The Experts below are selected from a list of 303 Experts worldwide ranked by ideXlab platform
Austin Roorda - One of the best experts on this subject based on the ideXlab platform.
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relationship between foveal Cone Structure and visual acuity measured with adaptive optics scanning laser ophthalmoscopy in retinal degeneration
Investigative Ophthalmology & Visual Science, 2018Co-Authors: Kavitha Ratnam, Austin Roorda, Travis C Porco, Katharina G Foote, Panagiota Loumou, Shane Griffin, Jacque L DuncanAbstract:Purpose:To evaluate foveal function in patients with inherited retinal degenerations (IRD) by measuring visual acuity (VA) after correction of higher-order aberrations. Methods:Adaptive optics scanning laser ophthalmoscopy (AOSLO) was used to image Cones in 4 healthy subjects and 15 patients with IRD. The 840-nm scanning laser delivered an "E" optotype to measure AOSLO-mediated VA (AOSLO-VA). Cone spacing was measured at the preferred retinal locus by two independent graders and the percentage of Cones below the average density of 47 age-similar healthy subjects was computed. Cone spacing was correlated with best-corrected VA measured with the Early Treatment of Diabetic Retinopathy Study protocol (ETDRS-VA), AOSLO-VA, and foveal sensitivity. Results:ETDRS-VA significantly correlated with AOSLO-VA (ρ = 0.79, 95% confidence interval [CI] 0.5-0.9). Cone spacing correlated with AOSLO-VA (ρ = 0.54, 95% CI 0.02-0.7), and negatively correlated with ETDRS letters read (ρ = -0.64, 95% CI -0.8 to -0.2). AOSLO-VA remained ≥20/20 until Cones decreased to 40.2% (CI 31.1-45.5) below normal. Similarly, ETDRS-VA remained ≥20/20 until Cones were 42.0% (95% CI 36.5-46.1) below normal. Cone spacing z scores negatively correlated with foveal sensitivity (ρ = -0.79, 95% CI -0.9 to -0.4) and foveal sensitivity was ≥35 dB until Cones were 43.1% (95% CI 39.3-46.6) below average. Conclusions:VA and foveal Cone spacing were weakly correlated until Cones were reduced by 40% to 43% below normal. The relationship suggests that VA is an insensitive measure of foveal Cone survival; Cone spacing may be a more sensitive measure of Cone loss.
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Cone Structure imaged with adaptive optics scanning laser ophthalmoscopy in eyes with nonneovascular age related macular degeneration
Investigative Ophthalmology & Visual Science, 2013Co-Authors: Shiri Zayitsoudry, Jacque L Duncan, Reema Syed, Moreno Menghini, Austin RoordaAbstract:PURPOSE: To evaluate Cone spacing using adaptive optics scanning laser ophthalmoscopy (AOSLO) in eyes with nonneovascular AMD, and to correlate progression of AOSLO-derived Cone measures with standard measures of macular Structure. METHODS: Adaptive optics scanning laser ophthalmoscopy images were obtained over 12 to 21 months from seven patients with AMD including four eyes with geographic atrophy (GA) and four eyes with drusen. Adaptive optics scanning laser ophthalmoscopy images were overlaid with color, infrared, and autofluorescence fundus photographs and spectral domain optical coherence tomography (SD-OCT) images to allow direct correlation of Cone parameters with macular Structure. Cone spacing was measured for each visit in selected regions including areas over drusen (n = 29), at GA margins (n = 14), and regions without drusen or GA (n = 13) and compared with normal, age-similar values. RESULTS: Adaptive optics scanning laser ophthalmoscopy imaging revealed continuous Cone mosaics up to the GA edge and overlying drusen, although reduced Cone reflectivity often resulted in hyporeflective AOSLO signals at these locations. Baseline Cone spacing measures were normal in 13/13 unaffected regions, 26/28 drusen regions, and 12/14 GA margin regions. Although standard clinical measures showed progression of GA in all study eyes, Cone spacing remained within normal ranges in most drusen regions and all GA margin regions. CONCLUSIONS: Adaptive optics scanning laser ophthalmoscopy provides adequate resolution for quantitative measurement of Cone spacing at the margin of GA and over drusen in eyes with AMD. Although Cone spacing was often normal at baseline and remained normal over time, these regions showed focal areas of decreased Cone reflectivity. These findings may provide insight into the pathophysiology of AMD progression. (ClinicalTrials.gov number, NCT00254605).
