) epigallocatechin gallate (EGCG) showed strikingly different excited state lifetimes in solution. Interaction of histone proteins with flavanols was indicated by the appearance of a significant τ2-component of 1.7 to 4.0ns. Tryptophan interference could be circumvented in the in vivo fluorescence lifetime imaging microscopy (FLIM) experiments with 2-photon excitation at 630nm. This enabled visualisation and semi-quantitative measurements that demonstrated unequivocally the absorption of (+)catechin, (-)epicatechin and EGCG by nuclei of onion cells. 3D FLIM revealed for the first time that externally added EGCG penetrated the whole nucleus in onion cells. The relative proportions of EGCG in cytoplasm: nucleus: nucleoli were ca. 1:10:100. FLIM experiments may therefore facilitate probing the health effects of EGCG, which is the major constituent of green tea

Innovations in the clinical care of mothers and children in South Africa: The contribution of district clinical specialist teams

The contribution of the District Clinical Specialist Teams (DCSTs) to improving maternal and child health outcomes in South Africa, through strengthening the four pillars of clinical governance, is reflected in innovative work presented at a ‘Promising Practices’ symposium and at various conferences. Of the 24 identified DCST innovations, 21% reflected the clinical effectiveness pillar, 17% clinical risk management, 41% staff development, and 21% user-related considerations. In order to ensure scale-up, the submitted best practices/ innovations were reviewed using the World Health Organization quality standards and ExpandNet parameters for likely scalability. Here we describe one case study from each pillar, illustrating the contribution of the innovations to improved patient outcomes. The development and scale-up of innovations needs to be institutionalised and must include effective support and action from the relevant health managers

Electroweak Sudakov Logarithms and Real Gauge-Boson Radiation in the TeV Region

Electroweak radiative corrections give rise to large negative, double-logarithmically enhanced corrections in the TeV region. These are partly compensated by real radiation and, moreover, affected by selecting isospin-noninvariant external states. We investigate the impact of real gauge boson radiation more quantitatively by considering different restricted final state configurations. We consider successively a massive abelian gauge theory, a spontaneously broken SU(2) theory and the electroweak Standard Model. We find that details of the choice of the phase space cuts, in particular whether a fraction of collinear and soft radiation is included, have a strong impact on the relative amount of real and virtual corrections.Comment: 20 pages, 4 figure

Sudakov Electroweak effects in transversely polarized beams

We study Standard Model electroweak radiative corrections for fully inclusive observables with polarized fermionic beams. Our calculations are relevant in view of the possibility for Next Generation Linear colliders of having transversely and/or longitudinally polarized beams. The case of initial transverse polarization is particularly interesting because of the interplay of infrared/collinear logarithms of different origins, related both to the nonabelian SU(2) and abelian U(1) sectors. The Standard model effects turn out to be in the 10% range at the TeV scale, therefore particularly relevant in order to disentangle possible New Physics effects.Comment: 5 pages,4 figure

Return-to-activity after anatomical reconstruction of acute high-grade acromioclavicular separation

BACKGROUND: To evaluate return-to-activity (RtA) after anatomical reconstruction of acute high-grade acromioclavicular joint (ACJ) separation. METHODS: A total of 42 patients with anatomical reconstruction of acute high-grade ACJ-separation (Rockwood Type V) were surveyed to determine RtA at a mean 31 months follow-up (f-u). Sports disciplines, intensity, level of competition, participation in overhead and/or contact sports, as well as activity scales (DASH-Sport-Module, Tegner Activity Scale) were evaluated. Functional outcome evaluation included Constant score and QuickDASH. RESULTS: All patients (42/42) participated in sporting activities at f-u. Neither participation in overhead/contact sports, nor level of activity declined significantly (n.s.). 62 % (n = 26) of patients reported subjective sports specific ACJ integrity to be at least the same as prior to the trauma. Sporting intensity (hours/week: 7.3 h to 5.4 h, p = .004) and level of competition (p = .02) were reduced. If activity changed, in 50 % other reasons but clinical symptoms/impairment were named for modified behavior. QuickDASH (mean 6, range 0–54, SD 11) and DASH-Sport-Module (mean 6, range 0–56, SD 13) revealed only minor disabilities at f-u. Over time Constant score improved significant to an excellent score (mean 94, range 86–100, SD 4; p < .001). Functional outcome was not correlated with RtA (n.s.). CONCLUSION: All patients participated in sporting activities after anatomical reconstruction of high-grade (Rockwood Type V) ACJ-separation. With a high functional outcome there was no significant change in activity level (Tegner) and participation in overhead and/or contact sports observed. There was no correlation between functional outcome and RtA. Limiting, there were alterations in time spent for sporting activities and level of competition observed. But in 50 % those were not related to ACJ symptoms/impairment. Unrelated to successful re-established integrity and function of the ACJ it should be considered that patients decided not return-to-activity but are very content with the procedure

Microstructural morphology and visual acuity outcome in eyes with epiretinal membrane before, during, and after membrane peeling in intraoperative optical coherence tomography assisted macular surgery

AIM: To measure the difference of intraoperative central macular thickness (CMT) before, during, and after membrane peeling and investigate the influence of intraoperative macular stretching on postoperative best corrected visual acuity (BCVA) outcome and postoperative CMT development. METHODS: A total of 59 eyes of 59 patients who underwent vitreoretinal surgery for epiretinal membrane was analyzed. Videos with intraoperative optical coherence tomography (OCT) were recorded. Difference of intraoperative CMT before, during, and after peeling was measured. Pre- and postoperatively obtained BCVA and spectral-domain OCT images were analyzed. RESULTS: Mean age of the patients was 70±8.13y (range 46-86y). Mean baseline BCVA was 0.49±0.27 logMAR (range 0.1-1.3). Three and six months postoperatively the mean BCVA was 0.36±0.25 (P=0.01 vs baseline) and 0.38±0.35 (P=0.08 vs baseline) logMAR respectively. Mean stretch of the macula during surgery was 29% from baseline (range 2%-159%). Intraoperative findings of macular stretching did not correlate with visual acuity outcome within 6mo after surgery (r=-0.06, P=0.72). However, extent of macular stretching during surgery significantly correlated with less reduction of CMT at the fovea centralis (r=-0.43, P&#x003C;0.01) and 1 mm nasal and temporal from the fovea (r=-0.37, P=0.02 and r=-0.50, P&#x003C;0.01 respectively) 3mo postoperatively. CONCLUSION: The extent of retinal stretching during membrane peeling may predict the development of postoperative central retinal thickness, though there is no correlation with visual acuity development within the first 6mo postoperatively