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Factors Associated With Visual Loss in Patients With Advanced Glaucomatous Changes in the Optic Nerve Head
Factors Associated With Visual Loss in Patients With Advanced Glaucomatous Changes in the Optic Nerve Head William C. Stewart, M.D., Rosalind P. Chorak, B.S., Hurshell H. Hunt, Ph.D., and Gopalan Sethuraman, M.S.
We evaluated factors associated with decreased or stable visual function in 72 patients with primary open-angle glaucoma and complete cupping of the optic disk who were followed up five years or more. We found a significantly lower mean (15.4 ± 2.7 mm Hg) and peak (24.5 ± 6.9 mm Hg) intraocular pressure in those patients whose vision remained stable vs those whose vision decreased (21.3 ± 3.2 and 39.2 ± 11.0 mm Hg, respectively) (ttest, P < .001). Additionally, the variance of each patient's individual intraocular pressure readings measured during the follow-up period was lower in the group with stable vision (4.5 mm Hg) than in those in whom vision decreased (9.0 mm Hg) (F test, P < .001). Stepwise discriminant analysis disclosed that mean intraocular pressure, variance of an individual's intraocular pressure measurements over time, history of argon laser trabeculoplasty, and compliance with therapy discriminated 92.9% of patients (52 of 56) whose vision remained stable and 87.5% of patients (14 of 16) whose vision decreased. Reduction of intraocular pressure and compliance with therapy are important in patients with complete glaucomatous cupping of the optic disk. IN PATIENTS WITH GLAUCOMA, medical, laser, and conventional surgical therapy typically are used to control the intraocular pressure to a
Accepted for publication April 28, 1993. From the Glaucoma Service at the Department of Ophthalmology (Dr. Stewart and Ms. Chorak), and the Department of Biostatistics and Epidemiology (Dr. Hunt and Mr. Sethuraman), Medical University of South Carolina, Charleston, South Carolina. This study was sponsored in part by an unrestricted grant from Research to Prevent Blindness, Inc., New York, New York. Reprint requests to William C. Stewart, M.D., Storm Eye Institute, Medical University of South Carolina, 171 Ashley Ave., Charleston, SC 29425-2236.
176
level that prevents progressive loss of vision. Most investigators believe that in patients with advanced glaucomatous damage, the intraocular pressure should be controlled to within the normal range. 1,2 Previous studies that have investigated factors associated with advanced visual loss in glaucoma have used the visual field to determine the extent of damage.i" However, advanced glaucomatous damage may be diagnosed also by the appearance of the optic nerve head.' Little data exist on patients with advanced changes in the optic nerve head and factors associated with progressive glaucomatous damage. We studied consecutively examined patients with advanced glaucomatous changes in the optic nerve head who had been followed up for five years or more with or without surgical intervention. We examined for factors associated either with preservation or loss of visual acuity and visual field in these patients.
Patients and
Methods
We included in this study consecutive patients with advanced glaucomatous changes in the optic nerve head who were followed up by the glaucoma service at our institution and who met one of two criteria: stable glaucoma for at least five years, or progressed glaucoma that had been diagnosed within the past five years. Data were collected regarding stable glaucoma for as long as records were available. Data were collected from the records of patients with progressed glaucoma until the time the glaucoma worsened. Data were not collected after the time of progression; therefore, the information included in this study would reflect the status of the eye until the worsening of glaucoma. The criterion for advanced glaucomatous change of the optic nerve head was no observ-
©AMERICAN JOURNAL OF OPHTHALMOLOGY
116:176-181,
AUGUST,
1993
Vol. 116, No.2
Complete Optic Nerve Cupping and Glaucoma
able neural rim remaining within the optic disk (that is, a complete cup). Primary open-angle glaucoma had been diagnosed in each patient. Excluded from this study were patients with congenital, secondary, narrow-angle, or lowtension glaucoma. Also excluded from this study were patients thought to have progressive nonglaucomatous visual loss. Patients were followed up at outpatient visits every three months or more frequently as needed. At each outpatient visit, the intraocular pressure was measured by Goldmann applanation tonometry. Evaluation of the ocular adnexa, slit-lamp biomicroscopy, and optic disk examination by direct ophthalmoscopy also were performed. Examinations of the optic disk through a dilated pupil and the visual field were completed yearly or more frequently if the patient had split fixation or progression of glaucoma was suspected. The optic disk was examined by stereoscopic techniques, including the Goldmann lens and color photography. Progression or stability of each patient's glaucoma was assessed by using automated perimetry and Snellen visual acuity. Because each patient in this study had complete cupping of the optic disk, the optic nerve head could not be used as a measure of progression. Automated perimetry with the Humphrey Field Analyzer (program 30-2 or a 76-point screen with a quantified defect) (Humphrey Instruments, Inc., San Leandro, California) was used to measure the visual field. Each visual field was given one of the following five interpretations: within normal limits, early changes in the nerve fiber layer (that is, paracentral or Seidel's scotoma), late arcuate changes in the nerve fiber layer (that is, arcuate scotoma)," central island remaining with complete superior and inferior arcuate scotomas, or "unable to perform" because of deep diffuse depression of the field with coexistent loss of central vision. The inferior and superior hemifields were diagnosed separately. The criterion for reduction of a normal visual field was the development of changes in the nerve fiber layer. Criteria for progression of early changes in the nerve fiber layer included progression to an arcuate scotoma or development of a new defect in the nerve fiber layer in the opposite hemifield. The criterion for decrease in patients with an arcuate scotoma was the eventual development in the opposite hemifield of a defect of the nerve fiber layer. The criterion for progression of a central island was a narrowing of the remaining visual field. Pro-
