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Klin Monbl Augenheilkd 2020; 237(03): 275-287
DOI: 10.1055/a-1118-3705
Übersicht
Georg Thieme Verlag KG Stuttgart · New York

Hereditäre Netzhautdystrophien: Kombination ophthalmologischer Methoden zur Optimierung des Readout

Congenital Retinal Dystrophies: Combining Ophthalmological Techniques to Improve the Read-out
Ulrich Kellner
1   Zentrum für seltene Netzhauterkrankungen, AugenZentrum Siegburg, MVZ Augenärztliches Diagnostik- und Therapiecentrum Siegburg GmbH
2   RetinaScience, Bonn
,
Simone Kellner
1   Zentrum für seltene Netzhauterkrankungen, AugenZentrum Siegburg, MVZ Augenärztliches Diagnostik- und Therapiecentrum Siegburg GmbH
2   RetinaScience, Bonn
,
Mohammad Saleh
1   Zentrum für seltene Netzhauterkrankungen, AugenZentrum Siegburg, MVZ Augenärztliches Diagnostik- und Therapiecentrum Siegburg GmbH
,
Sebastian Deutsch
1   Zentrum für seltene Netzhauterkrankungen, AugenZentrum Siegburg, MVZ Augenärztliches Diagnostik- und Therapiecentrum Siegburg GmbH
,
Silke Weinitz
1   Zentrum für seltene Netzhauterkrankungen, AugenZentrum Siegburg, MVZ Augenärztliches Diagnostik- und Therapiecentrum Siegburg GmbH
2   RetinaScience, Bonn
,
Ghazaleh Farmand
1   Zentrum für seltene Netzhauterkrankungen, AugenZentrum Siegburg, MVZ Augenärztliches Diagnostik- und Therapiecentrum Siegburg GmbH
› Institutsangaben
Weitere Informationen

Publikationsverlauf

eingereicht 04. Oktober 2019

akzeptiert 11. Februar 2020

Publikationsdatum:
17. März 2020 (online)

Auch verfügbar auf
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Zusammenfassung

Für Patienten mit hereditären Netzhautdystrophien (auf Englisch: inherited retinal dystrophies, IRD) ist die Früherkennung, Differenzialdiagnose und mögliche Therapieentscheidung von erheblicher persönlicher und sozialer Bedeutung. Für den Augenarzt kann dies aufgrund der Heterogenität der Erkrankungen und Verläufe sowie der Seltenheit der IRD eine Herausforderung sein. Die vorliegende Übersicht empfiehlt eine zielorientierte klinisch-ophthalmologische Diagnostik bei Verdacht auf IRD mit einer Bewertung der Relevanz der einzelnen Methoden und ihrer Kombination für Diagnose, Differenzialdiagnose und Beurteilung der Progression im Verlauf. Nach einer umfassenden Anamnese ist initial die Kombination von optischer Kohärenztomografie (OCT), Fundus- und Nahinfrarot-Autofluoreszenz zur Frühdiagnose einer IRD ggf. vor ophthalmoskopisch sichtbaren Läsionen sinnvoll. Spektrale Reflexionsfotografie, OCT-Angiografie und Fluorescence Lifetime Imaging Ophthalmoscopy sind bei einzelnen IRD hilfreich. Erlaubt die retinale Bildgebung keine sichere Diagnose, ist das multifokale Elektroretinogramm zur Frühdiagnose und das Ganzfeld-Elektroretinogramm zur Differenzialdiagnose von IRD geeignet. Eine Vorstellung in Schwerpunktzentren für IRD zur Differenzialdiagnostik und Therapie ist empfehlenswert.

Abstract

An early diagnosis, differential diagnosis and possible decision about therapeutic interventions has considerable consequences for the personal and social life of patients affected with inherited retinal dystrophies (IRD). For the ophthalmologist, the clinical heterogeneity interferes with a simple diagnostic approach. The present review suggests a structured clinical approach for the ophthalmological diagnosis of IRD and discusses the relevance of different methods for diagnosis, differential diagnosis and the evaluation of progression. A detailed history should be followed by non-invasive retinal imaging. An early diagnosis prior to visible fundus alterations is facilitated by combining optical coherence tomography, fundus and near-infrared autofluorescence. Spectral reflectance photography, OCT angiography and fluorescence lifetime imaging ophthalmoscopy are helpful in the early diagnosis of specific IRD. If retinal imaging is not sufficient for a diagnosis the multifocal electroretinogram is useful for early diagnosis and full-field electroretinogram for differential diagnosis of IRD. Patients should be referred to specialised IRD-centres for differential diagnosis and possible treatment.

