How to Cite
Copyright notice
Authors who publish with this journal agree to the following terms:
Authors retain copyright and grant the journal right of first publication, with the work twelve (12) months after publication simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work’s authorship and initial publication in this journal.
- After 12 months from the date of publication, authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
Keywords
Abstract
Purpose: To evaluate the variations of intraocular pressure (IOP), morphometric papillary characteristics, perimetric indices and electrophysiological parameters (Pattern electroretinogram and visual evoked potentials) before and after topic hypotonization therapy in patients with suspect normal tension glaucoma.
Methods: we evaluated 38 eyes of 20 patients with intraocular pressure < 21 mmHg (measured with Goldman applanation tonometry), initial glaucomatous optic neuropathy (valued with HRT: retinal fiber layer (RNFL) and/or linear cup/disk (linear C/D), minimal visual defects (Octopus 101: G2 program), visual acuity more than 15/20 with best correction and pathological electrophysiological parameters (valued with pattern electroretinogram and visual evoked potentials), free of systemic or other ocular diseases. All parameters were evaluated at the beginning of the study (T0) and after 12 months from the beginning of the therapy (T12). A randomized normal control group (27 eyes of 14 subjects) with apparent larger disc cupping underwent all exams at initial of study and after 12 months.
Results:At T0, P100 Latency VEPs in LTG was slightly increased either at 15’ (12,9 msec) and 30’ (8,9 msec). At T0, P100 Amplitude VEPs in LTG group were reduced compared to normal subjects, with average differences of: -6.4 µV (95% C.I.: (-9.8, -3.0) µV) for 15'; and: -5.4 µV (95% C.I.: ( -8.9, -2.0) µV) for 30’. P50N95 complex amplitude PERG was reduced at T0 in LTG, with average differences: -0.9 (95% C.I.: ( -1.4, -0.4) µV), -0.8 (-1.3, -0.3) µV) for 15’ and 30’, respectively; than it improved after therapy, with average differences between T12 and T0 of 0.3 µV (95% C.I.: (0.1, 0.6) µV) and 0.5 µV (95% C.I.: ( 0.2, 0.8) µV). So IOP decreased at T12 in LTG group, with an average difference between T12 and T0 of -5.2 mmHg (95% C.I.: (-5.9, -4.4). mmHg). Finally, CRT was slight delayed in LTG group at T0.
Conclusion: In a viewpoint of an integrated diagnostic, electrophysiological tests (VEPs and PERG) could provide a more sensitive measure of retinal ganglion cell integrity and help to distinguish between suspect normal-pressure glaucoma patients before perimetric alterations are evident and normal subjects with apparent larger disc cupping.
References
Heijl A, Leske MC, Bengtsson B, Hyman L, Hussein M. Reduction of intraocular pressure and glaucoma progression: results from the early manifest glaucoma trial. Arch Ophthalmol 2002; 120: 1268-1279
Kass MA, Heuer DK, Higginbotham EJ, Johnson CA, Keltner JL, Miller JP, Parrish RK II, Wilson MR, Gordon MO. The ocular hypertension treatment study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol 2002; 120: 701-713
Krupin T: Special considerations in low-tension glaucoma. Can J Ophthalmol 2007; 42: 414-417
Sowka J. New thoughts on normal tension glaucoma. Optometry 2005; 76 (10): 600-608
Hayamizu F, Yamazaki Y, Nakagami T, Mizuki K. Opic disc size and progression of visual field damage in patients with normal-tension glaucoma. Clinical Opthalmology 2013; 7: 807-813
Bonomi L, Marchini G, Marraffa M, et al Prevalence of glaucoma and intraocular distribution in a definite population. The Enge-Neumarkt Study. Ophthalmology 1998
Dielemans I, Vingerling JR, Wolfs RC, et al. The prevalence of primary open angle glaucoma in a population based study in the Netherlands. The Rotterdam Study. Ophthalmology 1994; 101: 1851-1855
Collaborative normal tension glaucoma study group. Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures. Am J Ophthalmol 1998; 126: 487-497
