Etiology and Diagnosis of Fungal Postoperative Endophthalmitis

Etiology and Diagnosis of Fungal Postoperative Endophthalmitis

Symposium: Postoperative Endophthalmitis f f f ETIOLOGY AND DIAGNOSIS OF FUNGAL POSTOPERATIVE ENDOPHTHALMITIS FREDERICK H. THEODORE, NEW YORK, NEW ...

3MB Sizes 0 Downloads 22 Views

Symposium: Postoperative Endophthalmitis f

f

f

ETIOLOGY AND DIAGNOSIS OF FUNGAL POSTOPERATIVE ENDOPHTHALMITIS FREDERICK H. THEODORE, NEW YORK, NEW YORK

Delayed infections after ocular surgery (especially cataract) are usually due to saprophytic contaminant fungi of relatively low pathogenicity. About 20 different varieties of fungi have been cultured from such eyes. Thus, as far as the eye is concerned, there is no such thing as a harmless, benign fungus. Mycotic postoperative endophthalmitis is a distinct entity with a typical clinical picture, easily diagnosed once learned. Laboratory tests are often positive. Since the visual result is poor even if the eye is saved, prevention and early recognition are our primary concerns. In this regard, a recent episode of 12 infections from contaminated intraocular lens neutralizing solutions as well as other sporadic instances of fungal infection after lens implantation must be noted.

HISTORICAL REVIEW

IN the past 20 years a new entity has been increasingly recognized as an important factor in postoperative endophthalmitis: infection by fungi of low pathogenicity, socalled benign contaminant fungi. Originally, such infections were first discovered after enucleation and then only after special fungus

Submitted for publication Oct 3, 1977. F rom the External D iseases a nd Infections Clinic, Manha tta n Eye, Ea r and Throat Hospita l, a nd the Mount Sinai School of Medicine, New York. Presented at the Eighty·second An nual Meeting of t he American Academy o f Ophth a lmology and Otola ryngology, Dalla s, Oct 2-6, 1977. Reprint r equests to 625 P ark Ave, New York, NY 10021.

MD

stains were employed for histologic examination. However, early workers in the field soon delineated a rather typical clinical picture, easily diagnosed once learned. Thus, it is now usually possible, as long as the index of suspicion is high enough, to either demonstrate conclusively by microbiologic methods that mycotic postoperative infection is present, or else to implicate such infection inferentially by the presence of this clinical picture and the absence of evidence pointing to other types of causation. Moreover, as in bacterial postoperative infection; instances of fungal infection need not only be single sporadic episodes but may appear as multiple infections due to a common contaminated source. The early literature in regard to intraocular mycotic infections is documented in detail in the papers of Fine and Zimmermanl and in an earlier paper by my co-workers and me. 2 Fungi in general, and saprophytic contaminant fungi in particular, were largely ignored as a cause of postoperative eye infections, usually after cataract extraction, until 1958. Only three such instances had been previously reported. Solely on morphologic grounds, two of these were believed to be the result of infection with Actinomyces, and the other was due to an unidentified fungus. Other reported instances of fungal endophthalmitis were mainly of

327

328

FREDERICK H. THEODORE

nonsurgical ongm. Most appeared to be endogenous in character; only a few followed intraocular trauma. The fungi involved were assumed to be ocular pathogens and not saprophytes, although actual identifications of the responsible fungi could not be made by cultural means since the diagnosis was generally made on the basis of histopathologic examination of enucleated eyes. In 1958, three instances of fungus endophthalmitis, two in a single patient following cataract extraction, were reported. 3 In each of these, Volutella mold species were isolated late in the course of the infection. This fungus, which is related to Cephalosporium, is generally considered to be nonpathogenic. It is of special interest, but was not then reported, that the organism was also isolated from the cocaine used during surgery. In August 1959, based on the histologic studies of material submitted from various regions of the United States and from abroad, Fine and Zimmerman 1 reported 13 instances of postsurgical and posttraumatic fungus infections of the intraocular tissues. In each instance, the diagnosis had been made only after removal of the eye and subsequent pathologic examination, including the use of special fungus stains. Of these 13 cases, 9 followed intraocular surgery; eight patients had undergone cataract extractions and the other patient had a magnetic extraction of an intraocular foreign body. As an addendum, the authors noted two additional cases occurring after cataract surgery. In other words, they demonstrated the presence of ocular fungus infection in ten patients who had lost their eyes due to undiagnosed endophthalmitis fol-

