Endophthalmitis

Endophthalmitis Current Approaches

J. JAMES ROWSEY, MD,*t DAVID L. NEWSOM, MS,* DANIEL J. SEXTON, MD,:!: WILLARD K. HARMS, MDt

Abstract: Seventy patients referred with a diagnosis of endophthalmitis underwent anterior chamber and vitreous taps with intracameral antibiotic injections. Fifty-four eyes were culture positive, 34 (63%) after previous intraocular surgery, 12 (22%) had sustained penetrating trauma, and 8 (15%) resulted from a metastatic infection. Of 61 total isolates, 48 (79%) were gram positive, 9 (15%) were gram negative, and 5 (8%) were fungi. Visual recovery after surgery was related to the relative virulence of the organisms isolated. Twenty-four (44%) eyes achieved 20/400 or better vision, but only seven (13%) obtained 20/40 or better vision. Patients with a markedly abnormal ERG operatively demonstrated poor visual acuity recovery, while patients with near normal ERG recovered better vision. The authors currently recommend vitrectomy in patients with endophthalmitis whenever the retina cannot be visualized. [Key words: antibiotic penetration, endophthalmitis, intraocular antibiotics, intraocular steroids, vitrectomy.] Ophthalmology 89: 1055-1 066, 1982

Extant endophthalmitis regimens in ophthalmology do not routinely salvage vision. From 1944 to 1966, nine reviews reporting 103 cases of endophthalmitis appeared in the English literature. Of these 103 cases, 75 patients (73%) retained no useful vision (defined as less than counting fingers visual acuity). Twenty-eight patients (27%) demonstrated visual acuities of finger counting or better. 1 Maylath and Leopold investigated From the Dean McGee Eye Institute, * the Department of Ophthalmology,t University of Oklahoma, and the Department of Medlcine,t DIvIsion of Infectious Diseases, Oklahoma City Clinic, Oklahoma City, Oklahoma. Supported by the Pfeiffer Foundation, an unrestricted grant from Research to Prevent Blindness, and the private philanthropy of the citizens of the state of Oklahoma Presented at the Eighty-sixth Annual Meeting of the American Academy of Ophthalmology, Atlanta, Georgia, November 1-6,

1982

Reprint requests to J James Rowsey, MD, Dean McGee Eye Institute, 608 Stanton L Young Drive, Oklahoma City, OK 73104 0161-6420/82/0900/1055/$1.40

© American Academy of Ophthalmology

the cultivation of both vitreous and aqueous, attempting to improve diagnosis and visual prognosis. They determined that it was possible for the anterior chamber aspirate to be culture negative while the vitreous was culture positive 2 in rabbits. Using anterior chamber paracentesis alone, Allensmith et aP in 1970 recovered positive cultures in five of 14 cases of postoperative endophthalmitis. Three of these five culture-positive cases had prophylactic systemic antibiotics prior to surgery. Although useful vision temporarily recovered, two of these three systemically treated cases eventually required enucleation. Systemic antibiotics, therefore, neither prevent endophthalmitis routinely when used prophylactically nor control endophthalmitis in all cases after the infection develops. In addition, anterior chamber cultures are not uniformly satisfactory to confirm the clinical impression of intraocular infection. Endophthalmitis was associated with a high percentage (55-87%) of visual loss from 1944 to 1970. New avenues of investigation were necessary. 1055

OPHTHALMOLOGY • SEPTEMBER 1982 • VOLUME 89 • NUMBER 9

MATERIALS AND METHODS All patients referred to the McGee Eye Institute, Department of Ophthalmology, University of Oklahoma, from July 1976 to July 1981 were included, if examined and followed by one of the authors (JJR). The clinical criteria used in diagnosis included increasing ocular pain and discomfort, conjunctival and upper eyelid chemosis and hyperemia, a precipitous decrease in visual acuity, and excessive intraocular inflammation, considering the extent and complications of recent surgery or trauma. Twelve eyes underwent anterior chamber tap alone. Fifty-eight eyes underwent diagnostic vitrectomy under sterile operating room conditions. We performed the vitrecto my primarily with a limbal approach, carefully dissecting all inflammatory membranes off the intraocular lens and iris with subsequent dilation of the pupil, using the limbus as a fulcrum. The vitreous base and associated retina were avoided, assiduously and the vitrectomy proceeded until normal posterior retinal details could be observed. The intraocular aspirate was filtered in a closed, sterile system through a 0.22-micron filter. The filtrate was inoculated immediately onto blood agar, chocolate agar, thioglycolate, and sabourad's media, and incubated at both 25 C and 37 C. Lactophenyl cotton blue stains and smears ofthe specimens were examined by Gram's and Giemsa stains. The operative procedure was completed with the Ocutome® unit, using hand suction to bypass machine suction and allow for controlled aspiration of membranes in the anterior segment and surrounding intraocular lenses. Following the acquisition of a diagnostic specimen for diagnosis, therapeutic drainage of the vitreous abscess was undertaken, using a limbal or pars plana approach, until the retina could be visualized. If a bacterial etiology was suspected on the basis of Gram's stain, gentamicin (100 /J-g), cephaloridine (250 /J-g), each in 0.1 cc volume, were slowly injected into the midcameral space with the needle port directed anteriorly, away from the retina. Dexamethasone 400 /J-g was injected into the vitreous cavity if purulent exudate covered the retina. If hyphal elements or budding yeasts, indicative of a fungal etiology, were noted on the smears, 5 /J-g of amphotericin B in 0.1 cc volume were also injected into the eye. Gentamicin (40 mg), cephaloridine (250 mg), and dexamethasone (4 mg) were injected subconjunctivally. If a fungal infection was suspected, steroids were deleted from the regimen. Daily subconjunctival injections of these antibiotics were continued for five days. Parenteral gentamicin and cefazolin were continued for five days in dosages appropriate for the patient's renal status and weight. Most patients received 2 g of cefazolin IV every eight hours. Serum gentamicin peak (under 12 /J-g/ml) and valley (over 2 /J-g/ml) levels were determined on each patient after initiation of IV therapy and doses of aminoglycosides were adjusted. Serum BUN 1056

