GONIOSCOPIC DIFFERENCES B E T W E E N PRIMARY OPEN-ANGLE GLAUCOMA AND NORMAL SUBJECTS OVER 40 YEARS O F AGE R. KlMURA, M.D., AND R. Z. LEVENE, M . D . Birmingham, Alabama
Although gonioscopic abnormalities occur in patients with congenital and juvenile glau coma, their presence in patients with openangle glaucoma has been debated. A compari son between primary open-angle glaucoma and normal subjects should not be limited to a search for qualitative differences but should also include quantitative differences in the frequency distribution of various fea tures. A lower incidence of blood reflux into Schlemm's canal in primary open-angle glau coma was noted by several authors. 1-10 Ex cluding pigmentary glaucoma, excessive trabecular pigmentation in primary openangle glaucoma was observed by some inves tigators11"14 but not by others.6-15 An excess of felt-like or woolly substance in primary open-angle glaucoma was also observed.6-16'17 The central anterior chamber depth is slightly shallower in primary open-angle glaucoma compared with carefully matched normal control subjects. 1821 Lichter and Shaffer22 found a higher incidence of iris processes in serting anterior to the scleral spur in primary open-angle glaucoma as compared with nor mal subjects. This is a further study of gonioscopic differences. SUBJECTS AND METHODS
We selected normal and primary openangle glaucoma subjects, over the age of 40, from the clinic, private practice, and volun teers. All subjects had a complete ocular From the Combined Program in Ophthalmology, University of Alabama and the Eye Foundation Hospital, Birmingham, Alabama. This study was supported by grant-in-aid 5R01-EY01119, National Eye Institute. Presented before the 102nd American Ophthalmological Society meeting, Hot Springs, Virginia, May 29, 1975. Reprint requests to R. Levene, M.D., 2000-D Brookwood Medical Center Dr., Birmingham, AL 35209.
examination, and Goldmann perimetry studies were performed on all glaucoma pa tients. Gonioscopy was performed in all four quadrants of one or both eyes with the Goldmann three-mirror goniolens and the Haag-Streit 900 slit lamp. Subjects with a contributory history of ocular trauma, ocular surgery, or significant anterior segment dis ease other than cataract, in both eyes, were excluded. In addition, a subject was dis qualified if the angle was not medium to wide open in at least two quadrants, accord ing to Shaffer's classification.23 One observer performed all gonioscopic examinations. We thought angle features would show a better correlation with ocular pressure rather than with disk or visual field changes and the subjects were classified primarily by pres sure. The first group—normal subjects—had applanation pressures in both eyes equal to or less than 20 mm Hg on at least two occasions, and normal disks. They were subdivided into two subgroups: a larger group 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 openangle glaucoma patients and suspects—had applanation pressures over 20 mm Hg in one or both eyes on at least two occasions. This group could have been subdivided either into those with definite visual field loss, or not, or those receiving medication, or not. We thought the latter might be a more pertinent factor in relation to angle features. Subjects receiving or those who had received medica tion had the more severe cases, with 60% of them having definite glaucomatous visual field loss. Subjects without a history of medi cation had a 4% incidence of definite visual field loss caused by glaucoma. The glaucomatous group and the larger subgroup of normal subjects with a noncontributory history were individually matched 56
57
GONIOSCOPIC ABNORMALITIES
