June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Assessing cone photoreceptor structure in patients with mutations in the OPN1LW/OPN1MW gene array
Author Affiliations & Notes
  • Emily J Patterson
    Ophthalmology & Visual Science, Medical College of Winconsin, Milwaukee, Wisconsin, United States
  • Melissa Kasilian
    UCL Institute of Ophthalmology, London, United Kingdom
  • Angelos Kalitzeos
    UCL Institute of Ophthalmology, London, United Kingdom
  • Conor Patrick Malone
    The Research Foundation, The Royal Victoria Eye & Ear Hospital, Dublin, Ireland
  • Matthew Carrigan
    The Ocular Genetics Unit, Trinity College, Dublin, Ireland
  • Andrew Green
    Department of Clinical Genetics, Our Lady’s Hospital for Sick Children, Dublin, Crumlin, Ireland
    UCD School of Medicine and Medical Science, University College Dublin, Dublin, Ireland
  • G. Jane Farrar
    Department of Clinical Genetics, Our Lady’s Hospital for Sick Children, Dublin, Crumlin, Ireland
  • Maureen Neitz
    Department of Ophthalmology, University of Washington, Seattle, Washington, United States
  • Paul F Kenna
    The Research Foundation, The Royal Victoria Eye & Ear Hospital, Dublin, Ireland
    The Ocular Genetics Unit, Trinity College, Dublin, Ireland
  • Michel Michaelides
    UCL Institute of Ophthalmology, London, United Kingdom
    Moorfields Eye Hospital, London, United Kingdom
  • Joseph Carroll
    Ophthalmology & Visual Science, Medical College of Winconsin, Milwaukee, Wisconsin, United States
  • Footnotes
    Commercial Relationships   Emily Patterson, None; Melissa Kasilian, None; Angelos Kalitzeos, None; Conor Malone, None; Matthew Carrigan, None; Andrew Green, None; G. Farrar, None; Maureen Neitz, None; Paul Kenna, None; Michel Michaelides, None; Joseph Carroll, AGTC (F), MeiraGTx (C), MeiraGTx (F), Optovue (F)
  • Footnotes
    Support  NIH grants P30EY001931 R01EY017607 P30EY001730, NIHR TRC-RD, Fighting Blindness Ireland, Health Research Board of Ireland, and Wellcome Trust
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 1257. doi:
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      Emily J Patterson, Melissa Kasilian, Angelos Kalitzeos, Conor Patrick Malone, Matthew Carrigan, Andrew Green, G. Jane Farrar, Maureen Neitz, Paul F Kenna, Michel Michaelides, Joseph Carroll; Assessing cone photoreceptor structure in patients with mutations in the OPN1LW/OPN1MW gene array. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1257.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Blue cone monochromacy (BCM) is a cone dysfunction syndrome associated with mutations in the OPN1LW /OPN1MW gene array. Although the condition typically manifests with poor visual acuity, nystagmus, photophobia, and color vision defects, the severity of the phenotype is highly variable. Here we examined the genotype, clinical phenotype and cone structure in subjects with a clinical diagnosis of BCM.

Methods : Eleven males (aged 10 to 51 years) with suspected BCM were recruited and had their OPN1LW/OPN1MW gene arrays characterized. In 10 subjects, thickness and integrity of the retinal layers was evaluated using optical coherence tomography (OCT). Confocal and split-detection images of the cone mosaic were acquired using adaptive optics scanning light ophthalmoscopy (AOSLO). Imaging took place either at the Medical College of Wisconsin or at Moorfields Eye Hospital, London. Cone density was measured at foveal and parafoveal regions of interest using semi-automated cone-counting software in 9 subjects. Color vision was screened using the AO-HRR; 5 subjects also completed the Rayleigh match and 4 of those completed the Color Assessment and Diagnosis test.

Results : Genotypes varied and included deletions of the locus control region, point mutations and OPN1LW/OPN1MW interchange variants; as the latter can yield minor amounts of correctly spliced transcript, a BCM diagnosis is questionable in such cases. While all subjects had severe red-green color vision defects, some subjects demonstrated residual discrimination along the tritan axis. OCT revealed reduced retinal thickness (31 - 77% of normal), and reflectivity in confocal AOSLO was diminished for all subjects. Foveal inner-segment (IS) integrity was highly variable (661 - 35,041 cones/mm2) with large differences in cone packing geometry observed between subjects.

Conclusions : While the number of waveguiding cones was reduced, we found evidence of remnant cone IS structure in all subjects, albeit to a variable degree. In contrast to previous observations in patients with BCM, some subjects had a contiguous IS arrangement at the fovea. These data suggest that many BCM patients may be viable candidates for gene therapy efforts to restore cone function.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

 

AOSLO reveals highly variable cone packing and reflectivity. While confocal images (left) show reduced waveguiding, there is evidence for remnant IS structure in split-detection images (right).

AOSLO reveals highly variable cone packing and reflectivity. While confocal images (left) show reduced waveguiding, there is evidence for remnant IS structure in split-detection images (right).

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