and creatinine levels were monitored simultaneously. Topical cycloplegics and steroids were also·used. At the end of five days, systemic and subconjunctival antibiotics were discontinued. If no further inflammation was noted in the infected eye, the patient was discharged after seven days and followed as an outpatient. Topical gentamicin and prednisolone acetate 1% were used during the postoperative period four to six times a day, depending on the degree of inflammation noted. Benemid (500 MG BID) was used in 1980-1981 orally to inhibit retinal excretion of cephalosporins, and rifampin 300 mg BID orally was used for Staphylococcus epidermidis. The following patient presentations demonstrate unique features of endophthalmitis that we feel warrant additional emphasis.

CASE REPORTS Case 1. A 36-year-old white man sustained a penetrating metallic foreign body to his left eye in July 1976. The foreign body was removed within 24 hours of the injury. Forty-eight hours later marked vitreal inflammatory reaction was present. A vitreous tap was performed from which Acinitobacter calicoaceticus (Moraxella nonliquefaciens) was grown. The patient was treated with systemic antibiotics and topical and subconjunctival steroids over the next two months and underwent an undulating course with vision ranging from 20/40 to 20/80. The patient achieved 20/40 vision in September 1976, and was able to maintain this acuity until June 1977 when he presented with a marked anterior chamber inflammatory reaction that was treated successfully with topical steroids. In October 1977, the patient underwent an uncomplicated cataract extraction in his left eye and recovered uneventfully for several months. In early 1978 the patient presented with pain, erythema, and hypopyon in his left eye. Over the next 18 months, the patient had intermittent anterior chamber and vitreous inflammation in his left eye, with visual acuity fluctuating between 20/60 and finger counting. We first examined the patient in July 1979. His right eye was found to be normal. His left eye was corrected to 20/60 visual acuity. His anterior chamber demonstrated 4+ cells and flare and fine endothelial keratic precipitates. There were discrete loculations of white blood cells on the lens capsular remnants, and moderate debris in the vitreous (Fig 1). This material had been considered residual lens material. However, the yellow gossamer edge of the material suggested infected debris. We have subsequently observed similar material around two intraocular lenses, both of which proved to be infected over one year after surgery. There was no detectable inflammation of the retina, however. The patient was started on prednisone 40 mg/day and azathioprine 150 mg/day. The patient was seen again in August 1979. His vision was 20/100, with no significant clearing of his inflammatory response. In September 1979, the patient returned with no significant change in his ocular examination. In view of the chronicity of the inflammation and the infectious possibility, the patient underwent a diagnostic vitrectomy and capsulectomy in October 1979. Multiple cultures of the vitreous specimen were positive for Flavobacterium meningosepticum. Cytologic examination of the vitreous aspirate demonstrated a moderate number of polymorphonuclear leukocytes and a rare mononuclear cell.

ROWSEY, et al • ENDOPHTHALMITIS-CURRENT APPROACHES

Fig 1. Flavobacterium memngoseptlcum endophthalmltls The purulent yellow exudate with a thin Inflammatory border suggests continued infection (arrow) The loculatIOn of matenal within the lens capsule should suggest Inflammatory debns

After surgery the patient was treated daily with gentamicin 40 mg and cephaloridine 250 mg subconjunctivally, and dexamethasone 4 mg. Systemic cefazolin and gentamicin were continued for seven days. One month after surgery the patient's vision in his left eye had returned to 20/80. He has remained without subsequent recrudescence of inflammation or infection after surgery and has required no further therapy. This organism was sensitive to ampicillin, carbenicillin, cephalothin, chloramphenicol, erythromycin, gentamicin, polymyxin, and tetracycline; it was resistant to triple sulfa. This case illustrates the need for continued suspicion of infection over three years after traumatic injury with possible microbial inoculation. The gradual clearing of this patient's inflammation on topical steroids may be associated with the heat sensitivity of the organism. Flavobacterium meningosepticum is inactivated at 38 C, but grows at 37 C. In the face ofrepeated steroid use, his inflammation repeatedly cleared prior to the final development of inflammation that could not be controlled with topical and systemic immunosuppressive agents. Case 2. An 83-year-old white woman underwent uneventful cataract extraction and intraocular lens insertion in her right eye in September 1978. Thirteen days following surgery she presented to the McGee Eye Institute with a 48-hour history of decreasing vision, eyelid swelling, and pain. On examination, the left eye was normal. Visual acuity in the right eye was light perception, and a hypopyon obscured fundus details. She underwent immediate vitreous tap, followed by complete vitrectomy using fluid with gentamicin 10 ""g/ml, and dexamethasone 10 ""g/ml. She received 100 ""g gentamicin and 250 ""g cephaloridine intracamerally, and 20 mg gentamicin, along with 150 mg cephaloridine and 4 mg dexamethasone subconjunctivally. Cultures of the anterior chamber and vitreous aspirate revealed Serratia marcescens. After surgery the patient was treated with 20 mg gentamicin, 150 mg cephaloridine and 4 mg dexamethasone subconjunctivally each day, as well as systemic gentamicin and cefazolin. The anterior chamber refilled with purulent material in 24 hours, and repeat abscess drainage with infusion of balanced salt solution and excision of the purulent material were accomplished with the Ocutome unit 48 hours after the first vitrectomy. The infusion fluid included 10 ""g/ml gentamicin and 10 ""g/ml

