Delayed-Onset Pseudophakie Endophthalmitis
Gregory Μ . Fox, M.D., Brian C. Joondeph, M . D . , Harry W. Flynn, Jr., M.D., Stephen C. Pflugfelder, M . D , , and Thomas J. Roussel, M . D .
We r e v i e w e d 1 9 c a s e s o f d e l a y e d - o n s e t P s e u dophakie e n d o p h t h a l m i t i s in which diagnos tic c u l t u r e s w e r e p e r f o r m e d a t o n e m o n t h o r more after cataract extraction with posterior chamber intraocular lens implantation. We i s o l a t e d f o u r different o r g a n i s m s i n t h e s e 1 9 c a s e s : 12 Propionibacterium s p e c i e s (63%), t h r e e Candida parapsilosis (16%), t h r e e Staph ylococcus epidermidis (16%), a n d o n e Corynebacterium s p e c i e s (5%). B e c a u s e o f t h e u n u s u al delayed-onset features of these cases a n d the retrospective nature of this study, a varie t y of t r e a t m e n t r e g i m e n s w e r e u s e d . T w e l v e p a t i e n t s h a d r e c u r r e n c e of m a r k e d i n f l a m m a tion despite an apparent initial cure, a n d ten of t h e s e p a t i e n t s h a d p o s i t i v e c u l t u r e r e s u l t s on r e p e a t e x a m i n a t i o n of i n t r a o c u l a r fluids. Nine patients continued to be treated with topical corticosteroids postoperatively to sup press low-grade inflammation. Of the 19 p a t i e n t s , 16 h a d final v i s u a l a c u i t y o f 2 0 / 4 0 0 o r better, Delayed-onset Pseudophakie endoph thalmitis had a more favorable visual progno sis, c o m p a r e d t o a c u t e - o n s e t e n d o p h t h a l m i t i s .
I N F E C T I O U S E N D O P H T H A L M I T I S is a n
uncommon
c o m p l i c a t i o n after c a t a r a c t s u r g e r y a n d i n t r a o c ular l e n s i m p l a n t a t i o n . A l t h o u g h t h i s c o n d i t i o n t y p i c a l l y o c c u r s in t h e e a r l y p o s t o p e r a t i v e p e r i od, a l e s s c o m m o n m a n i f e s t a t i o n o f p o s t o p e r a tive e n d o p h t h a l m i t i s h a s a c h r o n i c c o u r s e w i t h recurrent low-grade inflammation and has been called chronic bacterial endophthalmitis.' Even t h o u g h Propionibacterium acnes i s a f r e q u e n t e t i o l o g i c a g e n t in t h i s c a t e g o r y o f p o s t o p e r a t i v e
Accepted for publication Sept. 18, 1990. From the Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami School of Medicine, Miami, Florida. This study was supported in part by Fight For Sight, Inc. This study was presented in part at the 23rd Annual Meeting of the Retina Society, Key Largo, Florida, Oct. 5, 1990. Reprint requests to Harry W. Flynn, Jr., M.D., Bascom Palmer Eye Institute, P.O. Box 016880, Miami, FL 33101.
endophthalmitis,^"* d e l a y e d - o n s e t P s e u d o p h a kie e n d o p h t h a l m i t i s i s n o t a l w a y s c a u s e d b y P. acnes. I n 1 9 c u l t u r e - p r o v e n c a s e s o f d e l a y e d onset Pseudophakie endophthalmitis, we stud ied the spectrum o f organisms and the distin guishing clinical features o f these infections. B a s e d u p o n o u r e x p e r i e n c e in t h e m a n a g e m e n t of t h e s e e a s e s , specific t r e a t m e n t o p t i o n s a r e discussed.
