Wie läuft die Entstehung und Progression eines Optikusschadens bei einem primären Offenwinkelglaukom ab und welche Bedeutung haben diese Erkenntnisse für die Glaukomdiagnostik?

Zusammenfassung

Aufgrund der meist langwierigen Prozesse bei der Entwicklung einer glaukomatösen Optikusneuropathie kommt es bei den retinalen Ganglienzellen nicht spontan zu einem Zelluntergang, sondern zu einem schleichenden Zelltod. Daraus begründet sich die Vorstellung, dass funktionelle Tests besser geeignet sind für die Frühdiagnostik eines primären Offenwinkelglaukoms als bildgebende Verfahren, die erst dann Veränderungen aufzeigen können, wenn die retinalen Ganglienzellen und mit ihnen die retinalen Nervenfasern am Ende der biologischen Kaskade zugrunde gegangen sind. Durch neue perimetrische Verfahren wird die Frühdiagnostik beim Glaukom verbessert.

Abstract

The development of a glaucomatous optic neuropathy is a long-lasting process in which retinal ganglion cells do not die spontaneously. Therefore to detect early changes in this process, functional tests should be done to first detect those changes that imaging technologies miss because the latter methods can only detect changes when retinal ganglion cells have already died and a consecutive loss of retinal nerve fibres has occurred.

