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Macular Dystrophy (macular + dystrophy)
Selected Abstracts2461: Increasing complexity of ocular genetic diseases : the case of BEST diseaseACTA OPHTHALMOLOGICA, Issue 2010M ABITBOL Purpose Monogenic diseases until recently appeared simple from a molecular genetics point of view but correlations between genotypes and phenotypes still remain difficult to establish in many diseases and for many genes. For autosomal dominant diseases such as Best Vitelliform Macular Dystrophy, supposed to be a juvenile disease, it appears that mutations of BEST1 gene can cause multiple phenotypes including early onset and late onset phenotypes as well as unexpected phenotypes such as RP. We report several novel mutations and their associated phenotypes and describe phenotypes linked to previously reoported mutations for which the phenotype had not been describe at all previously. The role of SOX9, MITF and OTX2 in the incomplete penetrance and the variable expressivity of BVMDs is duscussed as well the potential roles of SNPs occuring in coding exons Methods We used genomic PCR with appropriate primers flanking all the exons of the BEST1 gene in order to amplify them. This Genomic PCR was followed by automated sequencing and careful analysis of the sequences obtained. Results We report the case of an unusual family where the Mother II2 of the proband III1, his maternal aunt II3, his brother III3 and his first cousin IIIIV, the son of his maternal aunt, carry a missense mutatation causing apparently only electrophysiological abnormalities. The Father II1 of the proband III1 turned out to carry a stop codon instead of the fifth normal BEST1 codon. The father did not display any electrophysiological nor any clinical abnormality and has a perfect monocular and binocular vision. In contrast the proband III1 carries both mutations with a severe phenotype. Conclusion This report exemplifies the necessity to study all family members in the case of BVMDs. [source] AER lecture: Some reflections on corneal thicknessACTA OPHTHALMOLOGICA, Issue 2007N EHLERS The corneal thickness as an object for studies was recognized in the renaissance. A value of 1 mm, representing the maximally swollen human cornea, was reported. Optical in vivo measurements were done by Blix in 1880 reporting a thickness of about 0.5 mm, the value that we today know is correct. Blix lived in "the golden age of physiologic optics". His interest was the contribution of the cornea to the optical refraction of the eye, and was thus the distance between the anterior and the posterior surface rather than the thickness of the cornea as such. A biomechanical interest in corneal thickness was initiated by the studies of tonometry, in particular Hans Goldmann's development of applanation tonometry. He predicted correctly that corneal thickness would influence the estimated pressure reading. Another physiological aspect of the cornea is its transparency. Earlier explanations by equal refractive index was revolutionized by the interference theory by David Maurice. Optical transparency required a regular fiber pattern, and thus a stabilized thickness and stromal hydration. This led to extensive interest in the permeability of the limiting layers, in particular the transport of fluid across the endothelium. The physiological concepts required a regulated or stabilized thickness. The thickness as such became interesting. The human cornea is thinner in the center than more peripherally and the central, presumably regulated central thickness (CCT) became a biometric and clinical study object. The exact individual value became of interest. Several optical and later ultrasonic principles were presented. Questions addressed were: Is CCT a life-long, age independent characteristics. Is CCT diagnostic for certain disease conditions (e.g. Macular dystrophy of Groenouw). Is CCT a useful clinical parameter to follow disease processes (e.g. progression in keratoconus or acute changes in graft rejections). Today refractive surgery has revived the interest in biomechanical and optical properties of the cornea. Modern computer technology allows for a description of the "thickness profile" of the entire cornea. This gives us access to an overwhelming amount of data, and reopen many issues of the past. We must realize, however, that what we see is the pendulum swinging back to the problems of the last century. The machinery is smarter but many of the basic questions remain to be solved. [source] 2111: Adaptive optics imaging in hereditary macular diseasesACTA OPHTHALMOLOGICA, Issue 2010K NAKASHIMA Purpose This research aimed at exploring and characterizing differences in vivo between healthy and pathology retinas, hereditary macular diseases at the microscopic scale using a compact adaptive optics (AO) retinal camera and high resolution OCT. Methods Seven RP patients, Cone-rod dystrophies (3), Stargardt diseases (5), Occult macular dystrophies (4) and indeterminate macular dystrophies (4) had undergone en face retinal imaging by AO camera "rtx1" (Imagine Eyes, France). AO images were taken at the eccentricities from 0 deg to 6 deg temporal and nasal from fovea. Each patient was examined using high resolution spectral domain (SD)-OCT and infrared SLO (Spectralis OCT). Results Cellular-resolution images could be obtained in most cases. In inherited retinal dystrophies, AO helped to better evaluate losses of cone cells across the retina. Other microstructures, slightly larger in size