Fundus autofluorescence in children and teenagers with hereditary retinal diseases

  • Bettina Wabbels
  • Anke Demmler
  • Karina Paunescu
  • Erika Wegscheider
  • Markus N. Preising
  • Birgit Lorenz
Clinical Investigation

Abstract

Introduction

In adults, evaluation of fundus autofluorescence (AF) plays an important role in the differential diagnosis of retinal diseases. The aim of this study was to evaluate the feasibility of recording AF in children and teenagers and to define typical AF findings of various hereditary retinal diseases during childhood.

Methods

Fifty patients aged 2 to 16 years with hereditary retinal diseases were analysed using the HRA (Heidelberg Retina Angiograph). To enhance the AF signal, a mean of up to 16 single images was calculated. Twenty healthy children (aged 4–16 years) served as controls.

Results

In many children as young as 5 years of age and even in one 2-year-old child good AF images could be obtained. To achieve high quality images, larger image series (about 50 single images) were taken and appropriate single images were chosen manually to calculate the mean. Characteristically, Stargardt disease shows a central oval area of reduced AF, often surrounded by more irregular AF. In patients with Best disease, a central round structure with regular or irregular intense AF is visualised. Some patients with X-linked retinoschisis show central radial structures. In many patients with rod-cone dystrophies, a central oval ring-shaped area of increased AF is present. In early-onset severe retinal dystrophy (EOSRD) with RPE65 mutations AF is completely absent, whereas in other forms of Leber congenital amaurosis, AF is normal.

Discussion

Fundus autofluorescence may visualise disease-specific distributions of lipofuscin in the retinal pigment epithelium, often not (yet) visible on ophthalmoscopy. AF images can be used in children to differentiate hereditary retinal diseases and to facilitate follow-up controls. In many cases, four single images are sufficient to analyse the AF pattern.