Patients and Methods We reviewed the microbiology laboratory files a n d c o r r e s p o n d i n g c l i n i c a l r e c o r d s o f 1 8 7 patients who had culture-proven endophthal m i t i s after e x t r a c a p s u l a r c a t a r a c t e x t r a c t i o n with placement of a posterior c h a m b e r intraoc u l a r l e n s . A l l p a t i e n t s w e r e e x a m i n e d at o u r institution between November 1 9 7 9 and June 1 9 8 9 . C h a r t s w e r e r e v i e w e d for t h e t i m i n g o f the onset of symptoms, previous topical antibi otic or corticosteroid treatment, a n d initial clin ical m a n i f e s t a t i o n . F o l l o w - u p i n f o r m a t i o n after t r e a t m e n t w a s o b t a i n e d t h r o u g h M a y 1 9 9 0 from t h e m e d i c a l r e c o r d s o r from t h e r e f e r r i n g p h y s i c i a n s a n d i n c l u d e d final v i s u a l a c u i t y , i n t r a o c u lar p r e s s u r e , a n d a n y o b s e r v e d c o m p l i c a t i o n s . Of the 1 8 7 patients with Pseudophakie en d o p h t h a l m i t i s in t h i s t e n - y e a r p e r i o d , 1 2 7 h a d d i a g n o s t i c c u l t u r e s p e r f o r m e d in t h e first f o u r w e e k s after c a t a r a c t e x t r a c t i o n . O f t h e s e 1 2 7 patients, 1 2 0 had positive cultures of intraocu lar s p e c i m e n s o b t a i n e d d u r i n g t h e first t w o weeks. S e v e n patients underwent vitreous tap d u r i n g t h e third w e e k after c a t a r a c t s u r g e r y , a n d in t w o p a t i e n t s t h e s e i n f e c t i o n s w e r e a s s o ciated with suture removal or vitreous wick syndrome. Of the 1 8 7 patients, 6 0 h a d the initial diag n o s t i c p r o c e d u r e p e r f o r m e d o n e m o n t h after extracapsular cataract surgery. O n e month was s e l e c t e d as a d i v i d i n g l i n e b e t w e e n e a r l y a n d delayed-onset Pseudophakie endophthalmitis. Of the 6 0 patients with delayed-onset Pseudo phakie endophthalmitis, we excluded 2 6 pa-
©AMERICAN JOURNAL OF OPHTHALMOLOGY 111:163-173, FEBRUARY, 1991
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tients with acute bleb-associated endophthal m i t i s , six p a t i e n t s w i t h r e c e n t p o s t o p e r a t i v e s u t u r e r e m o v a l , six p a t i e n t s w i t h t r a u m a t i c w o u n d d e h i s c e n c e s , a n d o n e c r i t i c a l l y ill p a tient w i t h s e p t i c e m i a w h o d e v e l o p e d e n d o g e n o u s b a c t e r i a l e n d o p h t h a l m i t i s . Two o f t h e s e 60 patients with positive intraocular cultures p e r f o r m e d in o u r m i c r o b i o l o g y l a b o r a t o r y w e r e t r e a t e d b y p h y s i c i a n s at a n o t h e r h o s p i t a l a n d were excluded because of inadequate informa tion regarding their clinical course and treat m e n t . In o n e of t h e s e two p a t i e n t s , b o t h Actino myces israelii a n d P. acnes w e r e c u l t u r e d from the v i t r e o u s , a n d this p a t i e n t a t t a i n e d final visual acuity of counting fingers. Propionibacte rium acnes w a s c u l t u r e d from the a q u e o u s s p e c i m e n o f the o t h e r p a t i e n t . T h i s s e c o n d p a t i e n t , d e s c r i b e d b y B r a d y , C o h e n , a n d F i s c h e r , ' at t a i n e d final visual a c u i t y o f 2 0 / 2 0 w i t h f o l l o w up at a n o t h e r h o s p i t a l . T h e r e m a i n i n g 19 p a t i e n t s w i t h c l i n i c a l e n d o p h t h a l m i t i s a n d di agnostic intraocular cultures performed one m o n t h after e x t r a c a p s u l a r c a t a r a c t e x t r a c t i o n and posterior chamber intraocular lens implan t a t i o n m e t our c r i t e r i a for d e l a y e d - o n s e t p s e u d o p h a k i c e n d o p h t h a l m i t i s . O f t h e s e 19 p a t i e n t s , four ( C a s e s 1, 7, 1 1 , a n d 1 2 ; T a b l e 1 ) have b e e n p r e v i o u s l y d e s c r i b e d by Z a m b r a n o a n d associates.^ I n t r a o c u l a r s p e c i m e n s w e r e o b t a i n e d from all patients and were inoculated into appropriate c u l t u r e media.*'" O u r c r i t e r i a for a p o s i t i v e c u l t u r e were the f o l l o w i n g : g r o w t h o f the s a m e o r g a n i s m on t w o or m o r e m e d i a ; or s e m i c o n fluent g r o w t h on o n e s o l i d m e d i u m ; o r g r o w t h at the i n o c u l a t i o n site on a m e d i u m a n d c o n firmed by o r g a n i s m s s e e n on G r a m s t a i n or histologic examination of intraocular tissues. All p a t i e n t s m e t t h e s e c r i t e r i a for p o s i t i v e c u l ture, e x c e p t for t h r e e p a t i e n t s in w h o m Propi onibacterium s p e c i e s g r e w from t h i o g l y c o l a t e m e d i u m o n l y b u t w h o h a d the t y p i c a l c l i n i c a l features o f P. acnes e n d o p h t h a l m i t i s ' ( C a s e s 8, 10, and 1 1 ; Table 1).
