Skip to main content
SpringerLink
Log in

Strukturelle Endpunkte für Glaukomstudien

Structural endpoints for glaucoma studies

  • Leitthema
  • Published:
Der Ophthalmologe Aims and scope Submit manuscript

Zusammenfassung

Hintergrund

Strukturelle Endpunkte wurden als Surrogatendpunkte für die Zulassung neuroprotektiver Substanzen bei Glaukom diskutiert.

Fragestellung

Ist die Evidenz stark genug, um strukturelle Endpunkte als Surrogatendpunkte zu etablieren?

Material und Methode

Es erfolgt eine Zusammenfassung des Verständnisses zwischen Struktur und Funktion bei Glaukom.

Ergebnisse

Die Einführung der optischen Kohärenztomographie hat die Bildgebung bei Glaukom revolutioniert. Klinisch können sowohl die retinale Nervenfaserschichtdicke entlang eines in der Papille zentrierten Kreises als auch die Ganglienzellschichtdicke im Bereich der Makula gemessen werden, wobei man Letztere in Kombination mit anderen retinalen Schichten quantifiziert. Auf mikroskopischer Ebene gibt es eine starke Korrelation zwischen dem Verlust von Struktur und Funktion. Diese ist aber mit den klinischen Methoden nur ungenügend etabliert. Das gilt insbesondere für den longitudinalen Verlauf der Erkrankung. Zukünftige bildgebende Verfahren, die heute noch nicht klinisch zur Verfügung stehen, könnten das Potenzial haben, ein klareres Verständnis zum Zusammenhang zwischen Struktur und Funktion zu etablieren.

Diskussion

Die derzeitige Evidenz lässt die Verwendung struktureller Endpunkte als Surrogatendpunkte für Phase-3-Studien bei Glaukom nicht zu. Neuroprotektive Medikamente müssen auf Basis von Gesichtsfelduntersuchungen zugelassen werden, da es sich dabei um den patientenrelevanten Endpunkt handelt. Strukturelle Endpunkte könnten aber in der Zukunft eine wichtige Rolle bei Phase-2-Studien oder Proof-of-concept-Studien spielen.

Abstract

Background

Structural endpoints have been discussed as surrogate endpoints for the approval of neuroprotective drugs in glaucoma.

Objective

Is the evidence strong enough to establish structural endpoints as surrogate endpoints?

Material and methods

Review of current understanding between structure and function in glaucoma.

Results

The introduction of optical coherence tomography has revolutionized imaging in glaucoma patients. Clinically either the nerve fiber layer thickness can be measured along a circle centered in the optic nerve head or the ganglion cell layer thickness can be assessed in the macular region, the latter being quantified in combination with other inner retinal layers. On a microscopic level there is a strong correlation between structural and functional loss but this relation can only partially be described with currently available clinical methods. This is particularly true for longitudinal course of the disease in glaucoma patients. Novel imaging techniques that are not yet used clinically may have the potential to increase our understanding between structure and function in glaucoma but further research in this field is required.

Conclusion

The current evidence does not allow the establishment of structural endpoints as surrogate endpoints for phase 3 studies in glaucoma. Neuroprotective drugs have to be approved on the basis of visual field data because this is the patient-relevant endpoint. Structural endpoints can, however, play an important role in phase 2 and proof of concept studies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Literatur

  1. Alencar LM, Zangwill LM, Weinreb RN et al (2010) A comparison of rates of change in neuroretinal rim area and retinal nerve fiber layer thickness in progressive glaucoma. Invest Ophthalmol Vis Sci 51:3531–3539

    PubMed  PubMed Central  Google Scholar 

  2. Aptel F, Aryal-Charles N, Giraud JM et al (2015) Progression of visual field in patients with primary open-angle glaucoma – ProgF study 1. Acta Ophthalmol 93:e615–e620

    PubMed  Google Scholar 

  3. Aref AA, Budenz DL (2017) Detecting visual field progression. Ophthalmology 124:S51–S56

    PubMed  Google Scholar 

  4. Baumann B, Potsaid B, Kraus MF et al (2011) Total retinal blood flow measurement with ultrahigh speed swept source/Fourier domain OCT. Biomed Opt Express 2:1539–1552