177
gressive loss in the visual field was diagnosed only if these visual field changes were observed for three successive examinations." The criterion for progressive loss in visual acuity was a decrease of two or more Snellen lines not attributable to other ocular disease despite the patient's best refraction. Data collection and statistical analysis between patients in whom glaucoma was stable or had progressed were performed as follows. A Student's t-test was used to analyze data for patient age and for the mean and peak intraocular pressures during the follow-up period. 9P. I22 An F test analyzed the differences between the variance of each patient's intraocular pressures measured during the follow-up period.9p.227 A X2 test was used to analyze differences between groups of nonordered scores, such as the eye operated on (left or right); gender; compliance (both with suggested medical treatment and in following surgical recommendations); a history of diabetes, arthritis, systemic hypertension, or pseudophakia; argon laser trabeculoplasty; and whether trabeculectomy had been performed during the follow-up period.9p.205 A Fisher's exact test was used to analyze differences of nonordered scores that had at least one expected value of less than 5 in a 2 x 2 table, and included race and history of heart disease." A Mann-Whitney U-test was used to determine statistical differences between groups of ordered scores, which included visual acuity, visual field defect, and number of glaucoma medicines. II If both eyes of a patient met the criteria for entrance into the study, only one was randomly chosen to be analyzed. We also performed a stepwise discriminant analysis to determine the ability of the factors evaluated in this study to predict whether the patients' glaucoma would be categorized as stable or progressed.
Results We included in this study 72 consecutively examined patients with complete cupping of the optic disk who met the study'S entrance criteria. Patients in whom glaucoma progressed were followed up for an average of 3.3 ± 1.3 years before decreased visual function was observed. Patients with stable glaucoma were followed up for an average of 5.4 ± 1.0 years. We compared the data related to patient history between patients with stable glaucoma and
178
August, 1993
AMERICAN JOURNAL OF OPHTHALMOLOGY
TABLE
1
DATA RELATED TO PATIENT HISTORY STABLE PROGRESSED GLAUCOMA GLAUCOMA
Age (yrs) 61.2 ± 13 71.5 ± 9.5 Gender Men: women 6:10 20:36 Race Black: white Eye
STATISTICAL VALUE
t
= 2.95
P VALUE
.006
K = 0.016
.876
14:2
46:10
Fisher's exact
.832
9:7
27:29
K = 0.311
.601
8 8
20 36
K = 1.07
.300
3 13
49
Yes No Ar.hritis
6 10
30 26
K = 1.29
.249
Yes No
6 10
15 41
K = 0.69
.421
Right: left Medical history Diabetes Yes No Heart disease Yes No Systemic hyper-
7
Fisher's exact> .900
tension
patients with progressed glaucoma (Table 1). Only the mean age showed a statistically significant difference between groups. We also compared the data related to the intraocular pressure and visual function between patients with stable glaucoma and patients with progressed glaucoma (Table 2). The mean and peak intraocular pressures were markedly lower in the patients with stable glaucoma than in the patients with progressed glaucoma. Also, each individual's variance of intraocular pressure measurements during the follow-up period was significantly lower in the stable (4.5 mm Hg) than the progressed category of glaucoma (9.0 mm Hg). We compared the distribution of the mean intraocular pressures (Fig. 1) and the distribution of the square root of the variance (Fig. 2) between patients with stable glaucoma and patients with progressed glaucoma. The extent of visual field damage (P = .006) and compliance (P < .001) during the follow-up period were significantly worse in patients with progressed glaucoma vs patients with stable glaucoma. Also, patients whose glaucoma progressed statistically more often had a history of previous filtering operations. In contrast, a history of argon laser trabeculoplasty, pseudo-
phakia, number of glaucoma medications, and Snellen visual acuity were similar between groups during the follow-up period. In the 16 patients whose glaucoma progressed, worsening disease was diagnosed by changes in the visual acuity and not by changes in the visual field. The stepwise discriminant analysis showed that the best discriminant variables were mean intraocular pressure, variance of each patient's intraocular pressure measurements, history of argon laser trabeculoplasty, and compliance with therapy. The discriminant function for the stable group was D = 2.1323 (mean) - 0.2752 (variance) + 1.11
(laser) + 5.0133 (compliance) - 23.5697. The discriminant function for the progressed group was D = 2.7586 (mean) + 0.5017 (variance) 0.6282 (laser) + 3.6175 (compliance) - 34.7767. These functions classified correctly 92.9 % of the patients with stable glaucoma (52 of 56) and 87.5% of the patients with progressed glaucoma (14 of 16).
