GONIOSCOPIC DIFFERENCES BETWEEN EYES WITH PRIMARY OPEN-ANGLE GLAUCOMA AND NORMAL EYES IN SUBJECTS OVER THE AGE OF FORTY* BYR. Kimura, MD (BY INVITATION), AND R. Z. Levene, MD INTRODUCTION
ALTHOUGH GONIOSCOPIC ABNORMALITIES OCCUR IN CONGENITAL AND
JUVENILE
glaucoma their presence in primary open-angle glaucoma has been debated. A comparison between the angles of primary open-angle glaucoma and normal angles should not be limited to a search for qualitative differences but should also include quantitative differences in the frequency distribution of various features. A lower incidence of blood reflux into Schlemm's canal in primary open-angle glaucoma has been noted by a number of authors.1-10 Excluding pigmentary glaucoma, excessive trabecular pigmentation in primary open-angle glaucoma has been observed by some investigators, 11-14 but not by others. 6"15 An excess of felt-like or wooly substance in primary open-angle glaucoma has also been observed.6"16'17 The central anterior chamber depth is slightly shallower in primary open-angle glaucoma by comparison with carefully matched normal controls. 8-21 Lichter and Shaffer22 found a higher incidence of iris processes inserting anterior to the scleral spur in primary open-angle glaucoma as compared to normal subjects. The present paper is a further study of gonioscopic differences. MATERIALS ANI) METHOI)S
Normal and primary open-angle glaucoma subjects, over the age of 40, were selected for study. All subjects had a complete eye examination. Goldmann visual fields were plotted in all patients with glaucoma. Gonioscopy was done in all four quadrants of one or both eyes with the Goldmann three-mirror goniolens and the Haag Streit 900 slit lamp. *From The Combined Program in Ophthalmology, University of Alabama and The Eye Foundation Hospital, Birmingham, Alabama. This study was supported by grant-inaid No. 5ROI-EY01119. T. A\I Opii'rlii So: vol. LXXIII, 1975
Gonioscopic Differences
Subjects with
a
history of ocular trauma, ocular
75 surgery, or
significant
anterior segment disease other than cataract, in both eyes, were excluded. In addition, the subject was disqualified if the angle was not medium to wide open in at least two quadrants according to Shaffer's23 classification. All gonioscopy was done by one observer. We thought that angle features might show a better correlation with
intraocular pressure rather than with disc or field changes and the subjects were classified primarily by pressure. The first group, consisting of normal subjects, had an applanation pressure in both eyes equal to or less than 20 on at least two occasions and a normal disc. They were subdivided into a larger subgroup with no known family history of glaucoma and a smaller one with a history of glaucoma in a first degree relative. The second group, primary open-angle glaucoma and suspects, had an applanation pressure over 20 in one or both eyes on at least 2 occasions. This group could have been subdivided by the presence of definite glaucomatous field loss or by the use of glaucoma medication. Since we thought SUBJECTS
Normal Age Group
Black
Normal with family history of glaucoma
Primary open-angle glaucoma
Black
White
White
Black
White
no history on or with no history on or with of of history of history of medication medication medication medication
40s
7
1
3
4
1
0
1
0
50s
17
7
6
11
1
6
5
1
60s
30
20
5
25
7
13
0
3
70s
16
6
3
13
1
5
0
0
80s
4
1
0
4
0
1
0
0
90S
1
0
0
1
0
0
0
0
17
58
10
25
75
35
6
4
75
Totals 110
35 110 10
220
230 TABLE I
76
76Kimura and Levene
that the latter might be a more pertinent factor in relation to angle features this group was subdivided on that basis. Subjects using medication or with a history of using medication generally had more severe glaucoma with 60% of them having definite glaucomatous field loss. Subjects without a history of using medication had a 4% incidence of definite glaucomatous field loss. The group with glaucoma and the larger subgroup of normal subjects without a family history of glaucoma were individually matched by race (black or white) and by age (decades). This was accomplished by random exclusion of subjects in a given category from the larger group until a match was obtained. Only one eye of each subject was included in the analysis. The right eye was selected unless it was excluded by the criteria noted above. Table I shows the number of subjects by diagnosis and race. Although normal subjects and subjects with glaucoma were not matched individually by refractive error this measurement was available in 206 