OPHTH AAOO

lowing cataract extraction. Because of the fact that this was a histopathologic study, none of the fungi involved could be specifically identified by microbiologic methods, but they were thought to resemble species of Aspergillus, Cephalosporium, Fusarium, and Volutella. In a later report,4 the same authors were able to diagnose fungal infection in a patient on a clinical basis eight months after cataract extraction. Enucleation and pathologic examination confirmed the diagnosis, but cultures were again, unfortunately, unobtainable. Early in 1959, before the publication of Fine's and Zimmerman's paper, I observed a patient who developed mycotic endophthalmitis due to Neurospora sitophila 5 following cataract extraction (Fig 1 and 2). On the basis of the unusual clinical picture, the diagnosis was suspected within a week of its onset and was quickly confirmed by

Fig I.-Mycotic endophthalmitis due to Neurospora sitophila, 15 days after cataract extraction. Note hypopyon and cottony anterior hyaloid abscess a dj acent t o p upillary margin and other early lesions o n vitreous face (from Theodore et al').

~~:;::"Ml~~g

SYMPOSIUM ON POSTOPERATIVE ENDOPHTHALMITIS

Fig 2.-Subculture of Neurospora sitophiia from anterior chamber aspiration of patient shown in Fig 1 (from Theodore et al·').

microbiologic methods. Because of this experience, sections of the enucleated eye of another patient previously seen in consultation who had presented a strikingl; similar clinical picture, were studied by the periodic acid-Schiff stain and found on histopathologic examination to have an extensive mycotic infection of the anterior vitreous (Fig 3 through 5). The organism involved in this case resembled Neurospora or Oospora morphologically.

Fig 3.-Mycotic endophthalmitis 20 days after cataract extraction (from Theodore et ai').

329

Fig 4.-Section of eye shown in Fig 3 after enucleation on 83rd day, showing characteristic involvement of anterior vitreous (from Theodore et ai').

Experimental inoculation of rabbit eyes with Neurospora obtained from the original patient resulted in the production of similar fungal endophthalmitis, confirmed by histopathologic examination. 6 In 1960, Paiva and his associates 7 reported an instance of mycotic postcataract endophthalmitis which was first manifested 60 days after surgery by the appearance of a deep corneal infiltration. This progressed in spite of intensive local and systemic treatment with corticosteroids and antibiotics. A fraction of affected tissue was obtained by anterior chamber paracentesis, and cultures revealed a fungus, Hyalopus bogolepofii, apparently related to Cephalosporium. Since it was not possible to check the evolution of the disease, the eye was enucleated. The same fungus was cultivated from all parts of the removed eye. Histopathology showed fungal involvement of all the internal structures as well as in the cornea.

330

FREDERICK H. THEODORE

OPHTH AAOO

Fig 5.-Photomicrograph of Fig 4 showing fungi in vitreous (PAS, X440) (from Theodore et a\2).

By 1961, we had collected enough data to publish a definitive clinical and laboratory study on the diagnosis of fungus endophthalmitis following cataract extraction. 2 In the paper, an apparently typical clinical picture of the entity was delineated, methods of clinical and laboratory diagnosis described, and treatment discussed in detail. Eight cases were reported. Three were proved by microbiologic cultures to be due to so-called contaminant fungi: Neurospora sitophila, Cephalosporium, and Volutella. One case was proved by histopathology. The other four showed the typical clinical picture but anterior chamber aspirations were either not performed or, when performed, fungal cultures were not taken. We stressed the following: (1) a significant number of postoperative infections after cataract surgery