Discussion
Controversy still exists over the proper treatment of patients with advanced primary openangle glaucoma. In general, treatment consists of using medical, laser, then conventional surgical therapy as needed to lower the intraocular pressure to a level that the clinician believes will prevent progressive glaucomatous damage. Chandler! and Shaffer! indicated that the intraocular pressure should be kept in a normal range in patients with advanced glaucomatous changes in the visual field to prevent progressive damage. More recent reports have implied that the glaucoma in patients with advanced visual field loss usually remains stable with an intraocular pressure between 15.0 and 18.0 mm Hg,3'5,!2 although this finding has not been consistent." Additionally, several studies have noted that both the extent":" and rate of visual field 10ss15 are worse with higher mean and peak" intraocular pressures. Previous reports have defined advanced glaucomatous damage on the basis of the appearance of the visual field.!" However, interpreting advanced visual field changes in glaucoma is complicated by greater unreliability" and
Vol. 116, No.2
Complete Optic Nerve Cupping and Glaucoma
TABLE
179
2
DATA RELATED TO INTRAOCULAR PRESSURE AND VISION PROGRESSED
STABLE
STATISTICAL
GLAUCOMA
GLAUCOMA
VALUE
21.3 ± 3.2 39.2 ± 11
15.4 ± 2.7 24.5 ± 6.9
9.0
4.5
CF-LP
4
20/400-20/100
2 4
6 11 16
6
23
PVALUE
Intraocular pressure (mm Hg) Mean Peak Mean standard deviation' Visual acuityt
20/80-20/50 20/40-20/20 Visual field (mean defect in decibels) Within normal limits Early arcuate Late arcuate Deep diffuse depression
0 0 2
5 5 15
4
21
10
10
1
8
3
5
21
2 1
8 2
20 7
0 Argon laser trabeculoplasty
0
0
Yes No Filtering surgery
11 5
40 16
None
6
38
Combined with cataract extraction Filter only
2
15
8
3
6 10
15
Unable to do Number of glaucoma medications 4
Pseudophakia Yes No Compliance with treatment regimen Good Poor
5 13
t = 6.72 t = 5.07
< .001 < .001 < .001
F
= 4.00
z
= 0.669
.504
z
= 3.73
.006
z
= 1.67
.095
JI = 1.67
.195
JI = 19.2
< .001
¥ = 0.69
.427
JI = 14.9
< .001
41
43 13
'Represents the mean distribution of all the intraocular pressure measurements for each individual. tCF indicates counting fingers; LP indicates light perception.
threshold fluctuation than in visual fields with less glaucomatous damage." Patients with loss of all clinically apparent rim tissue within the optic nerve head also typically are described as having advanced glaucomatous damage." This clinical sign may represent a reliable guide for glaucoma treatment! because interpreting the
optic nerve does not depend on subjective patient responses during visual field testing. In our study, we wished to determine factors associated with decreased or stable visual function in patients with complete glaucomatous cupping of the optic disk. We showed the importance of intraocular
180
(f)
I-
12 11 10
Z
9
l-
S
0-
7
ill
0
August, 1993
AMERICAN JOURNAL OF OPHTHALMOLOGY
• •
PROGRESSED STABLE
Fig. 1 (Stewart and associates). Distribution of each patient's mean intraocular pressures over the follow-up period in patients with stable glaucoma and patients with progressed glaucoma.
6
5
a:: 4 en
ill ~
3
z
2 1 0
::)
<10 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 MEAN INTRAOCULAR PRESSURE (mm Hg)
pressure reduction in patients with advanced glaucomatous changes in the optic nerve head to maintain stable visual function for five years. Only two patients with an average intraocular pressure controlled to less than 19.0 mm Hg during routine outpatient follow-up lost vision. In contrast, no patient maintained stable visual function with an average intraocular pressure of 24.0 mm Hg or more. In addition to the importance of mean intraocular pressure reduction, a low variance in intraocular pressure measurements over time also may be important. No patient with a square root of the variance of greater than 8.0 mm Hg in their intraocular pressures maintained stable visual function, including the two patients with a mean intraocular pressure less
~
~
i=
o
than 19.0 mm Hg who lost vision. Conversely, only one patient lost vision who had a square root of the variance of 4.0 mm Hg or less. Patients in our study who lost visual function were significantly more noncompliant with medical or surgical recommendations for treatment than those patients whose vision remained stable (P < .001). Glaucoma progressed in 50% of all patients noted to have poor compliance, whereas glaucoma remained stable in 90% of compliant patients. Our findings contrast with those of Granstrom," who observed no relation to compliance and progressive loss of visual field. The relationship of poor compliance to progressive, glaucomatous loss in visual function has long been suspected." Of the factors studied, mean intraocular pres-
12 11 10 9
• •
8
PROGRESSED STABLE
Fig. 2 (Stewart and associates). The distribution of the standard deviation of each patient's intraocular pressure readings over the follow-up period in patients with stable glaucoma and patients with progressed glaucoma.
