Wet Age Research Articles

Biomarkers of oxidative stress in patients with wet age related macular degeneration.

The aim of this study was to analyze biomarkers of oxidative stress in patients with wet age related macular degeneration (AMD). Case-control study that includes 163 patients with wet AMD (age group of 55-82 years with the mean age of 71 years and 170 age-matched healthy controls in the age group of 55-78 years with the mean age of 71 years. The following parameters were determined: reduced and oxidized Glutathione (GSH/GSSH), protein carbonyl groups, total antioxidant activity in plasma and the activity of endogenous antioxidant enzymes, such as, gluthatione peroxidase, gluthatione reductase and superoxide dismutase. We observed total antioxidant activity higher in control group (CG) compared with patients with wet AMD (7.1 ± 1.2 μM Trolox vs 5.8 ± 1.1 μM Trolox). Values of superoxide dismutase activity (SOD), gluthatione reductase (GR) and gluthatione peroxidase (GPx) are higher in control group than in patients with wet AMD. According to the GSH/GSSH results, average values were higher in the CG than in patients with wet AMD and data were not significantly different.. Values of protein carbonyl groups were higher in patients with wet AMD than in CG and significant differences were found. The finding of the present study suggests that the patients with wet AMD are an altered metabolic state of oxidation-reduction and that it is convenient to give therapeutic interventions with antioxidants. We have demonstrated that systematic oxidative stress, measured by different biomarkers is closely associated with the wet AMD.

The wet Little Ice Age recorded by sediments in Huguangyan Lake, tropical South China

Although temperature decreased in a similar trend in many regions around the word during the Little Ice Age (LIA), the reconstructed humidity is remarkably different from region to region. The precipitation history during the LIA is poorly understood as compared to the temperature history in tropical South China. In this study, a sediment core with a length of 117.5 cm was recovered in the central part of Huguangyan Lake in tropical South China. Total organic carbon (TOC), total nitrogen (TN), inorganic carbon (IC) and non-residual strontium (Sr) were analyzed at approximately 1 cm intervals to study the regional precipitation changes during the LIA. Generally, Sr-containing minerals are sensitive to chemical weathering which is dominated by the precipitation in tropical South China. Thus the non-residual Sr in Huguangyan sediments can be used as an indicator of precipitation changes, which is also verified by the downcore variations of TOC, TN and IC in Huguangyan Lake. The non-residual Sr correlated positively with TOC and TN but negatively with IC in the sediment profile. TOC, TN, IC and the non-residual Sr jointly demonstrated a wet period from AD 1500 to 1750, which corresponds to the LIA. Coincidently, both the total solar irradiance (TSI) and Northern Hemisphere temperature have the lowest values between AD 1500 and 1750 over the past millennium. Therefore, the wet LIA in tropical South China was most likely caused by the low solar irradiation. During the LIA, the low solar irradiation likely resulted in the decrease of the Northern Hemisphere temperature, which weakened the intensity of the East Asian summer monsoon (EASM) and synchronously moved the north edge of the Asian summer monsoon southward, leading to an increase in the precipitation in tropical South China.

Bevacizumab in wet age related macular degeneration - one year clinical experience

Bevacizumab in wet age related macular degeneration - one year clinical experience

Is quantitative spectral‐domain superior to time‐domain optical coherence tomography (OCT) in eyes with age‐related macular degeneration?

The aim of this study was to determine the variability of macular map measurements, for two generations of optical coherence tomography (OCT) instruments, in eyes with wet age related macular degeneration (AMD) and low visual acuity. Patients were examined with Stratus OCT and Cirrus HD-OCT. The macular thickness was assessed with the 'macular thickness map scan' and 'fast protocol' in Stratus and with the 512 × 128 and 200 × 200 cube protocols in Cirrus OCT. Two measurements were taken one directly after the other, at the first visit to analyse repeatability. Approximately 1 week later, a third measurement was taken to analyse reproducibility. In Cirrus OCT, a manual correction of foveal location was also performed. Repeatability and reproducibility were calculated as a coefficient of variance (CoV) and a coefficient of repeatability/reproducibility. Repeatability for central macular thickness (expressed as CoV) was about three per cent for all protocols, and the coefficient of repeatability between 34 and 54 μm. Reproducibility (also expressed as CoV) was between four to seven per cent and coefficient of repeatability between 64 and 89 μm. After manual adjustment of foveal location in Cirrus OCT, the coefficient of repeatability improved to 12-18 μm, and the coefficient of reproducibility to 44-47 μm. In eyes affected by wet AMD, there were small differences in repeatability and reproducibility when comparing quantitative maps in Stratus and Cirrus OCT. However, when the software for manual correction of foveal position in Cirrus OCT was used, the variability decreased markedly, and the repeatability was close to what had been reported in normal eyes, demonstrating a significant, potential advantage of spectral-domain over time-domain OCT.

