KRUKENBERG'S SPINDLES

JACOB T. WILENSKY, M.D., '. AND STEVEN M

St. Louis,

In 1899, Krukenberg first described verti­cally oriented, spindle-shaped, centrally lo­cated pigmentary deposits on the corneal en-dothelium. However, it was not until 50 years later that Sugar and Barbour1 estab­lished an association between the spindles and open-angle glaucoma in young men. Their patients had spindles, abnormally pig-mented open angles, and glaucomatous field defects. In subsequent reports of large series of patients with pigmentary glaucoma, Kru-kenberg's spindles were present in most pa­tients.2'3

Because of this finding, Krukenberg's spindles have been accepted as an indicator of patients who have an increased risk of developing glaucoma. Yet a majority of nonglaucomatous individuals with Kruken­berg's spindles are women/ in comparison to reports of pigmentary glaucoma occurring primarily in men.2·3 We questioned the sig­nificance of Krukenberg's spindles in a given individual. Accordingly, we attempted to evaluate the prognostic implications of the presence of Krukenberg's spindles.

PATIENTS AND METHODS

A Krukenberg's spindle in at least one eye of a nonglaucomatous patient was re­quired. Patients with exfoliation syndrome, a history of trauma, or a history of acute angle-closure glaucoma were excluded. All patients from the Glaucoma Center, Wash­ington University, who met these criteria were included in the study. In addition, four

From the Glaucoma Center, Department of Ophthalmology, Washington University School of Medicine, St. Louis, Missouri. This study was sup­ported in part by grant EY 00336, special fellow­ships EY 53710 (Dr. Wilensky), and EY S2947 (Dr. Buerk), National Eye Institute.

Reprint requests to Steven M. Podos, M.D., De­partment of Ophthalmology, Washington Univer­sity School of Medicine, 660 S. Euclid Ave., St Louis, MO 63110.

KENNETH M. BUERK, M.D., :. PODOS, M.D. Missouri

patients referred from another source met these criteria.

The patients were subjected to part or all of a battery of diagnostic or prognostic tests routinely employed in the Glaucoma Center to identify patients with increased risk of de­veloping glaucoma. These tests included ap-planation intraocular pressures ( IOP) , man­ifest refraction, serial kinetic Goldmann pe-rimetry, measurement of serum protein bound iodine (ΡΒΙ) , the response of IOP to topical corticosteroids, dexamethasone (0.25 mg) suppression of plasma cortisol, glucose tolerance, ability to taste phenyl-thiocarbamide (PTC) , and the family his­tory of glaucoma. The topical corticosteroid response was measured by having the pa­tient use dexamethasone 0.1% drops in one eye, four times a day, for six weeks.5 The method of measuring dexamethasone sup­pression of plasma cortisol has been de­scribed elsewhere.6 A ratio of day 1/day 0 < .75 was considered to show suppression. Glucose tolerance was determined by ad­ministering 1 g/kg glucose. A sum of plasma glucose at zero, one, two, and three hours > 600 mg/100 ml was considered abnormal. A patient was labeled a "nontaster" if he failed to report a bitter taste when a PTC solution containing 8.1 mg/100 ml was placed on his tongue. The patient's refrac­tive status was based on the spherical equiva­lent of the more myopic or less hyperopic of the two eyes.

RESULTS

Forty-three patients, 17 men and 26 women, met the criteria for inclusion in this study. Seven of the patients were black. These patients had been under observation for three months to 17 years with an average follow-up of 5.8 years. Twenty-two of these patients had been followed for a minimum

VOL. 79, NO. 2 KRUKENBERG'S SPINDLES 221

of five years with an average of nine years. The average age of these patients at exami­nation was 55.7 years. The men, as a group, were 12.3 years younger than the women. The average age of the entire group was 49 years of age.

Nine (52.9%) of the men and 15 (57.7%) of the women had intraocular pressures greater than 21 mm Hg at initial examination. The course of the IOP in these patients can be seen in Table 1. Nine of these patients exhibited a spontaneous drop of IOP to below 22 mm Hg. On the other hand, three patients whose initial IOP was normal recently have shown values in the hypertensive range (Table 2) .

Both men and women responded similarly to topical corticosteroid testing (Table 3). Ten of the men and 18 of the women com­pleted this test. Using Becker's5 criterion of final pressure, five of the men and eight of the women had high IOP ( >31 mm Hg) re­

sponses to topical corticosteroids ; when Armaly's7 change in pressure criterion was employed, three of the men and five of the women had high IOP responses. Three addi­tional patients, one man and two women, had spontaneous IOP higher than 31 mm Hg.

