F U R T H E R OBSERVATIONS ON T H E DIAGNOSIS, CAUSE, AND T R E A T M E N T O F E N D O P H T H A L M I T I S RICHARD K. FORSTER, M.D., ANDREW J. COTTINGHAM, JR., M.D.,

IHOR G. ZACHARY,

M.D.,

AND EDWARD W. D. NORTON,

M.D.

Miami, Florida

Infectious endophthalmitis is a cata­ strophic complication of intraocular surgery and penetrating injuries of the eye. Deter­ mination of cause and treatment success has been confused because of failure to ob­ tain cultures from the intraocular contents. Rational therapy necessitates determining if the inflammation is infectious or sterile.1"3 The purpose of this report is to consider and emphasize : ( 1 ) a technique for obtain­ ing cultures, utilization of specific media, and the importance of diagnostic vitreous aspira­ tion; (2) the relative frequency of etiologic agents in specific types of infectious endophthalmitis; and (3) the rationale and results of intraocular antibiotics augmenting conventional therapeutic routes.

totomy was made with a razor blade, in an attempt to incise the cornea deeply but not to enter the anterior chamber.4 A 25-gauge needle attached to a 1-ml tuberculin syringe was used to enter the anterior chamber through this incision. The yield of 0.1 to 0.2 ml of fluid was then immediately inoculated onto media and placed on slides for staining. In patients with aphakia, a second tuberculin syringe fitted to a 22-gauge needle was passed through the keratotomy wound into the vitreous body and manipulated until 0.2 to 0.3 ml of aspirate was obtained. In pa­ tients suspected of endophthalmitis com­ plicating filtering blebs, trauma, or meta­ static infection, vitreous fluid was aspirated through a sclerötomy in the pars plana with or without an anterior chamber paracentesis.

MATERIAL AND METHODS

The specimens aspirated from the anterior chamber and vitreous body were then trans­ ferred in aliquots to blood agar, thioglycolate liquid, and brain-heart infusion to be main­ tained at 37° C, and to blood agar, Sabouraud's agar, and brain-heart infusion with gentamicin (50 jig/ml ) to be maintained at 25°C for fungal isolation. Care was taken to place the drops of aspirate away from the edge of the plates, and the mouths of the tubes containing liquid media were flamed before and after inoculation. Slides for Gram, Giemsa, and recently modified Gomori methenamine silver staining were also prepared from each aspirate. Interpretation of cultures—The criteria for a positive culture consisted of growth of the same organism on two or more media, or semiconfluent growth on one or more solid medium at the inoculation site. An equivocal culture was defined as growth in one liquid medium or scant growth on one solid medium only. Intraocular and conventional antibiotic

One of us (R.K.F.) has seen in consulta­ tion, for diagnosis and treatment, 54 cases of suspected endophthalmitis between July 1969 and March 1975. Diagnostic technique—Patients suspected of harboring endophthalmitis, whether recent postoperative, long-term postoperative, trau­ matic, or metastatic, were taken to the oper­ ating room, and after appropriate sedation and retrobulbar anesthesia the anterior chamber and vitreous fluid were aspirated for culture. This was accomplished by the following technique: A limbal-corneal keraFrom the Bascom Palmer Eye Institute, Depart­ ment of Ophthalmology, University of Miami School of Medicine, Miami, Florida. This study was supported in part by the Public Health Service training grant EY-0028 from the National Eye In­ stitute, the Flournory and Mae Knight Clark Re­ search Fund, and the Florida Lions Eye Bank. Presented at the 111th Annual Meeting of the American Ophthalmological Society, Hot Springs, Virginia, May 31, 1975. Reprint requests to Richard K. Forster, M.D., Bascom Palmer Eye Institute, P.O. Box 875, Biscayne Annex, Miami, FL 33152.

