title: Three-dimensional distribution of the vitelliform lesion, photoreceptors, and retinal pigment epithelium in the macula of patients with best vitelliform macular dystrophy.
abstract: OBJECTIVE
  To describe the anatomical phenotypes of Best vitelliform macular dystrophy (BVMD) with spectral-domain optical coherence tomography (SD-OCT) in a large series of patients with confirmed mutations in the BEST1 gene.
  
  
  METHODS
  In our retrospective observational case series, we assessed 15 patients (30 eyes) with a clinical diagnosis of vitelliform macular dystrophy who were found to have mutations in the BEST1 gene. Color fundus photographs and SD-OCT images were evaluated and compared with those of 15 age-matched controls (30 eyes). Using a validated 3-dimensional SD-OCT segmentation algorithm, we calculated the equivalent thickness of photoreceptors and the equivalent thickness of the retinal pigment epithelium for each patient. The photoreceptor equivalent thickness and the retinal pigment epithelium (RPE) equivalent thickness were compared in all patients, in a region of the macula outside the central lesion for patients with BVMD and outside the fovea in control patients. Paired t tests were used for statistical analysis.
  
  
  RESULTS
  The SD-OCT findings revealed that the vitelliform lesion consists of material above the RPE and below the outer segment tips. Additionally, drusen-like deposition of sub-RPE material was notable, and several patients exhibited a sub-RPE fibrotic nodule. Patients with BVMD had a mean photoreceptor equivalent thickness of 28.3 μm, and control patients had a mean photoreceptor equivalent thickness of 21.8 μm, a mean difference of 6.5 μm (P < .01), whereas the mean RPE equivalent thickness was not statistically different between patients with BVMD and control patients (P = .53).
  
  
  CONCLUSIONS
  The SD-OCT findings suggest that vitelliform material is located in the subretinal space and that BVMD is associated with diffuse photoreceptor outer segment abnormalities overlying a structurally normal RPE.
  