of the 230 subjects. In 101 normal subjects with no known family history of glaucoma the distribution by spherical equivalent was as follows: 46% of subjects had more than +1.00 diopter of hyperopia, 46% had between +1.00 and -1.00, and 9% had more than -1.00 diopter of myopia. The analagous distribution in 95 subjects with glaucoma was 29, 46, and 24% respectively. There were more myopes in the glaucoma group. All normal subjects had refractive errors between plus and minus 5 diopters. In the glaucoma group, 3 subjects had more than -5.00 myopia and 2 had more than +5.00 hyperopia. Table II shows the various angle features studied and the numerical method of grading each one. The degree of abnormality increases with the grade number. The iris root normally inserts into the ciliary body with a grade of 0. The other grades refer to a more anterior or higher insertion. The term iris process refers to what some observers call mesodermal remnants, rudimentary pectinate fibers or uveal meshwork. Each quadrant was graded separately. In a small percent of eyes one or more quadrants could not be graded for the insertion of iris root or iris processes to the ciliary band because an iris roll prevented an adequate view of the angle. To simplify the presentation and analysis of data a mean value and standard deviation was calculated from the frequency distribution of grades for each angle feature. Statistical analysis was based upon the number of subjects rather than the number of quadrants. Statistical compparison of means was done with the Students t-test. The F test was also used for analysis of variance among groups. A two-tailed test was used for determining probability values.
Gonioscopic Differences
77
ANGLE FEATURES AND CLASSIFICATION
Grde Feature Pigmentation of trabeculae Insertion of iris root
2
1
0
marked
moderate
minimum
none
to
to
to
to
Schwalbe's line
trabecu lae
scieral spur
ciliary body
marked
moderate
minimum
none
to ciliary body band
marked
moderate
minimum
none
to
marked
moderate
minimum
none
marked
moderate
minimum
none
Prominence of Schwalbe's line
Number of iris processes
3
trabeculae to
Schwalbe's line TABLE II
RESUL TS
In normal eyes the trabecular pigmentation was most marked inferiorly followed by the nasal quadrant. The number of iris processes to the trabecular meshwork was most marked nasally followed by the inferior quadrant. Table III shows the degree of trabecular pigmentation by age for both normal and glaucoma subjects. There is no statistically significant trend with age for either group. However, visual inspection of the data between the ages of 39 and 79, the age range with most of the subjects, shows a steady decrease for normals but a minimum in the 60's for the glaucoma subjects. There were more iris processes to the trabeculae in blacks but this could be caused by better visualization of the processes in the more pigmented eye. Trabecular pigmentation appeared to be greater in whites but this could be caused by a better contrast in the less pigmented eve.
Kimura and Levene
78
TRABECULAR PIGMENTATION BY AGE GRADING BY MEAN + S.D. Age Groups
Number of Subjects
Normal
G laucoma
40's
8
0.63 + 1.06
1.50 + 0.76
50's
24
0.91 + 0.72
1.33 + 1.05
60's
50
0.82 + 0.75
1.20 + 0.81
70's
22
0.64 + 0.66
1.41 + 0.91
80's
5
1.00 + 0.71
1.20 + 1.30
TABLE III
For comparison between the glaucoma and the normal groups the blacks and whites were combined. An analysis of blacks and whites separately gave similar results. Table IV presents the values for the various angle features in the four groups of subjects. Based upon this data, Table V presents the statistical comparisons among the groups. Glaucoma patients with medication have more trabecular pigmentation, higher insertion of the iris root, and more iris processes at all levels than the subjects in the normal group. Glaucoma patients with medication also have greater trabecular pigmentation and more iris processes than glaucoma patients without medication. Normal subjects with a family history of glaucoma have a higher insertion of the iris root and a more prominent Schwalbe's line than normal subjects without such a history. Table IV shows that the values are almost all higher in the former group. It is likely that the small number of subjects in this group masks a statistically significant difference for more individual features. Table VI shows the relationship between refractive error and two angle features in the normal and glaucoma groups. There is no statistical interaction in that both groups showed a similar relationship with refractive error. Myopes have significantly more trabecular pigmentation (p
