Symposium: Postoperative Endophthalmitis l'
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ETIOLOGY AND DIAGNOSIS OF BACTERIAL POSTOPERATIVE ENDOPHTHALMITIS RICHARD K. FORSTER, MIAMI, FLORIDA
MD
It is necessary to determine if postoperative endophthalmitis is of infectious or sterile etiology. Intraocular contents should be cultured and were positive in 50% of 58 eyes tested at our institute with suspected postoperative endophthalmitis. The vitreous aspirate is more sensitive than the anterior chamber aspirate in making a diagnosis. The use of a membrane filter to concentrate vitreous samples obtained at vitrectomy increases diagnostic yield. Fifty percent of culture-positive eyes yielded gram-positive organisms. Stained smears were consistent with the cultured organism in half of the cases.
diagnostic technique and media used for obtaining intraocular cultures and the criteria for determining if the endophthalmitis is infectious or sterile, (2) the importance of obtaining the intraocular cultures from the vitreous body, and (3) the specific etiologic agents causing bacterial endophthalmitis.
LIMITED treatment success and newer routes of antibiotic delivery necessitate more specific diagnosis in the management of postoperative endophthalmitis. Determination of cause and success of treatment have frequently been confusing because of failure to obtain and confirm cultures from the intraocular contents. Therefore, it is necessary to determine if the etiology is infectious or sterile.
In the majority of cases, bacterial endophthalmitis develops suddenly, progresses rapidly,l and usually becomes manifest in the first 24 to 48 hours after surgery. Symptoms out of proportion to the expected inflammatory response should alert the surgeon to a diagnosis of endophthalmitis and to suspect an infectious etiology. Since prompt diagnosis is critical if therapy is to be effective, postoperative evaluation of anterior chamber and vitreous reaction is mandatory rather than waiting for the more classic signs of an infection such as pain, hypopyon, or loss of fundus reflex.
The purpose of this report is to emphasize and consider (1) the
Submitted for publication Oct 3, 1977. From the Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami School of Medicine. Presented at the Eighty-second Annual Meeting of the America n Academy of Ophthalmology and Otolaryngology, Dallas, Oct 2-6, 1977. Reprint requests to Bascom Palmer Eye Institute, 900 NW 17th St, Miami, FL 33152.
DIAGNOSIS
Clinical Features
In patients with a delayed onset of inflammation, unexpected signs or symptoms may be of more importance in clinical diagnosis. This is especially the case in eyes with inadvertent postcataract extraction blebs, or following glaucoma filtering surgery. There are
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two other situations in which endophthalmitis caused by a bacterial agent may appear in a delayed manner after intraocular surgery. Organisms of lesser virulence, such as Staphylococcus epidermidis or Propionibacterium acnes, may develop clinical endophthalmitis at 24 to 72 hours but more often are present as an indolent, inflammatory reaction in which diagnosis may be delayed four to eight weeks postoperatively. The other situation is with more virulent organisms in which inflammation is delayed because of prophylactic treatment at surgery with periocular antibiotics. Background on Diagnostic Cultures Until recently, there was a difference of opinion as to the need for obtaining intraocular cultures. Theodore} emphasized the limited value of conjunctival cultures and stressed that the nature of the infection inside the eye may be entirely different from that outside. He concluded that it is far more conservative to perform such a tap than not to do so. Maylath and Leopold 2 demonstrated that, in the rabbit, the anterior chamber has greater ability to resist an infecting agent than does the vitreous. While there was conflicting and limited data available on the value of anterior chamber cultures, information on vitreous cultures was even less. Although not emphasizing it, Allansmith3 reported four cultures that were positive from the vitreous but negative from the anterior chamber in ten cases of nonpostoperative endophthalmitis. Culture Technique Patients suspected of harboring infectious endophthalmitis are taken
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to the operating room and, after appropriate sedation and retrobulbar or general anesthesia, the anterior chamber and vitreous fluid are aspirated for culture and stained smears. Aspiration is accomplished by the following technique: A beveled keratotomy is made through peripheral clear cornea with a razor blade to incise the cornea deeply but not enter the anterior chamber.} A 25- or 27~gauge needle attached to a 1-cc tuberculin syringe is then introduced into the anterior chamber through this incision. Care should be exercised to avoid touching the corneal endothelium and the lens in phakic patients. The yield of 0.1 to 0.2 ml of fluid is obtained and immediately inoculated onto media in the operating room. Several drops should be placed on the media or one drop allowed to flow several centimeters on the surface of the solid media. In aphakic patients, a second tuberculin syringe is fitted to a 22-gauge needle and passed through a slightly enlarged keratotomy incision and into the vitreous where it is manipulated until 0.2 to 0.3 ml of aspirate is obtained. In phakic eyes with endophthalmitis complicating filtering blebs, vitreous is aspirated through a sclerotomy at the pars plana, 4.5 mm posterior to the limbus. 4 If an inadequate vitreous sample is obtained or if one suspects a fungal etiology, the keratotomy or pars plana incision is enlarged to approximately 2.3 mm and a vitreous instrument such as the vitreous infusion suction cutter (VIS C) is introduced to remove and sample formed vitreous. Such a sample, diluted by the irrigating solution, is then passed through a disposable membrane filter system.
