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Nontraumatic Leukomas
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AMERICAN JOURNAL OF OPHTHALMOLOGY
3. de Roetth, A., Jr. : Lens opacities in glaucoma patients on phospholine iodide therapy, Am. J. Ophth. 62:619, 1966. 4. Shaffer, R. N., and Hetherington, J. Jr. : Anticholinesterase drugs and cataracts. Am. J. Ophth. 62:613, 1966. 5. Torkkanen, A., and Karjalainen, K. : Cataract formation during miotic treatment for chronic open-angle glaucoma. Acta Ophth. 44:932, 1966. 6. Thoft, R. A. : Incidence of lens changes in pa tients treated with echothiophate iodide. Arch. Ophth. 80:317, 1966. 7. Harrison, R. : Bilateral lens opacities asso ciated with use of di-isopropyl fluorophosphate eyedrops. Am. J. Ophth. 50:153, 1960. 8. Axelsson, U., and Holmberg, A. : The fre quency of cataract after miotic therapy. Acta Ophth. 44:421, 1966. 9. Michon, J., Jr., and Kinoshita, J. H. : Cholines terase in the lens. Arch. Ophth. 77 :804, 1967. 10. Michon, J., Jr., and Kinoshita, J. H. : Experi mental miotic cataract. Effects of miotics on lens structure, cation content and hydration. Arch. Ophth. 79:79, 1968.
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11. Haddad, H. M., Shore, B., Furman, M., and Okas, S. : Lens organ culture TT. Am. J. Ophth. 63:6, 1967. 12. Diamant, H. : Cataract due to cholinesterase inhibitors in the guinea pig. Acta Ophth. 32 :357, 1954. 13. Grant, W. M. : Toxicology of the Eye. Springfield, Illinois, Thomas, 1962, p. 369. 14. Fraunfelder, F. T., and Burns, R. P. : Effect of lid closure in drug-induced experimental cata racts. Arch. Ophth. 76:599,1966. 15. Fraunfelder, F. T., and Burns, R. P.: Produc tion of unilateral reversible cataracts in the ham ster. Proc. Soc. Exp. Biol. Med. 110:72, 1962. 16. Goldmann, H., and Rabinowitz, G. : Ueber eine unbekannte, reversible Kataraktform bei jun gen Ratten. Klin. Mbl. Augenheilk. 81:771, 1928. 17. Weinstock, M., and Scott, J. D. : Effect of various agents on drug-induced opacities of the lens. Exp. Eye Res. 6:368, 1967. 18. Lazar, M. : Mannitol in ophthalmic prepara tions. In New Orleans Academy of Ophthalmology Symposium on Ocular Pharmacology and Thera peutics. To be published.
NONTRAUMATIC
LEUKOMAS
L o u i s J. R O S E N B A U M , M.D., J O H N C H E N , M.D., A N D ISAO H O S H I W A R A , M . D .
Phoenix, Arizona Nontraumatic leukomas are relatively rare among the lesions encountered in the usual ophthalmologic office. However, in the past year, we have seen 13 at the Phoenix Indian Hospital, where the patient population is comprised of Indians of all tribes from Ari zona, Utah, Nevada, and southern Califor nia. Four etiologies have been established for these leukomas: congenital, secondary to systemic disease, secondary to local disease, and idiopathic (Table 1). CASE REPORTS
Case 1—A 63-year-old Apache man was seen February 29, 1968, for a routine examination. Visual acuity was RE: 20/200, LE: 20/50. In his right eye, in which he had had poor vision all his life, he had a From the Ophthalmology Service, Phoenix Medi cal Center and the Trachoma Control Unit, Indian Health Service, U.S. Public Health Service. This paper was read before the Section of Ophthalmol ogy, Public Health Service Clinical Society Meet ing, June 3,1969. Reprint requests to Louis J. Rosenbaum, M.D., 777 East Brill, Phoenix, Arizona 85006.
2.5-mm dense leukoma slightly nasal to the pupil lary area with iris adherent to the posterior sur face of the cornea. The right lens had a dense central anterior polar cataract. The fundi and in traocular tension were normal in both eyes (Fig. 1). Case 2—A 17-year-old Pima girl, first seen in June, 1953, was found to have a comeal scar in her left eye present since birth, and a left exotropia. During the next six months, she had strabis mus surgery, and a tattoo of the left cornea for cosmetic reasons. She was next seen January 31, 1968, because of decreased visual acuity in her right eye. Refraction was RE: —3.25 = + 2 . 0 0 X 80, 20/30; in her left eye she had light perception only. The left eye was noted to be microphthalmic. She was orthophoric by the Krimsky test, but had an intermittant horizontal nystagmus, TABLE 1 CLASSIFICATION OF NONTRAUMATIC LEUKOMAS
Classification Congenital Secondary to systemic disease Secondary to local disease Idiopathic
No. Cases 4 2 5 2
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greatest on left gaze. Ductions were full. There was a dense, central leukoma, 3.S mm in diameter, with superficial pigment deposition overlying it. The iris was adherent to the leukoma so that no pupil was apparent. The fundus was normal in the right eye.
stroma with iris adherent, just nasal to the pupil lary area. Slightly temporal was a superficial stromal, round, 2.0-mm opacity. A large vessel ran from the limbus at four o'clock to both lesions. A dense anterior polar cataract was present in his left eye.