52

therapy—In the operating room, after as­ piration of anterior chamber or vitreous ma­ terial, or both, and appropriate inoculation onto media and slides, antibiotics were slowly injected through the previously pre­ pared site into the approximate center of the vitreous cavity or anterior chamber, or both. All patients received 0,1 mg of gentamicin (100 μg), in 0.1 or 0.25 ml into the vitreous cavity, and 0.25 mg of cephaloridine (250 μg), in 0.1 ml into the anterior chamber or vitreous cavity. In selected cases, 0.005 mg of amphotericin B (5 μ-g) was injected into the vitreous body. This regimen was augmented at surgery and for several days by subconjunctival or periocular injections of 20 mg of gentamicin and 40 mg of triamcinolone (Kenalog). The patient then usually received 500 mg of cephaloridine every six hours intravenously or intramuscularly after a baseline creatinine level was obtained. Additionally, appropriate topical antibiotics and corticosteroids were used. RESULTS

From the 54 cases of endophthalmitis, microorganisms were isolated in 27 cases, cultures were considered equivocal in five cases, and in 22 cases the cultures were nega­ tive. Culture site—Eighteen of the 27 eyes yielding positive cultures had an anterior chamber paracentesis and ten of these were culture-positive. Twenty of the 27 eyes had a TABLE 1 CULTURE SITES OF 27 POSITIVE ISOLATES

Culture Site Anterior chamber Vitreous body Wound

S3

ENDOPHTHALMITIS

VOL. 81, NO. 1

No. of Samples

CulturePositive

18 20 4

20f 4

10*

* In each instance, if the vitreous body was cul­ tured, it was positive. fin seven eyes, concommitant cultures of the anterior chamber were negative.

TABLE 2 ISOLATES FROM 27 CULTURE-POSITIVE EYES

GramPositive Recent post­ operative* Long-term post­ operative f Trauma Metastatic Total

GramNegative

Fungi

6

6

1

3 5 1 IS



1

1 1 2 S

— 7

* Within two weeks of surgery, with two ex­ ceptions. t Inadvertent or filtering blebs. vitreous aspiration and all 20 were culturepositive (Table 1). Additionally, cultures from four dehiscent wounds or ruptured blebs were all positive. In seven cases the vitreous sample was culture-positive while the anterior chamber had no growth. In five of these seven cases the eyes were aphakic. In no case was the aqueous tap positive and the vitreous aspirate negative. Etiologic agents—Of 27 eyes with positive cultures, gram-positive bacteria were identi­ fied in 15, gram-negative bacteria in seven, and fungi in five (Table 2 ) . Of 13 recently operated eyes, six yielded gram-positive bac­ teria, six gram-negative bacteria, and one a fungus. On the other hand, of six traumatic cases, five showed gram-positive bacteria, none gram-negative bacteria, and one a fungus. Table 3 lists the specific isolates. Intraocular antibiotic therapy—Visual acuity of 20/400 or better resulted in seven of the 27 culture-positive eyes, two of five culture-equivocal eyes, and 18 of 22 eyes with negative cultures for a total of 27 of 54 cases of suspected endophthalmitis. We treated 26 eyes with both gentamicin and cephaloridine (Table 4 ) , of which 15 yielded positive cultures, two were cultureequivocal, and nine, culture-negative. Useful visual acuity of 20/400 or better was achieved in six of 15 culture-positive cases, one of two equivocal cases, and seven of nine culture-negative cases, for a total of 14 of 26 cases.

54

AMERICAN JOURNAL OF OPHTHALMOLOGY

JANUARY, 1976

TABLE 3

TABLE 4

27 ENDOPHTHALMITIS ISOLATES

TREATMENT WITH INTRAOCULAR ANTIBIOTICS

S. aureus S. epidermidis Streptococci P. acnes Fungi Candida Fusarium

4 7 3 1

Proteus species Pseudomonas Klebsietta Hemophilus influenza

3 2 1 1

2 3

The 12 eyes that failed to respond to in­ traocular antibiotics contained eight virulent organisms and an equivocal Bacillus species (Table 5). Only two had negative cultures. However, trauma (six of 12 cases) played a significant role in final visual function. On the other hand, of the 14 eyes that retained some vision (Table 6 ) , five yielded Staphylococcus epidermidis, and one Propionibacterium acnes. In two eyes, the visual deficit was attributed to either a cataract or clearing vitreous reaction. These eyes are presumed to have the potential to regain useful sight. Of 14 successfully treated patients receiv­ ing intraocular antibiotics, 12 underwent sub­ sequent electroretinography one to four months after treatment (Table 7). Normal or only slightly abnormal tracings were present in three cases, and were moderately abnormal in eight. A markedly abnormal electroretinogram was seen in one case in which visual acuity of 20/60 was achieved after a subtotal

