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Full-field electroretinography, visual acuity and visual fields in Usher syndrome: a multicentre European study

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Abstract

Purpose

Usher syndrome (USH) is a multisensory deficiency involving vision, hearing and the vestibular system. The purpose of this study is to report on the functional data (i.e. electroretinography, visual fields, visual acuity) of patients with retinitis pigmentosa (RP) due to Usher syndrome that were collected in a multicentre European study (TREATRUSH).

Methods

A total of 268 genetically confirmed USH patients underwent electrophysiological examinations in the context of multimodal ophthalmological examination in the study (75 USH1, 189 USH2 and four USH3). Full-field electroretinography (ERG) was performed according to ISCEV standards, visual field determination was carried out with either the Octopus or Goldmann perimeters and visual acuity was examined with either ETDRS or Snellen charts. The data were compared between USH subtypes (USH1/USH2/USH3) and correlated with age.

Results

Visual acuity decreases significantly with age for both USH1 and USH2 (p < 0.001), without a difference between the two cohorts. When corrected for age, the preserved kinetic visual field was significantly larger in USH2 than in USH1 (p = 0.04). Furthermore, the preserved kinetic visual field area showed a significant decrease with age (based on an exponential fit) in both USH1 and USH2 (p < 0.001). In USH1 patients, however, the visual field was already vastly reduced at an early age. The ERG results were abnormal in all patients. Detectable data for scotopic ERG were obtained from nine patients, and data of photopic ERG were obtained from 24 patients, without a difference between USH1 and USH2 subtypes.

Conclusions

There are differences in the phenotypes of RP in USH subtypes, most visible in the progression of visual fields between USH1 and USH2. The perimetric reduction occurs earlier in USH1 than in USH2. In both subtypes, visual acuity decreases significantly with age and the ERG is not detectable already at early ages.

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References

  1. Zrada SE, Braat K, Doty RL, Laties AM (1996) Olfactory loss in Usher syndrome: Another sensory deficit? Am J Med Genet 64(4):602–603

    Article  CAS  PubMed  Google Scholar 

  2. Petit C (2001) Usher syndrome: from genetics to pathogenesis. Annu Rev Genom Hum Genet 2:271–297

    Article  CAS  Google Scholar 

  3. Fakin A, Jarc-Vidmar M, Glavač D, Bonnet C, Petit C, Hawlina M (2012) Fundus autofluorescence and optical coherence tomography in relation to visual function in Usher syndrome type 1 and 2. Vision Res 15(75):60–70

    Article  Google Scholar 

  4. Pakarinen L, Tuppurainen K, Laippala P, Mäntyjärvi M, Puhakka H (1995–1996) The ophthalmological course of Usher syndrome type III. Int Ophthalmol 19(5):307–11

  5. Ness SL, Ben-Yosef T, Bar-Lev A, Madeo AC, Brewer CC, Avraham KB et al (2003) Genetic homogeneity and phenotypic variability among Ashkenazi Jews with Usher syndrome type III. J Med Genet 40(10):767–772

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Bonnet C, Riahi Z, Chantot-Bastaraud S, Smagghe L, Letexier M, Marcaillou C et al (2016) An innovative strategy for the molecular diagnosis of Usher syndrome identifies causal biallelic mutations in 93% of European patients. Eur J Hum Genet EJHG 24(12):1730–1738

    Article  CAS  PubMed  Google Scholar 

  7. Iannaccone A, Kritchevsky SB, Ciccarelli ML, Tedesco SA, Macaluso C, Kimberling WJ et al (2004) Kinetics of visual field loss in Usher syndrome Type II. Invest Ophthalmol Vis Sci 45(3):784–792

    Article  PubMed  Google Scholar 

  8. Pierrache LHM, Hartel BP, van Wijk E, Meester-Smoor MA, Cremers FPM, de Baere E et al (2016) Visual prognosis in USH2A-associated retinitis pigmentosa is worse for patients with usher syndrome type IIa than for those with nonsyndromic retinitis pigmentosa. Ophthalmology 123(5):1151–1160

    Article  PubMed  Google Scholar 

  9. Sengillo JD, Cabral T, Schuerch K, Duong J, Lee W, Boudreault K et al (2017) Electroretinography reveals difference in cone function between syndromic and nonsyndromic USH2A patients. Sci Rep 7(1):11170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Lenassi E, Saihan Z, Cipriani V, Le Quesne Stabej P, Moore AT, Luxon LM et al (2014) Natural history and retinal structure in patients with Usher syndrome type 1 owing to MYO7A mutation. Ophthalmology 121(2):580–587