Results The s p e c t r u m o f c a u s a t i v e o r g a n i s m s in t h e s e patients with delayed-onset p s e u d o p h a k i c en d o p h t h a l m i t i s is s h o w n in T a b l e 1. T h e c u l t u r e r e p o r t s i n d i c a t e d that of the 19 c a s e s , 12 ( 6 3 % ) w e r e c a u s e d b y Propionibacterium species (one b y P. arachnia a n d 11 b y P. acnes); t h r e e c a s e s ( 1 6 % ) w e r e c a u s e d b y Candida parapsilosis;
February, 1991
three cases ( 1 6 % ) were caused by Staphylococ cus epidermidis; a n d the r e m a i n i n g c a s e ( 5 % ) w a s c a u s e d by a Corynebacterium species. T h e v i t r e o u s w a s c u l t u r e - p o s i t i v e in all 1 9 p a t i e n t s . T h e a n t e r i o r c h a m b e r fluid w a s c u l t u r e d in six p a t i e n t s a n d w a s p o s i t i v e in five o f t h e s e p a t i e n t s . G r a m s t a i n s of t h e initial i n t r a o c u l a r s p e c i m e n w e r e p o s i t i v e in o n l y o n e o f 12 p a t i e n t s w i t h Propionibacterium species infec t i o n , in o n e o f t h r e e p a t i e n t s w i t h C. para psilosis i n f e c t i o n , in t w o o f t h r e e p a t i e n t s w i t h S. epidermidis e n d o p h t h a l m i t i s , a n d in the p a t i e n t w i t h Corynebacterium species endophthal mitis. R e v i e w o f the c l i n i c a l c o u r s e o f t h e s e 19 patients showed that recurrent episodes of p o s t o p e r a t i v e i n f l a m m a t i o n w e r e t y p i c a l o f all p a t i e n t s . In the p a t i e n t s w i t h Propionibacterium s p e c i e s i n f e c t i o n , the t i m e o f d i a g n o s i s by p o s i tive c u l t u r e o f i n t r a o c u l a r fluid a v e r a g e d e i g h t m o n t h s a n d r a n g e d from six w e e k s to 3 6 m o n t h s after s u r g e r y . T h e o t h e r c a s e s w e r e c o n f i r m e d by p o s i t i v e c u l t u r e s at v a r i a b l e t i m e s after c a t a r a c t s u r g e r y (C. parapsilosis, one m o n t h to 2 3 m o n t h s ; S. epidermidis, o n e to t h r e e m o n t h s ; a n d Corynebacterium species, two m o n t h s ) . All p a t i e n t s w e r e r e f e r r e d b y a n t e r i o r s e g m e n t s u r g e o n s for t r e a t m e n t . M a n y o f t h e s e p a t i e n t s w e r e n o t e d to have c o r t i c o s t e r o i d - r e s p o n s i v e iritis, v i t r e i t i s , or b o t h , b e f o r e t h e i r referral. C o n t i n u e d t o p i c a l c o r t i c o s t e r o i d t r e a t m e n t of p r e s u m e d s t e r i l e i n t r a o c u l a r i n f l a m m a tion d e l a y e d the d i a g n o s i s in 15 o f 19 p a t i e n t s . Ten o f 12 p a t i e n t s w i t h Propionibacterium spe c i e s i n f e c t i o n (all e x c e p t C a s e s 1 a n d 1 0 ) , all t h r e e p a t i e n t s w i t h S. epidermidis infection, and the p a t i e n t w i t h Corynebacterium endophthal m i t i s h a d r e d u c e d or s t a b l e i n t r a o c u l a r inflam m a t i o n for a v a r i a b l e l e n g t h o f t i m e w h i l e taking topical corticosteroids. However, only o n e o f the t h r e e p a t i e n t s w i t h fungal e n d o p h thalmitis (Case 19) clinically improved while taking topical corticosteroids. All 12 p a t i e n t s w i t h Propionibacterium spe cies e n d o p h t h a l m i t i s d e m o n s t r a t e d a p r o m i n e n t w h i t e p l a q u e w i t h i n the c a p s u l e (Fig. 1) and vitreitis (Table 1). C h r o n i c granulomatous inflammation and keratic precipitates were not ed in six o f the 12 p a t i e n t s . B e a d e d fibrin strands extending across the anterior c h a m b e r w e r e s e e n in two p a t i e n t s ( C a s e s 1 0 a n d 1 1 ) . E i g h t p a t i e n t s w i t h Propionibacterium species endophthalmitis had initial visual acuity of 2 0 / 2 0 0 or b e t t e r . A s u b s e t o f two p a t i e n t s (Cases 2 and 5 ) , however, initially had more
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TABLE 1
CLINICAL FEATURES ON INITIAL EXAMINATION TIME FROM CATARACT EXTRACTION TO
INITIAL
INITIAL INFLAMMATION
CASE NO..