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relationship between foveal Cone Structure and clinical measures of visual function in patients with inherited retinal degenerations
Investigative Ophthalmology & Visual Science, 2013Co-Authors: Jacque L Duncan, Kavitha Ratnam, Joseph Carroll, Travis C Porco, Austin RoordaAbstract:PURPOSE. To study the relationship between Cone spacing and density and clinical measures of visual function near the fovea. METHODS. High-resolution images of the photoreceptor mosaic were obtained with adaptive optics scanning laser ophthalmoscopy from 26 patients with inherited retinal degenerations. Cone spacing measures were made close to or at the foveal center (mean [SD] eccentricity, 0.02 [0.03] degree; maximum eccentricity, 0.13 degree) and were converted to Z-scores, fraction of Cones, and percentage-of-Cones-below-average compared with normal values for each location (based on 37 age-similar visually normal eyes). Z-scores and percentage of Cones below average were compared with best-corrected visual acuity (VA) and foveal sensitivity. RESULTS. Visual acuity was significantly correlated with Cone spacing (Spearman rank correlation q ¼� 0.60, P ¼ 0.003) and was preserved (‡80 letters), despite Cone density measures that were 52% below normal. Foveal sensitivity showed significant correlation with Cone spacing (q ¼� 0.47, P ¼ 0.017) and remained normal (‡35 decibels), despite density measures that were approximately 52% to 62% below normal. CONCLUSIONS. Cone density was reduced by up to 62% below normal at or near the fovea in eyes with VA and sensitivity that remained within normal limits. Despite a significant correlation with foveal Cone spacing, VA and sensitivity are insensitive indicators of the integrity of the foveal Cone mosaic. Direct, objective measures of Cone Structure may be more sensitive indicators of disease severity than VA or foveal sensitivity in eyes with inherited retinal degenerations. (ClinicalTrials.gov number, NCT00254605.)
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Cone Structure in patients with usher syndrome type iii and mutations in the clarin 1 gene
JAMA Ophthalmology, 2013Co-Authors: Kavitha Ratnam, Austin Roorda, Hanna Vastinsalo, Eevamarja Kaarina Sankila, Jacque L DuncanAbstract:Objective To study macular Structure and function in patients with Usher syndrome type III (USH3) caused by mutations in the Clarin 1 gene (CLRN1). Methods High-resolution macular images were obtained by adaptive optics scanning laser ophthalmoscopy and spectral domain optical coherence tomography in 3 patients with USH3 and were compared with those of age-similar control subjects. Vision function measures included best-corrected visual acuity, kinetic and static perimetry, and full-field electroretinography. Coding regions of the CLRN1 gene were sequenced. Results CLRN1 mutations were present in all the patients; a 20-year-old man showed compound heterozygous mutations (p.N48K and p.S188X), and 2 unrelated women aged 25 and 32 years had homozygous mutations (p.N48K). Best-corrected visual acuity ranged from 20/16 to 20/40, with scotomas beginning at 3° eccentricity. The inner segment–outer segment junction or the inner segment ellipsoid band was disrupted within 1° to 4° of the fovea, and the foveal inner and outer segment layers were significantly thinner than normal. Cones near the fovea in patients 1 and 2 showed normal spacing, and the preserved region ended abruptly. Retinal pigment epithelial cells were visible in patient 3 where Cones were lost. Conclusions Cones were observed centrally but not in regions with scotomas, and retinal pigment epithelial cells were visible in regions without Cones in patients with CLRN1 mutations. High-resolution measures of retinal Structure demonstrate patterns of Cone loss associated with CLRN1 mutations. Clinical Relevance These findings provide insight into the effect of CLRN1 mutations on macular Cone Structure, which has implications for the development of treatments for USH3. Trial Registration clinicaltrials.gov Identifier: NCT00254605
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abnormal Cone Structure in foveal schisis cavities in x linked retinoschisis from mutations in exon 6 of the rs1 gene