ALTHOUGH GONIOSCOPIC ABNORMALITIES OCCUR IN CONGENITAL AND
JUVENILE
glaucoma their presence in primary open-angle glaucoma has been debated. A comparison between the angles of primary open-angle glaucoma and normal angles should not be limited to a search for qualitative differences but should also include quantitative differences in the frequency distribution of various features. A lower incidence of blood reflux into Schlemm's canal in primary open-angle glaucoma has been noted by a number of authors.1-10 Excluding pigmentary glaucoma, excessive trabecular pigmentation in primary open-angle glaucoma has been observed by some investigators, 11-14 but not by others. 6"15 An excess of felt-like or wooly substance in primary open-angle glaucoma has also been observed.6"16'17 The central anterior chamber depth is slightly shallower in primary open-angle glaucoma by comparison with carefully matched normal controls. 8-21 Lichter and Shaffer22 found a higher incidence of iris processes inserting anterior to the scleral spur in primary open-angle glaucoma as compared to normal subjects. The present paper is a further study of gonioscopic differences. MATERIALS ANI) METHOI)S
Normal and primary open-angle glaucoma subjects, over the age of 40, were selected for study. All subjects had a complete eye examination. Goldmann visual fields were plotted in all patients with glaucoma. Gonioscopy was done in all four quadrants of one or both eyes with the Goldmann three-mirror goniolens and the Haag Streit 900 slit lamp. *From The Combined Program in Ophthalmology, University of Alabama and The Eye Foundation Hospital, Birmingham, Alabama. This study was supported by grant-inaid No. 5ROI-EY01119. T. A\I Opii'rlii So: vol. LXXIII, 1975
Gonioscopic Differences
Subjects with
a
history of ocular trauma, ocular
75 surgery, or
significant
anterior segment disease other than cataract, in both eyes, were excluded. In addition, the subject was disqualified if the angle was not medium to wide open in at least two quadrants according to Shaffer's23 classification. All gonioscopy was done by one observer. We thought that angle features might show a better correlation with
intraocular pressure rather than with disc or field changes and the subjects were classified primarily by pressure. The first group, consisting of normal subjects, had an applanation pressure in both eyes equal to or less than 20 on at least two occasions and a normal disc. They were subdivided into a larger subgroup with no known family history of glaucoma and a smaller one with a history of glaucoma in a first degree relative. The second group, primary open-angle glaucoma and suspects, had an applanation pressure over 20 in one or both eyes on at least 2 occasions. This group could have been subdivided by the presence of definite glaucomatous field loss or by the use of glaucoma medication. Since we thought SUBJECTS
Normal Age Group
Black
Normal with family history of glaucoma
Primary open-angle glaucoma
Black
White
White
Black
White
no history on or with no history on or with of of history of history of medication medication medication medication
40s
7
1
3
4
1
0
1
0
50s
17
7
6
11
1
6
5
1
60s
30
20
5
25
7
13
0
3
70s
16
6
3
13
1
5
0
0
80s
4
1
0
4
0
1
0
0
90S
1
0
0
1
0
0
0
0
17
58
10
25
75
35
6
4
75
Totals 110
35 110 10
220
230 TABLE I
76
76Kimura and Levene
that the latter might be a more pertinent factor in relation to angle features this group was subdivided on that basis. Subjects using medication or with a history of using medication generally had more severe glaucoma with 60% of them having definite glaucomatous field loss. Subjects without a history of using medication had a 4% incidence of definite glaucomatous field loss. The group with glaucoma and the larger subgroup of normal subjects without a family history of glaucoma were individually matched by race (black or white) and by age (decades). This was accomplished by random exclusion of subjects in a given category from the larger group until a match was obtained. Only one eye of each subject was included in the analysis. The right eye was selected unless it was excluded by the criteria noted above. Table I shows the number of subjects by diagnosis and race. Although normal subjects and subjects with glaucoma were not matched individually by refractive error this measurement was available in 206 of the 230 subjects. In 101 normal subjects with no known family history of glaucoma the