7 6
a:: 5 en 4
ill
::E
::)
z
3 2 1
o
2
3
4
5
6
7
8
9
10
STANDARD DEVIATION (mm HG)
11
12
13
Vol. 116, No.2
Complete Optic Nerve Capping and Glaucoma
sure, variance of each individual's intraocular pressure measurements, history of argon laser trabeculoplasty, and compliance with therapy provided the best discrimination between the patients in whom glaucoma progressed and patients in whom glaucoma remained stable. The other factors evaluated did not improve the discriminant analysis, including several factors that were markedly different between the patients with stable glaucoma and patients with progressed glaucoma, such as age, peak intraocular pressure, visual field loss, and history of filtering procedures. This study suggests the importance of consistent reduction of intraocular pressure and compliance with therapy in patients with advanced glaucomatous cupping of the optic disk. We did not examine the long-term (> 5 years) requirements for stable visual function in patients with advanced glaucomatous cupping of the optic disk. Also, the factors associated with visual loss in our predominantly black population in a southeastern coastal community may differ from other locations with a different ethnic composition. Further study is required to understand the factors associated with progressive glaucomatous visual loss.
References 1. Chandler, P. A.: Long-term results in glaucoma therapy. The Sanford R. Gifford lecture. Am. J. Ophthalmol. 49:221,1960. 2. Shaffer, R. N.: Open-angle glaucoma. Trans. Am. Acad. Ophthalmol. Otol. 67:467, 1963. 3. Kolker, A. E.: Visual prognosis in advanced glaucoma. A comparison of medical and surgical therapy for retention of vision in 101 eyes with advanced glaucoma. Trans. Am. Ophthalmol. Soc. 75:5390P, 1977. 4. Odberg, T.: Visual field prognosis in advanced glaucoma. Acta Ophthalmol. 65:27, 1987. 5. Schulzer, M., Mikelberg, F. S., and Drance, S. M.: Some observations on the relation between intraocular pressure reduction and the progression of glaucomatous visual loss. Br. J. Ophthalmol. 71:486, 1987.
181
6. Grant, W. M., and Burke, J. F.: Why do some people go blind from glaucoma? Ophthalmology 89:991,1982. 7. Stewart, W. c.: Clinical Practice of Glaucoma. Thorofare, New Jersey, Slack Inc., 1990, pp. 52-53. 8. Mao, L. K., Stewart, W. c.. and Shields, M. B.: Correlation between intraocular pressure control and progressive glaucomatous damage in primary open-angle glaucoma. Am. J. Ophthalmol. 111:51, 1991. 9. Book, S. A.: Essentials of Statistics. New York, McGraw-HilI Book Company, 1978, pp. 122, 205, 227. 10. Swinscow, T. D. V.: Statistics at Square One. London, British Medical Association, 1976, pp. 5457. 11. Moses, L. E., Emerson, J. D., and Hosseini, H.: Statistics in practice. Analyzing data from ordered categories. N. Eng!. J. Med. 311:442,1984. 12. Quigley, H. A., and Maumenee, A. E.: Longterm follow-up of treated open-angle glaucoma. Am. J. Ophthalmol. 87:519, 1979. 13. Gramer, E., and Althaus, G.: The impact of intraocular pressure on visual field loss in primary open angle glaucoma. Klin. Monatsbl. Augenheilkd. 197:218,1990. 14. Vogel, R., Crick, R. P., Newson, R. B., Shipley, M., Blackmore, H., and Bulpitt, C. J.: Association between intraocular pressure and loss of visual field in chronic simple glaucoma. Br. J. Ophthalmol. 74:3, 1990. 15. O'Brien, c., Schwartz, B., Takamoto, T., and Wu, D. c.: Intraocular pressure and the rate of visual field loss in chronic open-angle glaucoma. Am. J. Ophthalmol. 111:491, 1991. 16. Zeimer, R. c., Wilensky, J. T., Gieser, D. K., and Viana, M. A. G.: Association between intraocular pressure peaks and progression of visual field loss. Ophthalmology 98:64, 1991. 17. Reynolds, M., Stewart, W. c., and Sutherland, S.: Factors which influence the prevalence of positive catch trials in glaucoma patients. Graefes Arch. Clin. Exp. Ophthalmo!. 228:338, 1990. 18. Heijl, A., Lindgren, A., and Lindgren, G.: Testretest variability in glaucomatous visual fields. Am. J. Ophthalmol. 108:130, 1989. 19. Granstrom, P.-A.: Progression of visual field defects in glaucoma. Relation to compliance with pilocarpine therapy. Arch. Ophthalmo!. 103:529, 1985. 20. Kass, M. A.: Compliance and prognosis in glaucoma. Arch. Ophthalmol. 103:504, 1985.