ORGANISM
ONSET OF
DIAGNOSTIC
VISUAL
IMPROVED OR STABILIZED WITH
AGE (YRS). SEX
CULTURED
SYMPTOMS
CULTURE
ACUITY*
20/200 White plaque, hypopyon, vitreitis LP White plaque, hypopyon, vitreitis 20/30 White plaque, keratic precipitates, vitreitis 20/200 White plaque, keratic precipitates, vitreitis HM White plaque, keratic precipitates, hypopyon, vitreitis 20/200 White plaque, vitreitis 20/100 White plaque, hypopyon, vitreitis 20/70 White plaque, keratic precipitates, vitreitis 20/200 White plaque, fibrin in anterior chamber, vitreitis HM White plaque, keratic precipitates, beaded strands, vitreitis, central retinal vein occlusion HM White plaque, keratic precipitates, beaded strands, vitreitis, central retinal vein occlusion 20/100 White plaque, vitreitis 1/200 Fibrin in anterior chamber, dense vitreitis 3/200 Hypopyon, keratic precipi tates, dense vitreitis LP Keratic precipitates, fibrin in anterior chamber, dense vitreitis LP White plaque, hypopyon, dense vitreitis 20/300 Keratic precipitates, iso lated vitreous infiltrates, vitreitis 20/60 Keratic precipitates, Iso lated vitreous infiltrates, vitreitis 20/25 White plaque, keratic precip itates. Isolated vitreous infiltrates, vitreitis
1, 63, Ft
P. acnes
6 wks
6 wks
2, 73, Μ
p. acnes
4 mos
11 mos
3, 77, F
P. acnes
4 mos
13 mos
4, 75, Μ
P. acnes
2 wks
4 mos
5, 75, F
P. arachnia
6 wks
3 mos
6, 62, Μ 7, 74, W
P. acnes P. acnes
4 mos 8 mos
21 mos 36 mos
8, 57, Μ
P. acnes*
2 mos
5 mos
9, 76, Μ
P. acnes
2 wks
6 wks
10, 76, F
P. acnes*
2 mos
12 mos
11, 81, Mt
P. acnes*
2 mos
24 mos
12, 68, Mt P. acnes 13, 75, F S. epidermidis
2 wks 5 days
4 mos 6 wks
14, 71. Μ
S. epidermidis
1 mo
3 mos
15, 78, Μ
S. epidermidis
2 days
1 mo
16, 91, F
Corynebacterium
6 wks
2 mos
17, 81, Μ
C. parapsilosis
3 days
2 mos
18, 76, Μ
C. parapsilosis
3 days
1 mo
19, 66, Μ
C. parapsilosis
2 mos
23 mos
CLINICAL FEATURES
• LP indicates light perception and HM indicates hand motions. t Cases have been reported previously in reference 5 (Cases 1, 7, 11, and 12). * Equivocal culture grovrth found in Cases 8, 10, and 11.
TOPICAL CORTICOSTEROIDS
No Yes Yes Yes Yes
Yes Yes Yes Yes
Not given
Yes
Yes Yes Yes Yes Yes No Not given Yes
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Fig. 1 (FOX and associates). Case 4. Propionibacteri um acnes endoplithalmitis on initial examination demonstrating a prominent white plaque within the capsule and inferior keratic precipitates.
