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Multimodal morphological and functional characterization of Malattia Leventinese

  • Giuseppe QuerquesEmail author
  • Benjamin Guigui
  • Nicolas Leveziel
  • Lea Querques
  • Francesco Bandello
  • Eric H. Souied
Retinal Disorders

Abstract

Background

To analyze the morphological and functional characteristics of malattia leventinese.

Methods

This was a chart review of patients with Malattia Leventinese. All patients underwent a complete ophthalmologic examination, including best-corrected visual acuity (BCVA), fundus autofluorescence (FAF), fluorescein angiography (FA), indocyanine green angiography (ICGA), and optical coherence tomography (OCT). Microperimetry and Preferential Hyperacuity Perimeter (PHP) were performed in a subset of patients.

Results

Twelve eyes of six patients were included. BCVA ranged from 20/25 to 20/200. The largest drusen were round, not radially distributed, localized in the perimacular area and around the optic disc. The smallest drusen were not round, radially distributed, mostly localized temporally to the macula. FAF revealed an intense autofluorescence of large drusen. On both FA and ICGA, large round drusen turned to hyperfluorescent in the late phase, while small radial drusen progressively decreased their fluorescence. OCT showed the large round drusen as focal or diffuse deposition of hyperreflective material between the RPE and Bruch membrane within the macula, determining focal dome-shaped or diffuse RPE elevation respectively, and the small radial drusen, which ranged from irregular slight thickening of the RPE/Bruch membrane complex to sawtooth RPE elevation. In three patients (six eyes) that underwent microperimetry and PHP, there was a good correspondence between macular sensitivity and PHP score. Functional impairment correlated topographically to sub-RPE deposition of drusenoid material.

Conclusions

In this series, large round drusen of Malattia Leventinese appeared similar to drusen in age-related macular degeneration, while small radial drusen of Malattia Leventinese shared similarities with early-onset cuticular drusen.

Keywords

Age-related macular degeneration Autofluorescence Doyne honeycomb retinal dystrophy Fluorescein angiography Drusen Malattia leventinese Indocyanine green angiography Optical coherence tomography 

Notes

Financial or material support for the research and the work

None.

The authors have no proprietary interest in the materials used in this study.

