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Postoperative Intraocular Aspergillosis*
1124
NOTES, CASES,
INSTRUMENTS patient w a s discharged f r o m the hospital and followed a course of gradual reduction of the steroid therapy until it w a s discontinued. SUMMARY
F i g . 4 ( S o l o m o n , M o s e s and V o l k ) . A f t e r 39 days of steroid therapy, both eyes w e r e normal, e x cept for redundancy of the bulbar conjunctiva. therapy w a s begun on the 37th hospital day. T h e initial dose of prednisone w a s 4 0 mg. on the first day followed by 30 mg. orally each day thereafter. T w o days after the initiation of steroid therapy, there w a s definite reduction of the proptosis and improvement in the extraocular muscle function and in the appearance of the conjunctiva. T h i s improvement continued (fig. 2 ) and, b y the 62nd hospital day, the patient's left eye w a s normal in all respects (fig. 3 ) . W i t h i n the n e x t t w o w e e k s the right eye had completely cleared (fig. 4 ) . T h e
The use of corticosteroids in the treatment of cavernous sinus thrombosis was a useful adjunct to the usual antibacterial and anticoagulant regimen. The patient described in this report progressed from a unilateral to a bilateral cavernous sinus thrombosis with absolute ophthalmoplegia over a sixweek period in spite of vigorous antibiotic and anticoagulant therapy. Improvement began two days after the introduction of corticosteroids into the therapeutic regimen and, in 39 days, both eyes were completely normal. 1020 Huron Road
(15).
REFERENCES
1. M a c N e a l , W . J., and Cavallo, M . E . : J . A . M . A . , 109:2039, 1937. 2. L y o n s , C : A n n . Surg., 1 1 3 : 1 1 3 , 1941. 3. Florey, H . W . , et al.: Lancet, 2:177, 1941.
POSTOPERATIVE INTRAOCULAR ASPERGILLOSIS* MARSHALL
A.
DIAMOND,
Portsmouth,
M.D.
Virginia
AND HAROLD
Oak
Q.
Park,
KIRK,
M.D.
Illinois
A number of intraocular fungus infections following surgical or traumatic perforations of the eyeball have been reported in the recent literature. The infections connected with surgical procedures in the anterior segment follow a characteristic pattern. After a latent period of several weeks, an anterior endophthalmitis develops which temporarily seems
* F r o m the Department of Ophthalmology, U n i versity of Illinois, and the Illinois E y e and E a r Infirmary, Chicago.
to respond to vigorous antibiotic and steroid therapy. A few weeks later, however, a mass of white exudate, either in the anterior chamber or in the anterior vitreous, becomes more and more prominent. This alarming development in the anterior segment may remain for months and is in sharp contrast to an apparent state of uninvolvement of the posterior segment, as evidenced by good light perception and projection. The hopelessness of the disease is not realized until quite late in its course. When severe pain sets in and persists, together with loss of all useful vision, the patient usually consents or requests enucleation. The case reported here is one of similar disastrous outcome but most unusual in that the site of the pathologic process was within the posterior ocular coats and was without endophthalmitis.
NOTES, CASES, CASE
INSTRUMENTS
1125
REPORT
T h i s 72-year-old white man w a s first seen at the Illinois E y e and E a r Infirmary in N o v e m b e r , 1959, with the history of bilateral, painless gradual decrease in vision for several years. T h e u n corrected visual acuity of his right eye w a s 1 0 / 2 0 0 m d 2 0 / 1 0 0 + 1 with a pinhole. T h e vision of the eft eye w a s excellent light projection with hand movements. T h e visual impairment w a s attributed to senile cataracts, moderately advanced in the right :ye and mature in the left eye. T h e other ocular î n d i n g s were within normal limits. General e x a m i nation revealed moderate pulmonary emphysema m d loss of the right l o w e r extremity through trauma many years before. O n N o v e m b e r 23, 1959, an intracapsular lens extraction with full iridectomy w a s performed on the left eye. T h e operation and the recovery w e r e uneventful, w i t h 2 0 / 5 0 — 2 visual acuity through a plus-10 lens and a pinhole, one w e e k postoperatively. T h e patient's left e y e w a s found to be in g o o d condition w h e n he again entered the hospital s i x w e e k s later. O n January 11, 1960, an intracapsular lens extraction with full iridectomy w a s performed on the right eye. T h i s included a superior limbusbased conjunctival flap, t w o preplaced corneoscleral black-silk sutures of the M c L e a n type, and delivery of the lens by tumbling w i t h an erisophake. A prophylactic subconjunctival injection of penicillin and streptomycin w a s given at the conclusion of the procedure. D u r i n g the n e x t five days the postoperative course appeared to be normal. O n the sixth postoperative day, a small hyphema w a s noted. T h e patient stated that another patient had bumped against his e y e shield on the d a y before. T h e hyphema absorbed rapidly e x c e p t f o r a small strand of clot located temporally but, on the 15th postoperative day, a flat chamber w i t h an e x t e n s i v e choroidal detachment w a s noted. Treatment during the immediate postoperative period had included moderate mydriasis but, w h e n the anterior chamber became shallow, the e y e w a s vigorously dilated ( u p t o nine m m . ) and local steroids w e r e started. N e o s p o r i n solution had been given daily. T h e sutures w e r e removed on the 15th postoperative day. Since the anterior chamber w a s flat, a posterior sclerotomy w a s performed on the 18th postoperative day in the inferotemporal quadrant; it yielded a considerable amount of serous suprachoroidal fluid. T h e chamber w a s restored by air injection. A l t o gether five instrument entries w e r e made into the interior and posterior eyeball. Subconjunctival i n jections of pilocarpine ( f o u r percent) and penicillin-streptomycin w e r e the terminal steps. S i x days f o l l o w i n g this procedure the chamber w a s again flat e x c e p t w h e r e a small amount o f injected air remained. E x p l o r a t i o n of the cataract incision revealed a questionable g a p w h i c h w a s closed by n e w sutures. T h i s operation included reopening and release of m o r e suprachoroidal fluid; air and saline were injected into the anterior c h a m -
F i g . 1 ( D i a m o n d and K i r k ) . A n approximately vertical section, s h o w i n g location and extent of the granulomatous process.