are due to fungi; (2) fungal endophthalmitis caused by saprophytic organisms is an entity of definite clinical importance; (3) it presents a rather typical clinical picture, easily diagnosed once learned; and (4) since the visual result in the patient is poor even if the eye is saved, prevention of such fungal infection is our primary concern. We also pointed out that whenever the infecting fungi could be identified by cultural methods, they were shown to be so-called saprophytic contaminant organisms. This indicated that the major problem at the present time lies with the large group of soil and air contaminants rather than with recognized fungal pathogens. It was our conclusion that, despite the opinion of mycologists that such fungi were nonpathogenic because elsewhere in the body they did not cause infection, as far as the eye was con-

~~~~M1~~g

SYMPOSIUM ON POSTOPERATIVE ENDOPHTHALMITIS

331

cerned, there was no such thing as a harmless fungus. s Further reports of postcataract fungal endophthalmitis rapidly became available on an almost worldwide basis. In 1962, Francois and his group9 from Belgium reported two instances. One was found on smears and cultures believed to be due to Hormodendrum. The other was caused by an infection with Sporotrichum schenckii. In this patient who, like the first, required enucleation, smears of the vitreous were negative at the time of enucleation. However, positive cultures grew out in ten days. Kuper,lo in Germany (also in 1962), observed two additional cases. In one patient, S schenckii was grown on cultures; in the other, cultures revealed Cephalosporium. Strampelli and Maggi,!1 in Italy, reported an infection with Scopulariopsis breuicaulis . Important communications from South America also appeared such as those of De Rezende,12 Salles,13 and De Aimeida I4 who, in a series of 2,076 cataract extractions, found 77 postoperative infections (3.75%), of which 13 (0.62%) were mycotic. Queiroga reported infection with Aspergillus. 15 Cephalosporium postcataract infection in three patients caused by contaminated eye solutions has been observed by Crompton16 in Australia. I have personally been consulted on a mycotic infection occurring in Nepal, in central Asia. Curiously, although Penicillium is a rather ubiquitous environmental fungus and is known to be a frequent cause of mycotic keratitis (Fig 6), no proved and documented case of postcataract infection due to this fungus was noted prior to 1970 when I encountered a clearly

Fig 6.-Intr a ocular infection with Penicillium species when first seen 78 days after cataract surgery. Note posterior abscess of cornea, clouding of a nterior vitreous, a nd small hypopyon. Ra pid progression to descemetocele and imminent per· foration occurred in n ine days.

diagnosed and mycologically proved instarice. 17 A fairly large number of reports of postoperative mycotic endophthalmitis have now been published. References not noted here are available in the summary tables of papers by De Rezende,1 2 Strampelli and Maggi,ll myself,IB Jones,19 Francois and Rysselaere 20 (who also include one infection after retinal detachment surgery), and De Voe and Silva-Hunter,21 who note cases following keratoplasty. However, no such infections complicating glaucoma surgery are listed in any of these compendia, although two have come to my attention. Litricin and Parunovic 22 have reported an instance diagnosed histopathologically on enucleation 171f2 months after iridencleisis for glaucoma. Inflammatory symptoms first occurred several months after the glaucoma surgery. Malbran et al 23 have reported an infection with Penicillium lilacinum,

332

FREDERICK H. THEODORE

proved on culture, beginning one week after iridencleisis. The globe was saved after subconjunctival and intracameral injection of am ph otericin B, but visual acuity was reduced to light perception only. In addition, Curvularia,24 Petriellidium boydii (Allescheria baydii or Monosporium),25 and Trichosporon cutaneum 26 have also been found on culture to be responsible for postoperative endophthalmitis (POE) after cataract extraction. Nocardia asteroides 27 has been diagnosed on histopathologic examination of an enucleated eye. All reported instances of POE caused by fungi had been sporadic in occurrence until late in 1975, when Pettit28 first reported a disastrous series of infections following the implantation of intraocular lenses after cataract extraction. Pettit personally observed five cases and was aware of seven others. The responsible fungus was found in all instances to be Paecilomyces lilacinus, known as the "bottle imp" which, in 11 instances, was traced to bottles of the sodium bicarbonate neutralizing solution supplied by the manufacturer along with the lenses. With the exception of one instance following the placement of a Binkhorst four-loop lens (Rayner) reported in detail by Mosier et al,29 all other cases followed the use of the Luminex lens. 30 In ten of these cases cultures were positive. Seven eyes were enucleated. One eye achieved 20/25 visual acuity after removal of the lens without any antifungal treatment. 31 Another patient, after lens removal, radical vitrectomy, iridectomy, and intraocular, topical, and systemic antimycotic drugs, achieved

OPHTH AAOO

20/60 visual acuity.32 This later dropped to 20/80- due to corneal edema following secondary glaucoma.

A change in nomenclature from Penicillium lilacinum to Paecilomyces lilac in us has occurred in the last few years. Thus, the case of postcataract infection with Penicillium lilacinum mentioned by Barrie Jones in 197533 and that of Malbran et al in 197323 are now considered as instances of Paecilomyces lilacinus infections by Miller et a1. 32 Actually, Paecilomyces lilacinus, along with Scopulariopsis and Gliocadium (the most closely related) have long been separated from Penicillium but treated as related genera. However, the relationship may not be as close genetically as originally postulated. Individual instances of mycotic POE following intraocular lens implants due to different fungi have also been observed. Forster34 isolated Acremonium species from the vitreous in one patient and found yeast histopathologically in another patient whose eye was sent to him after enucleation. I am also aware of an Aspergillus species infection resulting in eventual enucleation after lens implantation. Table 1 lists fungi isolated on cultures from instances of postcataract mycotic endophthalmitis. In addition to those listed in Table 1, fungi (eg, Actinomyces and Nocardia) have been responsible for additional instances of POE following cataract extraction which were not diagnosed until histopathologic examination, using special fungus stains following enucleation, was performed. Table 2 notes the fungi identified by cultural methods after

