The EuroNet paediatric hodgkin network - modern imaging data management for real time central review in multicentre trials.

Since 2007, children and adolescents with Hodgkin lymphomas are treated in the Europe-wide EuroNet-PHL trials. A real time central review process for stratification of the patients enhances quality control and efficient therapy management. This process includes reading of all cross-sectional-images. Since reference evaluation is time critical, a fast, easy to handle and safe data transfer is important. In addition, immediate and constant access to all the data has to be guaranteed in case of queries and for regulatory reasons. To meet the mentioned requirements the EuroNet Paediatric Hodgkin Data Network (funded by the European Union - Project Number: 2007108) was established between 2008 and 2011. A respective tailored data protection plan was formulated. The aim of this article is to describe the networks' mode of operation and the advantages for multi-centre trials that include centralized image review.

Haemophilic arthropathy of the ankle treated by total ankle replacement: a case series.

The standard treatment for end-stage osteoarthritis of the ankle joint in haemophilic patients has been fusion of the ankle joint. Total ankle replacement is still controversial as a treatment option. The objective of this prospective study was to evaluate the mid-term outcome in patients treated with total ankle replacement using an unconstrained three-component ankle implant. Ten haemophilic ankles in eight patients (mean age: 43.2 years, range 26.7-57.5) treated with total ankle replacement were followed up for a minimum of 2.7 years (mean: 5.6, range 2.7-7.6). The outcome was measured with clinical and radiological evaluations. There were no intra- or peri-operative complications. The AOFAS-hindfoot-score increased from 38 (range 8-57) preoperatively to 81 (range 69-95) postoperatively. All patients were satisfied with the results. Four patients became pain free; in the whole patient cohort pain level decreased from 7.1 (range 4-9) preoperatively to 0.8 (range 0-3) postoperatively. All categories of SF-36 score showed significant improvements in quality of life. In one patient, open ankle arthrolysis was performed because of painful arthrofibrosis. For patients with haemophilic osteoarthritis of the ankle joint, total ankle replacement is a valuable alternative treatment to ankle fusion.

Specific surface area and volume fraction of the cherry-pit model with packed pits.

This paper investigates volume fraction phi and specific surface area s for statistically homogeneous systems of partially penetrating spheres, i.e. so-called 'cherry-pit models'. In contrast to the version where the pits form an equilibrium system of hard spheres, here pits or hard spheres are considered which are packed, can be in direct contact, and form a nonequilibrium distribution. For this kind of system, new formulas for phi and s are given, which yield values in good agreement with the ones for large models constructed from hard sphere packings generated both experimentally and numerically. Surprisingly, the existing formulas for phi and s in the equilibrium cherry-pit model lead to values which deviate substantially from the values obtained here.

Mueller matrix retinal imager with optimized polarization conditions.

A new Mueller matrix polarimeter was used to image the retinas of normal subjects. Light from a linearly polarized 780 nm laser was passed through a system of variable retarders and scanned across the retina. Light returned from the eye passed through a second system of retarders and a polarizing beamsplitter to two confocal detection channels. Optimization of the polarimetric data reduction matrix was via a condition number metric. The accuracy and repeatability of polarization parameter measurements were within +/- 5%. The magnitudes and orientations of retardance and diattenuation, plus depolarization, were measured over 15 degrees of retina for 15 normal eyes.

Blue on yellow perimetry with scanning laser ophthalmoscopy in patients with age related macular disease.

BACKGROUND/AIM: The loss of short wavelength sensitive (SWS) cone mechanism sensitivity is related to severe vision loss in patients with age related maculopathy (ARM). A case-control study of patients with ARM and age matched controls was performed, using blue on yellow static perimetry. METHODS: A bright yellow background at 594 nm isolated the responses of short wavelength cone mechanisms to 458 nm targets. A scanning laser ophthalmoscope produced stimuli and provided real time, simultaneous fundus illumination. The macula was probed with 16 Goldmann IV targets, 1-10 degrees from fixation, using a staircase method. RESULTS: 24 patients with non-exudative ARM were matched to 24 subjects with normal fundus appearance. SWS cone pathway sensitivity for macular targets was significantly reduced in the patients with ARM compared to normals--15.45 (SD 4.56) dB v 17.22 (0.28) dB, respectively (p<0.0005). There was not only a diffuse loss of sensitivity in ARM patients, but also a localised loss of sensitivity over drusen (p<0.025). Neither the mean age, 69 (8) years, nor the mean visual acuity differed between groups, logMAR 0.09 (0.10) v 0.05 (0.06) for ARM patients v normals, respectively. Patients with soft drusen had lower sensitivity than those with hard drusen (p<0.05). CONCLUSION: A loss of SWS cone pathway sensitivity occurred in most patients with early ARM, despite good visual acuity, demonstrating a loss of visual function that cannot be attributed to ageing changes. The loss of sensitivity, despite good visual acuity, included both a diffuse loss and localised losses.

