Blue cone monochromacy: visual function and efficacy outcome measures for clinical trials.
<h4>Background</h4>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 w...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0125700 |
| _version_ | 1818725212105998336 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Xunda Luo |
| collection | DOAJ |
| description | <h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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. |
| first_indexed | 2024-12-17T21:38:43Z |
| format | Article |
| id | doaj.art-7333ba2a4f0b4ff18b5b7e307b7439f4 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-17T21:38:43Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-7333ba2a4f0b4ff18b5b7e307b7439f42022-12-21T21:31:41ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01104e012570010.1371/journal.pone.0125700Blue cone monochromacy: visual function and efficacy outcome measures for clinical trials.Xunda LuoArtur V CideciyanAlessandro IannacconeAlejandro J RomanLauren C DittaBarbara J JenningsSvetlana A YatsenkoRebecca SheplockAlexander SumarokaMalgorzata SwiderSharon B SchwartzBernd WissingerSusanne KohlSamuel G Jacobson<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.https://doi.org/10.1371/journal.pone.0125700 |
| spellingShingle | 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 Blue cone monochromacy: visual function and efficacy outcome measures for clinical trials. PLoS ONE |
| title | Blue cone monochromacy: visual function and efficacy outcome measures for clinical trials. |
| title_full | Blue cone monochromacy: visual function and efficacy outcome measures for clinical trials. |
| title_fullStr | Blue cone monochromacy: visual function and efficacy outcome measures for clinical trials. |
| title_full_unstemmed | Blue cone monochromacy: visual function and efficacy outcome measures for clinical trials. |
| title_short | Blue cone monochromacy: visual function and efficacy outcome measures for clinical trials. |
| title_sort | blue cone monochromacy visual function and efficacy outcome measures for clinical trials |
| url | https://doi.org/10.1371/journal.pone.0125700 |
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