    Article  PubMed  Google Scholar 

  11. Fleischhauer J, Njoh WA, Niemeyer G (2005) Syndromic retinitis pigmentosa: ERG and phenotypic changes. Klin Monatsbl Augenheilkd 222(3):186–190

    Article  CAS  PubMed  Google Scholar 

  12. Malm E, Ponjavic V, Möller C, Kimberling WJ, Stone ES, Andréasson S (2011) Alteration of rod and cone function in children with Usher syndrome. Eur J Ophthalmol 21(1):30–38

    Article  PubMed  Google Scholar 

  13. Mets MB, Young NM, Pass A, Lasky JB (2000) Early diagnosis of Usher syndrome in children. Trans Am Ophthalmol Soc 98:237–242 discussion 243-245

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Sandberg MA, Rosner B, Weigel-DiFranco C, McGee TL, Dryja TP, Berson EL (2008) Disease course in patients with autosomal recessive retinitis pigmentosa due to the USH2A gene. Invest Ophthalmol Vis Sci 49(12):5532–5539

    Article  PubMed  PubMed Central  Google Scholar 

  15. Tsilou ET, Rubin BI, Caruso RC, Reed GF, Pikus A, Hejtmancik JF et al (2002) Usher syndrome clinical types I and II: Could ocular symptoms and signs differentiate between the two types? Acta Ophthalmol Scand 80(2):196–201

    Article  PubMed  Google Scholar 

  16. Edwards A, Fishman GA, Anderson RJ, Grover S, Derlacki DJ (1998) Visual acuity and visual field impairment in Usher syndrome. Arch Ophthalmol 116(2):165–168

    Article  CAS  PubMed  Google Scholar 

  17. Testa F, Melillo P, Bonnet C, Marcelli V, de Benedictis A, Colucci R et al (2017) Clinical presentation and disease course of usher syndrome because of mutations in MYO7A OR USH2A. c Phila PA 37(8):1581–1590

    CAS  Google Scholar 

  18. Pennings RJE, Huygen PLM, Orten DJ, Wagenaar M, van Aarem A, Kremer H et al (2004) Evaluation of visual impairment in Usher syndrome 1b and Usher syndrome 2a. Acta Ophthalmol Scand 82(2):131–139

    Article  PubMed  Google Scholar 

  19. Nagy D, Schönfisch B, Zrenner E, Jägle H (2008) Long-term follow-up of retinitis pigmentosa patients with multifocal electroretinography. Invest Ophthalmol Vis Sci 49(10):4664–4671

    Article  PubMed  Google Scholar 

  20. Mendieta L, Berezovsky A, Salomão SR, Sacai PY, Pereira JM, Fantini SC (2005) Visual acuity and full-field electroretinography in patients with Usher’s syndrome. Arq Bras Oftalmol 68(2):171–176

    Article  PubMed  Google Scholar 

  21. Zein WM, Falsini B, Tsilou ET, Turriff AE, Schultz JM, Friedman TB et al (2015) Cone responses in Usher syndrome types 1 and 2 by microvolt electroretinography. Invest Ophthalmol Vis Sci 56(1):107–114

    Article  CAS  PubMed Central  Google Scholar 

  22. Sieving PA, Arnold EB, Jamison J, Liepa A, Coats C (1998) Submicrovolt flicker electroretinogram: cycle-by-cycle recording of multiple harmonics with statistical estimation of measurement uncertainty. Invest Ophthalmol Vis Sci 39(8):1462–1469

    CAS  PubMed  Google Scholar 

  23. Iannaccone A (2003) Usher syndrome: correlation between visual field size and maximal ERG response b-wave amplitude. Adv Exp Med Biol 533:123–131

    Article  PubMed  Google Scholar 

  24. Sahly I, Dufour E, Schietroma C, Michel V, Bahloul A, Perfettini I et al (2012) Localization of Usher 1 proteins to the photoreceptor calyceal processes, which are absent from mice. J Cell Biol 199(2):381–399

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Schietroma C, Parain K, Estivalet A, Aghaie A, Boutet de Monvel J, Picaud S et al (2017) Usher syndrome type 1-associated cadherins shape the photoreceptor outer segment. J Cell Biol 216(6):1849–1864

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Liu X, Bulgakov OV, Darrow KN, Pawlyk B, Adamian M, Liberman MC et al (2007) Usherin is required for maintenance of retinal photoreceptors and normal development of cochlear hair cells. Proc Natl Acad Sci U S A 104(11):4413–4418