Fig. 2 (Fox and associates). Case 18. Candida parapsilosis endophthalmitis on initial examination dem onstrating stringy, isolated, white infiltrates in the anterior vitreous adjacent to capsular remnants.
advanced intraocular inflammation, including hypopyon, vitreitis, and visual acuity of hand motions or worse. The remaining two patients with p o o r i n i t i a l v i s u a l a c u i t y ( C a s e s 1 0 a n d 1 1 ) h a d diffuse i n t r a r e t i n a l h e m o r r h a g e s r e s e m b l i n g a c e n t r a l r e t i n a l vein o c c l u s i o n at the t i m e of the initial d i a g n o s i s . All p a t i e n t s with i n f e c t i o n s c a u s e d by S. epi dermidis h a d m a r k e d a n t e r i o r c h a m b e r inflam m a t i o n , but o n l y o n e p a t i e n t h a d h y p o p y o n formation (Case 1 4 ) . A white intracapsular p l a q u e was n o t o b s e r v e d in a n y o f t h e s e pa t i e n t s , but d e n s e v i t r e i t i s was n o t e d in all t h r e e p a t i e n t s . In t h e s e t h r e e p a t i e n t s , i n i t i a l v i s u a l a c u i t y varied from light p e r c e p t i o n to 3 / 2 0 0 . s p e c i e s in T h e p a t i e n t with Corynebacterium fection ( C a s e 1 6 ) i n i t i a l l y h a d m a r k e d a n t e r i o r chamber inflammation, hypopyon, and dense v i t r e i t i s . A w h i t e p l a q u e a d j a c e n t to t h e p o s t e r i or c a p s u l e was a l s o n o t e d . I n i t i a l v i s u a l a c u i t y was light p e r c e p t i o n . S i m i l a r to the p a t i e n t s with Propionibacteri um s p e c i e s i n f e c t i o n , all p a t i e n t s w i t h c h r o n i c fungal e n d o p h t h a l m i t i s h a d a v a r i a b l e d e c r e a s e o f v i s u a l a c u i t y r a n g i n g from 2 0 / 2 5 to 2 0 / 3 0 0 on initial m a n i f e s t a t i o n . T h e s e i n f e c t i o n s w e r e c h a r a c t e r i z e d at s o m e p o i n t d u r i n g their c l i n i cal c o u r s e by l o c a l i z e d w h i t e infiltrates in the a n t e r i o r v i t r e o u s a d j a c e n t to the c a p s u l e (Fig. 2 ) . A w h i t e p l a q u e i n s i d e the p o s t e r i o r c a p s u l e , r e s e m b l i n g t h o s e s e e n in Propionibacterium s p e c i e s e n d o p h t h a l m i t i s , w a s o b s e r v e d in o n e of t h r e e p a t i e n t s ( C a s e 1 9 ) . G r a n u l o m a t o u s anterior segment inflammation was seen ini tially in o n l y two o f the t h r e e p a t i e n t s ( C a s e s 17 a n d 1 8 ) , a n d the third p a t i e n t ( C a s e 1 9 )
d e v e l o p e d g r a n u l o m a t o u s i n f l a m m a t i o n later during recurrent episodes of infection. Five p a t i e n t s w i t h Propionibacterium species infection were treated initially with intraocular a n t i b i o t i c s a l o n e ( C a s e s 1, 4 , 7, 8, a n d 1 2 ; T a b l e 2). Because of suspected recurrent infection, four o f t h e s e five p a t i e n t s h a d f u r t h e r s u r g e r y . T h r e e p a t i e n t s h a d pars p l a n a v i t r e c t o m y a n d c e n t r a l c a p s u l e c t o m y , i n c l u d i n g r e m o v a l o f the a r e a o f the w h i t e p l a q u e a n d r e p e a t i n j e c t i o n o f i n t r a o c u l a r a n t i b i o t i c s d u r i n g the f o l l o w - u p course. T h e fourth patient had complete cap sule removal and intraocular lens exchange. V i t r e o u s s p e c i m e n s t a k e n d u r i n g the s e c o n d o p e r a t i v e p r o c e d u r e in t h e s e four p a t i e n t s w e r e still p o s i t i v e for Propionibacterium species de spite p r e v i o u s t r e a t m e n t . All five o f t h e s e p a t i e n t s a t t a i n e d final v i s u a l a c u i t y o f 2 0 / 4 0 0 or better. O f the 1 2 p a t i e n t s w i t h Propionibacterium s p e c i e s i n f e c t i o n s , six ( C a s e s 2, 3 , 5, 6 , 9 , a n d 10; Table 2) were initially treated with a stan dard three-port vitrectomy, central capsulecto my with s e l e c t i v e r e m o v a l o f the a r e a o f w h i t e plaque, and injection