Fuchs' Heterochromic Cyclitis*

MALIGNANT GLAUCOMA

4. If, as in the last case, the findings suggest the possibility of malignant glau­ coma, evacuation of the anterior chamber by a fistualizing operation might lead to a posterior block. The better treatment would seem to be to close the anterior chamber tightly by performing a simple basal iridectomy. 5. After a fistualizing operation, if the chambers become shallow, the bleb flat and the pressure elevated, cycloplegia, meas­ ures to suppress aqueous formation and systemic, topical and anti-inflammatory measures should be instituted. If, as in the present cases, the pressure does not sub­ side and the chamber does not reform, surgical measures must be employed and the cycloplegic, anti-inflammatory and aqueous suppression measures continued. SUMMARY

627

form of secondary narrow-angle glaucoma initiated by posterior block, hyperirritability and hypersécrétion of the ciliary body, posterior aqueous lacunation and retrolensciliary body spasm, resulting in anterior displacement of lens. A concept of posterior block is presented and three potential zones of block due to aqueous flow are designated as posterior, middle and anterior. Four possible clinical states of flat anterior chamber are discussed. A theory of the mechanism causing choroidal and ciliary body detachment is offered to ex­ plain the flat chambers and low tensions in one of the cases presented. The physical findings in cases likely to develop malignant glaucoma are stressed. The medical and surgical treatment successfully employed in seven eyes is presented.

On the basis of gonioscopic findings, malignant glaucoma would seem to be a

910 Medical Arts Building

(1).

REFERENCES

1. Chandler, P. A.: Malignant glaucoma. Am. J. Ophth., 34:993, 1951. 2. Shaffer, R. N.: Role of vitreous detachment in aphakic and malignant glaucoma. Tr. Am. Acad. Ophth., 58:217, 1954. 3. Wolf, E. The Anatomy of the Eye and Orbit. Philadelphia, Blakiston, 1948, ed. 3, p. 39. 4. Duke-Elder: System of Ophthalmology. Vol. II: The Anatomy of the Visual System. St. Louis, Mosby, 1961, p. 157. 5. Scott, A. S., and Smith, V. H.: Retrolental decompression for malignant glaucoma. Brit. J. Ophth., 45:654, 1961. 6. Barkan, O.: Narrow-angle glaucoma pupillary block: Narrow-angle mechanism. Am. J. Ophth., 37:332-350 (Mar.) 1954. 7. Nordenson, J. W. : Ueber die Ursachen der Verengerung der Vorderen Augenkammer beim Primaren Glaukom. Lakareforenings forhandlingar. Ny foljd., 29:1-15, 1924.

F U C H S ' H E T E R O C H R O M I C CYCLITIS* A S S O C I A T E D

H.

W I T H

SAUL

FACIAL

SUGAR,

H E M I A T R O P H Y

M.D.,

AND

( S C L E R O D E R M A E N

THOMAS

L.

COUP D E

BANKS,

S A B R E )

M.D.

Detroit, Michigan

Fuchs 1 syndrome, a mild chronic cyclitis associated with heterochromia iridis and, sometimes, with cataract and secondary glau* From Sinai Hospital of Detroit and Wayne State University College of Medicine.

coma, has been recognized for many years. Its clinical picture has been well described by Fuchs 1 after whom the disease has been named, although the condition was first rec­ ognized by Lawrence.2 Excellent reviews of the subject have been published by Frances-

