title: A prospective longitudinal study of retinal structure and function in achromatopsia.
abstract: OBJECTIVE
  To longitudinally characterize retinal structure and function in achromatopsia (ACHM) in preparation for clinical gene therapy trials.
  
  
  METHODS
  Thirty-eight molecularly confirmed ACHM subjects underwent serial assessments, including spectral domain optical coherence tomography (SD-OCT), microperimetry, and fundus autofluorescence (FAF). Foveal structure on SD-OCT was graded and compared for evidence of progression, along with serial measurements of foveal total retinal thickness (FTRT) and outer nuclear layer (ONL) thickness. Fundus autofluorescence patterns were characterized and compared over time.
  
  
  RESULTS
  Mean follow-up was 19.5 months (age range at baseline, 6-52 years). Only 2 (5%) of 37 subjects demonstrated change in serial foveal SD-OCT scans. There was no statistically significant change over time in FTRT (P = 0.83), ONL thickness (P = 0.27), hyporeflective zone diameter (P = 0.42), visual acuity (P = 0.89), contrast sensitivity (P = 0.22), mean retinal sensitivity (P = 0.84), and fixation stability (P = 0.58). Three distinct FAF patterns were observed (n = 30): central increased FAF (n = 4), normal FAF (n = 11), and well-demarcated reduced FAF (n = 15); with the latter group displaying a slow increase in the area of reduced FAF of 0.03 mm(2) over 19.3 months (P = 0.002).
  