~~~::'MI9rs

SYMPOSIUM ON POSTOPERATIVE ENDOPHTHALMITIS

333

TABLE 1 fuNGi GROWN ON CULTURES FOLLOWING POSTCATARACT MYCOTIC ENDOPHTHALMITIS

Acremonium species Aspergillus fumigatus A niger Candida albicans C lipolytica C parakrusei Cephalosporium species Curvularia species Hormodendrum species Hyalopus bogolepofii

TABLE

Hyalosporus Neurospora sitophila Paecilomyces lilacinus Penicillium species Petriellidium boydii (Allescheria or Monosporium) Scopulariopsis brevicaulis Sporotrichum schenckii Trichosporon cutaneum Volutella cinerescens Volutella species

2

FUNGI RESPONSIBLE FOR MYCOTIC INFECTIONS FOLLOWING OTHER OCULAR SURGERY TYPES

Keratoplasty (all on cultures): Aspergillus nidulans Candida species Cephalosporium species Pullularia pullulans Trichophyton rubrum Retinal detachment surgery: Blastomycetes (histopathology) Glaucoma surgery: Penicillium lilacinum (culture) Unidentified fungus (histopathology)

other types of ocular surgery. No doubt other organisms causing such infections have been reported, but have escaped my attention. SOURCES OF MYCOTIC INFECTION These are discussed in detail elsewhere in this symposium. However, in addition to the problems inherent to all surgical eye infections including the preoperative

medication, preparation of the patient, basic principles of surgical technique, and instrument sterilization, some other aspects must be stressed. Except for the three Volutella infections caused by infected cocaine mentioned early in this paper, until recently instances of mycotic POE were sporadic and individual, not multiple in occurrence. My own impressionis has been that operating room air contamination may be an important factor in addition to the skin, eyelids, and conjunctival sac of patients. In line with this is the potential role of starch-derivative glove powders in the causation of both bacterial and mycotic POE, as originally pointed out by Posner.35 This investigator showed that such types of glove powder, substituted over 25 years ago for talc to avoid granuloma formation, contain large numbers of fungi and bacteria in their natural state. Sterilization of generously applied powder in gloves and in the small paper packets then included in the package is difficult and, sometimes, incomplete. Happily, the powder packets appear to have been discontinued, but powder is still used

334

FREDERICK H. THEODORE

in small amounts in the gloves themselves. Another important factor may have been the introduction of corticosteroids in the 1950s, which would appear to inhibit normal body resistance to otherwise easily overcome slight infections with "benign" fungi as noted elsewhere. 2 •18 Since then, the great popularity of intraocular lens implant surgery (IOL) has again highlighted the constant danger of infection from solutions originally noted by me long ago. 36 Recently, several series of multiple infections from contaminated solutions used in connection with the IOL have occurred. Details concerning 12 cases of P lilacinus pseudophakos infections (11 from one manufacturer and 1 from a different laboratory) have been described above. In addition, ten instances of infection with Pseudomonas aeruginosa due to contamination of one lot of intraocular lenses supplied by a third manufacturer have also occurred. Fortunately, five of the infected eyes recovered good vision, in contrast to the disastrous results from fungal infection. I know of a fourth contaminated solution from still another company fortunately discovered before use, from which Acremonium species were grown.

OPHTH

AAOO

endophthalmitis," all of serious outcome in which the cause was never determined. On this basis, the question arises whether, aside from the catastrophic episodes just mentioned, implantation of an IOL results in higher incidence of POE. Certainly, the longer duration of the surgery and the customary use of more intensive postoperative corticosteroid therapy may be predisposing factors in this regard. Furthermore, foreign bodies appear more prone to cause infections. Such a conclusion may require careful detailed analysis of reliable data. Already, several manufacturers have changed to gas sterilization of their IOL. CLINICAL PICTURE OF FUNGAL ENDOPHTHALMITIS

As already mentioned, fungal endophthalmitis almost always has a characteristic, rather pathognomonic, clinical picture and course. As distinguished from postoperative bacterial infection which usually is apparent within 24 to 48 hours after surgery, there generally is little indication of any abnormality until at least two weeks or even months after surgery. One case showed clinical findings on the eighth postoperative day. Usually, however, the patient appears to be doing well and has been discharged from the hospital long before any difficulties arise.