ber. B o t h w o u n d sites w e r e e x p o s e d this time. A g a i n a subconjunctival injection of penicillinstreptomycin w a s given. D u r i n g the n e x t t w o and one-half months, the anterior chamber w a s gradually restored to a c o m parative phakic depth and the choroidal detachment w a s reduced. In the region of the original cataract incision the epibulbar tissues, a s well a s the scleral w o u n d lip, became the site of a gradual s l o u g h i n g process, first e x p o s i n g the deeper sclera and finally a n e x t r e m e l y thin fibrous layer coveri n g the anterior uvea. T h i s s l o u g h i n g process w a s associated with a persistent mucopurulent to chalky secretion. V i g o r o u s therapy w i t h both local and systemic antibiotics (Chloromycetin, terramycin, neosporin and e r y t h o m y c i n ) had n o demonstrable effect on the s l o u g h i n g process. T h e tension remained normal and the pupil became partially bound d o w n by posterior synechias. T h e left e y e remained in g o o d condition. S i x w e e k s a f t e r the third surgical procedure one attempt w a s made to culture f u n g i f r o m the external secretions o n Sabouraud media ; n o g r o w t h of a n y kind w a s obtained but some gram-positive cocci w e r e found. O n M a y 17, 1960, four months after the original lens extraction, the scleral d e f e c t had reached a size of 15 by 11 m m . A f e w l a r g e conjunctival vessels had g r o w n into the thin fibrous layer that w a s covering the ciliary body at the bottom of the defect. T h e fundus could be seen clearly. T h e visual acuity of the right eye w a s 2 0 / 7 0 + 2 with + 1 0 D . sph. and a pinhole. T h e ocular tension w a s low. I n June, 1960, the patient w a s readmitted for repair of the scleral d e f e c t by conjunctivoplasty. T h i s w a s performed o n June 7th, mobilizing the upper bulbar and f o r n i x conjunctiva as much as possible. In this manner a thick, apparently healthy
1126
NOTES, CASES,
INSTRUMENTS had w o r k e d s o well, repair o f the lower scleral ulcers b y conjunctivoplasty w a s considered f o r several days. V i s i b l e day-to-day w o r s e n i n g of the scleral disease together w i t h posterior exudation made this plan seem futile. N e w developments were noted in the posterior segment through the n o w diffusely hazy vitreous. A localized large chorioretinal elevation could be seen b e l o w the disc, with numerous horizontal ripples in the o v e r l y i n g retina. V i s i o n had dropped to 3 / 2 0 0 with a -f-lOD. sph. and with and without pinhole. A number of attempts to g r o w micro-organisms f r o m the scleral exudate again failed.
Fig. 2
( D i a m o n d and K i r k ) . H y p h a e in well-preserved sclera.
fairly
flap w a s brought over the defect and sutured to the cornea. Radial incisions of the flap w e r e necessary to lessen the tension created. B e f o r e the sutures w e r e tied the area of defect w a s scraped with a BardP a r k e r knife and Gill dissector. Penicillin and streptomycin w e r e a g a i n injected subconjunctivally below. U p o n discharge 13 days later, the flap appeared uniformly hyperemic and adherent to the defect e x cept j u s t adjacent to the limbus w h e r e it had retracted slightly upward in several areas. T h e sticky mucopurulent discharge w a s still p r e s e n t A s o n previous admissions, blood count, urinalysis and serology w e r e normal. T w o m o r e cultures of the exudate failed to reveal significant g r o w t h . T w o months later w h e n seen in the out-patient department the scleral defect w a s well covered and the e y e showed moderately active chronic anterior uveitis. T r e a t m e n t with topical antibiotic, steroid and mydriatic solutions w a s restarted. A b o u t the middle of October, 1960, marked pain began behind and above the right eye. It persisted with slightly v a r y i n g severity until the time of the enucleation. B y December, 1960, a n e w development w a s seen in the lower half of the globe. A g a i n s t the background of the deep red t o purplish Tenon's capsule, three distinct scleral ulcers had formed, exuding a gritty w h i t e material. T h e right e y e had become proptosed and its m o v e m e n t down and out w a s limited. T h e visual acuity w a s 2 0 / 2 0 0 w i t h -(-10D. sph. and pinhole. T h e ocular tension w a s low. T h e r e w a s still only a moderate degree of anterior uveitis. T h e fundus could be seen fairly well, the undulating slightly opacified anterior vitreous face being the principal optical barrier. On fourth count, normal
D e c e m b e r 7th, the time of the patient's admission to the hospital, complete blood urinalysis and serology w e r e still within limits. S i n c e the earlier conjunctivoplasty
A scleral biopsy f r o m the edge of o n e of the ulcers revealed neutrophils, a f e w of which contained globular inclusions. A second biopsy from the edge of the ulcers s h o w e d definite mycelia for the first t i m e ; cultures, h o w e v e r , w e r e sterile. O n D e c e m b e r 28th, the patient w a s placed on amphotericin-B therapy, w i t h daily intravenous inin fusions of 10 to 2 0 mg. each (0.25 mg./kg.) 5.0-percent dextrose in water, g i v e n over s i x hours. A f t e r eight injections it became necessary to discontinue the medication because of severe arm inflammation. B y January 14, 1961, the visual acuity had further decreased to hand m o v e m e n t s and good light projection. T h e r e were signs of improvement in that s o m e of the scleral defects had virtually filled in and the l o w e r aspect of the globe had become almost white. T h e disc n o w appeared several diopters endematous, w i t h marked engorgement. D u r i n g all this time the ocular pain had persisted and much medication w a s needed to relieve it. T h e patient w a s placed on erythromycin ointment ( f o u r times d a i l y ) during the latter half of J a n u a r y ; discoloration of the sclera reappeared but the secretion lessened.