Culture Positive Equivocal Negative Total

No. of Cases

Useful Vision

Vision Lost

IS 2 9 26

6 1 7 14

9 1 2 12

vitrectomy with instillation of both 0.1 mg of gentamicin and 0.005 mg of amphotericin B. Although fungal endophthalmitis was suspected P. acnes was isolated. Of the 12 electroretinograms, seven manifested pri­ marily a decrease in the b wave with a rela­ tively normal a wave. DISCUSSION

Although paracentesis of the anterior chamber is a rational and often rewarding diagnostic approach in suspected infectious endophthalmitis, in this series aspiration of the vitreous proved more specific. Cultures were positive in each instance of 20 positive cultures that included vitreous aspiration. In no case was the aqueous humor positive when the vitreous yielded no growth. There­ fore, in aphakic eyes or eyes with cloud­ ing of the vitreous humor, an aspiration of the vitreous fluid must be performed if the greatest return of positive cultures is the goal. In recently operated eyes, the kera-

TABLE 5 TREATMENT FAILURES WITH INTRAOCULAR ANTIBIOTICS

Type

Culture

Postoperative Postoperative Postoperative Postoperative Bleb Bleb Trauma Trauma Trauma Trauma Trauma Trauma

+ + + + + + + + + +



Organism Proteus rettgeri Pseudomonas aeruginosa P. mirabilis P. mirabilis Hemophilus influenza S. aureus Aipha-Streptococcus Fusarium solani S. epidermidis Bacillus species

Final Visual Acuity LP NLP HM NLP LP NLP LP LP NLP LP NLP HM

55

ENDOPHTHALMITIS

VOL. 81, N O . 1

TABLE 6 TREATMENT SUCCESS WITH INTRAOCULAR ANTIBIOTICS

Type Postoperative Postoperative Postoperative Postoperative Postoperative Trauma Postoperative Postoperative Postoperative Postoperative Postoperative Postoperative Trauma Metastatic

Culture

Organism

Final Visual Acuity

+ + + + + +

5. epidermidis S. epidermidis S. epidermidis S. epidermidis P. acnes S. epidermidis Streptococcus

20/200 20/60 20/30 20/30 20/60 LP* 20/40 20/40 20/70 LPf 20/400 20/100 20/60 20/200

+

* Mature cataract, good potential function by light projection and electroretinogram. t Vitreous opacity, normal ultrasound and electroretinogram.

totomy should be enlarged slightly before in­ serting a 22-gauge needle into the vitreous fluid to prevent wound dehisence. Approximately one half of recent post­ operative endophthalmitis was caused by gram-positive bacteria, and half by gramnegative bacteria. On the other hand, five of six infections of traumatized eyes were caused by gram-positive bacteria. Such in­ formation if confirmed by future experience may influence the initial choice of antibiotics in these two types of intraocular infection. Examination of smears in this series con­ tributed little to selection of therapeutic agents. Staphylococcus epidermidis may be a more common cause of bacterial endophthalmitis

than previously known. Two cases reported by Valenton, Brubaker, and Allen5 and our seven isolates of S. epidermidis emphasize the pathogenicity of this common conjunctival inhabitant for the interior of the eye. The eye containing P. acnes may represent the first reported case of endophthalmitis due to this organism. Propionibacterium acnes may be recovered more often in the future, since in a recent study by Perkins and associates6 approximately 44% of nor­ mal conjunctivae, when cultured with anaero­ bic media, grew P. acnes. Although this or­ ganism grew easily on all media at 37° from the anterior chamber and vitreous body in this report, inoculation of specimens into an anaerobic medium should be routine.

TABLE 7 ELECTRORETINOGRAPHIC RESULTS OF SUCCESSFUL TREATMENT WITH INTRAOCULAR ANTIBIOTICS

Culture Positive Equivocal Negative Total Decreased b wave

Normal or Slightly Abnormal

1



2 3 (1)

* Reduction also in untreated, "normal" fellow eye (two eyes).

