INFLUENCE OF OPTIC DISC APPEARANCE AND DIURNAL VARIATION OF INTRAOCULAR PRESSURE ON VISUAL FIELD DEFECT IN NORMAL TENSION GLAUCOMA

YOSHIO YAMAZAKI, TAKAKO NAKAGAMI, TAIKI OSHIDA, KENJI MIZUKI, FUKUKO HAYAMIZU and CHIZURU TANAKA

Department of Ophthalmology, Nihon University School of Medicine, Tokyo, Japan

Abstract

One hundred and eleven stereo optic disc photographs of patients with normal tension glaucoma (NTG) were reviewed in order to identify the characteristics of four types of NTG: focal ischemic (FINTG), generalized cup enlargement (GENTG), myopic (MYNTG), and senile sclerotic (SSNTG). Twenty-five patients with FINTG, 45 with GENTG, 28 with MYNTG, and 14 with SSNTG were identified. The four groups showed significant differences in the presence of localized or diffuse visual field defects (p = 0.008). Patients with FINTG and MYNTG had localized visual field defects only. Conversely, in half of the patients with GENTG and SSNTG, diffuse and localized loss were both present. There was a significant difference in the pattern of diurnal intraocular pressure (IOP) variation among the four groups (p = 0.002). Patients with MYNTG showed a flat type of diurnal IOP variation more frequently than those in the other three groups. These results suggested that NTG has pathogenic mechanisms which differ according to the optic disc type and degree of IOP variation.

Introduction

Normal tension glaucoma (NTG) refers to a type of glaucoma that is clinically similar to primary open-angle glaucoma (POAG), except for the absence of statistically high intraocular pressure (IOP).1 Many clinical factors, with or without elevated IOP, have been implicated in the development of visual field defects in NTG. Vascular disorders have been associated with NTG including hypertension,2 migraine,3 and Raynaud’s phenomenon.4 Spasms of peripheral vessels have been found to be more frequent in patients with NTG than in normal subjects.5 Disc hemorrhage, viewed as an ocular vasospastic sign, had a higher prevalence in patients with NTG than in those with POAG.6 In color Doppler-imaging studies of ophthalmic arteries, we found that patients with NTG showed a statistically significant correlation between the vascular resistance of the ophthalmic artery and the mean depression of retinal sensitivity, but

Address for correspondence: Yoshio Yamazaki, MD, Department of Ophthalmology, Nihon University School of Medicine, 30-1, Oyaguchikami-machi, Itabashi-ku, Tokyo, 173-8610, Japan. Email: yama@med. nihon-u.ac.jp

Perimetry Update 2002/2003, pp. 165–171

Proceedings of the XVth International Perimetric Society Meeting, Stratford-upon-Avon, England, June 26–29, 2002

edited by David B. Henson and Michael Wall

© 2004 Kugler Publications, The Hague, The Netherlands

166 Y. Yamazaki et al.

those with POAG showed no correlation.7 However, when the mean IOP is asymmetric in NTG, the visual field defect appears to be greater on the side with the higher mean IOP.8,9 It seems that both IOP and other clinical factors influence the development of glaucomatous damage in NTG.

Various patterns of disc damage in glaucoma have been described, suggesting that NTG may result from different pathogenic mechanisms. Spaeth pointed out that some glaucoma patients develop a focal loss of disc tissue, usually at the inferior pole, and called it focal ischemic glaucoma because of the presence of a corresponding localized ischemic area found on fluorescein angiography.13 Geijssen and Greve described the senile sclerotic discs in glaucoma, which is characterized by the presence of a pale and saucerized disc, peripapillary atrophy and choroidal sclerosis.4 Cup size, disc size and the presence of areas of peripapillary atrophy are indices of an increased vulnerability of the optic nerve head in glaucomatous damage. In this study, we investigated the relationships between the optic disc appearances, diurnal IOP variation, and visual field defects in patients with NTG.

Subjects and methods

Subjects

Our diagnostic criteria for NTG were: 1. glaucomatous optic disc cupping with progressive visual field defect in one or both eyes; 2. IOP not exceeding 21 mmHg (including all measurements from a 24-hour diurnal curve) without any anti-glauco- matous medication; 3. normal open angle; and 4. no other ocular pathology to account for the visual field defects or the appearance of the optic nerve head.

To be included in the study, eyes had to have a best-corrected visual acuity of 20/ 20 or better with no clinical evidence of media opacity. Patients with a history of intraocular surgery, except argon laser trabeculoplasty, were excluded from this study.