of intraocular antibiotics. O n e o f t h e s e six p a t i e n t s ( C a s e 3 ) h a d r e c u r r e n t inflammation and documented recurrent infec t i o n . An a n t e r i o r v i t r e c t o m y , c o m p l e t e c a p s u l e removal using alpha-chymotrypsin, and intra o c u l a r l e n s e x c h a n g e with r e p e a t i n t r a v i t r e a l a n t i b i o t i c s w e r e p e r f o r m e d in this p a t i e n t . T h e cultures of removed capsular remnants were p o s i t i v e for P. acnes. O f the six p a t i e n t s w i t h Propionibacterium species infection treated with initial v i t r e c t o m y , five o f six a t t a i n e d final v i s u a l a c u i t y o f 2 0 / 4 0 0 or b e t t e r . O n e p a t i e n t
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TABLE 2
TREATMENT AND FINAL VISUAL RESULTS INITIAL TREATMENT
CASE NO., ORGANISM
INTRAOCULAR ANTIBIOTICS* (INTRAOCULAR CORTICOSTEROIDS)
2, P. acnes
Vancomycin, tobra mycin (No) Vancomycin (No)
3, P. acnes
Vancomycin (Yes)
4, P. acnes
Vancomycin (Yes)
5, P. arachnia
Vancomycin (No)
6, P. acnes
None (No)
7, P. acnes
Vancomycin, tobra mycin (No)
8, P. acnes
1, P. acnes
SURGERY
FOLLOW-UP TREATMENT INTRAOCULAR ANTIBIOTICS* (INTRAOCULAR CORTICOSTEROIDS)
SURGERY
FINAL VISUAL ACUITY'
FOLLOW-UP (MOS)
6
Vitreous aspiration
None
None
20/40
Pars plana vitrec tomy, central capsulectomy Pars plana vitrec tomy, central capsulectomy Vitreous tap
None
None
LP
Vancomycin (No)
20/60
6
20/100
4
None
Anterior vitrectomy, intraocular lens exctiange Pars plana vitrec tomy, central capsu lectomy None
20/30
15
Vancomycin (No)
10
Pars plana vitrec tomy, central capsulectomy Pars plana vitrec tomy, intraocular lens exctiange Vitreous tap
None
None
20/20
13
Cefazolln (No)
20/30
16
Vancomycin, tobra mycin (No)
Vitreous tap
Vancomycin (No)
20/20
10
9, P. acnes
Vancomycin (No)
None
20/40
18
10, P. acnes
Vancomycin (No)
None
None
20/400
12
11, P. acnes
Vancomycin, tobra mycin (No)
Pars plana vitrec tomy, central capsulectomy Pars plana vitrec tomy, central capsulectomy Two-port subtotal pars plana vitrectomy
Pars plana vitrec tomy, central capsu lectomy Pars plana vitrec tomy, central capsu lectomy None
20/100
48
12, P. acnes
Cefazolln, gentamicin (No)
20/30
36
None
20/40
9
None
20/70
3
Three-port pars plana vitrectomy, central capsu lectomy
20/25
7
13, S. epidermidis
14, S. epidermidis
15, S. epidermidis
Vancomycin, genta- Ttiree-portmore micin (Yes) complete pars plana vitrectomy, central capsulectomy Intraocular lens No Intraocular exctiange antibiotics
Vitreous aspiration, pars plana vitrectomy, central capsulectomy None Vancomycin (No) Pars plana vitrec tomy, central capsulectomy None Vancomycin (No) Pars plana vitrec tomy, central capsulectomy Vancomycin (Yes) Vancomycin, genta- Two-port subtotal micin (No) pars plana vitrectomy
Contir)ued on pg 1 6 8
AMERICAN JOURNAL OF OPHTHALMOLOGY
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February, 1991
TABLE 2 {continued) TREATMENT AND FINAL VISUAL RESULTS INITIAL TREATMENT
CASE NO., ORGANISM
INTRAOCULAR ANTIBIOTICS* (INTRAOCULAR CORTICOSTEROIDS)
FOLLOW-UP TREATMENT
SURGERY
INTRAOCULAR ANTIBIOTICS* (INTRAOCULAR CORTICOSTEROIDS)
16, Corynebacterium
Cefazolin, gentamicin (No)
Vitreous aspiration
Vancomycin (No)
17, C. parapsilosis
Amphotericin Β (No)
Amphotericin Β x2 (No)
18, C. parapsilosis
Amphotericin Β (No)
19, C. parapsilosis
Amphotericin Β (No)
Pars plana vitrec tomy, central capsulectomy Pars plana vitrec tomy, central capsulectomy Pars plana vitrec tomy, central capsulectomy
Amphotericin Β (No) Amphotericin Β x2 (No)
SURGERY
Pars plana vitrec tomy, central capsulectomy Pars plana vitrec tomy, central capsulectomy (x2) None
Pars plana vitrec tomy, capsulectomy, and intraocular lens removal
FINAL VISUAL ACUITY'
FOLLOW-UP (MOS)
HM
4
HM
12
20/70
60
20/25
7
*Dose of intraocular antibiotic or antifungal agents: vancomycin, 1 mg; cefazolin, 2.25 mg; gentamicin, 0.1 mg; tobramycin, 0.1 mg; and amptiotericin B, 5 μς. 'LP indicates light perception and HM indicates hand motions.