VOL. 80, NO. 1
TABLE 1 SUBJECTS
Primary Open-Angle Glaucoma Patients Age Group. yrs in decades
40-49 50-59 60-69 70-79 80-89 90-99 Total
Normal Subjects With. Family No Contributory History of Glaucoma No Contributory MediHistory MediHistory Black White cation of cation of History Medication History Medication Black
Normal Subjects Black
White
7 17 30 16 4 1
1 7 20 6 1 0
75
35
3 6 5 3 0 0 17
75
by race (black or white) and age (in dec ades), by using random exclusion of sub jects in a given category from the larger group until a match was obtained (Table 1). Only one eye of each subject was included in the analysis. The right eye was selected unless it was excluded by these criteria. Although normal and glaucomatous sub jects were not matched individually by re fractive error, this measurement was avail able in 206 of the 230 subjects. In 101 normal subjects, with no known contributory glau coma history, the distribution by spherical equivalent was as follows: 46% of subjects had more than +1.00 diopter hyperopia, 46% were between +1.00 and -1.00, and 9% had more than —1.00 myopia. The analogous
White
1 1 7 1 0 0 10
4 11 25 13 4 1 58
0 6 13 5 1 0 25
35
1 5 0 0 0 0
0 1 3 0 0 0
6
4
distribution in 95 glaucoma subjects was 29, 46, and 24% respectively. There were more myopes in the glaucoma group. All normal subjects had between +5.00 and —5.00 diopters. In the glaucoma group three sub jects had more than —5.00 myopia and two had more than +5.00 hyperopia. The various angle features studied and the numeric method of grading each one were compiled (Table 2 ) . The degree of abnormality increased with the grade number. The iris root normally inserts into the ciliary body with a grade of 0, while the other grades refer to a more anterior or higher insertion. The term iris process refers to what some observers call mesodermal rem nants, rudimentary pectinate fibers, or uveal
TABLE 2 ANGLE FEATURES AND CLASSIFICATION
Grade
Feature Pigmentation of trabeculae Insertion of iris root Prominence of Schwalbe's line No. of iris processes To ciliary body band To trabeculae To Schwalbe's line
3
2
1
0
Moderate Minimum Marked None To Schwalbe's line To trabeculae To scleral spur To ciliary body Marked Moderate Minimum None Marked Marked Marked
Moderate Moderate Moderate
Minimum Minimum Minimum
None None None
58
AMERICAN JOURNAL OF OPHTHALMOLOGY
meshwork. Each quadrant was graded sep arately. In a small percentage 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, we calculated a mean value and standard deviation from the frequency distri bution of grades for each angle feature. Sta tistical analysis was based on the number of subjects rather than the number of quad rants. Statistical comparison of means was done with the Student's t-test. The F test was also used for analysis of variance among groups. A two-tailed test was used for deter mining probability values. RESULTS
In normal eyes the trabecular pigmenta tion was most marked inferiorly, followed by the nasal quadrant. The number of iris proc esses to the trabecular meshwork was most marked nasally, followed by the inferior quadrant. Table 3 shows the degree of trabecular pigmentation by age for both normal and giaucomatous subjects. There was no sta tistically significant trend with age for either group. However, an inspection of the data between the fourth and eighth decades, the age range of most of the subjects, shows steady decreases in pigmentation in normal subjects but only minimal decreases in giau comatous patients in the sixth decade. Black and white subjects were generally similar in both groups. There were more iris TABLE 3 TRABECULAR PIGMENTATION BY AGE, GRADING BY MEAN ±S.D.