  
  CONCLUSIONS
  Previously published cross-sectional studies have described conflicting findings with respect to the age-dependency of progression. This study, which constitutes the largest and longest prospective longitudinal study of ACHM to date, suggests that although ACHM may be progressive, any such progression is slow and subtle in most patients, and does not correlate with age or genotype. We also describe the first serial assessment of FAF, which is highly variable between individuals, even of similar age and genotype.
authors.affiliation: UCL Institute of Ophthalmology, University College London, London, United Kingdom Moorfields Eye Hospital, London, United Kingdom.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Aboshiha
authors.affiliation: UCL Institute of Ophthalmology, University College London, London, United Kingdom Moorfields Eye Hospital, London, United Kingdom.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Dubis
authors.affiliation: UCL Institute of Ophthalmology, University College London, London, United Kingdom.
authors.forename: Jill
authors.initials: J
authors.lastname: Cowing
authors.affiliation: UCL Institute of Ophthalmology, University College London, London, United Kingdom.
authors.forename: Rachel T A
authors.initials: RT
authors.lastname: Fahy
authors.affiliation: Moorfields Eye Hospital, London, United Kingdom.
authors.forename: Venki
authors.initials: V
authors.lastname: Sundaram
authors.affiliation: UCL Institute of Ophthalmology, University College London, London, United Kingdom Moorfields Eye Hospital, London, United Kingdom.
authors.forename: James W
authors.initials: JW
authors.lastname: Bainbridge
authors.affiliation: UCL Institute of Ophthalmology, University College London, London, United Kingdom.
authors.forename: Robin R
authors.initials: RR
authors.lastname: Ali
authors.affiliation: Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States Department of Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Dubra
authors.affiliation: Department of Psychology, Durham University, Durham, United Kingdom.
authors.forename: Marko
authors.initials: M
authors.lastname: Nardini
authors.affiliation: UCL Institute of Ophthalmology, University College London, London, United Kingdom Moorfields Eye Hospital, London, United Kingdom.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Webster
authors.affiliation: UCL Institute of Ophthalmology, University College London, London, United Kingdom Moorfields Eye Hospital, London, United Kingdom.
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Moore
authors.affiliation: UCL Institute of Ophthalmology, University College London, London, United Kingdom.
authors.forename: Gary
authors.initials: G
authors.lastname: Rubin
authors.affiliation: Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States Department of Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
authors.forename: Joseph
authors.initials: J
authors.lastname: Carroll
authors.affiliation: UCL Institute of Ophthalmology, University College London, London, United Kingdom Moorfields Eye Hospital, London, United Kingdom.
authors.forename: Michel
authors.initials: M
authors.lastname: Michaelides
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D003117:Color Vision Defects / Q000503:physiopathology*; D015350:Contrast Sensitivity / Q000502:physiology; D018450:Disease Progression; D005260:Female; D005451:Fluorescein Angiography; D005500:Follow-Up Studies; D005584:Fovea Centralis; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012160:Retina / Q000503:physiopathology*; D041623:Tomography, Optical Coherence; D014792:Visual Acuity / Q000502:physiology; D058609:Visual Field Tests; D014794:Visual Fields / Q000502:physiology; D055815:Young Adult
keywords: achromatopsia; gene therapy; optical coherence tomography; retinal degeneration; retinal dystrophy
references.citation: J Med Genet. 2004 Feb;41(2):e20
references.pmid: 14757870
references.citation: Retina. 2008 Mar;28(3):385-409
references.pmid: 18327131
references.citation: Invest Ophthalmol Vis Sci. 2010 Jul;51(7):3673-9
references.pmid: 20164460
references.citation: JAMA Ophthalmol. 2014 Apr 1;132(4):437-45
references.pmid: 24504161
references.citation: Retina. 2009 May;29(5):651-6
references.pmid: 19262440
references.citation: Invest Ophthalmol Vis Sci. 2005 Aug;46(8):2940-6
references.pmid: 16043869
references.citation: Am J Hum Genet. 2002 Aug;71(2):422-5
references.pmid: 12077706
references.citation: Mol Ther. 2010 Dec;18(12):2057-63
references.pmid: 20628362
references.citation: Ophthalmology. 2009 Oct;116(10):1984-9.e1
references.pmid: 19592100
references.citation: Nat Genet. 2000 Jul;25(3):289-93
references.pmid: 10888875
references.citation: Hum Mol Genet. 2011 Aug 15;20(16):3161-75
references.pmid: 21576125
references.citation: Ophthalmology. 2014 Jan;121(1):234-245
references.pmid: 24148654
references.citation: Vision Res. 2008 Nov;48(26):2564-8
references.pmid: 18499214
references.citation: Invest Ophthalmol Vis Sci. 2007 Aug;48(8):3864-71
references.pmid: 17652762
references.citation: Br J Ophthalmol. 2004 Feb;88(2):291-7
references.pmid: 14736794
references.citation: Ophthalmology. 2011 May;118(5):882-7
references.pmid: 21211844
references.citation: Am J Ophthalmol. 2009 Mar;147(3):467-72
references.pmid: 19026403
references.citation: Invest Ophthalmol Vis Sci. 2009 Aug;50(8):3953-9
references.pmid: 19324865
references.citation: Acta Ophthalmol (Copenh). 1991 Dec;69(6):711-6
references.pmid: 1789084
references.citation: Br J Ophthalmol. 2008 Jan;92(1):95-102
references.pmid: 17962389
references.citation: Biomed Opt Express. 2011 Aug 1;2(8):2189-201
references.pmid: 21833357
references.citation: Nat Med. 2007 Jun;13(6):685-7
references.pmid: 17515894
references.citation: Ophthalmic Epidemiol. 2005 Dec;12(6):353-62
references.pmid: 16283987
references.citation: Br J Ophthalmol. 2003 Nov;87(11):1317-20
references.pmid: 14609822
references.citation: Genomics. 1998 Aug 1;51(3):325-31
references.pmid: 9721202
references.citation: Invest Ophthalmol Vis Sci. 2007 May;48(5):2249-53
references.pmid: 17460287
references.citation: Invest Ophthalmol Vis Sci. 1995 Mar;36(3):718-29
references.pmid: 7890502
references.citation: Am J Ophthalmol. 2007 Mar;143(3):463-72
references.pmid: 17239336
references.citation: Proc Natl Acad Sci U S A. 2009 Nov 17;106(46):19581-6
references.pmid: 19887631
references.citation: Invest Ophthalmol Vis Sci. 2011 Sep 21;52(10):7298-308
references.pmid: 21778272
references.citation: Am J Ophthalmol. 2013 Dec;156(6):1211-1219.e2
references.pmid: 23972307
references.citation: Prog Retin Eye Res. 2012 Mar;31(2):136-51
references.pmid: 22182585
references.citation: Am J Hum Genet. 2012 Sep 7;91(3):527-32
references.pmid: 22901948
references.citation: Hum Mol Genet. 2010 Jul 1;19(13):2581-93
references.pmid: 20378608
references.citation: Am J Ophthalmol. 2010 Jul;150(1):63-67.e1
references.pmid: 20451897
references.citation: Hum Mutat. 2005 Mar;25(3):248-58
references.pmid: 15712225
references.citation: Invest Ophthalmol Vis Sci. 2004 Feb;45(2):574-83
references.pmid: 14744901
references.citation: Br J Ophthalmol. 2012 Sep;96(9):1232-6
references.pmid: 22790432
references.citation: Invest Ophthalmol Vis Sci. 2010 Nov;51(11):5952-7
references.pmid: 20574029
references.citation: Retina. 2010 May;30(5):713-8
references.pmid: 20038861
references.citation: Invest Ophthalmol Vis Sci. 2006 Mar;47(3):1161-6
references.pmid: 16505054
references.citation: J Physiol. 1986 Feb;371:365-85
references.pmid: 3486271