Retinal Angiomatous Proliferation

Retinal angiomatous proliferation (RAP) is a distinct form of choroidal neovascularization which may complicate a wet age related macular degeneration (AMD). This exudative-AMD has a peculiar clinical history and prognosis. RAP accounts from 8% to 22% of newly diagnosed cases among patients previously diagnosed as exudative AMD, and up to 25% of the occult or minimally classic CNV. The disease is more prevalent in women (90% of cases) and in elderly patients (around 75 years), and is characterized by a very poor prognosis. The neovascular process, whose retinal or choroidal origin is still object of discussion, often hesitates in the formation of a disciform scar, that evolves into a severe loss of central vision. Treatment for RAP is not yet well established; herein are described the most used therapeutic strategies, starting from laser photocoagulation until the nearest anti VEGF. The opportunity of combination among various treatments to obtain a better effectiveness and a lower frequency of recurrence is also discussed.

Moisture changes over the last millennium in arid central Asia: a review, synthesis and comparison with monsoon region

There is a strong chance that 20th century warming will cause differences in precipitation distribution, hydrological cycle and effective moisture changes over the globe. Arid central Asia (ACA), a unique dry-land area whose atmospheric circulation is dominated today by the westerlies, is one of the specific regions that are likely to be strongly impacted by global warming. An understanding of past variations in effective moisture in such regions is an important prerequisite for the prediction of future hydrological change. Here we evaluate spatial and temporal patterns of effective moisture variations documented by different proxies from 17 records in ACA, and synthesize a decadal-resolution moisture curve for ACA over the past millennium, using 5 of the 17 records selected on the basis of reliable chronologies and robust proxies. The high- and low-resolution data all show that, over the past millennium, ACA has been characterized by a relatively dry Medieval Warm Period (MWP; the period from ∼1000 to 1350 AD), a wet Little Ice Age (LIA; from ∼1500 to 1850 AD) and increasing moisture during recent decades. As a whole, the LIA in the ACA was not only relatively humid but also had high precipitation. Over the past millennium, the multi-centennial moisture changes in ACA show a generally inverse relationship with the temperature changes in the Northern Hemisphere, China, and western central Asia. The effective moisture history in ACA also shows an out-of-phase relationship with that in monsoon Asia (especially during the LIA). We propose that the humid LIA in ACA, possibly extending to Mediterranean Sea and Western Europe, may have resulted from increased precipitation due to more frequent mid-latitude cyclone activities as a result of the strengthening and equator-ward shift of the westerly jet stream, and the predominantly negative North Atlantic Oscillation conditions, coupled with a decrease in evapotranspiration caused by the cooling at that time.

An oxygen-isotope record of Holocene climate change in the south-central Brooks Range, Alaska

Understanding the ecological and socio-economic impacts of climatic warming requires knowledge of associated changes in moisture balance. Reconstructions of Holocene moisture-balance variation offer indispensible baseline information against which recent changes can be evaluated. We analyzed Chara-stem encrustations in the sediments of Takahula Lake, located in the south-central Brooks Range of Alaska, for oxygen and carbon-isotope composition to infer climatic change over the past 8000 years. To help constrain climatic interpretations of the sediment δ 18O record, we also analyzed water samples from Takahula and other lakes in the region for oxygen and hydrogen isotope composition. Results show that winter precipitation dominates the water balance of these lakes and that post-input evaporation is a key control of lake-water isotope composition of Takahula Lake. Stratigraphic patterns in Chara-δ 18O, supplemented by those in δ 13C and sediment lithology, reveal distinct changes in effective moisture (precipitation minus evaporation) over the past 8000 years. Effective moisture was relatively high from 8000 to 5000 cal BP, with marked fluctuations between 6800 and 5000 cal BP. It then decreased to reach a minimum around 4000 cal BP and increased with fluctuations from 4000 to ∼2500 cal BP, followed by a decreasing trend toward the present that was interrupted by a wet Little Ice Age (centered at 400 cal BP). Aridity during the 20th century was among the highest of the entire 8000-year record. At the millennial timescale, the temporal patterns of moisture-balance shifts at Takahula Lake are broadly coherent with those inferred from previous paleoclimate records from the region. The Chara-δ 18O values around 5600 cal BP and during the Little Ice Age are up to 5‰ lower than at present and 3.6‰ lower than that of the modern input-water to the lake. These exceptionally low values suggest that factors other than effective moisture must have contributed to the pronounced variations in the Takahula Lake δ 18O record. Increased winter precipitation associated with a westerly Aleutian Low position may account for 1‰ of the δ 18O decrease. Other factors leading to the 18O-depletion during these periods probably include decreased temperatures, as well as increased lake-ice cover and associated reductions in evaporation.