Age No. Groups, of yrs Subjects 40-49 50-59 60-69 70-79 80-89
8 24 50 22 5
Subjects Normal
Giaucomatous
0.63±1.06 0.91±0.72 0.82 ±0.75 0.64±0.66 1.00±0.71
1.50±0.76 1.33 ±1.05 1.20±0.81 1.41 ±0.91 1.20±1.30
JULY, 1975
processes to the trabeculae in blacks but this may have been caused by better visualization of the processes in the more pigmented eye. Trabecular pigmentation appeared to be greater in whites but this could have been caused by a better contrast in the less pig mented eye. To compare the glaucoma and normal groups, the black and white subjects were combined. An analysis of blacks and whites separately gave similar results. Table 4 pre sents the values for the various angle fea tures in the four groups. Based on these data, Table 5 presents the statistical com parisons among the groups. Glaucoma pa tients with medication had more trabecular pigmentation, higher insertion of the iris root, and more iris processes at all levels than the normal subjects. Glaucoma patients with medication also had greater trabecular pigmentation and more iris processes than glaucoma patients without medication. Nor mal subjects with a family history had a higher insertion of the iris root and a more prominent Schwalbe's line than normal sub jects without a family history. The values were almost consistently higher in the former group (Table 4 ) . The few subjects in this group probably mask a statistically significant difference for more individual features. Table 6 shows the relationship between re fractive error and two angle features in the normal and giaucomatous subjects. There was no statistical interaction in that both groups showed a similar relationship with refractive error. Myopes had significantly more trabecular pigmentation ( P < .05) and iris processes ( P < .01). In all categories, the findings were more marked in the glau coma group ( P < .001). DISCUSSION
Our findings that iris processes are most marked nasally agree with the observations of Chandler and Grant24 and Lichter." Our observation that trabecular pigmentation does not vary with age in normal subjects appears to differ with the widespread view that pig-
VOL. 80, NO. 1
GONIOSCOPIC ABNORMALITIES
59
TABLE 4 ANGLE FEATURES IN FOUR GROUPS OF SUBJECTS,* GRADING BY MEAN±S.D.
Normal with Glaucoma without Glaucoma with Family History Medication Medication (27) (83) (10)
Normal (110) Pigmentation of .trabeculae Insertion of iris root Prominence of Schwalbe's line No. of iris processes To ciliary body band To trabeculae To Schwalbe's line
0.79±0.74 0.01±0.10 0.05±0.27
1.20±1.03 0.22±0.45 0.50±0.71
1.07 ±0.87 0.24±0.44 0.19±0.48
1.39±0.88 0.18±0.39 0.13 ±0.41
1.82±0.81 0.73 ±0.72 0±0
2.29±0.76 1.10±0.88 0±0
2.05±0.97 1.07 ±0.87 0.04±0.19
2.42±0.69 l.S2±0.86 0.14±0.S0
Parentheses indicate number of subjects in each group.
TABLE 5 STATISTICAL COMPARISON OF ANGLE FACTORS AMONG VARIOUS GROUPS OF SUBJECTS* (P
Although gonioscopic abnormalities occur in patients with congenital and juvenile glau coma, their presence in patients with openangle glaucoma has been debated. A compari son between primary open-angle glaucoma and normal subjects should not be limited to a search for qualitative differences but should also include quantitative differences in the frequency distribution of various fea tures. A lower incidence of blood reflux into Schlemm's canal in primary open-angle glau coma was noted by several authors. 1-10 Ex cluding pigmentary glaucoma, excessive trabecular pigmentation in primary openangle glaucoma was observed by some inves tigators11"14 but not by others.6-15 An excess of felt-like or woolly substance in primary open-angle glaucoma was also observed.6-16'17 The central anterior chamber depth is slightly shallower in primary open-angle glaucoma compared with carefully matched normal control subjects. 1821 Lichter and Shaffer22 found a higher incidence of iris processes in serting anterior to the scleral spur in primary open-angle glaucoma as compared with nor mal subjects. This is a further study of gonioscopic differences. SUBJECTS AND METHODS
We selected normal and primary openangle glaucoma subjects, over the age of 40, from the clinic, private practice, and volun teers. All subjects had a complete ocular From the Combined Program in Ophthalmology, University of Alabama and the Eye Foundation Hospital, Birmingham, Alabama. This study was supported by grant-in-aid 5R01-EY01119, National Eye Institute. Presented before the 102nd American Ophthalmological Society meeting, Hot Springs, Virginia, May 29, 1975. Reprint requests to R. Levene, M.D., 2000-D Brookwood Medical Center Dr., Birmingham, AL 35209.
