Blue Cone Monochromacy: Visual Function and Efficacy Outcome Measures for Clinical Trials
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{"title"=>"Blue cone monochromacy: Visual function and efficacy outcome measures for clinical trials", "type"=>"journal", "authors"=>[{"first_name"=>"Xunda", "last_name"=>"Luo", "scopus_author_id"=>"42461912500"}, {"first_name"=>"Artur V.", "last_name"=>"Cideciyan", "scopus_author_id"=>"54790498100"}, {"first_name"=>"Alessandro", "last_name"=>"Iannaccone", "scopus_author_id"=>"7004329515"}, {"first_name"=>"Alejandro J.", "last_name"=>"Roman", "scopus_author_id"=>"7102169182"}, {"first_name"=>"Lauren C.", "last_name"=>"Ditta", "scopus_author_id"=>"38061372000"}, {"first_name"=>"Barbara J.", "last_name"=>"Jennings", "scopus_author_id"=>"7101813103"}, {"first_name"=>"Svetlana A.", "last_name"=>"Yatsenko", "scopus_author_id"=>"7003710203"}, {"first_name"=>"Rebecca", "last_name"=>"Sheplock", "scopus_author_id"=>"36656488600"}, {"first_name"=>"Alexander", "last_name"=>"Sumaroka", "scopus_author_id"=>"8359728700"}, {"first_name"=>"Malgorzata", "last_name"=>"Swider", "scopus_author_id"=>"6602715028"}, {"first_name"=>"Sharon B.", "last_name"=>"Schwartz", "scopus_author_id"=>"35270089300"}, {"first_name"=>"Bernd", "last_name"=>"Wissinger", "scopus_author_id"=>"57200775813"}, {"first_name"=>"Susanne", "last_name"=>"Kohl", "scopus_author_id"=>"7102175423"}, {"first_name"=>"Samuel G.", "last_name"=>"Jacobson", "scopus_author_id"=>"7402234497"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"25909963", "doi"=>"10.1371/journal.pone.0125700", "sgr"=>"84929380122", "scopus"=>"2-s2.0-84929380122", "issn"=>"19326203", "pui"=>"604371921"}, "id"=>"0c074984-5724-367b-a387-cf571fa125bc", "abstract"=>"Background: Blue Cone Monochromacy (BCM) is an X-linked retinopathy caused by mutations in the OPN1LW / OPN1MW gene cluster, encoding long (L)- and middle (M)-wavelength sensitive cone opsins. Recent evidence shows sufficient structural integrity of cone photoreceptors in BCM to warrant consideration of a gene therapy approach to the disease. In the present study, the vision in BCM is examined, specifically seeking clinically-feasible outcomes for a future clinical trial. Methods: BCM patients (n = 25, ages 5–72) were studied with kinetic and static chromatic perimetry, full-field sensitivity testing, and eye movement recordings. Vision at the fovea and parafovea was probed with chromatic microperimetry. Results: Kinetic fields with a Goldmann size V target were generally full. Short-wavelength (S-) sensitive cone function was normal or near normal in most patients. Light-adapted perimetry results on conventional background lights were abnormally reduced; 600-nm stimuli were seen by rods whereas white stimuli were seen by both rods and S-cones. Under dark-adapted conditions, 500-nm stimuli were seen by rods in both BCM and normals. Spectral sensitivity functions in the superior retina showed retained rod and S-cone functions in BCM under dark-adapted and light-adapted conditions. In the fovea, normal subjects showed L/M-cone mediation using a 650-nm stimulus under dark-adapted conditions, whereas BCM patients had reduced sensitivity driven by rod vision. Full-field red stimuli on bright blue backgrounds were seen by L/M-cones in normal subjects whereas BCM patients had abnormally reduced and rod-mediated sensitivities. Fixation location could vary from fovea to parafovea. Chromatic microperimetry demonstrated a large loss of sensitivity to red stimuli presented on a cyan adapting background at the anatomical fovea and surrounding parafovea. Conclusions: BCM rods continue to signal vision under conditions normally associated with daylight vision. Localized and retina-wide outcome measures were examined to evaluate possible improvement of L/M-cone-based vision in a clinical trial. (PsycINFO Database Record (c) 2015 APA, all rights reserved)", "link"=>"http://www.mendeley.com/research/blue-cone-monochromacy-visual-function-efficacy-outcome-measures-clinical-trials", "reader_count"=>20, "reader_count_by_academic_status"=>{"Unspecified"=>4, "Researcher"=>1, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>6, "Student > Master"=>2, "Other"=>1, "Student > Bachelor"=>1, "Professor"=>4}, "reader_count_by_user_role"=>{"Unspecified"=>4, "Researcher"=>1, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>6, "Student > Master"=>2, "Other"=>1, "Student > Bachelor"=>1, "Professor"=>4}, "reader_count_by_subject_area"=>{"Unspecified"=>6, "Biochemistry, Genetics and Molecular Biology"=>1, "Medicine and Dentistry"=>7, "Agricultural and Biological Sciences"=>3, "Neuroscience"=>1, "Psychology"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>7}, "Neuroscience"=>{"Neuroscience"=>1}, "Psychology"=>{"Psychology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>3}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>6}}, "reader_count_by_country"=>{"Turkey"=>1, "Mexico"=>1, "Chile"=>1}, "group_count"=>2}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2038667"], "description"=>"<p>(A) Fixation