dexamethasone. At the termination of the procedure a repeat injection of 100 ""g gentamicin and 400 ""g dexamethasone were injected intracamerally. Multiple cultures of the aspirate were again positive for S. marcescens. Intraocular inflammation increased, and a third abscess drainage with excision of the purulent material with the Ocutome unit was performed 72 hours later. Intracameral gentamicin 100 ""g, ticarcillin 200 ""g, and dexamethasone 400 ""g, as well as subconjunctival gentamicin 20 mg, ticarcillin 200 mg, and dexamethasone 4 mg, were injected at the termination of the third procedure. All cultures on this specimen were negative. The inflammatory reaction gradually subsided, and at six weeks the patient's vision in the right eye remained at light perception. This patient's course emphasizes the clinician's frustration with virulent organisms. Although the Serratia was sensitive to the gentamicin antibiotics injected intracamerally, the infectious process destroyed the eye before the organism could be eliminated. The Serratia had the following sensitivities: tobramycin, sulfa, gentamicin, and amikacin; resistance to tetracycline, chloramphenicol, cephalothin, carbenicillin, and ampicillin. Case 3. A 48-year-old white woman was first referred to us 48 hours after being struck in the right eye by a projectile thrown from a lawnmower. She was complaining of24 hours of pain, decreased vision, and swelling of her right eye. Her vision was light perception with diffuse corneal edema and a 20% anterior chamber hypopyon. The fundus could not be visualized. The left eye was normal to examination with 20/20 vision. The anterior chamber of the right eye was tapped without instillation of intracameral antibiotics. Daily SUbconjunctival injections of gentamicin 40 mg, and methicillin 100 mg were administered along with systemic gentamicin and methicillin. Multiple cultures of the anterior chamber aspirate were positive for S. epidermidis. Four weeks after the initial injury, the patient's acuity in the infected eye was light perception with a markedly reduced electroretinogram (ERG) response. Over the next six months the patient's eye became phthisical. This case represents a more aggressive S. epidermidis that can destroy the eye, despite treatment with antibiotics to which the microbe is sensitive in vitro. The antibiotic sensitivities of this organism were as follows: bacitracin, cephalothin, chloramphenicol, erythromycin, gentamicin, lincomycin, methicillin, neomycin, oxacillin, and vancomycin. Case 4. An 80-year-old white man underwent uncomplicated cataract extraction on his left eye in December 1978. Forty-eight hours later he presented with increasing pain and decreasing vision in his left eye. Subconjunctival, systemic, and topical antibiotics were initiated, along with topical steroids. His anterior chamber and vitreous reactions continued to increase. Twelve days following his original cataract surgery he was referred to the University of Oklahoma. Visual acuity in his left eye was hand motion, the cornea was totally edematous, the anterior chamber had a 20% hypopyon, and marked vitreous debris was noted. No fundus details could be visualized. His ERG in the left eye at this time was reduced mildly, and his VER demonstrated gross normal macular function. A vitreous specimen was obtained, followed by a complete vitrectomy, using gentamicin 10 ""g/cc in the infusion fluid. Intracameral gentamicin 100 ""g and cephaloridine 250 ""g were injected at the termination of the procedure. Multiple cultures of the vitreous aspirate were positive for S. epidermidis. Subconjunctival gentamicin 20 mg and cephaloridine 250 mg and dexametha-

1057

OPHTHALMOLOGY. SEPTEMBER 1982 • VOLUME 89 • NUMBER 9

Table 1. S. epidermidis Onset to Clin. Eva!. (days)

ERG

10 11 12 13

5 4 5 10 6 1 1 2 3 3 1 1 1

NO NO ABN N ABN NO NO NO ABN N ABN ABN NO

14 15

1 6

16

2

Patient No. 1 2 3 4 5 6 7 8 9

Key*' N ABN ND T E

S

* Key

IS

= = = = = =

Preop VA

Best Corr. VA

T E T S S T T S S S S S S

LP HM BLP HM LP LP 20/100 CF 1/ HM HM HM CF HM

NLP 20/80 HM 20/200 20/80 NLP 20170 20/25 20/200 20/50 20/200 20/40 20170

NO NO

S S

HM HM

NO

S

CF

Source

normal abnormal not done trauma endogenous surgery

AC V sc sys top ab BLP amp

the same for Tables 1-8.

Gram's Stain Org. Present

Cult. Site

Previous Treatment

+ + + + + + + NO NO

AC AC AC V V V AC V V V V V V

20/30 CF

NO +

V V

20/20

+

V

none none none ab sc ab sc none none neosporin gm sc ab sys neodec., Maxitrol ab gm sc, cortisporin, Maxitrol amp sc terramycin, chloro., neosporin gm sc, Maxitrol

+

gm ERG VA LP HM CF

= anterior chamber = vitreous = subconjunctivally = systemically = topically = antibiotic = bare light perception = ampicillin

= garamycin = electroretinogram = visual acuity = light perceptIOn = hand motions =countlng fingers

Table 2. S. aureus

Patient No.

Onset to Clin. Eva!. (days)

ERG

Source

Preop VA

S S S S S S S

NLP LP CF 2/ CF BLP LP LP

NLP 20/60 20170 senile BLP HM NLP

+ + + + NO + +

AC V V V V V V

S

LP

LP

+

V

1 2 3 4 5 6 7

4 2 1 1 1 28 9

ABN N ABN ABN flat ABN NO

8

4

N

sone 4 mg, and systemic cefazolin and gentamicin were continued for seven days. Three weeks following vitrectomy, the patient's visual acuity in his left eye had improved to 201200. The antibiotic sensitivities to this organism were bacitracin, cephalothin, chloramphenicol, erythromycin, gentamicin, lincomycin, methicillin, oxacillin, tetracycline, and vancomycin; resistance to ampicillin. This patient's history suggests that systemic, subconjunctival, and topical antibiotics may be insufficient to eliminate S. epidermidis from the eye, and only intracameral antibiotics may eliminate the infections.