    PubMed  PubMed Central  Google Scholar 

  5. Burgoyne CF, Downs JC (2008) Premise and prediction-how optic nerve head biomechanics underlies the susceptibility and clinical behavior of the aged optic nerve head. J Glaucoma 17:318–328

    PubMed  PubMed Central  Google Scholar 

  6. Bussel II, Wollstein G, Schuman JS (2014) OCT for glaucoma diagnosis, screening and detection of glaucoma progression. Br J Ophthalmol 98(Suppl 2):ii15–ii19

    PubMed  Google Scholar 

  7. Caprioli J, Mock D, Bitrian E et al (2011) A method to measure and predict rates of regional visual field decay in glaucoma. Invest Ophthalmol Vis Sci 52:4765–4773

    PubMed  Google Scholar 

  8. Cettomai D, Hiremath G, Ratchford J et al (2010) Associations between retinal nerve fiber layer abnormalities and optic nerve examination. Neurology 75:1318–1325

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Chauhan BC, Garway-Heath DF, Goni FJ et al (2008) Practical recommendations for measuring rates of visual field change in glaucoma. Br J Ophthalmol 92:569–573

    CAS  PubMed  Google Scholar 

  10. Chen CL, Wang RK (2017) Optical coherence tomography based angiography [Invited]. Biomed Opt Express 8:1056–1082

    PubMed  PubMed Central  Google Scholar 

  11. Cherecheanu AP, Garhofer G, Schmidl D et al (2013) Ocular perfusion pressure and ocular blood flow in glaucoma. Curr Opin Pharmacol 13:36–42

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Cheung CY, Ong YT, Hilal S et al (2015) Retinal ganglion cell analysis using high-definition optical coherence tomography in patients with mild cognitive impairment and Alzheimer’s disease. J Alzheimers Dis 45:45–56

    CAS  PubMed  Google Scholar 

  13. Chung JK, Hwang YH, Wi JM et al (2017) Glaucoma diagnostic ability of the optical coherence tomography angiography vessel density parameters. Curr Eye Res 42:1458–1467

    PubMed  Google Scholar 

  14. Cordeiro MF, Guo L, Luong V et al (2004) Real-time imaging of single nerve cell apoptosis in retinal neurodegeneration. Proc Natl Acad Sci USA 101:13352–13356

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Cordeiro MF, Normando EM, Cardoso MJ et al (2017) Real-time imaging of single neuronal cell apoptosis in patients with glaucoma. Brain 140:1757–1767

    PubMed  PubMed Central  Google Scholar 

  16. Costa VP, Harris A, Anderson D et al (2014) Ocular perfusion pressure in glaucoma. Acta Ophthalmol 92:e252–e266

    PubMed  Google Scholar 

  17. Dehghani C, Srinivasan S, Edwards K et al (2017) Presence of peripheral neuropathy is associated with progressive thinning of retinal nerve fiber layer in type 1 diabetes. Invest Ophthalmol Vis Sci 58:Bio234–Bio239

    PubMed  Google Scholar 

  18. Den Haan J, Verbraak FD, Visser PJ et al (2017) Retinal thickness in Alzheimer’s disease: a systematic review and meta-analysis. Alzheimers Dement (Amst) 6:162–170

    Google Scholar 

  19. Doblhoff-Dier V, Schmetterer L, Vilser W et al (2014) Measurement of the total retinal blood flow using dual beam Fourier-domain Doppler optical coherence tomography with orthogonal detection planes. Biomed Opt Express 5:630–642

    PubMed  PubMed Central  Google Scholar 

  20. Dong ZM, Wollstein G, Wang B et al (2017) Adaptive optics optical coherence tomography in glaucoma. Prog Retin Eye Res 57:76–88

    PubMed  Google Scholar 

  21. Downs JC, Girkin CA (2017) Lamina cribrosa in glaucoma. Curr Opin Ophthalmol 28:113–119

    PubMed  PubMed Central  Google Scholar 

  22. Fischer MD, Synofzik M, Kernstock C et al (2013) Decreased retinal sensitivity and loss of retinal nerve fibers in multiple system atrophy. Graefes Arch Clin Exp Ophthalmol 251:235–241