Case 3—A 10-month-old Pima girl, product of a full-term pregnancy and normal delivery, was seen July 17, 1967, because of a white spot on her left eye since birth. Examination under general anesthesia showed a deep central opacity of the left cornea, approximately 4 mm. in diameter. Corneal diameters were R E : 11.S mm, and L E : 10.5. The right fundus was normal. The left fundus could not be seen. Intraocular pressure was nor mal.
Case 5—A 41-year-old Papago woman gave a history of scarring of both eyes since the age of three years, following measles. She had had progressive loss of vision in the left eye, and it had lost light perception five years earlier. She was first seen October 12, 1967. Visual acuity was RE: 20/60 with correction. Slit lamp examination showed dense leukomas, 4.0-mm in diameter inferiorly in both eyes, with both irises adherent to the posterior surface. The left eye also had epithelial edema. The fundi could not be seen in either eye. Intraocular pressure was 2/5.5, 6/10, RE ; 0/10, LE. On gonioscopy, two-thirds of the angle in the right eye was sealed, and the rest of the angle was Grade 1 ; the angle was completely sealed in the left eye. Central fields in the right eye were within normal limits. The patient was begun on pilocarpine, 2%, and acetazolamide (Diamox), 250 mg, every six hours, and the pressure became normal. Tonography showed Po 20 mm Hg and C 0.18. The patient had a right sector iridectomy. Postoperatively, the right fundus could be seen, and the disk was thought to have early, shallow cupping (Figs. 2 and 3).
Case 4—A 15-year-old Apache boy was first noted to have a left corneal opacity at the age of two, according to his chart. He was the product of a full term pregnancy and a normal delivery. He denied any history of trauma or inflammation when he was seen on October 10, 1968. At that time, he had a visual acuity of RE: 20/20, and L E : 20/200. The left pupil was slightly distorted nasally, but reacted to light. He had 20 prism di opters of left esotropia. Ductions were full. Fundi were normal in both eyes. Slit lamp examination showed a dense, round 2-mm leukoma in the deep
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Fig. 1 (Rosenbaum, Chen, and Hoshiwara). Case 1. Congenital leukoma, also anterior polar cataract.
862
AMERICAN JOURNAL OF OPHTHALMOLOGY
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Fig. 2 (Rosenbaum, Chen, and Hoshiwara). Case 5. Leukoma, RE, secondary to measles. Case 6—A 72-year-old Pima woman gave a his tory of having had measles when she was a little girl, which her doctor told her had caused the scars on her eyes. Intracapsular cataract surgery had been performed on her right eye in January, 1963, but a flat anterior chamber developed five weeks later. The intraocular pressure was 59 mm Hg, and gonioscopy showed the angle to be sealed except be tween three and five o-clock, and between eight and 10 o'clock. Unfortunately, no record of preoperative intraocular pressure or gonioscopy could be found. The glaucoma could not be controlled medically after the anterior chamber was reformed surgically. In April, 1963, she had a cyclodialysis, which re
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duced the tension to the mid-twenties. Pilocarpine, 2%, four times a day, brought the intraocular pres sure to the mid-teens. In April, 1964, an intracapsu lar cataract extraction performed on her left eye was successful. When seen on July 7, 1968, visual acuity was RE : hand motion, LE : 20/80. Slit lamp examination showed dense leukomas inferior-temporally in both eyes, with iris adherent to the endothelial surface of the cornea in both. The anterior chamber was deep elsewhere. The vitreous face was broken in both eyes. The right disk was pale and markedly cupped, and the left disk was normal. The maculae were slightly granular. Applanation tonometry was RE : 22, and LE : 18 mm Hg.
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Fig. 3 (Rosenbaum, Chen, and Hoshiwara). Case 5. Leukoma, LE, secondary to measles.
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Case 7—A 62-year-old Papago woman was seen October 26, 1967, because of decreased vision. An adequate history, even through in interpreter, was difficult to obtain. She denied any trauma or in flammation of her eyes. Visual acuity in her right eye was counting fingers, and in her left eye, hand motion at three feet. She had adherent leukomas with superficial wedges of vessels extending from the right limbus at five o'clock and in the left eye, at six and nine o'clock. (Fig. 4). The right fundus showed a temporal crescent to the disk, but was otherwise normal. The left fundus could not be seen. Intraocular pressure was R E : 7/5.5 and LE: 3/5. On December 20, 1967, she was presented to our Division of Indian Health consultant, who said the patient had had phlyctenular keratoconjunctivitis with perforations of both corneas secon dary to that disease. Case 8—A 43-year-old Hopi woman was seen on January 8, 1968, because of "black spots" before her right eye. She gave a history of having had poor vision in her left eye for a long time. Cor rected visual acuity was RE: 20/30, and LE: count ing fingers. The left pupil was tear shaped, pointing interiorly. On slit lamp examination, her left eye showed a wedge of vessels with superficial scarring, and a dense adherent leukoma inferiorly. The right fundus was normal, but the left fundus could not be seen. Case 9—A 24-year-old Pima woman was seen on January 30, 1968, to check the prosthesis replacing her right eye. In the winter of 1950, the patient was treated for "gonorrhea of the eye" at the Sacaton Indian Hospital. In November, 1951, she was ad mitted to the Phoenix Indian Hospital. The admis sion workup said the doctor had been unable to get a history from the patient, but noted "bilateral corneal ulcers from the old record." (The record to which he referred is not available now.) The blind right eye was enucleated at that time "for cosmetic
863