Bevacizumab for neovascular age related macular degeneration (ABC Trial): multicentre randomised double masked study

Objectives To evaluate the efficacy and safety of intravitreous bevacizumab injections for the treatment of neovascular age related macular degeneration.Design Prospective, double masked, multicentre, randomised controlled trial.Setting Three ophthalmology centres...

Anti‐VEGF therapy and influence of vitreomacular traction in wet AMD

Abstract Purpose The aim of this study is to describe the results of anti Vascular Endothelial Growth Factor (VEGF) therapy in Wet Age Macular Degeneration (Wet‐AMD) and the posible rol of vitreomacular traction (VMT). Methods Descriptive, retrospective, interventional case series study of Wet‐AMD patients diagnosed by angiography (AFG) and optical coherence tomography (OCT) and treated with anti‐VEG . All patients received an initial charge course of three doses, and consecutive new doses if required by monthly follow up. Vitreomacular status was evaluated by OCT. Inactivation was defined by the absense of new subretinal fluid on OCT and AFG. Minimun follow up of six months after the last dose. Results Of 76 treated patients, 27 met the inclusion criteria, 12 men and 15 women with a mean age of 79,9 years (standar deviation of 6,2). 11 had VMT and 16 had not. 48% (13/27) of patients became inactive after initial charge course, 18% (5/27) after initial good response became active despite consecutive aditional doses and 33% (9/27) required more dosis but finally achieved inactivation, but did not improve visual acuity. Between patients with VMT there were more prevalence of patients who needed seven or more doses to stabilize the disease (p=0,003). Conclusion Consecutive dosis of anti‐VEGF after inicial charge course are needed to inactivate one third of patients, but these patients have poorer funtional results. VMT seems to be a bad prognosis factor.

Outcome following ranibizimab therapy for neovascular age related macular degeneration in patients with poor, intermediate and good vision

Abstract Purpose To assess the visual outcome following intravitreal ranibizumab in eyes with wet age related macular degeneration(AMD) in patients with three different baseline vision viz; <35, 35‐54 and >54 ETDRS letters. Methods This study assessed the ETDRS visual acuity at diferent time points in a total of 98 patients.Optical coherent tomography and fundus fluorescein angiography FFA was carried out at baseline and thereafter when required. Intravitreal ranibizumab was administered monthly for 3 months and when necessary as guided by vision and OCT. Follow up period was 6 months. Results In the 27 patients with baseline vision < 35 letters, the mean change in vision at 6 months from baseline is +8 (p=0.04). None of the patients lost more than 15 letters (floor effect) and 35% gained more than 15 letters. In 43 patients with baseline vision 35‐54 letters the mean change in vision at 6 months is +10 letters(p=0.0003). None of the patients lost more than 15 letters or gained more than 15 letters.Twenty‐eight patients baseline vision > 54 letters had a mean change in vision at 6 months of +6 (p=0.4). Only 16% gained more than 15 letters(ceiling effect). All the three groups were observed to have improvement of vision in the 3rd month which was sustained in the 6 month.Patients with baseline vision more than 54 letters receive an average of 3.52 injections over the 6 month period. Those with vision 35‐54 and <35 received an average of 3.42 and 3.56 injections respectively over the same period. Conclusion Response to ranibizumab in patients with good and intermediate and poor vision at baseline was similar to the ANCHOR and MARINA studies up to 6 months.