Synthetic as compared with natural vitamin E is preferentially excreted as alpha-CEHC in human urine: studies using deuterated alpha-tocopheryl acetates.

Alpha-CEHC (2,5,7,8-tetramethyl-2(2'-carboxyethyl)-6-hydroxychroman) is a urinary vitamin E metabolite with a truncated phytyl tail. To test whether natural and synthetic vitamin E are similarly converted to alpha-CEHC, 6 humans consumed 150 mg each RRR-alpha-[5-(C2H3)]- and all rac-alpha-[5,7(C2H3)2]-tocopheryl acetates (d3RRR-alpha- and d6all rac-alpha-tocopheryl acetates, respectively). Plasma was collected at 0, 6, 12 and 24 h; urine (24 h) at 0, 1, 2, 3, 4 and 8 days. Following dosing, plasma was enriched with d3RRR-alpha-tocopherol, while urine was enriched with alpha-CEHC derived from d6all rac-alpha-tocopherol. Thus, synthetic compared with natural vitamin E is preferentially metabolized to alpha-CEHC and excreted.

Angioscotometry with the scanning laser ophthalmoscope. Comparison of the effect of different wavelengths.

PURPOSE: Angioscotomas are scotomata caused by vessel shadows. Their extent may be influenced by physiological and pharmacologic conditions and disease. In this study, the authors quantified angioscotomas in normal subjects using a fundus perimetry technique with a scanning laser ophthalmoscope. They further investigated the influence of two different wavelengths on scotoma depth. METHODS: For blue-on-yellow perimetry, the authors used two different lasers--an argon laser (lambda = 458 nm) for stimuli and a low background and a HeNE (lambda = 594 nm) for a superimposed yellow background. For red-on-red perimetry, the authors used another HeNe laser (lambda = 633 nm). Fundus illumination was provided by an infrared light. Five healthy subjects were examined. Twenty-one to 24 stimuli (200 msec duration, 0.4 degree x 0.4 degree) were presented at different intensities in randomized order in a 5 degrees x 2.5 degrees retinal test field, directly inferior and adjacent to the disk. RESULTS: The depth of scotomas caused by major vessels varied in all subjects and depended on perimetry condition. To quantify the influence of vessels on sensitivity, the authors analyzed psychometric functions for stimuli projected on the vessels and for those far from the vessels. The authors found a significant difference for targets on the vessel compared to those far, which was more pronounced for the blue-on-yellow condition. CONCLUSIONS: Angioscotomas are detected better with blue targets on a yellow background than with red-on-red perimetry. The greater light absorption by hemoglobin and oxyhemoglobin at short wavelengths compared to longer wavelengths is not compensated for by visual mechanisms.

Foveal cone photopigment distribution: small alterations associated with macular pigment distribution.

PURPOSE: To map the photopigment distribution of central foveal cones in healthy adult subjects before potential onset of age-related macular degeneration. To compare alterations in cone photopigment distribution to those of macular pigment and examine those loci for subretinal changes. METHODS: Eleven healthy subjects (age range, 31-59 years) underwent reflectometry with a scanning laser ophthalmoscope. The difference in cone photopigment density in the fovea was mapped for the long-wavelength- and middle-wavelength-sensitive cones, using 594-nm light. Macular pigment was mapped with 488-nm and 514-nm light. Subretinal changes were investigated with infrared imaging (830-860 nm). RESULTS: Most subjects had small alterations in the regularity of their foveal cone photopigment distribution. Alterations were spatially related to macular pigment alterations but not to the presence of subretinal defects. Subjects were classified into three groups according to the type of alterations in the regularity of pigment distributions: central peak of photopigment and macular pigment, small foveal alterations, and broad distribution with missing central peak of photopigment or macular pigment. The resultant groups differed significantly in age, 43, 46, and 59 years, for groups 1, 2, and 3, respectively (P < 0.05). CONCLUSIONS: Small alterations in the distributions of foveal cone photopigment or macular pigment were found that varied among the subjects. Larger alterations in older subjects may indicate changes in foveal architecture with age, including potential vulnerability of central cones before the onset of clinically significant changes in the retinal pigment epithelium.

A psychophysical technique for measuring cone photopigment bleaching.

