The role of altered hemodynamics in ocular physiopathology

1
The role of altered hemodynamics in ocular
physiopathology

• Leopold Schmetterer
• Department of Clinical Pharmacology
• Department of Biomedical Engineering and Physics
• Medical University of Vienna

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Theory of glaucoma pathogenesis
1. Mechanical damage due to increased
intraocular pressure (IOP) 2. Damage due to
optic nerve head (ONH) ischemia
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Results of recent multicenter trials
A reduction in intraocular pressure reduces the
progression of visual field loss in glaucoma
patients
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AGIS StudyAdvanced Glaucoma Intervention Study
Am J Ophthalmol 2000130429-440
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AGIS- StudyDesign I
789 eyes of 591 subjects with primary open angle
glaucoma IOP not manageable with
pharmacological therapy 2 groups A
ALT-Trab-Trab B Trab-ALT-Trab
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AGIS- StudyDesign II
Aim IOP lt 18 mmHg If the aim was not achieved
(even with additional pharmacological therapy)
another surgical intervention was scheduled
Period of observation 8 years Main outcome
parameters Changes in visual field parameters
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AGIS- StudyResults
Group A IOP lt 18 mmHg (100) 12.3 mmHg Group B
IOP lt 18 mmHg (75-100) 14.7 mmHg Group C IOP lt
18 mmHg (50-75) 16.9 mmHg Group D IOP lt 18
mmHg (0-50) 20.2 mmHg
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Patient (59 years IOP 13 mmHg)
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Patient (59 years IOP 13 mmHg)
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Patient (59 years IOP 13 mmHg)
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Collaborative NTG - Study
Am J Ophthalmol. 1998126498-505.
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Collaborative NTG - Study
Am J Ophthalmol. 2001 Jun131(6)699-708
Am J Ophthalmol. 200113699-708
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Collaborative NTG - Study
Am J Ophthalmol. 200113699-708
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Collaborative NTG - Study
Am J Ophthalmol. 200113699-708
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Early Manifest Glaucoma Trial
Heijl et al. Arch Ophthalmol. 2002
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Optic disc hemorrhages
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Optic disc hemorrhages and glaucoma
Kono et al. Am J Ophthalmol. 2003
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Peripapillary choroidal atrophy
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Relation systemic blood pressure, IOP and ocular
perfusion pressure
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Ocular perfusion pressure (OPP), blood pressure
(MAP), intraocular pressure (IOP) und ocular
blood flow (Q)
OPP MAP - IOP
Q OPP/R R ..... Vascular resistance
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Reduction in IOP

• Reduces venous pressure in the eye
• Increases ocular perfusion pressure

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Vascular risk factors for primary open angle
glaucoma - Prevalence
Egna-Neumarkt Study Bonomi et al. 2000
Ophthalmology
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Vascular risk factors for primary open angle
glaucoma - Incidence
Leske et al. 2007 Ophthalmology
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Vascular risk factors for primary open angle
glaucoma - Progression
Leske et al. 2007 Ophthalmology
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Vascular risk factors for primary open angle
glaucoma - Progression
Leske et al. 2007 Ophthalmology
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Vascular risk factors for primary open angle
glaucoma - Progression
Leske et al. 2007 Ophthalmology
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Blood flow parameters in patients with primary
open angle glaucoma
Findl et al. 2000 Am J Ophthalmol
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Progression und ocular blood flow
Satilmis et al. 2003 Am J Ophthalmol
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Progression und ocular blood flow
Galassi et al. 2003 Arch Ophthalmol
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Circadian Fluctuations OPP
Choi et al. 2006 IOVS
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Circadian Fluctuations OPP
Choi et al. 2007 IOVS
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Circadian Fluctuations Blood Flow
Pemp et al. 2008 submitted
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Is reduced blood flow causative in glaucoma?
Animal models ONH ischemia IOP elevation
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• ET-1 induced model of ischemia in the rabbit

ET-1 treated eyes
Oku et al. 1999 Surv Ophthalmol
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• ET-1 induced model of chronic ischemia in the rat

ET-1
Sham
Chauhan et al. 2004 IOVS
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Systemic vascular dysregulation in patients with
open angle glaucoma
Ghergel et al. 2004 IOVS
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Ocular vascular dysregulation in patients with
open angle glaucoma
Controls
POAG or OHT
Fuchsjäger-Mayrl et al. 2003 IOVS
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Effects of L-NMMA or placebo on blood flow in the
ONH and the choroid (LDF)



Luksch et al. 2000 IOVS
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Endothelial dysfunction in glaucoma
Polak et al. 2006 Arch Ophthalmol
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Flicker induced retinal vasodilatation
Polak et al. 2002 IOVS
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Effect of L-NMMA on flicker induced retinal
vasodilatation
Placebo
3 mg/kg L-NMMA
Dorner et al. 2003 Am J Physiol Heart Circ Physiol
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Flicker Responses in open angle glaucoma
Garhofer et al. 2004 J Glaucoma
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Statins and glaucoma
Mc Gwin et al. 2004 Arch Ophthalmol
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Statins and endothelial dysfunction
Bayerle-Eder et al. 2004 Atherosclerosis
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• Conclusions

• Reduced diastolic perfusion pressure is a
  significant risk factor for primary open angle
  glaucoma
• Ocular blood flow disturbances appear to play a
  causative role in the pathogenesis of glaucoma

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Pathophysiological Concept
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Thank you for your attention
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Good luck!!!!