reasons," and the globe was sent to the National Institutes of Health (S-32619). The pathology re port described "a 3 x 2-mm bulging corneal opacity grossly." The microscopic section revealed "promi nent anterior adhesion of the iris to the periphery of the cornea. At this site there is focal scarring involving the iris and the cornea, spillage of mela nin pigment into the scar tissue, slightly increased vascularity, and a slight infiltration of lymphocytes and macrophages" (Fig. 5). Corrected left visual acuity was 20/40. The pupil was peaked downward, and a dense adherent leukoma was present inferi orly. The fundus was normal (Fig. 6). Case 10—An eight-year-old Pima boy was first admitted in December, 1962, at the age of three; years. He had been treated at the Sacaton Indian Hospital for a red left eye for two weeks with tetracycline (Achromycin) ointment. When he re turned to this hospital, his left eye was noted to have a corneal opacity, and he was referred to the Phoe nix Indian Hospital. The mother denied any knowl edge of trauma to her son's eye, but admitted that the boy sometimes played with sticks around the house. The cornea showed an irregular central opac ity, approximately 5 mm in diameter, with marked temporal pannus, and a central necrotic area. Cor neal sensitivity was normal in both eyes. The child was taken to surgery and, under general anesthesia, corneal scrapings were obtained. PeniciHum species fungus was grown on Sabaraud's medium. The boy had been started on topical and systemic antibiotics, but was switched to amphotericin B drops every hour. Over the next four days the ulcer improved markedly, and one week later was completely reepithelialized. Because of a "leash of vessels" tem porally, phlyctenular disease was considered as the basic etiology, but was felt to be atypical and the consideration was dismissed. A large central leuko ma developed, and on February 28, 1963, a lamellar transplant was performed ; it was 8 mm in diameter, and 0.5 mm thick. The corneal button was sent to
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Fig. 4 (Rosenbaum, Chen, and Hoshiwara). Case 7. Leukoma secondary to phlyctenular keratoconjunctivitis.
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AMERICAN JOURNAL OF OPHTHALMOLOGY
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Fig. S (Rosenbaum, Chen, and Hoshiwara). Case 9. Histologie section of LE. Leukoma secondary to bacterial ulcer (hematoxylin-eosin, XlS). the National Institute of Health (S-60147). The microscopic description reported "the corneal stroma is vascularized and infiltrated with a few round cells, Bowman's membrane is absent, and the epithelial surface shows a loss of regular orientation of cells." Postoperatively, the child did well for two months, but the graft then became cloudy. Steroids were
used without benefit. He was lost to followup for two years, and when next seen, his visual acuity was RE: 20/20, and L E : 20/60. Sixteen months later he returned because of blurred vision and a red left eye. The graft was cloudy with bullous keratopathy. The anterior chamber was normal. Culture and scrappings were negative. The patient was begun on
Fig. 6 (Rosenbaum, Chen, and Hoshiwara). Case 9. Leukoma, LE, secondary to bacterial ulcer.
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chloramphenicol and dexamethasone drops in his left eye, and prednisone systemically. The bullous keratopathy cleared, but the scarring in the graft and recipient stroma remained. His acuity is L E : 7/100. Case 11—A 45-year-old Papago man was seen October 10, 1967, for routine examination. He had had trachoma as a child and both eyes had corneal ulcers. He denied any trauma. Corrected visual acuity was RE : 20/80, LE : 20/60. He had Stage IV trachoma with 3-mm pannus superiorly and 1+ scarring of the upper eyelids in both eyes. The right eye had a 3.5-mm, central leukoma with superficial vessels coming from the limbus at 11 o'clock, and pigment granules on the endothelial surface. The left cornea was similar, except the leu koma was 2.5 mm in diameter, slightly nasal to the optic axis. The anterior chamber and iris were nor mal. Nuclear sclerosis was present bilaterally. The right fundus could not be seen; the left fundus was normal. The intraocular tension was normal in both eyes. Case 12—A 62-year-old Papago woman was first seen in November, 1966, because of decreased vision in both eyes. At that time she had visual acuity of RE: 20/200, and L E : 20/300. Bilateral cataracts, bilateral central corneal opacities, and bilateral macular degeneration were noted. She was seen in August, 1967, and her vision had diminished to counting fingers in both eyes. The corneas had not changed. However, in October, 1967, the left cornea was found to be markedly thinned centrally with an impending descemetocele. There were no signs of inflammation. The intraocular pressure was normal
in both eyes. She denied any history of arthritis. Complete blood count, urinalysis, serology, blood urea nitrogen, and fasting blood sugar were within normal limits. On November 10, 1967, she had a 7mm lamellar transplant in her left eye. The corneal button was sent to the University of California De partment of Ophthalmic Pathology (EP-67-934). The report of the microscopic examination stated: "The corneal epithelium showed thinning centrally, but in the center of the thinned area there is a focal area of thickening. Bowman's membrane shows areas of fraying and fragmentation centrally. The corneal stroma shows superficial scarring throughout and an area of marked thinning cen trally" (Fig. 7). The graft has remained clear, but when last seen there was questionable thinning be ginning in the other eye. Case 13—A 17-year-old Papago boy was re ferred for a refraction. He had been aware of a white spot on his right eye for several years. He denied any history of trauma or inflammation. Cor rected visual acuity was RE: 20/60 and LE: 20/25. He had a right tear drop pupil with the iris adherent to a 2.0-mm leukoma centrally just below the visual axis (Fig. 8). The rest of the examina tion was within normal limits. COMMENT
Congenital leukomata can be either ectodermal or mesodermal in origin. The former type is associated with congenital cataracts. It is the result of "a failure or delay in the separation of the lens vesicle from the sur-
Fig. 7 (Rosenbaum, Chen, and Hoshiwara). Case 12. Histologie section of corneal button, LE Leukoma of unknown origin (hematoxylin-eosin, X64).
