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
Financial Interest
I have received research reimbursement from Alcon and
Allergan 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
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
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
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)
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 < 21 mm Hg
Pseudoexfoliative glaucoma:• IOP > 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
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 – 70C 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 – 70C until analysis
Results Pseudoexfoliation
Syndrome(n=37)
PseudoexfoliationGlaucoma
(n= 15)
Controls
(n=32)
P value
Age (years)
Range 55-78 53-70 55-80
Mean±SD 72.3 ± 6.3 70.7 ± 8.2 69.6 ± 10.3 0.75
Sex
Male, n(%) 20 (54) 8 (53) 17 (53)
Female, n(%) 17 (46) 7 (47) 15 (47) 0.82
PseudoexfoliationSyndrome
(n=37)
PseudoexfoliationGlaucoma
(n= 15)
Controls
(n=32)Aqueous humor
VEGF (µmol/mL) 176.15 ± 55.47* 190.42 ± 46.65* 111.39 ± 18.54
NO (ng/mL) 34.96 ± 16.55$ 41.89 ± 21.82# 23.01 ± 12.49
Plasma
VEGF (µmol/mL) 72.82 ± 23.82* 83.70 ± 16.35* 44.08 ± 23.18
NO (ng/mL) 18.89 ± 7.18 20.66 ± 7.69 17.10 ± 5.60
Results
VEGF: vascular endothelial growth factor; NO: nitric oxide*: P < .001, PXS vs control, PXG vs control#: P = .001, PXG vs control$: P < .05, PXS vs control
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 1994;3:148-532. Tripathi RC,et al. Ophthalmology 1998;105:232-2373. Hu DN, et al. J Glaucoma 2002;11:406-410 4. Chang CJ, et al. 2000;16:399-4065. Galassi F, et al. J Ophthalmol 2004;88:757-7606. Kosior-Jarecka E, et al. Klin Oczna 2004;106:158-1597. Kotikoski H, et al. Acta Ophthalmol Scand 2002;80:191-195
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
NAME: Yonca Aydın 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
2000:Professor 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 : Başkent 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 : Başkent 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 : Başkent University, School of Medicine, Department of Ophthalmology
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 : Başkent University, School of Medicine, Department of Bıochemistry
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
2007:Professor of Ophthalmology, Baskent University, School of Medicine, Department of Ophthalmology, Ankara, Turkey