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Myopia and advanced-stage open-angle glaucoma
Myopia and Advanced-stage Openangle Glaucoma Chihiro Mayama, MD,1 Yasuyuki Suzuki, MD,1 Makoto Araie, MD,1 Kyoko Ishida, MD,2 Tsuji Akira, MD,2 Tetsuya Yamamoto, MD,2 Yoshiaki Kitazawa, MD,2 Shigeo Funaki, MD,3 Motohiro Shirakashi, MD,3 Haruki Abe, MD,3 Hidetoshi Tsukamoto, MD,4 Koji Okada, MD,4 Hiromu K. Mishima, MD4 Objective: To investigate the effect of myopic refraction on the central visual field in patients with advanced open-angle glaucoma (OAG). Design: Multicenter cross-sectional study. Participants: Three hundred thirteen OAG eyes (176 eyes of 176 primary open-angle glaucoma [POAG] patients and 137 eyes of 137 normal-tension glaucoma [NTG] patients) with clear ocular media and a mean deviation (MD) ⬍⫺15 dB. Patients with a recorded maximum intraocular pressure (IOP) of 22 mmHg or greater were classified as POAG, and those with an IOP of 21 mmHg or less were classified as NTG. Methods: Multiple regression analysis was used to study the influence of refraction on 12 central test points of the C30-2 Humphrey program, and the differences in visual field defects between POAG and NTG eyes were examined using logistic discriminant analysis. In the multiple regression analysis, total deviation (TD) of the 12 test points was graded and used as the dependent variable, and MD and the spherical equivalent refraction were the explanatory variables. In the logistic discrimination analysis, TD, MD, and refraction were covariants that determined the OAG subtypes. Main Outcome Measures: TD values of the 12 central test points (C30-2 program). Results: Higher myopic refraction was significantly associated with more damage at a point just temporal and inferior to the fixation point in POAG eyes, whereas it was significantly associated with less damage at test points just temporal and superior to the fixation point in NTG eyes. After correcting for the influence of refraction, POAG eyes had significantly more damage at a test point just temporal and inferior to the fixation point, whereas NTG eyes had significantly more damage at those test points nasal and inferior to the fixation point. Conclusions: High myopia constitutes a threat to the remaining lower cecocentral visual field and is one of the factors that interfere with the quality of vision in advanced OAG with high IOP but not low IOP. Ophthalmology 2002;109:2072–2077 © 2002 by the American Academy of Ophthalmology, Inc.
The prevalence of myopia in Japan is much higher than that in the West,1 and its prevalence might be higher still in some populations with recent births and higher education.2,3 Myopia is associated with higher intraocular pressure (IOP) and occurs more often in glaucoma patients than in the normal population,4 – 8 particularly in the aged population.4 Furthermore, glaucomatous visual field damage tends to be worse in myopic eyes than in nonmyopic eyes and is more likely to progress.6,9 –11 In the early to moderately advanced stage of open-angle glaucoma (OAG), myopia is positively Originally received: May 29, 2001. Accepted: March 5, 2002.
Manuscript no. 210360.
1
Department of Ophthalmology, the University of Tokyo School of Medicine, Tokyo, Japan.
2
Department of Ophthalmology, Gifu University School of Medicine, Gifu, Japan.
associated with a change in the cecocentral visual field, especially in the lower cecocentral field.12,13 The lower cecocentral field is usually spared until a very advanced stage of the disease in nonmyopic eyes14,15 and has great functional importance.15 Thus, if myopia influences the cecocentral field in the advanced stage of the disease, as well as in the earlier stages,13 there will be a clinical impact on the quality of vision in patients with advanced glaucoma. This study investigated the effect of myopic refraction on the central visual field in patients with advanced OAG. OAG with high IOP (primary open-angle glaucoma [POAG]) and OAG with normal IOP (normal-tension glaucoma; NTG) groups were analyzed separately, because many studies suggest that there are IOP-related differences in the pattern of visual field damage in the early to moderately advanced stage,16 –21 as well as in the advanced stage of the disease.22
3
Department of Ophthalmology, Niigata University School of Medicine, Niigata, Japan.
4
Department of Ophthalmology, Hiroshima University School of Medicine, Hiroshima, Japan. Reprint requests to Yasuyuki Suzuki, MD, Department of Ophthalmology, the University of Tokyo School of Medicine, 7-3-1 Hongo Bunkyo-ku Tokyo, 113-8655 Japan.
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© 2002 by the American Academy of Ophthalmology, Inc. Published by Elsevier Science Inc.
Subjects and Methods Subjects The subjects were 313 patients with OAG (176 eyes of 176 POAG patients and 137 eyes of 137 NTG patients) who visited the ISSN 0161-6420/02/$–see front matter PII S0161-6420(02)01175-2
Mayama et al 䡠 Influence of Myopia on Central Visual Field in Advanced-stage Glaucoma Table 1. Characteristics of Subjects
No. of eyes Age (yrs) Refraction (diopters) Mean IOP (mmHg) MD (dB)
Total
Primary Open-angle Glaucoma
Normal-tension Glaucoma
313 57.3 ⫾ 12.1 ⫺2.4 ⫾ 3.5 D (⫺13.0:⫹4.0) 18.0 ⫾ 5.5 ⫺21.4 ⫾ 4.1 (⫺15.1:⫺31.5)
176 56.9 ⫾ 12.1 ⫺2.4 ⫾ 3.6 D (⫺13.0:⫹4.0) 19.6 ⫾ 6.2 ⫺21.9 ⫾ 4.4* (⫺15.1:⫺31.5)
137 57.9 ⫾ 12.3 ⫺2.4 ⫾ 3.5 D (⫺13.0:⫹2.5) 15.3 ⫾ 2.4 ⫺20.7 ⫾ 3.6* (⫺15.1:⫺30.0)
* P ⫽ 0.013. Values are (mean ⫾ standard deviation) and (range). D ⫽ diopters; IOP ⫽ intraocular pressure; MD ⫽ mean deviation.