A new, clinically applicable test has been developed to measure the bleaching of the foveal cone photopigments. This noninvasive test is called steady-state color matching. Steady-state color matching is based on the dependence of a color match on the optical density of the cone photopigments. By measuring the color match as a function of retinal illuminance, it is possible to compute the optical density of the cone photopigments at each illuminance. Thus, abnormalities of photopigment bleaching can be detected. This study demonstrates that the technique is readily performed by a clinical population. Patients with central serous retinopathy and retinitis pigmentosa are shown to have low effective optical densities.

Cone photopigment bleaching abnormalities in diabetes.

We have used a color-matching technique to obtain estimates of the optical density of cone photopigments as a function of retinal illuminance in patients with insulin-dependent diabetes mellitus (IDDM). We found that the half-bleach illuminance of some patients is abnormally high. That is, it takes more light to bleach an equivalent amount of photopigment in these patients. Since low illuminance color matches for these patients are normal, this implies that these patients have normal amounts of photopigment, but the photopigment is not bleaching normally. This result clearly points to abnormalities in the outer retina of these diabetic patients. The most likely causes of this abnormality are either decreases in the ability of the cones to absorb light, or an increased rate of regeneration of the cone photopigments.

Quantification of cystoid changes in diabetic maculopathy.

PURPOSE: In patients with diabetic macular edema and cysts, quantification of the extent of the cystoid formation has been difficult. This study was performed to introduce reliable measurements of cysts, the quantification of the extent, and its relation to visual acuity. METHODS: Fluorescein angiography generated with a scanning laser ophthalmoscope provided detailed recognition not only of the foveal microvasculature, but also of well-demarcated cystoid formations in the early phases. The sampling area included the central 2.5 degrees of the fovea. Using digital image analysis, two independent observers estimated the area covered by cysts, the number of cysts, and the foveal avascular zone (FAZ). RESULTS: Twenty-three subjects with diabetes and macular cysts were enrolled in the current study. The mean area of the cysts was 0.315 +/- 0.241 mm2 (0.05 mm2 to 0.9 mm2), and the number of cysts ranged from 1 to 7. Both parameters, area of cysts (r2 = 0.61), and number of cysts (r2 = 0.48) showed a significant correlation with visual acuity (P < 0.01), whereas FAZ (0.08 to 0.58 mm2) showed no significant correlation with visual acuity. CONCLUSIONS: Fluorescein angiography allows a reproducible quantification of the extent of macular cysts. The relation of visual acuity to the number of cysts and to the area covered by the cystoid formation is highly significant. Thus, both these measures can provide an objective criterion for the estimation of visual prognosis and an outcome for evaluation therapy techniques.

Three dimensional imaging in age-related macular degeneration.

The ability of confocal scanning laser tomography to quantify the subretinal features was investigated. The slope ratios (anterior slope/posterior slope) of the axial intensity profiles were analyzed. The data fromnormal subjects showed only minimal influence of individual ocular pigmentation. In the eyes with agerelated macular degeneration, the light-tissue interactions vary according to the type of retinal features. Three-dimensional information could be obtained from the axial intensity profiles.

Scanning laser reflectometry of retinal and subretinal tissues.

Measurements of the human ocular fundus that make use of the light returning through the pupil are called reflectometry. Early reflectometry studies were limited by poor light return from the retina and strong reflections from the anterior surface of the eye. Artifacts produced misleading results in diseases like age-related macular degeneration. Novel laser sources, scanning, confocal optics, and digital imaging provide improved sampling of the signal from the tissues of interest: photoreceptors and retinal pigment epithelial cells. A wider range of wavelengths is now compared, including the near infrared. Reflectometry now provides functional mapping, even in severe pathology.

Multiply scattered light tomography and confocal imaging: detecting neovascularization in age-related macular degeneration.

A novel technique, Multiply Scattered Light Tomography (MSLT), and confocal Infrared Imaging are used to provide diagnostic information using a comfortable, rapid, and noninvasive method. We investigated these techniques in detecting neovascularization in age-related macular degeneration. The MSLT used a Vertical Cavity Surface Emitting Laser (VCSEL) at 850 nm, while the confocal imaging technique used either the VCSEL or a 790 nm laser diode. Both were implemented into the topographical scanning system (TopSS, Laser Diagnostic Technologies, Inc.) Confocal imaging with both lasers provided different information about neovascularization as a function of focal plane, and different also from MSLT.

The inverse electro-oculogram.

An electro-oculogram ratio of less than one was found to be caused by limited ocular excursions under photopic conditions in a patient with a rod-cone dystrophy. Because this inverse electro-oculogram ratio was not caused by a decrease in standing potential under photopic conditions, it should be considered an artefact.