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Fig. 8 (Rosenbaum, Chen, and Hoshiwara). Case 13. Leukoma of unknown origin. face epithelium.1" The latter type, which is most typical, is "a dense white diskoid cen tral or paracentral lesion in the deeper parts of the stroma associated with adherent rem nants of the pupillary membrane or anterior synechiae whereby the iris is firmly linked up with the opacity.1" Our cases 1 and 4 seem to be a combination of ectodermal and mesodermal origin. Intrauterine inflamma tion limited to the anterior segment is an other possible cause of this picture. The relatively high incidence of congenital leukomas in our population may be accounted for by intermarriage among members of the var ious Indian tribes and groups, thus produc ing a higher gene frequency in our popula tion. Those patients with congenital leukomas had severe amblyopia, as one would expect. Those with acquired leukomas, and without other causes of decreased vision, had reason ably good and useful vision. Case 5 is espe cially interesting since the onset of this pa tient's visual problem dates from the age of three years, and her acuity was compatible with the view with an ophthalmoscope. Cases 1 and 4, which were of congenital origin, had much poorer vision than the view with an oph
thalmoscope. This information supports von Noorden's concept of "stimulus deprivation amblyopia,2" and Picetti and Fine's 3 recom mendation of keratoplasty for corneal opaci ties before the age of three years. Systemic viral infections may involve the cornea. Measles commonly produces a super ficial punctate keratitis, which causes photo phobia. Duke-Elder states that corneal com plications such as ulcération have occurred in certain Africans.4 Cases 5 and 6 are the first cases of measles causing corneal perfor ation reported in this country. The measles vaccine will hopefully make these lesions of historical interest only. Mumps may involve the cornea, usually unilaterally, and may as sume the form of an interstitial infiltrate, which may progress rapidly to a thickened, opaque cornea or just a central opaque disk. Ulcération, leaving a central leukoma, has been reported.5 Smallpox may produce a similar result.5 In severe, deep scrofulous form of phlyctenular keratoconjunctivitis, suppuration de velops with extensive necrosis. If secondary infection occurs, perforation may result.4 Cases 7 and 8 are illustrations of the severe complications which may occur in this dis-
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ease. Rarely, an ulcer may result from the breakdown of old leukomatous scars, and proceed to perforation.4 "Melting away" of the corneal stroma has been associated with several of the collagen diseases.0-8 Topical steroids may accelerate this process. Neither Case 12 nor 13 had a history or signs of arthritis, nor had they re ceived steroid therapy. The process which produced bilateral, symmetrical involvement in Case 12 remains a mystery. Cases 9 and 11 were also bilateral, and relatively symmetri cal, but were attributed to bacterial ulcéra tion primarily, although they may have been secondarily infected, and the basic problem remains unknown. Case 13, which had an absence of vascularization, and relatively good acuity, is one of unilateral idiopathic origin. One cannot rule out an ulcer of bacterial origin which progressed to perfora tion so rapidly that vascularization did not occur. Such a virulent process, untreated, would be unlikely to leave an eye with as good an acuity as in this case. Finally, patients with adherent leukomas should be gonioscoped in order to evaluate the patency of the anterior chamber angle. Even though the pupil cannot dilate, and the usual sequence of occlusion of the anterior chamber angle seem likely, Case 5 proves it can hap pen. The growth of the lens probably ac counts for the mechanism, whereby the iris is displaced and encroaches on the angle.
SUMMARY
Thirteen cases of nontraumatic corneal leukoma are discussed. They have been clas sified as congenital, as secondary to systemic disease (i.e. measles), as secondary to lo cal disease (i.e., phlyctenular keratoconjunctivities, bacterial ulcers, and fungal ul cers), and as idiopathic. Early corneal trans plantation is necessary to prevent amblyopia in congenital cases. Presence of narrowangle glaucoma must be considered. ACKNOWLEDGMENTS
We thank Dr. Phillips Thygeson for examining the patient reported in Case 7, and Dr. Bernard Becker for reviewing the manuscript. REFERENCES
1. Duke-Elder, S. : System of Ophthalmology, vol. 3. Mosby, St. Louis, 1965, p. SIS. 2. Von Noorden, G., and Maumenee, A., : Clinical observations on stimulus-deprivation amblyopia (amblyopia ex anopsia). Am. J. Ophth. 65:220, 1968. 3. Picetti, B., and Fine, M. : Keratoplasty in chil dren. Am. J. Ophth. 61:782, 1966. 4. Duke-Elder, S.: System of Ophthalmology. vol. 8. Mosby, St. Louis, 1965, pp. 33S, 470. 5. Thomas, C: The Cornea. Thomas, Springfield. Illinois, 1955, pp. 635, 638, 422. 6. Anderson, B. : Ocular lesions in relapsing polychondritis and other rheumatoid syndromes. Am. J. Ophth. 64:35, 1967. 7. Hogan, M., and Zimmerman, L. : Ophthalmic Pathology. Saunders, Philadelphia, 1962, p. 339. 8. Barth, W., and Berson, E. : Relapsing poly chondritis, rheumatoid arthritis, and blindness. Am. J. Ophth. 66:890, 1968.
