EVALUATION OF GLUTAMATE AND OTHER AMINO ACID LEVELS IN GLAUCOMA PATIENT WITH MR SPECTROSCOPY: PRELIMINARY STUDY

1
EVALUATION OF GLUTAMATE AND OTHER AMINO ACID
LEVELS IN GLAUCOMA PATIENT WITH MR SPECTROSCOPY
PRELIMINARY STUDY

• Selim Doganay, MD¹ Cem Cankaya, MD¹
• Alpay Alkan, MD²
• Inonu University School of Medicine,
  Malatya-Turkey
• ¹ Department of
  Ophthalmology, ² Department of Radiology
• Authors have no financial or proprietary
  interest in any instrument or products used in
  this study

2
EVALUATION OF GLUTAMATE AND OTHER AMINO ACID
LEVELS IN GLAUCOMA PATIENT WITH MR SPECTROSCOPY
PRELIMINARY STUDY

• Purpose
• To determine whether metabolite changes in
  cellular level occur in vitreous fluid and corpus
  geniculatum laterale (CGL) in patients with
  glaucoma by magnetic resonance spectroscopy
  (MRS).

3
EVALUATION OF GLUTAMATE AND OTHER AMINO ACID
LEVELS IN GLAUCOMA PATIENT WITH MR SPECTROSCOPY
PRELIMINARY STUDY

• Introduction
• Glutamate is an important transmitter existing
  widely in central nervous system (CNS) and
  responsible for excitatory transmission.1
• Under the light of the apoptosis theory indicated
  as a factor in glaucoma pathophysiology, an
  increase in the level of glutamate, which has
  known neurotoxic effects on optic disc, vitreous
  fluid and corpus geniculatum laterale, is
  expected.2-7
• Magnetic Resonance Spectroscopy (MRS) is a
  diagnostic method which is able to evaluate
  biochemical structure and metabolites of tissues
  non-invasively and to show them in single
  spectrum.8

4
EVALUATION OF GLUTAMATE AND OTHER AMINO ACID
LEVELS IN GLAUCOMA PATIENT WITH MR SPECTROSCOPY
PRELIMINARY STUDY

• Materials and methods
• 29 eyes of 29 patients with glaucoma, no existing
  ocular pathology and systemic disease (group 1)
  and 13 eyes of 13 healthy individuals whose
  routine ophthalmologic examinations were normal
  (group 2) were included in the study.
• Single voxel MRS examination was performed by
  placing ROI (Region of interest) in vitreous
  fluid and corpus geniculatum laterale (CGL).
  Glutamate-glutamine (Glx)/Creatin (Cr) ratios and
  lactate peaks in the vitreous fluid, and the
  Glx/Cr, N-acetyl aspartate (NAA)/Cr, Choline
  (Cho)/Cr ratios in the ipsilateral area of CGL
  were evaluated.

5
EVALUATION OF GLUTAMATE AND OTHER AMINO ACID
LEVELS IN GLAUCOMA PATIENT WITH MR SPECTROSCOPY
PRELIMINARY STUDY

• Patients who had conditions such as previous
  ocular surgery, laser therapy, trauma history,
  corneal and lens pathologies preventing perform
  ocular fundus examination, uveitis, posterior
  segment pathologies, neurodegenerative diseases
  of central nervous system, and systemic diseases
  like diabetes and hypertension that may
  predispose to these situations were excluded from
  the study.

6
EVALUATION OF GLUTAMATE AND OTHER AMINO ACID
LEVELS IN GLAUCOMA PATIENT WITH MR SPECTROSCOPY
PRELIMINARY STUDY

• MRS Technique
• Single voxel MRS examination was performed by
  placing ROI (region of interest) in corpus
  vitreous and corpus geniculatum laterale (CGL) on
  the same side.
• During placing ROI, it was avoided to contact to
  bone, vessel, air and fat.
• A 13x13 mm (TE 31 ms) ROI in vitreous fluid and
  a 12x12 mm (TE 136 ms) ROI in CGL were placed
  using PRESS (Point Resolved Spectroscopy)
  technique.
• ROI was placed by localizing CGL anatomically
  with 3 plane thin section MRI views.