F i g . 3 ( D i a m o n d and K i r k ) . H y p h a e in necrotic sclera.
NOTES, CASES, Enucleation of the right e y e w a s recommended and readily accepted by the patient. S h a r p dissection w a s necessary to separate the extraocular m u s cles and the posterior sclera f r o m the orbital t i s sues w h i c h appeared normal and free of palpable indurations. Tenon's fascia w a s closed with 4 - 0 chromic purse-string and interrupted sutures. T h e available conjunctiva w a s undermined and secured with 6-0 interrupted black silk sutures. I n doing s o the l o w e r cul-de-sac w a s obliterated and there w a s l o w e r lid inversion, m a k i n g it necessary to pass a 4-0 black silk suture through both tarsi. T h i s t e m porary closure secured the lids in normal apposition. A pressure d r e s s i n g w a s applied and the patient w a s returned to his room in good condition. T h e globe, w h i c h w a s calotted immediately, e x hibited marked thickening and induration of the outer layers, posteriorly. O n e portion w a s retained f o r tissue study and the remainder w a s submitted for cultures and smears. F o u r to five days after inoculation, numerous colonies of aspergillus fungi w e r e found g r o w i n g o n Sabouraud medium. O n l y a f e w bacteria w e r e cultured f r o m the pulverized calotte. O n e dose of amphotericin-B w a s g i v e n intravenously on the first postoperative day. T h e patient h a s continued to improve and, w h e n last seen 10 months postoperative, there w a s good healing of the socket with n o further mucopurulent exudate. A t n o time w a s he febrile o r w a s there other remarkable illness. PATHOLOGIC
FINDINGS
The enucleated specimen had a good deal of extraneous soft tissue, overlying and firmly connected with inferoposterior portion of the eyeball wall. A temporal calotte was removed in the operating room and used for bactériologie study. The remaining segment was fixed in formalin, embedded in paraffin and sectioned in an approximately parasaggital plane. The gross pathologic changes were located in and alongside the inferoposterior portion of the eyeball wall. They were essentially granulomatous in the choroid, suprachoroid and in the epibulbar tissues, resulting in an over-all thickening of the eyeball wall up to five times its normal thickness. The granulomas were made up of plasma, epithelioid and Langhans-type giant cells, in addition to polymorphonuclear leukocytes, lymphocytes and fibrocytes. Large hemorrhages had occurred between suprachoroid and sclera and in the epibulbar tissues. Some of these hemorrhages were
1127
INSTRUMENTS
fresh and probably occurred during the difficult enucleation. The sclera occupying the central position between the granulomas was profoundly altered. In most places it was much reduced in substance and broken up into fiber bundle fragments by multiple foci of necrosis. In several places there was practically no sclera left and the intra- and extraocular granulomas coalesced. Fungi were identified in large numbers as nonseptate, straight and branching hyphae as well as spores. The organisms were most numerous in the areas of fragmented sclera, immediately surrounding the areas of necrosis; fungi were also present in numerous, more or less isolated, microabscesses in parts of the sclera away from the principal focus. The fungi were also identified, though in very much smaller numbers, in the choroidal as well as in the episcleral granulomas. With regard to the rest of the eye it may suffice to state that there was no major involvement of iris, ciliary body and retina or of the chambers of the eye. There was not even a vestige of the fungal endophthalmitis described by Fine and Zimmerman and Theodore, et al. There was, however, a marked and probably significant degree of chronic edema of choroid and suprachoroid outside the area of greatest pathologic alteration in the eyeball wall. The pathologic findings may be summed up as chronic, partly granulomatous, partly necrotizing fungal scleritis with secondary choroiditis and episcleritis. DISCUSSION
The clinical and pathologic findings in this case characterize the disease as a chronic granulomatous sclerochoroiditis without an endophthalmitis component. The clinical, pathologic and mycologie findings were characteristic of exogenous fungal infection. From the available evidence the actual course of the disease can be fairly well reconstructed. The first unusual finding was
1128
NOTES. CASES, INSTRUMENTS
sloughing of the epibulbar tissues and of the posterior, scleral wound lip in the area of the original cataract incision. This sloughing was associated with profuse mucopurulent external exudation but only minimal reaction in the anterior chamber. When this process was brought partly under control by several antibiotics and the response of the eye to the conjunctivoplasty seemed favorable, the assumption of a traumatic slough with minimal secondary infection seemed tenable. In retrospect, it is more likely that the inoculation of fungi into the anterior sclera took place at the time of the original cataract incision or at the time of repair of the incision. Steroids and antibiotics and particularly streptomycin, which was given subconjunctivally after each of the four operations, may have been a factor in producing the infection and in its relentless progression.
inoculation occurred at the same surgical sitting. The small ulcers of the anterior sclera observed during the late stages of the disease probably represented fringes of the principal focus which was the granuloma in the inferoposterior portion of the eyeball wall. The pathologic examination clearly revealed active proliferation of the fungus. Whether or not this would have been brought under control by larger doses of antibiotics or other forms of chemotherapy also calls for experimental study. In our case the enucleation, even in retrospect, appears justified by the magnitude of the disease as revealed by the pathologic findings, by the persistent severe pain and by the patient's general debilitation during the last two months of the disease.
The massive granulomatous formation with microabscesses in adjacent as well as in more remote portions of the sclera separates this case from all reported intraocular fungus infections after cataract extraction. This unusual pathologic feature may be related to massive choroidal detachment secondary to delayed restoration of the anterior chamber. This hypothesis should lend itself to experimental confirmation by animal inoculation, including the possible auxiliary factors (streptomycin and steroids).