AMERICAN JOURNAL OF OPHTHALMOLOGY
3. de Roetth, A., Jr. : Lens opacities in glaucoma patients on phospholine iodide therapy, Am. J. Ophth. 62:619, 1966. 4. Shaffer, R. N., and Hetherington, J. Jr. : Anticholinesterase drugs and cataracts. Am. J. Ophth. 62:613, 1966. 5. Torkkanen, A., and Karjalainen, K. : Cataract formation during miotic treatment for chronic open-angle glaucoma. Acta Ophth. 44:932, 1966. 6. Thoft, R. A. : Incidence of lens changes in pa tients treated with echothiophate iodide. Arch. Ophth. 80:317, 1966. 7. Harrison, R. : Bilateral lens opacities asso ciated with use of di-isopropyl fluorophosphate eyedrops. Am. J. Ophth. 50:153, 1960. 8. Axelsson, U., and Holmberg, A. : The fre quency of cataract after miotic therapy. Acta Ophth. 44:421, 1966. 9. Michon, J., Jr., and Kinoshita, J. H. : Cholines terase in the lens. Arch. Ophth. 77 :804, 1967. 10. Michon, J., Jr., and Kinoshita, J. H. : Experi mental miotic cataract. Effects of miotics on lens structure, cation content and hydration. Arch. Ophth. 79:79, 1968.
MAY, 1970
11. Haddad, H. M., Shore, B., Furman, M., and Okas, S. : Lens organ culture TT. Am. J. Ophth. 63:6, 1967. 12. Diamant, H. : Cataract due to cholinesterase inhibitors in the guinea pig. Acta Ophth. 32 :357, 1954. 13. Grant, W. M. : Toxicology of the Eye. Springfield, Illinois, Thomas, 1962, p. 369. 14. Fraunfelder, F. T., and Burns, R. P. : Effect of lid closure in drug-induced experimental cata racts. Arch. Ophth. 76:599,1966. 15. Fraunfelder, F. T., and Burns, R. P.: Produc tion of unilateral reversible cataracts in the ham ster. Proc. Soc. Exp. Biol. Med. 110:72, 1962. 16. Goldmann, H., and Rabinowitz, G. : Ueber eine unbekannte, reversible Kataraktform bei jun gen Ratten. Klin. Mbl. Augenheilk. 81:771, 1928. 17. Weinstock, M., and Scott, J. D. : Effect of various agents on drug-induced opacities of the lens. Exp. Eye Res. 6:368, 1967. 18. Lazar, M. : Mannitol in ophthalmic prepara tions. In New Orleans Academy of Ophthalmology Symposium on Ocular Pharmacology and Thera peutics. To be published.
NONTRAUMATIC
LEUKOMAS
L o u i s J. R O S E N B A U M , M.D., J O H N C H E N , M.D., A N D ISAO H O S H I W A R A , M . D .
Phoenix, Arizona Nontraumatic leukomas are relatively rare among the lesions encountered in the usual ophthalmologic office. However, in the past year, we have seen 13 at the Phoenix Indian Hospital, where the patient population is comprised of Indians of all tribes from Ari zona, Utah, Nevada, and southern Califor nia. Four etiologies have been established for these leukomas: congenital, secondary to systemic disease, secondary to local disease, and idiopathic (Table 1). CASE REPORTS
Case 1—A 63-year-old Apache man was seen February 29, 1968, for a routine examination. Visual acuity was RE: 20/200, LE: 20/50. In his right eye, in which he had had poor vision all his life, he had a From the Ophthalmology Service, Phoenix Medi cal Center and the Trachoma Control Unit, Indian Health Service, U.S. Public Health Service. This paper was read before the Section of Ophthalmol ogy, Public Health Service Clinical Society Meet ing, June 3,1969. Reprint requests to Louis J. Rosenbaum, M.D., 777 East Brill, Phoenix, Arizona 85006.
2.5-mm dense leukoma slightly nasal to the pupil lary area with iris adherent to the posterior sur face of the cornea. The right lens had a dense central anterior polar cataract. The fundi and in traocular tension were normal in both eyes (Fig. 1). Case 2—A 17-year-old Pima girl, first seen in June, 1953, was found to have a comeal scar in her left eye present since birth, and a left exotropia. During the next six months, she had strabis mus surgery, and a tattoo of the left cornea for cosmetic reasons. She was next seen January 31, 1968, because of decreased visual acuity in her right eye. Refraction was RE: —3.25 = + 2 . 0 0 X 80, 20/30; in her left eye she had light perception only. The left eye was noted to be microphthalmic. She was orthophoric by the Krimsky test, but had an intermittant horizontal nystagmus, TABLE 1 CLASSIFICATION OF NONTRAUMATIC LEUKOMAS
Classification Congenital Secondary to systemic disease Secondary to local disease Idiopathic
No. Cases 4 2 5 2
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greatest on left gaze. Ductions were full. There was a dense, central leukoma, 3.S mm in diameter, with superficial pigment deposition overlying it. The iris was adherent to the leukoma so that no pupil was apparent. The fundus was normal in the right eye.
stroma with iris adherent, just nasal to the pupil lary area. Slightly temporal was a superficial stromal, round, 2.0-mm opacity. A large vessel ran from the limbus at four o'clock to both lesions. A dense anterior polar cataract was present in his left eye.
