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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

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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 - PowerPoint PPT Presentation

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Page 1: Yonca A . Akova , MD, Mehmet Borazan, MD; Aylin Karalezli, MD; Cem Kucukerdonmez, MD ; Ahmet Akman , MD; Sevsen Kulaksizoglu, MD

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

Page 2: Yonca A . Akova , MD, Mehmet Borazan, MD; Aylin Karalezli, MD; Cem Kucukerdonmez, MD ; Ahmet Akman , MD; Sevsen Kulaksizoglu, MD

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

Page 3: Yonca A . Akova , MD, Mehmet Borazan, MD; Aylin Karalezli, MD; Cem Kucukerdonmez, MD ; Ahmet Akman , MD; Sevsen Kulaksizoglu, MD

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

Page 4: Yonca A . Akova , MD, Mehmet Borazan, MD; Aylin Karalezli, MD; Cem Kucukerdonmez, MD ; Ahmet Akman , MD; Sevsen Kulaksizoglu, MD

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

Page 5: Yonca A . Akova , MD, Mehmet Borazan, MD; Aylin Karalezli, MD; Cem Kucukerdonmez, MD ; Ahmet Akman , MD; Sevsen Kulaksizoglu, MD

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)

Page 6: Yonca A . Akova , MD, Mehmet Borazan, MD; Aylin Karalezli, MD; Cem Kucukerdonmez, MD ; Ahmet Akman , MD; Sevsen Kulaksizoglu, MD

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

Page 7: Yonca A . Akova , MD, Mehmet Borazan, MD; Aylin Karalezli, MD; Cem Kucukerdonmez, MD ; Ahmet Akman , MD; Sevsen Kulaksizoglu, MD

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

Page 8: Yonca A . Akova , MD, Mehmet Borazan, MD; Aylin Karalezli, MD; Cem Kucukerdonmez, MD ; Ahmet Akman , MD; Sevsen Kulaksizoglu, MD

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

Page 9: Yonca A . Akova , MD, Mehmet Borazan, MD; Aylin Karalezli, MD; Cem Kucukerdonmez, MD ; Ahmet Akman , MD; Sevsen Kulaksizoglu, MD

  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

Page 10: Yonca A . Akova , MD, Mehmet Borazan, MD; Aylin Karalezli, MD; Cem Kucukerdonmez, MD ; Ahmet Akman , MD; Sevsen Kulaksizoglu, MD

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

Page 11: Yonca A . Akova , MD, Mehmet Borazan, MD; Aylin Karalezli, MD; Cem Kucukerdonmez, MD ; Ahmet Akman , MD; Sevsen Kulaksizoglu, MD

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

Page 12: Yonca A . Akova , MD, Mehmet Borazan, MD; Aylin Karalezli, MD; Cem Kucukerdonmez, MD ; Ahmet Akman , MD; Sevsen Kulaksizoglu, MD

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


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