Schlüsselwörter

Glaukom - Perimetrie - Frühdiagnostik - HRT - OCT - GDx

Key words

glaucoma - perimetry - early diagnosis - HRT - OCT - GDx

• Literatur

• 1 Hoffmann E. Stellenwert der Optischen Kohärenztomographie (OCT) für die Glaukomdiagnostik. Klin Monatsbl Augenheilkd 2012; x: a-b
• 2 European Glaucoma Society. Terminologie und Handlungsrichtlinien zum Glaukom: Klassifikation und Terminologie. Savona Editrice DOGMA 1999; 63
• 3 Leske MC, Heijl A, Hyman L et al. Predictors of long-term progression in the early manifest glaucoma trial. Ophthalmology 2007; 114: 1965-1972
• 4 The Advanced Glaucoma Intervention Study (AGIS). 7. The relationship between control of intraocular pressure and visual field deterioration. The AGIS Investigators. Am J Ophthalmol 2000; 130: 429-440
• 5 Shirakashi M, Iwata K, Sawaguchi S et al. Intraocular pressure-dependent progression of visual field loss in advanced primary open-angle glaucoma: a 15-year follow-up. Ophthalmologica 1993; 207: 1-5
• 6 Newman-Casey PA, Talwar N, Nan B et al. The relationship between components of metabolic syndrome and open-angle glaucoma. Ophthalmology 2011; 118: 1318-1326
• 7 Chauhan BC, Mikelberg FS, Balaszi AG et al. Canadian Glaucoma Study: 2. risk factors for the progression of open-angle glaucoma. Arch Ophthalmol 2008; 126: 1030-1036
• 8 Roedl JB, Bleich S, Schlötzer-Schrehardt U et al. Increased homocysteine levels in tear fluid of patients with primary open-angle glaucoma. Ophthalmic Res 2008; 40: 249-256
• 9 Abu-Amero KK, Morales J, Bosley TM. Mitochondrial abnormalities in patients with primary open-angle glaucoma. Invest Ophthalmol Vis Sci 2006; 47: 2533-2541
• 10 Ferreira SM, Lerner SF, Brunzini R et al. Oxidative stress markers in aqueous humour of glaucoma patients. Am J Ophthalmol 2004; 137: 62-69
• 11 He Y, Leung KW, Zhang YH et al. Mitochondrial complex I defect induces ROS release and degeneration in trabecular meshwork cells of POAG patients: protection by antioxidants. Invest Ophthalmol Vis Sci 2008; 49: 1447-1458
• 12 Erb C, Heinke M. Oxidative stress in primary open-angle glaucoma. Front Biosci (Elite Ed) 2011; 3: 1524-1533
• 13 Erb C. Bedeutung des nukleären Faktors kappaB für das primäre Offenwinkelglaukom – eine Hypothese. Klin Monatsbl Augenheilkd 2010; 227: 120-127
• 14 Grus F. Zusammenhang zwischen oxidativem Stress und immunologischen Störungen beim Glaukom. Klin Monatsbl Augenheilkd 2010; 227: 114-119
• 15 Rao RC, Tchedre KT, Malik MTA et al. Dynamic patterns of histone lysine methylation in the developing retina. Invest Ophthalmol Vis Sci 2010; 51: 6784-6792
• 16 Deva NC, Insull E, Gamble G et al. Risk factors for first presentation of glaucoma with significant visual field loss. Clin Experiment Ophthalmol 2008; 36: 217-221
• 17 Triyoso DH, Good TA. Pulsatile shear stress leads to DNA fragmentation in human SH-SY5Y neuroblastoma cell line. J Physiol 1999; 515: 355-365
• 18 Göbel K, Rüfer F, Erb C. Physiologie der Kammerwasserproduktion sowie der Tagesdruckschwankungen und deren Bedeutung für das Glaukom. Klin Monatsbl Augenheilkd 2011; 228: 104-108
• 19 Gao F, Miller JP, Miglior S et al. A Joint Model for Prognostic Effect of Biomarker Variability on Outcomes: long-term intraocular pressure (IOP) fluctuation on the risk of developing primary open-angle glaucoma (POAG). JP J Biostat 2011; 5: 73-96
• 20 Tripathi RC, Li J, Chan WF et al. Aqueous humor in glaucomatous eyes contains an increased level of TGF-beta 2. Exp Eye Res 1994; 59: 723-727
• 21 Fuchshofer R, Birke M, Welge-Lüssen U et al. Transforming growth factor-beta 2 modulated extracellular matrix component expression in cultured human optic nerve head astrocytes. Invest Ophthalmol Vis Sci 2005; 46: 568-578
• 22 Gottanka J, Chan D, Eichhorn M et al. Effects of TGF-ß2 in perfused human eyes. Invest Ophthalmol Vis Sci 2004; 45: 153-158
• 23 Fuchshofer R. Pathogenic role of transforming growth factor-ß2 in glaucomatous damage to the optic nerve head. Exp Eye Res 2011; 93: 165-169
• 24 O'Reilly S, Pollock N, Currie L et al. Inducers of cross-linked actin networks in trabecular meshwork cells. Invest Ophthalmol Vis Sci 2011; 52: 7316-7324
• 25 Yao K, Tan J, Gu WZ et al. Reactive oxygen species mediates the apoptosis induced by transforming growth factor beta(2) in human lens epithelial cells. Biochem Biophys Res Commun 2007; 354: 278-83
• 26 Zhong Y, Leung CK, Pang CP. Glial cells and glaucomatous neuropathy. Chin Med J 2007; 120: 326-335
• 27 Moore D, Harris A, Wudun D et al. Dysfunctional regulation of ocular blood flow: A risk factor for glaucoma?. Clin Ophthalmol 2008; 2: 849-861
• 28 Dreyer EB, Zurakowski D, Schumer RA et al. Elevated glutamate levels in the vitreous body of humans and monkeys with glaucoma. Arch Ophthalmol 1996; 114: 299-305
• 29 Osborne N. Neuroprotektion beim Glaukom-weiterhin ein Konzept?. In: Erb C, Arend O, (Hrsg) Neuronale Konzepte beim Glaukom.. Bremen: Uni-Med Science; 2005: 11-19