Stereo optic disc photographs of 212 NTG patients, taken with a stereo-fundus camera (3-DX; Nidek, Tokyo) were classified on the basis of the optic disc appearance into the following four groups, by three investigators (YY, FH, CT). The investigators were unaware of the clinical status of the patients.

•Focal ischemic NTG (FINTG): localized tissue loss in the superior or inferior poles but a relatively intact neuroretinal rim in the other areas

•Generalized cup enlargement NTG (GENTG): diffusely enlarged round cup with no localized defect of the neuroretinal rim

•Myopic disc NTG (MYNTG): tilted discs with myopic temporal conus and additional evidence of glaucomatous damage, characterized by thinning of either the superior rim, inferior rim, or both. Discs with degenerative myopia were excluded

•Senile sclerotic NTG (SSNTG): saucerized and shallow cup, called a ‘moth-eaten appearance’, with peripapillary atrophy (PPA) and choroidal sclerosis including

fundus tessellation. The remaining neuroretinal rim is usually pale Non-classifiable discs included discs which appeared normal, discs with poor pho-

tographs, discs with advanced glaucomatous damage that could no longer be securely classified into any of the four groups, and discs with mixtures of more than one pattern. These discs were excluded from further study.

Whenever there was a disagreement as to group classification by all three observers, the discs were excluded from the study. When both discs of the same patient were eligible for the study, only one eye was selected. If both discs were similar, the eye with a more characteristic disc pattern was chosen or the selected eye was chosen at random.

Methods

After the subjects had been selected and classified from their disc photographs, information was collected from their clinical chart: demographic data, including sex, age, refraction, and axial length.

We examined visual fields using program 30-2 of the Humphrey field analyzer (Carl-Zeiss, San Leandro, CA) and calculated the mean deviation (MD) and corrected pattern standard deviation (CPSD) as indices for visual field defects, using statistical analysis software (Statpac 2, Carl-Zeiss). Visual field defects were classified into the three patterns; localized, diffuse, or a combination. Localized defects were defined as the presence of a cluster of two points whose pattern deviation probability level was less than 0.01, located above or below the horizontal meridian. Diffuse defects were defined as having at least 80% of the points plotted in a cumulative curve (Bebié curve)16 located below the 95th percentile and parallel to the normal curve. Combined localized and diffuse defects were defined as a presence of a localized cluster associated with a diffuse defect of the remaining points. Also noted was any visual field defect that threatened fixation, based on a depression of at least 10 dB in one or more of the four most central points.

Each patient was hospitalized for one day, and the IOP was measured at 10:00, 12:00, 14:00, 16:00, 18:00, 20:00, 22:00, 24:00 hours, and at 6:00, 8:00, and 10:00 hours to confirm that the IOP was consistently less than or equal to 21 mmHg over a 24-hour period. The mean, peak, trough, and magnitude of the diurnal range were evaluated. We classified the type of diurnal tension curve into four groups, as follows:17

•morning type: a peak IOP was shown at 6:00-8:00 hours

•day type: a peak IOP was shown at 16:00-18:00 hours

•double variation type: two peak IOPs were shown at 10:00-12:00 and 18:00-20:00 hours

•flat type: variation in IOP of less than 3 mmHg

The data were analyzed using the SPSS statistic package (SPSS, Chicago, IL). Statistical analysis of numeric data was performed by analysis of variance. Categorical data were analyzed by the chi-square test; p values equal to or less than 0.05 were considered as significant.

Results

One hundred and eleven eyes of 111 patients with FINTG (25 patients), GENTG (45 patients), MYNTG (28 patients), and SSNTG (13 patients) met the inclusion criteria for this study. Clinical data are shown in Table 1. There was a significant difference

Table 3. Mean, peak, trough, magnitude and pattern of the 24-hour intraocular pressure in patients with different disc appearances

Mean±SD, No. (%). #: Chi-square test

Information regarding the diurnal IOP variation is shown in Table 3. The pattern of diurnal IOP variation differed significantly between the four groups (p = 0.002). Patients with MYNTG (32.1%) showed the flat type of diurnal IOP variation more frequently than patients in the other three groups.

