Early Detection of Retinal Ganglion Cell Damage in Glaucoma and Ocular Hypertensive Patients
Introduction
Glaucoma refers to a multifocal disease characterized by retinal ganglion cell (RGC) loss and progressive optic neuropathy followed by gradual visual field loss.1 It is the second most common cause of blindness worldwide.2 Although elevated intraocular pressure (IOP) has now been removed from the definition of glaucoma, it remains one of the most important risk factor because there is a convincing evidence that glaucoma is an IOP-sensitive optic neuropathy. 3-7 In the world, about 50% of glaucoma patients are undiagnosed because visual field can deteriorate without alarming elevated IOP!6 Furthermore ocular hypertension (OHT) is a condition characterized by elevated IOP without glaucomatous functional and structural damage. OHT can transform into glaucoma with the prevalence of 10% in between untreated patients.3 Beside controlling IOP and progression of the anatomical alterations of the optic disc, the regularly used visual field examination can give some information of the functional deficit of the retinal ganglion cells.3 Visual field examination is a subjective method therefore it might be
beneficial to check objective functional tests regularly as well. Table No. 1
OHT patient were divided into two groups: high risk and low risk ones. High risk OHT patients had (i) corrected IOP >25 mmHg and/or (ii) positive family history and/or (iii) older age, and/or (iv) known general circulatory disturbances but had negative perimetric and gonioscopic findings. Patients with low risk OHT had only corrected IOP >21 mmHg. ** p<0.001, * p<0.05
Kocsis PB. MD. A , Vanya M. MD. B , Janaky M. MD. Ph.D. A , Facsko A. MD. Ph.D. A
A University of Szeged, Department of Ophthalmology, Hungary B University of Szeged, Department of Gynecology and Obstetrics, Hungary
Purpose
The aim of our work was to find a sensitive objective method for the early detection of glaucomatous defect.
References
1, Costa VP, Harris A, Stefánsson E, Flammer J, Krieglstein GK, Orzalesi N, Heijl A, Renard JP, Serra LM. Prog Retin Eye Res. 2003 Nov;22(6):769-805. Review.
2, Quigley HA. Number of people with glaucoma worldwide. Br J Ophthalmol 1996; 80 (5): 389-93.
3, Kass MA. Heuer DK, Higginbotham EJ at al. The Ocular Hypertension treatment Study: a randomized trial determines that topical ocular hypertensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Opthalom. 2002; 120 (6): 701-13
4, Collaborative Normal-Tension Glaucoma Study Group. Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressure. Am J Ophthalmol 1998; 126 (4):487-497.
5, The Advanced Glaucoma Invention Study (AGIS). The relationship between control of intraocular pressure and visual field deterioration. The AGIS Investigators Am. J Ophthalmol 2000; 130 (4): 429-440.
6, Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol 2006; 90 (3):262- 267
7, Leskea MC, Heijl A, Hyman L at al. Factors for progression and glaucoma treatment: The Early Manifest Glaucoma Trial. Curr Opin Ophthalmol 2004; (15 (2): 102-6.
8, O’Donaghue E, Arden GB, O’SullivanF, Falcao-Reis F, Moriarty B, Hitchings RA, Spilleers W et al The pattern electroretinogram in glaucoma and ocular hypertension. Br. I Ophthalmol 1992, (76): 387-94.
9, Bach M, Hoffmann MB.: Update on the pattern electroretinogram in glaucoma. Optometry and Vis Sci 2008;85(6):386-395.
Patients & Methods
Altogether 68 (45 female, 23 male, mean age: 42.28±17.65 years) patients with manifest glaucoma (n=32) and with OHT (n=36) were evolved into the study. Age matched control groups were created (n=36)
Inclusion criteria were (i) vertical and horizontal optic disc cupping ratio >0.4-0.5, (ii) corrected IOP >21 mmHg among non-treated patients, (iii) positive gonioscopic findings, (iv) known general circulatory disturbances and (v) positive family history.
Exclusion criteria were (i) visual acuity <0.625 (ETDRS), (ii) high grade ametropia, (iii) opaque media, and (iv) any kind of retinal alterations (degeneration, diabetes etc).