VEGF165b is more potent at inhibiting endothelial cell migration than Pegabtanib and is cytoprotective for retinal pigmented epithelial cells

Ocular angiogenesis, stimulated by VEGF165 in the retina and choroid, is the principal cause of vision loss in patients with diabetic retinopathy and wet age related macular degeneration. In these conditions there is an excess of VEGF165 over the anti‐angiogenic splice variant VEGF165b. Inhibitors of VEGF such as ranibizumab and pegabtanib are used clinically to treat AMD patients. We have compared the effect of VEGF165b with these anti‐VEGF antibody treatments. Western blotting showed that pegabtanib did not bind VEGF165b, whereas bevacizumab (the antibody from which ranibizumab was derived) bound VEGF165b. Chemotaxis assays of HMVE Cells using a Boyden chamber showed a 2.6 fold decrease of HMVEC migration at 10nM pegabtanib after challenging the cells with 1nM VEGF165 (p<0.01). The same impairment in migration occurred with only 1nM VEGF165b. Treatment of RPE cells with 10mg/ml neutralising antibody to VEGF165b showed a significant increase in cytotoxicity compared to control IgG, measured by lactase dehydrogenase release, indicating that VEGF165b is a survival factor for retinal pigmented epithelial cells. Together these results support the use of VEGF165b as an anti‐angiogenic treatment in ocular neovascularization.

Optical coherence tomography of the choroid at 1050nm

Abstract Purpose: Optical coherence tomography is a well established imaging modality for the retina at 800 nm, but is limited in its capability to visualize through scattering tissue, like through cataract or into the choroid. Methods: Utilizing the lower scattering at longer wavelengths (1050 nm) high speed (>17 kHz), high axial resolution (~7 μm) optical coherence tomography (OCT) demonstrates its abil‐ity to exploit the three dimensional anatomic microstructure of the choroid. Volumetric images, obtained with spectrometer based frequency domain OCT system are presented and compared with their counterparts acquired at the commonly used 800 nm range. Results: Tomograms of normals and patients with pathologic morphological changes of the retinal structure as well as with cataract depict improved signal strength and image contrast at the longer wavelength. The deeper penetration allows reconstruction of the choroidal vascular structure despite strong scattering of superficial tissues at the retinal pigment epithelium, the choriocapillaris also including pathologic retinal thickening. Visualisation of modifications in the choroidal vascular structure associated with wet age related macu‐lar degeneration or diabetic retinopathy indicate the diagnostic potential of this technique. Furthermore, being well outside the spectral sensitivity of the eye the wavelength band at 1050 nm also allows for depth resolved profiling of reflectivity changes to directly moni‐tor light stimulus related retinal activity, without interference due to the sampling OCT beam. Conclusions: Imaging at 1050 nm enables not only to track morphological but also functional changes of the retina.

Expression of adiponectin in choroidal tissue and inhibition of laser induced choroidal neovascularization by adiponectin

The aim of this study was to investigate the role of adiponectin (APN) in a mouse model of laser induced choroidal neovascularization (CNV). We have shown by immunohistochemistry that the expression of APN, adiponectin receptor 1, adiponectin receptor 2 and T cadherin gradually increased from day 1 to day 7 post-laser in laser treated mice compared to controls. Recombinant APN (rAPN) was injected intraperitoneally (i.p., 25 μg/mouse) or intravitreally (2 μg/eye) in lasered mice. Another set of lasered mice received APN peptide via i.p. (75 μg/mouse) or intravitreal (30 μg/eye) route. Control mice received a similar treatment with PBS, control protein or control peptide after laser treatment. We found that in the i.p. and intravitreal injection of rAPN resulted in 78% and 68% inhibition respectively in the size of CNV complex compared to control mice. Similar results were observed when APN peptide was injected intravitreally or i.p. Treatment with rAPN or the peptide resulted in decreased levels of vascular endothelial growth factor. Thus, APN inhibited choroidal angiogenesis and may have therapeutic implications in the treatment of wet age related macular degeneration.