Case 3—A 10-month-old Pima girl, product of a full-term pregnancy and normal delivery, was seen July 17, 1967, because of a white spot on her left eye since birth. Examination under general anesthesia showed a deep central opacity of the left cornea, approximately 4 mm. in diameter. Corneal diameters were R E : 11.S mm, and L E : 10.5. The right fundus was normal. The left fundus could not be seen. Intraocular pressure was nor mal.
Case 5—A 41-year-old Papago woman gave a history of scarring of both eyes since the age of three years, following measles. She had had progressive loss of vision in the left eye, and it had lost light perception five years earlier. She was first seen October 12, 1967. Visual acuity was RE: 20/60 with correction. Slit lamp examination showed dense leukomas, 4.0-mm in diameter inferiorly in both eyes, with both irises adherent to the posterior surface. The left eye also had epithelial edema. The fundi could not be seen in either eye. Intraocular pressure was 2/5.5, 6/10, RE ; 0/10, LE. On gonioscopy, two-thirds of the angle in the right eye was sealed, and the rest of the angle was Grade 1 ; the angle was completely sealed in the left eye. Central fields in the right eye were within normal limits. The patient was begun on pilocarpine, 2%, and acetazolamide (Diamox), 250 mg, every six hours, and the pressure became normal. Tonography showed Po 20 mm Hg and C 0.18. The patient had a right sector iridectomy. Postoperatively, the right fundus could be seen, and the disk was thought to have early, shallow cupping (Figs. 2 and 3).
Case 4—A 15-year-old Apache boy was first noted to have a left corneal opacity at the age of two, according to his chart. He was the product of a full term pregnancy and a normal delivery. He denied any history of trauma or inflammation when he was seen on October 10, 1968. At that time, he had a visual acuity of RE: 20/20, and L E : 20/200. The left pupil was slightly distorted nasally, but reacted to light. He had 20 prism di opters of left esotropia. Ductions were full. Fundi were normal in both eyes. Slit lamp examination showed a dense, round 2-mm leukoma in the deep
.tlf|fe'»k!^
Fig. 1 (Rosenbaum, Chen, and Hoshiwara). Case 1. Congenital leukoma, also anterior polar cataract.
862
AMERICAN JOURNAL OF OPHTHALMOLOGY
MAY, 1970
fg\Kv' ■
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. 'Ψ ^
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Fig. 2 (Rosenbaum, Chen, and Hoshiwara). Case 5. Leukoma, RE, secondary to measles. Case 6—A 72-year-old Pima woman gave a his tory of having had measles when she was a little girl, which her doctor told her had caused the scars on her eyes. Intracapsular cataract surgery had been performed on her right eye in January, 1963, but a flat anterior chamber developed five weeks later. The intraocular pressure was 59 mm Hg, and gonioscopy showed the angle to be sealed except be tween three and five o-clock, and between eight and 10 o'clock. Unfortunately, no record of preoperative intraocular pressure or gonioscopy could be found. The glaucoma could not be controlled medically after the anterior chamber was reformed surgically. In April, 1963, she had a cyclodialysis, which re
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duced the tension to the mid-twenties. Pilocarpine, 2%, four times a day, brought the intraocular pres sure to the mid-teens. In April, 1964, an intracapsu lar cataract extraction performed on her left eye was successful. When seen on July 7, 1968, visual acuity was RE : hand motion, LE : 20/80. Slit lamp examination showed dense leukomas inferior-temporally in both eyes, with iris adherent to the endothelial surface of the cornea in both. The anterior chamber was deep elsewhere. The vitreous face was broken in both eyes. The right disk was pale and markedly cupped, and the left disk was normal. The maculae were slightly granular. Applanation tonometry was RE : 22, and LE : 18 mm Hg.
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Fig. 3 (Rosenbaum, Chen, and Hoshiwara). Case 5. Leukoma, LE, secondary to measles.
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Case 7—A 62-year-old Papago woman was seen October 26, 1967, because of decreased vision. An adequate history, even through in interpreter, was difficult to obtain. She denied any trauma or in flammation of her eyes. Visual acuity in her right eye was counting fingers, and in her left eye, hand motion at three feet. She had adherent leukomas with superficial wedges of vessels extending from the right limbus at five o'clock and in the left eye, at six and nine o'clock. (Fig. 4). The right fundus showed a temporal crescent to the disk, but was otherwise normal. The left fundus could not be seen. Intraocular pressure was R E : 7/5.5 and LE: 3/5. On December 20, 1967, she was presented to our Division of Indian Health consultant, who said the patient had had phlyctenular keratoconjunctivitis with perforations of both corneas secon dary to that disease. Case 8—A 43-year-old Hopi woman was seen on January 8, 1968, because of "black spots" before her right eye. She gave a history of having had poor vision in her left eye for a long time. Cor rected visual acuity was RE: 20/30, and LE: count ing fingers. The left pupil was tear shaped, pointing interiorly. On slit lamp examination, her left eye showed a wedge of vessels with superficial scarring, and a dense adherent leukoma inferiorly. The right fundus was normal, but the left fundus could not be seen. Case 9—A 24-year-old Pima woman was seen on January 30, 1968, to check the prosthesis replacing her right eye. In the winter of 1950, the patient was treated for "gonorrhea of the eye" at the Sacaton Indian Hospital. In November, 1951, she was ad mitted to the Phoenix Indian Hospital. The admis sion workup said the doctor had been unable to get a history from the patient, but noted "bilateral corneal ulcers from the old record." (The record to which he referred is not available now.) The blind right eye was enucleated at that time "for cosmetic