locations in a normal subject and 3 BCM patients. For each subject, 10 s long epochs of eye movement data during fixation to a large visible red target (Target I) are shown in spatial (left) and spatio-temporal (right) coordinates. Spatial distribution of fixation clouds are shown on infrared SLO images of each macula with standard circles centered on the anatomical foveal depression. Spatio-temporal distribution of eye movements are shown on chart records for X and Y directions; up is nasal retina for X and superior retina for Y. All results are presented as equivalent right eyes for comparability. Horizontal dashed lines on the chart records depict the location of the anatomical fovea. (B) Fixation location and instability in BCM patients as a function of the bright red standard target (I), a green target (II) scotopically-matched to the standard target but expected to show greater visibility to S-cones, and a dim red target (III). N.S., not significant; *, P<0.05. (C) Distribution of fixation locations with the standard target in all patients. I = inferior, N = nasal, S = superior, and T = temporal retina. (D) Fixation location and instability as a function of best-corrected visual acuity. (E) Test pattern used with microperimetric stimuli to evaluate visual function under chromatic adaptation displayed on a normal near-infrared reflectance image. Stimulus locations are divided into 5 groups; f, foveal region, s, superior, i, inferior, t, temporal and n, nasal retina. (F,G) Sensitivities to blue stimuli on yellow background (BonY) and red stimuli on cyan background (RonC) in individual BCM patients (bars left to right; P2, P3, P4, P6, P8, P9, P10, P15, P16, P17, P18, P20, P25, P26, P28, and P29) compared to normal results (symbols; mean ±1sd) at the five regions shown in panel E. BCM results plotted below the zero line in Panel G represent those cases where the brightest available stimulus was not seen.</p>", "links"=>[], "tags"=>["Blue Cone Monochromacy", "eye movement recordings", "fovea", "Spectral sensitivity functions", "background", "Efficacy Outcome Measures", "1MW", "Goldmann size V target", "gene therapy approach", "BCM patients", "opn", "1LW", "stimuli", "Clinical Trials BackgroundBlue Cone Monochromacy", "nm"], "article_id"=>1393506, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["Xunda Luo", "Artur V. Cideciyan", "Alessandro Iannaccone", "Alejandro J. Roman", "Lauren C. Ditta", "Barbara J. Jennings", "Svetlana A. Yatsenko", "Rebecca Sheplock", "Alexander Sumaroka", "Malgorzata Swider", "Sharon B. Schwartz", "Bernd Wissinger", "Susanne Kohl", "Samuel G. Jacobson"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0125700.g004", "stats"=>{"downloads"=>0, "page_views"=>50, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Nystagmus_and_foveal_function_in_BCM_/1393506", "title"=>"Nystagmus and foveal function in BCM.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-04-24 02:43:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/2038668", "https://ndownloader.figshare.com/files/2038670"], "description"=>"<div><p>Background</p><p>Blue Cone Monochromacy (BCM) is an X-linked retinopathy caused by mutations in the <i>OPN1LW / OPN1MW</i> gene cluster, encoding long (L)- and middle (M)-wavelength sensitive cone opsins. Recent evidence shows sufficient structural integrity of cone photoreceptors in BCM to warrant consideration of a gene therapy approach to the disease. In the present study, the vision in BCM is examined, specifically seeking clinically-feasible outcomes for a future clinical trial.</p><p>Methods</p><p>BCM patients (n = 25, ages 5–72) were studied with kinetic and static chromatic perimetry, full-field sensitivity testing, and eye movement recordings. Vision at the fovea and parafovea was probed with chromatic microperimetry.</p><p>Results</p><p>Kinetic fields with a Goldmann size V target were generally full. Short-wavelength (S-) sensitive cone function was normal or near normal in most patients. Light-adapted perimetry results on conventional background lights were abnormally reduced; 600-nm stimuli were seen by rods whereas white stimuli were seen by both rods and S-cones. Under dark-adapted conditions, 500-nm stimuli were seen by rods in both BCM and normals. Spectral sensitivity functions in the superior retina showed retained rod and S-cone functions in BCM under dark-adapted and light-adapted conditions. In the fovea, normal subjects showed L/M-cone mediation using a 650-nm stimulus under dark-adapted conditions, whereas BCM patients had reduced sensitivity driven by rod vision. Full-field red stimuli on bright blue backgrounds were seen by L/M-cones in normal subjects whereas BCM patients had abnormally reduced and rod-mediated sensitivities. Fixation location could vary from fovea to parafovea. Chromatic microperimetry demonstrated a large loss of sensitivity to red stimuli presented on a cyan adapting background at the anatomical fovea and surrounding parafovea.