Aqueous Humor and Plasma Levels of Vascular Endothelial Growth Factor and Nitric Oxide in Patients with Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma

1
Aqueous Humor and Plasma Levels of Vascular
Endothelial Growth Factor and Nitric Oxide in
Patients with Pseudoexfoliation Syndrome and
Pseudoexfoliation Glaucoma

• Yonca A. Akova, MD, Mehmet Borazan, MD Aylin
  Karalezli, MD Cem Kucukerdonmez, MD Ahmet
  Akman, MD Sevsen Kulaksizoglu, MD
• Baskent University, School of Medicine
  Department of Ophthalmology, Ankara, Turkey

2
Financial Interest

• I have received research reimbursement from Alcon
  andAllergan which  was not relevant to the
  subject matter of this poster
• None of the authors have financial interest in
  the subject matter of this poster

3
Introduction

• Pseudoexfoliation syndrome (PXS)
• Common
• Age-related
• May lead to pseudoexfoliative glaucoma (PXG)
• Specific pathogenetic mechanism and its
  progression to PXG remain, poorly understood
• Pseudoexfoliation fibrils
• Multifocal
• Produced by various intraocular cell types

4
Purpose

• To investigate the levels of vascular
  endothelial growth factor (VEGF) and nitric oxide
  (NO) in aqueous humor and plasma in eyes with
  pseudoexfoliation syndrome (PXS),
  pseudoexfoliative glaucoma (PXG), and normal
  controls

5
Patients and Methods

• Prospective, randomized clinical study
• 37 patients with PXS
• 15 patients with PXG
• 32 control subjects

• VEGF levels
• Measured with enzyme-linked immunosorbent assay
• NO levels
• Measured with chemiluminescence method
  (nitrate/nitrite colorimetric assay kit)

6
Patients and Methods

• Pseudoexfoliation syndrome
• Presence of typical pseudoexfoliation material on
  the anterior lens capsule in one or both eyes
• A normal optic disk appearance and visual field
  testing (Humphrey 30-2 SITA standard test)
• IOP lt 21 mm Hg

• Pseudoexfoliative glaucoma
• IOP gt 21 mm Hg
• Typical glaucomatous cupping and visual field
  loss in one or both eyes
• Pseudoexfoliative material on the anterior lens
  capsule
• Control group
• Age-and sex-matched patients with cataracts
• Absence of any pseudoexfoliation material at the
  anterior segment of the eye

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Patients and Methods

• Aqueous humor samples
• (0.1mL)
• Collected at the beginning of, phacoemulsification
  surgery through a clear corneal paracentesis
• Aspirated from the central pupillary area using a
  27- gauge needle on a tuberculin syringe
• Cooled at 70?C until analyses

• Venous blood samples
• (5 mL)
• Collected in the fasting state just before
  patients were prepared for cataract surgery
• Stored in chilled tubes containing EDTA (1mg/mL
  blood) and heparin (100 IU/mL blood)
• Centrifuged to obtain plasma
• Cooled 70?C until analysis

8
Results
9
Results
VEGF vascular endothelial growth factor NO
nitric oxide P lt .001, PXS vs control, PXG vs
control P .001, PXG vs control P lt .05,
PXS vs control
10
Discussion

• Well documented iris vasculopathy, with
  manifestations of blood aqueous barrier defects,
  vessel dropout, microneovascularization,
  hypoperfusion, and anterior chamber hypoxia in
  PSX1
• Aqueous humor VEGF levels were found higher in
  neovascular glaucoma, POAG, angle-closure
  glaucoma and PXG2,3
• Controversial findings about aqueous NO levels in
  glaucoma in the literature4-6
• Kotikoski et al (only report on the aqueous
  concentration of NO in eyes with PXG) showed
  lower NO levels in 6 patients with PXG and 2
  patients with PXS compared with controls7
• 1. Helbig H, et al. Ger J Ophthalmol
  19943148-53
• 2. Tripathi RC,et al. Ophthalmology
  1998105232-237
• 3. Hu DN, et al. J Glaucoma 200211406-410
• 4. Chang CJ, et al. 200016399-406
• 5. Galassi F, et al. J Ophthalmol 200488757-760
• 6. Kosior-Jarecka E, et al. Klin Oczna
  2004106158-159
• 7. Kotikoski H, et al. Acta Ophthalmol Scand
  200280191-195

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Conclusions

• Aqueous humor VEGF and NO levels and plasma VEGF
  levels in patients with PXS and PXG were found
  higher than in controls
• No significant difference was found in plasma NO
  concentrations compared with controls
• The aqueous humor and plasma VEGF and NO levels
  were not significantly different in eyes with PXS
  compared with PXG
• Improved understanding of the role of VEGF and NO
  in the pathogenesis of PXS and related glaucoma
  may change anti-glaucomatous treatment and
  anti-VEGF drugs may be an option for these
  patients

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NAME Yonca Aydin Akova, M.D. TITLE Professor in
Ophthalmology DATE AND PLACE OF BIRTH October
21, 1960, Turkey 1983 Doctor of Medicine,
Istanbul University, School of Medicine 1990
Istanbul University, School of Medicine,
Department of Ophthalmology 2000Professor of
Ophthalmology, Baskent University, School of
Medicine, Department of Ophthalmology, Ankara,
Turkey 2002 Chairperson, Baskent University,
School of Medicine, Department of Ophthalmology,
Ankara, Turkey
NAME Mehmet Borazan, M.D. TITLE Fellow in
Ophthalmology DATE AND PLACE OF BIRTH August
10, 1974, Turkey 1998 Doctor of Medicine, Inonu
University, School of Medicine 2005 Baskent
University, School of Medicine, Department of
Ophthalmology
NAME Aylin Karalezli, M.D. TITLE Fellow in
Ophthalmology DATE AND PLACE OF BIRTH July 4,
1974, Turkey 1998 Doctor of Medicine, Ankara
University, School of Medicine 2005 Baskent
University, School of Medicine, Department of
Ophthalmology
NAME Cem Küçükerdönmez, M.D. TITLE Fellow in
Ophthalmology DATE AND PLACE OF BIRTH October
9, 1975, Turkey 1999 Doctor of Medicine,
Hacettepe University, School of Medicine 2003
Baskent University, School of Medicine,
Department of Ophthalmology
NAME Ahmet Akman, M.D. TITLE Professor in
Ophthalmology DATE AND PLACE OF BIRTH March 20,
1968, Turkey 1991 Doctor of Medicine, Hacettepe
University, School of Medicine 1995 Hacettepe
University, School of Medicine, Department of
Ophthalmology 2007Professor of Ophthalmology,
Baskent University, School of Medicine,
Department of Ophthalmology, Ankara, Turkey
NAME Sevsen Kulasizoglu, M.D TITLE Fellow in
Biochemistry DATE AND PLACE OF BIRTH April 10,
1974, Turkey 1998 Doctor of Medicine, Hacettepe
University, School of Medicine 2003 Baskent
University, School of Medicine, Department of
Biochemistry