than cones, were also visible in several pathological retinas. Hereditary macular disease cases showed loss of cone mosaics. Some of these cases, there were patchy areas of increased reflectance. In Cone rod dystrophy and some other cases, the RPE mosaic was visible where cone had disappeared. Conclusion Cellular-resolution images could be obtained in most cases. In inherited retinal dystrophies, AO helped to better evaluate losses of cone cells across the retina. Other microstructures, slightly larger in size than cones, were also visible in several pathological retinas. Hereditary macular disease cases showed loss of cone mosaics. Some of these cases, there were patchy areas of increased reflectance. In Cone rod dystrophy and some other cases, the RPE mosaic was visible where cone had disappeared. [source] Custom-devised and generic digital enhancement of images for people with maculopathyOPHTHALMIC AND PHYSIOLOGICAL OPTICS, Issue 4 2009Susan J. Leat Abstract Aim:, The purpose of this study was to compare the effectivity, in terms of the potential usefulness, of digital filters based on either contrast sensitivity (CS) or supra-threshold contrast matching (CM) in enhancing pictures images for people with maculopathy and to investigate whether generic filters (not based on an individual's vision loss) are equally as effective. Effectivity is measured by changes in perceived visibility. Methods:, Thirty-five subjects with maculopathy, aged 20,92 years, took part [13 atrophic age-related macular degeneration (ARMD), 14 exudative ARMD, and 8 juvenile macular dystrophy (JMD)]. CS and supra-threshold CM were measured. A range of CS filters (1 or 2-octave wide band-pass filter using a Gabor or polynomial envelope) with different strengths were developed based on the ratio of the individual's contrast threshold and that of a normal age-related group. Similarly filters were developed based on CM at 3.6% and 27.9% contrast. The following generic filters were also applied with different ,strengths': edge enhancement; sharpening; contrast enhancement; Peli's adaptive enhancement; difference of Gaussian; and an equi-emphasis band-pass filter. The filters were applied to images of faces and general scenes. Subjects were asked to rank the perceived visibility of images (to obtain the best version of each filter) and then to rate the perceived visibility of each image filtered with a particular filter. Results:, In general, subjects with atrophic ARMD and JMD preferred the weaker versions of most of the filters, while those with exudative ARMD did not show such a clear preference. Generally, images of faces were preferred with less enhancement than scenes. The filters based on CM were rated as giving significant improvement, while those based on CS and peak emphasis were not preferred. Of the generic filters, the Peli adaptive enhancement filter was most frequently rated as giving a significant improvement (p < 0.05) followed by the contrast enhancement filter. They gave the same perceived enhancement as the custom-devised filters. Conclusions:, Generic filters, which are easier to apply than the custom-devised filters, are appropriate for rehabilitation purposes. [source] Dysregulation of human bestrophin-1 by ceramide-induced dephosphorylationTHE JOURNAL OF PHYSIOLOGY, Issue 18 2009Qinghuan Xiao Best vitelliform macular dystrophy is an inherited autosomal dominant, juvenile onset form of macular degeneration caused by mutations in a chloride ion channel, human bestrophin-1 (hBest1). Mutations in Best1 have also been linked to several other forms of retinopathy. In addition to mutations, hBest1 dysfunction might come about by disruption of other processes that regulate Best1 function. Here we show that hBest1 chloride channel activity is regulated by ceramide and phosphorylation. We have identified a protein kinase C (PKC) phosphorylation site (serine 358) in hBest1 that is important for sustained channel function. Channel activity is maintained by PKC activators, protein phosphatase inhibitors, or pseudo-phosphorylation by substitution of glutamic acid for serine 358. When ceramide levels are elevated by exogenous addition of ceramide to the bath, by addition of bacterial sphingomyelinase, or by hypertonic stress, S358 is rapidly dephosphorylated. The dephosphorylation is mediated by protein phosphatase 2A. Hypertonic stress-induced dephosphorylation is blocked by a dihydroceramide, an inactive form of ceramide, and manumycin, an inhibitor of neutral sphingomyelinase. Our results support a model in which ceramide accumulation during early stages of retinopathy inhibits hBest1 function, leading to abnormal fluid transport across the retina, and enhanced inflammation. [source] 4222: Potential retinal causes: when and how to investigateACTA OPHTHALMOLOGICA, Issue 2010BP LEROY Purpose To describe the retinal conditions that need to be excluded when non-organic visual loss is suspected, and the investigations required to either confirm or exclude them. Methods A case presentation format will be used to illustrate those conditions which can be discovered using psychophysical and electrophysiological tests as well as special imaging including autofluorescence, infrared and red free imaging and spectral-domain optical coherence tomography, in patients in whom a non-organic origin for visual loss is suspected. Results Inherited retinal diseases such as Stargardt macular dystrophy, X-linked retinoschisis and cone dystrophy as well as Batten disease in their early