Schlüsselwörter

Netzhautdystrophie - Genetik - optische Kohärenztomografie - Fundusautofluoreszenz - Nahinfrarot-Autofluoreszenz

Key words

retinal dystrophy - genetic - optical coherence tomography - fundus autofluorescence - near-infrared autofluorescence
 

  • Literatur

  • 1 Birtel J, Eisenberger T, Gliem M. et al. Clinical and genetic characteristics of 251 consecutive patients with macular and cone/cone-rod dystrophy. Sci Rep 2018; 8: 4824
    CrossrefPubMedGoogle Scholar
  • 2 Martin-Merida I, Aguilera-Garcia D, Fernandez-San Jose P. et al. Toward the mutational landscape of autosomal dominant retinitis pigmentosa: a comprehensive analysis of 258 Spanish families. Invest Ophthalmol Vis Sci 2018; 59: 2345-2354
    CrossrefPubMedGoogle Scholar
  • 3 Haer-Wigman L, van Zelst-Stams WA, Pfundt R. et al. Diagnostic exome sequencing in 266 Dutch patients with visual impairment. Eur J Hum Genet 2017; 25: 591-599
    PubMedGoogle Scholar
  • 4 Elbaz H, Schulz A, Ponto KA. et al. Posterior segment eye lesions: prevalence and associations with ocular and systemic parameters: result from the Gutenberg health study. Graefes Arch Clin Exp Ophthalmol 2019; 257: 2127-2135
    CrossrefPubMedGoogle Scholar
  • 5 Brunsmann F, von Gizycki R, Rybalko A. et al. Patientenselbsthilfe und seltene Erkrankungen: Mitgestaltung der Versorgungsrealität am Beispiel seltener Netzhautdegenerationen. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2007; 50: 1494-1501
    CrossrefPubMedGoogle Scholar
  • 6 Tsui I, Song BJ, Lin CS. et al. A practical approach to retinal dystrophies. Adv Exp Med Biol 2018; 1085: 245-259
    PubMedGoogle Scholar
  • 7 Birtel J, Gliem M, Holz FG. et al. Bildgebung und molekulargenetische Diagnostik zur Charakterisierung von Netzhautdystrophien. Ophthalmologe 2018; 115: 1021-2017
    CrossrefPubMedGoogle Scholar
  • 8 Bax NM, Lambertus S, Cremers FP. et al. The absence of fundus abnormalities in Stargardt disease. Graefes Arch Clin Exp Ophthalmol 2019; 257: 1147-1157
    CrossrefPubMedGoogle Scholar
  • 9 Maguire AM, Russell S, Wellman JA. et al. Efficacy, safety, and durability of voretigene neparvovec-rzyl in RPE65 mutation-associated inherited retinal dystrophy: results of phase 1 and 3 trials. Ophthalmology 2019; 216: 1273-1285
    PubMedGoogle Scholar
  • 10 Dedania VS, Liu JY, Schlegel D. et al. Reliability of kinetic visual field testing in children with mutation-proven retinal dystrophies: implications for therapeutic clinical trials. Ophthalmic Genet 2018; 39: 22-28
    CrossrefPubMedGoogle Scholar
  • 11 Frampton GK, Kalita N, Payne L. et al. Fundus autofluorescence imaging: systematic review of test accuracy for the diagnosis and monitoring of retinal conditions. Eye (Lond) 2017; 31: 995-1007
    PubMedGoogle Scholar
  • 12 Kong X, Ho A, Munoz B. et al. Reproducibility of measurements of retinal structural parameters using optical coherence tomography in Stargardt disease. Transl Vis Sci Technol 2019; 8: 46
    CrossrefPubMedGoogle Scholar
  • 13 Tee JJL, Kalitzeos A, Webster AR. et al. Quantitative analysis of hyperautofluorescent rings to characterize the natural history and progression in RPGR-associated retinopathy. Retina 2018; 38: 2401-2414
    CrossrefPubMedGoogle Scholar