We evaluated factors associated with decreased or stable visual function in 72 patients with primary open-angle glaucoma and complete cupping of the optic disk who were followed up five years or more. We found a significantly lower mean (15.4 ± 2.7 mm Hg) and peak (24.5 ± 6.9 mm Hg) intraocular pressure in those patients whose vision remained stable vs those whose vision decreased (21.3 ± 3.2 and 39.2 ± 11.0 mm Hg, respectively) (ttest, P < .001). Additionally, the variance of each patient's individual intraocular pressure readings measured during the follow-up period was lower in the group with stable vision (4.5 mm Hg) than in those in whom vision decreased (9.0 mm Hg) (F test, P < .001). Stepwise discriminant analysis disclosed that mean intraocular pressure, variance of an individual's intraocular pressure measurements over time, history of argon laser trabeculoplasty, and compliance with therapy discriminated 92.9% of patients (52 of 56) whose vision remained stable and 87.5% of patients (14 of 16) whose vision decreased. Reduction of intraocular pressure and compliance with therapy are important in patients with complete glaucomatous cupping of the optic disk. IN PATIENTS WITH GLAUCOMA, medical, laser, and conventional surgical therapy typically are used to control the intraocular pressure to a
Accepted for publication April 28, 1993. From the Glaucoma Service at the Department of Ophthalmology (Dr. Stewart and Ms. Chorak), and the Department of Biostatistics and Epidemiology (Dr. Hunt and Mr. Sethuraman), Medical University of South Carolina, Charleston, South Carolina. This study was sponsored in part by an unrestricted grant from Research to Prevent Blindness, Inc., New York, New York. Reprint requests to William C. Stewart, M.D., Storm Eye Institute, Medical University of South Carolina, 171 Ashley Ave., Charleston, SC 29425-2236.
176
level that prevents progressive loss of vision. Most investigators believe that in patients with advanced glaucomatous damage, the intraocular pressure should be controlled to within the normal range. 1,2 Previous studies that have investigated factors associated with advanced visual loss in glaucoma have used the visual field to determine the extent of damage.i" However, advanced glaucomatous damage may be diagnosed also by the appearance of the optic nerve head.' Little data exist on patients with advanced changes in the optic nerve head and factors associated with progressive glaucomatous damage. We studied consecutively examined patients with advanced glaucomatous changes in the optic nerve head who had been followed up for five years or more with or without surgical intervention. We examined for factors associated either with preservation or loss of visual acuity and visual field in these patients.
Patients and
Methods
We included in this study consecutive patients with advanced glaucomatous changes in the optic nerve head who were followed up by the glaucoma service at our institution and who met one of two criteria: stable glaucoma for at least five years, or progressed glaucoma that had been diagnosed within the past five years. Data were collected regarding stable glaucoma for as long as records were available. Data were collected from the records of patients with progressed glaucoma until the time the glaucoma worsened. Data were not collected after the time of progression; therefore, the information included in this study would reflect the status of the eye until the worsening of glaucoma. The criterion for advanced glaucomatous change of the optic nerve head was no observ-
©AMERICAN JOURNAL OF OPHTHALMOLOGY
116:176-181,
AUGUST,
1993
Vol. 116, No.2
Complete Optic Nerve Cupping and Glaucoma
able neural rim remaining within the optic disk (that is, a complete cup). Primary open-angle glaucoma had been diagnosed in each patient. Excluded from this study were patients with congenital, secondary, narrow-angle, or lowtension glaucoma. Also excluded from this study were patients thought to have progressive nonglaucomatous visual loss. Patients were followed up at outpatient visits every three months or more frequently as needed. At each outpatient visit, the intraocular pressure was measured by Goldmann applanation tonometry. Evaluation of the ocular adnexa, slit-lamp biomicroscopy, and optic disk examination by direct ophthalmoscopy also were performed. Examinations of the optic disk through a dilated pupil and the visual field were completed yearly or more frequently if the patient had split fixation or progression of glaucoma was suspected. The optic disk was examined by stereoscopic techniques, including the Goldmann lens and color photography. Progression or stability of each patient's glaucoma was assessed by using automated perimetry and Snellen visual acuity. Because each patient in this study had complete cupping of the optic disk, the optic nerve head could not be used as a measure of progression. Automated perimetry with the Humphrey Field Analyzer (program 30-2 or a 76-point screen with a quantified defect) (Humphrey Instruments, Inc., San Leandro, California) was used to measure the visual field. Each visual field was given one of the following five interpretations: within normal limits, early changes in the nerve fiber layer (that is, paracentral or Seidel's scotoma), late arcuate changes in the nerve fiber layer (that is, arcuate scotoma)," central island remaining with complete superior and inferior arcuate scotomas, or "unable to perform" because of deep diffuse depression of the field with coexistent loss of central vision. The inferior and superior hemifields were diagnosed separately. The criterion for reduction of a normal visual field was the development of changes in the nerve fiber layer. Criteria for progression of early changes in the nerve fiber layer included progression to an arcuate scotoma or development of a new defect in the nerve fiber layer in the opposite hemifield. The criterion for decrease in patients with an arcuate scotoma was the eventual development in the opposite hemifield of a defect of the nerve fiber layer. The criterion for progression of a central island was a narrowing of the remaining visual field. Pro-
