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Residual Cone Structure in Patients With X-Linked Cone Opsin Mutations. Invest Ophthalmol Vis Sci 2018 08 01;59(10):4238-4248 PMID: 30128495 PMCID: PMC6103386

Pubmed ID





Purpose: To assess residual cone structure in subjects with mutations in exon 2, 3, and 4 of the OPN1LW or OPN1MW opsin.

Methods: Thirteen males had their OPN1LW/OPN1MW opsin genes characterized. The cone mosaic was imaged using both confocal and nonconfocal split-detection adaptive optics scanning light ophthalmoscopy (AOSLO), and retinal thickness was evaluated using optical coherence tomography (OCT). Six subjects completed serial imaging over a maximum period of 18 months and cone density was measured across imaging sessions.

Results: Ten subjects had an OPN1LW/OPN1MW "interchange" opsin mutation designated as LIAVA or LVAVA, which both introduce exon 3 splicing defects leading to a lack of functional photopigment in cones expressing LIAVA and greatly reduced functional photopigment in cones expressing LVAVA. Despite disrupted cone reflectivity and reduced numerosity, residual inner segments could be visualized. Similar patterns were observed in individuals with an exon 2 insertion, or an exon 4 splice defect, both of which are also expected to produce cones that are devoid of functional opsin protein. OCT revealed variably reduced retinal thickness. A significant inverse relationship was found between the proportion of waveguiding cones and axial length.

Conclusions: Split-detection imaging revealed that the altered appearance of the cone mosaic in confocal images for subjects with exon 2, 3, and 4 mutations was generally due to disrupted waveguiding, rather than structural loss, making them possible candidates for gene therapy to restore cone function. The relative fraction of waveguiding cones was highly variable across subjects, which appears to influence emmetropization in these subjects.

Author List

Patterson EJ, Kalitzeos A, Kasilian M, Gardner JC, Neitz J, Hardcastle AJ, Neitz M, Carroll J, Michaelides M


Joseph J. Carroll PhD Director, Professor in the Ophthalmology and Visual Sciences department at Medical College of Wisconsin


2-s2.0-85052696691   1 Citations

MESH terms used to index this publication - Major topics in bold

Axial Length, Eye
Color Vision Defects
Cone Opsins
Genes, X-Linked
Middle Aged
Retinal Cone Photoreceptor Cells
Rod Opsins
jenkins-FCD Prod-353 9ccd8489072cb19f5b9f808bb23ed672c582f41e