Investigative Ophthalmology & Visual Science, 2011Co-Authors: Jacque L Duncan, Kavitha Ratnam, S Sundquist, Yuhua Zhang, David G Birch, Anna S Lucero, M R Meltzer, Nizar Smaoui, Austin RoordaAbstract:PURPOSE. To evaluate macular Cone Structure in patients with X-linked retinoschisis (XLRS) caused by mutations in exon 6 of the RS1 gene. METHODS. High-resolution macular images were obtained with adaptive optics scanning laser ophthalmoscopy (AOSLO) and spectral domain optical coherence tomography (SD-OCT) in two patients with XLRS and 27 age-similar healthy subjects. Retinal Structure was correlated with best-corrected visual acuity, kinetic and static perimetry, fundus-guided microperimetry, full-field electroretinography (ERG), and multifocal ERG. The six coding exons and the flanking intronic regions of the RS1 gene were sequenced in each patient. RESULTS. Two unrelated males, ages 14 and 29, with visual acuity ranging from 20/32 to 20/63, had macular schisis with small relative central scotomas in each eye. The mixed scotopic ERG b-wave was reduced more than the a-wave. SD-OCT showed schisis cavities in the outer and inner nuclear and plexiform layers. Cone spacing was increased within the largest foveal schisis cavities but was normal elsewhere. In each patient, a mutation in exon 6 of the RS1 gene was identified and was predicted to change the amino acid sequence in the discoidin domain of the retinoschisin protein. CONCLUSIONS. AOSLO images of two patients with molecularly characterized XLRS revealed increased Cone spacing and abnormal packing in the macula of each patient, but Cone coverage and function were near normal outside the central foveal schisis cavities. Although Cone density is reduced, the preservation of wave-guiding Cones at the fovea and eccentric macular regions has prognostic and therapeutic implications for XLRS patients with foveal schisis. (Clinical Trials.gov number, NCT00254605.) (Invest Ophthalmol Vis Sci. 2011;52:9614‐9623) DOI:10.1167/iovs.11-8600
Jacque L Duncan - One of the best experts on this subject based on the ideXlab platform.
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relationship between foveal Cone Structure and visual acuity measured with adaptive optics scanning laser ophthalmoscopy in retinal degeneration
Investigative Ophthalmology & Visual Science, 2018Co-Authors: Kavitha Ratnam, Austin Roorda, Travis C Porco, Katharina G Foote, Panagiota Loumou, Shane Griffin, Jacque L DuncanAbstract:Purpose:To evaluate foveal function in patients with inherited retinal degenerations (IRD) by measuring visual acuity (VA) after correction of higher-order aberrations. Methods:Adaptive optics scanning laser ophthalmoscopy (AOSLO) was used to image Cones in 4 healthy subjects and 15 patients with IRD. The 840-nm scanning laser delivered an "E" optotype to measure AOSLO-mediated VA (AOSLO-VA). Cone spacing was measured at the preferred retinal locus by two independent graders and the percentage of Cones below the average density of 47 age-similar healthy subjects was computed. Cone spacing was correlated with best-corrected VA measured with the Early Treatment of Diabetic Retinopathy Study protocol (ETDRS-VA), AOSLO-VA, and foveal sensitivity. Results:ETDRS-VA significantly correlated with AOSLO-VA (ρ = 0.79, 95% confidence interval [CI] 0.5-0.9). Cone spacing correlated with AOSLO-VA (ρ = 0.54, 95% CI 0.02-0.7), and negatively correlated with ETDRS letters read (ρ = -0.64, 95% CI -0.8 to -0.2). AOSLO-VA remained ≥20/20 until Cones decreased to 40.2% (CI 31.1-45.5) below normal. Similarly, ETDRS-VA remained ≥20/20 until Cones were 42.0% (95% CI 36.5-46.1) below normal. Cone spacing z scores negatively correlated with foveal sensitivity (ρ = -0.79, 95% CI -0.9 to -0.4) and foveal sensitivity was ≥35 dB until Cones were 43.1% (95% CI 39.3-46.6) below average. Conclusions:VA and foveal Cone spacing were weakly correlated until Cones were reduced by 40% to 43% below normal. The relationship suggests that VA is an insensitive measure of foveal Cone survival; Cone spacing may be a more sensitive measure of Cone loss.