Department of Ophthalmology, the University of Tokyo School of Medicine, Gifu University School of Medicine, Niigata University School of Medicine, or Hiroshima University School of Medicine from January 1996 to December 1997 and met inclusion criteria. Characteristics of the subjects are shown in Table 1. The inclusion criteria were corrected visual acuity of 0.7 or better; clear ocular media without any clinically significant cataracts, including nuclear cataracts, which can cause lens-induced myopia; absence of any other ocular or intracranial conditions that might affect the visual field; at least two previous examinations using the Humphrey Visual Field Analyzer (Zeiss Humphrey Systems, Dublin, CA) C30-2 program with good reliability (fixation loss ⬍20%, false-negative or false-positive responses ⬍33%); and eyes with mean deviation (MD) given by STATPAC of less than ⫺15 dB. Patients with myopic conus or peripapillary atrophy or other chorioretinal degeneration within a central 10° area of the fovea were excluded. All patients were clinically diagnosed with OAG on the basis of glaucomatous optic nerve head changes14 with corresponding visual field defects and an unoccludable normal open angle. Patients with a maximum IOP of 22 mmHg or greater during clinical follow-up were classified as POAG. Patients with a maximum IOP of 21 mmHg or less during clinical follow-up (including 24-hour IOP fluctuation), no other ocular abnormalities or history of other ocular disease, no nonocular abnormalities that might cause visual field defects, and no history of massive bleeding or hemodynamic crisis were classified as NTG. When both eyes of one patient fulfilled the criteria, one eye was randomly chosen and used for the study. Data from left eyes were converted to the mirror image to facilitate comparison with right eyes.
point of the Humphrey Field Analyzer C30-2 program. Test points at which 2i was significantly different from zero were considered to be significantly influenced by refraction. The differences in visual field defects between POAG and NTG eyes were also examined using logistic discriminant analysis, with TD, MD, and refraction as covariants.
logit共p NTGi 兲 ⫽  0i ⫹  1i 共MD兲 ⫹  2i 共Refraction兲 ⫹  3i 共TDi 兲
(1)
where pNTGi is the probability that the subject eye has NTG rather than POAG, based on the difference in TD of the i-th test point after correcting for possible influences of MD and refraction. A P value of ⬍ 0.05 in each analysis was considered to be statistically significant.
Results Figure 2 shows the results of the multiple regression analysis of the 12 central points of the C30-2 program in the POAG eyes. After
Data Analysis Multiple regression analysis was used to study the influence of refraction on damage at clinically important central test points within 10° of the fixation point in the Humphrey Field Analyzer central 30-2 (C30-2) program (Fig 1). Explanatory variables were MD, as an index of the extent of overall visual field damage in the central 30° visual field, and spherical equivalent refraction, and the dependent variable was the total deviation value (TD, the deviation of patients’ threshold value from the normal value given by STATPAC), which was graded into the following eight grades: (1) TD ⱕ ⫺30 dB, (2) ⫺30 dB ⬍TD ⱕ⫺25 dB, (3) ⫺25dB ⬍TD ⱕ⫺20 dB, (4) ⫺20 dB ⬍TD ⱕ⫺15 dB, (5) ⫺15 dB ⬍TD ⱕ⫺10 dB, (6) ⫺10 dB ⬍TD ⱕ⫺5 dB, (7) ⫺5 dB ⬍TD ⱕ0 dB, and (8) TD ⬎ 0 dB.
共Graded TDi 兲 ⫽  0i ⫹  1i 共MD兲 ⫹  2i 共Refraction兲 (1) where Graded TDi indicates grade number of TD of the i-th test
Figure 1. Dotted squares indicate distribution of 12 central test points that were considered in this study among entire test points of the Humphrey central 30-2 program of the right eye. (Black squares indicate blind spot.)
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Figure 2. Results of multiple regression analysis in primary open-angle glaucoma eyes. Test points at which there was a significant positive correlation between damage and myopic power (hatched square, P ⫽ 0.035; dotted squares, P ⫽ 0.059; and P ⫽ 0.082).
correcting for the influence of overall damage in the central 30° visual field, high myopic refraction was significantly associated with more damage at a point just temporal and inferior to the fixation point (hatched square, P ⫽ 0.035). At two neighboring points, one just nasal and inferior to the preceding point and the other temporal (dotted squares), there was a similar tendency (P ⫽ 0.059; P ⫽ 0.082). Figure 3 shows the results in NTG eyes. There were no points at which higher myopic refraction was significantly associated with more damage. In contrast, there was a significant or borderline significant positive correlation between higher myopic refraction and less damage in the superior area (hatched square, P ⫽ 0.042; dotted square, P ⫽ 0.059). That is, higher myopic refraction was significantly associated with less damage at test points just temporal and superior to the fixation point.
Figure 4. Results of logistic discriminant analysis. Damage was significantly more severe at a point just temporal to the fixation point in primary open-angle glaucoma eyes (hatched square, P ⫽ 0.024), whereas at two contiguous points in the inferior arcuate area, damage was significantly more severe in normal-tension glaucoma eyes (dotted squares, P ⫽ 0.010 and P ⫽ 0.013).
The result of the discriminant analysis is shown in Figure 4. After correcting for the possible influence of myopic refraction and overall damage in the central 30° visual field, damage was significantly more severe at a point just temporal and inferior to the fixation point in the POAG eyes (hatched square, P ⫽ 0.024), whereas at two contiguous points in the nasal inferior paracentral area, damage was significantly more severe in NTG eyes (dotted squares, P ⫽ 0.010; P ⫽ 0.013).
Discussion
Figure 3. Results of multiple regression analysis in normal-tension glaucoma eyes. Test points where there was a significant negative correlation between damage and myopic refraction (hatched square, P ⫽ 0.042; dotted square, P ⫽ 0.059).