  • 14 Jauregui R, Park KS, Duong JK. et al. Quantitative Comparison of near-infrared versus short-wave autofluorescence imaging in monitoring progression of retinitis pigmentosa. Am J Ophthalmol 2018; 194: 120-125
    CrossrefPubMedGoogle Scholar
  • 15 Sujirakul T, Lin MK, Duong J. et al. Multimodal imaging of central retinal disease progression in a 2-year follow-up of retinitis pigmentosa. Am J Ophthalmol 2015; 160: 786-798.e4
    CrossrefPubMedGoogle Scholar
  • 16 Tee JJL, Yang Y, Kalitzeos A. et al. Natural history study of retinal structure, progression, and symmetry using ellipsoid zone metrics in RPGR-associated retinopathy. Am J Ophthalmol 2019; 198: 111-123
    CrossrefPubMedGoogle Scholar
  • 17 Jolly JK, Edwards TL, Moules J. et al. A qualitative and quantitative assessment of fundus autofluorescence patterns in patients with choroideremia. Invest Ophthalmol Vis Sci 2016; 57: 4498-4503
    CrossrefPubMedGoogle Scholar
  • 18 Müller PL, Pfau M, Mauschitz MM. et al. Comparison of green versus blue fundus autofluorescence in ABCA4-related retinopathy. Transl Vis Sci Technol 2018; 7: 13
    PubMedGoogle Scholar
  • 19 Georgiou M, Kane T, Tanna P. et al. Prospective cohort study of childhood-onset Stargardt disease: fundus autofluorescence imaging, progression, comparison with adult-onset disease and disease symmetry. Am J Ophthalmol 2019; DOI: 10.1016/j.ajo.2019.11.008.
    CrossrefPubMedGoogle Scholar
  • 20 Tanna P, Kasilian M, Strauss R. et al. Reliability and repeatability of cone density measurements in patients with Stargardt disease and RPGR-associated retinopathy. Invest Ophthalmol Vis Sci 2017; 58: 3608-3615
    CrossrefPubMedGoogle Scholar
  • 21 Takahashi VKL, Takiuti JT, Jauregui R. et al. Correlation between B-scan optical coherence tomography, en face thickness map ring and hyperautofluorescent ring in retinitis pigmentosa. Graefes Arch Clin Exp Ophthalmol 2019; 257: 1601-1609
    CrossrefPubMedGoogle Scholar
  • 22 Cetin EN, Parca O, Akkaya HS. et al. Association of retinal biomarkers and choroidal vascularity index on optical coherence tomography using binarization method in retinitis pigmentosa. Graefes Arch Clin Exp Ophthalmol 2020; 258: 23-30
    CrossrefPubMedGoogle Scholar
  • 23 Pichi F, Abboud EB, Ghazi NG. et al. Fundus autofluorescence imaging in hereditary retinal disease. Acta Ophthalmol 2018; 96: e549-e561
    CrossrefPubMedGoogle Scholar
  • 24 Oishi A, Miyata M, Numa S. et al. Wide-field fundus autofluorescence imaging in patients with hereditary retinal degeneration: a literature review. Int J Retina Vitreous 2019; 5 (Suppl. 01) S23
    PubMedGoogle Scholar
  • 25 Kellner U, Kellner S, Weber BHF. et al. Lipofuscin- and melanin-related fundus autofluorescence visualize different retinal pigment epithelial alterations in patients with retinitis pigmentosa. Eye (Lond) 2009; 23: 1349-1359
    PubMedGoogle Scholar
  • 26 Kellner S, Kellner U, Weber BHF. et al. Lipofuscin- and melanin-related fundus autofluorescence in patients with ABCA4-associated retinal dystrophies. Am J Ophthalmol 2009; 147: 895-902
    CrossrefPubMedGoogle Scholar
  • 27 Müller PL, Birtel J, Herrmann P. et al. Functional relevance and structural correlates of near-infrared and short wavelength fundus autofluorescence imaging in ABCA4-related retinopathy. Transl Vis Sci Technol 2019; 8: 46