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Cone Structure imaged with adaptive optics scanning laser ophthalmoscopy in eyes with nonneovascular age related macular degeneration
Investigative Ophthalmology & Visual Science, 2013Co-Authors: Shiri Zayitsoudry, Jacque L Duncan, Reema Syed, Moreno Menghini, Austin RoordaAbstract:PURPOSE: To evaluate Cone spacing using adaptive optics scanning laser ophthalmoscopy (AOSLO) in eyes with nonneovascular AMD, and to correlate progression of AOSLO-derived Cone measures with standard measures of macular Structure. METHODS: Adaptive optics scanning laser ophthalmoscopy images were obtained over 12 to 21 months from seven patients with AMD including four eyes with geographic atrophy (GA) and four eyes with drusen. Adaptive optics scanning laser ophthalmoscopy images were overlaid with color, infrared, and autofluorescence fundus photographs and spectral domain optical coherence tomography (SD-OCT) images to allow direct correlation of Cone parameters with macular Structure. Cone spacing was measured for each visit in selected regions including areas over drusen (n = 29), at GA margins (n = 14), and regions without drusen or GA (n = 13) and compared with normal, age-similar values. RESULTS: Adaptive optics scanning laser ophthalmoscopy imaging revealed continuous Cone mosaics up to the GA edge and overlying drusen, although reduced Cone reflectivity often resulted in hyporeflective AOSLO signals at these locations. Baseline Cone spacing measures were normal in 13/13 unaffected regions, 26/28 drusen regions, and 12/14 GA margin regions. Although standard clinical measures showed progression of GA in all study eyes, Cone spacing remained within normal ranges in most drusen regions and all GA margin regions. CONCLUSIONS: Adaptive optics scanning laser ophthalmoscopy provides adequate resolution for quantitative measurement of Cone spacing at the margin of GA and over drusen in eyes with AMD. Although Cone spacing was often normal at baseline and remained normal over time, these regions showed focal areas of decreased Cone reflectivity. These findings may provide insight into the pathophysiology of AMD progression. (ClinicalTrials.gov number, NCT00254605).
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relationship between foveal Cone Structure and clinical measures of visual function in patients with inherited retinal degenerations
Investigative Ophthalmology & Visual Science, 2013Co-Authors: Jacque L Duncan, Kavitha Ratnam, Joseph Carroll, Travis C Porco, Austin RoordaAbstract:PURPOSE. To study the relationship between Cone spacing and density and clinical measures of visual function near the fovea. METHODS. High-resolution images of the photoreceptor mosaic were obtained with adaptive optics scanning laser ophthalmoscopy from 26 patients with inherited retinal degenerations. Cone spacing measures were made close to or at the foveal center (mean [SD] eccentricity, 0.02 [0.03] degree; maximum eccentricity, 0.13 degree) and were converted to Z-scores, fraction of Cones, and percentage-of-Cones-below-average compared with normal values for each location (based on 37 age-similar visually normal eyes). Z-scores and percentage of Cones below average were compared with best-corrected visual acuity (VA) and foveal sensitivity. RESULTS. Visual acuity was significantly correlated with Cone spacing (Spearman rank correlation q ¼� 0.60, P ¼ 0.003) and was preserved (‡80 letters), despite Cone density measures that were 52% below normal. Foveal sensitivity showed significant correlation with Cone spacing (q ¼� 0.47, P ¼ 0.017) and remained normal (‡35 decibels), despite density measures that were approximately 52% to 62% below normal. CONCLUSIONS. Cone density was reduced by up to 62% below normal at or near the fovea in eyes with VA and sensitivity that remained within normal limits. Despite a significant correlation with foveal Cone spacing, VA and sensitivity are insensitive indicators of the integrity of the foveal Cone mosaic. Direct, objective measures of Cone Structure may be more sensitive indicators of disease severity than VA or foveal sensitivity in eyes with inherited retinal degenerations. (ClinicalTrials.gov number, NCT00254605.)
