Documenta Ophthalmologica

, Volume 118, Issue 3, pp 239–246 | Cite as

Detailed analysis of retinal function and morphology in a patient with autosomal recessive bestrophinopathy (ARB)

  • Christina GerthEmail author
  • Robert J. Zawadzki
  • John S. Werner
  • Elise Héon
Case Report


The objective of the paper is to study the retinal microstructure and function in a patient with autosomal recessive bestrophinopathy (ARB). Retinal function and morphology assessment in a patient diagnosed with a biallelic mutation in the BEST1 gene (heterozygote mutations: Leu88del17 and A195V) included: full-field electroretinogram (ffERG) and multifocal electroretinogram (mfERG), electro-oculogram (EOG) testing, and imaging with a high-resolution Fourier-domain optical coherence tomography (Fd-OCT) system (UC Davis Medical Center; axial resolution: 4.5 μm, acquisition speed: 9 frames/s, 1,000 A-scans/frame) combined with a flexible scanning head (Bioptigen Inc.). The 11-year old asymptomatic boy showed a well-demarcated retinopathy with deposits. Functional assessment revealed normal visual acuity, reduced central mfERG responses, delayed rod and rod-cone b-wave ffERG responses, and reduced light rise in the EOG. Fd-OCT demonstrated RPE deposits, photoreceptor detachment, elongated and thickened photoreceptor outer segments, but preserved inner retinal layers. In conclusion, ARB associated retinal dystrophy shows functional and morphological changes that overlap with classic Best disease. For the first time, high-resolution imaging provided in vivo evidence of RPE and photoreceptor involvement in ARB.


Autosomal recessive bestrophinopathy ARB Fourier-domain OCT Multifocal ERG Electro-oculogram 





Fourier-domain optical coherence tomography


Full-field electroretinogram


International Society for Clinical Electrophysiology of Vision


Multifocal electroretinogram


Retinal pigment epithelium



This study was supported by NIH/NEI grant 014743 (JSW), Research to Prevent Blindness Senior Scientist Award (JSW), the Mira Godard Fund (EH) and the Albrecht Fund (JSW) in collaboration with Bioptigen, Inc. We thank Yesmino Elia for study coordination, Carmelina Trimboli-Heidler for fundus photography, and Tom Wright and Carole Panton for help with data analysis.


