Facial mimicry in the congenitally blind.

Imitation is one of the core building blocks of human social cognition, supporting capacities as diverse as empathy, social learning, and knowledge acquisition1. Newborns' ability to match others' motor acts, while quite limited initially, drastically improves during the first months of development2. Of notable importance to human sociality is our tendency to rapidly mimic facial expressions of emotion. Facial mimicry develops around six months of age3, but because of its late emergence, the factors supporting its development are relatively unknown. One possibility is that the development of facial mimicry depends on seeing emotional imitative behavior in others4. Alternatively, the drive to imitate facial expressions of emotion may be independent of visual learning and be supported by modality-general processes. Here we report evidence for the latter, by showing that congenitally blind participants facially imitate smiles heard in speech, despite having never seen a facial expression.

Uveal melanoma: management and outcome of patients with extraocular spread.

BACKGROUND Extraocular spread is thought to be a negative prognostic factor on the survival in patients with uveal melanoma. Enucleation was the standard treatment in these patients. Today, depending on the size of the tumour and the type of extraocular extension, eye-preserving irradiation treatments, such as proton beams or radioactive plaques, may be employed. METHODS 2256 patients were treated between 2000 and 2007 at the Institut Curie, Paris, France for a uveal melanoma. 67 patients (3.0%) presented an extraocular extension. A retrospective study was performed to evaluate the patients' outcomes with regard to tumour recurrence and survival. RESULTS Eye-conserving treatment was employed in 38 (52.8%) patients. Enucleation was performed in 29 (47.2%) patients. The median follow-up was 38 (range 7 to 79) months with an overall survival rate at 5 years of 40.4% in enucleated patients and 79.3% in the eye-conserving treatment group (protons n=19, iodine-125 plaque n=19) (p=0.01; Kaplan-Meier analysis). No tumour recurrence was observed in any group. The degree of extraocular spread as well as the clinical characteristics tumour location, retinal detachment, ciliary body involvement (p<0.01; chi(2) test) and tumour thickness (p=0.04; chi(2) test) influenced the choice of treatment. Age, tumour diameter, involvement of optic nerve, vitreous haemorrhage and the amount of pigment did not have any influence. CONCLUSIONS Tumour recurrence rates and survival rates were not adversely affected in patients receiving conservative eye treatment. This may thus represent a therapeutic option in certain patients with extraocular spread.

Gaze changes with binocular versus monocular viewing in age-related macular degeneration.

PURPOSE: To determine and explain gaze changes during binocular versus monocular viewing in patients with age-related macular degeneration (AMD). DESIGN: Cross-sectional study. PARTICIPANTS: Twenty-nine patients with bilateral late-stage AMD. METHODS: Distance acuity and fundus pathologic features were evaluated. Eye position was recorded while viewing a circular fixation target under monocular and binocular viewing conditions using an infrared eye tracker (SMI Gazetracker, SensoMotoric, Germany; Eyelink Software 2.04). Gaze changes were quantified by calculating the mean x-coordinate and y-coordinate eye position of the center of the bivariate contour ellipse area for a 30-second fixation task under both viewing conditions. Retinal loci used for monocular fixation for each eye were determined using the scanning laser ophthalmoscope (SLO; SLO 101, Rodenstock, Munich, Germany). MAIN OUTCOME MEASURE: Gaze position. RESULTS: Nine patients showed no shift in gaze position from monocular to binocular viewing. Three patients demonstrated a shift in both eyes, and 17 patients demonstrated a shift in only 1 eye. The mean shift was 4.7+/-5 degrees (standard deviation). The shift in gaze position in the worse eye was predictive of the distance between the 2 monocular preferred retinal loci (PRLs; better and worse eye; r(2) = 0.59; P<0.0001), whereas there was no association between the shift in gaze position in the better eye and distance (r(2) = 0.00; P = 0.91). CONCLUSIONS: Most AMD patients shift gaze position in 1 or both eyes when viewing binocularly compared with monocularly. These changes suggest that different retinal locations are used for fixation under the 2 viewing conditions. The SLO data showed that these patients are likely to demonstrate monocular PRLs that fall on noncorresponding areas. These results may have implications for the effective development of eccentric viewing and binocular behavior of AMD patients.

Age-related macular disease: how to assess the retina using scanning laser techniques?

