Residual foveal cone structure in CNGB3-associated achromatopsia

ACHM-001 Study Group

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Purpose: Congenital achromatopsia (ACHM) is an autosomal recessive disorder in which cone function is absent or severely reduced. Gene therapy in animal models of ACHM have shown restoration of cone function, though translation of these results to humans relies, in part, on the presence of viable cone photoreceptors at the time of treatment. Here, we characterized residual cone structure in subjects with CNGB3-associated ACHM. Methods: High-resolution imaging (optical coherence tomography [OCT] and adaptive optics scanning light ophthalmoscopy [AOSLO]) was performed in 51 subjects with CNGB3-associated ACHM. Peak cone density and inter-cone spacing at the fovea was measured using split-detection AOSLO. Foveal outer nuclear layer thickness was measured in OCT images, and the integrity of the photoreceptor layer was assessed using a previously published OCT grading scheme. Results: Analyzable images of the foveal cones were obtained in 26 of 51 subjects, with nystagmus representing the major obstacle to obtaining high-quality images. Peak foveal cone density ranged from 7,273 to 53,554 cones/mm2, significantly lower than normal (range, 84,733–234,391 cones/mm2), with the remnant cones being either contiguously or sparsely arranged. Peak cone density was correlated with OCT integrity grade; however, there was overlap of the density ranges between OCT grades. Conclusions: The degree of residual foveal cone structure varies greatly among subjects with CNGB3-associated ACHM. Such measurements may be useful in estimating the therapeutic potential of a given retina, providing affected individuals and physicians with valuable information to more accurately assess the risk-benefit ratio as they consider enrolling in experimental gene therapy trials. (www.clinicaltrials.gov, NCT01846052.)

Original languageEnglish (US)
Pages (from-to)3984-3995
Number of pages12
JournalInvestigative Ophthalmology and Visual Science
Volume57
Issue number10
DOIs
StatePublished - Aug 1 2016

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Color Vision Defects
Optical Coherence Tomography
Ophthalmoscopy
Genetic Therapy
Retinal Cone Photoreceptor Cells
Light
Investigational Therapies
Retina
Reference Values
Animal Models
Odds Ratio
Physicians
Therapeutics

Keywords

  • Achromatopsia
  • Adaptive optics
  • CNGB3
  • Cone photoreceptor
  • Fovea
  • Gene therapy

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Residual foveal cone structure in CNGB3-associated achromatopsia. / ACHM-001 Study Group.

In: Investigative Ophthalmology and Visual Science, Vol. 57, No. 10, 01.08.2016, p. 3984-3995.

Research output: Contribution to journalArticle

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abstract = "Purpose: Congenital achromatopsia (ACHM) is an autosomal recessive disorder in which cone function is absent or severely reduced. Gene therapy in animal models of ACHM have shown restoration of cone function, though translation of these results to humans relies, in part, on the presence of viable cone photoreceptors at the time of treatment. Here, we characterized residual cone structure in subjects with CNGB3-associated ACHM. Methods: High-resolution imaging (optical coherence tomography [OCT] and adaptive optics scanning light ophthalmoscopy [AOSLO]) was performed in 51 subjects with CNGB3-associated ACHM. Peak cone density and inter-cone spacing at the fovea was measured using split-detection AOSLO. Foveal outer nuclear layer thickness was measured in OCT images, and the integrity of the photoreceptor layer was assessed using a previously published OCT grading scheme. Results: Analyzable images of the foveal cones were obtained in 26 of 51 subjects, with nystagmus representing the major obstacle to obtaining high-quality images. Peak foveal cone density ranged from 7,273 to 53,554 cones/mm2, significantly lower than normal (range, 84,733–234,391 cones/mm2), with the remnant cones being either contiguously or sparsely arranged. Peak cone density was correlated with OCT integrity grade; however, there was overlap of the density ranges between OCT grades. Conclusions: The degree of residual foveal cone structure varies greatly among subjects with CNGB3-associated ACHM. Such measurements may be useful in estimating the therapeutic potential of a given retina, providing affected individuals and physicians with valuable information to more accurately assess the risk-benefit ratio as they consider enrolling in experimental gene therapy trials. (www.clinicaltrials.gov, NCT01846052.)",
keywords = "Achromatopsia, Adaptive optics, CNGB3, Cone photoreceptor, Fovea, Gene therapy",
author = "{ACHM-001 Study Group} and Langlo, {Christopher S.} and Patterson, {Emily J.} and Higgins, {Brian P.} and Phyllis Summerfelt and Razeen, {Moataz M.} and Laura Erker and Maria Parker and Collison, {Frederick T.} and Fishman, {Gerald A.} and Kay, {Christine N.} and Jing Zhang and Richard Weleber and Paul Yang and David Wilson and Mark Pennesi and Lam, {Byron L.} and Pei-Wen Chiang and Chulay, {Jeffrey D.} and Alfredo Dubra and Hauswirth, {William W.} and Joseph Carroll",
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AU - ACHM-001 Study Group

AU - Langlo, Christopher S.

AU - Patterson, Emily J.

AU - Higgins, Brian P.

AU - Summerfelt, Phyllis

AU - Razeen, Moataz M.

AU - Erker, Laura

AU - Parker, Maria

AU - Collison, Frederick T.

AU - Fishman, Gerald A.

AU - Kay, Christine N.

AU - Zhang, Jing

AU - Weleber, Richard

AU - Yang, Paul

AU - Wilson, David

AU - Pennesi, Mark

AU - Lam, Byron L.

AU - Chiang, Pei-Wen

AU - Chulay, Jeffrey D.

AU - Dubra, Alfredo

AU - Hauswirth, William W.

AU - Carroll, Joseph

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N2 - Purpose: Congenital achromatopsia (ACHM) is an autosomal recessive disorder in which cone function is absent or severely reduced. Gene therapy in animal models of ACHM have shown restoration of cone function, though translation of these results to humans relies, in part, on the presence of viable cone photoreceptors at the time of treatment. Here, we characterized residual cone structure in subjects with CNGB3-associated ACHM. Methods: High-resolution imaging (optical coherence tomography [OCT] and adaptive optics scanning light ophthalmoscopy [AOSLO]) was performed in 51 subjects with CNGB3-associated ACHM. Peak cone density and inter-cone spacing at the fovea was measured using split-detection AOSLO. Foveal outer nuclear layer thickness was measured in OCT images, and the integrity of the photoreceptor layer was assessed using a previously published OCT grading scheme. Results: Analyzable images of the foveal cones were obtained in 26 of 51 subjects, with nystagmus representing the major obstacle to obtaining high-quality images. Peak foveal cone density ranged from 7,273 to 53,554 cones/mm2, significantly lower than normal (range, 84,733–234,391 cones/mm2), with the remnant cones being either contiguously or sparsely arranged. Peak cone density was correlated with OCT integrity grade; however, there was overlap of the density ranges between OCT grades. Conclusions: The degree of residual foveal cone structure varies greatly among subjects with CNGB3-associated ACHM. Such measurements may be useful in estimating the therapeutic potential of a given retina, providing affected individuals and physicians with valuable information to more accurately assess the risk-benefit ratio as they consider enrolling in experimental gene therapy trials. (www.clinicaltrials.gov, NCT01846052.)

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KW - Adaptive optics

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