Little Ice Age drought in equatorial Africa: Intertropical Convergence Zone migrations and El Niño–Southern Oscillation variability

High-resolution analyses of the Mg concentration in authigenic calcite in five cores from Lake Edward provide a water balance history of central equatorial Africa spanning the past 1400 yr. A high ratio of Mg to Ca (%Mg) indicates strong droughts in central Africa during the Little Ice Age (A.D. 1400–1750), in contrast to records from Lake Naivasha, Kenya, which suggest a wet Little Ice Age. This spatial pattern in Africa likely arose due to coupled changes in the high latitudes, the position of the Intertropical Convergence Zone, and the El Nino–Southern Oscillation (ENSO) system. Our results further suggest that the patterns and variability of twentieth-century rainfall in central Africa have been unusually conducive to human welfare in the context of the past 1400 yr.

The effects of inoculum dose, duration of wet period, temperature and wound age on infection by Nectria galligena of pruning wounds on apple

Four experiments were conducted with potted trees of several apple cultivars to study the effects of several factors on the incidence of canker and the length of the incubation period following the inoculation of pruning cuts with conidia of Nectria galligena. These factors included wound age (the interval between pruning and inoculation), inoculum dose and environment (wet-period temperature and duration). The most important factors affecting the incidence of canker and the incubation period were inoculum dose, cultivar and wound age. Low inoculum dose resulted in low incidence of canker. The incidence of canker decreased as the age of the pruning wound increased. The incubation period lengthened with low inoculum dose and increasing age of the wound. The degree of resistance related to the age of the wound varied with cultivar; likewise, it also varied with the time of year, but this was not due to temperature alone. On fresh wounds, the incidence of canker and the incubation period were not affected by temperature during the wet period. The effect of duration of wetness on canker incidence was significant in only one out of three experiments: the longer wet periods resulted in a slightly lower incidence on fresh wounds. In another experiment, wet periods longer than 2 h resulted in shorter incubation periods. The results are discussed in relation to wound healing.

Vegetation changes along gradients of long-term soil development in the Hawaiian montane rainforest zone

The development of the Hawaiian montane rainforest was investigated along a 4.1-million-year soil age gradient at 1200 m elevation under two levels of precipitation, the mesic (c. 2500 mm annual rainfall) vs. wet (>4000 mm) age gradient. Earlier analyses suggested that soil fertility and foliar nutrient concentrations of common canopy species changed unimodally on the same gradients, with peak values at the 20,000–150,000 yr old sites, and that foliar concentrations were consistently lower under the wet than under the mesic conditions. Our objectives were to assay the influences of soil aging and moisture on forest development using the patterns and rates of species displacements. The canopies at all sites were dominated by Metrosideros polymorpha. Mean height and dbh of upper canopy Metrosideros trees increased from the youngest site to peak values at the 2100–9000 yr sites, and successively declined to older sites. A detrended correspondence analysis applied to mean species cover values revealed that significant variation among sites occurred only on one axis (axis 1), for both soil-age gradients. Sample scores along axis 1 were perfectly correlated with soil age on the mesic gradient, and significantly correlated on the wet gradient. Higher rainfall appeared to be responsible for the higher rates of species turnover on the wet gradient probably through faster rock weathering and greater leaching of soil elements. We concluded that the changes in species cover values and size of the canopy species was a reflection of the changing pattern of nutrient availability associated with soil aging.

Growth related changes to functional parameters in the bovine lens

Dimensions, volumes and protein contents were measured for bovine lenses with wet weights ranging from 0.17–3.07 g (2 months gestation to 19 years post-natal). All increase in a non-linear fashion. The lens becomes flater with age due to a more rapid increase in the equatorial plane, but the ratio of anterior to posterior sagittal distances remains constant (1.19). The radius of curvature increases from 4.9 to 15 for the anterior surface and from 4.4 to 13 for the posterior. Protein content increases more rapidly than volume resulting in an increased average protein concentration from around 18% in the early prenatal lens to nearly 50% in the 19 year old. Total protein content (TPC) was found to be related to wet weight ( We) according to the equation, TPC = 0.3 We 1.33. It is suggested that TPC is a better parameter for describing growth than wet weight or age. The refractive index, in the equatorial plane, increases towards the centre, from 1.38 at the edge of the lens. The maximum index, in the centre, increases with lens size up to 1.474 in the largest lens studied. This corresponds to a protein concentration of 70%. In all lenses, refractive index and protein concentration gradients were superimposable when plotted from the outside towards the centre. The optical performance of the lenses was assessed by measuring the back focal length with increases gradually from 24 to 51.5 mm over the 0.17 to 3.07 g size range. This was attributed to the increased radii of curvature.