    PubMed  Google Scholar 

  23. Fondi K, Wozniak PA, Howorka K et al (2017) Retinal oxygen extraction in individuals with type 1 diabetes with no or mild diabetic retinopathy. Diabetologia 60:1534–1540

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Garcia-Martin E, Garcia-Campayo J, Puebla-Guedea M et al (2016) Fibromyalgia is correlated with retinal nerve fiber layer thinning. PLoS ONE 11:e161574

    PubMed  PubMed Central  Google Scholar 

  25. Garway-Heath DF, Caprioli J, Fitzke FW et al (2000) Scaling the hill of vision: the physiological relationship between light sensitivity and ganglion cell numbers. Invest Ophthalmol Vis Sci 41:1774–1782

    CAS  PubMed  Google Scholar 

  26. Garway-Heath DF, Crabb DP, Bunce C et al (2015) Latanoprost for open-angle glaucoma (UKGTS): a randomised, multicentre, placebo-controlled trial. Lancet 385:1295–1304

    CAS  PubMed  Google Scholar 

  27. Garway-Heath DF, Poinoosawmy D, Fitzke FW et al (2000) Mapping the visual field to the optic disc in normal tension glaucoma eyes. Ophthalmology 107:1809–1815

    CAS  PubMed  Google Scholar 

  28. Gill R, Foster AC, Woodruff GN (1987) Systemic administration of MK-801 protects against ischemia-induced hippocampal neurodegeneration in the gerbil. J Neurosci 7:3343–3349

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Gracitelli CP, Abe RY, Tatham AJ et al (2015) Association between progressive retinal nerve fiber layer loss and longitudinal change in quality of life in glaucoma. JAMA Ophthalmol 133:384–390

    PubMed  PubMed Central  Google Scholar 

  30. Han M, Zhao C, Han QH et al (2016) Change of retinal nerve layer thickness in non-arteritic anterior ischemic optic neuropathy revealed by Fourier domain optical coherence tomography. Curr Eye Res 41:1076–1081

    CAS  PubMed  Google Scholar 

  31. Harwerth RS, Wheat JL, Fredette MJ et al (2010) Linking structure and function in glaucoma. Prog Retin Eye Res 29:249–271

    CAS  PubMed  PubMed Central  Google Scholar 

  32. He S, Stankowska DL, Ellis DZ et al (2017) Targets of neuroprotection in glaucoma. J Ocul Pharmacol Ther. https://doi.org/10.1089/jop.2017.0041

    Article  PubMed  Google Scholar 

  33. Hood DC (2017) Improving our understanding, and detection, of glaucomatous damage: an approach based upon optical coherence tomography (OCT). Prog Retin Eye Res 57:46–75

    PubMed  Google Scholar 

  34. Hood DC, Kardon RH (2007) A framework for comparing structural and functional measures of glaucomatous damage. Prog Retin Eye Res 26:688–710

    PubMed  PubMed Central  Google Scholar 

  35. Hood DC, Raza AS, De Moraes CG et al (2013) Glaucomatous damage of the macula. Prog Retin Eye Res 32:1–21

    PubMed  Google Scholar 

  36. Hu R, Marin-Franch I, Racette L (2014) Prediction accuracy of a novel dynamic structure-function model for glaucoma progression. Invest Ophthalmol Vis Sci 55:8086–8094

    PubMed  PubMed Central  Google Scholar 

  37. Jansonius NM, Nevalainen J, Selig B et al (2009) A mathematical description of nerve fiber bundle trajectories and their variability in the human retina. Vision Res 49:2157–2163

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Jansonius NM, Schiefer J, Nevalainen J et al (2012) A mathematical model for describing the retinal nerve fiber bundle trajectories in the human eye: average course, variability, and influence of refraction, optic disc size and optic disc position. Exp Eye Res 105:70–78

    CAS  PubMed  Google Scholar 

  39. Jonas JB, Aung T, Bourne RR et al (2017) Glaucoma. Lancet 390:2183–2193

    PubMed  Google Scholar 

  40. Jutley G, Luk SM, Dehabadi MH et al (2017) Management of glaucoma as a neurodegenerative disease. Neurodegener Dis Manag 7:157–172