Age-related macular disease (AMD) is the leading cause of legal blindness among the elderly in Western nations. The magnitude of the problem will undoubtedly grow, as age is a significant risk factor and the number of people aged 65 and over is projected to increase. The most frequent cause of severe visual loss associated with AMD is irreversible degeneration of the overlying neurosensory retina, caused by the growth of choroidal neovascularization or, alternatively, the development of geographic atrophy of the retinal pigment epithelium. Today, we are able to image the human retina in vivo. Recently developed imaging techniques provide better assessment of retinal pathology than conventional ophthalmoscopy alone. This overview presents the most recent devices available for retinal imaging, which mainly exploit laser technology such as scanning laser ophthalmoscopy. Its basic principles, as well as its characteristics for imaging and functional assessment of the retina, are described. Lastly, potential benefits for clinical routine, rehabilitation strategies in AMD, and future research aspects are discussed.

Fixation stability using central and pericentral fixation targets in patients with age-related macular degeneration.

PURPOSE: To determine fixation stability for central and pericentral fixation targets in patients with age-related macular degeneration (AMD). DESIGN: Comparative study. PARTICIPANTS: Twelve patients having late-stage AMD involving the fovea and 10 age-matched controls having no other eye diseases and visual acuity better than 20/25. METHODS: Six different fixation targets (1 degrees cross; 1 degrees filled circle; 1 degrees letter x; small 4-point diamond; large 4-point diamond using dimensions as in a field analyzer; large-crossover whole-image diagonal with open 1 degrees center) were presented on a high-resolution monitor. Before examination, subjects were given verbal instructions to move their eye to see the center of the target best. Fixation stability was measured for the preferred eye, with the fellow eye occluded, using a gaze tracker. Fixation stability was quantified by calculating the bivariate contour ellipse area (BCEA) over 30 seconds for each target. For statistical analysis, BCEA values (minutes of arc2) were converted into their logarithms. The absolute retinal scotoma for the study eye was determined using a scanning laser ophthalmoscope. MAIN OUTCOME MEASURE: Bivariate contour ellipse area. RESULTS: Visual acuity in patients (age range, 57-87 years) ranged from 20/32 to 20/600. The lowest BCEA values were found for the 1 degrees letter x in patients (mean, 12052.2%+/-254.0%) and for the 1 degrees cross in normal subjects (mean, 1286.9%+/-47.8%); the highest BCEA values were found for the small 4-point diamond in patients (mean, 23109.5%+/-298.3%) and for the large 4-point diamond in normals (age range, 62-79 years) (mean, 3229.2%+/-105.4%). The difference between the targets was significant for normal subjects (analysis of variance [ANOVA], P<0.01) but not for patients (ANOVA, P>0.05). In normals, BCEA values were significantly lower for central fixation targets than for pericentral fixation targets (P<0.01). CONCLUSION: Fixation is significantly less stable for pericentral fixation targets in normal subjects, indicating an advantage for central fixation targets. These results are particularly significant for any clinical and experimental testing method that requires the patient to maintain stable fixation.

Localized retinal electrophysiological and fundus autofluorescence imaging abnormalities in maternal inherited diabetes and deafness.

PURPOSE: To investigate retinal function in patients with maternally inherited diabetes and deafness (MIDD) and to correlate the findings with fundus autofluorescence (FAF) imaging. METHODS: FAF was imaged in five patients (age range, 49-60 years) confirmed to have the mitochondrial DNA nucleotide A3243G point mutation. Retinal function was measured by full-field (Ganzfeld) electroretinography (ERG) and pattern ERG, incorporating the International Society for Clinical Electrophysiology of Vision (ISCEV) standards. Multifocal ERG (mfERG) was also performed. For analysis of the mfERG data, five regional ring groups of equal eccentricity were formed. For each ring, the peak amplitude (defined as the difference between P1 and N1) and the implicit time of P1 were determined and compared with normative values. RESULTS: Visual acuity in the patients was between 20/20 and 20/40 (Early Treatment Diabetic Retinopathy Study [ETDRS] chart). Irregular increased FAF signals were observed adjacent to and between areas of atrophy of the retinal pigment epithelium (RPE). Ganzfeld ERGs were within normal limits in three patients. Pattern ERG was abnormal in five eyes of three patients. mfERG peak amplitude abnormalities were particularly present in rings 2 and 3 and were consistent with the distribution of FAF abnormalities. In all but one eye, no implicit times changes were present. CONCLUSIONS: Significant mfERG abnormalities with normal Ganzfeld ERG are consistent with nonuniform damage to the central retina in MIDD, in keeping with the FAF findings. Reduced peak amplitudes with normal implicit times in the mfERG suggest localized loss of function and may indicate damage to the cone photoreceptor outer segments or cone photoreceptor loss in MIDD.