1058

Gram's Stain Org. Present

Best Corr. VA

Cult. Site

Previous Treatment ab sys & top gm sc Maxitrol ab Maxitrol, gm sc gm sc gm sc, econochlor pre; gm top post gm sc

RESULTS Tables 1- 8 summarize the time interval between the onset of inflammation and our clinical evaluation, the organisms cultured, the ERG response before and after surgery, the source of the infection, the preoperative and postoperative visual acuity, the Gram's stain of the vitreous aspirate, the culture site, and the treatment undertaken prior to our examina-

ROWSEY, et al •

ENDOPHTHALMITI8-CURRENT APPROACHES

Table 3. Bacillus

Patient No.

Onset to Clin. Eval. (days)

1 2

60 6

3 4 5 6

1 2 2 2 1

7

B. B. B. B. B. B. B. B.

Gram's Stain Org. Present

Cult. Site

Species

ERG

Source

Preop VA

Best Corr. VA

coagulans megaterium coagulans cereus cereus coagulans coagulans coagulans

NO NO

E E

LP 20/400

enucl. LP

+ +

V V

none none

NO flat ABN ABN ABN

T T T E E

LP CF 3' LP LP LP

NLP NLP enucl. CF LP

+ + + + +

V V V V V

none gm top none none none

Previous Treatment

Table 4. Other Gram Positives

Patient No.

Onset to Clin. Eval. (days)

Organism

ERG

Source

3 21 2 1 3 10 14

M. luteus Corynebacterium Lactobacillus C. oortii C. oortii C. pseudodiphth S. sanguis

NO N NO NO NO NO NO

S S S S E S S

1 2 3 4 5 6

7

Best Corr. VA

Preop VA 20/60

Gram's Stain Org. Present

unknown

HM HM

20170

HM

Previous Treatment

V V V V V V V

cortisporin gm sc gm sc gm sc none gm sc gm sc

NO

20/50 20/30 CF 8' CF 20/400 CF CF

HM

Cult. Site

+ +

Table 5. Gram-negative Rods

Patient No. 1 2 3 4 5 6

7

8

Onset to Clin. Eval. (days) 11 14 3 2 1 3.3 yr 1 1

P. E. E. S.

Preop VA

Organism

ERG

Source

mirabilis agio. cloacae marcescens

NO flat NO ABN

T S S S

20170 LP

NO ABN ABN N

S T S S

LP 20/400 LP CF

S. marcescens F. meningosepticum Ps. fluorescens Ps. maltophilia

tion, either prophylactically or aggressively for the endophthalrnitis itself. All 70 patients included in this series were referred with signs of endophthalrnitis, and therefore 58 underwent diagnostic vitrectorny, and 12 underwent anterior charnber taps. Sixty-nine patients were treated with intracarneral antibiotic injection. Fifty-four patients (77%) had organisrns isolated frorn the intraocular culture specirnen. Of the 54 eyes with positive cultures, 34 (63%) had undergone previous intraocular surgery, 12 (22%) had sustained penetrating traurna, and 8 (15%) resulted frorn a rnetastatic infection.

NLP

HM

Best Corr. VA enucl. NLP 20/30

HM

enucl. 20/80 CF 4' CF

Gram's Stain Org. Present

+

NO

+ +

+

Cult. Site

Previous Treatment

conj. AC V AC

none gm sc gm sc gm, chloroptic, erythromycin sc, preop gm subtenons ab top chloroptic maxitrol

AC V V V

Seven eyes were infected with rnultiple organisrns. Of the 61 total isolates, 48 were grarn positive (79%), nine were grarn negative (15%), and five were fungi (8%). In 12 of the 70 eyes, an anterior charnber tap was perforrned. None of the anterior charnber taps were culture positive in the presence of a culture negative aspirate ofthe vitreous. Grarn's and Giernsa stains done on the intraocular aspirate at the tirne of vitrectorny were consistent with the final culture results in only 36 of the 54 positive cultures (67%). Patients with an anterior charnber tap achieved a visual acuity of 20/200 or better in 17% of the cases, whereas patients with a 1059

OPHTHALMOLOGY • SEPTEMBER 1982 • VOLUME 89 • NUMBER 9

Table 6. Mixed Infection

Patient No.

Onset to Clin. Eval. (days) 2

2

5

3 4

7

5

Organism S. epi C. renale S. aureus C. xerosis S. pneumoniae B. polymyxa S. faecium B. cereus Helmintho. B. megaterium E. cloacae

Preop VA

Best Corr. VA

Gram's Stain Org. Present

Cult. Site

Previous Treatment

+

AC

gm sc

LP

+

AC

gm sc

20/200

enucl.

+

V

gm top

T

LP

NLP

NO

ulcer

none

T

CF

NLP

+

AC

none

Gram's Stain Org. Present

ERG

Source

NO

S

HM

NLP

NO

S

LP

NO

S

ABN

NO

Table 7. Fungus

Patient No.

Onset to Clin. Eval. (days)

Organism

ERG

Source

Preop VA

Best Corr. VA

1 2 3 4

12 58 14 10

Fusarium Fusarium C. albicans C. albicans

N NO NO NO

T T E E

20/50 HM 20/300 20/200

20/20 HM 20/60 20170

+ NO

Cult. Site

Previous Treatment

V V V V

neosporin ab none amph.-B

Table 8. Negative Cultures

Patient No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Onset to Clin. Eval. (days) 7 1 5 3 2 3 53 6 9 17 4 mos 6 wks 32 25 5

ERG

Source

NO ABN ABN NO N N ABN NO N N NO NO flat ABN ABN

E T T T S S E T S E T T T T T

Preop VA

Best Corr. VA

LP BLP LP 20/200 LP LP BLP LP CF 5' 20/200 LP 20/100 HM HM LP

NLP HM LP 20/30 20/25 20/40 enucl. NLP 20/40 20/50 20/40 20170 20/40 LP enucl.