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reasons," and the globe was sent to the National Institutes of Health (S-32619). The pathology re port described "a 3 x 2-mm bulging corneal opacity grossly." The microscopic section revealed "promi nent anterior adhesion of the iris to the periphery of the cornea. At this site there is focal scarring involving the iris and the cornea, spillage of mela nin pigment into the scar tissue, slightly increased vascularity, and a slight infiltration of lymphocytes and macrophages" (Fig. 5). Corrected left visual acuity was 20/40. The pupil was peaked downward, and a dense adherent leukoma was present inferi orly. The fundus was normal (Fig. 6). Case 10—An eight-year-old Pima boy was first admitted in December, 1962, at the age of three; years. He had been treated at the Sacaton Indian Hospital for a red left eye for two weeks with tetracycline (Achromycin) ointment. When he re turned to this hospital, his left eye was noted to have a corneal opacity, and he was referred to the Phoe nix Indian Hospital. The mother denied any knowl edge of trauma to her son's eye, but admitted that the boy sometimes played with sticks around the house. The cornea showed an irregular central opac ity, approximately 5 mm in diameter, with marked temporal pannus, and a central necrotic area. Cor neal sensitivity was normal in both eyes. The child was taken to surgery and, under general anesthesia, corneal scrapings were obtained. PeniciHum species fungus was grown on Sabaraud's medium. The boy had been started on topical and systemic antibiotics, but was switched to amphotericin B drops every hour. Over the next four days the ulcer improved markedly, and one week later was completely reepithelialized. Because of a "leash of vessels" tem porally, phlyctenular disease was considered as the basic etiology, but was felt to be atypical and the consideration was dismissed. A large central leuko ma developed, and on February 28, 1963, a lamellar transplant was performed ; it was 8 mm in diameter, and 0.5 mm thick. The corneal button was sent to
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Fig. 4 (Rosenbaum, Chen, and Hoshiwara). Case 7. Leukoma secondary to phlyctenular keratoconjunctivitis.
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Fig. S (Rosenbaum, Chen, and Hoshiwara). Case 9. Histologie section of LE. Leukoma secondary to bacterial ulcer (hematoxylin-eosin, XlS). the National Institute of Health (S-60147). The microscopic description reported "the corneal stroma is vascularized and infiltrated with a few round cells, Bowman's membrane is absent, and the epithelial surface shows a loss of regular orientation of cells." Postoperatively, the child did well for two months, but the graft then became cloudy. Steroids were
used without benefit. He was lost to followup for two years, and when next seen, his visual acuity was RE: 20/20, and L E : 20/60. Sixteen months later he returned because of blurred vision and a red left eye. The graft was cloudy with bullous keratopathy. The anterior chamber was normal. Culture and scrappings were negative. The patient was begun on
Fig. 6 (Rosenbaum, Chen, and Hoshiwara). Case 9. Leukoma, LE, secondary to bacterial ulcer.
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chloramphenicol and dexamethasone drops in his left eye, and prednisone systemically. The bullous keratopathy cleared, but the scarring in the graft and recipient stroma remained. His acuity is L E : 7/100. Case 11—A 45-year-old Papago man was seen October 10, 1967, for routine examination. He had had trachoma as a child and both eyes had corneal ulcers. He denied any trauma. Corrected visual acuity was RE : 20/80, LE : 20/60. He had Stage IV trachoma with 3-mm pannus superiorly and 1+ scarring of the upper eyelids in both eyes. The right eye had a 3.5-mm, central leukoma with superficial vessels coming from the limbus at 11 o'clock, and pigment granules on the endothelial surface. The left cornea was similar, except the leu koma was 2.5 mm in diameter, slightly nasal to the optic axis. The anterior chamber and iris were nor mal. Nuclear sclerosis was present bilaterally. The right fundus could not be seen; the left fundus was normal. The intraocular tension was normal in both eyes. Case 12—A 62-year-old Papago woman was first seen in November, 1966, because of decreased vision in both eyes. At that time she had visual acuity of RE: 20/200, and L E : 20/300. Bilateral cataracts, bilateral central corneal opacities, and bilateral macular degeneration were noted. She was seen in August, 1967, and her vision had diminished to counting fingers in both eyes. The corneas had not changed. However, in October, 1967, the left cornea was found to be markedly thinned centrally with an impending descemetocele. There were no signs of inflammation. The intraocular pressure was normal
in both eyes. She denied any history of arthritis. Complete blood count, urinalysis, serology, blood urea nitrogen, and fasting blood sugar were within normal limits. On November 10, 1967, she had a 7mm lamellar transplant in her left eye. The corneal button was sent to the University of California De partment of Ophthalmic Pathology (EP-67-934). The report of the microscopic examination stated: "The corneal epithelium showed thinning centrally, but in the center of the thinned area there is a focal area of thickening. Bowman's membrane shows areas of fraying and fragmentation centrally. The corneal stroma shows superficial scarring throughout and an area of marked thinning cen trally" (Fig. 7). The graft has remained clear, but when last seen there was questionable thinning be ginning in the other eye. Case 13—A 17-year-old Papago boy was re ferred for a refraction. He had been aware of a white spot on his right eye for several years. He denied any history of trauma or inflammation. Cor rected visual acuity was RE: 20/60 and LE: 20/25. He had a right tear drop pupil with the iris adherent to a 2.0-mm leukoma centrally just below the visual axis (Fig. 8). The rest of the examina tion was within normal limits. COMMENT
Congenital leukomata can be either ectodermal or mesodermal in origin. The former type is associated with congenital cataracts. It is the result of "a failure or delay in the separation of the lens vesicle from the sur-
Fig. 7 (Rosenbaum, Chen, and Hoshiwara). Case 12. Histologie section of corneal button, LE Leukoma of unknown origin (hematoxylin-eosin, X64).
