Randomized Trial to Evaluate Tandosporine in Geographic Atrophy Secondary to Age-Related Macular Degeneration: the GATE Study.

PURPOSE To determine the safety and efficacy of AL-8309B (tandospirone) in the management of patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) and obtain standardized data on GA lesion growth progression. DESIGN Prospective, controlled, double-masked, randomized, multicenter phase 3 clinical trial. METHODS Setting: 48 clinical sites. PATIENTS Patients with GA associated with AMD were enrolled. All patients were followed for a minimum of 30 months, and up to 36 months. Intervention Procedures: Patients were randomized (1:1:1) to receive AL-8309B ophthalmic solution 1.0%, 1.75%, or vehicle, administered as a twice-daily topical ocular drop. MAIN OUTCOME MEASURES The primary efficacy endpoint was mean annualized lesion enlargement from baseline as assessed with fundus autofluorescence (FAF) imaging. RESULTS A total of 768 eyes of 768 patients were enrolled and treated with AL-8309B 1.0% (N=250), AL-8309B 1.75% (N=258), or vehicle (N= 260). An increase in mean lesion size was observed in both the AL-8309B and vehicle treatment groups, and growth rates were similar in all treatment groups. Annualized lesion growth rates were 1.73, 1.76 and 1.71 mm(2) for AL-8309B 1.0%, AL-8309B 1.75%, and vehicle, respectively. CONCLUSIONS AL-8309B 1.0% and 1.75% did not affect lesion growth in eyes with GA secondary to AMD. There were no clinically relevant safety issues identified for AL-8309B. The large natural history dataset from this study is a valuable repository for future comparisons.

Selective retina therapy (SRT) in patients with geographic atrophy due to age-related macular degeneration

For geographic atrophy (GA) due to age-related macular degeneration (AMD) there is so far no approved treatment option. Usually, increased autofluorescence (AF) levels of different patterns adjacent to the atrophic area indicate lipofuscin-laden retinal pigment epithelium (RPE) cells at a high risk for apoptosis. Herein, SRT was used to selectively treat these cells to stimulate RPE proliferation, in order to reduce or ideally stop further growth of the atrophic area.

Geometric facial comparisons in speed-check photographs

In many cases, it is not possible to call the motorists to account for their considerable excess in speeding, because they deny being the driver on the speed-check photograph. An anthropological comparison of facial features using a photo-to-photo comparison can be very difficult depending on the quality of the photographs. One difficulty of that analysis method is that the comparison photographs of the presumed driver are taken with a different camera or camera lens and from a different angle than for the speed-check photo. To take a comparison photograph with exactly the same camera setup is almost impossible. Therefore, only an imprecise comparison of the individual facial features is possible. The geometry and position of each facial feature, for example the distances between the eyes or the positions of the ears, etc., cannot be taken into consideration. We applied a new method using 3D laser scanning, optical surface digitalization, and photogrammetric calculation of the speed-check photo, which enables a geometric comparison. Thus, the influence of the focal length and the distortion of the objective lens are eliminated and the precise position and the viewing direction of the speed-check camera are calculated. Even in cases of low-quality images or when the face of the driver is partly hidden, good results are delivered using this method. This new method, Geometric Comparison, is evaluated and validated in a prepared study which is described in this article.

[Imaging diagostics of geographic atrophy]

The development of imaging technologies has contributed to the understanding of the genesis and pathophysiological mechanisms of geographic atrophy (GA) secondary to age-related macular degeneration (AMD). Fundus autofluorescence (FAF) imaging allows accurate discrimination of the boundaries of atrophic patches. Furthermore, predictive markers for disease progression can be identified. Non-invasive FAF imaging now represents the gold standard for evaluating progressive enlargement of atrophic areas. By means of high resolution optical coherence tomography (OCT) microstructural retinal changes in GA can be identified. Anatomical endpoints are now being used in interventional GA trials and represent meaningful outcome parameters as surrogate markers in an overall slowly progressive disease which may not affect the fovea until later stages of the disease.

Insights on the role of diabetes and geographic variation in patients with critical limb ischaemia

Patients with critical limb ischaemia (CLI) unsuitable for revascularisation have a high rate of amputation and mortality (30% and 25% at 1 year, respectively). Localised gene therapy using plasmid DNA encoding acidic fibroblast growth factor (NV1FGF, riferminogene pecaplasmid) has showed an increased amputation-free survival in a phase II trial. This article provides the rationale, design and baseline characteristics of CLI patients enrolled in the pivotal phase III trial (EFC6145/TAMARIS).

Blue Light versus Green Light Autofluorescence: Lesion Size of Areas with Geographic Atrophy

Blue-light fundus autofluorescence (FAF) imaging is currently widely used for assessing dry age-related macular degeneration (ARMD). However, at this wavelength, the fovea appears as circular zone of marked hypofluorescence, due to the absorption of macular pigment (MP). This dark spot could be misinterpreted as an atrophic area and could lead to difficulties in identifying small, central changes. The purpose of the study was to analyze differences in image quality, FAF patterns, and lesion size, when using conventional blue-light (Λ(1) = 488 nm) and green-light (Λ(2) = 514 nm) FAF.