    PubMed  Google Scholar 

  41. Kim KE, Park KH (2017) Macular imaging by optical coherence tomography in the diagnosis and management of glaucoma. Br J Ophthalmol. https://doi.org/10.1136/bjophthalmol-2017-310869

    Article  PubMed  Google Scholar 

  42. Kiyota N, Kunikata H, Shiga Y et al (2017) Relationship between laser speckle flowgraphy and optical coherence tomography angiography measurements of ocular microcirculation. Graefes Arch Clin Exp Ophthalmol 255:1633–1642

    PubMed  Google Scholar 

  43. Kupersmith MJ, Garvin MK, Wang JK et al (2016) Retinal ganglion cell layer thinning within one month of presentation for non-arteritic anterior ischemic optic neuropathy. Invest Ophthalmol Vis Sci 57:3588–3593

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Lee EK, Yu HG (2015) Ganglion cell-inner plexiform layer and peripapillary retinal nerve fiber layer thicknesses in age-related macular degeneration. Invest Ophthalmol Vis Sci 56:3976–3983

    CAS  PubMed  Google Scholar 

  45. Lee YH, Kim KN, Heo DW et al (2017) Difference in patterns of retinal ganglion cell damage between primary open-angle glaucoma and non-arteritic anterior ischaemic optic neuropathy. PLoS ONE 12:e187093

    PubMed  PubMed Central  Google Scholar 

  46. Leitgeb RA, Werkmeister RM, Blatter C et al (2014) Doppler optical coherence tomography. Prog Retin Eye Res 41:26–43

    PubMed  PubMed Central  Google Scholar 

  47. Leske MC, Heijl A, Hussein M et al (2003) Factors for glaucoma progression and the effect of treatment: the early manifest glaucoma trial. Arch Ophthalmol 121:48–56

    PubMed  Google Scholar 

  48. Leung CK, Yu M, Weinreb RN et al (2012) Retinal nerve fiber layer imaging with spectral-domain optical coherence tomography: patterns of retinal nerve fiber layer progression. Ophthalmology 119:1858–1866. https://doi.org/10.1016/j.ophtha.2011.10.010

    Article  PubMed  Google Scholar 

  49. Leung CK, Yu M, Weinreb RN et al (2012) Retinal nerve fiber layer imaging with spectral-domain optical coherence tomography: a prospective analysis of age-related loss. Ophthalmology 119:731–737

    PubMed  Google Scholar 

  50. Li F, Huang W, Zhang X (2017) Efficacy and safety of different regimens for primary open-angle glaucoma or ocular hypertension: a systematic review and network meta-analysis. Acta Ophthalmol (Copenh). https://doi.org/10.1111/aos.13568

    Article  Google Scholar 

  51. Lin SC, Singh K, Jampel HD et al (2007) Optic nerve head and retinal nerve fiber layer analysis: a report by the American Academy of Ophthalmology. Ophthalmology 114:1937–1949

    PubMed  Google Scholar 

  52. Malik R, Swanson WH, Garway-Heath DF (2012) ‘Structure-function relationship’ in glaucoma: past thinking and current concepts. Clin Experiment Ophthalmol 40:369–380

    PubMed  PubMed Central  Google Scholar 

  53. Medeiros FA, Leite MT, Zangwill LM et al (2011) Combining structural and functional measurements to improve detection of glaucoma progression using Bayesian hierarchical models. Invest Ophthalmol Vis Sci 52:5794–5803

    PubMed  PubMed Central  Google Scholar 

  54. Medeiros FA, Weinreb RN, Moore G et al (2012) Integrating event- and trend-based analyses to improve detection of glaucomatous visual field progression. Ophthalmology 119:458–467

    PubMed  Google Scholar 

  55. Medeiros FA, Zangwill LM, Alencar LM et al (2009) Detection of glaucoma progression with stratus OCT retinal nerve fiber layer, optic nerve head, and macular thickness measurements. Invest Ophthalmol Vis Sci 50:5741–5748