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In this study, OAG eyes were categorized into two subtypes, those with high IOP (POAG) and those with normal IOP (NTG), and the effects of myopic refraction were analyzed separately to determine a possible correlation of IOP to the damage at each test point examined.18 –22 This correlation might be examined more adequately by including the mean or highest IOP in the follow-up period as a covariant in the analyses; in advanced cases such as those in this study, however, IOP in the follow-up period might be considerably different from those during the period when the patients had not been observed and the visual field defect had been established, which might confound the analyses. In this multicenter study, patient data were gathered from several glaucoma clinics to obtain a sufficient number of advanced-stage OAG cases that met the inclusion criteria. Obtaining data only from glaucoma clinics might induce sampling bias of patients. Such bias seems, however, minor in this study, because the included cases were all advanced stage, and the diagnosis of the disease could have easily been performed not only by glaucoma specialists but also by general ophthalmologic clinicians. Because we analyzed the influence of myopic refraction
Mayama et al 䡠 Influence of Myopia on Central Visual Field in Advanced-stage Glaucoma on the central visual field, some of the subjects with high myopia had to use high-power lenses to correct near vision for visual field examinations. To perform the examination under conditions normal for daily life, contact lenses were not used in patients who did not normally use them. Thus, the prismatic deviations at extraaxial points must be taken into consideration, particularly when the visual field examination was performed at peripheral test points in patients wearing high-power glass lenses. The ray from an off-axis object entering a minus power lens is bent closer to the optic axis of the lens. Calculation of this effect by computer ray tracing using Gullstrand’s model eye revealed that the angle of the discharging ray to a point 30° outward from the optic axis was 23° instead of 30° with a ⫺10-diopter lens placed 12 mm in front of the corneal apex. Thus, the results of visual field examination at peripheral test points without modifications among eyes with a highly different refractive status cannot be compared directly. In this study, only the 12 central test points within 10° from the fixation point were analyzed (Fig 1). In our subjects (Table 1), the highest lens power used in the visual field examination was ⫺10 diopters, and the maximum prismatic deviation was 2° at a point 10° apart from the fixation point, which is thought to be relatively small compared with the between-test point distance of 6° in the C30-2 program. It is also possible that a high-power lens reduces the stimulus size. The stimulus size might be reduced by approximately 20%, which could affect the visual field test performance of highly myopic patients. The effects of a high-power lens on the stimulation size should be the same in the 12 test points studied, and there were no significant differences in the distribution of refraction between the subjects with NTG and POAG. Therefore, for comparison of the 12 test points or that between NTG and POAG, the possible effect of the highpower lens on stimulus size is not expected to be significant. A point-wise analysis was performed using the TD at each test point (TDi) from the 12 central test points of the C30-2 program. Thus, the P value obtained at each test point will not produce a true type I (␣) error. If TDi (i ⫽ 1, 2. . .12) is completely independent, or the interpoint correlation is zero, then a type I error could be produced using a P value/12. If the interpoint correlation is always 1.0, it should be given by the P value obtained at any of the 12 test points. Because there should be a strong intertest point correlation among TDi, especially between neighboring test points23 in the glaucomatous visual field, a type I error in this study is thought to be somewhere between (P value/12) and (P value/1). A mathematical method of taking intertest point correlation coefficients into consideration to correct the P value in such a case, however, has not yet been established. Clinically, this problem is usually treated by requiring a significant point-wise change at two or more contiguous test points to be considered clinically significant.24 In this study, a test point with a significant influence or difference was always accompanied by a contiguous test point with significant or borderline significant influence or difference (Figs 2 , 3, and 4), except for one occasion (Fig 4). Furthermore, distribution of these contiguous test points was compatible with retinal nerve fiber bundle anatomy. On
the basis of these findings, the probability of a type I error in this study is within an acceptable range. The prevalence of OAG in the population of those 40 or older is 1.1% to 3.3% based on recent population-based studies in the West25–27 and in Japan.28 All studies demonstrated an increase in the prevalence of OAG with an increase in age.25–28 Because OAG is a chronically progressive disease in which visual field damage is irreversible once established, the proportion of patients in an advanced stage of the disease also increases with age. Visual field loss has a major influence on the quality of life of glaucoma patients.29 –31 In an advanced stage of the disease, when the patient’s visual function is mostly lost in the midperipheral to peripheral field,14,15 the spared central visual field (the so-called central island) is very important for quality of life.32 Thus, the principal aim in the treatment of such glaucoma patients is to maintain the spared central island. The results of this study demonstrated that in OAG patients with high IOP and advanced damage, higher myopia is associated with significantly more damage to an area just temporal and inferior to the fixation point. This finding is consistent with that in earlier stage POAG eyes.13 Because this area is usually spared until very advanced stages of the disease in nonmyopic eyes14,15 and is of great functional importance,32–34 higher myopia is thought to be a factor that threatens the quality of vision in OAG patients with high IOP. Structural changes associated with myopia, such as longer axial length, larger and/or tilted optic disc, and peripapillary atrophy might make the upper maculopapillary bundle (lower cecocentral field) more susceptible to glaucomatous injury.35 Population-based studies indicate that myopia is associated with higher IOP.4,5 There was no significant correlation between refraction and mean IOP or MD in the entire patient group or in the POAG and NTG groups in this study. There remains the possibility, however, that a patient with higher myopia has a higher untreated IOP, and the obtained results are due to the history of higher IOP. This possibility seems rather unlikely, however, because the effect of higher IOP, if any, would be diffuse rather than localized.20,21,36,37 In this study, the distribution of test points with a significant correlation with myopic refraction was localized and conformed to the retinal nerve fiber bundle anatomy. A longterm longitudinal study using both myopic refraction and IOP as follow-up covariants is needed to completely isolate the possible effect of IOP from that of myopic refraction. In OAG eyes with normal IOP (NTG), however, there was no significant positive correlation of damage with myopic refraction at any test point analyzed. On the contrary, a test point just superotemporal to the fixation point had a significant negative correlation; that is, higher myopia was associated with less damage. There was a similar finding in NTG eyes in an earlier stage of damage.13 Although we do not have a good explanation for this apparently paradoxical finding at present, this finding might be partly due to myopia-induced structural changes in the optic nerve head, such as tilting. A tilting disc is often encountered in myopic eyes and might change the supporting structure of the optic nerve head. In addition, there are several reports suggesting a difference in the pattern of visual field damage between
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Ophthalmology Volume 109, Number 11, November 2002
Figure 5. Visual field simulation of emmetropic normal-tension glaucoma eye (NTG) (upper line) and highly myopic (⫺10 diopters [D]) primary open-angle glaucoma eye (POAG) (lower line) based on the results of multiple regression analysis.