Collaborative normal tension glaucoma study group. The effectiveness of intraocular pressure reduction in the treatment of normal tension glaucoma. Am J Ophthalmol 1998; 126: 498-505
Collaborative normal tension glaucoma study group. Risk factors for progression of visual field abnormalities in normal tension glaucoma. Am J Ophthalmol 2001; 131: 699-708
Collaborative normal tension glaucoma study group. Factors that predict the benefit of lowering intraocular pressure in normal tension glaucoma. Am J Ophthalmol 2003; 136: 820-829
Sergi M, Salerno DE, Rizzi M, Blini M, Andreoli A, Messenio D, pecis M, Bertoni G: Prevalence of normal tension glaucoma in obstructive sleep apnea syndrome patients. J Glaucoma 2007; 16: 42-46
Meyer JH, Brandi- Dohrn J, Funk J. Twenty four hour blood pressure monitoring in normal tension glaucoma. Br J Ophthalmol 1996; 80: 864-867
Collignon N, Dewe W, Guillaume S, Collignon-Brach J. Ambulatory blood pressure monitoring in glaucoma patients. The nocturnal systolic dip and its relationship with disease progression. Int Ophthalmol 1998; 22: 19-25
Liu JH. Diurnal measurement of intraocular pressure. J Glaucoma 2001; 10: S39-41
Gupta N, Yucel YH. Glaucoma in the brain: a piece of the puzzle. Can J Ophthalmol 2006; 41 (5): 541
Weber AJ, Harman C. Structure-function relations of parasol in the normal and glaucomatous primate retina. Invest Ophthalmol Vis Sci 2005; 46, 3197-3207
Yucel YH, Zhand Q, Gupta N, Kaufman PL, Weinreb RN. Loss of neurons in magnocellular and parvocellular layers of the lateral geniculate nucleus in glaucoma. Arch Ophthalmol 2000; 118: 378-384
Yucel YH, Zhang Q, Weinreb RN, Kaufman PL, Gupta N. Effects of retinal ganglion cell loss on magno-, parvo-, koniocellular pathways in the lateral geniculate nucleus and visual cortex in glaucoma. Prog Retin Eye Res 2003; 22, 465-481
Gupta N, Yucel YH. Glaucoma and the brain. J Glaucoma 2001; 10, S28-S29
Maffei L, Fiorentini A. Electroretinographic responses to alternating gratings before and after section of the optic nerve. Science. 1981; 211: 953-954
Bach M, Gerling J, Geiger K: Optic atrophy reduces the pattern-electroretinogram for both fine and coarse stimulus pattern. Clin Vis Sci 1992: 327-333
Trick GL, Neshe R, Cooper DG, et al: The human pattern ERG: alterations of response properties with aging. Optom Vis Sci 1992; 1992: 122-128
Porciatti V, Burr DC, Morrone MC, Fiorentini A The effects of aging on the pattern electroretinogram and visual evoked potentials in humans: Vision Res 1992; 32: 1199-1209
Bach M. Electrophysiological approaches for early detection of glaucoma. Eur J Ophthalmol 2001; suppl 2: S41-S49
Bach M, Hoffmann MB. Update on the Pattern Electroretinogram in Glaucoma. Optometry and Vision science 2008; 85: 386-395
Van den Berg TJ, Riemslag FC, de Vos GW, Verduyn Lunel HF. Pattern ERG and glaucomatous visual field defects. Doc Ophthalmol 1986; 61: 335-341
Bach M, Sulimma F, Gerling J. Little correlation of the pattern electroretinogram (PERG) and visual filed measures in early glaucoma. Doc Ophthalmol 1997; 94: 253-263
Quigley HA, Addicks EM, Green WR: Optic nerve damage in human glaucoma. III Quantitative correlation of nerve fiber loss and visual field defect in glaucoma, ischemic neuropathy, papilledema and toxic neuropathy. Arch Ophthalmol 1982; 100: 135-146
Porciatti V, Falsini B, Brunori S, et al. Pattern electroretinogram as a function of spatial frequency in ocular hypertension and early glaucoma. Doc Ophthalmol 1987; 65: 349-355
Ventura LM, Porciatti DS. Restoration of retinal ganglion cell function in early glaucoma after intraocular pressure reduction. A pilot study. Ophthalmology 2005a; 112: 20-27
Caprioli J, Sears M, Miller JM. Patterns of early visual field loss in open-angle glaucoma. Am J Ophthalmol 1987; 104: 98
Wanger P, Persson HE: Pattern-reversal electroretinograms in unilateral glaucoma. Invest Ophthalmol Vis Sci. 1983; 24: 749-753
Papst N, Bopp M, Schnaudigel OE. The pattern evoked electroretinogram associated with elevated intraocular pressure. Graefe's archive for clinical and experimental ophthalmology. 1984 Oct 28;222(1):34-7.