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Cone Structure in patients with usher syndrome type iii and mutations in the clarin 1 gene
JAMA Ophthalmology, 2013Co-Authors: Kavitha Ratnam, Austin Roorda, Hanna Vastinsalo, Eevamarja Kaarina Sankila, Jacque L DuncanAbstract:Objective To study macular Structure and function in patients with Usher syndrome type III (USH3) caused by mutations in the Clarin 1 gene (CLRN1). Methods High-resolution macular images were obtained by adaptive optics scanning laser ophthalmoscopy and spectral domain optical coherence tomography in 3 patients with USH3 and were compared with those of age-similar control subjects. Vision function measures included best-corrected visual acuity, kinetic and static perimetry, and full-field electroretinography. Coding regions of the CLRN1 gene were sequenced. Results CLRN1 mutations were present in all the patients; a 20-year-old man showed compound heterozygous mutations (p.N48K and p.S188X), and 2 unrelated women aged 25 and 32 years had homozygous mutations (p.N48K). Best-corrected visual acuity ranged from 20/16 to 20/40, with scotomas beginning at 3° eccentricity. The inner segment–outer segment junction or the inner segment ellipsoid band was disrupted within 1° to 4° of the fovea, and the foveal inner and outer segment layers were significantly thinner than normal. Cones near the fovea in patients 1 and 2 showed normal spacing, and the preserved region ended abruptly. Retinal pigment epithelial cells were visible in patient 3 where Cones were lost. Conclusions Cones were observed centrally but not in regions with scotomas, and retinal pigment epithelial cells were visible in regions without Cones in patients with CLRN1 mutations. High-resolution measures of retinal Structure demonstrate patterns of Cone loss associated with CLRN1 mutations. Clinical Relevance These findings provide insight into the effect of CLRN1 mutations on macular Cone Structure, which has implications for the development of treatments for USH3. Trial Registration clinicaltrials.gov Identifier: NCT00254605
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abnormal Cone Structure in foveal schisis cavities in x linked retinoschisis from mutations in exon 6 of the rs1 gene
Investigative Ophthalmology & Visual Science, 2011Co-Authors: Jacque L Duncan, Kavitha Ratnam, S Sundquist, Yuhua Zhang, David G Birch, Anna S Lucero, M R Meltzer, Nizar Smaoui, Austin RoordaAbstract:PURPOSE. To evaluate macular Cone Structure in patients with X-linked retinoschisis (XLRS) caused by mutations in exon 6 of the RS1 gene. METHODS. High-resolution macular images were obtained with adaptive optics scanning laser ophthalmoscopy (AOSLO) and spectral domain optical coherence tomography (SD-OCT) in two patients with XLRS and 27 age-similar healthy subjects. Retinal Structure was correlated with best-corrected visual acuity, kinetic and static perimetry, fundus-guided microperimetry, full-field electroretinography (ERG), and multifocal ERG. The six coding exons and the flanking intronic regions of the RS1 gene were sequenced in each patient. RESULTS. Two unrelated males, ages 14 and 29, with visual acuity ranging from 20/32 to 20/63, had macular schisis with small relative central scotomas in each eye. The mixed scotopic ERG b-wave was reduced more than the a-wave. SD-OCT showed schisis cavities in the outer and inner nuclear and plexiform layers. Cone spacing was increased within the largest foveal schisis cavities but was normal elsewhere. In each patient, a mutation in exon 6 of the RS1 gene was identified and was predicted to change the amino acid sequence in the discoidin domain of the retinoschisin protein. CONCLUSIONS. AOSLO images of two patients with molecularly characterized XLRS revealed increased Cone spacing and abnormal packing in the macula of each patient, but Cone coverage and function were near normal outside the central foveal schisis cavities. Although Cone density is reduced, the preservation of wave-guiding Cones at the fovea and eccentric macular regions has prognostic and therapeutic implications for XLRS patients with foveal schisis. (Clinical Trials.gov number, NCT00254605.) (Invest Ophthalmol Vis Sci. 2011;52:9614‐9623) DOI:10.1167/iovs.11-8600
Kavitha Ratnam - One of the best experts on this subject based on the ideXlab platform.
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relationship between foveal Cone Structure and visual acuity measured with adaptive optics scanning laser ophthalmoscopy in retinal degeneration
Investigative Ophthalmology & Visual Science, 2018Co-Authors: Kavitha Ratnam, Austin Roorda, Travis C Porco, Katharina G Foote, Panagiota Loumou, Shane Griffin, Jacque L DuncanAbstract:Purpose:To evaluate foveal function in patients with inherited retinal degenerations (IRD) by measuring visual acuity (VA) after correction of higher-order aberrations. Methods:Adaptive optics scanning laser ophthalmoscopy (AOSLO) was used to image Cones in 4 healthy subjects and 15 patients with IRD. The 840-nm scanning laser delivered an "E" optotype to measure AOSLO-mediated VA (AOSLO-VA). Cone spacing was measured at the preferred retinal locus by two independent graders and the percentage of Cones below the average density of 47 age-similar healthy subjects was computed. Cone spacing was correlated with best-corrected VA measured with the Early Treatment of Diabetic Retinopathy Study protocol (ETDRS-VA), AOSLO-VA, and foveal sensitivity. Results:ETDRS-VA significantly correlated with AOSLO-VA (ρ = 0.79, 95% confidence interval [CI] 0.5-0.9). Cone spacing correlated with AOSLO-VA (ρ = 0.54, 95% CI 0.02-0.7), and negatively correlated with ETDRS letters read (ρ = -0.64, 95% CI -0.8 to -0.2). AOSLO-VA remained ≥20/20 until Cones decreased to 40.2% (CI 31.1-45.5) below normal. Similarly, ETDRS-VA remained ≥20/20 until Cones were 42.0% (95% CI 36.5-46.1) below normal. Cone spacing z scores negatively correlated with foveal sensitivity (ρ = -0.79, 95% CI -0.9 to -0.4) and foveal sensitivity was ≥35 dB until Cones were 43.1% (95% CI 39.3-46.6) below average. Conclusions:VA and foveal Cone spacing were weakly correlated until Cones were reduced by 40% to 43% below normal. The relationship suggests that VA is an insensitive measure of foveal Cone survival; Cone spacing may be a more sensitive measure of Cone loss.