distribution by spherical equivalent was as follows: 46% of subjects had more than +1.00 diopter of hyperopia, 46% had between +1.00 and -1.00, and 9% had more than -1.00 diopter of myopia. The analagous distribution in 95 subjects with glaucoma was 29, 46, and 24% respectively. There were more myopes in the glaucoma group. All normal subjects had refractive errors between plus and minus 5 diopters. In the glaucoma group, 3 subjects had more than -5.00 myopia and 2 had more than +5.00 hyperopia. Table II shows the various angle features studied and the numerical method of grading each one. The degree of abnormality increases with the grade number. The iris root normally inserts into the ciliary body with a grade of 0. The other grades refer to a more anterior or higher insertion. The term iris process refers to what some observers call mesodermal remnants, rudimentary pectinate fibers or uveal meshwork. Each quadrant was graded separately. In a small percent of eyes one or more quadrants could not be graded for the insertion of iris root or iris processes to the ciliary band because an iris roll prevented an adequate view of the angle. To simplify the presentation and analysis of data a mean value and standard deviation was calculated from the frequency distribution of grades for each angle feature. Statistical analysis was based upon the number of subjects rather than the number of quadrants. Statistical compparison of means was done with the Students t-test. The F test was also used for analysis of variance among groups. A two-tailed test was used for determining probability values.
Gonioscopic Differences
77
ANGLE FEATURES AND CLASSIFICATION
Grde Feature Pigmentation of trabeculae Insertion of iris root
2
1
0
marked
moderate
minimum
none
to
to
to
to
Schwalbe's line
trabecu lae
scieral spur
ciliary body
marked
moderate
minimum
none
to ciliary body band
marked
moderate
minimum
none
to
marked
moderate
minimum
none
marked
moderate
minimum
none
Prominence of Schwalbe's line
Number of iris processes
3
trabeculae to
Schwalbe's line TABLE II
RESUL TS
In normal eyes the trabecular pigmentation was most marked inferiorly followed by the nasal quadrant. The number of iris processes to the trabecular meshwork was most marked nasally followed by the inferior quadrant. Table III shows the degree of trabecular pigmentation by age for both normal and glaucoma subjects. There is no statistically significant trend with age for either group. However, visual inspection of the data between the ages of 39 and 79, the age range with most of the subjects, shows a steady decrease for normals but a minimum in the 60's for the glaucoma subjects. There were more iris processes to the trabeculae in blacks but this could be caused by better visualization of the processes in the more pigmented eye. Trabecular pigmentation appeared to be greater in whites but this could be caused by a better contrast in the less pigmented eve.
Kimura and Levene
78
TRABECULAR PIGMENTATION BY AGE GRADING BY MEAN + S.D. Age Groups
Number of Subjects
Normal
G laucoma
40's
8
0.63 + 1.06
1.50 + 0.76
50's
24
0.91 + 0.72
1.33 + 1.05
60's
50
0.82 + 0.75
1.20 + 0.81
70's
22
0.64 + 0.66
1.41 + 0.91
80's
5
1.00 + 0.71
1.20 + 1.30
TABLE III
For comparison between the glaucoma and the normal groups the blacks and whites were combined. An analysis of blacks and whites separately gave similar results. Table IV presents the values for the various angle features in the four groups of subjects. Based upon this data, Table V presents the statistical comparisons among the groups. Glaucoma patients with medication have more trabecular pigmentation, higher insertion of the iris root, and more iris processes at all levels than the subjects in the normal group. Glaucoma patients with medication also have greater trabecular pigmentation and more iris processes than glaucoma patients without medication. Normal subjects with a family history of glaucoma have a higher insertion of the iris root and a more prominent Schwalbe's line than normal subjects without such a history. Table IV shows that the values are almost all higher in the former group. It is likely that the small number of subjects in this group masks a statistically significant difference for more individual features. Table VI shows the relationship between refractive error and two angle features in the normal and glaucoma groups. There is no statistical interaction in that both groups showed a similar relationship with refractive error. Myopes have significantly more trabecular pigmentation (p