Price MJ, Drance SM, Price M, Schulzer M, Douglas GR, Tansley B. The pattern electroretinogram and visual-evoked potential in glaucoma. Graefe's archive for clinical and experimental ophthalmology. 1988 Nov 29;226(6):542-7.
Weinstein GW, Arden GB, Hitchings RA. The pattern electroretinogram (PERG) in ocular hypertension and glaucoma. Arch Ophthalmol 1988; 106: 923-928
Arai M, Yoshimura N, Sakaue H, Chihara E, Honda Y. A 3-year follow-up study of ocular hypertension by pattern electroretinogram. Ophthalmologica. 1993;207(4):187-95.
Gonzalvo Ibanes FJ, Fernandez Tirado FJ, Almarcegui Lafita C, Polo Llorens V, Sanches Perez A, Honrubia Lopez FM. Predictive value of the pattern-electroretinogram in glaucoma (in Spanish). Arch Soc Esp Oftalmol 2001; 76:485-491
Unsoeld AS, Walter S, Meyer J, Funk J, Bach M. Pattern ERG as an early risk indicator in ocular hypertension – a 9-year prospective study. Invest Ophthalmol Vis Sci (Suppl): S146.2001
Bach M, Unsoeld AS, Philippin H, et al. Pattern ERG as an early indicator in ocular hypertension: a long -term prospective study. Invest Ophthalmol Vis Sci 2006; 47: 4881-4887
Pfeiffer N, Tillmon B, Bach M. Predictive value of pattern electroretinogram in high-risk ocular hypertension. Invest Ophthalmol Vis Sci 1993; 34: 1710-1715
Philippin H, Unsoeld A, Maier P, Walter S, Bach M, Funk J. Ten-year results: detection of long-term progressive optic disc changes with confocal laser tomography. Graefes Arch Clin Exp Ophthalmol 2005; 244: 1-5
Marx MS, Podos SM, Bodis-Wollner I, et al: Signs of early damage in glaucomatous monkey eyes: low spatial frequency losses in the pattern ERG and VEP. Exp Eye Res 1988: 46: 173-184
Saleh M, Nagaraju M, Porciatti V. Longitudinal evaluation of retinal ganglion cell function and IOP in the DBA/2J mouse model of glaucoma. Invest Ophthalmol Vis Sci 2007; 48: 4564-4572
Porciatti V, Saleh M, Nagaraju M. The pattern electroretinogram as a tool to monitor progressive retinal ganglion cell dysfunction in the DBA/2J mouse model of glaucoma. Invest Ophthalmol Vis Sci 2007; 48: 745-751
Ventura LM, Porciatti V. Pattern electroretinogram and glaucoma. Curr Opin Ophthalmol 2006b; 17 (2): 196-202
Parisi V, Manni G, Centofanti M, Gandolfi SA, Olzi D, Bucci MG. Correlation between optical coherence tomography, pattern electroretinogram, and visual evoked potentials in open-angle glaucoma patients. Ophthalmology. 2001 May 31;108(5):905-12.