628

H. SAUL SUGAR AND THOMAS L. BANKS

chetti3 and Kimura, Hogan and Thygeson.4 The significance of the condition has been the subject of considerable controversy. It is the purpose of this paper to present a series of cases from the literature and one of our own patients with Fuchs 1 syndrome and facial hemiatrophy (scleroderma en coup de sabre) which suggest a common origin of the two conditions, possibly in neurovascular or neurotrophic changes resulting from dis­ turbances of parts of the sympathetic nerv­ ous system, perhaps of a heredodegenerative nature. Romberg's syndrome of progressive facial hemiatrophy has, itself, been the subject of considerable discussion in the dermatologie and ophthalmologic literature, especially in regard to its relation to scleroderma en coup de sabre. It is characterized by pro­ gressive atrophy of subcutaneous tissue and fat, usually also involving epidermis, connec­ tive tissue, muscle, bone and cartilage. It may halt in its progress at any point and consist of only a mild atrophy of facial fat or it may progress to severe deformity. It is ap­ parent that facial hemiatrophy and the sabre-slash type of scleroderma are either the same disease or are so closely related as to be considered together. Wartenberg 5 states that scleroderma en coup de sabre is an abortive form of progressive facial hemi­ atrophy in which progression has stopped early. From a review of the literature on scleroderma and facial hemiatrophy, it ap­ pears that two schools of thought exist. One is that very well expressed by Wartenberg, in which the two are manifestations of a single heredodegenerative disease where the local disturbances are believed to result from an irritative lesion of the brain on the homolateral side with a state of irritation in the peripheral trophic sympathetic nervous sys­ tem. The other school does not consider the two diseases to be identical. However, they do believe that both are connected with the nervous system (Segal 6 ). The association of heterochromia and

heterochromic cyclitis with facial hemiatro­ phy appears to be more than a coincidence. Fuchs, 1 and later Lutz, 7 pointed out the association. A review of the literature has revealed a total of 14 such cases to which we are adding one of our own. The descrip­ tions of some of these cases are sometimes vague about details involving the eyes. The entire series is shown in Table 1. Seven are typical sabre-slash cases while eight are de­ scribed as facial hemiatrophy. Of those with scleroderma en coup de sabre, two, including our own case, showed evidence of cyclitis without heterochromia; one showed a pos­ terior synechia; another, one episode of iritis which subsided entirely; two showed glassy keratic precipitates and one showed heterochromia without evidence of cyclitis. Of the eight without the sabre-slash ap­ pearance, seven had heterochromia with cy­ clitis and one had heterochromia alone. Of those with cyclitis, one was described as having "remnants of tuberculous uveitis" and another as having rheumatic iritis. CASE REPORT

L. M. J., a 35-year-old Negress born in Jamaica, was first seen in November, 1962, complaining of mild right visual blur for near for three years. She first noted a dark area on the right side of the fore­ head at about the junction of the lateral and the mid­ dle third 15 years previously. Three years ago she noted that the area of increased pigmentation was depressed and that the globe had receded, making her right eye seem smaller. She also noted that vision in the right was not as clear as in the left, espe­ cially for near. There also was a questionably re­ lated history of blunt trauma (bilateral "black eyes") 11 years ago. Examination showed a young obese Negro female with a four-inch wide patch of hyperpigmented atrophie skin on the right side of her forehead at the junction of the lateral and middle thirds. In this area a half-inch wide vertical furrow was present (fig. 1). This was best appreciated by palpation in which there was loss of substance in both skin and subcutaneous tissue. The skin was not adherent to the underlying structures at any point. The hair color was black but alopecia was present, most marked in the right temporofrontal region continuous with the band of atrophie skin on the forehead. The face was asymmetrical with a definite flattening of the right contours to a point about level with the lip line. The left eye and orbit were entirely normal. The right

629

FUCHS' HETEROCHROMIC CYCLITIS TABLE 1 DISTRIBUTION OF FINDINGS IN CASES

1

Facial Hernia trophy

Author

NT

Rosselet15

Saber-Slash Scleroderma

Simple Heterochromia

X

X 16

Heterochromic Cyclitis X No heterochromia

X

2

Franceschetti & Maeder

X

3

Bistis"

X

4

Franceschetti & Koenig18

X

X

5

Franceschetti & Koenig8

X

X

X Mother also he­ terochromic cyclitis X Posterior synechia X

6

Paufique & Chavanne

19

X

X

7

Paufique & Chavanne1'

X

X Bilateral

8

Holtschmidt"

X

9

Perkins"

X

X

X Glasslike keratic precipitates

10

Wartenberg6

X

X

X (Iris darker on side of skin in­ volvement)

11

Wartenberg6

X

X ("Remnants of tuberculous uveitis")

12

Lévy-Valensi22

X

X "Iritis same side"

13

Thibierge & Chaillous23

X

14

6

Segai et al.