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relationship between foveal Cone Structure and clinical measures of visual function in patients with inherited retinal degenerations
Investigative Ophthalmology & Visual Science, 2013Co-Authors: Jacque L Duncan, Kavitha Ratnam, Joseph Carroll, Travis C Porco, Austin RoordaAbstract:PURPOSE. To study the relationship between Cone spacing and density and clinical measures of visual function near the fovea. METHODS. High-resolution images of the photoreceptor mosaic were obtained with adaptive optics scanning laser ophthalmoscopy from 26 patients with inherited retinal degenerations. Cone spacing measures were made close to or at the foveal center (mean [SD] eccentricity, 0.02 [0.03] degree; maximum eccentricity, 0.13 degree) and were converted to Z-scores, fraction of Cones, and percentage-of-Cones-below-average compared with normal values for each location (based on 37 age-similar visually normal eyes). Z-scores and percentage of Cones below average were compared with best-corrected visual acuity (VA) and foveal sensitivity. RESULTS. Visual acuity was significantly correlated with Cone spacing (Spearman rank correlation q ¼� 0.60, P ¼ 0.003) and was preserved (‡80 letters), despite Cone density measures that were 52% below normal. Foveal sensitivity showed significant correlation with Cone spacing (q ¼� 0.47, P ¼ 0.017) and remained normal (‡35 decibels), despite density measures that were approximately 52% to 62% below normal. CONCLUSIONS. Cone density was reduced by up to 62% below normal at or near the fovea in eyes with VA and sensitivity that remained within normal limits. Despite a significant correlation with foveal Cone spacing, VA and sensitivity are insensitive indicators of the integrity of the foveal Cone mosaic. Direct, objective measures of Cone Structure may be more sensitive indicators of disease severity than VA or foveal sensitivity in eyes with inherited retinal degenerations. (ClinicalTrials.gov number, NCT00254605.)
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Cone Structure in patients with usher syndrome type iii and mutations in the clarin 1 gene
JAMA Ophthalmology, 2013Co-Authors: Kavitha Ratnam, Austin Roorda, Hanna Vastinsalo, Eevamarja Kaarina Sankila, Jacque L DuncanAbstract:Objective To study macular Structure and function in patients with Usher syndrome type III (USH3) caused by mutations in the Clarin 1 gene (CLRN1). Methods High-resolution macular images were obtained by adaptive optics scanning laser ophthalmoscopy and spectral domain optical coherence tomography in 3 patients with USH3 and were compared with those of age-similar control subjects. Vision function measures included best-corrected visual acuity, kinetic and static perimetry, and full-field electroretinography. Coding regions of the CLRN1 gene were sequenced. Results CLRN1 mutations were present in all the patients; a 20-year-old man showed compound heterozygous mutations (p.N48K and p.S188X), and 2 unrelated women aged 25 and 32 years had homozygous mutations (p.N48K). Best-corrected visual acuity ranged from 20/16 to 20/40, with scotomas beginning at 3° eccentricity. The inner segment–outer segment junction or the inner segment ellipsoid band was disrupted within 1° to 4° of the fovea, and the foveal inner and outer segment layers were significantly thinner than normal. Cones near the fovea in patients 1 and 2 showed normal spacing, and the preserved region ended abruptly. Retinal pigment epithelial cells were visible in patient 3 where Cones were lost. Conclusions Cones were observed centrally but not in regions with scotomas, and retinal pigment epithelial cells were visible in regions without Cones in patients with CLRN1 mutations. High-resolution measures of retinal Structure demonstrate patterns of Cone loss associated with CLRN1 mutations. Clinical Relevance These findings provide insight into the effect of CLRN1 mutations on macular Cone Structure, which has implications for the development of treatments for USH3. Trial Registration clinicaltrials.gov Identifier: NCT00254605
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abnormal Cone Structure in foveal schisis cavities in x linked retinoschisis from mutations in exon 6 of the rs1 gene
Investigative Ophthalmology & Visual Science, 2011Co-Authors: Jacque L Duncan, Kavitha Ratnam, S Sundquist, Yuhua Zhang, David G Birch, Anna S Lucero, M R Meltzer, Nizar Smaoui, Austin RoordaAbstract:PURPOSE. To evaluate macular Cone Structure in patients with X-linked retinoschisis (XLRS) caused by mutations in exon 6 of the RS1 gene. METHODS. High-resolution macular images were obtained with adaptive optics scanning laser ophthalmoscopy (AOSLO) and spectral domain optical coherence tomography (SD-OCT) in two patients with XLRS and 27 age-similar healthy subjects. Retinal Structure was correlated with best-corrected visual acuity, kinetic and static perimetry, fundus-guided microperimetry, full-field electroretinography (ERG), and multifocal ERG. The six coding exons and the flanking intronic regions of the RS1 gene were sequenced in each patient. RESULTS. Two unrelated