177
gressive loss in the visual field was diagnosed only if these visual field changes were observed for three successive examinations." The criterion for progressive loss in visual acuity was a decrease of two or more Snellen lines not attributable to other ocular disease despite the patient's best refraction. Data collection and statistical analysis between patients in whom glaucoma was stable or had progressed were performed as follows. A Student's t-test was used to analyze data for patient age and for the mean and peak intraocular pressures during the follow-up period. 9P. I22 An F test analyzed the differences between the variance of each patient's intraocular pressures measured during the follow-up period.9p.227 A X2 test was used to analyze differences between groups of nonordered scores, such as the eye operated on (left or right); gender; compliance (both with suggested medical treatment and in following surgical recommendations); a history of diabetes, arthritis, systemic hypertension, or pseudophakia; argon laser trabeculoplasty; and whether trabeculectomy had been performed during the follow-up period.9p.205 A Fisher's exact test was used to analyze differences of nonordered scores that had at least one expected value of less than 5 in a 2 x 2 table, and included race and history of heart disease." A Mann-Whitney U-test was used to determine statistical differences between groups of ordered scores, which included visual acuity, visual field defect, and number of glaucoma medicines. II If both eyes of a patient met the criteria for entrance into the study, only one was randomly chosen to be analyzed. We also performed a stepwise discriminant analysis to determine the ability of the factors evaluated in this study to predict whether the patients' glaucoma would be categorized as stable or progressed.
Results We included in this study 72 consecutively examined patients with complete cupping of the optic disk who met the study'S entrance criteria. Patients in whom glaucoma progressed were followed up for an average of 3.3 ± 1.3 years before decreased visual function was observed. Patients with stable glaucoma were followed up for an average of 5.4 ± 1.0 years. We compared the data related to patient history between patients with stable glaucoma and
178
August, 1993
AMERICAN JOURNAL OF OPHTHALMOLOGY
TABLE
1
DATA RELATED TO PATIENT HISTORY STABLE PROGRESSED GLAUCOMA GLAUCOMA
Age (yrs) 61.2 ± 13 71.5 ± 9.5 Gender Men: women 6:10 20:36 Race Black: white Eye
STATISTICAL VALUE
t
= 2.95
P VALUE
.006
K = 0.016
.876
14:2
46:10
Fisher's exact
.832
9:7
27:29
K = 0.311
.601
8 8
20 36
K = 1.07
.300
3 13
49
Yes No Ar.hritis
6 10
30 26
K = 1.29
.249
Yes No
6 10
15 41
K = 0.69
.421
Right: left Medical history Diabetes Yes No Heart disease Yes No Systemic hyper-
7
Fisher's exact> .900
tension
patients with progressed glaucoma (Table 1). Only the mean age showed a statistically significant difference between groups. We also compared the data related to the intraocular pressure and visual function between patients with stable glaucoma and patients with progressed glaucoma (Table 2). The mean and peak intraocular pressures were markedly lower in the patients with stable glaucoma than in the patients with progressed glaucoma. Also, each individual's variance of intraocular pressure measurements during the follow-up period was significantly lower in the stable (4.5 mm Hg) than the progressed category of glaucoma (9.0 mm Hg). We compared the distribution of the mean intraocular pressures (Fig. 1) and the distribution of the square root of the variance (Fig. 2) between patients with stable glaucoma and patients with progressed glaucoma. The extent of visual field damage (P = .006) and compliance (P < .001) during the follow-up period were significantly worse in patients with progressed glaucoma vs patients with stable glaucoma. Also, patients whose glaucoma progressed statistically more often had a history of previous filtering operations. In contrast, a history of argon laser trabeculoplasty, pseudo-
phakia, number of glaucoma medications, and Snellen visual acuity were similar between groups during the follow-up period. In the 16 patients whose glaucoma progressed, worsening disease was diagnosed by changes in the visual acuity and not by changes in the visual field. The stepwise discriminant analysis showed that the best discriminant variables were mean intraocular pressure, variance of each patient's intraocular pressure measurements, history of argon laser trabeculoplasty, and compliance with therapy. The discriminant function for the stable group was D = 2.1323 (mean) - 0.2752 (variance) + 1.11
(laser) + 5.0133 (compliance) - 23.5697. The discriminant function for the progressed group was D = 2.7586 (mean) + 0.5017 (variance) 0.6282 (laser) + 3.6175 (compliance) - 34.7767. These functions classified correctly 92.9 % of the patients with stable glaucoma (52 of 56) and 87.5% of the patients with progressed glaucoma (14 of 16).