SUMMARY
A fungus infection was first suspected because of the anterosuperior scleral defect and peculiar exudate. The propogation of the infection in the posteroinferior site could have been explained by a direct extension of the original focus to the edematous unfolded suprachoroid below. Direct inoculation of the posteroinferior sclera and suprachoroid by either of the posterior sclerotomies constitutes another possibility though there was no discernible early inferior scleral involvement. With this latter reasoning one may assume that anterior
A case of granulomatous sclerochoroiditis following intracapsular cataract extraction in a 72-year-old white man is reported. The postoperative course was characterized by delayed restoration of the anterior chamber with massive choroidal detachment which was treated surgically by repair of the wound, release of the suprachoroidal fluid and reinflation of the anterior chamber. The unusual clinical features were extensive sloughing of the posterior lip of the cataract incision, multiple small ulcers of the anterior sclera and, finally, the development of a large granulomatous lesion in the posterior segment. Biopsy specimens from the edge of one of the scleral ulcers, as well as the histologic section of the enucleated eye, revealed proliferating mycelia in large numbers. Aspergillus fumigatus was grown from one portion of the enucleated eye: two previous in vivo cultures were negative. U. S. Naval Hospital. 715 Lake Street.
NOTES, CASES,
INSTRUMENTS
1129
REFERENCES
1. Fine, B . S , and Zimmerman, L. E . : E x o g e n o u s intraocular f u n g u s infection with particular reference to complications of intraocular surgery. A m . J. O p h t h , 4 8 : 1 5 1 - 1 6 5 ( A u g . ) 1959. 2. Ley, A . P . : E x p e r i m e n t a l fungus infections of the cornea: A preliminary report. A m . J. O p h t h , 4 2 : 5 9 - 7 0 ( O c t . pt. I I ) 1956. 3. Greetham, J. S , and Mackley, T . A , Jr.: Intraocular f u n g u s infection f o l l o w i n g cataract surgery. Α Μ Α A r c h . O p h t h , 5 8 : 5 5 8 - 5 6 1 , 1957. 4. Rychener, R. O . : Intraocular mycoses. T r . A m . Ophth. S o c , 31:477-495, 1933. 5. Fine, B . S , and Zimmerman, L . : Postoperative mycotic endophthalmitis diagnosed clinically and verified. Brit. J. O p h t h , 4 3 : 7 5 3 , 1959. 6. Makley, T . A , Kissen, A . T , and Suie, T . : M y c o t i c infections of the e y e : ( R e p o r t of s i x c a s e s ) . O h i o State M. J , 5 4 : 1 ( J a n . ) 1961. 7. Cogan, D . G.: E n d o g e n o u s intraocular fungus i n f e c t i o n : Report of a case. A r c h . O p h t h , 4 2 : 6 6 6 82, N o v . 1949. 8. Verhoeff, F . H . : M y c o s i s of the choroid f o l l o w i n g cataract extraction and metastatic choroiditis of the other eye, producing the clinical picture of sympathetic uveitis. A r c h . O p h t h , 5 3 : 5 1 7 ( N o v . ) 1924. 9. Theodore, F. H , Littman, M . L , and A l m e d a , E . : T h e diagnosis and management of fungus endophthalmitis f o l l o w i n g cataract extraction. Α Μ Α A r c h . O p h t h , 6 6 : 1 6 3 - 1 7 5 ( A u g . ) 1961.
EMBOLUS CENTRAL SUCCESSFULLY N O E L T.
OF
RETINAL TREATED
BY
SIMMONDS,
Alexandria,
ARTERY PARACENTESIS M.D.
Louisiana
W . R. S , aged 42 years, a white man, called me at 6 : 3 0 A . M . on October 11, 1952, stating that he had a w a k e n e d with slight pain in his right eye and noted that he could not see with the eye. A vascular accident w a s suspected s o I s a w him immediately. V i s i o n w a s reduced t o light perception. T h e pupil w a s dilated and inactive to direct light but reacted to indirect light. T h e blood columns in the retinal vessels showed segmentation, with a t o - a n d - f r o motion. T h e retina w a s beginning to become edematous and the macula showed the red spot characteristic of embolus of the central artery. H e w a s immediately sent to the hospital and the physician w h o had been treating him for hypertension w a s called. H e advised 100 mg. of nicotinic acid as a vasodilator preliminary t o surgery. A t about 7:00 A . M . , a paracentesis of the cornea w i t h a Ziegler k n i f e needle w a s done, e m p t y i n g the anterior chamber and reducing the intraocular pressure to zero. A dressing w a s applied and three hours later at 10:00 A . M . the dressing w a s removed and the patient stated that he could see. T h e f u n dus showed much improvement. H e w a s discharged that afternoon and resumed his antihypertension treatment. O n October 27th visual acuity w a s normal in both eyes. A l t h o u g h there w a s s o m e blurring of the upper nasal disc, R . E , the capillaries seemed normal. T h e arteries were small and irregular in :aliber, the A - V ratio being about four to one. T h e
Fig.