  
  CONCLUSIONS
  These findings provide new insight into the pathophysiology of BVMD and thus have implications for the development of therapeutic interventions.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Iowa Institute for Vision Research, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Christine N
authors.initials: CN
authors.lastname: Kay
authors.forename: Michael D
authors.initials: MD
authors.lastname: Abramoff
authors.forename: Robert F
authors.initials: RF
authors.lastname: Mullins
authors.forename: Tyson R
authors.initials: TR
authors.lastname: Kinnick
authors.forename: Kyuongmoo
authors.initials: K
authors.lastname: Lee
authors.forename: Mari E
authors.initials: ME
authors.lastname: Eyestone
authors.forename: Mina M
authors.initials: MM
authors.lastname: Chung
authors.forename: Elliott H
authors.initials: EH
authors.lastname: Sohn
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Stone
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000075002:Bestrophins; D018118:Chloride Channels / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D005355:Fibrosis; D006801:Humans; D021621:Imaging, Three-Dimensional; D008266:Macula Lutea / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology*; D015593:Retinal Drusen / Q000235:genetics / Q000473:pathology; D055213:Retinal Pigment Epithelium / Q000473:pathology*; D012189:Retrospective Studies; D041623:Tomography, Optical Coherence / Q000379:methods; D057826:Vitelliform Macular Dystrophy / Q000235:genetics / Q000473:pathology*; D055815:Young Adult
chemical_list: C113133:BEST1 protein, human; D000075002:Bestrophins; D018118:Chloride Channels; D005136:Eye Proteins
references.citation: Invest Ophthalmol Vis Sci. 2007 Jul;48(7):3372-80
references.pmid: 17591911
references.citation: Am J Hum Genet. 1994 Dec;55(6):1182-7
references.pmid: 7977378
references.citation: Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):4008-13
references.pmid: 11904445
references.citation: Arch Ophthalmol. 2009 Jul;127(7):913-20
references.pmid: 19597114
references.citation: Vision Res. 2011 Jan 28;51(2):224-8
references.pmid: 20801146
references.citation: Am J Hum Genet. 2008 Jan;82(1):19-31
references.pmid: 18179881
references.citation: IEEE Trans Med Imaging. 2009 Sep;28(9):1436-47
references.pmid: 19278927
references.citation: J Gen Physiol. 2008 Dec;132(6):681-92
references.pmid: 19029375
references.citation: Physiol Rev. 2008 Apr;88(2):639-72
references.pmid: 18391176
references.citation: Eur J Hum Genet. 2000 Apr;8(4):286-92
references.pmid: 10854112
references.citation: Retina. 2011 Mar;31(3):581-95
references.pmid: 21273940
references.citation: J Biol Chem. 2003 Oct 17;278(42):41114-25
references.pmid: 12907679
references.citation: FASEB J. 2006 Jan;20(1):178-80
references.pmid: 16282372
references.citation: Arch Ophthalmol. 1982 Feb;100(2):272-8
references.pmid: 7065944
references.citation: Am J Hum Genet. 2009 Nov;85(5):581-92
references.pmid: 19853238
references.citation: Arch Ophthalmol. 1988 Sep;106(9):1261-8
references.pmid: 3415551
references.citation: Arch Ophthalmol. 1982 Jul;100(7):1108-14
references.pmid: 7092654
references.citation: Nat Genet. 1992 Jul;1(4):246-50
references.pmid: 1302019
references.citation: Am J Ophthalmol. 1966 Jun;61(6):1405-15
references.pmid: 5938308
references.citation: Proc Natl Acad Sci U S A. 2000 Nov 7;97(23):12758-63
references.pmid: 11050159
references.citation: J Ultrastruct Res. 1979 Apr;67(1):23-32
references.pmid: 109622
references.citation: Invest Ophthalmol Vis Sci. 2000 May;41(6):1291-6
references.pmid: 10798642
references.citation: Br J Ophthalmol. 1962 Aug;46(8):449-67
references.pmid: 18170802
references.citation: Ophthalmology. 1993 Nov;100(11):1665-70
references.pmid: 8233392
references.citation: Hum Mol Genet. 1998 Sep;7(9):1517-25
references.pmid: 9700209
references.citation: Hum Mol Genet. 2010 Mar 15;19(6):1108-18
references.pmid: 20053664
references.citation: Ophthalmology. 1985 Dec;92(12):1712-8
references.pmid: 4088624
references.citation: Am J Ophthalmol. 2008 Oct;146(4):501-507
references.pmid: 18619572
references.citation: Exp Eye Res. 2007 Oct;85(4):423-4
references.pmid: 16720022
references.citation: J Gen Physiol. 2006 May;127(5):577-89
references.pmid: 16636205
references.citation: Graefes Arch Clin Exp Ophthalmol. 2010 Oct;248(10):1377-86
references.pmid: 20414784
references.citation: Hum Genet. 1999 May;104(5):383-9
references.pmid: 10394929
references.citation: Nat Genet. 1998 Jul;19(3):241-7
references.pmid: 9662395
references.citation: J Neurosci. 2008 May 28;28(22):5660-70
references.pmid: 18509027
references.citation: J Neurosci. 1989 Jun;9(6):1977-84
references.pmid: 2723762
references.citation: Eye (Lond). 1990;4 ( Pt 2):333-9
references.pmid: 2199241
references.citation: Arch Ophthalmol. 1982 Jul;100(7):1115-21
references.pmid: 7092655
references.citation: Physiology (Bethesda). 2005 Oct;20:292-302
references.pmid: 16174869
references.citation: Trans Am Ophthalmol Soc. 1974;72:139-56
references.pmid: 4142662
references.citation: Arch Ophthalmol. 2005 Nov;123(11):1588-94
references.pmid: 16286623
references.citation: Exp Eye Res. 2007 Jul;85(1):34-43
references.pmid: 17477921