7
EVALUATION OF GLUTAMATE AND OTHER AMINO ACID
LEVELS IN GLAUCOMA PATIENT WITH MR SPECTROSCOPY
PRELIMINARY STUDY
Results
The mean Glx/Cr, NAA/Cr, and Cho/Cr ratios in
both vitreous body and corpus geniculatum
laterale region in Groups.
Vitreous fluid Corpus geniculatum laterale Corpus geniculatum laterale Corpus geniculatum laterale
Glx/Cr (MeanSD) (min-max) Glx/Cr (MeanSD) (min-max) NAA/Cr (MeanSD) (min-max) Cho/Cr (MeanSD) (min-max)
Group 1 10.878.58 (1.06-38.53) 1.291.21 (0.39-6.30) 1.150.56 (0.34-2.67) 1.361.30 (0.28-6.53)
Group 2 2.241.51 (0.13-5.05) 0.380.35 (0.04-1.39) 1.440.57 (0.36-2.22) 0.790.32 (0.36-1.49)
SD Standard deviation, Min Minimum, Max
Maximum, Glx Glutamate-glutamine, Cr Creatine,
NAA N-acetylaspartate, Cho Choline Group1
Patients with glaucoma, Group 2 Healthy
individuals
8
EVALUATION OF GLUTAMATE AND OTHER AMINO ACID
LEVELS IN GLAUCOMA PATIENT WITH MR SPECTROSCOPY
PRELIMINARY STUDY
plt0.05, VF Vitreous fluid, CGL Corpus
geniculatum laterale , Glx Glutamate-glutamine,
Cr Creatine, NAA N-acetylaspartate , Cho
Choline , 1 Patients with glaucoma (Group 1),
2 Healthy individuals (Group 2)
9
EVALUATION OF GLUTAMATE AND OTHER AMINO ACID
LEVELS IN GLAUCOMA PATIENT WITH MR SPECTROSCOPY
PRELIMINARY STUDY
Increased Glx/Cr ratio was detected between
2.1-2.5 ppm in a glaucoma patients vitreous
fluid by MRS
Glx Glutamate-glutamine
10
EVALUATION OF GLUTAMATE AND OTHER AMINO ACID
LEVELS IN GLAUCOMA PATIENT WITH MR SPECTROSCOPY
PRELIMINARY STUDY
NAA peaks were detected at 2,0 ppm, Glx peaks
were detected at 2,1-2,5 ppm, Cr peaks were
detected at 3,02 ppm, and Cho peaks were detected
at 3,2 ppm in the corpus geniculatum laterale
region of a patient with glaucoma by MRS.
NAA N-acetylaspartate, Glx Glutamate-glutamine,
Cr Creatine, Cho Choline
11
EVALUATION OF GLUTAMATE AND OTHER AMINO ACID
LEVELS IN GLAUCOMA PATIENT WITH MR SPECTROSCOPY
PRELIMINARY STUDY
A lactate peak was detected at 1.32 ppm in 11
glaucoma patients vitreous fluid by MRS.
Lactate peak
12

EVALUATION OF GLUTAMATE AND OTHER AMINO ACID
LEVELS IN GLAUCOMA PATIENT WITH MR SPECTROSCOPY
PRELIMINARY STUDY

• Discussion
• Studies show that glaucoma leads to neuronal loss
  in optic nerve and CGL region. It is a natural
  consequence that these changes occurred in CGL
  alter some metabolites.2-5,7 Our study has
  demonstrated that MRS method reveals these
  changes.
• We think that MRS method, which is able to
  measure biochemical structure and metabolites of
  tissues non-invasively, would move the diagnosis
  of glaucoma one-step forward and open new
  horizons in understanding and diagnosing of
  glaucoma at cellular level.

13

EVALUATION OF GLUTAMATE AND OTHER AMINO ACID
LEVELS IN GLAUCOMA PATIENT WITH MR SPECTROSCOPY
PRELIMINARY STUDY

• References
• Honkanen RA, Baruah S, Zimmerman MB, et al.
  Vitreous aminoasid concentrations in patients
  with glaucoma undergoing vitrectomy. Arch
  Ophthalmol 2003 121183-88.
• Gupta N, Greenberg G, Tilly NL, et al. Atrophy of
  the lateral geniculate nucleus in human glaucoma
  detected by magnetic resonance imaging. Br J
  Ophthalmol 2009 9356-60.
• Yucel YH, Zhang Q, Weinreb RN, et al. Atrophy of
  Relay Neurons in Magno- and Parvocellular Layers
  in the Lateral Geniculate Nucleus in Experimental
  Glaucoma. Invest Ophthalmol Vis Sci 2001
  423216-22.
• RJ Casson. Possible role of excitotoxicity in the
  pathogenesis of glaucoma. Clin Exp Ophthalmol
  2006 3454-63.
• Okuno T, Oku H, Sugiyama T, et al. Glutamate
  level in optic nevre head is increased by
  artificial elevation of intraocular pressure in
  rabbits. Exp Eye Res 2006 82465-70.
• Dreyer EB, Zurakowski D, Schumer RA, et al.
  Elevated glutamate levels in vitreous body of
  humans and monkeys with glaucoma. Arch Ophthalmol
  1996 114299-305.
• Gupta N, Ang LC, Tilly NL, et al. Human glaucoma
  and neural degeneration in intracranial optic
  nevre, lateral geniculate nucleus and visual
  cortex. Br J Ophthalmol 2006 90674-78.
• Castillo M, Kwock L, Mukherji SK. Clinical
  applications of proton MR spectroscopy. Am J
  Neuroradiol 1996 171-15.