males, ages 14 and 29, with visual acuity ranging from 20/32 to 20/63, had macular schisis with small relative central scotomas in each eye. The mixed scotopic ERG b-wave was reduced more than the a-wave. SD-OCT showed schisis cavities in the outer and inner nuclear and plexiform layers. Cone spacing was increased within the largest foveal schisis cavities but was normal elsewhere. In each patient, a mutation in exon 6 of the RS1 gene was identified and was predicted to change the amino acid sequence in the discoidin domain of the retinoschisin protein. CONCLUSIONS. AOSLO images of two patients with molecularly characterized XLRS revealed increased Cone spacing and abnormal packing in the macula of each patient, but Cone coverage and function were near normal outside the central foveal schisis cavities. Although Cone density is reduced, the preservation of wave-guiding Cones at the fovea and eccentric macular regions has prognostic and therapeutic implications for XLRS patients with foveal schisis. (Clinical Trials.gov number, NCT00254605.) (Invest Ophthalmol Vis Sci. 2011;52:9614‐9623) DOI:10.1167/iovs.11-8600
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Cone Structure in retinal degeneration associated with mutations in the peripherin rds gene
Investigative Ophthalmology & Visual Science, 2011Co-Authors: Jacque L Duncan, Katherine E Talcott, Kavitha Ratnam, S Sundquist, Anya S Lucero, Yuhua Zhang, Austin RoordaAbstract:Peripherin/RDS is an integral membrane glycoprotein involved in photoreceptor outer segment formation.1 peripherin/RDS mutations on chromosome 6p were first reported to cause autosomal dominant retinitis pigmentosa (RP)2,3 but have since been shown to cause a wide variety of retinal phenotypes including pattern dystrophy,4,5 Cone-rod dystrophy,6 adult vitelliform macular dystrophy,7 central areolar choroidal dystrophy,8,9 and autosomal dominant macular dystrophy.10 Peripherin/RDS forms a complex with ROM1, which also plays a role in photoreceptor outer segment disc formation, and heterozygous mutations in peripherin/RDS and ROM1 may produce a digenic form of RP.11 The highly conserved second intradiscal loop is thought to be integral for peripherin/RDS protein function and, thus, for outer segment disc generation and stabilization.6,12 More than 90 different mutations in the peripherin/RDS gene have been associated with retinal degeneration, and mutations at the same amino acid position have been associated with diverse clinical phenotypes (http://www.retina-international.org/sci-news/rdsmut.htm). Mutations affecting the intradiscal D2 domain of peripherin/RDS manifest a variety of different retinal degeneration phenotypes, supporting the importance of this region for normal photoreceptor outer segment Structure and survival. Altering the DNA from cysteine to thymidine at position 514 of the peripherin/RDS cDNA causes an arginine to tryptophan substitution at position 172 (R172W), which has been associated with macular dystrophy, central areolar choroidal dystrophy, Cone dystrophy, and Cone rod dystrophy.6,10,13–23 Changing guanine to adenosine at position 623 alters the amino acid at position 208 from glycine to aspartic acid (G208D) and is thought to alter the secondary Structure of the protein.24 The G208D mutation has been associated with atypical autosomal dominant RP,25 pattern macular dystrophy,10 and central areolar dystrophy.13 Substituting guanine for cysteine at position 629 changes the amino acid at position 210 from proline to arginine (P210R)23,26 and produces adult foveomacular dystrophy26 and both macular and peripheral retinal degeneration, including Cone-rod degeneration and RP.23,27 Finally, substituting guanine for adenosine at position 637 changes the amino acid at position 213 from cysteine to tyrosine and causes pattern dystrophy.4 This cysteine is thought to play an important role in intrachain or interchain disulfide bond formation, and mutations at this location may disrupt photoreceptor disc membrane integrity, resulting in photoreceptor degeneration and lipofuscin accumulation in RPE cells.4 Given the dramatic phenotypic variation observed within and between families with the same mutation, the effect of peripherin/RDS mutations on Cone Structure in living eyes is not clearly understood. Adaptive optics scanning laser ophthalmoscopy (AOSLO) uses adaptive optics to overcome optical imperfections in living eyes and can be used to obtain retinal images with lateral resolution of approximately 2 μm, allowing direct visualization of photoreceptors.28–31 Direct visualization of the Cone mosaic in patients with retinal degeneration allows comparison of Cone spacing, density, and regularity with healthy subjects.32–35 In combination with other imaging and diagnostic modalities, measures of Cone Structure provide insight into the effect different types of retinal degeneration have on macular Cones.32,33,36–38 Here we present high-resolution retinal images for four patients with mutations in the peripherin/RDS gene, allowing direct in vivo genotype-phenotype correlation of Cone photoreceptor Structure and function at the cellular level.