References

  1. 1.
    Gass JD (1973) Drusen and disciform macular detachment and degeneration. Arch Ophthalmol 90:206–217PubMedCrossRefGoogle Scholar
  2. 2.
    Pauleikhoff D, Barondes MJ, Minassian D, Chisholm IH, Bird AC (1990) Drusen as risk factors in age-related macular disease. Am J Ophthalmol 109:38–43PubMedGoogle Scholar
  3. 3.
    Vogt A (1925) Die Ophthalmoskopie im rotfreien Licht. In: Graefe A, Saemisch T (eds) Handbuch der gesamten Augenheilkunde. Untersuchungsmethoden, 3rd ed. Verlag von Wilhelm Engelman, Leipzig, pp 1–118Google Scholar
  4. 4.
    Piguet B, Haimovici R, Bird AC (1995) Dominantly inherited drusen represent more than one disorder: a historical review. Eye 9:34–41PubMedCrossRefGoogle Scholar
  5. 5.
    Stone EM, Lotery AJ, Munier FL, Héon E, Piguet B, Guymer RH, Vandenburgh K, Cousin P, Nishimura D, Swiderski RE, Silvestri G, Mackey DA, Hageman GS, Bird AC, Sheffield VC, Schorderet DF (1999) A single EFEMP1 mutation associated with both Malattia Leventinese and Doyne honeycomb retinal dystrophy. Nat Genet 22:199–202PubMedCrossRefGoogle Scholar
  6. 6.
    Matsumoto M, Traboulsi EI (2001) Dominant radial drusen and Arg345Trp EFEMP1 mutation. Am J Ophthalmol 131:810–812PubMedCrossRefGoogle Scholar
  7. 7.
    Michaelides M, Jenkins SA, Brantley MA Jr, Andrews RM, Waseem N, Luong V, Gregory-Evans K, Bhattacharya SS, Fitzke FW, Webster AR (2006) Maculopathy due to the R345W substitution in fibulin-3: distinct clinical features, disease variability, and extent of retinal dysfunction. Invest Ophthalmol Vis Sci 47:3085–3097PubMedCrossRefGoogle Scholar
  8. 8.
    Marmorstein LY, Munier FL, Arsenijevic Y, Schorderet DF, McLaughlin PJ, Chung D, Traboulsi E, Marmorstein AD (2002) Aberrant accumulation of EFEMP1 underlies drusen formation in Malattia Leventinese and age-related macular degeneration. Proc Natl Acad Sci USA 99:13067–13072PubMedCrossRefGoogle Scholar
  9. 9.
    Guigui B, Leveziel N, Martinet V, Massamba N, Sterkers M, Coscas G, Souied EH (2011) Angiography features of early onset drusen. Br J Ophthalmol 95:238–244PubMedCrossRefGoogle Scholar
  10. 10.
    Landa G, Rosen RB, Garcia PM, Seiple WH (2009) Combined three-dimensional spectral OCT/SLO topography and microperimetry: steps toward achieving functional spectral OCT/SLO. Ophthalmic Res 43:92–98PubMedCrossRefGoogle Scholar
  11. 11.
    Alster Y, Bressler NM, Bressler SB, Brimacombe JA, Crompton RM, Duh YJ, Gabel VP, Heier JS, Ip MS, Loewenstein A, Packo KH, Stur M, Toaff T, Preferential Hyperacuity Perimetry Research Group (2005) Preferential hyperacuity perimeter (PreView) for detecting choroidal neovascularization study. Ophthalmology 112:1758–1765PubMedCrossRefGoogle Scholar
  12. 12.
    Bloom SM, Singal IP (2011) The outer Bruch membrane layer: A previously undescribed spectral-domain optical coherence tomography finding. Retina 31:316–323PubMedCrossRefGoogle Scholar
  13. 13.
    Zweifel SA, Engelbert M, Laud K, Margolis R, Spaide RF, Freund KB (2009) Outer retinal tubulation: A novel optical coherence tomography finding. Arch Ophthalmol 127:1596–1602PubMedCrossRefGoogle Scholar
  14. 14.
    Cohen SY, Dubois L, Nghiem-Buffet S, Ayrault S, Fajnkuchen F, Guiberteau B, Delahaye-Mazza C, Quentel G, Tadayoni R (2010) Retinal pseudocysts in age-related geographic atrophy. Am J Ophthalmol 150:211–217PubMedCrossRefGoogle Scholar
  15. 15.
    von Ruckmann 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 237:1–9CrossRefGoogle Scholar
  16. 16.
    von Ruckmann A, Schmidt KG, Fitzke FW, Bird AC, Jacobi KW (1998) Fundus autofluorescence in patients with hereditary macular dystrophies, Malattia Leventinese, familial dominant and aged-related drusen. Klin Monatsbl Augenheilkd 213:81–86CrossRefGoogle Scholar
  17. 17.
    von Ruckmann A, Fitzke FW, Bird AC (1997) Fundus autofluorescence in age related macular disease imaged with a scanning laser ophthalmoscope. Invest Ophthalmol Vis Sci 38:478–486Google Scholar