    CrossrefPubMedGoogle Scholar
  • 28 Lorenz B, Wabbels B, Wegscheider E. et al. Lack of fundus autofluorescence to 488 nanometers from childhood on in patients with early-onset severe retinal dystrophy associated with mutations in RPE65. Ophthalmology 2004; 111: 1585-1594
    CrossrefPubMedGoogle Scholar
  • 29 Paavo M, Carvalho JRL, Lee W. et al. Patterns and intensities of near-infrared and short wavelength fundus autofluorescence in choroideremia probands and carriers. Invest Ophthalmol Vis Sci 2019; 60: 3752-3761
    CrossrefPubMedGoogle Scholar
  • 30 Duncker T, Tabacaru MR, Lee W. et al. Comparison of near-infrared and short-wavelength autofluorescence in retinitis pigmentosa. Invest Ophthalmol Vis Sci 2013; 54: 585-591
    CrossrefPubMedGoogle Scholar
  • 31 Duncker T, Marsiglia M, Lee W. et al. Correlations amongst near-infrared and short-wavelength autofluorescence and spectral domain optical coherence tomography in recessive Stargardt disease. Invest Ophthalmol Vis Sci 2014; 55: 8134-8143
    CrossrefPubMedGoogle Scholar
  • 32 Carvalho JRL, Paavo M, Chen L. et al. Multimodal imaging in Best vitelliform macular dystrophy. Invest Ophthalmol Vis Sci 2019; 60: 2012-2022
    CrossrefPubMedGoogle Scholar
  • 33 Querques G, Souied EH. Combined angiography for high-quality near-infrared autofluorescence images. Optom Vis Sci 2014; 91: e9-e13
    CrossrefPubMedGoogle Scholar
  • 34 Charbel Issa P, Berendschot TT, Staurenghi G. et al. Confocal blue reflectance imaging in type 2 idiopathic macular telangiectasia. Invest Ophthalmol Vis Sci 2008; 49: 1172-1177
    CrossrefPubMedGoogle Scholar
  • 35 Charbel Issa P, Finger RP, Holz FG. et al. Multimodal imaging including spectral domain OCT and confocal near infrared reflectance for characterization of outer retinal pathology in pseudoxanthoma elasticum. Invest Ophthalmol Vis Sci 2009; 50: 5913-5918
    CrossrefPubMedGoogle Scholar
  • 36 Arrigo A, Romano F, Albertini G. et al. Vascular patterns in retinitis pigmentosa on swept-source optical coherence tomography angiography. J Clin Med 2019; 8: 1425
    CrossrefPubMedGoogle Scholar
  • 37 Murro V, Muccioloo DP, Giorgio D. et al. Optical coherence tomography angiography (OCT-A) in young choroideremia (CHM) patients. Ophthalmic Genet 2019; 40: 201-206
    CrossrefPubMedGoogle Scholar
  • 38 Jaurequi R, Park KS, Duong JK. et al. Quantitative progression of retinitis pigmentosa by optical coherence tomography angiography. Sci Rep 2018; 8: 13130
    CrossrefPubMedGoogle Scholar
  • 39 Guduru A, Lupidi M, Gupta A. et al. Comparative analysis of autofluorescence and OCT angiography in Stargardt disease. Br J Ophthalmol 2018; 102: 1204-1207
    CrossrefPubMedGoogle Scholar
  • 40 Tanaka K, Lee W, Zernant J. et al. The rapid-onset chorioretinopathy phenotype of ABCA4 disease. Ophthalmology 2018; 125: 89-99
    CrossrefPubMedGoogle Scholar
  • 41 Dysli C, Wolf S, Hatz K. et al. Fluorescence lifetime imaging in Stargardt disease: potential marker for disease progression. Invest Ophthalmol Vis Sci 2016; 57: 832-841
    CrossrefPubMedGoogle Scholar