• 30 Jonas JB, Mardin CY, Schlötzer-Schrehardt U et al. Morphometry of the human lamina cribrosa surface. Invest Ophthalmol Vis Sci 1991; 32: 401-405
• 31 Clarke G, Collins RA, Leavitt BR et al. A one-hit model of cell death in inherited neuronal degenerations. Nature 2000; 406: 195-199
• 32 Kerrigan-Baumrind LA, Quigley HA, Pease ME et al. Number of ganglion cells in glaucoma eyes compared with threshold visual field tests in the same persons. Invest Ophthalmol Vis Sci 2000; 41: 741-747
• 33 Quigley HA, Addicks EM, Green WR. Optic nerve damage in human glaucoma. III. Quantitative correlation of nerve fiber loss and visual field de-fect in glaucoma, ischemic neuropathy, papilledema, and toxic neuropathy. Arch Ophthalmol 1982; 100: 135-146
• 34 Heijl A, Leske C, Bengtsson B et al. Reduction of intraocular pressure and glaucoma progression. Arch Ophthalmol 2002; 120: 1268-1279
• 35 Dandona L, Hendrickson A, Quigley HA. Selective effects of experimental glaucoma on axonal transport by retinal ganglion cells to the dorsal lateral geniculate nucleus. Invest Ophthalmol Vis Sci 1991; 32: 1593-1599
• 36 Morgan JE, Uchida H, Caprioli J. Retinal ganglion cell death in experimental glaucoma. Br J Ophthalmol 2000; 84: 303-310
• 37 Yücel YH, Zhang Q, Gupta N et al. Loss of neurons in magnocellular and parvocellular layers of the lateral geniculate nucleus in glaucoma. Arch Ophthalmol 2000; 118: 378-384
• 38 Martin L, Wanger P, Vancea L et al. Concordance of high-pass resolution perimetry and frequency-doubling technology perimetry results in glaucoma: no support for selective ganglion cell damage. J Glaucoma 2003; 12: 40-44
• 39 Spry P, Johnson C, Mansberger SL et al. Psychophysical investigation of ganglion loss in early glaucoma. J Glaucoma 2005; 14: 11-19
• 40 Spry PGD, Hussin HM, Sparrow JM. Clinical evaluation of frequency doubling technology perimetry using the Humphrey Matrix 24-2 threshold strategy. Br J Ophthalmol 2005; 89: 1031-1035
• 41 Aulhorn E, Köst G. Rauschfeldkampimetrie. Eine neuartige perimetrische Untersuchungsweise. Klin Monatsbl Augenheilk 1988; 192: 284-288
• 42 Gramer E, Roesen B, Siebert M. Sensitivität der Rauschfeldkampimetrie als Screeninguntersuchung bei Glaukom. Fortschr Ophthalmol 1991; 88: 538-545
• 43 Erb C, Göbel K. Funktionelle Glaukomdiagnostik. Ophthalmologe 2009; 106: 375-386
• 44 White AJR, Sun H, Swanson WH et al. An examination of physiological mechanisms underlying the frequency-doublin illusion. Invest Ophthalmol Vis Sci 2002; 43: 3590-3599
• 45 Swanson WH, Sun H, Lee BB et al. Responses of primate retinal ganglion cells to perimetric stimuli. Invest Ophthalmol Vis Sci 2011; 52: 764-771
• 46 Mowatt G, Burr JM, Cook JA et al. Screening tests for detecting open-angle glaucoma: systematic review and meta-analysis. Invest Ophthalmol Vis Sci 2008; 49: 5373-5385
• 47 Gardiner SK, Demirel S, Johnson CA et al. Assessment of linear-scale indices for perimetry in terms of progression in early glaucoma. Vision Research 2011; 51: 1801-1810
• 48 Gupta N, Krishnadev N, Hamstra SJ et al. Depth perception deficits in glaucoma suspects. Br J Ophthalmol 2006; 90: 979-981
• 49 Ramulu P. Glaucoma and disability: which tasks are affected, and at what stage of disease?. Curr Opin Ophthalmol 2009; 20: 92-98
• 50 Ramulu PY, West SK, Munoz B et al. Glaucoma and reading speed: the Salisbury Eye Evaluation project. Arch Ophthalmol 2009; 127: 82-87
• 51 Richman J, Lorenzana LL, Lankaranian D et al. Importance of visual acuity and contrast sensitivity in patients with glaucoma. Arch Ophthalmol 2010; 128: 1576-1582
• 52 Varma R, Lee PP, Goldberg I et al. An assessment of the health and economic burdens of glaucoma. Am J Ophthalmol 2011; 152: 515-522
• 53 Stein DM, Wollstein G, Ishikawa H et al. Effect of corneal drying on optical coherence tomography. Ophthalmology 2006; 113: 985-991
• 54 Zheng Y, Cheung CY, Wong TY et al. Determinants of image quality of Heidelberg Retina Tomography II and its association with optic disc parameters in a population-based setting. Am J Ophthalmol 2011; 151: 663-670
• 55 Hermann MM, Garway-Heath DF, Jonescu-Cuypers CP et al. Interobserver variability in confocal optic nerve analysis (HRT). Int Ophthalmol 2005; 26: 143-149
• 56 Andersson S, Heijl A, Bengtsson B. Optic disc classification by the Heidelberg Retina Tomograph and by physicians with varying experience of glaucoma. Eye 2011; 25: 1401-1407
• 57 Hougaard JL, Heijl A, Bengtsson B. Glaucomatous retinal nerve fibre layer defects may be identified in Stratus OCT images classified as normal. Acta Ophthalmol 2008; 86: 569-575
• 58 Swinnen S, Stalmans I, Zeyen T. Reversal of optic disc cupping with improvement of visual field and stereometric parameters after trabeculectomy in young adult patients (two case reports). Bull Soc Belge Ophthalmol 2011; 317: 5