  1. 1.
    Burgess R, Millar ID, Leroy BP et al (2008) Biallelic mutation of BEST1 causes a distinct retinopathy in humans. Am J Hum Genet 82:19–31. doi: 10.1016/j.ajhg.2007.08.004 PubMedCrossRefGoogle Scholar
  2. 2.
    Petrukhin K, Koisti MJ, Bakall B et al (1998) Identification of the gene responsible for Best macular dystrophy. Nat Genet 19:241–247. doi: 10.1038/915 PubMedCrossRefGoogle Scholar
  3. 3.
    Stohr H, Marquardt A, Rivera A et al (1998) A gene map of the Best’s vitelliform macular dystrophy region in chromosome 11q12–q13.1. Genome Res 8:48–56PubMedGoogle Scholar
  4. 4.
    Marquardt A, Stohr H, Passmore LA et al (1998) Mutations in a novel gene, VMD2, encoding a protein of unknown properties cause juvenile-onset vitelliform macular dystrophy (Best’s disease). Hum Mol Genet 7:1517–1525. doi: 10.1093/hmg/7.9.1517 PubMedCrossRefGoogle Scholar
  5. 5.
    Marmor MF, Holder GE, Seeliger MW, Yamamoto S (2004) Standard for clinical electroretinography (2004 update). Doc Ophthalmol 108:107–114. doi: 10.1023/B:DOOP.0000036793.44912.45 PubMedCrossRefGoogle Scholar
  6. 6.
    Hood DC, Birch DG (1996) Assessing abnormal rod photoreceptor activity with the a-wave of the electroretinogram: applications and methods. Doc Ophthalmol 92:253–267. doi: 10.1007/BF02584080 PubMedCrossRefGoogle Scholar
  7. 7.
    Marmor MF, Zrenner E (1993) Standard for clinical electro-oculography. International society for clinical electrophysiology of vision. Arch Ophthalmol 111:601–604PubMedGoogle Scholar
  8. 8.
    Wojtkowski M, Leitgeb R, Kowalczyk A et al (2002) In vivo human retinal imaging by Fourier domain optical coherence tomography. J Biomed Opt 7:457–463. doi: 10.1117/1.1482379 PubMedCrossRefGoogle Scholar
  9. 9.
    Zawadzki RJ, Jones SM, Olivier SS et al (2005) Adaptive-optics optical coherence tomography for high-resolution and high-speed 3D retinal in-vivo imaging. Opt Express 13:8532–8546. doi: 10.1364/OPEX.13.008532 PubMedCrossRefGoogle Scholar
  10. 10.
    Zawadzki RJ, Fuller AR, Wiley DF et al (2007) Adaptation of a support vector machine algorithm for segmentation and visualization of retinal structures in volumetric optical coherence tomography data sets. J Biomed Opt 12:041206. doi: 10.1117/1.2772658 PubMedCrossRefGoogle Scholar
  11. 11.
    Wabbels B, Preising MN, Kretschmann U et al (2006) Genotype-phenotype correlation and longitudinal course in ten families with Best vitelliform macular dystrophy. Graefes Arch Clin Exp Ophthalmol 244:1453–1466. doi: 10.1007/s00417-006-0286-6 PubMedCrossRefGoogle Scholar
  12. 12.
    Spaide RF, Noble K, Morgan A, Freund KB (2006) Vitelliform macular dystrophy. Ophthalmology 113:1392–1400. doi: 10.1016/j.ophtha.2006.03.023 PubMedCrossRefGoogle Scholar
  13. 13.
    Weingeist TA, Kobrin JL, Watzke RC (1982) Histopathology of Best’s macular dystrophy. Arch Ophthalmol 100:1108–1114PubMedGoogle Scholar
  14. 14.
    Frangieh GT, Green WR, Fine SL (1982) A histopathologic study of Best’s macular dystrophy. Arch Ophthalmol 100:1115–1121PubMedGoogle Scholar
  15. 15.
    Mullins RF, Oh KT, Heffron E et al (2005) Late development of vitelliform lesions and flecks in a patient with Best disease: clinicopathologic correlation. Arch Ophthalmol 123:1588–1594. doi: 10.1001/archopht.123.11.1588 PubMedCrossRefGoogle Scholar
  16. 16.
    Bakall B, Radu RA, Stanton JB et al (2007) Enhanced accumulation of A2E in individuals homozygous or heterozygous for mutations in BEST1 (VMD2). Exp Eye Res 85:34–43. doi: 10.1016/j.exer.2007.02.018 PubMedCrossRefGoogle Scholar
  17. 17.
    Marmorstein AD, Marmorstein LY, Rayborn M et al (2000) Bestrophin, the product of the Best vitelliform macular dystrophy gene (VMD2), localizes to the basolateral plasma membrane of the retinal pigment epithelium. Proc Natl Acad Sci USA 97:12758–12763. doi: 10.1073/pnas.220402097 PubMedCrossRefGoogle Scholar
  18. 18.
    Marmorstein AD, Stanton JB, Yocom J et al (2004) A model of Best vitelliform macular dystrophy in rats. Invest Ophthalmol Vis Sci 45:3733–3739. doi: 10.1167/iovs.04-0307 PubMedCrossRefGoogle Scholar
  19. 19.
    Rosenthal R, Bakall B, Kinnick T et al (2006) Expression of bestrophin-1, the product of the VMD2 gene, modulates voltage-dependent Ca2+ channels in retinal pigment epithelial cells. FASEB J 20:178–180PubMedGoogle Scholar
  20. 20.
    Wachtmeister L, Dowling JE (1978) The oscillatory potentials of the mudpuppy retina. Invest Ophthalmol Vis Sci 17:1176–1188PubMedGoogle Scholar
  21. 21.
    King-Smith PE, Loffing DH, Jones R (1986) Rod and cone ERGs and their oscillatory potentials. Invest Ophthalmol Vis Sci 27:270–273PubMedGoogle Scholar
  22. 22.
    Hood DC, Frishman LJ, Saszik S, Viswanathan S (2002) Retinal origins of the primate multifocal ERG: implications for the human response. Invest Ophthalmol Vis Sci 43:1673–1685PubMedGoogle Scholar
  23. 23.
    Holder GE (1987) Significance of abnormal pattern electroretinography in anterior visual pathway dysfunction. Br J Ophthalmol 71:166–171. doi: 10.1136/bjo.71.3.166 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Christina Gerth
    • 1
    • 2
    Email author
  • Robert J. Zawadzki
    • 3
  • John S. Werner
    • 3
  • Elise Héon
    • 1
  1. 1.Department of Ophthalmology and Vision Sciences, The Hospital for Sick ChildrenUniversity of TorontoTorontoCanada
  2. 2.Department of OphthalmologyUniversity of RostockRostockGermany
  3. 3.Department of Ophthalmology & Vision Science, Vision Science and Advanced Retinal Imaging Laboratory (VSRI)University of CaliforniaDavisUSA

Personalised recommendations