  • 42 Grover S, Fishman GA, Birch DG. et al. Variability of full-field electroretinogram responses in subjects without diffuse photoreceptor cell disease. Ophthalmology 2003; 110: 1159-1163
    CrossrefPubMedGoogle Scholar
  • 43 Fishman GA, Chappelow AV, Anderson RJ. et al. Short-term variability of ERG amplitudes in normal subjects and patients with retinitis pigmentosa. Retina 2005; 25: 1014-1021
    CrossrefPubMedGoogle Scholar
  • 44 Manzinani BA, Repas T, Weinberger AW. et al. Amplitude calculation in multifocal ERG: comparison of repeatability in 30 Hz flicker and first order kernel stimulation. Graefes Arch Clin Exp Ophthalmol 2007; 245: 338-344
    CrossrefPubMedGoogle Scholar
  • 45 Hamilton R, Al Abdlseaed A, Healy J. et al. Multi-centre variability of ISCEV standard ERGs in two normal adults. Doc Ophthalmol 2015; 130: 83-101
    CrossrefPubMedGoogle Scholar
  • 46 Vincent A, Robson AG, Holder GE. Pathognomonic (diagnostic) ERGs. A review and update. Retina 2013; 33: 5-12
    CrossrefPubMedGoogle Scholar
  • 47 Liew G, Moore AT, Bradley PD. et al. Factors associated with visual acuity in patients with cystoid macular edema and retinitis pigmentosa. Ophthalmic Epidemiol 2018; 25: 183-186
    CrossrefPubMedGoogle Scholar
  • 48 Verbakel SK, van Huet RAC, Boon CJF. et al. Non-syndromic retinitis pigmentosa. Prog Retin Eye Res 2018; 66: 157-186
    CrossrefPubMedGoogle Scholar
  • 49 Pierrache LHM, Ghafaryasi B, Khan MI. et al. Longitudinal study of RPE65-associated inherited retinal degenerations. Retina 2020; DOI: 10.1097/IAE.0000000000002681.
    CrossrefPubMedGoogle Scholar
  • 50 Ehrenberg M, Pierce EA, Cox GF. et al. CRB1: one gene, many phenotypes. Semin Ophthalmol 2013; 28: 397-405
    CrossrefPubMedGoogle Scholar
  • 51 Wu AL, Wang JP, Tseng YJ. et al. Multimodal imaging of mosaic retinopathy in carriers of hereditary x-linked recessive disease. Retina 2018; 38: 1047-1057
    CrossrefPubMedGoogle Scholar
  • 52 Sergouniotis PI, Davidson AE, Lenassi E. et al. Retinal structure, function, and molecular pathologic features in gyrate atrophy. Ophthalmology 2012; 119: 596-605
    CrossrefPubMedGoogle Scholar
  • 53 Brambati M, Borrelli E, Saccobi R. et al. Choroideremia: update on clinical features and emerging treatments. Clin Ophthalmol 2019; 13: 2225-2231
    CrossrefPubMedGoogle Scholar
  • 54 Boulanger-Scemama E, Mohand-Said S, El Shamieh S. et al. Phenotype analysis of retinal dystrophies in light of the underlying genetic defects. Application to cone and cone-rod dystrophies. Int J Mol Sci 2019; 20: 4854 doi:10.3390/ijms20194854
    CrossrefPubMedGoogle Scholar
  • 55 Abdelkader E, Yasir ZH, Khan AM. et al. Analysis of retinal structure and function in cone dystrophy with supernormal rod response. Doc Ophthalmol 2020; DOI: 10.1007/s10633-020-09748-1.
    CrossrefPubMedGoogle Scholar
  • 56 Termühlen J, Alex AF, Glöckle N. et al. A new mutation in enhanced S-cone syndrome. Acta Ophthalmol 2018; 96: e539-e540
    CrossrefPubMedGoogle Scholar
  • 57 Oishi A, Oishi M, Miyata M. et al. Multimodal imaging for differential diagnosis of Bietti crystalline dystrophy. Ophthalmol Retina 2018; 2: 1071-1077
    PubMedGoogle Scholar
  • 58 Renner AB, Kellner U. Hereditäre Makuladystrophien. Klin Monatsbl Augenheilkd 2016; 233: 1124-1141