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After applying appropriate vacuum the system is disassembled, the filter is sterilly removed to a sterile Petri dish, and it is cut into pieces for appropriate inoculation onto the media (Fig 1 and 2).
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Sabouraud agar and blood agar are inoculated and maintained at room temperature (25 C) for fungal isolation. Careful application of the drops of aspirate away from the edges of the plate and flaming of the tubes of liquid media before and after inoculation will prevent or reduce contamination. Slides are routinely prepared for Gram and Giemsa stains and, more recently, for the modified Grocott's methenamine silver (GMS) stain for fungi. 5 Culture Criteria and Interpretation
Culture criteria have been established to more accurately confirm the etiology in endophthalmitis. A positive culture is defined as growth of the same organism on two or more media, or semiconfluent growth on one or more solid media at the inoculation site (Fig 3). An equivocal culture is defined as growth in one liquid medium or scant growth on one solid medium only. Culture Results Fig i.-Membrane filter culture technique. Vitreous sample is transferred into filter-v acuum system.
Culture Media
Specimens aspirated from the anterior chamber and vitreous or sections of the membrane filter, through which a vitreous sample is concentrated, are inoculated onto blood agar and chocolate agar and into liquid brain-heart infusion and thioglycolate to be incubated at body temperature (37 C). Likewise,
Fifty-eight eyes with clinical postoperative endophthalmitis have been cultured at the Bascom Palmer Eye Institute in Miami from July 1969 to July 1977. Of these, 44 eyes with suspected infectious endophthalmitis were seen in patients who had recently undergone intraocular surgery (39 following cataract surgery, one following keratoplasty, and four following elective vitrectomy). Inadvertent postcataract and postglaucoma surgical filtering blebs accounted for 14 eyes with delayed -endophthalmitis and occurred months or years after surgery.
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Fig 2.-Con tinuation of Fig l. Top left, Membrane filter (451' pore size) is removed and transferred to sterile Petri dish. Top right, Filter is cut into four or more sections. Bottom left, Sections of filter are placed on agar media (top surface side up). Bottom right, Growth after 24 hours of Alpha strep· tococcus on membrane filter.
side red equivocal in five (three recently and two delayed postoperative), since growth was present in only one liquid medium or scant on one solid medium. In 22 eyes cultures were negative-18 recent and 4 delayed postoperative.
Fig 3.- C ulture·positive P acnes on chocolate agar. Each cluster of colonies represents growth from one drop of vitreous fI uid.
Thirty-one positive microbial isolates were cultured from the 58 eyes, including 23 of 44 eyes recently postoperative and 8 of 14 with delayed onset. Isolates were con-
Vitreous aspiration was more accurate than anterior chamber paracentesis in making a culturepositive diagnosis. 6 There were 13 eyes in which the vitreous culture was positive but the concomitant anterior chamber culture was negative. Eight of the 13 eyes were aphakic and included three with intraocular lenses. In no case have we observed a negative culture from the vitreous and a positive culture from the anterior chamber.
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RICHARD K. FORSTER
These findings support the recommendation to aspirate vitreous in all cases of suspected endophthalmitis and confirm the observation that a negative anterior chamber aspiration does not rule out an intraocular infection. We recently examined and managed a patient who underwent uncomplicated cataract surgery. One week following the operation the eye became inflamed and an anterior chamber aspiration was culture negative. After treatment with systemic antibiotics and topical and systemic corticosteroids, the eye developed a hypopyon and vitritis. A diagnostic anterior chamber and vitreous aspiration was performed with installation of intraocular antibiotics; the cultures were again negative. After an additional three weeks of corticosteroid therapy, the inflammatory reaction became more fulminant and we performed a diagnostic and therapeutic subtotal vitrectomy. Vitreous aspirate passed through a membrane filter was positive for Alpha streptococcus (Fig 4).
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Fig 4.- Top, Postcataract endophthalmitis three weeks after culture-negative anterior chamber and vitreous aspiration. Bottom, Concentrated growth of A streptococcus on membrane filter. Vitreous sample obtained at time of diagnostic and therapeutic vitrectomy.
Only culture-positive isolates from the anterior chamber and the vitreous reliably indicate the causative etiology in endophthalmitis.
Fourteen postcataract eyes were cultured by anterior chamber paracentesis and reported by Allansmith et al,9 and five were culture positive. These included three S aureus, one paracolon bacillus, and one Bacillus subtilis.
