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- Title
Blue Cone Monochromacy: Visual Function and Efficacy Outcome Measures for Clinical Trials.
- Authors
Luo, Xunda; Cideciyan, Artur V.; Iannaccone, Alessandro; Roman, Alejandro J.; Ditta, Lauren C.; Jennings, Barbara J.; Yatsenko, Svetlana A.; Sheplock, Rebecca; Sumaroka, Alexander; Swider, Malgorzata; Schwartz, Sharon B.; Wissinger, Bernd; Kohl, Susanne; Jacobson, Samuel G.
- 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.
- Subjects
CLINICAL trials; HEALTH outcome assessment; X-linked genetic disorders; GENETIC mutation; OPSINS; PHOTORECEPTORS; RETINAL diseases; TREATMENT of eye diseases; GENE therapy
- Publication
PLoS ONE, 2015, Vol 10, Issue 4, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0125700