X

X

X Iritis receded entirely

15

Sugar & Banks

X

X

X No heterochromia

orbit showed an enophthalmos of three mm. (right IS mm., left 18 mm., Hertel). There was a narrow­ ing of the right palpebrai fissure as follows: PALPEBRAI, FISSURES

Upward gaze Straight Down

R.E. (mm.) 10 8 3

L.E. (mm.) 13 11 4

On the posterior surface of the right cornea there were five centrally located, irregularly round, glassy precipitates with slight pigmentation at their centers.

X

X

Their hyaline surface appeared as if a layer of trans­ parent material had been laid down over an old mut­ ton-fat precipitate. There was no increase in cells nor was there any flare in the aqueous. The pupil was round, regular and equal to the left pupil in size, reaction to light and accommodation. Many small glassy glistening dots were present on the an­ terior iris surface, especially over the nasal portion of the sphincter area (figs. 2 and 3). No posterior synechiae were present. There was no heterochromia or iris atrophy. The lens was clear and the fundus was normal. The visual fields, muscle balance and intraocular pressure were entirely normal.

630

H. SAUL SUGAR AND THOMAS L. BANKS

Fig. 1 (Sugar and Banks). Case 1. Photograph of patient, showing saber-slash scar on forehead and enophthalmos on right side. General physical examination showed osteoarthritis of both knee joints and shoulder bursitis. Skull and orbit roentgenography was normal. The serologie examination was normal. Blood counts, EEG and chest X-ray films were normal. EKG showed incomplete left bundle branch block. Sedi­ mentation rate was 18 minutes. Skin biopsy in the involved area of the forehead was reported simply as a cicatrix, possibly as the result of trauma be­ cause of pigmentation surrounding the deeper ves­ sels in the dermis.

cases in the literature were actually cases of heterochromic cyclitis and that the case with a posterior synechia may not have been a true Fuchs' cyclitis. Certainly no distinc­ tion has been made in the literature as to the degree of activity of the cyclitis. In our own case, which is the only one in which iris nodules have been described, there was no evidence of recent activity although glassy precipitates on the cornea and glassy no­ dules on the iris attest to the past existence of a cyclitis which may have lasted for a period of time and then become quiescent. It is suggested that the cyclitis was active during the period of progression of the sabre-slash scleroderma and that both ceased their activity and have remained unchanged for years. It is also suggested that the ab­ sence of heterochromia is further evidence of a limited period of activity. The same explanation would apply to Case 2 in Table 1 (Franceschetti and Maeder).

DISCUSSION

Our experience with the case reported here and the vague descriptions in some of the cases reported elsewhere suggest that it is likely that some of the heterochromia

Fig. 2 (Sugar and Banks). Case 1. Photograph of right iris, showing glassy deposits on iris border and posterior corneal surface.

Fig. 3 (Sugar and Banks). Case 1. An enlargement of the section outlined in Figure 2.