Although such information is difficult to obtain, as noted earlier in this paper, I am aware of three Earliest symptoms include inadditional sporadic instances of creasing redness and some pain, fungal infections following pseudo- with varying degrees of visual phakos implantation, as well as impairment marring a hitherto exfive bacterial infections following cellent postoperative course. Exsuch surgery. In none of these was amination reveals marked aqueous the source of infection established. flare and cells (often, but not I am also aware of other instances always), followed within a few days of what might be called "implant by a characteristic small hypopyon.

~~;~1Ml

SYMPOSIUM ON POSTOPERATIVE ENDOPHTHALMITIS

At the same time, one or more hazy gray-white areas appear in the anterior vitreous, just behind the hyaloid face, adjacent to the pupillary border (Fig 7). These findings usually prompt the institution of intensive antibiotic or corticosteroid therapy, or both. However, regardless of treatment, the hypopyon may soon disappear, with improvement in appearance of the eye.

Fig 7.-Ty pical clinical picture of mycotic POE with hy popyon and s ma ll vitreous a bscesses. Anterior cha mber tap was negati ve for bacteri a a nd fun gi. There was gradua l clearin g.

Nevertheless, the fungal invasion continues in an inexorable fashion. Localized involvement of the anterior vitreous increases by direct extension of the fungus. New zones of vitreous involvement may begin in different locations, almost always, curiously, adjacent to the pupillary margin. Associated with this, the aqueous increases in turbidity and develops stringy, gelatinous strands often running from the anterior vitreous to the bottom of the anterior chamber. The increased viscosity of the aqueous finally develops into a thick fibrin-

335

opurulent exudate. In many instances, rounded spots resembling balls of cotton with fuzzy edges are noted near the face of the vitreous next to the border of the Ins. Most striking in the majority of patients is the relatively low-grade tempo of the process. Although there often is some pain early in the infection, later it may not be an important finding. Light perception remains good. As far as the patient is concerned, his main complaints are visual. Meanwhile there is a gradual increase in aqueous turbidity with the development of a stringy, filamentous labyrinthine meshwork in the anterior chamber. Floating cells appear to be almost, but not quite, motionless. As the fungal invasion advances, deeper vitreous abscess formation develops, usually in one large area, with parts of the hyaloid relatively clear and parts of the fundus visible. The intraocular tension is usually low or normal. Occasionally, it may be moderately elevated. In the further progression of the infection, I have noted several other, again almost pathognomonic, developments. The anterior vitreous process may proliferate anteriorly over the face of the iris, bulging forward in a horn-like fashion (Fig 8). In other cases, although the vitreous abscess itself does not progress anteriorly, fungi in the aqueous invade the posterior cornea, resulting in a posterior corneal a bscess. Once the cornea becomes involved from the back, inflammation becomes more intense and, in my experience,17 destruction of the cornea at that location occurs in only a matter of a few weeks' time.

336

FREDERICK H. THEODORE

Fig S.-Case of presumed mycotic POE 35 days after cataract extraction, showing large hornlike process originating in anterior vitreous growing over surface of iris and protruding into anterior chamber. Small hypopyon is present.

Sometimes, following the initial hypopyon the course is more explosive and the entire pupillary area is involved in a massive exudative abscess bulging into the anterior chamber. The clinical picture of mycotic infection after intraocular lens implantation is essentially similar in onset and tempo. In the one case fully described,29 posterior corneal involvement was the initial major objective finding. In other cases, the lens becomes covered with purulent exudate and the usual characteristic picture is somewhat different, as well as obscured. CLINICAL COURSE

This paper is not concerned with therapy. However, it may be stressed that until now, with only a few exceptions, end results in culturally proved instances of mycotic POE

OPHTH AAOO

have been disappointing, culminating in either loss of the eye or loss of useful vision. Nevertheless, instances of presumed mycotic POE, diagnosed by the typical clinical picture where cultures and smears of the aqueous were either negative or not done, have been observed that eventually cleared completely on treatment of varying intensity. However, there are a few reported culturally proved instances of mycotic POE, one due to Candida parakrusei37 and the other to Monosporium,25 in which good vision was restored. Interestingly, both cases, reported individually, were treated at the same institution. In addition, the two salvaged eyes following P lilacinus infection due to pseudophakos, previously described, are to be noted. LABORATORY DIAGNOSIS