Ventura LM, Sorokac N, De Los Santos R, Feuer WJ, Porciatti V: The relationship between retinal ganglion cell function and retinal nerve fiber thickness in early glaucoma. Invest Ophthalmol Vis Sci 2006; 47: 3904-3911
Salgarello T, Colotto A, Falsini B, et al: Correlation of pattern electroretinogram with optic disc cup shape measure in ocular hypertension. Invest Ophthalmol Vis Sci 1999; 40: 1989-1997
Salgarello T, Falsini B, Stifano G, et al: Morpho-functional follow-up of the optic nerve in treated ocular hypertension: disc morfometry and steady-state pattern electroretinogram. Curr Eye Res 33: 709-721, 2008
Parisi V, Miglior S, Manni G, Centofanti M, Bucci M: Clinical ability of pattern electroretinograms and visual evoked potentials in detecting visual dysfunction in ocular hypertension and glaucoma. Ophthalmology 216-228, 2006
Bayer AU, Maag KP, Erb C: Detection of optic neuropathy in glaucomatous eyes with normal standard visual fields using a test battery of short-wavelength automated perimetry and pattern electroretinography. Opthalmology 2002; 109: 1350-1361
Ventura LM, Porciatti V, et al. Pattern electroretinogram abnormality and glaucoma. Ophtalmology 2005a; 112: 10-19
Hood DC, Xu L, Thienprasiddhi P, Greenstein VC, Odel JG, Grippo TM, Liehmann JM, Rithc R: The pattern electroretinogram in glaucoma patients with confirmated visual field deficit. Invest Opthalmol Vis Sci 2005; 46: 2411-2418
Ventura LM, Porciatti DS. Restoration of retinal ganglion cell function in early glaucoma after intraocular pressure reduction. A pilot study. Ophthalmology 2005; 112: 20-27
North RV, Jones AL, Drasdo N, Wild JM, Morgan JE. Electrophysiological evidence of early functional damage in glaucoma and ocular hypertension. Inv Ophthalmol Vis Sci 2010; 51: 1216-1222
Ventura LM, Feuer JW, Porciatti V. Progressive loss of retinal ganglion cell function is hindered with IOP-lowering treatment in early glaucoma. Invest Ophthalmol Vis Sci 2012; 53: 659-663
Marx MS, Podos SM, Bodis-Wollner, et al. Flash and pattern electroretinograms in normal and laser-induced glaucomatous primate eyes. Invest Ophthalmol Vis Sci 1986; 27: 378-386
Parisi V, Pernini C, Guinetti C, et al. Electrophysiological assesment of visual pathways in glaucoma. Eur J Ophthalmol 1997; 7: 229-235
Horn FK, Jonas JB, Budde WM, Junemann AM, Mardin CY, Korth M. Monitoring glaucoma progression with visual evoked potentials of the blue-sensitive pathway. Invest Ophthalmol Vis Sci 2002; 43: 1828-1834
Celesia GG, Kaufman D, Cone SB. Simultaneous recording of pattern electroretinography and visual evoked potentials in multiple sclerosis. A method to separate demyelination from axonal damage to the optic nerve. Arch Neurol 1986; 43: 1247–52.
Brusini P. Clinical use of a new method for visual field damage classification in glaucoma. Eur J Ophthalmol 1996; 6: 402-407
Brusini P, Filacorda S. Enhanced Glaucoma Staging System (GSS2) for Classifying Function Damage in Glaucoma. J Glaucoma 2006; 15: 40-46
Garway-Heath DF, Wollstein G, Hitchings RA. Agong changes of the optic nerve head in relationship to open angle glaucoma. Br J Ophthalmol 1997; 81: 840-845
Kamal DS, Viswanathan AC, Garway-Heath DF, et al. Detection of optic disc change in ocular hypertensives converting to early glaucoma. Br J Ophthalmol 1999; 83: 290-294
Medvev N, Cvenkel B. Diagnostic accuracy of the Moorfields Regression Analysis using the Heidelberg Retina Tomography in glaucoma patients with visual field defects. Eur J Opthalmol 2007; (17): 216-222
Jolliffe I: Principal component analysis: John Wiley & Sons, Ltd 2002
Gabriel KR: The biplot graphic display of matrices with application to principal component analysis. Biometrika 1971; 58(3): 453-467.
Murdoch IE, Morris SS, & Cousens SN: People and eyes: statistical approaches in ophthalmology. British Journal of Ophthalmology (1998). 82(8): 971-973.
Team RC. R: A Language and Environment for Statistical Computing (Version 3.1. 2): R Foundation for Statistical Computing. Vienna, Austria. Available from URL http://www. R-project. org. 2015.