Haag-Streit Octopus 1-2-3 static perimeter was used (30-2 normal program with dynamic strategy) to assess the mean sensitivity (MS) and mean defect (MD) of the central visual field. For statistical analysis (SPSS 15.0 - IBM SPSS Statistics® - Independent Samples T-test with the CI of 95%) and for IOP correction (Reichert IOPac® standard PDA pachymeter - Reichert® INC. Depew, N.Y. USA) were used. Electrophysiological examinations were performed with Roland Consult Electrophysiological Diagnostic Systems® Retiport Science 4.9.8.9. (Wiesbaden, Germany). The ERG were detected via DTL-electrodes. (Figure No. 1-3)
For evaluation the transient PERG (t-PERG), P50 implicit time and P50, N95 amplitudes were assessed. To reduce inter individual and intersession variability P50N95/N35P50 ratio, t-PERG ratio were introduced.8 The frequency of the pattern-reversal stimulation was 1.8 Hz, and the size of the stimuli were 0.8°. Eye-monitor distance in case of t-PERG:
100 cm. To assess steady-state PERG (ss-PERG) the PERG amplitude to 0.8° checks and the amplitude to 16° checks were recorded and their ratio, the ss-PERG ratio was assessed.9 (Figure No. 4)
Acknowledgements
This poster is supported TÁMOP-4.2.2/B-10/1-2010-0012 project: “Broadening the knowledge base and supporting the long term professional sustainability of the Research University Center of Excellence at the University of Szeged by ensuring the rising generation of excellent scientists.”
Figure No. 1 and No. 2
Active electrodes are in the lower conjunctival folds, indifferent electrodes are on the temples, ground is on the top of the head (Fz point)
Figure No. 3
Single-use Dawson, Trick and Litzkow (DTL) silver- chloride/nylon electrodes
Figure No. 5
In the upper row results of a glaucomatous patient (perimetry: MS: 25.3, MD: 1.0, t- PERG P50N95/N35P50 ratio:
0.74-0.82, ss-PERG ratio: 0.691) in the lower row, records of a control patient (perimetry: MS:
30.3, MD: -1.7, t-PERG N95/P50 ratio: 1.6-1.67, ss-PERG ratio:
1.7) can be seen
Corresponding author:
Peter Balazs Kocsis MD., Ph.D student
University of Szeged, Faculty of Medicine, Department of Ophthalmology Business phone: +36-62-54-54-87
E-mail: peter_balazs_kocsis@yahoo.co.uk
categories n mean age ± SD
perimetry
t-PERG ratio ± SD ss-PERG ratio ± SD MS ± SD MD ± SD
glaucoma 40+ 25 61.93±10.9
2 26.2±1.19** 2.2±1.75** 1.41±0.53 0.79±0.17**
glaucoma 40- 7 30.57±6.1 26.8±1.15** 0.8±1,04** 1.55±0.3 0.9±0.23*
high risk OHT
40+ 11 54.08±8.44 28.17±1.42 1.03±1.74 1.44±0.36 0.84±0.22*
high risk OHT 40- 7 23±7.17 28.3±1.59 -0.75±1,52 1.31±0.29 1.03±0.08 low risk OHT 40+ 7 46.63±6.85 28.48±0.96 -0.35±0.99 1.52±0.5 0.95±0.21 low risk OHT 40- 11 25±7.36 29.51±0.91 -0.75±0.86 1.34±0.19 1.08±0.18 control 40+ 20 56±12.19 28.94±0.83 -0.16±0.78 1.55±0.46 0.98±0.09 control 40- 16 24.35±6.46 29.14±0.91 -1.37±0.83 1.43±0.27 1.09±0.22
Results
(table No. 1)In our patients t-PERG ratio seemed not sensitive enough to distinguish glaucoma and OTH patients from controls. The ss-PERG ratio in patients with manifest glaucoma significantly differed from the control groups under (p=0.042) and above (p<0.001) the age of 40. In the same patients, indexes of static perimetry (MS p<0.001, MD p<0.001) showed significant difference as well. These results suggest that static ss-PERG ratio can similarly show functional alterations as static perimetry in both glaucoma patient groups. In contrast with in high risk OHT patients the ss-PERG ratio showed significant difference (p=0.012) from control patients over the age of 40 but static perimetry failed to differ these two groups.
Conclusions
Beside perimetry, ss-PERG ratio, as an objective indicator of the retinal ganglion-cell function, can enhance the sensitivity of glaucoma screening, which is peculiarly important in patients with high risk OHT.
Figure No. 4
Checkerboard stimuli for ss-PERG ratio. On the left side 16°, on the right side 0.8°
checkerboard stimuli size can be seen. The frequency of the pattern-reversal stimuli were 4.28 Hz. Eye-monitor distance 57 cm. (figure: reference No. 9)