vitrectomy alone achieved a visual acuity of 201200 or better in 39% of the cases. The apparent poor visual outcome with anterior chamber taps is associated with the totally disorganized anterior segment filled with pus in which vitrectomy was impossible upon admission. Despite the wide variety of isolated organisms capable of causing endophthalmitis, gram-positive or1060

Gram's Stain Org. Present

+

+

Cult. Site V AC AC V V V V V V V V V V V V

Previous Treatment ab top none gm sc none Maxitrol Maxitrol, gm sc none none gm sc none maxitrol none maxitrol, ab po none ab top

ganisms predominated. S. epidermidis was seen in 17 eyes, and S. aureus in nine eyes (one of each was a mixed infection). These two organisms accounted for almost half of the culture-positive cases. When the three eyes from which the gram-positive Bacillus species alone were cultured, and the three eyes with multiple isolates are included, 76% of the eyes

ROWSEY, et al • ENDOPHTHALMITIS-CURRENT APPROACHES

of CUlture-positive cases were due to gram-positive organisms. Gram-negative organisms were less common and were distributed evenly among genera. The two Candida infections were both endogenous in origin. The recovery of visual function after resolution of the inflammatory process was related largely to the relative virulence of the organism cultured. We feel that the proteases and exotoxins produced by the organisms influence the visual result. In the 54 culture positive eyes, 24 (44%) achieved 20/400 or better vision after resolution of the inflammatory process, but only seven (13%) obtained 20/40 or better vision. In the 15 eyes from which no organism could be cultured, eight (53%) obtained 20/400 or better vision, and six (40%) returned to 20/40 or better vision. Eleven of the 17 (65%) eyes with S. epidermidis isolates obtained 20/400 or better vision (Fig 2). Two of the eight (25%) S. aureus isolates and none of the five gram-negative isolates achieved 20/400 or better vision (Figs 3, 6). We present the pre- and post-operative visual acuity results vs time from symptoms to treatment in Figures 2-8. We have attempted to correlate these factors with the proposed virulence of the infectious organisms. Patients with Bacillus endophthalmitis demonstrated uniformly poor visual acuity until clindamycin was added routinely to the intracameral regimen. Staphylococcus epidermidis stains (Fig 2) demonstrated that most patients with this organism have significant improvement in their visual acuity after surgery. The length of time between the onset of symptoms and treatment did not seem to influence the final visual acuity. However, six of 17 S. epidermidis patients treated with vitrectomy and intracameral antibiotic injection obtained visual acuities poorer than 20/400. The benignity of this organism, therefore, comes under question in view of patient 3, who lost vision and patient 4, whose vitreous could not be sterilized without intracameral antibiotics. Careful analysis of the proteases from these isolates is continuing at this time. Rapidity of treatment, however, appears to be important for S. aureus infected eyes. Eyes that are treated more promptly appear to end up with in a better visual acuity (Fig 3). The final visual acuity in eyes infected with Bacillus species (Fig 4) was uniformly poor until the intracameral regimen included clindamycin. Prompt treatment and intracameral clindamycin may be associated with improved visual potential. The data from four additional cases of gram-positive species are summarized in Figure 5. The results in these four patients were similar to those of S. epidermidis. Three of the eyes had better postoperative vision than pretreatment vision. The case of Corynebacterium pseudodiphtheriticum had significantly poorer vision after treatment than before treatment. Eyes with gram-negative rod infections routinely lost useful vision (Fig 6). The patients with counting fingers vision who were treated within 24 hours of injury maintained a counting fingers vision. Prompt and aggressive treatment of virulent gram-negative or-

S. EPIDERMIDIS PRE-OP

VISUAL ACUITY

POST-OP

20/20

25 30

40

eo eo 100

200 400

HM LP NLP ENUCLEATE~r-'-~--~-r__~~-,__~~.~

3

5

7

II

2

11

13

3

15

17

4

111 DAYS

fWEEKS

- - - - let eymptome-eurll.ry det.

Fig 2. Staphylococcus epidermitis endophthalmitis demonstrates improvement in visual acuity even after vitrectomy delay time following injury or signs of infection. S. epidermitis is not a benign organism, however, and three patients demonstrate no light perception vision.

ganisms cannot be correlated to recovery of vision. Prompt treatment may only preclude enucleation in gram-negative rod infections. Combinations of microorganisms appear to cause more visual loss than would be expected by any of the organisms individually (Fig 7). None of the three cases developed improved vision following therapy. Although fungal infections are often viewed with considerable alarm because of their difficulty in diagnosis, resistance to many antimicrobial agents, and subsequent drug toxicity, our small number of isolates suggests that the final visual function is potentially retrievable (Fig 8). To determine if the prognosis of visual recovery could be predicted in early endophthalmitis treatment, electroretinography was performed on 28 patients during the first week of hospitalization. Thirteen of these patients had early post-treatment ERGs reported as normal or mildly abnormal. All of these patients achieved at least 20/200 as the final visual acuity. Twelve patients had ERGs reported as markedly abnormal shortly after beginning aggressive treatment of endophthalmitis. Eight patients had ERGs performed immediately prior to, as well as shortly after, the initiation of endophthalmitis therapy, including vitrectomy and intracameral antibiotic injection. In each case, the post-treatment ERG demonstrated no change from that done before surgery. 1061

OPHTHALMOLOGY. SEPTEMBER 1982 • VOLUME 89 • NUMBER 9

S.AUREUS POST-OP

PRE-OP

VISUAL ACUITY

BACILLUS SPECIES PRE-OP

VISUAL ACUITY

20/20

20/20

25

25

30

30

40

40

80

60

80

80

100

100

200

200

400

400

POST-OP

c c

CF

HM LP

HLP

·~--~~~----------~c

HLP

ENUCLEATE~r--r----r--r

3

5

7

____r--r____~-r~~-r-'~ t 11 13 15 11 1Q DAYS

- - - - "t aymptoma-aurg.ry date

EHUCLEATE~r--r---r--r---r--r

3

5

7

t

11

____~-r____~~'~ 13

15

17

19 DAYS

- - - - tat aymptoma-aurg.ry date

Fig 3. Staphylococcus aureus endophthalmitis demonstrates improved visual acuity if prompt treatment is instituted.