NTG and POAG,8 –22 which might be attributed to differences in the contribution of IOP to the damage. One possibility is that this difference in the damaging mechanism between NTG and POAG is related to a difference in the effects of a tilt-induced change in the supporting structure on the retinal nerve fiber. Similar results were also reported in earlier stages of the disease.21 The intergroup difference in the pattern of visual field damage was also confirmed in this study after correcting for the influence of myopic refraction and overall visual field damage. A test point just inferior and temporal to the fixation point was significantly more depressed in POAG eyes than in NTG eyes, indicating vulnerability of this functionally important area to both IOP and myopic change. The clinical implication of this study is that higher myopia threatens the remaining lower cecocentral visual field and might be one of the factors threatening the quality of vision in an advanced stage of OAG eyes with high IOP but not with low IOP. On the basis of the data of this cross-sectional study and using multiple regression analysis, the TD can be estimated at each test point under a given refraction, MD as an index of the disease stage, and a clinical diagnosis of POAG or NTG. Examples of such a calculation are shown in Figure 5 (a POAG eye with high myopia of ⫺10 diopters and an emmetropic NTG eye); lower cecocentral field, which is functionally important for the quality of vision in advanced stage OAG,15,32 is gradually lost as the disease progresses in a POAG eye with high myopia, whereas it is relatively well spared until very advanced stages of the disease in an emmetropic NTG eye. This simulation also demonstrates that both IOP value and myopic refraction are very important prognostic factors for the remaining central visual field in advanced stage OAG eyes.
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References 1. Tokoro T. Refractive Error and its Correction, 2nd ed. Tokyo: Kanehara. 1991 chap.4. 2. Familial aggregation and prevalence of myopia in the Framingham Offspring Eye Study. The Framingham Offspring Eye Study Group Arch Ophthalmol 1996;114:326 –32. 3. Wensor M, McCarty CA, Taylor HR. Prevalence and risk factors of myopia in Victoria, Australia. Arch Ophthalmol 1999;117:658 – 63. 4. Mitchell P, Hourihan F, Sandbach J, Wang JJ. The relationship between glaucoma and myopia. The Blue Mountain Eye Study. Ophthalmology 1999;106:2010 –5. 5. David R, Zangwill LM, Tessler Z, Yassur Y. The correlation between intraocular pressure and refractive status. Arch Ophthalmol 1985;103:1812–5. 6. Perkins ES, Phelps CD. Open angle glaucoma, ocular hypertension, low-tension glaucoma, and refraction. Arch Ophthalmol 1982;100:1464 –7. 7. Lotufo D, Ritch R, Szmyd L Jr, Burris JE. Juvenile glaucoma, race, and refraction. JAMA 1989;261:249 –52. 8. Mastropasqua L, Lobefalo L, Mancini A, et al. Prevalence of myopia in open angle glaucoma. Eur J Ophthalmol 1992;2: 33–5. 9. Wilson MR, Hertzmark E, Walker AM, et al. A case-control study of risk factors in open angle glaucoma. Arch Ophthalmol 1987;105:1066 –71. 10. Chihara E, Liu X, Dong J, et al. Severe myopia as a risk factor for progressive visual field loss in primary open-angle glaucoma. Ophthalmologica 1997;211:66 –71. 11. Huang SJ. Early change of visual field function in high myopia—measured and analyzed by octopus automated perimeter. Nippon Ganka Gakkai Zasshi 1993;97:881–7. 12. Greve EL, Furuno F. Myopia and glaucoma. Graefes Arch Clin Exp Ophthalmol 1980;213:33– 41. 13. Araie M, Arai M, Koseki N, Suzuki Y. Influence of myopic
Mayama et al 䡠 Influence of Myopia on Central Visual Field in Advanced-stage Glaucoma
14. 15. 16.
17. 18. 19. 20. 21. 22.
23.
24. 25.
refraction on visual field defects in normal tension and primary open angle glaucoma. Jpn J Ophthalmol 1995;39:60 – 4. Shields MB. Textbook of Glaucoma, 4th ed. Baltimore: Williams & Wilkins, 1998; chap. 5– 6. Weber J, Schultze T, Ulrich H. The visual field in advanced glaucoma. Int Ophthalmol 1989;13:47–50. Motolko M, Drance SM, Douglas GR. Visual field defects in low-tension glaucoma. Comparison of defects in low-tension glaucoma and chronic open angle glaucoma. Arch Ophthalmol 1982;100:1074 –7. King D, Drance SM, Douglas G, et al. Comparison of visual field defects in normal-tension glaucoma and high-tension glaucoma. Am J Ophthalmol 1986;101:204 –7. Caprioli J, Spaeth GL. Comparison of visual field defects in the low-tension glaucomas with those in the high-tension glaucomas. Am J Ophthalmol 1984;97:730 –7. Hitchings RA, Anderson SA. A comparative study of visual field defects seen in patients with low-tension glaucoma and chronic simple glaucoma. Br J Ophthalmol 1983;67:818 –21. Chauhan BC, Drance SM, Douglas GR, Johnson CA. Visual field damage in normal-tension and high-tension glaucoma. Am J Ophthalmol 1989;108:636 – 42. Araie M, Yamagami J, Suziki Y. Visual field defects in normal-tension and high-tension glaucoma. Ophthalmology 1993;100:1808 –14. Araie M, Hori J, Koseki N. Comparison of visual field defects between normal-tension and primary open-angle glaucoma in the late stage of the disease. Graefes Arch Clin Exp Ophthalmol 1995;233:610 – 6. Heijl A, Lindgren N, Lindgren G. Inter-point correlations of deviations of threshold values in normal and glaucomatous visual fields. In: Heijl A, ed. Perimetry Update 1988/1989 Proc 8th Intl Perimetric Society Mtg. Berkeley: Kugler & Ghedini, 1989;177– 83. Caprioli J. Automated perimetry in glaucoma. Am J Ophthalmol 1991;111:235–9. Klein BEK, Klein R, Sponsel WE, et al. Prevalence of glau-
26.
27. 28. 29. 30. 31. 32. 33. 34. 35. 36.