1 ( S i m m o n d s ) . Visual field taken w i t h the E t i e n n e perimeter.
superior nasal artery w a s more or less threadlike, appearing to be completely occluded. E x a m i n a t i o n of the left e y e revealed a slight blurring of the upper disc with normal capillaries and an A - V ratio of approximately t w o to one. A small f u s i f o r m dilatation of the superior temporal artery w a s also present. Visual fields, taken on October 27th, revealed loss of peripheral vision e v e r y w h e r e e x c e p t above, with a more marked loss in the lower temporal quadrant. Repeated field examinations have been essentially the s a m e ; a recent one taken with the Etienne perimeter is s h o w n in F i g u r e 1. S i n c e this time, the patient h a s had numerous sieges of vascular emboli and thromboses, par-
NOTES, CASES,
INSTRUMENTS patient w a s discharged f r o m the hospital and followed a course of gradual reduction of the steroid therapy until it w a s discontinued. SUMMARY
F i g . 4 ( S o l o m o n , M o s e s and V o l k ) . A f t e r 39 days of steroid therapy, both eyes w e r e normal, e x cept for redundancy of the bulbar conjunctiva. therapy w a s begun on the 37th hospital day. T h e initial dose of prednisone w a s 4 0 mg. on the first day followed by 30 mg. orally each day thereafter. T w o days after the initiation of steroid therapy, there w a s definite reduction of the proptosis and improvement in the extraocular muscle function and in the appearance of the conjunctiva. T h i s improvement continued (fig. 2 ) and, b y the 62nd hospital day, the patient's left eye w a s normal in all respects (fig. 3 ) . W i t h i n the n e x t t w o w e e k s the right eye had completely cleared (fig. 4 ) . T h e
The use of corticosteroids in the treatment of cavernous sinus thrombosis was a useful adjunct to the usual antibacterial and anticoagulant regimen. The patient described in this report progressed from a unilateral to a bilateral cavernous sinus thrombosis with absolute ophthalmoplegia over a sixweek period in spite of vigorous antibiotic and anticoagulant therapy. Improvement began two days after the introduction of corticosteroids into the therapeutic regimen and, in 39 days, both eyes were completely normal. 1020 Huron Road
(15).
REFERENCES
1. M a c N e a l , W . J., and Cavallo, M . E . : J . A . M . A . , 109:2039, 1937. 2. L y o n s , C : A n n . Surg., 1 1 3 : 1 1 3 , 1941. 3. Florey, H . W . , et al.: Lancet, 2:177, 1941.
POSTOPERATIVE INTRAOCULAR ASPERGILLOSIS* MARSHALL
A.
DIAMOND,
Portsmouth,
M.D.
Virginia
AND HAROLD
Oak
Q.
Park,
KIRK,
M.D.
Illinois
A number of intraocular fungus infections following surgical or traumatic perforations of the eyeball have been reported in the recent literature. The infections connected with surgical procedures in the anterior segment follow a characteristic pattern. After a latent period of several weeks, an anterior endophthalmitis develops which temporarily seems
* F r o m the Department of Ophthalmology, U n i versity of Illinois, and the Illinois E y e and E a r Infirmary, Chicago.
to respond to vigorous antibiotic and steroid therapy. A few weeks later, however, a mass of white exudate, either in the anterior chamber or in the anterior vitreous, becomes more and more prominent. This alarming development in the anterior segment may remain for months and is in sharp contrast to an apparent state of uninvolvement of the posterior segment, as evidenced by good light perception and projection. The hopelessness of the disease is not realized until quite late in its course. When severe pain sets in and persists, together with loss of all useful vision, the patient usually consents or requests enucleation. The case reported here is one of similar disastrous outcome but most unusual in that the site of the pathologic process was within the posterior ocular coats and was without endophthalmitis.
NOTES, CASES, CASE
INSTRUMENTS
1125
REPORT
T h i s 72-year-old white man w a s first seen at the Illinois E y e and E a r Infirmary in N o v e m b e r , 1959, with the history of bilateral, painless gradual decrease in vision for several years. T h e u n corrected visual acuity of his right eye w a s 1 0 / 2 0 0 m d 2 0 / 1 0 0 + 1 with a pinhole. T h e vision of the eft eye w a s excellent light projection with hand movements. T h e visual impairment w a s attributed to senile cataracts, moderately advanced in the right :ye and mature in the left eye. T h e other ocular î n d i n g s were within normal limits. General e x a m i nation revealed moderate pulmonary emphysema m d loss of the right l o w e r extremity through trauma many years before. O n N o v e m b e r 23, 1959, an intracapsular lens extraction with full iridectomy w a s performed on the left eye. T h e operation and the recovery w e r e uneventful, w i t h 2 0 / 5 0 — 2 visual acuity through a plus-10 lens and a pinhole, one w e e k postoperatively. T h e patient's left e y e w a s found to be in g o o d condition w h e n he again entered the hospital s i x w e e k s later. O n January 11, 1960, an intracapsular lens extraction with full iridectomy w a s performed on the right eye. T h i s included a superior limbusbased conjunctival flap, t w o preplaced corneoscleral black-silk sutures of the M c L e a n type, and delivery of the lens by tumbling w i t h an erisophake. A prophylactic subconjunctival injection of penicillin and streptomycin w a s given at the conclusion of the procedure. D u r i n g the n e x t five days the postoperative course appeared to be normal. O n the sixth postoperative day, a small hyphema w a s noted. T h e patient stated that another patient had bumped against his e y e shield on the d a y before. T h e hyphema absorbed rapidly e x c e p t f o r a small strand of clot located temporally but, on the 15th postoperative day, a flat chamber w i t h an e x t e n s i v e choroidal detachment w a s noted. Treatment during the immediate postoperative period had included moderate mydriasis but, w h e n the anterior chamber became shallow, the e y e w a s vigorously dilated ( u p t o nine m m . ) and local steroids w e r e started. N e o s p o r i n solution had been given daily. T h e sutures w e r e removed on the 15th postoperative day. Since the anterior chamber w a s flat, a posterior sclerotomy w a s performed on the 18th postoperative day in the inferotemporal quadrant; it yielded a considerable amount of serous suprachoroidal fluid. T h e chamber w a s restored by air injection. A l t o gether five instrument entries w e r e made into the interior and posterior eyeball. Subconjunctival i n jections of pilocarpine ( f o u r percent) and penicillin-streptomycin w e r e the terminal steps. S i x days f o l l o w i n g this procedure the chamber w a s again flat e x c e p t w h e r e a small amount o f injected air remained. E x p l o r a t i o n of the cataract incision revealed a questionable g a p w h i c h w a s closed by n e w sutures. T h i s operation included reopening and release of m o r e suprachoroidal fluid; air and saline were injected into the anterior c h a m -
F i g . 1 ( D i a m o n d and K i r k ) . A n approximately vertical section, s h o w i n g location and extent of the granulomatous process.