examination, and Goldmann perimetry studies were performed on all glaucoma pa tients. Gonioscopy was performed in all four quadrants of one or both eyes with the Goldmann three-mirror goniolens and the Haag-Streit 900 slit lamp. Subjects with a contributory history of ocular trauma, ocular surgery, or significant anterior segment dis ease other than cataract, in both eyes, were excluded. In addition, a subject was dis qualified if the angle was not medium to wide open in at least two quadrants, accord ing to Shaffer's classification.23 One observer performed all gonioscopic examinations. We thought angle features would show a better correlation with ocular pressure rather than with disk or visual field changes and the subjects were classified primarily by pres sure. The first group—normal subjects—had applanation pressures in both eyes equal to or less than 20 mm Hg on at least two occasions, and normal disks. They were subdivided into two subgroups: a larger group 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 openangle glaucoma patients and suspects—had applanation pressures over 20 mm Hg in one or both eyes on at least two occasions. This group could have been subdivided either into those with definite visual field loss, or not, or those receiving medication, or not. We thought the latter might be a more pertinent factor in relation to angle features. Subjects receiving or those who had received medica tion had the more severe cases, with 60% of them having definite glaucomatous visual field loss. Subjects without a history of medi cation had a 4% incidence of definite visual field loss caused by glaucoma. The glaucomatous group and the larger subgroup of normal subjects with a noncontributory history were individually matched 56
57
GONIOSCOPIC ABNORMALITIES
VOL. 80, NO. 1
TABLE 1 SUBJECTS
Primary Open-Angle Glaucoma Patients Age Group. yrs in decades
40-49 50-59 60-69 70-79 80-89 90-99 Total
Normal Subjects With. Family No Contributory History of Glaucoma No Contributory MediHistory MediHistory Black White cation of cation of History Medication History Medication Black
Normal Subjects Black
White
7 17 30 16 4 1
1 7 20 6 1 0
75
35
3 6 5 3 0 0 17
75
by race (black or white) and age (in dec ades), by using random exclusion of sub jects in a given category from the larger group until a match was obtained (Table 1). Only one eye of each subject was included in the analysis. The right eye was selected unless it was excluded by these criteria. Although normal and glaucomatous sub jects were not matched individually by re fractive error, this measurement was avail able in 206 of the 230 subjects. In 101 normal subjects, with no known contributory glau coma history, the distribution by spherical equivalent was as follows: 46% of subjects had more than +1.00 diopter hyperopia, 46% were between +1.00 and -1.00, and 9% had more than —1.00 myopia. The analogous
White
1 1 7 1 0 0 10
4 11 25 13 4 1 58
0 6 13 5 1 0 25
35
1 5 0 0 0 0
0 1 3 0 0 0
6
4
distribution in 95 glaucoma subjects was 29, 46, and 24% respectively. There were more myopes in the glaucoma group. All normal subjects had between +5.00 and —5.00 diopters. In the glaucoma group three sub jects had more than —5.00 myopia and two had more than +5.00 hyperopia. The various angle features studied and the numeric method of grading each one were compiled (Table 2 ) . The degree of abnormality increased with the grade number. The iris root normally inserts into the ciliary body with a grade of 0, while the other grades refer to a more anterior or higher insertion. The term iris process refers to what some observers call mesodermal rem nants, rudimentary pectinate fibers, or uveal
TABLE 2 ANGLE FEATURES AND CLASSIFICATION
Grade
Feature Pigmentation of trabeculae Insertion of iris root Prominence of Schwalbe's line No. of iris processes To ciliary body band To trabeculae To Schwalbe's line
3
2
1
0
Moderate Minimum Marked None To Schwalbe's line To trabeculae To scleral spur To ciliary body Marked Moderate Minimum None Marked Marked Marked
Moderate Moderate Moderate
Minimum Minimum Minimum
None None None
58
AMERICAN JOURNAL OF OPHTHALMOLOGY
meshwork. Each quadrant was graded sep arately. In a small percentage 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, we calculated a mean value and standard deviation from the frequency distri bution of grades for each angle feature. Sta tistical analysis was based on the number of subjects rather than the number of quad rants. Statistical comparison of means was done with the Student's t-test. The F test was also used for analysis of variance among groups. A two-tailed test was used for deter mining probability values. RESULTS
In normal eyes the trabecular pigmenta tion was most marked inferiorly, followed by the nasal quadrant. The number of iris proc esses to the trabecular meshwork was most marked nasally, followed by the inferior quadrant. Table 3 shows the degree of trabecular pigmentation by age for both normal and giaucomatous subjects. There was no sta tistically significant trend with age for either group. However, an inspection of the data between the fourth and eighth decades, the age range of most of the subjects, shows steady decreases in pigmentation in normal subjects but only minimal decreases in giau comatous patients in the sixth decade. Black and white subjects were generally similar in both groups. There were more iris TABLE 3 TRABECULAR PIGMENTATION BY AGE, GRADING BY MEAN ±S.D.
