An evaluation of photographic screening for neovascular age-related macular degeneration.

BACKGROUND: Photographic screening for neovascular age-related macular degeneration (AMD) is not commonly employed because the prevalence of treatable disease is low and fluorescein angiography is considered necessary for the diagnosis of this form of AMD. However, there may be a role for colour retinal imaging in assisting with the diagnosis and triage of subjects with neovascular AMD. The purpose of this study was to evaluate the utility of colour fundus photographs for identifying subjects with potentially treatable neovascular AMD. METHODS: A total of 74 stereo pairs of Kodachrome colour slides of subjects with AMD were evaluated (i) nonstereoscopically, (ii) stereoscopically, and (iii) stereoscopically with visual acuity and visual symptom data. Two retina specialists read the images to identify active exudative lesions. RESULTS: The kappa statistic comparing the retinal specialists diagnosis of treatable neovascular AMD from color slides was excellent. The sensitivity and specificity of nonstereo images for the appropriate categorization of lesions was 0.95 and 0.90 respectively. The evaluation of stereo pairs was more sensitive, but less specific, 0.98, 0.83, as was the evaluation of stereo-pairs with clinical histories and visual acuities, 1.00, 0.77. CONCLUSIONS: The evaluation of colour images for subjects with suspected exudative macular degeneration can be diagnostic for neovascular AMD and may expedite the appropriate referral of patients for more timely angiography and treatment. Incorporating more clinical information for the image evaluators ((i) stereo image pairs and/or (ii) presenting symptomatology and visual acuity data) led to a decrease in the false-negative rate, but also decreased the screening specificity.

Co-occurrence of multiple sclerosis and myasthenia gravis in British Columbia.

We describe eight patients with associated multiple sclerosis (MS) and myasthenia gravis (MG). Patients were less than 50 years old at the time of onset, and seven were female. The clinical course of both MS and MG was mild in most patients. To our knowledge, this represents the largest reported series. We provide further evidence for a nonrandom association of these two diseases and discuss common mechanisms of pathogenesis.

Mechanisms of growth cone guidance and motility in the developing grasshopper embryo.

During neuronal pathfinding in vivo, growth cones must reorient their direction of migration in response to extracellular guidance cues. The developing grasshopper limb bud has proved to be a model system in which to examine mechanisms of growth cone guidance and motility in vivo. In this review we examine the contributions of adhesion and multiple guidance cues (semaphorins 1 and 2) in directing a growth cone steering event. Recent observations have suggested that the tibial pioneer growth cones are not directed via mechanisms of differential adhesivity. We present a model of growth cone steering that suggests a combination of adhesive and guidance receptors are important for a correct steering event and that guidance molecules may be important regulators of adhesive interactions with the actin cytoskeleton.

Discrete roles for secreted and transmembrane semaphorins in neuronal growth cone guidance in vivo.

From the initial stages of axon outgrowth to the formation of a functioning synapse, neuronal growth cones continuously integrate and respond to multiple guidance cues. To investigate the role of semaphorins in the establishment of appropriate axon trajectories, we have characterized a novel secreted semaphorin in grasshopper, gSema 2a. Sema 2a is expressed in a gradient in the developing limb bud epithelium during Ti pioneer axon outgrowth. We demonstrate that Sema 2a acts as chemorepulsive guidance molecule critical for axon fasciculation and for determining both the initial direction and subsequent pathfinding events of the Ti axon projection. Interestingly, simultaneous perturbation of both secreted Sema 2a and transmembrane Sema I results in a broader range and increased incidence of abnormal Ti pioneer axon phenotypes, indicating that different semaphorin family members can provide functionally distinct guidance information to the same growth cone in vivo.

Filopodial adhesion does not predict growth cone steering events in vivo.

Migration of growth cones is in part mediated by adhesive interactions between filopodia and the extracellular environment, transmitting forces and signals necessary for pathfinding. To elucidate the role of substrate adhesivity in growth cone pathfinding, we developed an in vivo assay for measuring filopodial-substrate adhesivity using the well-characterized Ti pioneer neuron pathway of the embryonic grasshopper limb. Using time-lapse imaging and a combination of rhodamine-phalloidin injections and DiI labeling, we demonstrate that the filopodial retraction rate after treatment with cytochalasin D or elastase reflects the degree of filopodial-substrate adhesivity. Measurements of filopodial retraction rates along regions of known differing substrate adhesivities confirmed the use of this assay to examine filopodial-substrate adhesion during in vivo pathfinding events. We analyzed 359 filopodia from 22 Ti growth cones and found that there is no difference between the retraction rates of filopodia extending toward the correct target (on-axis) and filopodia extending away from the correct target (off-axis). These results indicate on-axis and off-axis filopodia have similar substrate adherence. Interestingly, we observed a 300% increase in the extension rates of on-axis filopodia during Ti growth cone turning events. Therefore, in addition to providing filopodia with important guidance information, regional cues are capable of modulating the filopodial extension rate. The homogeneity in filopodial retraction rates, even among these turning growth cones in which differential adhesivity might be expected to be greatest, strongly establishes that differential adhesion does not govern Ti pioneer neuron migration rate or pathfinding. We propose that the presence of local differences in receptor-mediated second messenger cascades and the resulting assembly of force-generating machinery may underlie the ability of filopodial contacts to regulate growth cone steering in vivo.