ber. B o t h w o u n d sites w e r e e x p o s e d this time. A g a i n a subconjunctival injection of penicillinstreptomycin w a s given. D u r i n g the n e x t t w o and one-half months, the anterior chamber w a s gradually restored to a c o m parative phakic depth and the choroidal detachment w a s reduced. In the region of the original cataract incision the epibulbar tissues, a s well a s the scleral w o u n d lip, became the site of a gradual s l o u g h i n g process, first e x p o s i n g the deeper sclera and finally a n e x t r e m e l y thin fibrous layer coveri n g the anterior uvea. T h i s s l o u g h i n g process w a s associated with a persistent mucopurulent to chalky secretion. V i g o r o u s therapy w i t h both local and systemic antibiotics (Chloromycetin, terramycin, neosporin and e r y t h o m y c i n ) had n o demonstrable effect on the s l o u g h i n g process. T h e tension remained normal and the pupil became partially bound d o w n by posterior synechias. T h e left e y e remained in g o o d condition. S i x w e e k s a f t e r the third surgical procedure one attempt w a s made to culture f u n g i f r o m the external secretions o n Sabouraud media ; n o g r o w t h of a n y kind w a s obtained but some gram-positive cocci w e r e found. O n M a y 17, 1960, four months after the original lens extraction, the scleral d e f e c t had reached a size of 15 by 11 m m . A f e w l a r g e conjunctival vessels had g r o w n into the thin fibrous layer that w a s covering the ciliary body at the bottom of the defect. T h e fundus could be seen clearly. T h e visual acuity of the right eye w a s 2 0 / 7 0 + 2 with + 1 0 D . sph. and a pinhole. T h e ocular tension w a s low. I n June, 1960, the patient w a s readmitted for repair of the scleral d e f e c t by conjunctivoplasty. T h i s w a s performed o n June 7th, mobilizing the upper bulbar and f o r n i x conjunctiva as much as possible. In this manner a thick, apparently healthy
1126
NOTES, CASES,
INSTRUMENTS had w o r k e d s o well, repair o f the lower scleral ulcers b y conjunctivoplasty w a s considered f o r several days. V i s i b l e day-to-day w o r s e n i n g of the scleral disease together w i t h posterior exudation made this plan seem futile. N e w developments were noted in the posterior segment through the n o w diffusely hazy vitreous. A localized large chorioretinal elevation could be seen b e l o w the disc, with numerous horizontal ripples in the o v e r l y i n g retina. V i s i o n had dropped to 3 / 2 0 0 with a -f-lOD. sph. and with and without pinhole. A number of attempts to g r o w micro-organisms f r o m the scleral exudate again failed.
Fig. 2
( D i a m o n d and K i r k ) . H y p h a e in well-preserved sclera.
fairly
flap w a s brought over the defect and sutured to the cornea. Radial incisions of the flap w e r e necessary to lessen the tension created. B e f o r e the sutures w e r e tied the area of defect w a s scraped with a BardP a r k e r knife and Gill dissector. Penicillin and streptomycin w e r e a g a i n injected subconjunctivally below. U p o n discharge 13 days later, the flap appeared uniformly hyperemic and adherent to the defect e x cept j u s t adjacent to the limbus w h e r e it had retracted slightly upward in several areas. T h e sticky mucopurulent discharge w a s still p r e s e n t A s o n previous admissions, blood count, urinalysis and serology w e r e normal. T w o m o r e cultures of the exudate failed to reveal significant g r o w t h . T w o months later w h e n seen in the out-patient department the scleral defect w a s well covered and the e y e showed moderately active chronic anterior uveitis. T r e a t m e n t with topical antibiotic, steroid and mydriatic solutions w a s restarted. A b o u t the middle of October, 1960, marked pain began behind and above the right eye. It persisted with slightly v a r y i n g severity until the time of the enucleation. B y December, 1960, a n e w development w a s seen in the lower half of the globe. A g a i n s t the background of the deep red t o purplish Tenon's capsule, three distinct scleral ulcers had formed, exuding a gritty w h i t e material. T h e right e y e had become proptosed and its m o v e m e n t down and out w a s limited. T h e visual acuity w a s 2 0 / 2 0 0 w i t h -(-10D. sph. and pinhole. T h e ocular tension w a s low. T h e r e w a s still only a moderate degree of anterior uveitis. T h e fundus could be seen fairly well, the undulating slightly opacified anterior vitreous face being the principal optical barrier. On fourth count, normal
D e c e m b e r 7th, the time of the patient's admission to the hospital, complete blood urinalysis and serology w e r e still within limits. S i n c e the earlier conjunctivoplasty
A scleral biopsy f r o m the edge of o n e of the ulcers revealed neutrophils, a f e w of which contained globular inclusions. A second biopsy from the edge of the ulcers s h o w e d definite mycelia for the first t i m e ; cultures, h o w e v e r , w e r e sterile. O n D e c e m b e r 28th, the patient w a s placed on amphotericin-B therapy, w i t h daily intravenous inin fusions of 10 to 2 0 mg. each (0.25 mg./kg.) 5.0-percent dextrose in water, g i v e n over s i x hours. A f t e r eight injections it became necessary to discontinue the medication because of severe arm inflammation. B y January 14, 1961, the visual acuity had further decreased to hand m o v e m e n t s and good light projection. T h e r e were signs of improvement in that s o m e of the scleral defects had virtually filled in and the l o w e r aspect of the globe had become almost white. T h e disc n o w appeared several diopters endematous, w i t h marked engorgement. D u r i n g all this time the ocular pain had persisted and much medication w a s needed to relieve it. T h e patient w a s placed on erythromycin ointment ( f o u r times d a i l y ) during the latter half of J a n u a r y ; discoloration of the sclera reappeared but the secretion lessened.