Accepted reports indicate that approximatley 50% of postcataract endophthalmitis is due to S aureus and tha t 25% is due to gramnegative species. In the initial 22 cases of endophthalmitis reported by Allen and Mangiaracine, 7 11 infections were attributed to S aureus and four to Pseudomonas. However, in the most recent series, six of nine infections were due to gram-negative species. 8
The Table lists the 28 specific postoperative bacterial isolates obtained in 31 eyes with positive cultures in Miami. These isolates include 16 gram-positive, 12 gramnegative, and three fungal organisms. Only 3 of 16 gram-positive organisms were S aureus, and among the gram-negatives, Proteus species predominated with five cases. It should be noted that, with increasingly specific diagnoses, ad-
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POSTOPERATIVE BACTERIAL ENDOPHTHALMITIS GRAM POSITIVE
GRAM NEGATIVE
NO. PATIENTS
NO. PATIENTS
S epidermidis
5
Proteus species
5
S aureus
3
Pseudomonas species
3
Streptococci
6
Hemophilus influenzae
3
P acnes
2
Klebsiella species
1
Total
16
12
ditional etiologic agents are being described. Our experience in culturing S epidermidis confirms the initial isolates of Valenton et aPD and Allansmith et al. 9 We have cultured S epidermidis in five postoperative eyes and in four other eyes, including three following trauma and one from a metastatic endophthalmitis in a drug addict with a mixed infection caused by S epidermidis and Aspergillus {lavus (Fig 5). We cultured P acnes in two eyes following intraocular lens insertion. Both eyes had a smouldering clinical inflammation with late onset, and in one an anterior chamber culture was negative at the time of lens removal. The eyes infected by S epidermidis and P acnes emphasize the fact that any organism, regardless of apparent virulence, is capable of eliciting an infectious, intraocular process. Three of the eight infected blebs (described earlier) were due to streptococcal species and three to Hemophilus in{luenzae, an organism not previously considered an etiologic agent in endophthalmitis. This finding reinforces the need to use chocolate agar as an isolation media since the growth requirement for this organism is lacking in sheep blood agar and most liquid media.
Fig 5.-Mixed growth from vitrectomy specimen concentrated on membrane filter obtained from drug addict with metastatic endophthalmitis. Top, Confluent growth of S epidermidis on blood agar (note one colony of fungus). Bottom, Growth of A flavus on Sabouraud agar.
As we have previously reported,4 with the exception of trauma, when cultures from the vitreous are negative, the visual prognosis is favorable, indicating that the endophthalmitis is usually of sterile etiology.
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Whereas examination of smears contributed little diagnostically or to the selection of therapeutic agents in our initial reported series,4 14 smears showed organisms consistent with the cultured isolate in the last 18 culture-positive eyes. Other Diagnostic Tests In an attempt to determine etiology promptly, we have investigated the limulus lysate test for detecting endotoxin released by gram-negative organisms. 11 Although results are encouraging in the animal model, our results in clinical endophthalmitis are inconclusive. However, the limulus lysate test combined with the Gram stain may enable us to make a more rapid and specific etiologic diagnosis and guide appropriate initial therapy. Key Words: Endophthalmitis; infectious endophthalmitis; sterile endophthalmitis; bacterial endophthalmitis; postoperative endophthalmitis; anterior chamber paracentesis; vitreous aspirate; membrane filter; vitrectomy; diagnostic vitrectomy.
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2. Maylath FR, Leopold IH: Study of experimental intraocular infection. Am J Ophthalmol 40:86-101, 1955. 3. Allansmith MR, Skaggs C, Kimura SJ: Anterior chamber paracentesis. Arch Ophthalmol 84:745-748, 1970. 4. Forster RK: Endophthalmitis: Diagnostic cultures and visual results. Arch Ophthalmol 92:387-392, 1974. 5. Forster RK, Wirta MG, Solis M, et al: Methenamine-silver-stained corneal scrapings in keratomycosis. Am J Ophthalmol 82:261-265, 1976. 6. Forster RK, Zachary IG, Cottingham AJ, et al: Further observations on the diagnosis, cause, and treatment of endophthalmitis. Am J Ophthalmol 81:52-56, 1976. 7. Allen HF, Mangiaracine AB: Bacterial endophthalmitis after cataract extraction: A study of 22 infections in 20,000 operations. Arch Ophthalmol 72:454-462, 1964. 8. _ _ _: Bacterial endophthalmitis after cataract extraction: II. Incidence in 36,000 consecutive operations with special reference to preoperative topical antibiotics. Trans Am Acad Ophthalmol Otolaryngol 77:581-588, 1973. 9. Allansmith MR, Skaggs C, Kimura SJ: The diagnostic value of anterior chamber paracentesis in 14 cases of postoperative endophthalmitis. Trans Am Ophthalmol Soc 68:335-355, 1970.
REFERENCES
10. Valenton MJ, Brubaker RF, Allen HF: Staphylococcus epidermidis (albus) endophthalmitis. Arch Ophthalmol 89:94-96, 1973.
1. Theodore FH (ed): Bacterial endoph· thalmitis after cataract surgery, in Complications After Cataract Surgery. Boston, Little Brown & Co, 1965.
11. McBeath J, Forster RK, Rebell G: Diagnostic limulus lysate assay for endophthalmitis and keratitis. Arc'h Ophthalmol (In press).