OOG/ZOG: Van huet foveal sparing in patienten met m. stargardt

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OOG/ZOG: Van huet foveal sparing in patienten met m. stargardt

  1. 1. Foveal sparing in patients with Stargardt disease Ramon van Huet OOG/ZOG Hotel Val Monte December 1st, 2012
  2. 2. Introduction | Foveal sparing• Macular atrophy that spares the fovea• Atrophy surrounds the fovea for at least 180
  3. 3. Introduction | Foveal sparing in Stargardt patientsFoveal sparing is observed in:• Stargardt disease• Maternally Inherited Diabetes & Deafness (MIDD)• Age-related macular degeneration (AMD)• Some PRPH2 (RDS) related diseases (e.g. pseudostargardt phenotype)
  4. 4. Introduction | Purpose• To give a clinical description of foveal sparing in Stargardt patients• Provide some possible pathogenic pathways• Knowledge about the origin of the foveal sparing may be beneficial for the development of new therapeutic options
  5. 5. Methods | Patients 13 STGD1 patients with 149 patients foveal sparing who are genetically Database: analysed 136 patients without foveal 316 patients sparing 167 patients without genetic analyses
  6. 6. Methods | ParametersHistory• Age of onset• Initial symptom• Family historyOphthalmic examinations• Visual acuity• PerimetryImaging• Fundus photographs• Autofluorescence• OCT scans
  7. 7. Results | Genetics • 3 patients (23%) carried two mutations • 10 patients (77%) carried one mutation Mutation 1 (DNA) Mutation 1(Peptide) Mutation 2 (DNA) Mutation 2(Peptide)Patient 10 c.5461-10T>C - - -Patient 14 c.3113C>T p.Ala1038Val c.3874C>T p.Gln1292XPatient 17 c.5461-10T>C - - -Patient 24 c.4363T>C p.Cys1455Arg - -Patient 26 c.1822T>A p.Phe608Ile - -Patient 55 c.768G>T p.Val256Val c.3113C>T p.Ala1038ValPatient 84 c.768G>T p.Val256Val - -Patient 96 c.3874C>T p.Gln1292X - -Patient 102 c.4771G>A p.Gly1591Arg - -Patient 117 c.5461-10T>C - - -Patient 118 c.2588G>C p.Gly863Ala - -Patient 244 c.3874C>T p.Gln1292X c.1928T>G p.Val643GlyPatient 311 c.5196+1G>T - - -
  8. 8. Results | HistoryAge of onset• Mean onset: 51,8 years (range: 39 - 81 years)Symptoms• Initial symptom:  Progressive visual acuity loss (92%)  Metamorphopsia (8%)Family history• 54% affected family members
  9. 9. Results | Ophthalmic examination Leeftijd BCVA ≤ 0.8 59.7 BCVA ≤ 0.4 74.6 BCVA ≤ 0.1 78.6 BCVA ≤ 1/60 80.7 BCVA = Best corrected visual acuity
  10. 10. Results | Imaging Visual acuity 0.8-
  11. 11. Results | Perimetry
  12. 12. Results | Imaging 4.5 yearVisual acuity 0.8+ Visual acuity 0.8-
  13. 13. Results | ImagingNormal Visual acuity 0.8-
  14. 14. Results | Imaging Visual acuity 0.1-
  15. 15. Results | Perimetry
  16. 16. Results | Imaging Visual acuity 0.1-
  17. 17. Results | ImagingNormal Visual acuity 0.1-
  18. 18. But what causes this preservation of the foveal area??
  19. 19. Discussion | Possible causes of foveal sparingLate-onset Stargardt is on the mild side of the spectrum of retinal dystrophies caused by mutations in ABCA4Fovea spared because of:• Only one ABCA4 mutation• Mild mutations in ABCA4 Late-onset Stargardt
  20. 20. Discussion | Possible causes of foveal sparingInfluence of other genes:• Protective variants in modifier genes• Digenic phenotype On which cells/structures do these additional genes act? RPE? Photoreceptors? Müller cells? The ABCA4 gene? The ABCR channel? (Modifier) ABCA4 Gene X ABCR
  21. 21. Discussion | Possible causes of foveal sparing • Inhomogeneity in distribution of spectrally different cones Sparing of L- and M- cones which are more centrally located1 • Inhomogeneity in distribution of RPE cells  In the macula, RPE cells are thicker and narrowly spaced.11. D. Besch et al, Vision research 43 (2003) p. 3095-3108
  22. 22. Discussion | Possible causes of foveal sparing • Inhomogeneity in distribution of the Müller cells Differences in Müller cell density in fovea and periphery1 Various types of Müller cells21. Chao et al, (1997) Journal of Neurocytology 26(7), p.439-4542. Schnitzer et al (1987) Cell Tissue Research 248(1), 55-61
  23. 23. AcknowledgementsOphthalmologyMuhamad MuhamadCarla WestenengJeroen KleveringCarel HoyngHuman geneticsFrans CremersAnneke den Hollander

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