Discussion
Controversy still exists over the proper treatment of patients with advanced primary openangle glaucoma. In general, treatment consists of using medical, laser, then conventional surgical therapy as needed to lower the intraocular pressure to a level that the clinician believes will prevent progressive glaucomatous damage. Chandler! and Shaffer! indicated that the intraocular pressure should be kept in a normal range in patients with advanced glaucomatous changes in the visual field to prevent progressive damage. More recent reports have implied that the glaucoma in patients with advanced visual field loss usually remains stable with an intraocular pressure between 15.0 and 18.0 mm Hg,3'5,!2 although this finding has not been consistent." Additionally, several studies have noted that both the extent":" and rate of visual field 10ss15 are worse with higher mean and peak" intraocular pressures. Previous reports have defined advanced glaucomatous damage on the basis of the appearance of the visual field.!" However, interpreting advanced visual field changes in glaucoma is complicated by greater unreliability" and
Vol. 116, No.2
Complete Optic Nerve Cupping and Glaucoma
TABLE
179
2
DATA RELATED TO INTRAOCULAR PRESSURE AND VISION PROGRESSED
STABLE
STATISTICAL
GLAUCOMA
GLAUCOMA
VALUE
21.3 ± 3.2 39.2 ± 11
15.4 ± 2.7 24.5 ± 6.9
9.0
4.5
CF-LP
4
20/400-20/100
2 4
6 11 16
6
23
PVALUE
Intraocular pressure (mm Hg) Mean Peak Mean standard deviation' Visual acuityt
20/80-20/50 20/40-20/20 Visual field (mean defect in decibels) Within normal limits Early arcuate Late arcuate Deep diffuse depression
0 0 2
5 5 15
4
21
10
10
1
8
3
5
21
2 1
8 2
20 7
0 Argon laser trabeculoplasty
0
0
Yes No Filtering surgery
11 5
40 16
None
6
38
Combined with cataract extraction Filter only
2
15
8
3
6 10
15
Unable to do Number of glaucoma medications 4
Pseudophakia Yes No Compliance with treatment regimen Good Poor
5 13
t = 6.72 t = 5.07
< .001 < .001 < .001
F
= 4.00
z
= 0.669
.504
z
= 3.73
.006
z
= 1.67
.095
JI = 1.67
.195
JI = 19.2
< .001
¥ = 0.69
.427
JI = 14.9
< .001
41
43 13
'Represents the mean distribution of all the intraocular pressure measurements for each individual. tCF indicates counting fingers; LP indicates light perception.
threshold fluctuation than in visual fields with less glaucomatous damage." Patients with loss of all clinically apparent rim tissue within the optic nerve head also typically are described as having advanced glaucomatous damage." This clinical sign may represent a reliable guide for glaucoma treatment! because interpreting the
optic nerve does not depend on subjective patient responses during visual field testing. In our study, we wished to determine factors associated with decreased or stable visual function in patients with complete glaucomatous cupping of the optic disk. We showed the importance of intraocular
180
(f)
I-
12 11 10
Z
9
l-
S
0-
7
ill
0
August, 1993
AMERICAN JOURNAL OF OPHTHALMOLOGY
• •
PROGRESSED STABLE
Fig. 1 (Stewart and associates). Distribution of each patient's mean intraocular pressures over the follow-up period in patients with stable glaucoma and patients with progressed glaucoma.
6
5
a:: 4 en
ill ~
3
z
2 1 0
::)
<10 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 MEAN INTRAOCULAR PRESSURE (mm Hg)
pressure reduction in patients with advanced glaucomatous changes in the optic nerve head to maintain stable visual function for five years. Only two patients with an average intraocular pressure controlled to less than 19.0 mm Hg during routine outpatient follow-up lost vision. In contrast, no patient maintained stable visual function with an average intraocular pressure of 24.0 mm Hg or more. In addition to the importance of mean intraocular pressure reduction, a low variance in intraocular pressure measurements over time also may be important. No patient with a square root of the variance of greater than 8.0 mm Hg in their intraocular pressures maintained stable visual function, including the two patients with a mean intraocular pressure less
~
~
i=
o
than 19.0 mm Hg who lost vision. Conversely, only one patient lost vision who had a square root of the variance of 4.0 mm Hg or less. Patients in our study who lost visual function were significantly more noncompliant with medical or surgical recommendations for treatment than those patients whose vision remained stable (P < .001). Glaucoma progressed in 50% of all patients noted to have poor compliance, whereas glaucoma remained stable in 90% of compliant patients. Our findings contrast with those of Granstrom," who observed no relation to compliance and progressive loss of visual field. The relationship of poor compliance to progressive, glaucomatous loss in visual function has long been suspected." Of the factors studied, mean intraocular pres-
12 11 10 9
• •
8
PROGRESSED STABLE
Fig. 2 (Stewart and associates). The distribution of the standard deviation of each patient's intraocular pressure readings over the follow-up period in patients with stable glaucoma and patients with progressed glaucoma.