( C a s e 2 ) h a d final v i s u a l a c u i t y o f l i g h t p e r c e p tion because of optic atrophy, neovascular glau coma, and proliferative diabetic retinopathy. O n e p a t i e n t w i t h Propionibacterium species infection (Case 1 1 , Table 2) was treated initially w i t h a s u b t o t a l t w o - p o r t v i t r e c t o m y with i n j e c tion of intraocular antibiotics. Because of recur rent inflammation, a more complete three-port vitrectomy, central capsulectomy, and repeat injection of intraocular antibiotics were per f o r m e d . Propionibacterium acnes w a s a g a i n c u l t u r e d from t h e v i t r e c t o m y s p e c i m e n . T h i s p a t i e n t a t t a i n e d final v i s u a l a c u i t y o f 2 0 / 1 0 0 . Because of the high rate of recurrent infec tion, the determination o f a clinical cure was difficult in t h e s e p a t i e n t s w i t h Propionibacteri um s p e c i e s i n f e c t i o n ( T a b l e 3 ) . In t o t a l , six o f 1 2 p a t i e n t s c o n t i n u e d to u s e t o p i c a l c o r t i c o s t e r o i d s on l o n g - t e r m f o l l o w - u p ( C a s e s 2 t h r o u g h 5, 8, a n d 9 ) . D e s p i t e t h e r e c u r r e n c e s o f i n f l a m m a t i o n in t h e p a t i e n t s w i t h Propionibacterium s p e c i e s i n f e c t i o n , 11 of 1 2 p a t i e n t s a t t a i n e d final v i s u a l a c u i t y of 2 0 / 4 0 0 or b e t t e r . S e v e n o f 12 p a t i e n t s h a d v i s u a l a c u i t y o f 2 0 / 5 0 or b e t t e r . B e c a u s e o f t h e d e n s e v i t r e o u s infiltrates at t h e i n i t i a l e x a m i n a t i o n , all t h r e e p a t i e n t s w i t h S. epidermidis infection were treated by pars plana v i t r e c t o m y a n d i n j e c t i o n of i n t r a o c u l a r a n t i b i o t i c s . W i t h f o l l o w - u p o f t h r e e to n i n e m o n t h s .
t h e t h r e e p a t i e n t s a t t a i n e d v i s u a l a c u i t y of 2 0 / 2 5 , 2 0 / 4 0 , a n d 2 0 / 7 0 , r e s p e c t i v e l y . O n e of these patients (Case 15, Table 2) had marked recurrent inflammation, including vitreitis, anterior uveitis, hypopyon, and visual acuity of h a n d m o t i o n s , o n e m o n t h after i n i t i a l p r e sumed successful treatment with a subtotal vitrectomy without capsulectomy and injection of i n t r a o c u l a r a n t i b i o t i c s . A m o r e c o m p l e t e three-port pars plana vitrectomy with central capsulectomy and repeat injection of intraocu lar a n t i b i o t i c s a n d c o r t i c o s t e r o i d s w a s p e r formed. The repeat cultures of the vitreous s p e c i m e n w e r e n e g a t i v e . F i n a l v i s u a l a c u i t y in this patient was 2 0 / 2 5 . T h e p a t i e n t w i t h Corynebacterium species in f e c t i o n w a s i n i t i a l l y t r e a t e d w i t h v i t r e o u s tap and intraocular antibiotics. Visual acuity re mained hand motions because of persistent media opacities. W h e n visual acuity decreased to l i g h t p e r c e p t i o n o n l y a n d i n t r a o c u l a r p r e s sure b y a p p l a n a t i o n t o n o m e t r y d e c r e a s e d to 1 m m Hg, a pars plana vitrectomy was performed two m o n t h s after t h e i n i t i a l t r e a t m e n t . T h e e y e developed increasing inflammation six m o n t h s after v i t r e c t o m y , a n d r e p e a t v i t r e o u s tap w a s recommended. The patient refused further treatment, and visual acuity remained hand motions with hypotony.
Delayed-Onset Pseudophakie Endophthalmitis
Vol. I l l , No. 2
169
TABLE 3 ENDOPHTHALMITIS RECURRENCES CASE
NO. OF EPISODES OF
REPEAT CULTURE
LONG-TERM TOPICAL
NO.