stages all need to be excluded when visual loss is thought to be non-organic. In addition, several acquired retinal conditions such as acute acular neuroretinopathy need to be taken into account. visual field testing, ISCEV-standard full-field flash electroretinography, pattern electroretinography and visual evoked potentials and specialised imaging techniques contribute significantly to making the correct diagnosis. Conclusion Visual loss in a list of organic conditions may mimic non-organic visual loss. Functional testing as well as specialised imaging techniques are essential in differentiating true organic from non-organic visual loss. [source] 4125: Phenotypic variability in association with mutation in RDS/peripherinACTA OPHTHALMOLOGICA, Issue 2010GE HOLDER Purpose To report the clinical and electrophysiological findings associated with autosomal dominant maculopathy caused by mutations in Rds/peripherin. Methods Fifty three individuals with autosomal dominant macular dystrophy and a confirmed molecular diagnosis of Rds/peripherin mutation were ascertained between January 2002 and December 2008. International-standard pattern and full-field electroretinograms (PERG; ERG) were performed in 38 cases. Electro-oculograms (EOG) were performed in 25 cases. Results Fourteen different mutations were identified in the Rds/peripherin gene; 4 of which were novel. Twenty four (45%) patients had the common p.Arg172 Trp allele. The mean age at the time of first symptoms and at diagnosis was 35.0+/- 2.4 and 47.1 +/- 1.5 years old [SEM] respectively. Mean LogMAR visual acuity at presentation was 0.5+/- 0.08 [SEM]. Fundus phenotypes included central atrophy (19 cases), pattern dystrophy (10 cases), maculopathy with flecks (5 cases), and adult vitellifom dystrophy (4 cases). Pattern ERG P50 reduction was seen in 75 of 76 eyes; the majority having undetectable or residual responses, including some cases with preserved visual acuity. ERG ranged from normal to severe reduction in both cone and rod driven responses and were not predictable either from the fundus appearance or from the specific mutation in Rds/peripherin; on addition, marked intra-familial variation could be noted. Conclusion Mutations in the Rds/peripherin gene result in a wide variety of fundus and functional phenotypes. The same mutation can result in profoundly different phenotypes, even within family members. [source] 3335: New modalities for the treatment of corneal dystrophiesACTA OPHTHALMOLOGICA, Issue 2010I CLAERHOUT Purpose To give an overview of current treatment modalities of corneal dystrophies. Results New transplant techniques have changed the way that corneal dystrophies are being treated in the last few years. Phototherapeutic keratectomy is still a very valuable tool for superficial dystrophies. Depending on the layers involved the laser will be set to a depth of 5 to 100µm. DALK is now the preferred method of treatment of most stromal dystrophies, although macular dystrophy is an exception to this rule since there is evidence of endothelial involvement in this dystrophy. Endothelial dystrophies are now almost exclusively being treated by different types of endothelial grafts (DSAEK or DMEK). Conclusion Current treatment of corneal dystrophies has evolved from one size fits all to a more customised treatment schedule, still dependent on the layers involved in the disease. [source] The analysis of fundus autofluorescence patterns in retinal diseasesACTA OPHTHALMOLOGICA, Issue 2007P POPOVIC Purpose: Fundus autofluorescence (AF) imaging is a method that shows accumulation of lipofuscin in the retinal pigment epithelium cells in vivo. Fundus AF may be recorded in retinal diseases either by scanning laser ophthalmoscope or by fundus camera using the appropriate filter. The aim of this study was to analyze the AF pattern by both methods. Methods: 20 patients with different retinal diseases including retinitis pigmentosa, cone-rod dystrophy, Stargardt disease, Best macular dystrophy, central serous retinopathy and age-related macular degeneration were included in the study. AF images were obtained from each subject using a confocal scanning laser ophthalmosope and digital fundus camera. The distribution and amount of AF were compared by the use of both systems. Results: In all disease entities both instruments showed distinct pattern of AF typical for the disease. Areas of high intensity of AF recorded with HRA matched to areas of increased intensity of AF detected with fundus camera. The distribution of areas of low or absent AF also corresponded well in both systems. Images taken with conventional fundus camera were in general lower contrasted and therefore less sharp. This was particularly true for patients with even mild media opacity. The advantage of fundus camera was however a recording of AF of a greater field of view. Conclusions: AF imaging is a very useful noninvasive method for detecting RPE abnormalities. In clinical practice, when scanning laser ophthalmoscope for recording of AF is not available, conventional digital fundus camera can be used for screening of patients suspected to have retinal disease. Care should be taken in patients with nuclear cataract, as the AF image is influenced by the AF of the crystalline lens by a great amount. [source] A new phenotype of macular dystrophy associated with a mitochondrial A3243G mutationCLINICAL & EXPERIMENTAL OPHTHALMOLOGY, Issue 1 2008Sobha Sivaprasad FRCS No abstract is available for this article. [source] | ||||||||||