Age No. Groups, of yrs Subjects 40-49 50-59 60-69 70-79 80-89
8 24 50 22 5
Subjects Normal
Giaucomatous
0.63±1.06 0.91±0.72 0.82 ±0.75 0.64±0.66 1.00±0.71
1.50±0.76 1.33 ±1.05 1.20±0.81 1.41 ±0.91 1.20±1.30
JULY, 1975
processes to the trabeculae in blacks but this may have been caused by better visualization of the processes in the more pigmented eye. Trabecular pigmentation appeared to be greater in whites but this could have been caused by a better contrast in the less pig mented eye. To compare the glaucoma and normal groups, the black and white subjects were combined. An analysis of blacks and whites separately gave similar results. Table 4 pre sents the values for the various angle fea tures in the four groups. Based on these data, Table 5 presents the statistical com parisons among the groups. Glaucoma pa tients with medication had more trabecular pigmentation, higher insertion of the iris root, and more iris processes at all levels than the normal subjects. Glaucoma patients with medication also had greater trabecular pigmentation and more iris processes than glaucoma patients without medication. Nor mal subjects with a family history had a higher insertion of the iris root and a more prominent Schwalbe's line than normal sub jects without a family history. The values were almost consistently higher in the former group (Table 4 ) . The few subjects in this group probably mask a statistically significant difference for more individual features. Table 6 shows the relationship between re fractive error and two angle features in the normal and giaucomatous subjects. There was no statistical interaction in that both groups showed a similar relationship with refractive error. Myopes had significantly more trabecular pigmentation ( P < .05) and iris processes ( P < .01). In all categories, the findings were more marked in the glau coma group ( P < .001). DISCUSSION
Our findings that iris processes are most marked nasally agree with the observations of Chandler and Grant24 and Lichter." Our observation that trabecular pigmentation does not vary with age in normal subjects appears to differ with the widespread view that pig-
VOL. 80, NO. 1
GONIOSCOPIC ABNORMALITIES
59
TABLE 4 ANGLE FEATURES IN FOUR GROUPS OF SUBJECTS,* GRADING BY MEAN±S.D.
Normal with Glaucoma without Glaucoma with Family History Medication Medication (27) (83) (10)
Normal (110) Pigmentation of .trabeculae Insertion of iris root Prominence of Schwalbe's line No. of iris processes To ciliary body band To trabeculae To Schwalbe's line
0.79±0.74 0.01±0.10 0.05±0.27
1.20±1.03 0.22±0.45 0.50±0.71
1.07 ±0.87 0.24±0.44 0.19±0.48
1.39±0.88 0.18±0.39 0.13 ±0.41
1.82±0.81 0.73 ±0.72 0±0
2.29±0.76 1.10±0.88 0±0
2.05±0.97 1.07 ±0.87 0.04±0.19
2.42±0.69 l.S2±0.86 0.14±0.S0
Parentheses indicate number of subjects in each group.
TABLE 5 STATISTICAL COMPARISON OF ANGLE FACTORS AMONG VARIOUS GROUPS OF SUBJECTS* (P