</p><p>Conclusions</p><p>BCM rods continue to signal vision under conditions normally associated with daylight vision. Localized and retina-wide outcome measures were examined to evaluate possible improvement of L/M-cone-based vision in a clinical trial.</p></div>", "links"=>[], "tags"=>["Blue Cone Monochromacy", "eye movement recordings", "fovea", "Spectral sensitivity functions", "background", "Efficacy Outcome Measures", "1MW", "Goldmann size V target", "gene therapy approach", "BCM patients", "opn", "1LW", "stimuli", "Clinical Trials BackgroundBlue Cone Monochromacy", "nm"], "article_id"=>1393507, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["Xunda Luo", "Artur V. Cideciyan", "Alessandro Iannaccone", "Alejandro J. Roman", "Lauren C. Ditta", "Barbara J. Jennings", "Svetlana A. Yatsenko", "Rebecca Sheplock", "Alexander Sumaroka", "Malgorzata Swider", "Sharon B. Schwartz", "Bernd Wissinger", "Susanne Kohl", "Samuel G. Jacobson"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0125700.s001", "https://dx.doi.org/10.1371/journal.pone.0125700.s002"], "stats"=>{"downloads"=>7, "page_views"=>24, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Blue_Cone_Monochromacy_Visual_Function_and_Efficacy_Outcome_Measures_for_Clinical_Trials_/1393507", "title"=>"Blue Cone Monochromacy: Visual Function and Efficacy Outcome Measures for Clinical Trials", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-04-24 02:43:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/2038653"], "description"=>"<p>(A) Light-adapted (LA) vertical sensitivity profiles from a normal subject and a BCM patient using achromatic (black line) and 600-nm (orange line) stimuli on a 10 cd.m<sup>-2</sup> white background, or 440-nm (blue line) stimuli on a yellow background (YB). (B) S-cone sensitivity profiles (filled circles) of the BCM patients using a 440-nm stimulus on YB compared to normal limits (gray = ±2SD). (C) LA white vertical sensitivity profiles of BCM patients (filled circles) compared to normal (gray). Blue line is the S-cone sensitivities from Panel C shifted according to the difference in effectiveness between the white and 440-nm stimuli. (D) LA 600-nm vertical sensitivity profiles of BCM patients (filled circles) compared to normal (gray). (E) Sensitivity differences between LA white and LA 600-nm stimuli are shown for the BCM patients (filled circles) and normal (unfilled circles). Predicted differences for rod (green dashes) and L/M cone (orange dashes) mediation are shown. (F) Dark-adapted (DA) vertical sensitivity profiles from a normal subject and a BCM patient using 500-nm (green line) and 650-nm (red line) stimuli. Above the results it is shown whether there is rod (R) or mixed (M) mediation, as determined by the differences between sensitivities to the stimuli. (G) DA 500-nm vertical sensitivity profiles of BCM patients (filled circles) compared to normal (gray). (H) DA 650 nm vertical sensitivity profiles of BCM patients (filled circles) compared to normal (gray). (I) Sensitivity differences between DA 500- and DA 650-nm stimuli are consistent with rod mediation (gray) at all locations except for the normal results with 650 nm at fixation. S, superior; I, inferior. (J) DA 650-nm sensitivities at fixation in normal and BCM. Normal 650-nm sensitivities are mediated by the L/M cones (C) whereas BCM sensitivities are mediated by the rods (R). Error bars are ±1SD.</p>", "links"=>[], "tags"=>["Blue Cone Monochromacy", "eye movement recordings", "fovea", "Spectral sensitivity functions", "background", "Efficacy Outcome Measures", "1MW", "Goldmann size V target", "gene therapy approach", "BCM patients", "opn", "1LW", "stimuli", "Clinical Trials BackgroundBlue Cone Monochromacy", "nm"], "article_id"=>1393492, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["Xunda Luo", "Artur V. Cideciyan", "Alessandro Iannaccone", "Alejandro J. Roman", "Lauren C. Ditta", "Barbara J. Jennings", "Svetlana A. Yatsenko", "Rebecca Sheplock", "Alexander Sumaroka", "Malgorzata Swider", "Sharon B. Schwartz", "Bernd Wissinger", "Susanne Kohl", "Samuel G. Jacobson"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0125700.g001", "stats"=>{"downloads"=>1, "page_views"=>34, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Visual_fields_of_BCM_patients_evaluated_with_kinetic_and_static_perimetry_/1393492", "title"=>"Visual fields of BCM patients evaluated with kinetic and static perimetry.