Fig 4. Bacillus endophthalmitis demonstrates improved visual acuity with the recent installation of c1indamicin (C) following vitrectomy.

Figure 9 is a plot of the pretreatment or the posttreatment ERG results, with the percent of activity remaining vs the final visual acuity for 28 cases. As the ERG activity decreases at any time during treatment, so does the expectant final visual acuity. This data suggests that a preoperative or postoperative ERG may be potentially useful in predicting the eventual outcome of the visual acuity in patients with endophthai mitis . While the presence of a normal or a mildly abnormal ERG in the preoperative or early post-treatment follow-up does not necessarily suggest the eventual return to normal vision, a markedly abnormal ERG is often indicative of a poor visual prognosis.

tal animals the ability of the anterior chamber and iris to eliminate infection as opposed to the vitreous. Therefore, we might anticipate a lower culture positive rate from an aqueous tap than from a vitreous tap. Anterior chamber tap alone is a useful diagnostic modality in selected cases of endophthalmitis. When the abscess is localized anterior to the lens, or when a totally opaque cornea precludes retinal examination, a CUlture-positive anterior chamber tap may be anticipated. The eyes in our series undergoing an anterior chamber tap alone were filled generally with purulent material obscuring all iris details. This anterior segment necrosis on presentation may account for the relatively high culture positive (83%) rate for anterior chamber tap (10 of 12). We were unable to demonstrate a positive anterior chamber culture in the presence of a culture negative vitreous specimen. A possible reason for our relatively high CUlture-positive incidence with vitreous (77%) in comparison to the literature is the use of ultrafiltration of the vitreous aspirate prior to culture, as discussed by Forster. 4 A negative culture, however, by anterior chamber or vitreous tap does not guarantee a benign course. Sixteen of our cases with apparent endophthalmitis were culture negative, implying devitalized organisms or unsatisfactory microbiology methods to culture fastidious or cell wall deficient organisms at this time. Subconjunctival antibiotics alone do not prevent or eliminate endophthalmitis. Sixteen of our patients had

DISCUSSION Definitive evaluation and treatment of an eye with suspected endophthalmitis and posterior vitreous reaction requires vitrectomy. An abscess is a localized or relatively self-contained infection. In any other part of the body other than the eye, incision and drainage of a loculated infection is an established principle of good surgical management. To effect drainage of an intraocular infection, we believe controlled vitrectomy is important in all cases in which vitreous inflammation precludes retinal observation. Maylath and Leopold 2 demonstrated in experimen1062

ROWSEY, et al e ENDOPHTHALMITIS-CURRENT APPROACHES

OTHER GRAM POSITIVE BACTERIA VISUAL ACUITY

POST-OP

PRE-OP

GRAM NEGATIVE RODS POST-OP

20/20

20/20

25

25

30

30

40

40

80

80

80

80

100

100

200

200

400

400

CF

CF

HM

HM

PRE-OP

VISUAL ACUITY

............................... NLP

LP

ENUCLEATE ""'-r--r--'--"r--r--"--'---r.,;;;a't---r-'~-

NLP

3

5

7

9

11

13

15

17

19 DAYS

ENUCLEATE~~-,---r--~-,---r--~-,--~--~·~-

3

5

7

9

11

13

15

17

19 DAYS

- - - - 1st symptoms-surgery date

Fig 5. Gram-positive bacteria in general demonstrate better visual acuity after surgery than gram-negative organisms.

been treated with prophylactic subconjunctival antibiotics before the onset of endophthalmitis. One patient (case 4) had been treated with systemic, subconjunctival, and topical antibiotics for endophthalmitis without eradicating the S. epidermidis organism from the vitreous until intracameral antibiotics were used. In an effort to aid the eye's defense mechanisms, our results support the efficacy of intraocular injection of antimicrobial agents following vitrectomy. The use of intraocular antibiotics to treat experimental S. aureus endophthalmitis was first reported by Von Sallmann 19 in 1944, and by Leopold 20 in 1945. This technique has been expanded in several recent endophthalmitis series. 8 - 10 ,12-15 The results of our current protocol suggest that intraocular infections may not be eliminated routinely, even by intracameral antibiotics. Bacillus species and gram-negative rod infections have been controlled inadequately. The high incidence of these microbial invaders warrants continued broad spectrum antibiotic coverage. Clindamycin has been included in the intracameral antibiotic injection protocol in the last six months, with preservation of three eyes infected with Bacillus coagulans. 21 Except for the ring corneal infiltrate suggesting Bacillus infections, 21 the infectious organism cannot be determined on clinical grounds prior to vitreous or anterior chamber aspiration. Broad spectrum antibiotic coverage in endophthalmitis therefore remains of paramount importance.

- - - - 1st symptoms-surgery date

Fig 6. Gram-negative rod infections are associated with massive retinal destruction and poor visual acuity recovery.

MIXED INFECTION VISUAL ACUITY

POST-OP

PRE-OP

20/20

25 30

40 60 80

100 200

400 CF

HM LP

NLP ENUCLEATE""'-r--r--~~--,-~~-r--r--r--~·~-

3

5

7

g

11

13

15

17

19 DAYS

- - - - 1st symptoms-surgery date

Fig 7. Mixed infections of the vitreous demonstrate the cumulative toxicity of the individual organisms with modest visual acuity recovery anticipated.