Laboratory confirmation of the nature of the infection may be obtained by positive smears and cultures of the anterior chamber contents inoculated on suitable media. Unless there are strong contraindications against performing anterior chamber aspiration, this should be done routinely. Continuing experience in this field has confirmed my statement of 196436 that it is far more conservative to perform such a tap than not to do so. The procedure is essentially innocuous if done as I have advocated for almost 20 years. Mter a drop of fluorescein, a small Graefe knife or a Wheeler discission knife is introduced just inside the limbus in the inferotemporal quadrant and passed into the corneal stroma, almost but not quite through the posterior layers. A disposable 25gauge needle on a tuberculin syringe is then inserted into this tract

~~~~Ml~~g

SYMPOSIUM ON POSTOPERATIVE ENDOPHTHALMITIS

and entered into the anterior chamber. This size needle enters effortlessly and is less apt to be blocked by thick exudate than is a thinner needle. Usually about 0.25 cc of anterior chamber exudate can be aspirated. This is inoculated into suitable culture media, but it is important to save enough material for slide examination. Specimens obtained from the eye must be cultured on both bacterial and fungal culture media. Suitable bacterial media are brain-heart infusion and thioglycollate broths and blood agar. Recommended fungal media include slants of Sabouraud dextrose agar, liver-spleenglucose-blood agar, and Littman oxgall agar. Agar slants have been recommended in order to rule out accidental air-borne contamination. However, such slants are more difficult to work with. If one inoculates only the center of the plate, contamination may be ruled out with reasonable certainty. Although most fungi grow better on fungal media, quicker growth may sometimes occur on blood agar or the standard broth media. Room temperature (25 C) is recommended, but sometimes incubation at 37 C on blood agar may show faster growth. Slide examination of direct smears by Gram stain, periodic acid-Schiff, or other fungus stains are often valuable. My own experience with the use of 10% potassium hydroxide fresh mounts has been less rewarding. One cannot stress too strongly the value of direct smear diagnosis. When positive, it will save the 5 to 21 days required for a fungus culture to grow out. Moreover, it may be the only positive finding, should cultures prove negative (as

337

they often do). Finally, if cultures are positive, it proves conclusively that the bacteria or fungus growth is not a contaminant. When indicated, vitreous aspiration may prove positive in situations where simple anterior chamber tap might be negative. This is performed through the same corneal incision using a second tuberculin syringe fitted with a 22-gauge needle which is passed into the vitreous to obtain a 0.2- to 0.3-cc sample as advocated by Forster.38 If vitrectomy is performed, the same author concentrates the aspirates obtained by means of a millipore filter. Other methods of vitreous aspiration include that of Peyman,39 who inserts a fine needle into the pars plana after scleral incision. The justification for vitreous aspiration is further emphasized by the fact that negative smears and cultures of the anterior chamber may occur because the essential process is located in the anterior vitreous. Moreover, these relatively benign fungi apparently become so attenuated that they either eventually die in situ or become unviable on experimental culture media. It has been shown in experimentally infected rabbit eyes that fungus cultures of the vitreous as well as the anterior chamber, at the time of enucleation, may show no growth, despite the demonstration of large numbers of fungi in the vitreous on histopathologic examination. 6 Thus, negative fungus culture of either the anterior chamber or vitreous does not necessarily preclude the diagnosis of mycotic endophthalmitis. On the contrary, a negative bacterial culture and the occurrence of the unique clinical picture following cataract surgery

338

FREDERICK H. THEODORE

described previously should alert the ophthalmologist to the possibility of fungus infection. DIFFERENTIAL DIAGNOSIS