37.
coma. The Beaver Dam Eye Study. Ophthalmology 1992;99: 1499 –504. Dielemans I, Vingerling JR, Wolfs RCW, et al. The prevalence of primary open-angle glaucoma in population-based study in The Netherlands. The Rotterdam Study. Ophthalmology 1994;101:1851–5. Mitchell P, Smith W, Attebo K, Healey PR. Prevalence of open-angle glaucoma in Australia. The Blue Mountains Eye Study. Ophthalmology 1996;103:1661–9. Shiose Y, Kitazawa Y, Tsukahara S, et al. Epidemiology of glaucoma in Japan— a nationwide glaucoma survey. Jpn J Ophthalmol 1991;35:133–55. Parrish RK II, Gedde SJ, Scott IU, et al. Visual function and quality of life among patients with glaucoma. Arch Ophthalmol 1997;115:1447–55. Gutierrez P, Wilson MR, Johnson C, et al. Influence of glaucomatous visual field loss on health-related quality of life. Arch Ophthalmol 1997;115:777– 84. Sherwood MB, Garcia-Siekavizza A, Meltzer MI, et al. Glaucoma’s impact on quality of life and its relation to clinical indicators. A pilot study. Ophthalmology 1998;105:561– 6. Mills RP, Drance SM. Esterman disability rating in severe glaucoma. Ophthalmology 1986;93:371– 8. Esterman B. Grid for scoring visual fields. I. Tangent screen. Arch Ophthalmol 1967;77:780 – 6. Esterman B. Grid for scoring visual fields. II. Perimeter. Arch Ophthalmol 1968;79:400 – 6. Quigley HA, Addicks EM, Green WR, Maumenee AE. Optic nerve damage in human glaucoma. II. The site of injury and susceptibility to damage. Arch Ophthalmol 1981;99:635– 49. Caprioli J, Sears M, Miller JM. Patterns of early visual field loss in open-angle glaucoma [published erratum appears in Am J Ophthalmol 1987;104:98] Am J Ophthalmol 1987;103: 512–7. Samuelson TW, Spaeth GL. Focal and diffuse visual field defects: their relationship to intraocular pressure. Ophthalmic Surg 1993;24:519 –25.
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The prevalence of myopia in Japan is much higher than that in the West,1 and its prevalence might be higher still in some populations with recent births and higher education.2,3 Myopia is associated with higher intraocular pressure (IOP) and occurs more often in glaucoma patients than in the normal population,4 – 8 particularly in the aged population.4 Furthermore, glaucomatous visual field damage tends to be worse in myopic eyes than in nonmyopic eyes and is more likely to progress.6,9 –11 In the early to moderately advanced stage of open-angle glaucoma (OAG), myopia is positively Originally received: May 29, 2001. Accepted: March 5, 2002.
Manuscript no. 210360.
1
Department of Ophthalmology, the University of Tokyo School of Medicine, Tokyo, Japan.
2
Department of Ophthalmology, Gifu University School of Medicine, Gifu, Japan.
associated with a change in the cecocentral visual field, especially in the lower cecocentral field.12,13 The lower cecocentral field is usually spared until a very advanced stage of the disease in nonmyopic eyes14,15 and has great functional importance.15 Thus, if myopia influences the cecocentral field in the advanced stage of the disease, as well as in the earlier stages,13 there will be a clinical impact on the quality of vision in patients with advanced glaucoma. This study investigated the effect of myopic refraction on the central visual field in patients with advanced OAG. OAG with high IOP (primary open-angle glaucoma [POAG]) and OAG with normal IOP (normal-tension glaucoma; NTG) groups were analyzed separately, because many studies suggest that there are IOP-related differences in the pattern of visual field damage in the early to moderately advanced stage,16 –21 as well as in the advanced stage of the disease.22
3
Department of Ophthalmology, Niigata University School of Medicine, Niigata, Japan.
4
Department of Ophthalmology, Hiroshima University School of Medicine, Hiroshima, Japan. Reprint requests to Yasuyuki Suzuki, MD, Department of Ophthalmology, the University of Tokyo School of Medicine, 7-3-1 Hongo Bunkyo-ku Tokyo, 113-8655 Japan.
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© 2002 by the American Academy of Ophthalmology, Inc. Published by Elsevier Science Inc.
Subjects and Methods Subjects The subjects were 313 patients with OAG (176 eyes of 176 POAG patients and 137 eyes of 137 NTG patients) who visited the ISSN 0161-6420/02/$–see front matter PII S0161-6420(02)01175-2
Mayama et al 䡠 Influence of Myopia on Central Visual Field in Advanced-stage Glaucoma Table 1. Characteristics of Subjects
No. of eyes Age (yrs) Refraction (diopters) Mean IOP (mmHg) MD (dB)
Total
Primary Open-angle Glaucoma
Normal-tension Glaucoma
313 57.3 ⫾ 12.1 ⫺2.4 ⫾ 3.5 D (⫺13.0:⫹4.0) 18.0 ⫾ 5.5 ⫺21.4 ⫾ 4.1 (⫺15.1:⫺31.5)
176 56.9 ⫾ 12.1 ⫺2.4 ⫾ 3.6 D (⫺13.0:⫹4.0) 19.6 ⫾ 6.2 ⫺21.9 ⫾ 4.4* (⫺15.1:⫺31.5)
137 57.9 ⫾ 12.3 ⫺2.4 ⫾ 3.5 D (⫺13.0:⫹2.5) 15.3 ⫾ 2.4 ⫺20.7 ⫾ 3.6* (⫺15.1:⫺30.0)
* P ⫽ 0.013. Values are (mean ⫾ standard deviation) and (range). D ⫽ diopters; IOP ⫽ intraocular pressure; MD ⫽ mean deviation.
Department of Ophthalmology, the University of Tokyo School of Medicine, Gifu University School of Medicine, Niigata University School of Medicine, or Hiroshima University School of Medicine from January 1996 to December 1997 and met inclusion criteria. Characteristics of the subjects are shown in Table 1. The inclusion criteria were corrected visual acuity of 0.7 or better; clear ocular media without any clinically significant cataracts, including nuclear cataracts, which can cause lens-induced myopia; absence of any other ocular or intracranial conditions that might affect the visual field; at least two previous examinations using the Humphrey Visual Field Analyzer (Zeiss Humphrey Systems, Dublin, CA) C30-2 program with good reliability (fixation loss ⬍20%, false-negative or false-positive responses ⬍33%); and eyes with mean deviation (MD) given by STATPAC of less than ⫺15 dB. Patients with myopic conus or peripapillary atrophy or other chorioretinal degeneration within a central 10° area of the fovea were excluded. All patients were clinically diagnosed with OAG on the basis of glaucomatous optic nerve head changes14 with corresponding visual field defects and an unoccludable normal open angle. Patients with a maximum IOP of 22 mmHg or greater during clinical follow-up were classified as POAG. Patients with a maximum IOP of 21 mmHg or less during clinical follow-up (including 24-hour IOP fluctuation), no other ocular abnormalities or history of other ocular disease, no nonocular abnormalities that might cause visual field defects, and no history of massive bleeding or hemodynamic crisis were classified as NTG. When both eyes of one patient fulfilled the criteria, one eye was randomly chosen and used for the study. Data from left eyes were converted to the mirror image to facilitate comparison with right eyes.
point of the Humphrey Field Analyzer C30-2 program. Test points at which 2i was significantly different from zero were considered to be significantly influenced by refraction. The differences in visual field defects between POAG and NTG eyes were also examined using logistic discriminant analysis, with TD, MD, and refraction as covariants.
logit共p NTGi 兲 ⫽  0i ⫹  1i 共MD兲 ⫹  2i 共Refraction兲 ⫹  3i 共TDi 兲
(1)
where pNTGi is the probability that the subject eye has NTG rather than POAG, based on the difference in TD of the i-th test point after correcting for possible influences of MD and refraction. A P value of ⬍ 0.05 in each analysis was considered to be statistically significant.