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Maerker T, van Wijk E, Overlack N, Kersten FFJ, McGee J, Goldmann T et al (2008) A novel Usher protein network at the periciliary reloading point between molecular transport machineries in vertebrate photoreceptor cells. Hum Mol Genet 17(1):71–86

    Article  CAS  PubMed  Google Scholar 

  28. Yang J, Liu X, Zhao Y, Adamian M, Pawlyk B, Sun X et al (2010) Ablation of whirlin long isoform disrupts the USH2 protein complex and causes vision and hearing loss. PLoS Genet 6(5):1000955

    Article  CAS  Google Scholar 

  29. Kaiser PK (2009) Prospective evaluation of visual acuity assessment: a comparison of snellen versus ETDRS charts in clinical practice (An AOS Thesis). Trans Am Ophthalmol Soc 107:311–324

    PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was supported by the European Union Seventh Framework Programme under the Grant Agreement HEALTH-F2-2010-242013 (TREATRUSH) and the Tistou and Charlotte Kerstan Foundation.

Author information

Authors and Affiliations

  1. University Eye Hospital, Center for Ophthalmology, Elfriede-Aulhorn-Str. 7, 72076, Tuebingen, Germany

    Katarina Stingl, Gesa Hahn & Christoph Kernstock

  2. Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tuebingen, Elfriede-Aulhorn-Str. 7, 72076, Tuebingen, Germany

    Anne Kurtenbach, Stephanie Hipp, Ditta Zobor, Susanne Kohl & Eberhart Zrenner

  3. Werner Reichardt Centre for Integrative Neuroscience (CIN), University of Tuebingen, Elfriede-Aulhorn-Str. 7, 72076, Tuebingen, Germany

    Eberhart Zrenner

  4. UMRS 1120, INSERM, Institut de la Vision, Sorbonne Université, 17 rue Moreau, 75012, Paris, France

    Crystel Bonnet & Christine Petit

  5. INSERM, CNRS, Institut de la Vision, Sorbonne Université, 17 rue Moreau, 75012, Paris, France

    Saddek Mohand-Saïd, Isabelle Audo & Jose-Alain Sahel

  6. DHU Sight Restore, INSERM-DHOS CIC1423, CHNO des Quinze-Vingts, 28 rue de Charenton, 75012, Paris, France

    Saddek Mohand-Saïd, Isabelle Audo & Jose-Alain Sahel

  7. Eye Hospital, University Medical Centre Ljubljana, Zaloška cesta 7, 1000, Ljubljana, Slovenia

    Ana Fakin & Marko Hawlina

  8. Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania Luigi Vanvitelli, Viale Abramo Lincoln, 5, 81100, Caserta, CE, Italy

    Francesco Testa & Francesca Simonelli

  9. Laboratory of Genetics and Physiology of Hearing, Institut Pasteur, 75015, Paris, France

    Christine Petit

  10. Collège de France, 11 place Marcelin-Berthelot, 75005, Paris, France

    Christine Petit

  11. Fondation Ophtalmologique Adolphe de Rothschild, 29 Rue Manin, 75019, Paris, France

    Jose-Alain Sahel

  12. Académie des Sciences-Institut de France, 23 quai de Conti, 75006, Paris, France

    Jose-Alain Sahel

  13. Department of Ophthalmology, University of Pittsburgh School of Medicine, 203 Lothrop Street, Pittsburgh, PA, 15213, USA

    Jose-Alain Sahel

  14. Werner Reichardt Centre for Integrative Neuroscience (CIN), University of Tuebingen, Elfriede-Aulhorn-Str. 7, 72076, Tuebingen, Germany

    Eberhart Zrenner

Authors
  1. Katarina Stingl
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  2. Anne Kurtenbach
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  3. Gesa Hahn
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  4. Christoph Kernstock
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  5. Stephanie Hipp
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  6. Ditta Zobor
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  7. Susanne Kohl
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  8. Crystel Bonnet
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  9. Saddek Mohand-Saïd
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  10. Isabelle Audo
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  11. Ana Fakin
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  13. Francesco Testa
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  14. Francesca Simonelli
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  15. Christine Petit
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  16. Jose-Alain Sahel
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  17. Eberhart Zrenner
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Corresponding author

Correspondence to Katarina Stingl.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Stingl, K., Kurtenbach, A., Hahn, G. et al. Full-field electroretinography, visual acuity and visual fields in Usher syndrome: a multicentre European study. Doc Ophthalmol 139, 151–160 (2019). https://doi.org/10.1007/s10633-019-09704-8

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  • DOI: https://doi.org/10.1007/s10633-019-09704-8

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