Pinheiro J, Bates D, DebRoy S, Sarkar D and R Core Team 2015. nlme: Linear and Nonlinear Mixed Effects Models_. R package version 3.1. URL: http://CRAN.R-project.org/package=nlme
Hothorn T, Bretz F and Westfall P: Simultaneous Inference in General Parametric Models. Biometrical Journal 2008: 50(3), 346--363.
Sommer A, Tielsch JM, Katz J, et al. Clinically detectable nerve fiber atrophy precedes the onset of glaucomatous field loss. Arch Ophthalmol 1991; 109: 77-83
Burk RO, Rohrschneider K, Noack H, Volker HE. Are large optic nerve heads susceptible to glaucomatous damage at normal intraocular pressure? A three-dimensional study by laser scanning tomography. Greafes Arch Clin Exp Ophthalmol 1992; 230 (6): 552-560
Wang L, Damji KF, Munger R, et al. .Increased disk size in glaucomatous eyes versus normal eyes in the Reykjavik eye study. Am J Ophthalmol 2003; 135 (2): 226-228
Jonas Jb, Xu L, Zhang L, Wang Y. Optic disc size in chronic glaucoma: the Beijng eye study. Am J Ophthalmol 2006; 142 (1): 168-170
Tomita G, Nyman K, Raitta C, Kawamura M. Intraocular asymmetry of optic disc size and its relevance to visual field loss in normal-tension glaucoma. Graefes Arch Clin Exp Ophthalmol 1994; 232 (5): 290-296
Jonas JB, Sturmer J, Papastathopoulos KI, Meier-Gibbsons F, Dichtl A. Optic disc size and optic nerve damage in normal pressure glaucoma. Br J Ophthalmol 1995; 79 (12): 1102-1105
Bellezza AJ, Hart RT, & Burgoyne CF. The optic nerve head as a biomechanical structure: initial finite element modeling. Investigative ophthalmology & visual science 2000, 41(10), 2991-3000.
Tuulonen A, Lehtola J, Airaksinen PJ. Nerve fiber layer defects with normal visual field: do normal optic disc and normal visual field indicate absence of glaucomatous abnormality? Ophthalmology 1993; 100: 587-597
Garway-Heath DF, Holder GE, Fizke FW, et al. Relationship between electrophysiological, psychophysiological and anatomical measures in glaucoma. Invest Ophthalmol Vis Sci 2002; 43: 2213-2220
Harwerth RS, Crawford M, Frishman LJ, et al. Visual field defects and neural losses from experimental glaucoma. Prog Retin Eye Res 2002; 21: 91-125
Swanson WH, Felius J, Pan F. Perimetric defects and ganglion cell damage: interpreting linear relations using a two-stage neural model. Invest Ophthalmol Vis Sci 2004; 45: 466-472
Marx MS, Podos SM, Bodis-Wollner, et al. Flash and pattern electroretinograms in normal and laser-induced glaucomatous primate eyes. Invest Ophthalmol Vis Sci 27: 378-386, 1986
Kerrigan-Baumrind LA, Quigley HA, Pease ME, et al. Number of ganglion cells in glaucoma eyes compared with threshold visual filed tests in the same persons. Invest Ophthalmol Vis Sci 2000; 41: 741-748
Neoh C, Kaye SB, Brown M, et al. Pattern electroretinogram and automated perimetry in patients with glaucoma and ocular hypertension. Br J Ophthalmol 1994; 78: 359-362
Lestak J, Nutterova Elena, Pitrova Sarka, Krejcova H, Bartosova L, Forgacova V. High tension versus normal tension glaucoma. A comparison of structural and functione examinations. J Clinic Experiment Ophthalmol 2012, 1-4
Karaskiewicz J, Drobek-Slowik M, Libinski W. Pattern electroretinogram (PERG) in the early diagnosis of normal-tension glaucoma: a case report. Doc Ophthalmol 2014; 128: 53-58
Falsini B, Marangoni D, Salgarello T, et al. Structure-function relationship in ocular hypertension and glaucoma: interindividual and interocular analysis by OCT and pattern ERG. Graefes Arch Clin Exp Ophthalmol 2008; 246: 1153-1162