F i g . 3 ( D i a m o n d and K i r k ) . H y p h a e in necrotic sclera.
NOTES, CASES, Enucleation of the right e y e w a s recommended and readily accepted by the patient. S h a r p dissection w a s necessary to separate the extraocular m u s cles and the posterior sclera f r o m the orbital t i s sues w h i c h appeared normal and free of palpable indurations. Tenon's fascia w a s closed with 4 - 0 chromic purse-string and interrupted sutures. T h e available conjunctiva w a s undermined and secured with 6-0 interrupted black silk sutures. I n doing s o the l o w e r cul-de-sac w a s obliterated and there w a s l o w e r lid inversion, m a k i n g it necessary to pass a 4-0 black silk suture through both tarsi. T h i s t e m porary closure secured the lids in normal apposition. A pressure d r e s s i n g w a s applied and the patient w a s returned to his room in good condition. T h e globe, w h i c h w a s calotted immediately, e x hibited marked thickening and induration of the outer layers, posteriorly. O n e portion w a s retained f o r tissue study and the remainder w a s submitted for cultures and smears. F o u r to five days after inoculation, numerous colonies of aspergillus fungi w e r e found g r o w i n g o n Sabouraud medium. O n l y a f e w bacteria w e r e cultured f r o m the pulverized calotte. O n e dose of amphotericin-B w a s g i v e n intravenously on the first postoperative day. T h e patient h a s continued to improve and, w h e n last seen 10 months postoperative, there w a s good healing of the socket with n o further mucopurulent exudate. A t n o time w a s he febrile o r w a s there other remarkable illness. PATHOLOGIC
FINDINGS
The enucleated specimen had a good deal of extraneous soft tissue, overlying and firmly connected with inferoposterior portion of the eyeball wall. A temporal calotte was removed in the operating room and used for bactériologie study. The remaining segment was fixed in formalin, embedded in paraffin and sectioned in an approximately parasaggital plane. The gross pathologic changes were located in and alongside the inferoposterior portion of the eyeball wall. They were essentially granulomatous in the choroid, suprachoroid and in the epibulbar tissues, resulting in an over-all thickening of the eyeball wall up to five times its normal thickness. The granulomas were made up of plasma, epithelioid and Langhans-type giant cells, in addition to polymorphonuclear leukocytes, lymphocytes and fibrocytes. Large hemorrhages had occurred between suprachoroid and sclera and in the epibulbar tissues. Some of these hemorrhages were
1127
INSTRUMENTS
fresh and probably occurred during the difficult enucleation. The sclera occupying the central position between the granulomas was profoundly altered. In most places it was much reduced in substance and broken up into fiber bundle fragments by multiple foci of necrosis. In several places there was practically no sclera left and the intra- and extraocular granulomas coalesced. Fungi were identified in large numbers as nonseptate, straight and branching hyphae as well as spores. The organisms were most numerous in the areas of fragmented sclera, immediately surrounding the areas of necrosis; fungi were also present in numerous, more or less isolated, microabscesses in parts of the sclera away from the principal focus. The fungi were also identified, though in very much smaller numbers, in the choroidal as well as in the episcleral granulomas. With regard to the rest of the eye it may suffice to state that there was no major involvement of iris, ciliary body and retina or of the chambers of the eye. There was not even a vestige of the fungal endophthalmitis described by Fine and Zimmerman and Theodore, et al. There was, however, a marked and probably significant degree of chronic edema of choroid and suprachoroid outside the area of greatest pathologic alteration in the eyeball wall. The pathologic findings may be summed up as chronic, partly granulomatous, partly necrotizing fungal scleritis with secondary choroiditis and episcleritis. DISCUSSION
The clinical and pathologic findings in this case characterize the disease as a chronic granulomatous sclerochoroiditis without an endophthalmitis component. The clinical, pathologic and mycologie findings were characteristic of exogenous fungal infection. From the available evidence the actual course of the disease can be fairly well reconstructed. The first unusual finding was
1128
NOTES. CASES, INSTRUMENTS
sloughing of the epibulbar tissues and of the posterior, scleral wound lip in the area of the original cataract incision. This sloughing was associated with profuse mucopurulent external exudation but only minimal reaction in the anterior chamber. When this process was brought partly under control by several antibiotics and the response of the eye to the conjunctivoplasty seemed favorable, the assumption of a traumatic slough with minimal secondary infection seemed tenable. In retrospect, it is more likely that the inoculation of fungi into the anterior sclera took place at the time of the original cataract incision or at the time of repair of the incision. Steroids and antibiotics and particularly streptomycin, which was given subconjunctivally after each of the four operations, may have been a factor in producing the infection and in its relentless progression.
inoculation occurred at the same surgical sitting. The small ulcers of the anterior sclera observed during the late stages of the disease probably represented fringes of the principal focus which was the granuloma in the inferoposterior portion of the eyeball wall. The pathologic examination clearly revealed active proliferation of the fungus. Whether or not this would have been brought under control by larger doses of antibiotics or other forms of chemotherapy also calls for experimental study. In our case the enucleation, even in retrospect, appears justified by the magnitude of the disease as revealed by the pathologic findings, by the persistent severe pain and by the patient's general debilitation during the last two months of the disease.
The massive granulomatous formation with microabscesses in adjacent as well as in more remote portions of the sclera separates this case from all reported intraocular fungus infections after cataract extraction. This unusual pathologic feature may be related to massive choroidal detachment secondary to delayed restoration of the anterior chamber. This hypothesis should lend itself to experimental confirmation by animal inoculation, including the possible auxiliary factors (streptomycin and steroids).