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OPHTHALMOLOGY a SEPTEMBER 1982 a VOLUME 89 a NUMBER 9

FUNGUS POST-OP

PAE-OP

VISUAL ACUITY

30

40 60 80 100

200 400

100

.

EAG RESUL T5 we FINAL VISUAL ACUITV

• • • • •,

a·

.etl'f'ltv

o PRE-OP ERG • POST-OP ERG

remaining

20/20

25

..

ERG

80

----------_/ ~

80

70

eo

50

- - -- - -------

CF

•

•

40

30

o

HM 20

LP NLP

10

ENUCLEATE~r-~--~~--~~~~--r--r--~'~-

3

5

7

9

11

13

15

17

19 DAYS

20 20

30

40

eo

80

100

2 0

400

CF'

HM

~P

'ENJCLEATE

NLP

Visual ACUIty

- - - - 1st symptoms-surgary data

Fig 8. Fungal infections in the eye demonstrate good visual potential when Candia albicans is present (upper 2 lines).

Aggressive endophthalmitis therapy, including vitrectomy and intracameral antibiotic injection, is not injurious to the retina. Eight of our patients had ERGs performed on the infected eye immediately prior to and soon after endophthalmitis treatment began. None of the eight patients demonstrated any change from their preoperative ERG level. All of these patients recovered at least 201200 vision, and five of the eyes obtained 20/50 or better vision. Although the ERG is a test of gross retinal function, we feel the results from these eight patients indicate that the currently reported endophthalmitis therapy does not significantly impair retinal visual function.

SUMMARY Continued debate ensues in ophthalmology as to the safety and efficacy of vitrectomy and/or intracameral antibiotic injection. Our data suggests that in many eyes vitrectomy and intracameral antibiotic injection may be the best method to eliminate microbial organisms from the vitreous. We recommend that a vitrectomy be performed on all cases in which vitreous infection precludes examination of the retina. Organisms may continue to grow within the eye in the presence of systemic, SUbconjunctival, and topical an1064

Fig 9. ERG results, either preoperative or postoperative, demonstrate a moderate correlation with eventual visual acuity. Those individuals with markedly depressed ERG results do not routinely recover good visual acuity.

tibiotics. Based on our ERG findings, we feel that intracameral antibiotics have not been harmful to the retina. Therefore, we recommend that intracameral antibiotics be used on all patients with endophthalmitis when the vitreous is involved. Our current intracameral antibiotic regimen includes garamycin 100 JLg, cefazolin 250 JLg, and clindamycin 250 JLg, each in 0.1 cc in volume. Controls are not available in this study, obviously. Therefore, we wish to present this data for eventual comparison with subsequent investigations. The development of newer antibiotic penetration methods, control of microbial toxin and protease-induced intraocular inflammation, and the development of more efficacious prophylactic measures, are necessary before endophthalmitis may be prevented or better visual acuity routinely anticipated.

REFERENCES Leopold H Management of Intra-ocular infection Trans Ophthalmol Soc UK 1971; 91 575-610. 2. Maylath FR, Leopold IH. Study of experimental Intraocular infection. I The recoverabiilty of organisms Inoculated into ocular tissues and fluids. II The influence of antibiotiCS and cortisone, alone and combined, on Intraocular growth of these organisms Am J Ophthalmol 1955, 4086-101

ROWSEY, et al • ENOOPHTHALMITIS-CURRENT APPROACHES

3. Allansmlth MR, Skaggs C, Kimura SJ. The diagnostic value of anterior chamber paracentesIs In 14 cases of postoperative endophthalmltis. Trans Am Ophthalmol Soc 1970; 68:335-55. 4 Forster RK. Endophthalmitis: diagnostic cultures and visual results. Arch Ophthalmol 1974; 92:387-92 5. Baum JL The treatment of bacterial endophthalmltls. Ophthalmology 1978; 85'350-6. 6. Peyman GA, Vastine OW, Crouch ER, Herbst RW Jr Clinical use of intravitreal antibiotiCS to treat bacterial endophthalmitis Trans Am Acad Ophthalmol Otolaryngol 1974; 78:862-75 7 Baum JL, Rao G Treatment of postcataract bacterial endophthalmltis with periocular and systemic antibiotiCS and corticosteroids Trans Am Acad Ophthalmol Otolaryngol 1976;

vitrectomy as a prl mary treatment for acute bacterial en-

dophthalmltls. Am J Ophthalmol 1978, 86.167 -71 13 Peyman GA, Vastine OW, and Ralchand M. Symposium Postoperative Endophthalmltls. Experimental aspects and their clinical application Ophthalmology 1978; 85:374-85 14 Forster RK. Etiology and diagnosIs of bacterial postoperative endophthalmltls. Ophthalmology 1978, 85320-6 15 Vastine OW, Peyman GA, Guth SB Visual prognosIs In bacterial endophthalmitis treated with Intravltreal antibiotics Ophthalmic Surg 1979, 10(3) 76-83 16. Peyman GA, Ralchand M, Bennett TO Management of endophthalmltls with pars plana vltrectomy Br J Ophthalmol

1980, 64472-5 17 Forster RK, Abbott RL, Gelender H. Management of infectious endophthalmitis Ophthalmology 1980, 87:313-8 18 Peyman GA, Carroll CP, Ralchand M Prevention and management of traumatic endophthalmltls Ophthalmology 1980, 87'320-4 19 Von Sallman L, Meyer K, 01 Grandi J. Experimental study on