Keywords

Fundus autofluorescence Children Hereditary retinal disease 

References

  1. 1.
    Chung JE, Spaide RF (2004) Fundus autofluorescence and vitelliform macular dystrophy. Arch Ophthalmol 122:1078–1079CrossRefPubMedGoogle Scholar
  2. 2.
    Cideciyan AV, Aleman TS, Swider M, Schwartz SB, Steinberg JD, Brucker AJ, Maguire AM, Bennett J, Stone EM, Jacobson SG (2004) Mutations in ABCA4 result in accumulation of lipofuscin before slowing of the retinoid cycle: a reappraisal of the human disease sequence. Hum Mol Genet 13:525–534CrossRefPubMedGoogle Scholar
  3. 3.
    Delori FC, Dorey CK, Staurenghi G, Arend O, Goger DG, Weiter JJ (1995) In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics. Invest Ophthalmol Vis Sci 36:718–729PubMedGoogle Scholar
  4. 4.
    Delori FC, Staurenghi G, Arend O, Dorey CK, Goger DG, Weiter JJ (1995) In vivo measurement of lipofuscin in Stargardt's disease—fundus flavimaculatus. Invest Ophthalmol Vis Sci 36:2327–2331PubMedGoogle Scholar
  5. 5.
    Delori FC, Fleckner MR, Goger DG, Weiter JJ, Dorey CK (2000) Autofluorescence distribution associated with drusen in age-related macular degeneration. Invest Ophthalmol Vis Sci 41:496–504PubMedGoogle Scholar
  6. 6.
    Delori FC, Goger DG, Dorey CK (2001) Age-related accumulation and spatial distribution of lipofuscin in RPE of normal subjects. Invest Ophthalmol Vis Sci 42:1855–1866PubMedGoogle Scholar
  7. 7.
    Eriksson U, Larsson E, Holmstrom G (2004) Optical coherence tomography in the diagnosis of juvenile X-linked retinoschisis. Acta Ophthalmol Scand 82:218–223CrossRefPubMedGoogle Scholar
  8. 8.
    Gass JDM (1997) Heredodystrophic disorders affecting the pigment epithelium and retina. In: JDM Gass (ed) Stereoscopic atlas of macular diseases, diagnosis and treatment. Mosby, St. Louis, pp 303–312Google Scholar
  9. 9.
    Gerth C, Andrassi-Darida M, Bock M, Preising MN, Weber BH, Lorenz B (2002) Phenotypes of 16 Stargardt macular dystrophy/fundus flavimaculatus patients with known ABCA4 mutations and evaluation of genotype-phenotype correlation. Graefes Arch Clin Exp Ophthalmol 240:628–638CrossRefPubMedGoogle Scholar
  10. 10.
    Holz FG (2001) Autofluoreszenz-Imaging der Makula. Ophthalmologe 98:10–18CrossRefPubMedGoogle Scholar
  11. 11.
    Holz FG, Bellman C, Staudt S, Schütt F, Völcker HE (2001) Fundus autofluorescence and development of geographic atrophy in age-related macular degeneration. Trans Ophthalmol Soc UK 42:1051–1056Google Scholar
  12. 12.
    Jarc-Vidmar M, Kraut A, Hawlina M (2003) Fundus autofluorescence imaging in Best's vitelliform dystrophy. Klin Monatsbl Augenheilkd 220:861–867CrossRefPubMedGoogle Scholar
  13. 13.
    Kabanarou SA, Holder GE, Bird AC, Webster AR, Stanga PE, Vickers S, Harney BA (2003) Isolated foveal retinoschisis as a cause of visual loss in young females. Br J Ophthalmol 87:801–803CrossRefPubMedGoogle Scholar
  14. 14.
    Katz ML, Gao CL, Rice LM (1996) Formation of lipofuscin-like fluorophores by reaction of retinal with photoreceptor outer segments and liposomes. Mech Ageing Dev 92:159–174CrossRefPubMedGoogle Scholar
  15. 15.
    Katz ML, Wendt KD, Sanders DN (2005) RPE65 gene mutation prevents development of autofluorescence in retinal pigment epithelial phagosomes. Mech Ageing Dev 126:513–521CrossRefPubMedGoogle Scholar
  16. 16.
    Kennedy CJ, Rakoczy PE, Constable IJ (1995) Lipofuscin of the retinal pigment epithelium: a review. Eye 9:763–771PubMedGoogle Scholar
  17. 17.
    Lamb LE, Simon DJ (2004) A2E: a component of ocular lipofuscin. Photochem Photobiol 79:127–136CrossRefPubMedGoogle Scholar
  18. 18.
    Lois N, Halfyard AS, Bunce C, Bird AC, Fitzke FW (1999) Reproducibility of fundus autofluorescence measurements obtained using a confocal scanning laser ophthalmoscope. Br J Ophthalmol 83:276–279PubMedCrossRefGoogle Scholar
  19. 19.
    Lois N, Halfyard AS, Bird AC, Fitzke FW (2000) Quantitative evaluation of fundus autofluorescence imaged “in vivo” in eyes with retinal disease. Br J Ophthalmol 84:741–745CrossRefPubMedGoogle Scholar
  20. 20.
    Lois N, Holder GE, Bunce C, Fitzke FW, Bird AC (2001) Phenotypic subtypes of Stargardt macular dystrophy—fundus flavimaculatus. Arch Ophthalmol 119:359–369PubMedGoogle Scholar
  21. 21.