Effects of flicker adaptation and temporal gain control on the flicker ERG.

The flicker electroretinogram (ERG) to stimuli varying in temporal frequency and modulation depth was recorded to investigate retinal gain control. With increasing modulation of a sinusoidal flickering stimulus, the flicker ERG shows an amplitude compression and a phase retardation (of the fundamental component) at 16 Hz, an amplitude expansion and a phase advance around 40-48 Hz, and an approximately linear response at 72 Hz. With sum-of-two-sinusoids stimuli, the second stimulus enhances the fundamental response to a 40 or 48 Hz test stimulus at low modulations, and reduces the variation in phase with modulation. This interaction depends primarily on the amplitude of the response to the second stimulus, but not its frequency. With temporally alternating stimuli, a similar but smaller interaction effect is measured. The results suggest that there is an active nonlinear gain control mechanism in the outer retina and this gain control works by adjusting the phase delay of the retinal response. The phase control mechanism is set by the amplitude of the outer retinal response integrated over time.

The Abney effect: chromaticity coordinates of unique and other constant hues.

We compared unique and other constant hue loci measured at a fixed retinal illuminance for the same observers. When expressed in Judd chromaticity coordinates, unique hue and constant hue data agreed. Unique blue loci were curved, and unique red and green loci were noncollinear. These data imply that unique hues are not a linear transformation of color matching functions. Linear models are only an approximation, even at a single luminance level.

Short wavelength automated perimetry in age related maculopathy.

BACKGROUND/AIMS: Previous studies reported the predictive value of the short wavelength sensitive (SWS) cone mediated sensitivity for visual outcome in age related macular degeneration. In this study SWS sensitivity was measured by commercially available blue on yellow perimetry in patients with non-exudative age related maculopathy (ARM) and compared with the presence of morphological risk factors and the status of the fellow eye. METHODS: In a prospective cross sectional study, 126 patients (57 males, 69 females, mean age 71 (SD 6) years) with ARM (visual acuity >20/50) were tested. Central visual fields (blue on yellow) were obtained with a conventional perimeter. Fundus slides were graded by two independent observers for soft drusen and presence of focal hyperpigmentation. RESULTS: Mean sensitivity and standard deviation of all patients exhibited a significant reduction with age. Patients with soft drusen had significantly lower sensitivity than those without, whereas there were no differences in visual acuity (log MAR). Sensitivity was also reduced in those eyes with fellow eyes having a sight threatening complication of age related macular degeneration (AMD). Eyes with focal hyperpigmentation compared with those without had no loss of sensitivity, but did have a significant decrease in the central part of the field compared with the more eccentric. CONCLUSION: SWS sensitivity loss is associated with common risk factors for progression to AMD. Short wavelength automated perimetry is moderately rapid and readily available. It may serve as a tool in future ARM trials.

Foveal cone spacing and cone photopigment density difference: objective measurements in the same subjects.

Foveal cone spacing was measured in vivo using an objective technique: ocular speckle interferometry. Cone packing density was computed from cone spacing data. Foveal cone photopigment density difference was measured in the same subjects using retinal densitometry with a scanning laser ophthalmoscope. Both the cone packing density and cone photopigment density difference decreased sharply with increasing retinal eccentricity. From the comparison of both sets of measurements, the computed amounts of photopigment per cone increased slightly with increasing retinal eccentricity. Consistent with previous results, decreases in cone outer segment length are over-compensated by an increase in the outer segment area, at least in retinal eccentricities up to 1 deg.

Flicker brightness enhancement and visual nonlinearity.

The purpose of this study was to investigate the nonlinear mechanism underlying brightness enhancement, in which a flickering stimulus appears brighter than a steady stimulus of equal mean luminance. The flickering and matching stimuli were temporally alternated. Both were cosine windowed to minimize the potential effects of temporal transients. Subjects adjusted the amplitude of the matching stimulus to match it in brightness to the flickering stimulus. The temporal frequency, modulation, and waveform of the flickering stimulus were varied. With sinusoidal flicker, brightness enhancement increased with increasing modulation at all frequencies, peaking at about 16 Hz at full modulation. The results were modeled by a broad temporal filter followed by a single accelerating nonlinearity. The derived temporal sensitivity of the early filter inferred from brightness enhancement decreased more slowly at high frequencies than the filter(s) inferred from flicker modulation thresholds. With low frequency sawtooth flicker, brightness enhancement was phase-dependent at low, but not at high modulations, suggesting that multiple neural mechanisms may also be involved in addition to an early nonlinearity.