FUCHS" HETEROCHROMIC CYCLITIS If one reviews the literature to study the incidence of heterochromic cyclitis itself, it is apparent that many cases remain unrecog­ nized. Hollwich8 found that only 19 percent of 67 referred cases had been correctly recognized, partly because of the small differ­ ence in iris pigmentation in the two eyes in 65 percent, the presence of inverse hetero­ chromia in nine percent (see Case 10, Table 1), and the presence of the condition bi­ laterally in 12.5 percent (see Case 7, Table 1 ) . The cases of inverse heterochromia were those in which the involved blue eye had so much atrophie change as to bare the pig­ ment epithelium of the iris. The iris on the involved side then appeared darker than that of the fellow eye. Another obvious cause for the failure to recognize the disease is omis­ sion of biomicroscopic examination. As de­ scribed in our own case, there may be no active cyclitis present and the old deposits may be atypical in appearance. It is well known that simple heterochromia is found in cases of unilateral paresis or paralysis of the sympathetic nerve, not only in those caused by birth injury but in those with injury in later years. Walsh 24 stated that the sympathetic paralysis has to appear before the age of two years to cause hypopigmentation. There is evidence that heterochromia as­ sociated with Horner's syndrome may be familial. Calhoun (1919) 9 reported four cases in one family. Two of these showed unilateral anidrosis of the forehead and mild facial hemiatrophy (see Case 8, Table 1). François 10 considers the association of heter­ ochromia and Horner's syndrome to be transmitted as irregular dominant. Klingmann (1907) 11 described the association of heterochromia iridis with facial hemiatrophy as having dominant hereditary transmission. When we consider heterochromic cyclitis, it, too, is to be considered from a genetic point of view. Streiff12 has reported simple heterochromia and heterochromic cyclitis in the same family. Passow 13 found a connec­

631

tion between heterochromia and heterochro­ mic cyclitis as shown by the occurrence of both types of heterochromia in patients with unilateral hypoplasia of the mamma and hypopigmentation of its areola and nipple, and hereditary dystrophic symptoms. He found evidence of status dysraphicus (fail­ ure of closure of the neural tube) in 80 percent of his cases. Franceschetti 3 found mild evidences of this condition in nearly half of his cases. Hollwich8 found status dysraphicus in 75 percent of 67 patients with heterochromic cyclitis. These were di­ vided as follows: A. Disturbances in the skeletal system 1. Sternal dimpling, infundibular thorax 32.4% 2. Scoliosis, kyphosis, lordosis 67.1% 3. Overwide arm span 62.7% B. Unilateral atrophie disturbances 1. Horner's syndrome 43.2% 2. Hemiatrophy of face and body 71.8% 3. Hemiatrophy and hypochromia of female breast 43.2% C. Vasomotor and sensorial disturbances 1. Two-point discrimination, percep­ tion of cold, warm 17.9%

2. Acrocyanosis

20.9%

Intrafamilial cases of heterochromic cy­ clitis have been found rather frequently. They have been well documented by Fran­ çois10 and considered as irregular dominant in heredity. Case 3, Table 1 (Bistis 17 ) is interesting in this respect since the mother of the patient also suffered from Fuchs' syndrome. Two cases of heterochromic cy­ clitis in identical twins have been described by Makley.14 All of these interrelationships between heterochromia, heterochromic cy­ clitis, facial hemiatrophy and sabre-slash scleroderma suggest a genetic factor. Fran­ ceschetti and Maeder16 account for the rarity of the familial cases by suggesting that the defective gene is of low penetrance. The coexistence of facial hemiatrophia and heterochromic cyclitis, both relatively rare, appears to be more than accidental. A com­ mon genetic and causal origin appears prob-

632

H. SAUL SUGAR AND THOMAS L. BANKS

able. It is suggested that both may be the result of neurovascular or neurotrophic changes resulting, possibly, from disturb-

ances of parts of the sympathetic nervous system. 28 West Adams (26).