Moderately Abnormal

3" 1 4» 8 (6)

Markedly Abnormal

1 1 (1)

56

AMERICAN JOURNAL OF OPHTHALMOLOGY

The one case of Hemophilus influenza oc­ curred in an aphakic eye with a corneal bleb after keratoplasty ten years previously. The initial growth was not readily evident on blood agar owing to its requirement for spe­ cial culture media and nutrition. Therefore, chocolate agar at an increased C 0 2 tension should be considered in cases of endophthal­ mitis. As previously reported,7 with the excep­ tion of trauma, when the cultures are nega­ tive the visual prognosis is favorable sug­ gesting that the endophthalmitis was indeed sterile, or was successfully treated before obtaining cultures. Although results from studies using intra­ ocular antibiotics are encouraging,7-8 several aspects need to be examined. The six visually successful results occurred in five cases due to 5". epidermidis and one case due to P. acnes, both organisms that perhaps could be managed by conventional routes, while on the other hand no eye with a recognized viru­ lent pathogen retained any useful vision. The only eye with bacterial endophthalmitis not treated with intraocular antibiotics in which vision was salvaged, however, also contained S. epidermidis. This infection followed trauma and was treated by concomitant routes of topical, subconjunctival, and sys­ temic antibiotics.7 Our laboratory studies of gentamicin toxicity by intravitreal administration suggest that 0.1 to 0.2 mg is the maximum safe dose in the rabbit eye; this, however, is in con­ flict with the dosage of 0.4 mg reported by Peyman and associates.9 The 12 electroretinograms performed in culture-positive as well as culture-negative cases suggest that combined therapy of 0.1 mg of gentamicin and 0.25 mg of cephaloridine can be toler­ ated by the retina and should be considered as an adjunct to the treatment of endophthal­ mitis. The combination of subtotal vitrec-

JANUARY. 1976

tomy and intraocular antibiotics was used in three cases in this study; in one of these cases caused by P. acnes, the patient achieved visual acuity of 20/60. SUMMARY

In our study of 54 suspected cases of endophthalmitis, vitreous aspiration was more sensitive in making a culture-proven diagnosis than anterior chamber paracentesis ; Staphylococcus epidermidis was a more com­ mon cause of endophthalmitis than previ­ ously appreciated; and intraocular antibi­ otics in the recommended dosage are reason­ ably safe clinically and add a new dimension to the treatment of endophthalmitis. REFERENCES

1. Allen, H. F., and Mangiaracine, A. B. : Bac­ terial endophthalmitis after cataract extraction. 2. Incidence'in 36,000 consecutive operations with spe­ cial reference to preoperative topical antibiotics. Trans. Am. Acad. Ophthalmol. Otolaryngol. 77 : 581,1973. 2. : Bacterial endophthalmitis after cata­ ract extraction. Arch. Ophthalmol. 72:454, 1964. 3. Allansmith, M. R., Skaggs, C, and Kimura, S. J. : The diagnostic value of anterior chamber paracentesis in 14 cases of postoperative endoph­ thalmitis. Trans. Am. Ophthalmol. Soc. 68:335, 1970. 4. Theodore, F. H.: Bacterial endophthalmitis after cataract surgery. Int. Ophthalmol. Clin. 5 : 59, 1965. 5. Valenton, M. J., Brubaker, R. F., and Allen, H. F. : Staphylococcus epidermidis falbus) en­ dophthalmitis. Arch. Ophthalmol. 89:94, 1973. 6. Perkins, R. E., Kundsin, R. B., Pratt, M. V., Abrahamsen, I., and Leibowitz, H. M. : Bacteriol­ ogy of normal and infected conjunctiva. J. Clin. Microbiol. 1:147, 1975. 7. Forster, R. K. : Endophthalmitis. Diagnostic cultures and visual results. Arch. Ophthalmol. 92: 387, 1974. 8. Peyman, G. A., Vastine, D. W., Crouch, E. R., and Herbst, R. W. : Clinical use of intravitreal antibiotics to treat bacterial endophthalmitis. Trans. Am. Acad. Ophthalmol. Otolaryngol. 78:862, 1974. 9. Peyman, G. A., May, D. R., Ericson, E. S., and Apple, D.: Intraocular injection of gentamicin. Toxic effects and clearance. Arch. Ophthalmol. 92 : 42, 1974.

Further observations on the diagnosis cause, and treatment of endophthalmitis.

In our study of 54 suspected cases of endophthalmitis, vitreous aspiration was more sensitive in making a culture-proven diagnosis than anterior chamb...
578KB Sizes 0 Downloads 0 Views