The primary entities to be differentiated from mycotic POE are bacterial infections and noninfectious reactions (aseptic POE), including chemical reactions and reactions to retained lens matter. The characteristics of bacterial POE have already been detailed in this symposium. The early onset (usually within several days but sometimes as late as one week), severe pain, marked visual impairment, severe edema of eyelids and conjunctiva with marked inflammation, early hypopyon and massive explosive exudation in the anterior chamber and vitreous all are different from the gradual onset of mycotic POE. Anterior chamber and vitreous aspirations are usually most valuable. Late bacterial infections (occurring weeks to years after surgery) due to vitreous wicks, suture abscesses, suture necrosis, or cystic blebs are easily recognized by the findings, as well as by their sudden and rapidly progressing course. Aseptic reactions 40 also usually occur early after surgery but can appear up to three weeks later. Marked lid edema may occur. There is moderate pain and redness and, only rarely, hypopyon. Generally, unless there is corneal clouding, vision is good, and the vitreous uninvolved. Anterior chamber aspiration is negative. Response to corticosteroids is often dramatic. Chemical reactions to instilled medicaments may be noted immediately during the course of

OPHTH AAOO

surgery or, almost always, within 24 hours. There are clues at operation and the response is generally not purulent. Retained cortex is rarely as hyperacute. Cottony, fluffy cortex is seen in the anterior chamber, particularly in the pupillary zone. In infection, exudates extend over the face of the iris vitreous and posterior cornea. SUMMARY

Infection with "contaminant" fungi of low pathogenicity following intraocular surgery is now an established cause of POE. Such infections, until recently, were not recognized clinically and were often overlooked even after histopathologic examination of enucleated eyes unless special fungus stains were used. About 20 different varieties of so-called benign fungi have now been culturally identified as etiologic agents in POE; many other instances of mycotic POE due to unidentified fungi diagnosed only after enucleation, not on cultures, ha ve also been reported. While most instances of mycotic POE have occurred singly, a recent series of infections following intraocular lens implantation due to one organism-P lilacinus-involving 12 patients and traced to the neutralizing solution supplied by two different manufacturers, once again dramatically highlights the importance of such fungal infections. Contamination of solutions from two other IOL suppliers has also been noted. As in most proved instances of mycotic POE, the results in these patients were disastrous. Single mycotic infections following IOL implants have also been observed.

~~;J'i.Mt9~~

SYMPOSIUM ON POSTOPERATIVE ENDOPHTHALMITIS

Mycotic POE presents an almost typical picture, affording the ophthalmologist a high index of suspicion of fungal infection in practically every instance encountered. Precise diagnosis requires anterior chamber and, when indicated, vitreous aspiration for microbiologic material. At the onset, the infection is almost always localized to the anterior chamber, iris, and anterior vitreous where multiple abscesses are found. Later, the cornea may become involved through invasion of the posterior layers.

339

hyalopus bogolepofii. Rev Brasil Oftalmol 19:193-202, 1960. 8. Theodore FH: The role of so-called saprophytic fungi in eye infections, in Dalldorf G (ed): Fungi and Fungus Diseases. Springfield, Ill, Charles C Thomas Publisher, 1962, chap 3. 9. Francois J, De Vos E, Hanssen M, et al: Mycoses intraoculaires. Ann Oculist 195:97-119, 1962.

10. Kuper J: Zur Klinik postoperativer intraokularer Mykosen. Klin Monatsbl Augenheilkd 140:827-834, 1962. 11. Strampelli B, Maggi C: Endoftalmite micotica post·operatoria. Rev Ital Tracoma Patol Oculare Virale Esotica 15:168-189, 1963. 12. De Rezende C: Ocular mycosis, in XIX Concilium Ophthalmologicum. New Delhi, Acta I, 1962, pp 299-367.

Key Words: Fungus infections; ocular surgery; mycotic endophthalmitis; mycotic infections; intraocular lens implants; infections after cataract extraction; pseudophakos infections; aspiration of anterior chamber; aspiration of vitreous; mycotic corneal abscess.

13. Salles FJ Monteiro: Histopatologia das endoftalmites pos-operatoriasa, in De Rezende C: XIX Concilium Ophthalmologicum. New Delhi, Acta I, 1962, p 332.

REFERENCES

14. De Almeida AA: InfecdlO pos-operatoria bacteriana e micotica. Rev Brasil Oftalmol 22:53-64, 1963.

1. Fine BS, Zimmerman LE: Exogenous intraocular fungus infections with particular reference to complications of intraocular surgery. Am J Ophthalmol 48:151-165, 1959_