  18. 18.
    Lois N, Owens SL, Coco R, Hopkins J, Fitzke FW, Bird AC (2002) Fundus autofluorescence in patients with age-related macular degeneration and high risk of visual loss. Am J Ophthalmol 133:341–349PubMedCrossRefGoogle Scholar
  19. 19.
    Kitagawa K, Nishida S, Ogura Y (1989) In vivo quantitation of autofluorescence in human retinal pigment epithelium. Ophthalmologica 199:116–121PubMedCrossRefGoogle Scholar
  20. 20.
    Pauleikhoff D, Zuels S, Sheraidah GS, Marshall J, Wessing A, Bird AC (1992) Correlation between biochemical composition and fluorescein binding of deposits in Bruch’s membrane. Ophthalmology 99:1548–1553PubMedGoogle Scholar
  21. 21.
    Arnold JJ, Quaranta M, Soubrane G, Sarks SH, Coscas G (1997) Indocyanine green angiography of drusen. Am J Ophthalmol 124:344–356PubMedGoogle Scholar
  22. 22.
    Scheider A, Neuhauser L (1992) Fluorescence characteristics of drusen during indocyanine-green angiography and their possible correlation with choroidal perfusion. Ger J Ophthalmol 1:328–334PubMedGoogle Scholar
  23. 23.
    Curcio CA, Millican CL, Bailey T, Kruth HS (2001) Accumulation of cholesterol with age in human Bruch’s membrane. Invest Ophthalmol Vis Sci 42:265–274PubMedGoogle Scholar
  24. 24.
    Li CM, Clark ME, Rudolf M, Curcio CA (2007) Distribution and composition of esterified and unesterified cholesterol in extra-macular drusen. Exp Eye Res 85:192–201PubMedCrossRefGoogle Scholar
  25. 25.
    Russell SR, Gupta RR, Folk JC, Mullins RF, Hageman GS (2004) Comparison of color to fluorescein angiographic images from patients with early-adult onset grouped drusen suggests drusen substructure. Am J Ophthalmol 137:924–930PubMedCrossRefGoogle Scholar
  26. 26.
    Collins ET (1913) A pathological report upon a case of Doyne’s chorioditis (‘Honeycomb’ or ‘family’ choroiditis). The ophthalmoscope 11:537–538Google Scholar
  27. 27.
    Dusek J, Streicher T, Schmidt K (1982) Hereditary drusen of Bruch’s membrane II: Studies of semi-thin sections and electron microscopy results. Klin Monatsbl Augenheilkd 181:79–83PubMedCrossRefGoogle Scholar
  28. 28.
    Fu L, Garland D, Yang Z, Shukla D, Rajendran A, Pearson E, Stone EM, Zhang K, Pierce EA (2007) The R345W mutation in EFEMP1 is pathogenic and causes AMD-like deposits in mice. Hum Mol Genet 16:2411–2422PubMedCrossRefGoogle Scholar
  29. 29.
    Leng T, Rosenfeld PJ, Gregori G, Puliafito CA, Punjabi OS (2009) Spectral domain optical coherence tomography characteristics of cuticular drusen. Retina 29:988–993PubMedCrossRefGoogle Scholar
  30. 30.
    Querques G, Guigui B, Leveziel N, Querques L, Coscas G, Soubrane G, Souied EH (2011) Insights into pathology of cuticular drusen from integrated confocal scanning laser ophthalmoscopy imaging and corresponding spectral domain optical coherence tomography. Graefes Arch Clin Exp Ophthalmol 249:1617–1625PubMedCrossRefGoogle Scholar
  31. 31.
    Evans K, Gregory CY, Wijesuriya SD, Kermani S, Jay MR, Plant C, Bird AC (1997) Assessment of the phenotypic range seen in doyne honeycomb retinal dystrophy. Arch Ophthalmol 115:904–910PubMedCrossRefGoogle Scholar
  32. 32.
    Gass JDM, Jallow S, Davis B (1985) Adult vitelliform macular detachment occurring in patients with basal laminar drusen. Am J Ophthalmol 99:445–459PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Giuseppe Querques
    • 1
    Email author
  • Benjamin Guigui
    • 1
  • Nicolas Leveziel
    • 1
  • Lea Querques
    • 1
    • 2
  • Francesco Bandello
    • 2
  • Eric H. Souied
    • 1
  1. 1.Department of OphthalmologyUniversity Paris Est Creteil, Centre Hospitalier Intercommunal de CreteilCreteilFrance
  2. 2.Department of OphthalmologyHospital San Raffaele, University Vita Salute San RaffaeleMilanItaly

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