Discussion

In order to investigate whether there is an influence of optic disc appearance and IOP variation on the visual field in patients with NTG, we evaluated the pattern of visual field defect and diurnal IOP variation in patients with NTG with distinct appearances of the optic disc. Our results showed that over 80% patients with NTG revealed localized visual field defects, and approximately half the patients with GENTG and SSNTG had combined diffuse and localized visual field defects. There was no significant difference in visual field indices obtained with HFA between the four groups. Our data suggest that there may be a different pathogenesis of optic nerve damage in subgroups of NTG patients. Flammer reported that diffuse mechanical damage to the axons, such as that caused by increased IOP, results in diffuse retinal nerve fiber layer (RNFL) damage and diffuse depression of the visual field, and localized damage, possibly from a circulatory disorder in the optic nerve, may result in localized RNFL damage and localized depression of the visual field.18 Our study shows that the optic nerve damage in NTG is predominantly localized damage, but patients with GENTG and SSNTG had generalized damage as well. Several authors have described a relationship between the vulnerability of the optic nerve head and the absolute size of the optic disc with statistically normal IOP.14,15 Broadway and Yamazaki demonstrated that the GENTG and SSNTG groups had a significantly larger optic disc size than others,12,19 implying that the pathogenesis of optic disc damage in these groups may arise from the structural vulnerability of the larger optic disc.

Previous studies in which the diurnal IOP variation was determined every one to three hours demonstrated that the peak IOP occurred in the morning and the trough IOP in the afternoon, or the peak during the daytime and the trough early in the

morning.20 These phenomena were found in our sample of patients with NTG,21 although the magnitude of diurnal variation in NTG eyes was much smaller than that in POAG. In our study, there were no significant differences in mean, peak, trough or magnitude in the diurnal IOP variation between the four groups. However, approximately 30% of patients with MYNTG showed a horizontal curve with tiny fluctuation, and most patients with NTG revealed apparent IOP fluctuation. In this study, the MYNTG group showed significantly longer axial length than the other three groups. It is known that axial length and scleral thickness have a significant correlation with the degree of tension in the scleral lamella.22 We had assumed previously that, in patients with MYNTG, thinning of the lamina cribrosa might make the eye vulnerable at lower IOPs, due to the qualitative properties of the extracellular matrix.23 It is difficult to explain the differences in the type of diurnal IOP variation between the NTG subgroups.

NTG patients with different disc appearances showed differences in visual field defects and diurnal IOP variation. In conclusion, the present study has confirmed that NTG may have different pathogenic mechanisms, according to the type of optic disc appearance.

Acknowledgment

This study was supported by Grant-in-Aid for Scientific Research 14571690 from the Ministry of Education, Science, and Culture of Japan.

References

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2.Goldberg I, Hollows FC, Kass MA et al: Systemic factors in patients with low-tension glaucoma. Br J Ophthalmol 65:56-62, 1981

3.Phelps CD, Corbett JJ: Migraine and low-tension glaucoma: a case-control study. Invest Ophthalmol Vis Sci 26:1105-1108, 1985

4.Geijssen HC, Greve EL: The spectrum of primary open angle glaucoma. I. Senile sclerotic glaucoma versus high tension glaucoma. Ophthalmic Surg 18:207-213, 1987

5.Drance SM, Douglas GR, Wijman K et al: Response of blood flow to warm and cold in normal and low-tension glaucoma patients. Am J Ophthalmol 105:35-39, 1988

6.Caprioli J, Spaeth GL: Comparison of visual field defects in low-tension and high-tension glaucoma. Am J Ophthalmol 97:730-737, 1984

7.Yamazaki Y, Hayamizu F: Comparison of flow velocity of ophthalmic artery between primary open angle glaucoma and normal tension glaucoma. Br J Ophthalmol 79:732-734, 1995

8.Cartwright MJ, Anderson DR: Correlation of asymmetric damage with asymmetric intraocular pressure in normal tension glaucoma (low-tension glaucoma). Arch Ophthalmol 106:898-600, 1988

9.Crichton A, Drance SM, Douglas GR et al: Unequal intraocular pressure and its correlation to asymmetric visual field defects in low tension glaucoma. Ophthalmology 96:1312-1314, 1989

10.Geijssen HC: Studies in Normal Pressure Glaucoma. Amsterdam/New York: Kugler Publ 1991

11.Nicolela MT, Drance SM: Various glaucomatous optic nerve appearances: clinical correlation. Ophthalmology 103:640-649, 1996