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-04-24 02:43:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/2038660"], "description"=>"<p>(A) Sensitivities (mean±1 SD) to six spectrally distinct stimuli in normal subjects (n = 3) under dark-adapted (left), and on 1 (middle) and 10 cd.m<sup>-2</sup> (right) white backgrounds. (B) Sensitivities to the spectrally distinct stimuli in BCM patients for the same three adaptation conditions as in Panel A. Results from P8 are shown at the correct ordinate location; results from remaining patients have been adjusted by 1 log increments for visibility. Theoretical functions describing rod (green), S cone (blue), L/M cone (orange) sensitivities are shown after vertical shifts to fit relevant normal and BCM data in Panels A and B. (C) Comparison of individual normal and BCM sensitivities at 500 nm. (D,E) Comparison of individual normal and BCM sensitivities at 440, 500 and 560 nm. Symbols in Panels C, D, and E are painted by colors derived from the fit of theoretical functions to the spectral data. N = normal, B = BCM.</p>", "links"=>[], "tags"=>["Blue Cone Monochromacy", "eye movement recordings", "fovea", "Spectral sensitivity functions", "background", "Efficacy Outcome Measures", "1MW", "Goldmann size V target", "gene therapy approach", "BCM patients", "opn", "1LW", "stimuli", "Clinical Trials BackgroundBlue Cone Monochromacy", "nm"], "article_id"=>1393499, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["Xunda Luo", "Artur V. Cideciyan", "Alessandro Iannaccone", "Alejandro J. Roman", "Lauren C. Ditta", "Barbara J. Jennings", "Svetlana A. Yatsenko", "Rebecca Sheplock", "Alexander Sumaroka", "Malgorzata Swider", "Sharon B. Schwartz", "Bernd Wissinger", "Susanne Kohl", "Samuel G. Jacobson"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0125700.g002", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Spectral_sensitivity_functions_in_normal_subjects_and_BCM_patients_recorded_at_14_176_superior_field_/1393499", "title"=>"Spectral sensitivity functions in normal subjects and BCM patients recorded at 14° superior field.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-04-24 02:43:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/2038664"], "description"=>"<p>(A,B) FST-TVI with blue (A) and red (B) stimuli on white backgrounds in BCM patients and normals. Gray region defines the expected desensitization of the rod system. Rectangles define the data further explored in panels C-F. (C-F) Comparison of thresholds with chromatic and white backgrounds; blue stimuli on white (BonW) or yellow (BonY), and red stimuli on white (RonW) or on blue (RonB) backgrounds are shown. Different panels show the effectiveness of the background for the scotopic (C,D), S-cone (E) and photopic (F) systems. Lines with unity slope are fit to the data, and offset between the lines is shown in log units. (G,H) Sensitivity loss and predicted photoreceptor mediation using a pair of RonW and RonB FST thresholds. Both individual results and group averages (Avg) are shown. Error bars, when visible, are ±1SD.</p>", "links"=>[], "tags"=>["Blue Cone Monochromacy", "eye movement recordings", "fovea", "Spectral sensitivity functions", "background", "Efficacy Outcome Measures", "1MW", "Goldmann size V target", "gene therapy approach", "BCM patients", "opn", "1LW", "stimuli", "Clinical Trials BackgroundBlue Cone Monochromacy", "nm"], "article_id"=>1393503, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["Xunda Luo", "Artur V. Cideciyan", "Alessandro Iannaccone", "Alejandro J. Roman", "Lauren C. Ditta", "Barbara J. Jennings", "Svetlana A. Yatsenko", "Rebecca Sheplock", "Alexander Sumaroka", "Malgorzata Swider", "Sharon B. Schwartz", "Bernd Wissinger", "Susanne Kohl", "Samuel G. Jacobson"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0125700.g003", "stats"=>{"downloads"=>2, "page_views"=>35, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_FST_results_with_two_colors_under_dark_adapted_conditions_and_on_a_range_of_white_and_chromatic_backgrounds_/1393503", "title"=>"FST results with two colors under dark-adapted conditions and on a range of white and chromatic backgrounds.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-04-24 02:43:10"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"16", "full-text"=>"17", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2019", "month"=>"10"}
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  • {"unique-ip"=>"7", "full-text"=>"10", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"2"}
  • {"unique-ip"=>"16", "full-text"=>"14", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2020", "month"=>"3"}
  • {"unique-ip"=>"18", "full-text"=>"18", "pdf"=>"10", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2020", "month"=>"4"}
  • {"unique-ip"=>"9", "full-text"=>"10", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2020", "month"=>"5"}
  • {"unique-ip"=>"22", "full-text"=>"23", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2020", "month"=>"6"}

Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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