Results Figure 2 shows the results of the multiple regression analysis of the 12 central points of the C30-2 program in the POAG eyes. After
Data Analysis Multiple regression analysis was used to study the influence of refraction on damage at clinically important central test points within 10° of the fixation point in the Humphrey Field Analyzer central 30-2 (C30-2) program (Fig 1). Explanatory variables were MD, as an index of the extent of overall visual field damage in the central 30° visual field, and spherical equivalent refraction, and the dependent variable was the total deviation value (TD, the deviation of patients’ threshold value from the normal value given by STATPAC), which was graded into the following eight grades: (1) TD ⱕ ⫺30 dB, (2) ⫺30 dB ⬍TD ⱕ⫺25 dB, (3) ⫺25dB ⬍TD ⱕ⫺20 dB, (4) ⫺20 dB ⬍TD ⱕ⫺15 dB, (5) ⫺15 dB ⬍TD ⱕ⫺10 dB, (6) ⫺10 dB ⬍TD ⱕ⫺5 dB, (7) ⫺5 dB ⬍TD ⱕ0 dB, and (8) TD ⬎ 0 dB.
共Graded TDi 兲 ⫽  0i ⫹  1i 共MD兲 ⫹  2i 共Refraction兲 (1) where Graded TDi indicates grade number of TD of the i-th test
Figure 1. Dotted squares indicate distribution of 12 central test points that were considered in this study among entire test points of the Humphrey central 30-2 program of the right eye. (Black squares indicate blind spot.)
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Figure 2. Results of multiple regression analysis in primary open-angle glaucoma eyes. Test points at which there was a significant positive correlation between damage and myopic power (hatched square, P ⫽ 0.035; dotted squares, P ⫽ 0.059; and P ⫽ 0.082).
correcting for the influence of overall damage in the central 30° visual field, high myopic refraction was significantly associated with more damage at a point just temporal and inferior to the fixation point (hatched square, P ⫽ 0.035). At two neighboring points, one just nasal and inferior to the preceding point and the other temporal (dotted squares), there was a similar tendency (P ⫽ 0.059; P ⫽ 0.082). Figure 3 shows the results in NTG eyes. There were no points at which higher myopic refraction was significantly associated with more damage. In contrast, there was a significant or borderline significant positive correlation between higher myopic refraction and less damage in the superior area (hatched square, P ⫽ 0.042; dotted square, P ⫽ 0.059). That is, higher myopic refraction was significantly associated with less damage at test points just temporal and superior to the fixation point.
Figure 4. Results of logistic discriminant analysis. Damage was significantly more severe at a point just temporal to the fixation point in primary open-angle glaucoma eyes (hatched square, P ⫽ 0.024), whereas at two contiguous points in the inferior arcuate area, damage was significantly more severe in normal-tension glaucoma eyes (dotted squares, P ⫽ 0.010 and P ⫽ 0.013).
The result of the discriminant analysis is shown in Figure 4. After correcting for the possible influence of myopic refraction and overall damage in the central 30° visual field, damage was significantly more severe at a point just temporal and inferior to the fixation point in the POAG eyes (hatched square, P ⫽ 0.024), whereas at two contiguous points in the nasal inferior paracentral area, damage was significantly more severe in NTG eyes (dotted squares, P ⫽ 0.010; P ⫽ 0.013).
Discussion
Figure 3. Results of multiple regression analysis in normal-tension glaucoma eyes. Test points where there was a significant negative correlation between damage and myopic refraction (hatched square, P ⫽ 0.042; dotted square, P ⫽ 0.059).
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In this study, OAG eyes were categorized into two subtypes, those with high IOP (POAG) and those with normal IOP (NTG), and the effects of myopic refraction were analyzed separately to determine a possible correlation of IOP to the damage at each test point examined.18 –22 This correlation might be examined more adequately by including the mean or highest IOP in the follow-up period as a covariant in the analyses; in advanced cases such as those in this study, however, IOP in the follow-up period might be considerably different from those during the period when the patients had not been observed and the visual field defect had been established, which might confound the analyses. In this multicenter study, patient data were gathered from several glaucoma clinics to obtain a sufficient number of advanced-stage OAG cases that met the inclusion criteria. Obtaining data only from glaucoma clinics might induce sampling bias of patients. Such bias seems, however, minor in this study, because the included cases were all advanced stage, and the diagnosis of the disease could have easily been performed not only by glaucoma specialists but also by general ophthalmologic clinicians. Because we analyzed the influence of myopic refraction
Mayama et al 䡠 Influence of Myopia on Central Visual Field in Advanced-stage Glaucoma on the central visual field, some of the subjects with high myopia had to use high-power lenses to correct near vision for visual field examinations. To perform the examination under conditions normal for daily life, contact lenses were not used in patients who did not normally use them. Thus, the prismatic deviations at extraaxial points must be taken into consideration, particularly when the visual field examination was performed at peripheral test points in patients wearing high-power glass lenses. The ray from an off-axis object entering a minus power lens is bent closer to the optic axis of the lens. Calculation of this effect by computer ray tracing using Gullstrand’s model eye revealed that the angle of the discharging ray to a point 30° outward from the optic axis was 23° instead of 30° with a ⫺10-diopter lens placed 12 mm in front of the corneal apex. Thus, the results of visual field examination at peripheral test points without modifications among eyes with a highly different refractive status cannot be compared directly. In this study, only the 12 central test points within 10° from the fixation point were analyzed (Fig 1). In our subjects (Table 1), the highest lens power used in the visual field examination was ⫺10 diopters, and the maximum prismatic deviation was 2° at a point 10° apart from the fixation point, which is thought to be relatively small compared with the between-test point distance of 6° in the C30-2 program. It is also possible that a high-power lens reduces the stimulus size. The stimulus size might be reduced by approximately 20%, which could affect the visual field test performance of highly myopic patients. The effects of a high-power lens on the stimulation size should be the same in the 12 test points studied, and there were no significant differences in the distribution of refraction between the subjects with NTG and POAG. Therefore, for comparison of the 12 test points or that between NTG and POAG, the possible effect of the highpower lens on stimulus size is not expected to be significant. A point-wise analysis was