Cheng Peng Chang - One of the best experts on this subject based on the ideXlab platform.
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evolution and dimensional crossover from the bulk subbands in abc stacked graphene to a three dimensional dirac Cone Structure in rhombohedral graphite
Physical Review B, 2016Co-Authors: Ching Hong Ho, Cheng Peng ChangAbstract:The band Structure of ABC-stacked N-layer graphene comprises topologically corresponding flat surface and gapped bulk subbands, as a consequence of the unique stacking configuration. In this paper, the bulk subbands are for the first times ever obtained for arbitrary N. A non-perturbative effective Hamiltonian closed in the bulk subspace is derived and used. The gapped bulk subbands are shown to evolve towards the zero energy with increasing N and in the infinite limit, they touch linearly along a circle. This outcome is a manifestation of the dimensional crossover to a three-dimensional Dirac Cone Structure known to exist in the bulk of rhombohedral graphite. The Dirac points, forming continuous nodal lines in a spiraling fashion, are projected onto the circle, within which the surface subbands are confined and flatten.
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Evolution and crossover from bulk subbands in ABC-stacked graphene to a three-dimensional Dirac Cone Structure in rhombohedral graphite
arXiv: Mesoscale and Nanoscale Physics, 2015Co-Authors: Ching Hong Ho, Cheng Peng ChangAbstract:The band Structure of ABC-stacked $N$-layer graphene comprises topologically corresponding flat surface and gapped bulk subbands, as a result of the unique stacking configuration. In this paper, the bulk subbands are for the first times ever obtained for arbitrary $N$. A non-perturbative effective Hamiltonian closed in the bulk subspace is derived and used. The gapped bulk subbands are shown to evolve toward the zero energy with increasing $N$ and in the infinite limit, they touch linearly along a circle. This outcome is a manifestation of the dimensional crossover to a three-dimensional Dirac Cone Structure known to exist in the bulk of rhombohedral graphite. The Dirac points, forming continuous nodal lines in a spiraling fashion, are projected onto the circle, within which the flat surface subbands are confined.
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Optical magnetoplasmons in rhombohedral graphite with a three-dimensional Dirac Cone Structure
Journal of Physics: Condensed Matter, 2015Co-Authors: Ching Hong Ho, Cheng Peng ChangAbstract:Rhombohedral graphite has a three-dimensional Dirac Cone Structure, differing only perturbatively from the bulk stack of independent graphene layers, so that the three-dimensional integer quantum Hall effect can be well exhibited in this system. In this paper, optical magnetoplasmons are obtained by using the random phase approximation. Such collective excitations do not exist in monolayer graphene but are shown to originate from Landau level mixing due to interlayer Coulomb interaction in the quantum Hall effect regime. The three-dimensional character of rhombohedral graphite is thus demonstrated. The results should be realized in response to a longitudinal external electric field or an incident infrared electromagnetic wave.
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residual Cone Structure in patients with x linked Cone opsin mutations
Investigative Ophthalmology & Visual Science, 2018Co-Authors: Emily J Patterson, Angelos Kalitzeos, Melissa Kasilian, Jessica C Gardner, Jay Neitz, Alison J HardcastleAbstract:Purpose To assess residual Cone Structure in subjects with mutations in exon 2, 3, and 4 of the OPN1LW or OPN1MW opsin.