    PubMed  Google Scholar 

  56. Medeiros FA, Zangwill LM, Anderson DR et al (2012) Estimating the rate of retinal ganglion cell loss in glaucoma. Am J Ophthalmol 154:814–824.e811

    PubMed  PubMed Central  Google Scholar 

  57. Medeiros FA, Zangwill LM, Bowd C et al (2012) The structure and function relationship in glaucoma: implications for detection of progression and measurement of rates of change. Invest Ophthalmol Vis Sci 53:6939–6946

    PubMed  PubMed Central  Google Scholar 

  58. Mukherjee N, Mcburney-Lin S, Kuo A et al (2017) Retinal thinning in amyotrophic lateral sclerosis patients without ophthalmic disease. PLoS ONE 12:e185242

    PubMed  PubMed Central  Google Scholar 

  59. Mwanza J‑C, Budenz DL, Warren JL et al (2015) Retinal nerve fibre layer thickness floor and corresponding functional loss in glaucoma. Br J Ophthalmol 99:732–737

    PubMed  Google Scholar 

  60. Nadler Z, Wang B, Schuman JS et al (2014) In vivo three-dimensional characterization of the healthy human lamina cribrosa with adaptive optics spectral-domain optical coherence tomography. Invest Ophthalmol Vis Sci 55:6459–6466

    PubMed  PubMed Central  Google Scholar 

  61. Nakazawa T (2016) Ocular blood flow and influencing factors for glaucoma. Asia Pac J Ophthalmol (Phila) 5:38–44

    CAS  Google Scholar 

  62. Ng DS, Chiang PP, Tan G et al (2016) Retinal ganglion cell neuronal damage in diabetes and diabetic retinopathy. Clin Experiment Ophthalmol 44:243–250

    PubMed  Google Scholar 

  63. Nguyen TD, Ethier CR (2015) Biomechanical assessment in models of glaucomatous optic neuropathy. Exp Eye Res 141:125–138

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Nouri-Mahdavi K, Brigatti L, Weitzman M et al (1997) Comparison of methods to detect visual field progression in glaucoma. Ophthalmology 104:1228–1236

    CAS  PubMed  Google Scholar 

  65. Ohnell H, Heijl A, Anderson H et al (2017) Detection of glaucoma progression by perimetry and optic disc photography at different stages of the disease: results from the Early Manifest Glaucoma Trial. Acta Ophthalmol 95:281–287

    PubMed  Google Scholar 

  66. Osborne NN (2010) Mitochondria: their role in ganglion cell death and survival in primary open angle glaucoma. Exp Eye Res 90:750–757

    CAS  PubMed  Google Scholar 

  67. Osborne NN (2009) Recent clinical findings with memantine should not mean that the idea of neuroprotection in glaucoma is abandoned. Acta Ophthalmol 87:450–454

    PubMed  Google Scholar 

  68. Otarola F, Chen A, Morales E et al (2016) Course of glaucomatous visual field loss across the entire perimetric range. JAMA Ophthalmol. https://doi.org/10.1001/jamaophthalmol.2016.0118

    Article  PubMed  Google Scholar 

  69. Palkovits S, Lasta M, Told R et al (2014) Retinal oxygen metabolism during normoxia and hyperoxia in healthy subjects. Invest Ophthalmol Vis Sci 55:4707–4713

    PubMed  Google Scholar 

  70. Palkovits S, Told R, Schmidl D et al (2014) Regulation of retinal oxygen metabolism in humans during graded hypoxia. Am J Physiol Heart Circ Physiol 307:H1412–H1418

    CAS  PubMed  Google Scholar 

  71. Peters D, Bengtsson B, Heijl A (2015) Threat to fixation at diagnosis and lifetime risk of visual impairment in open-angle glaucoma. Ophthalmology 122:1034–1039

    PubMed  Google Scholar 

  72. Pircher M, Zawadzki RJ (2017) Review of adaptive optics OCT (AO-OCT): principles and applications for retinal imaging [Invited. Biomed Opt Express 8:2536–2562

    PubMed  PubMed Central  Google Scholar 

  73. Quigley HA (2012) Clinical trials for glaucoma neuroprotection are not impossible. Curr Opin Ophthalmol 23:144–154

    PubMed  Google Scholar 

  74. Raza AS, Hood DC (2015) Evaluation of the structure-function relationship in glaucoma using a novel method for estimating the number of retinal ganglion cells in the human retina. Invest Ophthalmol Vis Sci 56:5548–5556