performed using the TD at each test point (TDi) from the 12 central test points of the C30-2 program. Thus, the P value obtained at each test point will not produce a true type I (␣) error. If TDi (i ⫽ 1, 2. . .12) is completely independent, or the interpoint correlation is zero, then a type I error could be produced using a P value/12. If the interpoint correlation is always 1.0, it should be given by the P value obtained at any of the 12 test points. Because there should be a strong intertest point correlation among TDi, especially between neighboring test points23 in the glaucomatous visual field, a type I error in this study is thought to be somewhere between (P value/12) and (P value/1). A mathematical method of taking intertest point correlation coefficients into consideration to correct the P value in such a case, however, has not yet been established. Clinically, this problem is usually treated by requiring a significant point-wise change at two or more contiguous test points to be considered clinically significant.24 In this study, a test point with a significant influence or difference was always accompanied by a contiguous test point with significant or borderline significant influence or difference (Figs 2 , 3, and 4), except for one occasion (Fig 4). Furthermore, distribution of these contiguous test points was compatible with retinal nerve fiber bundle anatomy. On
the basis of these findings, the probability of a type I error in this study is within an acceptable range. The prevalence of OAG in the population of those 40 or older is 1.1% to 3.3% based on recent population-based studies in the West25–27 and in Japan.28 All studies demonstrated an increase in the prevalence of OAG with an increase in age.25–28 Because OAG is a chronically progressive disease in which visual field damage is irreversible once established, the proportion of patients in an advanced stage of the disease also increases with age. Visual field loss has a major influence on the quality of life of glaucoma patients.29 –31 In an advanced stage of the disease, when the patient’s visual function is mostly lost in the midperipheral to peripheral field,14,15 the spared central visual field (the so-called central island) is very important for quality of life.32 Thus, the principal aim in the treatment of such glaucoma patients is to maintain the spared central island. The results of this study demonstrated that in OAG patients with high IOP and advanced damage, higher myopia is associated with significantly more damage to an area just temporal and inferior to the fixation point. This finding is consistent with that in earlier stage POAG eyes.13 Because this area is usually spared until very advanced stages of the disease in nonmyopic eyes14,15 and is of great functional importance,32–34 higher myopia is thought to be a factor that threatens the quality of vision in OAG patients with high IOP. Structural changes associated with myopia, such as longer axial length, larger and/or tilted optic disc, and peripapillary atrophy might make the upper maculopapillary bundle (lower cecocentral field) more susceptible to glaucomatous injury.35 Population-based studies indicate that myopia is associated with higher IOP.4,5 There was no significant correlation between refraction and mean IOP or MD in the entire patient group or in the POAG and NTG groups in this study. There remains the possibility, however, that a patient with higher myopia has a higher untreated IOP, and the obtained results are due to the history of higher IOP. This possibility seems rather unlikely, however, because the effect of higher IOP, if any, would be diffuse rather than localized.20,21,36,37 In this study, the distribution of test points with a significant correlation with myopic refraction was localized and conformed to the retinal nerve fiber bundle anatomy. A longterm longitudinal study using both myopic refraction and IOP as follow-up covariants is needed to completely isolate the possible effect of IOP from that of myopic refraction. In OAG eyes with normal IOP (NTG), however, there was no significant positive correlation of damage with myopic refraction at any test point analyzed. On the contrary, a test point just superotemporal to the fixation point had a significant negative correlation; that is, higher myopia was associated with less damage. There was a similar finding in NTG eyes in an earlier stage of damage.13 Although we do not have a good explanation for this apparently paradoxical finding at present, this finding might be partly due to myopia-induced structural changes in the optic nerve head, such as tilting. A tilting disc is often encountered in myopic eyes and might change the supporting structure of the optic nerve head. In addition, there are several reports suggesting a difference in the pattern of visual field damage between
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Figure 5. Visual field simulation of emmetropic normal-tension glaucoma eye (NTG) (upper line) and highly myopic (⫺10 diopters [D]) primary open-angle glaucoma eye (POAG) (lower line) based on the results of multiple regression analysis.
NTG and POAG,8 –22 which might be attributed to differences in the contribution of IOP to the damage. One possibility is that this difference in the damaging mechanism between NTG and POAG is related to a difference in the effects of a tilt-induced change in the supporting structure on the retinal nerve fiber. Similar results were also reported in earlier stages of the disease.21 The intergroup difference in the pattern of visual field damage was also confirmed in this study after correcting for the influence of myopic refraction and overall visual field damage. A test point just inferior and temporal to the fixation point was significantly more depressed in POAG eyes than in NTG eyes, indicating vulnerability of this functionally important area to both IOP and myopic change. The clinical implication of this study is that higher myopia threatens the remaining lower cecocentral visual field and might be one of the factors threatening the quality of vision in an advanced stage of OAG eyes with high IOP but not with low IOP. On the basis of the data of this cross-sectional study and using multiple regression analysis, the TD can be estimated at each test point under a given refraction, MD as an index of the disease stage, and a clinical diagnosis of POAG or NTG. Examples of such a calculation are shown in Figure 5 (a POAG eye with high myopia of ⫺10 diopters and an emmetropic NTG eye); lower cecocentral field, which is functionally important for the quality of vision in advanced stage OAG,15,32 is gradually lost as the disease progresses in a POAG eye with high myopia, whereas it is relatively well spared until very advanced stages of the disease in an emmetropic NTG eye. This simulation also demonstrates that both IOP value and myopic refraction are very important prognostic factors for the remaining central visual field in advanced stage OAG eyes.