7 6
a:: 5 en 4
ill
::E
::)
z
3 2 1
o
2
3
4
5
6
7
8
9
10
STANDARD DEVIATION (mm HG)
11
12
13
Vol. 116, No.2
Complete Optic Nerve Capping and Glaucoma
sure, variance of each individual's intraocular pressure measurements, history of argon laser trabeculoplasty, and compliance with therapy provided the best discrimination between the patients in whom glaucoma progressed and patients in whom glaucoma remained stable. The other factors evaluated did not improve the discriminant analysis, including several factors that were markedly different between the patients with stable glaucoma and patients with progressed glaucoma, such as age, peak intraocular pressure, visual field loss, and history of filtering procedures. This study suggests the importance of consistent reduction of intraocular pressure and compliance with therapy in patients with advanced glaucomatous cupping of the optic disk. We did not examine the long-term (> 5 years) requirements for stable visual function in patients with advanced glaucomatous cupping of the optic disk. Also, the factors associated with visual loss in our predominantly black population in a southeastern coastal community may differ from other locations with a different ethnic composition. Further study is required to understand the factors associated with progressive glaucomatous visual loss.
References 1. Chandler, P. A.: Long-term results in glaucoma therapy. The Sanford R. Gifford lecture. Am. J. Ophthalmol. 49:221,1960. 2. Shaffer, R. N.: Open-angle glaucoma. Trans. Am. Acad. Ophthalmol. Otol. 67:467, 1963. 3. Kolker, A. E.: Visual prognosis in advanced glaucoma. A comparison of medical and surgical therapy for retention of vision in 101 eyes with advanced glaucoma. Trans. Am. Ophthalmol. Soc. 75:5390P, 1977. 4. Odberg, T.: Visual field prognosis in advanced glaucoma. Acta Ophthalmol. 65:27, 1987. 5. Schulzer, M., Mikelberg, F. S., and Drance, S. M.: Some observations on the relation between intraocular pressure reduction and the progression of glaucomatous visual loss. Br. J. Ophthalmol. 71:486, 1987.
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6. Grant, W. M., and Burke, J. F.: Why do some people go blind from glaucoma? Ophthalmology 89:991,1982. 7. Stewart, W. c.: Clinical Practice of Glaucoma. Thorofare, New Jersey, Slack Inc., 1990, pp. 52-53. 8. Mao, L. K., Stewart, W. c.. and Shields, M. B.: Correlation between intraocular pressure control and progressive glaucomatous damage in primary open-angle glaucoma. Am. J. Ophthalmol. 111:51, 1991. 9. Book, S. A.: Essentials of Statistics. New York, McGraw-HilI Book Company, 1978, pp. 122, 205, 227. 10. Swinscow, T. D. V.: Statistics at Square One. London, British Medical Association, 1976, pp. 5457. 11. Moses, L. E., Emerson, J. D., and Hosseini, H.: Statistics in practice. Analyzing data from ordered categories. N. Eng!. J. Med. 311:442,1984. 12. Quigley, H. A., and Maumenee, A. E.: Longterm follow-up of treated open-angle glaucoma. Am. J. Ophthalmol. 87:519, 1979. 13. Gramer, E., and Althaus, G.: The impact of intraocular pressure on visual field loss in primary open angle glaucoma. Klin. Monatsbl. Augenheilkd. 197:218,1990. 14. Vogel, R., Crick, R. P., Newson, R. B., Shipley, M., Blackmore, H., and Bulpitt, C. J.: Association between intraocular pressure and loss of visual field in chronic simple glaucoma. Br. J. Ophthalmol. 74:3, 1990. 15. O'Brien, c., Schwartz, B., Takamoto, T., and Wu, D. c.: Intraocular pressure and the rate of visual field loss in chronic open-angle glaucoma. Am. J. Ophthalmol. 111:491, 1991. 16. Zeimer, R. c., Wilensky, J. T., Gieser, D. K., and Viana, M. A. G.: Association between intraocular pressure peaks and progression of visual field loss. Ophthalmology 98:64, 1991. 17. Reynolds, M., Stewart, W. c., and Sutherland, S.: Factors which influence the prevalence of positive catch trials in glaucoma patients. Graefes Arch. Clin. Exp. Ophthalmo!. 228:338, 1990. 18. Heijl, A., Lindgren, A., and Lindgren, G.: Testretest variability in glaucomatous visual fields. Am. J. Ophthalmol. 108:130, 1989. 19. Granstrom, P.-A.: Progression of visual field defects in glaucoma. Relation to compliance with pilocarpine therapy. Arch. Ophthalmo!. 103:529, 1985. 20. Kass, M. A.: Compliance and prognosis in glaucoma. Arch. Ophthalmol. 103:504, 1985.