Photopic and scotopic fine matrix mapping of retinal areas of increased fundus autofluorescence in patients with age-related maculopathy.

PURPOSE: To investigate photopic and scotopic sensitivity of retinal areas that show increased fundus autofluorescence (FAF) in patients with age-related maculopathy (ARM). METHODS: FAF was imaged with a modified confocal scanning laser ophthalmoscope (cSLO). Fine matrix mapping (FMM) was performed with a modified field analyzer. Photopic and scotopic thresholds were obtained at 100 locations on a 9 degrees x 9 degrees matrix with 1 degrees spacing, centered on a macular area of increased FAF. Inclusion criteria included ARM fundus changes, areas of increased FAF, central and stable fixation, and visual acuity of 20/40 or better. RESULTS: FAF images were reviewed in 436 patients with age-related maculopathy (ARM), of whom 38 met the inclusion criteria. FMM was performed in seven eyes of seven patients. Areas of increased FAF in patients with late ARM (choroidal neovascularization or geographic atrophy) showed normal or only mildly abnormal photopic, but severely reduced scotopic, sensitivity. The central area of increased FAF corresponding to a large foveal druse in a patient with ARM showed moderately reduced photopic and severely reduced scotopic sensitivity. In the other patients with ARM with drusen, areas of increased FAF showed normal or near-normal photopic sensitivity, but moderately reduced scotopic sensitivity. CONCLUSIONS: In retinal areas of increased FAF in patients with ARM, scotopic sensitivity loss considerably exceeded photopic sensitivity loss. This finding is in line with histologic data that have demonstrated a preferential loss of rods in ARM, but does not explain the magnitude of sensitivity loss. The study shows that increased FAF in ARM has a functional correlate.

Visual acuity and contrast sensitivity in patients with neovascular age-related macular degeneration. Results from the Radiation Therapy for Age-Related Macular Degeneration (RAD-) Study.

BACKGROUND: Patients with advanced age-related macular degeneration (AMD) suffer not only from impairment in central visual acuity (VA), but also from reduction in contrast sensitivity (CS). We examined VA and CS changes over time in patients with subfoveal choroidal neovascularizations (CNV) as well as the correlation between the two parameters. METHODS: VA was determined according to a standardized protocol with the Early Treatment Diabetic Retinopathy (ETDRS) chart. CS was measured with Pelli-Robson charts. The angiographic characteristics of CNV and the presence of CNV in the fellow eye as well as gender and age were evaluated as possible prognostic factors of VA and CS progression. Two hundred and five patients with neovascular AMD were recruited within the Radiation Therapy for Age-Related Macular Degeneration (RAD) Study and were reviewed over 2 years. The treatment and control groups showed no significant difference for VA or for CS ( P>0.05), and both groups were considered together. RESULTS: At baseline, mean VA was 55.6+/-14.5 SD letters (EDTRS chart), and mean CS was 22.8+/-6.9 letters (Pelli-Robson chart). Spearman Correlation Coefficient ( r(s)) between VA and CS was r(s)=0.60, P=0.0001. Over 2 years the mean VA loss was 23.6+/-21.4 letters and mean CS reduction was 9.0+/-9.7 letters. Agreement between change of VA and change of CS was moderate ( r(s)=0.65, P=0.0001; kappa coefficient (grouped into VA loss < or =15, >15, >30 letters; CS loss < or =6, >6, >15 letters) kappa=0.43, 95% CI [0.32;0.54]). Proportional hazard models did not show any apparent influence of type of CNV, or CNV in the fellow eye, on change in VA and CS. CONCLUSION: The results indicate that VA and CS do not always show the same progression in visual function loss although they show a moderate correlation in eyes with neovascular AMD. Both parameters provide important information about visual disability and should be evaluated as outcome in interventional studies.