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Fig. 8 (Rosenbaum, Chen, and Hoshiwara). Case 13. Leukoma of unknown origin. face epithelium.1" The latter type, which is most typical, is "a dense white diskoid cen tral or paracentral lesion in the deeper parts of the stroma associated with adherent rem nants of the pupillary membrane or anterior synechiae whereby the iris is firmly linked up with the opacity.1" Our cases 1 and 4 seem to be a combination of ectodermal and mesodermal origin. Intrauterine inflamma tion limited to the anterior segment is an other possible cause of this picture. The relatively high incidence of congenital leukomas in our population may be accounted for by intermarriage among members of the var ious Indian tribes and groups, thus produc ing a higher gene frequency in our popula tion. Those patients with congenital leukomas had severe amblyopia, as one would expect. Those with acquired leukomas, and without other causes of decreased vision, had reason ably good and useful vision. Case 5 is espe cially interesting since the onset of this pa tient's visual problem dates from the age of three years, and her acuity was compatible with the view with an ophthalmoscope. Cases 1 and 4, which were of congenital origin, had much poorer vision than the view with an oph
thalmoscope. This information supports von Noorden's concept of "stimulus deprivation amblyopia,2" and Picetti and Fine's 3 recom mendation of keratoplasty for corneal opaci ties before the age of three years. Systemic viral infections may involve the cornea. Measles commonly produces a super ficial punctate keratitis, which causes photo phobia. Duke-Elder states that corneal com plications such as ulcération have occurred in certain Africans.4 Cases 5 and 6 are the first cases of measles causing corneal perfor ation reported in this country. The measles vaccine will hopefully make these lesions of historical interest only. Mumps may involve the cornea, usually unilaterally, and may as sume the form of an interstitial infiltrate, which may progress rapidly to a thickened, opaque cornea or just a central opaque disk. Ulcération, leaving a central leukoma, has been reported.5 Smallpox may produce a similar result.5 In severe, deep scrofulous form of phlyctenular keratoconjunctivitis, suppuration de velops with extensive necrosis. If secondary infection occurs, perforation may result.4 Cases 7 and 8 are illustrations of the severe complications which may occur in this dis-
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ease. Rarely, an ulcer may result from the breakdown of old leukomatous scars, and proceed to perforation.4 "Melting away" of the corneal stroma has been associated with several of the collagen diseases.0-8 Topical steroids may accelerate this process. Neither Case 12 nor 13 had a history or signs of arthritis, nor had they re ceived steroid therapy. The process which produced bilateral, symmetrical involvement in Case 12 remains a mystery. Cases 9 and 11 were also bilateral, and relatively symmetri cal, but were attributed to bacterial ulcéra tion primarily, although they may have been secondarily infected, and the basic problem remains unknown. Case 13, which had an absence of vascularization, and relatively good acuity, is one of unilateral idiopathic origin. One cannot rule out an ulcer of bacterial origin which progressed to perfora tion so rapidly that vascularization did not occur. Such a virulent process, untreated, would be unlikely to leave an eye with as good an acuity as in this case. Finally, patients with adherent leukomas should be gonioscoped in order to evaluate the patency of the anterior chamber angle. Even though the pupil cannot dilate, and the usual sequence of occlusion of the anterior chamber angle seem likely, Case 5 proves it can hap pen. The growth of the lens probably ac counts for the mechanism, whereby the iris is displaced and encroaches on the angle.
SUMMARY
Thirteen cases of nontraumatic corneal leukoma are discussed. They have been clas sified as congenital, as secondary to systemic disease (i.e. measles), as secondary to lo cal disease (i.e., phlyctenular keratoconjunctivities, bacterial ulcers, and fungal ul cers), and as idiopathic. Early corneal trans plantation is necessary to prevent amblyopia in congenital cases. Presence of narrowangle glaucoma must be considered. ACKNOWLEDGMENTS
We thank Dr. Phillips Thygeson for examining the patient reported in Case 7, and Dr. Bernard Becker for reviewing the manuscript. REFERENCES
1. Duke-Elder, S. : System of Ophthalmology, vol. 3. Mosby, St. Louis, 1965, p. SIS. 2. Von Noorden, G., and Maumenee, A., : Clinical observations on stimulus-deprivation amblyopia (amblyopia ex anopsia). Am. J. Ophth. 65:220, 1968. 3. Picetti, B., and Fine, M. : Keratoplasty in chil dren. Am. J. Ophth. 61:782, 1966. 4. Duke-Elder, S.: System of Ophthalmology. vol. 8. Mosby, St. Louis, 1965, pp. 33S, 470. 5. Thomas, C: The Cornea. Thomas, Springfield. Illinois, 1955, pp. 635, 638, 422. 6. Anderson, B. : Ocular lesions in relapsing polychondritis and other rheumatoid syndromes. Am. J. Ophth. 64:35, 1967. 7. Hogan, M., and Zimmerman, L. : Ophthalmic Pathology. Saunders, Philadelphia, 1962, p. 339. 8. Barth, W., and Berson, E. : Relapsing poly chondritis, rheumatoid arthritis, and blindness. Am. J. Ophth. 66:890, 1968.