15. Queiroga G: Endoftalmite mic6tica posoperat6ria, in De Rezende C: XIX Concilium Ophthalmologicum. New Delhi, Acta 1,1962, p 332.

2. Theodore FH, rittman ML, Almeda E: The diagnosis and management of fungus endophthalmitis following ,cataract extraction. Arch Ophthalmol 66:163-175, 1961.

16. Crompton DO: Prevention of sepsis, in Theodore FH (ed): Complications After Cataract Surgery. Boston, Little Brown & Co, 1965, pp 509-531.

3. Foster JBT, Almeda E , rittman ML, et al: Some intraocular and conjunctival effects of amphotericin B in man and in the rabbit. Arch Ophthalmol 60:555-564, 1958.

17. Theodore ' FH: Penicillium postcataract endophthalmitis. Read before the annual meeting of the Ocular Microbiology and Immunology Group, Dallas, Sept 20, 1975.

4. Fine BS, Zimmerman LE : Postoperative mycotic endophthalmitis diagnosed clinically and verified histopathologically. Br J Ophthalmol 43:753-758, 1959.

18. _ _ _: Mycotic endophthalmitis, in Theodore FH (ed): Complications After Cataract Surgery. Boston, rittle Brown & Co, 1965, pp 81-101.

5. Theodore FH, rittman ML, Almeda E: Endophthalmitis following cataract extraction due to Neurospora sitophila , a socalled nonpathogenic fungus. Am J Ophthalmol 53:35-39, 1962.

19. Jones BR, Richards AB, Morgan G: Direct fungal infection of the eye in Britain. Trans Ophthalmol Soc UK 89:727-741, 1969.

6. Prenner E, Laval J, Theodore FH: Experimental mycotic endophthalmitis. Am J Ophthalmol 54:817-821, 1962. 7. Paiva C, Chaves Batista A, Gomes A: Endoftalmite mic6tica posoperatoria por

20. Francois J , Rysselaere M: Oculomycoses. Springfield, Ill, Charles C Thomas Publisher, 1972, pp 79-81. 21. De Voe AG, Silva-Hunter M: Fungal infections of the eye, in Locatcher-Khorazo D, Seegal BC (eds): Microbiology of the Eye. St Louis, CV Mosby Co, 1972, pp 208-240.

340

FREDERICK H. THEODORE

22. Litricin 0, Parunovic A: Mycose intraoculaire post-operatoire. Ann d'Oculistique 197:164-171, 1964.

OPHTH AAOO

the Ocular Microbiology and Immunology Group, Las Vegas, Oct 5, 1976.

23. Malbran E, Albesi EJ, Daro H, et al: Endoftalmitis por penicillium lilacinum. Arch Oftalmol Buenos Aires 48:253-258, 1973.

32. Miller GR, Rebell G, Magoon RC, et al: Intravitreal antimycotic therapy and the cure of mycotic endophthalmitis caused by a Paecilomyces lilacinus contaminated pseudophakos. Ophthalmic Surg, to be published.

24. Aquino MV, Uy VK, Salceda SR: Fungus endophthalmitis following lens extraction. Phil J Ophthalmol 3:49-53, 1971.

33. Jones BR: Principles in the management of oculomycosis. Am J Ophthalmol 79:719-751, 1975.

25. Glassman MI, Henkind P, AltureWerber E: Monosporium apiospermum endophthalmitis. Am J Ophthalmol 76:821824, 1973.

34. Forster RK, in discussion, Pettit TH: An outbreak of Paecilomyces lilacinus postsurgical endophthalmitis due to contaminated intraocular lens solution. Read before the annual meeting of the Ocular Microbiology and Immunology Group, Las Vegas, Oct 5, 1976.

26. Sheikh HA, Mahgoub S, Badi K: Postoperative endophthalmitis due to Trichosporon cutaneum. Br J Ophthalmol 58: 591-594, 1974. 27. Meyer SL, Font RL, Sharer RP: Intraocular nocardiosis. Arch Ophthalmol 83: 536·541, 1970. 28. Pettit TH: Letter to the editor. Clin Trends 14:6, 1976. 29. Mosier MA, Lusk B, Pettit TH, et al: Fungal endophthalmitis following intraocular lens implantation. Am J Ophthalmol 83:1-8, 1977.

35. Posner A: Role of starch derivative glove powders in hospital infection. Eye Ear Nose Throat Mon 39:175-177, 1960. 36. Theodore FH: Bacterial endophthalmitis after cataract surgery. Int Ophthalmol Clin 4(No. 4):839-859, 1964. 37. Rosen R, Friedman AH: Successfully treated postoperative Candida parakrusei endophthalmitis. Am J Ophthalmol 76:575577, 1973. 38. Forster RK: Endophthalmitis. Arch Ophthalmol 92:387-392, 1974.

30. O'Day DM: Fungal endophthalmitis caused by Paecilomyces lilacinus after intraocular lens implantation. Am J Ophthalmol 83:130-131, 1977.

39. Graham RO, Peyman GA, Fishman G: Intravitreal injection of cephaloridine in the treatment of endophthalmitis. Arch Oph· thalmol 93:56-61, 1975.

31. Pettit TH: An outbreak of Paecilomyces lilacinus post-surgical endophthal· mitis due to contaminated intraocular lens solution. Read before the annual meeting of

40. Allen HF, Grove AS Jr: Early acute aseptic iritis after cataract extraction. Trans Am Acad Ophthalmol Otolaryngol 81:0P145-0P-150, 1976.