Progression of age-related geographic atrophy: role of the fellow eye

PURPOSE. To evaluate the role of fellow eye status in determining progression of geographic atrophy (GA) in patients with age-related macular degeneration (AMD). METHODS. A total of 300 eyes with GA of 193 patients from the prospective, longitudinal, natural history FAM Study were classified into three groups according to the AMD manifestation in the fellow eye at baseline examination: (1) bilateral GA, (2) early/intermediate AMD, and (3) exudative AMD. GA areas were quantified based on fundus autofluorescence images using a semiautomated image-processing method, and progression rates (PR) were estimated using two-level, linear, mixed-effects models. RESULTS. Crude GA-PR in the bilateral GA group (mean, 1.64 mm(2)/y; 95% CI, 1.478-1.803) was significantly higher than in the fellow eye early/intermediate group (0.74 mm(2)/y, 0.146-1.342). Although there was a significant difference in baseline GA size (P = 0.0013, t-test), and there was a significant increase in GA-PR by 0.11 mm(2)/y (0.05-0.17) per 1 disc area (DA; 2.54 mm(2)), an additional mean change of -0.79 (-1.43 to -0.15) was given to the PR beside the effect of baseline GA size. However, this difference was only significant when GA size was ?1 DA at baseline with a GA-PR of 1.70 mm(2)/y (1.54-1.85) in the bilateral and 0.95 mm(2)/y (0.37-1.54) in the early/intermediate group. There was no significant difference in PR compared with that in the fellow eye exudative group. CONCLUSIONS. The results indicate that the AMD manifestation of the fellow eye at baseline serves as an indicator for disease progression in eyes with GA ? 1 DA. Predictive characteristics not only contribute to the understanding of pathophysiological mechanisms, but also are useful for the design of future interventional trials in GA patients.

Farming Systems and Resilience Building in a Changing Climate On-Farm Comparisons of Organic and Conventional Cocoa Cultivation in Alto Beni, Bolivia

Resilience research has been applied to socioeconomic as well as for agroecological studies in the last 20 years. It provides a conceptual and methodological approach for a better understanding of interrelations between the performance of ecological and social systems. In the research area Alto Beni, Bolivia, the production of cocoa (Theobroma cacao L.), is one of the main sources of income. Farmers in the region have formed producers’ associations to enhance organic cocoa cultivation and obtain fair prices since the 1980s. In cooperation with the long-term system comparisons by the Research Institute of Organic Agriculture (FiBL) in Alto Beni, aspects of the field trial are applied for the use in on-farm research: a comparison of soil fertility, biomass and crop diversity is combined with qualitative interviews and participatory observation methods. Fieldwork is carried out together with Bolivian students through the Swiss KFPE-programme Echanges Universitaires. For the system comparisons, four different land-use types were classified according to their ecological complexity during a preliminary study in 2009: successional agroforestry systems, simple agroforestry systems (both organically managed and certified), traditional systems and conventional monocultures. The study focuses on interrelations between different ways of cocoa cultivation, livelihoods and the related socio-cultural rationales behind them. In particular this second aspect is innovative as it allows to broaden the biophysical perspective to a more comprehensive evaluation with socio-ecological aspects thereby increasing the relevance of the agronomic field studies for development policy and practice. Moreover, such a socio-ecological baseline allows to assess the potential of organic agriculture regarding resilience-building face to socio-environmental stress factors. Among others, the results of the pre-study illustrate local farmers’ perceptions of climate change and the consequences for the different crop-systems: all interviewees mentioned rising temperatures and/or an extended dry season as negative impacts more with regard to their own working conditions than to their crops. This was the case in particular for conventional monocultures and in plots where slash-and-burn cultivation was practised whereas for organic agroforestry systems the advantage of working in the shade was stressed indicating that their relevance rises in the context of climate change.

Geographic information system-based decision support for soil conservation planning in Tajikistan

Soil erosion on sloping agricultural land poses a serious problem for the environment, as well as for production. In areas with highly erodible soils, such as those in loess zones, application of soil and water conservation measures is crucial to sustain agricultural yields and to prevent or reduce land degradation. The present study, carried out in Faizabad, Tajikistan, was designed to evaluate the potential of local conservation measures on cropland using a spatial modelling approach to provide decision-making support for the planning of spatially explicit sustainable land use. A sampling design to support comparative analysis between well-conserved units and other field units was established in order to estimate factors that determine water erosion, according to the Revised Universal Soil Loss Equation (RUSLE). Such factor-based approaches allow ready application using a geographic information system (GIS) and facilitate straightforward scenario modelling in areas with limited data resources. The study showed first that assessment of erosion and conservation in an area with inhomogeneous vegetation cover requires the integration of plot-based cover. Plot-based vegetation cover can be effectively derived from high-resolution satellite imagery, providing a useful basis for plot-wise conservation planning. Furthermore, thorough field assessments showed that 25.7% of current total cropland is covered by conservation measures (terracing, agroforestry and perennial herbaceous fodder). Assessment of the effectiveness of these local measures, combined with the RUSLE calculations, revealed that current average soil loss could be reduced through low-cost measures such as contouring (by 11%), fodder plants (by 16%), and drainage ditches (by 53%). More expensive measures such as terracing and agroforestry can reduce erosion by as much as 63% (for agroforestry) and 93% (for agroforestry combined with terracing). Indeed, scenario runs for different levels of tolerable erosion rates showed that more cost-intensive and technologically advanced measures would lead to greater reduction of soil loss. However, given economic conditions in Tajikistan, it seems advisable to support the spread of low-cost and labourextensive measures.

Comparisons of sound processors based on osseointegrated implants in patients with conductive or mixed hearing loss

To compare the patient benefit of the Bone-Anchored Hearing Aid (Baha) Divino and the Baha BP100 sound processors.