    Lois N, Halfyard AS, Bird AC, Holder GE, Fitzke FW (2004) Fundus autofluorescence in Stargardt macular dystrophy—fundus flavimaculatus. Am J Ophthalmol 138:55–63CrossRefPubMedGoogle Scholar
  22. 22.
    Lorenz B, Wabbels B, Wegscheider E, Hamel CP, Drexler W, Preising MN (2004) Lack of fundus autofluorescence to 488 nm from childhood on in patients with early onset severe retinal dystrophy (EOSRD) associated with mutations in RPE65. Ophthalmology 111:1585–1594CrossRefPubMedGoogle Scholar
  23. 23.
    Mata NL, Weng J, Travis GH (2000) Biosynthesis of a major lipofuscin fluorophore in mice and humans with ABCR-mediated retinal and macular degeneration. Proc Natl Acad Sci USA 97:7154–7159CrossRefPubMedGoogle Scholar
  24. 24.
    Ozdemir H, Karacorlu S, Karacorlu M (2004) Optical coherence tomography findings in familial foveal retinoschisis. Am J Ophthalmol 137:179–181CrossRefPubMedGoogle Scholar
  25. 25.
    Paunescu K, Wabbels B, Preising M, Lorenz B (2004) Longitudinal and cross sectional study of patients with early onset severe retinal dystrophy (EOSRD) associated with RPE65 mutations. Graefes Arch Clin Exp Ophthalmol http://dx.doi.org/10.1007/s00417-004-1020-x
  26. 26.
    Robson AG, El Amir A, Bailey C, Egan CA, Fitzke FW, Webster AR, Bird AC, Holder GE (2003) Pattern ERG correlates of abnormal fundus autofluorescence in patients with retinitis pigmentosa and normal visual acuity. Invest Ophthalmol Vis Sci 44:3544–3550CrossRefPubMedGoogle Scholar
  27. 27.
    Robson AG, Moreland JD, Pauleikhoff D, Morrissey T, Holder GE, Fitzke FW, Bird AC, Van Kuijk FJ (2003) Macular pigment density and distribution: comparison of fundus autofluorescence with minimum motion photometry. Vision Res 43:1765–1775CrossRefPubMedGoogle Scholar
  28. 28.
    Robson AG, Egan CA, Luong VA, Bird AC, Holder GE, Fitzke FW (2004) Comparison of fundus autofluorescence with photopic and scotopic fine-matrix mapping in patients with retinitis pigmentosa and normal visual acuity. Invest Ophthalmol Vis Sci 45:4119–4125CrossRefPubMedGoogle Scholar
  29. 29.
    Scholl HP, Chong NH, Robson AG, Holder GE, Moore AT, Bird AC (2004) Fundus autofluorescence in patients with leber congenital amaurosis. Invest Ophthalmol Vis Sci 45:2747–2752CrossRefPubMedGoogle Scholar
  30. 30.
    Tantri A, Vrabec TR, Cu-Unjieng A, Frost A, Annesley WH Jr, Donoso LA (2004) X-linked retinoschisis: a clinical and molecular genetic review. Surv Ophthalmol 49:214–230CrossRefPubMedGoogle Scholar
  31. 31.
    Von Rückmann A, Fitzke FW, Bird AC (1997) In vivo fundus autofluorescence in macular dystrophies. Arch Ophthalmol 115:609–615PubMedGoogle Scholar
  32. 32.
    Von Rückmann A, Schmidt KG, Fitzke FW, Bird AC, Jacobi KW (1998) Studies of the distribution of lipofuscin in the retinal pigment epithelium using high-resolution TV laser scanning ophthalmoscopy. Ophthalmologe 95:699–705CrossRefPubMedGoogle Scholar
  33. 33.
    Von Rückmann A, Fitzke FW, Bird AC (1999) Distribution of pigment epithelium autofluorescence in retinal disease state recorded in vivo and its change over time. Graefes Arch Clin Exp Ophthalmol 237:1–9CrossRefPubMedGoogle Scholar
  34. 34.
    Wabbels B, Preising M, Kretschmann U, Andrassi-Darida M, Demmler A, Lorenz B (2005) Genotype-phenotype correlation and longitudinal course in 10 families with Best vitelliform macular dystrophy. Br J Ophthalmol (submitted)Google Scholar
  35. 35.
    Wegscheider E, Preising MN, Lorenz B (2004) Fundus autofluorescence in carriers of X-linked recessive retinitis pigmentosa associated with mutations in RPGR, and correlation with electrophysiological and psychophysical data. Graefes Arch Clin Exp Ophthalmol 242:501–511PubMedCrossRefGoogle Scholar
  36. 36.
    Weiter JJ, Delori FC, Wing GL, Fitch KA (1986) Retinal pigment epithelial lipofuscin and melanin and choroidal melanin in human eyes. Invest Ophthalmol Vis Sci 27:145–152PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Bettina Wabbels
    • 1
    • 2
  • Anke Demmler
    • 1
  • Karina Paunescu
    • 1
  • Erika Wegscheider
    • 1
  • Markus N. Preising
    • 1
  • Birgit Lorenz
    • 1
  1. 1.Department of Paediatric Ophthalmology, Strabismology and OphthalmogeneticsUniversity of Regensburg, KlinikumRegensburgGermany
  2. 2.Department of OphthalmologyUniversity of Bonn, KlinikumBonnGermany

Personalised recommendations