SUMMARY
A fungus infection was first suspected because of the anterosuperior scleral defect and peculiar exudate. The propogation of the infection in the posteroinferior site could have been explained by a direct extension of the original focus to the edematous unfolded suprachoroid below. Direct inoculation of the posteroinferior sclera and suprachoroid by either of the posterior sclerotomies constitutes another possibility though there was no discernible early inferior scleral involvement. With this latter reasoning one may assume that anterior
A case of granulomatous sclerochoroiditis following intracapsular cataract extraction in a 72-year-old white man is reported. The postoperative course was characterized by delayed restoration of the anterior chamber with massive choroidal detachment which was treated surgically by repair of the wound, release of the suprachoroidal fluid and reinflation of the anterior chamber. The unusual clinical features were extensive sloughing of the posterior lip of the cataract incision, multiple small ulcers of the anterior sclera and, finally, the development of a large granulomatous lesion in the posterior segment. Biopsy specimens from the edge of one of the scleral ulcers, as well as the histologic section of the enucleated eye, revealed proliferating mycelia in large numbers. Aspergillus fumigatus was grown from one portion of the enucleated eye: two previous in vivo cultures were negative. U. S. Naval Hospital. 715 Lake Street.
NOTES, CASES,
INSTRUMENTS
1129
REFERENCES
1. Fine, B . S , and Zimmerman, L. E . : E x o g e n o u s intraocular f u n g u s infection with particular reference to complications of intraocular surgery. A m . J. O p h t h , 4 8 : 1 5 1 - 1 6 5 ( A u g . ) 1959. 2. Ley, A . P . : E x p e r i m e n t a l fungus infections of the cornea: A preliminary report. A m . J. O p h t h , 4 2 : 5 9 - 7 0 ( O c t . pt. I I ) 1956. 3. Greetham, J. S , and Mackley, T . A , Jr.: Intraocular f u n g u s infection f o l l o w i n g cataract surgery. Α Μ Α A r c h . O p h t h , 5 8 : 5 5 8 - 5 6 1 , 1957. 4. Rychener, R. O . : Intraocular mycoses. T r . A m . Ophth. S o c , 31:477-495, 1933. 5. Fine, B . S , and Zimmerman, L . : Postoperative mycotic endophthalmitis diagnosed clinically and verified. Brit. J. O p h t h , 4 3 : 7 5 3 , 1959. 6. Makley, T . A , Kissen, A . T , and Suie, T . : M y c o t i c infections of the e y e : ( R e p o r t of s i x c a s e s ) . O h i o State M. J , 5 4 : 1 ( J a n . ) 1961. 7. Cogan, D . G.: E n d o g e n o u s intraocular fungus i n f e c t i o n : Report of a case. A r c h . O p h t h , 4 2 : 6 6 6 82, N o v . 1949. 8. Verhoeff, F . H . : M y c o s i s of the choroid f o l l o w i n g cataract extraction and metastatic choroiditis of the other eye, producing the clinical picture of sympathetic uveitis. A r c h . O p h t h , 5 3 : 5 1 7 ( N o v . ) 1924. 9. Theodore, F. H , Littman, M . L , and A l m e d a , E . : T h e diagnosis and management of fungus endophthalmitis f o l l o w i n g cataract extraction. Α Μ Α A r c h . O p h t h , 6 6 : 1 6 3 - 1 7 5 ( A u g . ) 1961.
EMBOLUS CENTRAL SUCCESSFULLY N O E L T.
OF
RETINAL TREATED
BY
SIMMONDS,
Alexandria,
ARTERY PARACENTESIS M.D.
Louisiana
W . R. S , aged 42 years, a white man, called me at 6 : 3 0 A . M . on October 11, 1952, stating that he had a w a k e n e d with slight pain in his right eye and noted that he could not see with the eye. A vascular accident w a s suspected s o I s a w him immediately. V i s i o n w a s reduced t o light perception. T h e pupil w a s dilated and inactive to direct light but reacted to indirect light. T h e blood columns in the retinal vessels showed segmentation, with a t o - a n d - f r o motion. T h e retina w a s beginning to become edematous and the macula showed the red spot characteristic of embolus of the central artery. H e w a s immediately sent to the hospital and the physician w h o had been treating him for hypertension w a s called. H e advised 100 mg. of nicotinic acid as a vasodilator preliminary t o surgery. A t about 7:00 A . M . , a paracentesis of the cornea w i t h a Ziegler k n i f e needle w a s done, e m p t y i n g the anterior chamber and reducing the intraocular pressure to zero. A dressing w a s applied and three hours later at 10:00 A . M . the dressing w a s removed and the patient stated that he could see. T h e f u n dus showed much improvement. H e w a s discharged that afternoon and resumed his antihypertension treatment. O n October 27th visual acuity w a s normal in both eyes. A l t h o u g h there w a s s o m e blurring of the upper nasal disc, R . E , the capillaries seemed normal. T h e arteries were small and irregular in :aliber, the A - V ratio being about four to one. T h e
Fig.
1 ( S i m m o n d s ) . Visual field taken w i t h the E t i e n n e perimeter.
superior nasal artery w a s more or less threadlike, appearing to be completely occluded. E x a m i n a t i o n of the left e y e revealed a slight blurring of the upper disc with normal capillaries and an A - V ratio of approximately t w o to one. A small f u s i f o r m dilatation of the superior temporal artery w a s also present. Visual fields, taken on October 27th, revealed loss of peripheral vision e v e r y w h e r e e x c e p t above, with a more marked loss in the lower temporal quadrant. Repeated field examinations have been essentially the s a m e ; a recent one taken with the Etienne perimeter is s h o w n in F i g u r e 1. S i n c e this time, the patient h a s had numerous sieges of vascular emboli and thromboses, par-