    PubMed  PubMed Central  Google Scholar 

  75. Rossi EA, Granger CE, Sharma R et al (2017) Imaging individual neurons in the retinal ganglion cell layer of the living eye. Proc Natl Acad Sci USA 114:586–591

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Rufa A, Pretegiani E, Frezzotti P et al (2011) Retinal nerve fiber layer thinning in CADASIL: an optical coherence tomography and MRI study. Cerebrovasc Dis 31:77–82

    PubMed  Google Scholar 

  77. Russell RA, Malik R, Chauhan BC et al (2012) Improved estimates of visual field progression using bayesian linear regression to integrate structural information in patients with ocular hypertension. Invest Ophthalmol Vis Sci 53:2760–2769

    PubMed  PubMed Central  Google Scholar 

  78. Schmetterer L, Garhofer G (2007) How can blood flow be measured? Surv Ophthalmol 52(Suppl 2):S134–S138

    PubMed  Google Scholar 

  79. Schmidl D, Werkmeister R, Garhofer G et al (2015) Ocular perfusion pressure and its relevance for glaucoma. Klin Monbl Augenheilkd 232:141–146

    CAS  PubMed  Google Scholar 

  80. Schonfeldt-Lecuona C, Kregel T, Schmidt A et al (2016) From imaging the brain to imaging the retina: Optical Coherence Tomography (OCT) in schizophrenia. Schizophr Bull 42:9–14

    PubMed  Google Scholar 

  81. Schwartz M, Belkin M, Yoles E et al (1996) Potential treatment modalities for glaucomatous neuropathy: neuroprotection and neuroregeneration. J Glaucoma 5:427–432

    CAS  PubMed  Google Scholar 

  82. Sehi M, Goharian I, Konduru R et al (2014) Retinal blood flow in glaucomatous eyes with single-hemifield damage. Ophthalmology 121:750–758

    PubMed  Google Scholar 

  83. Seth NG, Kaushik S, Kaur S et al (2017) 5‑year disease progression of patients across the glaucoma spectrum assessed by structural and functional tools. Br J Ophthalmol. https://doi.org/10.1136/bjophthalmol-2017-310731

    Article  PubMed  Google Scholar 

  84. Shin HY, Park HY, Jung KI et al (2014) Glaucoma diagnostic ability of ganglion cell-inner plexiform layer thickness differs according to the location of visual field loss. Ophthalmology 121:93–99

    PubMed  Google Scholar 

  85. Svrcinova T, Mares J, Chrapek O et al (2017) Changes in oxygen saturation and the retinal nerve fibre layer in patients with optic neuritis – a pilot study. Acta Ophthalmol. https://doi.org/10.1111/aos.13571

    Article  PubMed  Google Scholar 

  86. Vianna JR, Danthurebandara VM, Sharpe GP et al (2015) Importance of normal aging in estimating the rate of glaucomatous neuroretinal rim and retinal nerve fiber layer loss. Ophthalmology 122:2392–2398

    PubMed  Google Scholar 

  87. Wanek J, Blair NP, Chau FY et al (2016) Alterations in retinal layer thickness and reflectance at different stages of diabetic retinopathy by en face optical coherence tomography. Invest Ophthalmol Vis Sci 57:Oct341–Oct347

    PubMed  PubMed Central  Google Scholar 

  88. Weinreb RN, Kaufman PL (2011) Glaucoma research community and FDA look to the future, II: NEI/FDA glaucoma clinical trial design and endpoints symposium: measures of structural change and visual function. Invest Ophthalmol Vis Sci 52:7842–7851

    PubMed  PubMed Central  Google Scholar 

  89. Weinreb RN, Kaufman PL (2009) The glaucoma research community and FDA look to the future: a report from the NEI/FDA CDER glaucoma clinical trial design and endpoints symposium. Invest Ophthalmol Vis Sci 50:1497–1505