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 59 Rahman N, Georgiou M, Khan NH. et al. Macular dystrophies: clinical and imaging features, molecular genetics and therapeutic options. Br J Ophthalmol 2019; DOI: 10.1136/bjophthalmol-2019-315086.
    CrossrefPubMedGoogle Scholar
  • 60 Battaglia Parodi M, Romano F, Arrigo A. et al. Natural course of the vitelliform stage in Best vitelliform macular dystrophy: a five-year follow-up study. Graefes Arch Clin Exp Ophthalmol 2020; 258: 297-301
    CrossrefPubMedGoogle Scholar
  • 61 Johnson AA, Guziewicz KE, Lee CJ. et al. Bestrophin1 and retinal disease. Prog Retin Eye Res 2017; 58: 45-69
    CrossrefPubMedGoogle Scholar
  • 62 Brandl C, Schulz HL, Charbel Issa P. et al. Mutations in the genes for interphotoreceptor matrix proteoglycans, IMPG1 and IMPG2 in patients with vitelliforme macular lesions. Genes (Basel) 2017; 8: 170 doi:10.3390/genes8070170
    CrossrefPubMedGoogle Scholar
  • 63 Molday RS, Kellner U, Weber BHF. X-linked juvenile retinoschisis: clinical diagnosis, genetic analysis, and molecular mechanisms. Prog Retin Eye Res 2012; 31: 195-212
    CrossrefPubMedGoogle Scholar
  • 64 Parodi MB, Cicinelli MV, Iacono P. et al. Multimodal imaging of foveal cavitation in retinal dystrophies. Graefes Arch Clin Exp Ophthalmol 2017; 255: 271-279
    CrossrefPubMedGoogle Scholar
  • 65 Habibi I, Falfoul Y, Todorova MG. et al. Clinical and genetic findings of autosomal recessive bestrophinopathy (ARB). Genes (Basel) 2019; 10: 953
    CrossrefPubMedGoogle Scholar
  • 66 Hu Z, Wang K, Bertsch M. et al. Correlation between electroretinography, foveal anatomy and visual acuity in albinism. Doc Ophthalmol 2019; 139: 21-32
    CrossrefPubMedGoogle Scholar
  • 67 Chen RW, Greenberg JP, Lazow MA. et al. Autofluorescence imaging and spectral-domain optical coherence tomography in incomplete congenital night blindness and comparison with retinitis pigmentosa. Am J Ophthalmol 2012; 153: 143-154
    CrossrefPubMedGoogle Scholar
  • 68 Zeitz C, Robson AG, Audo I. Congenital stationary night blindness: an analysis and update of genotype-phenotype correlations and pathogenic mechanisms. Prog Retin Eye Res 2015; 45: 58-110
    CrossrefPubMedGoogle Scholar
  • 69 Nasser F, Kurtenbach A, Kohl S. et al. Retinal dystrophies with bullʼs eye maculopathy along with negative ERGs. Doc Ophthalmol 2019; 139: 45-57
    PubMedGoogle Scholar
  • 70 Renner AB, Kellner U, Cropp E. et al. Dysfunction of transmission in the inner retina: incidence and clinical causes of negative electroretinogram. Graefes Arch Clin Exp Ophthalmol 2006; 244: 1467-1473
    CrossrefPubMedGoogle Scholar
  • 71 Liu X, Liu L, Li H. et al. RDH5 retinopathy (fundus albipunctatus) with preserved rod function. Retina 2015; 35: 582-589
    CrossrefPubMedGoogle Scholar
  • 72 Nishiguchi KM, Ikeda Y, Fujita K. et al. Phenotypic features of Oguchi disease and retinitis pigmentosa in patients with S-antigen mutations: a long-term follow-up study. Ophthalmology 2019; 126: 1557-1566
    CrossrefPubMedGoogle Scholar
  • 73 Strauss RW, Dubis AM, Cooper RF. et al. Retinal architecture in RGS9- and R9AP-associated retinal dysfunction (bradyopsia). Am J Ophthalmol 2015; 160: 1269-1275
    CrossrefPubMedGoogle Scholar