The tests for systemic factors yielded mixed results. Results from three parameters showed no significant sex differences. Four of the 13 men (30.8%) and six of the 17 women (35.5%) tested had PBI < 5.5 μg. Four of the 15 men (26.7%) and eight of the 24 women (33.3%) tested with PTC were nontasters. Four of six men (66.7%) and 11 of 17 women (64.7%) showed sup­pression of plasma cortisol by 0.25 mg of dexamethasone. The fourth systemic param­eter, however, showed a marked sex differ­ence. None of the 13 men tested had an ab­normal glucose tolerance test as opposed to five of 20 women (25%).

Analysis of the refractive errors also re-

TABLE 1 COURSE OF PATIENTS WITH IOP > 22 MM H G ON INITIAL EXAMINATION

Patient's Sex

F M F F M M F F F

F M F M M F

F F F F M M F F M

Initial IOP,

R.E.

26 46 30 27 20 27 25 24 28

24 30 26 24 25 32

27 22 23 21 20 27 24 39 31

, mm Hg

L.E.

16 42 36 29 23 29 20 22 22

28 45 27 20 27 38

26 21 24 22 24 27 15 38 29

Most Recent IOP, mm Hg

R.E. L.E.

16 14 31 24 17 22 21 19 18

18 19 26 18 15 25

29 21 21 20 20 22 19 20 21

15 15 27 25 20' 24 21 26 17

23 26 34 16 17 28

22 21 21 21 20 24 17 24 21

Years Followed

8 10 13 2 2 9 2

12 10

6 2 9 5 7 4

3 8 4

<1 17 2

<1 4 2

Therapy

None Filtering surgery, both eyes Epinephrine 1%, both eyes None Epinephrine 1%, both eyes None None Field loss, L.E. Pilocarpine 4%, epinephrine 1%,

both eyes None None None None Epinephrine 1%, both eyes Field loss, L.E.; carbachol 3%,

epinephrine 2%, both eyes None None None None None None None None None

222 AMERICAN JOURNAL OF OPHTHALMOLOGY FEBRUARY, 197S

TABLE 2 COURSE OF PATIENTS DEVELOPING IOP, >22 MM HG

Patient's Sex

F M M

Initial IOP,

R.E.

17 15 18

mm Hg

L.E.

17 15 18

Recent IOP,

R.E.

22 22 17

mm Hg

L.E.

20 23 24

Years Followed

8 11

3

Therapy

None None Epinephrine 1%, R.E.

TABLE 3 INTRAOCULAR PRESSURE RESPONSE OF 28 PATIENTS TO TOPICAL CORTICOSTEROIDS

Response

Low Intermediate High

Volunteers

Final IOP (%)

58 36

6

ΔΙΟΡ (%)

66 29

5

Krukenberg's

Final IOP (%)

2 (7) 13 (47) 13 (47)

> Spindles

ΔΙΟΡ (%)

8(29) 12 (43)

8(29)

vealed some differences between the sexes. The men (58.8%) were myopic in at least one eye, the women, 34.5%. Almost all of the refractive errors were fairly small (Table 4) .

Data concerning a family history of glau­coma were obtained from 25 of the patients. Nine of them had a first-degree relative (parent, sibling, Or offspring) with glaucoma and two others had more distant relatives (aunt, uncle) with the disease. The other 14 patients had no known relatives with glau­coma.

Two of the patients, both women, de­veloped glaucomatous field loss subsequent to their initial examination. The first pa­tient, who initially presented with IOP in the range of 30, was followed for four years

TABLE 4 REFRACTIVE ERROR IN KRUKENBERG'S

SPINDLE PATIENTS

Refractive Error

> + 5 . 0 0 D + 1 .00-»+4.75 D P lano-*+0 .75 D

- 0 . 2 5 - ^ - 0 . 7 5 D - 1 . O 0 - + - 2 . 7 5 D - 3 . 0 0 - * - 4 . 7 5 D

Men

0 2 5 2 5 3

Women

1 9 7 4 1 3

when perimetry studies indicated a paracen-tral scotoma. She was 66 years old at the time. There was no family history of glau­coma. Her refractive error was —0.25 R.E., piano L.E. ; she tasted PTC, had diabetes, and suppressed her plasma cortisol nine hours after 0.25 mg of dexamethasone. The second patient, whose initial IOP had been in the range of the low 20s, had been fol­lowed for 12 years when perimetry studies first indicated a nasal step. She was 60 years old when the field defect was discovered. Her refractive error was plano R.E., —0.75 L.E. Test results showed a PBI of 5.2 μg, normal glucose tolerance test, no suppression of plasma cortisol after 0.25 mg of dexametha­sone, and nontasting of PTC. She had shown an intermediate IOP response to topical cor­ticosteroids. She had a sister with well-documented pigmentary glaucoma and a brother with primary open-angle glaucoma. Two other siblings had normal IOP and no pigmentary disturbances.