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References 1. Tokoro T. Refractive Error and its Correction, 2nd ed. Tokyo: Kanehara. 1991 chap.4. 2. Familial aggregation and prevalence of myopia in the Framingham Offspring Eye Study. The Framingham Offspring Eye Study Group Arch Ophthalmol 1996;114:326 –32. 3. Wensor M, McCarty CA, Taylor HR. Prevalence and risk factors of myopia in Victoria, Australia. Arch Ophthalmol 1999;117:658 – 63. 4. Mitchell P, Hourihan F, Sandbach J, Wang JJ. The relationship between glaucoma and myopia. The Blue Mountain Eye Study. Ophthalmology 1999;106:2010 –5. 5. David R, Zangwill LM, Tessler Z, Yassur Y. The correlation between intraocular pressure and refractive status. Arch Ophthalmol 1985;103:1812–5. 6. Perkins ES, Phelps CD. Open angle glaucoma, ocular hypertension, low-tension glaucoma, and refraction. Arch Ophthalmol 1982;100:1464 –7. 7. Lotufo D, Ritch R, Szmyd L Jr, Burris JE. Juvenile glaucoma, race, and refraction. JAMA 1989;261:249 –52. 8. Mastropasqua L, Lobefalo L, Mancini A, et al. Prevalence of myopia in open angle glaucoma. Eur J Ophthalmol 1992;2: 33–5. 9. Wilson MR, Hertzmark E, Walker AM, et al. A case-control study of risk factors in open angle glaucoma. Arch Ophthalmol 1987;105:1066 –71. 10. Chihara E, Liu X, Dong J, et al. Severe myopia as a risk factor for progressive visual field loss in primary open-angle glaucoma. Ophthalmologica 1997;211:66 –71. 11. Huang SJ. Early change of visual field function in high myopia—measured and analyzed by octopus automated perimeter. Nippon Ganka Gakkai Zasshi 1993;97:881–7. 12. Greve EL, Furuno F. Myopia and glaucoma. Graefes Arch Clin Exp Ophthalmol 1980;213:33– 41. 13. Araie M, Arai M, Koseki N, Suzuki Y. Influence of myopic
Mayama et al 䡠 Influence of Myopia on Central Visual Field in Advanced-stage Glaucoma
14. 15. 16.
17. 18. 19. 20. 21. 22.
23.
24. 25.
refraction on visual field defects in normal tension and primary open angle glaucoma. Jpn J Ophthalmol 1995;39:60 – 4. Shields MB. Textbook of Glaucoma, 4th ed. Baltimore: Williams & Wilkins, 1998; chap. 5– 6. Weber J, Schultze T, Ulrich H. The visual field in advanced glaucoma. Int Ophthalmol 1989;13:47–50. Motolko M, Drance SM, Douglas GR. Visual field defects in low-tension glaucoma. Comparison of defects in low-tension glaucoma and chronic open angle glaucoma. Arch Ophthalmol 1982;100:1074 –7. King D, Drance SM, Douglas G, et al. Comparison of visual field defects in normal-tension glaucoma and high-tension glaucoma. Am J Ophthalmol 1986;101:204 –7. Caprioli J, Spaeth GL. Comparison of visual field defects in the low-tension glaucomas with those in the high-tension glaucomas. Am J Ophthalmol 1984;97:730 –7. Hitchings RA, Anderson SA. A comparative study of visual field defects seen in patients with low-tension glaucoma and chronic simple glaucoma. Br J Ophthalmol 1983;67:818 –21. Chauhan BC, Drance SM, Douglas GR, Johnson CA. Visual field damage in normal-tension and high-tension glaucoma. Am J Ophthalmol 1989;108:636 – 42. Araie M, Yamagami J, Suziki Y. Visual field defects in normal-tension and high-tension glaucoma. Ophthalmology 1993;100:1808 –14. Araie M, Hori J, Koseki N. Comparison of visual field defects between normal-tension and primary open-angle glaucoma in the late stage of the disease. Graefes Arch Clin Exp Ophthalmol 1995;233:610 – 6. Heijl A, Lindgren N, Lindgren G. Inter-point correlations of deviations of threshold values in normal and glaucomatous visual fields. In: Heijl A, ed. Perimetry Update 1988/1989 Proc 8th Intl Perimetric Society Mtg. Berkeley: Kugler & Ghedini, 1989;177– 83. Caprioli J. Automated perimetry in glaucoma. Am J Ophthalmol 1991;111:235–9. Klein BEK, Klein R, Sponsel WE, et al. Prevalence of glau-
26.
27. 28. 29. 30. 31. 32. 33. 34. 35. 36.
37.
coma. The Beaver Dam Eye Study. Ophthalmology 1992;99: 1499 –504. Dielemans I, Vingerling JR, Wolfs RCW, et al. The prevalence of primary open-angle glaucoma in population-based study in The Netherlands. The Rotterdam Study. Ophthalmology 1994;101:1851–5. Mitchell P, Smith W, Attebo K, Healey PR. Prevalence of open-angle glaucoma in Australia. The Blue Mountains Eye Study. Ophthalmology 1996;103:1661–9. Shiose Y, Kitazawa Y, Tsukahara S, et al. Epidemiology of glaucoma in Japan— a nationwide glaucoma survey. Jpn J Ophthalmol 1991;35:133–55. Parrish RK II, Gedde SJ, Scott IU, et al. Visual function and quality of life among patients with glaucoma. Arch Ophthalmol 1997;115:1447–55. Gutierrez P, Wilson MR, Johnson C, et al. Influence of glaucomatous visual field loss on health-related quality of life. Arch Ophthalmol 1997;115:777– 84. Sherwood MB, Garcia-Siekavizza A, Meltzer MI, et al. Glaucoma’s impact on quality of life and its relation to clinical indicators. A pilot study. Ophthalmology 1998;105:561– 6. Mills RP, Drance SM. Esterman disability rating in severe glaucoma. Ophthalmology 1986;93:371– 8. Esterman B. Grid for scoring visual fields. I. Tangent screen. Arch Ophthalmol 1967;77:780 – 6. Esterman B. Grid for scoring visual fields. II. Perimeter. Arch Ophthalmol 1968;79:400 – 6. Quigley HA, Addicks EM, Green WR, Maumenee AE. Optic nerve damage in human glaucoma. II. The site of injury and susceptibility to damage. Arch Ophthalmol 1981;99:635– 49. Caprioli J, Sears M, Miller JM. Patterns of early visual field loss in open-angle glaucoma [published erratum appears in Am J Ophthalmol 1987;104:98] Am J Ophthalmol 1987;103: 512–7. Samuelson TW, Spaeth GL. Focal and diffuse visual field defects: their relationship to intraocular pressure. Ophthalmic Surg 1993;24:519 –25.
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