12.Yamazaki Y, Hayamizu F, Miyamoto S et al: Optic disc findings in normal tension glaucoma. Jpn J Ophthalmol 41:260-267, 1997

13.Spaeth GL: Fluorescein angiography. Its contribution toward understanding the mechanisms of visual field loss in glaucoma. Trans Am Ophthalmol Soc 73:491-553, 1975

14.Jonas JB, Gusel GC, Naumann GOH: Optic disc morphometry in chronic open angle glaucoma. Graefe’s Arch Clin Exp Ophthalmol 226:522-530, 1988

15.Burk ROW, Rohrschneider K, Noack H et al: Are large optic nerve heads susceptible to glaucomatous damage to normal intraocular pressure? A three-dimensional study by laser scanning tomography. Graefe’s Arch Clin Exp Ophthalmol 230:552-560, 1992

16.Bebié H, Flammer J, Bebié TH: The cumulative defect curve: separation of local and diffuse components of visual field damage. Graefe’s Arch Clin Exp Ophthalmol 227:9-12, 1989

17.Langley D, Swanljung H: Ocular hypertension in glaucoma simplex. Br J Ophthalmol 35:445-458, 1951

18.Flammer J: Psychophysics in glaucoma: a modified concept of the disease. Doc Ophthalmol Proc Ser 43:11-17, 1985

19.Broadway DC, Drance SM, Parfitt CM et al: The ability of scanning laser ophthalmoscopy to identify various glaucomatous optic disc appearances. Am J Ophthalmol 125:593-604, 1998

20.Zeimer RC: Circadian variations in intraocular pressure. In: Ritch R, Shields MB, Krupin T (eds) The Glaucomas, pp 429-445. St Louis/Baltimore: CV Mosby Co 1996

21.Yamagami J, Araie M, Aihara M et al: Diurnal variation in intraocular pressure of normal-tension glaucoma. Ophthalmology 100:643-650, 1993

22.Cahane M, Bartov E: Axial length and scleral thickness effect on susceptibility to glaucomatous damage. A theoretical mode of implementing Laplace’s law. Ophthalmic Res 96:1312-1314, 1989

23.Yamazaki Y, Oshida T: The influence of myopic refraction and intraocular pressure on the visual field in normal-tension glaucoma. In: Heijl A (ed) Perimetry Update 2000/2001, pp 301-305. The Hague: Kulger Publ 2001

AGING AND VARIABILITY IN NORMAL AND

GLAUCOMATOUS VISUAL FIELDS

PAUL H. ARTES, RAYMOND P. LEBLANC and BALWANTRAY C. CHAUHAN

Department of Ophthalmology, Dalhousie University, Halifax, Canada

Abstract

Purpose

To investigate the effects of age on visual fields, and to examine the variability of point-wise sensitivity estimates over time.

Methods

Visual field data (HFA 30-2 full threshold test) were collected, at intervals of six months, from one eye of 113 normal controls (age on study entry, 30–76 years; median, 47.5 years) and 108 patients with glaucoma (15–87 years; median, 61.5 years). Follow-up ranged from two to nine years (median, 7.5 years) for the glaucoma group, and from two to 11 years (median, 5.7 years) for the controls. Longitudinal analysis (sensitivity versus age relative to the patient’s mean value across follow-up) was compared to crosssectional analysis (sensitivity versus age). Variability was quantified by the distribution of residuals from point-wise linear regression, stratified for sensitivity.

Results

The longitudinal analyses gave lower estimates of age-related change than the cross-sectional analyses. The rate of sensitivity loss was largest in the upper periphery, and least in the inferior periphery of the field, and accelerated in patients older than 60 years. Variability varied strongly with sensitivity, but the differences between glaucoma patients and normal controls were small when the effect of sensitivity was accounted for.

Conclusions

Aging may affect the upper and lower parts of the visual field differently. It may not be appropriate to estimate trends in individuals by using slope estimates from cross-sectional analyses.

Address for correspondence: Paul H. Artes, PhD, Department of Ophthalmology, QEII Health Sciences Centre, Centennial Building, VG Site, 1278 Tower Rd, Halifax, Nova Scotia B3H 2Y5, Canada. Email: paul_h_artes@yahoo.co.uk

Perimetry Update 2002/2003, p. 173

Proceedings of the XVth International Perimetric Society Meeting, Stratford-upon-Avon, England, June 26–29, 2002

edited by David B. Henson and Michael Wall

© 2004 Kugler Publications, The Hague, The Netherlands