DISCUSSION

The greater frequency of Krukenberg's spindles in women than in men was most interesting. In 1941, Evans, Odom, and

VOL. 79, NO. 2 KRUKENBERG'S SPINDLES 223

Wenaas4 collected data on 202 patients with Krukenberg's spindles (11 had glaucoma), discovering a female majority (62.3%). This corresponded with the women (60.1%) in our study. Of Sugar's2 128 patients with pigmentary glaucoma, on the other hand, 98 (77.4%) were men. These two series seemed to be contradictory. In an attempt to resolve this dilemma, Bick8 analyzed the data from Evans, Odom, and Wenaas's4 paper and pointed out two findings: The average age of the men (37.1 years) was approximately nine years younger than that of the women (45.4 years) and, when patients under 30 years of age were considered, the number of men was greater than the number of women. Bick also found that more men had glaucoma (7.6%) among this population than women (4.9%). Based on these findings, he hy­pothesized that the pigmentary dispersion, while more frequent in women, occurred later and ran a milder course, thus causing less pigmentary glaucoma in women.

Our present data were equivocal on this point. Similar to Evans, Odom, and Wenaas's4 data we found that a majority of the patients with Krukenberg's spindles were women. While the average age of both sexes was somewhat older in our series, the men were significantly younger than the women. Even if we assumed that the man who had successful filtering surgery would develop visual field defects without therapy, we still were left with more women with glaucoma than men.

The results of the glucose tolerance tests showed that none of the men and 25% of the women had positive test results. In view of the well-known fact that diabetes mellitus affects the pigment epithelium of the iris and is more prevalent among women, diabetes mellitus may play a role in the female pre­dilection for Krukenberg's spindles.

Our data deviated from other studies in the incidence of refractive errors. Evans, Odom, and Wenaas's4 study showed that 69.8% of their patients were myopic. Of Sugar's2 128 patients with pigmentary glau­coma, only five were hyperopes and of his 19 personal cases, 78% were myopes of 1.0 di­opters or more. Similarly, 88% of the 202 eyes with Krukenberg's spindles or pigmen­tary glaucoma or both reported by Lichter and Shaffer3 were at least 0.50 diopter myopic. In our study, however, only 58.8% of the men and 34.6% of the women were myopic (Table 4) . There was no apparent explanation for this difference.

Two of us ( J.T.W. and S.M.P.) reviewed a series of parameters that showed a higher prevalence among patients with primary open-angle glaucoma than nonglaucomatous individuals.9 These parameters included a low PBI, inability to taste PTC, a positive glucose tolerance test, suppression of plasma cortisol by 0.25 mg of dexamethasone, and a high IOP response to topical corticoste-roids. Comparison of the data in Table 5 quickly revealed that with the exception of the PTC taste test, our results closely re-

TABLE 5 NORMAL AND PRIMARY OPEN-ANGLE GLAUCOMA POPULATIONS COMPARED

TO KRUKENBERG'S SPINDLE POPULATION

Parameter Normal9 Primary Open-angle9 Krukenberg's (%) Glaucoma (%) Spindle (%)

PBI <5.5 jig/lOO ml PTC nontasting Positive glucose tolerance test 0.25 mg dexamethasone suppression of plasma

cortisol > 2 5 % High topical corticosteroid response (Final I O P > 3 1

mmHg) Family history of glaucoma

8-12 28

2-1

27

6

34 S3

20-22

83

92 38

30 31 14

65

47 44

224 AMERICAN JOURNAL OF OPHTHALMOLOGY FEBRUARY, 197S

sembled a glaucomatous population rather than a normal one.

There has been considerable debate as to the etiology of pigmentary glaucoma. Sugar2

has theorized that pigmentary granules plug the pores of the filtering meshwork and com­promise outflow of aqueous from the an­terior chamber. Becker and Podos10 cite the increased incidence of IOP response to topi­cal corticosteroids in nonglaucomatous eyes with Krukenberg's spindles, the occurrence of open-angle glaucoma without abnormal pigmentation in the relatives of patients with Krukenberg's spindles, and state that pigmentary glaucoma is a variant of primary open-angle glaucoma modified by the pig­mentary dispersion.

Our patients showed an even higher inci­dence of high IOP response to topical cor­ticosteroids than previously reported.10 This was probably due to the fact that the other study excluded patients with ocular hyper­tension or a family history, while both were present in our population. Indeed, the inci­dence of a family history of glaucoma was rather high. Unfortunately, records were un­available for most of these relatives so we were unable to ascertain the nature of their glaucoma. Three of the relatives were seen in the Glaucoma Center. One had pigmen-try glaucoma while the others had primary open-angle glaucoma with no pigmentary ab­normalities.