REFERENCES

1. Fuchs, E.: Ueber Komplikationen der Heterochromie. Ztschr. Augenh., 15:191, 1906. 2. Lawrence, W. : Treatise on Diseases of the Eye. Philadelphia, Isaac Hays, 18S3, ed. 3. 3. Franceschetti, A.: Heterochromie cyclitis. Am. J. Ophth., 39:50,1955. 4. Kimura, S. J., Hogan, M. J., and Thygeson, P.: Fuchs' syndrome of heterochromie cyclitis. AMA Arch. Ophth., 54:179, 1955. 5. Wartenberg. R.: Progressive facial hemiatrophy. Arch. Neurol. & Psychiat, 54:75, 1945. 6. Segal, P., Jablonska, S., and Mrzyglod, S. : Ocular changes in linear scleroderma. Am. J. Ophth., 51:807,1961. 7. Lutz, A.: Ueber einige weitere Falle von Heterochromia iridis. Deutsch. Med. Wchnschr., 24:1125, 1910. 8. Hollwich, F.: Zur Differentialdiagnose der Heterochromiezyklitis, Klin. Monatsbl. Augenh., 142: 129, 1963. 9. Calhoun, P. F.: Causes of heterochromia iridis with special reference to paralysis of the cervical sympathetic. Am. J. Ophth., 2:256, 1948. 10. François, J.: Heredity in Ophthalmology. St. Louis, Mosby, 1961, p. 536. 11. Klingmann, T.: Facial hemiatrophy, J.A.M.A., 49:1888, 1907. 12. Streiff, J.: Ein neuer Irisbefund bei Fuchsscher Heterochromie und weitere Ergänzungen zum Heterochromieproblem. Klin. Monatsbl. Augenh., 76:321, 1926. 13. Passow, A. : Hornersyndrom, Heterochromie und Status dysraphicus, ein Symptomenkomplex. Arch. Augenh, 107:1, 1933. 14. Makley, T. A , Jr.: Heterochromie cyclitis in identical twins. Am. J. Ophth., 41:768, 1956. 15. Rosselet, E., and Dosseiet, G.: Syndrome de Romberg et Manifestations oculaires. Confìnia Neurologica, 15:98, 1955 16. Franceschetti, A , and Maeder, G. : Hémiatrophie faciale avec alopécie (Syndrome de Romberg) associée à une cyclite hétérochromique (Syndrome de Fuchs). J. Génét. hum, 7:116, 1958. 17. Bistis, J.: La paralysie du sympathique dans l'étiologie de l'heterochromie. Arch, ophtal, 32:578, 1912. 18. Franceschetti, A , and Koenig, H.: L'importance du facteur heredo-dégénératif dans l'hèmiatrophie facial progressive (Romberg). J. Génét. hum, 1:27, 1952. 19. Paufique, L , and Chavanne, H.: Cataracte avec heterochromie irienne, role du sympathique. Bull. et Mem. Soc. Franc. Ophtal, 59:209, 1946. 20. Holtschmidt, J.: Sympathicus-Heterochromie und Hemiatrophie und Hemiatrophia faciei pro­ gressiva. Hautarzt, 5 :255, 1957. 21. Perkins, E. S.: Uveitis and Toxoplasmosis. Boston, Little, Brown, 1961, p. 42. 22. Levy-Valensi, J.: Un cas d'hémiatrophie congénitale. Paris Med, 13:215, 1913. 23. Thibierge, G, and Chaillous, J.: Iritis chez une malade atteinte d'hémiatrophie de la face. Bull. Soc. ophtal. Paris, 1925, p. 258. 24. Walsh, F. B. : Clinical Neuroophthalmology. Baltimore, Williams & Wilkins, 1947.

OCULAR TOXICITY OF D I M E T H Y L A M I N O P R O P Y L A M I N E * GEORGE LINK SPAETH, M.D.,

and

IRVING H. LEOPOLD,

M.D.

Philadelphia, Pennsylvania Eleven employees of a large chemical firm were recently examined at the Wills Eye Hospital because of the sudden onset of blurred vision. Previous to this occasion they had noted similar symptoms toward * From the Wills Eye Hospital.

the end of their shifts. The difficulty had always cleared spontaneously by the time they returned to the plant the next day and so they gave little thought to the matter. It had become so commonplace among them that they had a name for it, "the blue vision." Apparently only the