81.151-62. 8 Peyman GA, May DR, Ericson ES, Apple 0 Intraocular inJection of gentamicin ToxIc effects and clearance Arch Ophthalmol 1974, 9242- 7. 9 Graham RO, Peyman GA, Fishman G. Intravitreal injection of cephalOridine In the treatment of endophthalmitis. Arch Ophthalmol 1975,93:56-61 10 Forster RK, Zachary IG, Cottingham AJ, Norton EWO Further observations on the diagnosIs, cause, and treatment of endophthalmltls. Am J Ophthalmol 1976; 81:52-6 11 Cottingham AJ Jr, Forster RK Vitrectomy in endophthalmltls Results of study using vitrectomy, Intraocular antibiotics, or a combination of both Arch Ophthalmol 1976; 94'2078-81 12. Eichenbaum OM, Jaffe NS, Clayman HM, Light OS. Pars plana

penicillin treatment of ectogenous infection of vitreous Arch Ophthalmol 1944, 32'179-89 20 Leopold IH Intravitreal penetration of penicillin and penicillin therapy of infections of the vitreous. Arch Ophthalmol 1945,

33'211-6 21 O'Oay OM, Smith RS, Gregg CR, et al The problem of BaCillus species infection with special emphasis on the Virulence of Bacillus cereus Ophthalmology 1981; 88.833-8

Discussion

by

Roger F. Meyer, MD

Endophthalmitis is a catastrophic and, fortunately, rare complication of intraocular surgery and penetrating injury of the eye. Dr. Rowsey and his colleagues are to be complimented on an excellent review of the treatment of seventy cases of endophthalmitis, demonstrating that current approaches using intravitreal antibiotics and vitrectomy give reasonable results. Similar results in other recent studies by Forster,! Peyman,2 Diamond,3 and their associates support the efficacy of this aggressive diagnostic and therapeutic approach to the management of infectious endophthalmitis. A point of controversy, however, is the precise role of early therapeutic vitrectomy in the management of endophthalmitis. Some investigators 4 feel that all eyes with infectious endophthalmitis should be treated with early therapeutic vitrectomy allowing the ocular media to be cleared more rapidly. Most investigators,I-3 though, advise that therapeutic vitrectomy be reserved for poor prognosis cases that show evidence of advanced vitreoretinal involvement or the presence of culture-proven virulent bacteria. Cases with less virulent bacteria, and culture-negative cases, frequently do well with intravitreal antibiotics alone, without From the Department of Ophthalmology, University of Michigan Medical School, Ann Arbor, Michigan

therapeutic vitrectomy.5-8 As a useful guide, it is recommended from the present study that intravitreal antibiotics be used on all patients with endophthalmitis when the vitreous is involved and that therapeutic vitrectomy be performed on cases in which vitreous infection precludes examination of the retina. The concept of using pretreatment electroretinography (ERG) to predict final visual outcome, as done in this study, could potentially be a useful clinical tool by serving as a guide in the use of repeated intravitreal antibiotic injections and therapeutic vitrectomy. Recent studies 9 have shown that the rate of decline of intravitreal antibiotic levels is dramatically accelerated in infected eyes. The data suggests that intravitreal antibiotic injection may need to be repeated and perhaps at shorter intervals than previously suggested. In cases where pretreatment ERG predicts a poor visual prognosis, repeated intravitreal antibiotic injections might be administered in an effort to maintain effective intravitreal antibiotic levels. Likewise, pretreatment ERG might be useful in selecting similar poor prognosis cases wherein early, and possibly repeated, therapeutic vitrectomy could potentially be helpful by removing the bulk of infectious organisms and inflammatory debris, hopefully resulting in improved visual recovery. When considering more aggressive thera-

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OPHTHALMOLOGY. SEPTEMBER 1982 • VOLUME 89 • NUMBER 9

peutic intervention, such as repeated intravitreaI antibiotic injections and repeated vitrectomy, it is important to establish that the treatment is not likely to be more harmful than the disease itself. Toward this end, it is encouraging to note in the current study that post-treatment ERGs demonstrated no change from those done before treatment with intravitreal antibiotic injection and vitrectomy. Even though improvement has been made, management of infectious endophthalmitis remains one of the most challenging problems in ophthalmology. Additional clinical studies are necessary, ideally in a prospective, controlled, randomized fashion to establish further guidelines for appropriate case selection and timing of therapeutic vitrectomy. Combined treatment with intravitreal antibiotics and therapeutic vitrectomy, as outlined in this study, although still experimental, shows promise for improved results in the management of infectious endophthalmitis. REFERENCES Forster RK, Abbott RL, Gelender H Managment of infectious endophthalmltis. Ophthalmology 1980, 87313-8 2 Peyman GA, Raichand M, Bennett TO. Management of en-

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dophthalmitis with pars plana vltrectomy Br J Ophthalmol

1980,64:472-5 3 Diamond JG Intraocular management of endophthalmitis. A systematic approach. Arch Ophthalmol 1981, 99:96-9. 4 Eichenbaum OM, Jaffe NS, Clayman HM, light OS Pars plana vitrectomy as a primary treatment for acute bacterial endophthalmitis Am J Ophthalmol 1978; 86:167-71 5 Forster RK. Endophthalmltis. Diagnostic cultures and Visual results. Arch Ophthalmol 1974; 92:387-92. 6. Cottingham AJ Jr, Forster RK. Vltrectomy In endophthalmltis. Results of study uSing vitrectomy, Intraocular antibiotiCS, or a combination of both. Arch Ophthalmol 1976, 94'2078-81. 7. Forster RK, Zachary IG, Cottingham AJ, Norton EWD Further observations on the diagnosIs, cause, and treatment of endophthalmitis Am J Ophthalmol 1976; 81 :52-6 8 Vastine OW, Peyman GA, Guth SB Visual prognosis In bacterial endophthalmltls treated with Intravitreal antibiotiCS OphthalmiC Surg 1979, 10(3).76-83 9. Kane A, Barza M, Baum J Intravltreallnjection of gentamicin in rabbits. Effect of inflammation and pigmentation on half-life and ocular distribution Invest Ophthalmol VIS Sci 1981,

20:593-7