In spite of the fact that the test results from our spindle population showed many similarities to a glaucomatous population, the actual incidence of glaucoma was low. Only two of the patients developed visual field de­fects, and even if one concedes that the filtered patient would have developed visual field loss, the overall incidence for the entire group was only 7%. Only one of the 22 pa­tients followed for a minimum of five years developed visual field loss. Thus, a Kruken­berg's spindle in conjunction with an ab­sence of field loss is not prognostically ominous.

One note of caution must be registered

here. Most of our patients were referred for various reasons such as ocular hypertension, a family history of glaucoma, or abnormal-appearing cups. Many of these patients were specifically referred to us because of our known interest in spindles. It is conceivable that the referral system created a population that was not representative of Krukenberg's spindle patients as a group. The strong simi­larities between our data and Evans, Odom, and Wenaas's4 data militate against this pos­sibility.

SUMMARY

Forty-three patients who initially pre­sented with Krukenberg's spindles but with no glaucomatous field defects were observed for an average of 5.8 years in an attempt to evaluate the prognostic implications of spindle presence. Twenty-two of the patients had been followed for a minimum of five years. Analysis of the study population revealed that there were more women than men (26 vs. 17), the women were older than the men, and more women had positive glucose toler­ance tests (25% vs. 0). Only two of the patients, both women, developed glaucoma­tous field defects during the period of ob­servation. Thus, the presence of a Kruken­berg's spindle in a patient with no visual field defect is not a particularly ominous sign.

ACKNOWLEDGMENTS

We thank Alan E. Kolher, M.D., who referred four patients, and also the entire staff of the Glau­coma Center, whose help and cooperation made this report possible.

REFERENCES

1. Sugar, H. S., and Barbour, F. A. : Pigmen­tary glaucoma. A rare clinical entity. Am. T. Ophthalmol. 32:90, 1949.

2. Sugar, H. S.: Pigmentary glaucoma. A 25-year review. Am. J. Ophthalmol. 62:499, 1966.

3. Lichter, P. R., and Shaffer, R. N. : Diagnostic and prognostic signs in pigmentary glaucoma. Trans. Am. Acad. Ophthalmol. Otolaryngol. 74:984, 1970.

4. Evans, W. H., Odom, R. E., and Wenaas, E. J. : Krukenberg's spindles. A study of collected cases. Arch. Ophthalmol. 26:1023, 1941.

VOL. 79, NO. 2 KRUKENBERG'S SPINDLES 225

5. Becker, B.: Intraocular pressure response to 8. Bick, M. W.: Sex differences in pigmentary topical corticosteroids. Invest. Ophthalmol. 4:198, glaucoma. Am. J. Ophthalmol. 54:831, 1962. 1965. 9. Wilensky, J. T., and Podos, S. M. : Prognostic

6. Becker, B., Podos, S. M., Asseff, C. F., and indicators in primary open-angle glaucoma. In Cooper, D. G. : Plasma cortisol suppression in Transactions of the New Orleans Academy of glaucoma. Am. J. Ophthalmol. 75:73, 1973. Ophthalmology Symposium on Glaucoma, 1974. In

7. Armaly, M. F. : Statistical attributes of the press. steroid hypertensive response in the clinically nor- 10. Becker, B., and Podos, S. M.: Krukenberg's mal eyes. 1. The demonstration of three levels of spindles and primary open-angle glaucoma. Arch. response. Invest. Ophthalmol. 4:187, 1965. Ophthalmol. 76:635, 1966.

OPHTHALMIC MINIATURE

It is high time the world was aroused from its slumbers, to a sense of the disastrous delusions and impositions under which it has so long and so unjustly been suffering. And these impositions, great as they have been speculatively, are equally so pecuniarily. We have heretofore made no allusions to the exorbitant charges made by physicians for their services, having declined doing so for fear that it might be thought an interference with private concerns in which the parties have a right to make their own contracts. But when we consider the delicacy which people generally feel in objecting to the bills of physicians, and the prerogative which they claim and enforce of fixing a price upon their own services in defiance of public sentiment, we feel an irresistible impulse to notice their extravagance in this particular.

Every impartial observer, in contemplating the rapid augmentation of the fees of physicians of the last thirty years, must be struck with astonishment at the magnitude of the imposition, and the oppressive amount of their extractions. If they go on for thirty years more at the rate they have for the thirty past, the whole community will be little better than the slaves of the medical faculty. . . . We are far from wishing to see medical fees reduced down to the mere compensation of an ordinary day laborer—far from it. But we desire to see them so modified that it may not require the wages of a laborer for a quarter of a year to pay the physician for one day's detention.

Horton Howard, An Improved System of Domestic Medicine Philadelphia, Queen City Publishing House, 1856