    PubMed  Google Scholar 

  90. Werkmeister RM, Dragostinoff N, Palkovits S et al (2012) Measurement of absolute blood flow velocity and blood flow in the human retina by dual-beam bidirectional Doppler fourier-domain optical coherence tomography. Invest Ophthalmol Vis Sci 53:6062–6071

    PubMed  Google Scholar 

  91. Werkmeister RM, Schmidl D, Aschinger G et al (2015) Retinal oxygen extraction in humans. Sci Rep 5:15763

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Wickstrom K, Moseley J (2017) Biomarkers and surrogate endpoints in drug development: a European regulatory view. Invest Ophthalmol Vis Sci 58:Bio27–Bio33

    PubMed  Google Scholar 

  93. Yarmohammadi A, Zangwill LM, Diniz-Filho A et al (2016) Relationship between optical coherence tomography angiography vessel density and severity of visual field loss in glaucoma. Ophthalmology 123:2498–2508

    PubMed  Google Scholar 

  94. Yu JG, Feng YF, Xiang Y et al (2014) Retinal nerve fiber layer thickness changes in Parkinson disease: a meta-analysis. PLoS ONE 9:e85718

    PubMed  PubMed Central  Google Scholar 

  95. Zhang Y, Wen W, Sun X (2016) Comparison of several parameters in two optical coherence tomography systems for detecting glaucomatous defects in high myopia. Invest Ophthalmol Vis Sci 57:4910–4915

    CAS  PubMed  Google Scholar 

  96. Zhao L, Wang Y, Chen CX et al (2014) Retinal nerve fibre layer thickness measured by spectralis spectral-domain optical coherence tomography: The Beijing Eye Study. Acta Ophthalmol 92:e35–e41

    PubMed  Google Scholar 

  97. Zhu H, Crabb DP, Schlottmann PG et al (2010) Predicting visual function from the measurements of retinal nerve fiber layer structure. Invest Ophthalmol Vis Sci 51:5657–5666

    PubMed  Google Scholar 

  98. Zmyslowska A, Fendler W, Waszczykowska A et al (2017) Retinal thickness as a marker of disease progression in longitudinal observation of patients with Wolfram syndrome. Acta Diabetol 54:1019–1024

    PubMed  PubMed Central  Google Scholar 

Download references

Danksagung

Finanzielle Unterstützung durch folgende Projekte wurde gewährt: Fonds zur Förderung der wissenschaftlichen Forschung (FWF): KLI 250, KLI 340, KLI 529, P26157.

Author information

Authors and Affiliations

  1. Universitätsklinik für Klinische Pharmakologie, Medizinische Universität Wien, Wien, Österreich

    A. Popa-Cherechenau, D. Schmidl, G. Garhöfer &  L. Schmetterer

  2. Medizinische und Pharmazeutische Universität Carol Davila, Bukarest, Rumänien

    A. Popa-Cherechenau

  3. Abteilung für Ophthalmologie, Notfallzentrum der Universitätsklinik Bukarest, Bukarest, Rumänien

    A. Popa-Cherechenau

  4. Singapore Eye Research Institute, SERI (Augenforschungszentrum Singapur), College Str. 20, Discovery Tower Ebene 6, 169856, Singapur, Singapur

    L. Schmetterer

  5. Lee Kong Chian Medical Schools, Nanyang Technological University (NTU), Singapur, Singapur

    L. Schmetterer

  6. Klinisches Fortbildungszentrum Ophthalmologie und Visual Sciences, Duke-NUS Medical School, Singapur, Singapur

    L. Schmetterer

  7. Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Medical School, Singapur, Singapur

    L. Schmetterer

Authors
  1. A. Popa-Cherechenau
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D. Schmidl
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G. Garhöfer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L. Schmetterer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to L. Schmetterer.

Ethics declarations

Interessenkonflikt

A. Popa-Cherechenau, D. Schmidl, G. Garhöfer und L. Schmetterer geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Popa-Cherechenau, A., Schmidl, D., Garhöfer, G. et al. Strukturelle Endpunkte für Glaukomstudien. Ophthalmologe 116, 5–13 (2019). https://doi.org/10.1007/s00347-018-0670-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00347-018-0670-8

Schlüsselwörter

Keywords

Search

Navigation