An early-onset autosomal dominant macular dystrophy (MCDR3) resembling North Carolina macular dystrophy maps to chromosome 5.

PURPOSE: To characterize the phenotype of an autosomal dominant macular dystrophy and identify the chromosomal locus. METHODS: Thirteen members of a four-generation, nonconsanguineous British family were examined clinically and also underwent automated perimetry, fundus fluorescein angiography, and fundus autofluorescence imaging. After informed consent was obtained, blood samples were taken for DNA extraction, and genetic linkage analysis was performed. RESULTS: The retinal changes have an early age of onset and are confined to the macular region. The macular abnormalities vary from mild retinal pigment epithelium (RPE) pigmentary change to atrophy. Drusen-like deposits are present to various degrees and are characteristic of the phenotype. Subretinal neovascular membrane (SRNVM) is an established complication. Genetic linkage analysis established linkage to chromosome 5, region p13.1-p15.33 with a maximum LOD score of 3.61 at a recombination fraction of 0.00 for marker D5S630. The locus for this autosomal dominant macular dystrophy lies between flanking markers D5S1981 and D5S2031. CONCLUSIONS: A novel locus has been identified for early-onset autosomal dominant macular dystrophy on chromosome 5.

An autosomal dominant bull's-eye macular dystrophy (MCDR2) that maps to the short arm of chromosome 4.

PURPOSE: To describe the phenotype of an autosomal dominant macular dystrophy and identify the chromosomal locus. METHODS: Eleven members of a five-generation, nonconsanguineous British family were examined clinically and also underwent automated perimetry, electrodiagnostic testing, fundus fluorescein angiography, and fundus autofluorescence imaging. Blood samples were taken for DNA extraction and linkage analysis was performed. RESULTS: The phenotype is characterized by bull's-eye macular dystrophy first evident in the first or second decade of life. There is mild visual impairment, central scotomata, and electrophysiological testing indicates that most affected individuals have disease confined to the central retina but older subjects have more widespread rod and cone abnormalities, demonstrated by flash ERG. Genetic linkage analysis established linkage to chromosome 4 at p15.2-16.3 with a maximum lod score of 3.03 at a recombination fraction of 0.00 for marker D4S391. The locus for this autosomal dominant macular dystrophy lies between flanking markers D4S3023 and D4S3022, and overlaps the Stargardt 4 locus. CONCLUSIONS: A new locus was identified for a bull's-eye macular dystrophy on the short arm of chromosome 4.

Symmetry of bilateral lesions in geographic atrophy in patients with age-related macular degeneration.

BACKGROUND: As a cause for severe visual loss, geographic atrophy of the retinal pigment epithelium is about half as common as choroidal neovascularization in patients with advanced age-related macular degeneration. To assess symmetry, we determined intraindividual variations of various features of bilateral geographic atrophy in patients with atrophic age-related macular degeneration in a cross-sectional study. METHODS: Patients were examined with the use of a confocal scanning laser ophthalmoscope (Heidelberg Retina Angiograph; Heidelberg Engineering, Heidelberg, Germany). Digital infrared reflection images (excitation, 830 nm) and fundus autofluorescence images (excitation, 488 nm) were recorded. The eyes of each patient were compared regarding number, size, and convex hull of the atrophic areas with the use of image analysis software and with respect to fundus autofluorescence changes in the junctional zone. RESULTS: Seventy-two patients (mean +/- SD age, 76.3 +/- 7.9 years) were examined. The number of atrophic areas ranged from 1 to 23 (mean +/- SD, 4.9 +/- 4.6); the size of geographic atrophy, from 0.18 to 30.20 (mean +/- SD, 7.0 +/- 6.6) mm(2); and the size of the convex hull, from 0.18 to 39.20 (mean +/- SD, 11.7 +/- 8.4) mm(2). No statistically significant difference was found when comparing these variables between each left and right eye: number, P =.62; size, P =.81; and convex hull, P =.78. Identical patterns of fundus autofluorescence were observed in 43 (80%) of 54 patients. CONCLUSIONS: There is intraindividual symmetry in eyes with bilateral geographic atrophy in the presence of a wide range of interindividual variability. The findings are in accordance with the view that age-related macular degeneration is not merely the result of a nonspecific aging process. Symmetric manifestations, rather, reflect specific individual determinants in the pathogenesis and manifestation of the disease.