RECURRENCE
RESULT*
CORTICOSTEROIDS
1 2 3
0 0 1
None None Positive
No Yes Yes
4
1
Positive
Yes
5
1
Not performed
Yes
6 7 8 9 10 11
0 1 1 0 0 1
None Positive Positive None None Positive
No No Yes Yes No No
12 13 14 15 16
1 0 0 1 2
Positive None None Negative Positive botti times
No No No Yes Yes
17
2
Positive twtti times
No
18 19
1 2
Positive Positive both times
No Yes
COMMENTS
No recurrent inflammation Proliferative diabetic retinopathy, neovascular glaucoma Recurred after pars plana vitrectomy, capsulectomy, and intraocular antibiotics Recurred after vitreous tap and intraocular antibiotics; age-related macular degeneration Recurrent anterior uveitis treated with topical corticosteroids No recurrent inflammation Recurred after vitreous tap and intraocular antibiotics Recurred after vitreous tap and intraocular antibiotics Intermittent episodes of intraocular inflammation Central retinal vein occlusion Recurred after subtotal pars plana vitrectomy and intraocular antibiotics; central retinal vein occlusion Recurred after vitreous tap and intraocular antibiotics No recurrent inflammation Macular hole Culture negative recurrence 1 month after apparent cure Recurred after vitreous tap and intraocular antibiotics; suspected recurrence after pars plana vitrectomy; patient refused further treatment Recurred after two pars plana vitrectomies; endstage chronic open-angle glaucoma Recurred after pars plana vitrectomy Recurred after two pars plana vitrectomies; required intraocular lens removal
* Repeat positive culture results were the same organism as initially cultured in all cases.
All t h r e e p a t i e n t s v^rith e n d o p h t h a l m i t i s c a u s e d b y C. parapsilosis had recurrent posttreatment inflammation and repeat culturep r o v e n p e r s i s t e n t i n f e c t i o n after i n i t i a l a p p a r ent cure with vitrectomy and intraocular am photericin B. One patient (Case 17) received a r e p e a t a m p h o t e r i c i n Β i n j e c t i o n (5 μ g ) , at t h e t i m e of the s e c o n d v i t r e c t o m y p r o c e d u r e . Five m o n t h s after t h e t h i r d v i t r e c t o m y p r o c e d u r e , the p a t i e n t r e q u i r e d filtering s u r g e r y a n d h a d final v i s u a l a c u i t y o f h a n d m o t i o n s b e c a u s e o f endstage glaucoma. Another patient (Case 18) had two vitrectomy procedures (each including 5 μ g o f a m p h o t e r i c i n B) a n d a t t a i n e d v i s u a l a c u i t y o f 2 0 / 7 0 , w i t h five y e a r s o f f o l l o w - u p after t h e s e c o n d v i t r e c t o m y . O n e p a t i e n t ( C a s e 19) required pars plana vitrectomy twice and intraocular amphotericin Β injection three times. Despite these procedures, this patient h a d i n c r e a s i n g i n f l a m m a t i o n in t h e v i t r e o u s
base region, which necessitated intraocular lens removal and complete capsulectomy using a l p h a - c h y m o t r y p s i n . T h i s p a t i e n t ( C a s e 1 9 ) at t a i n e d final v i s u a l a c u i t y o f 2 0 / 2 5 w i t h s e v e n m o n t h s o f f o l l o w - u p s i n c e t h e last s u r g i c a l treatment.
Discussion C a s e r e p o r t s or s m a l l s e r i e s o f p a t i e n t s w i t h delayed-onset postoperative endophthalmitis c a u s e d b y a v a r i e t y o f o r g a n i s m s , i n c l u d i n g P. acnes,^-^ P. granulosum,^^ S. aureus,^^ S. epider midis,^ Achromobacter species,' Cephalosporium s p e c i e s , ' ^ C. parapsilosis,^^ Acremonium spe cies,'^ Paecilomyces species,'^ and Aspergillus species'^ h a v e b e e n d e s c r i b e d . We h a v e a l s o previously reported a case of endophthalmitis
170
AMERICAN JOURNAL OF OPHTHALMOLOGY
m a n i f e s t i n g s e v e n weelcs after s e c o n d a r y i n t r a o c u l a r l e n s i m p l a n t a t i o n in w h i c h Mycobacteri um chelonae was isolated.'* In o u r p a t i e n t s w i t h c u l t u r e - p r o v e n i n f e c t i o n after e x t r a c a p s u l a r cataract e x t r a c t i o n a n d p o s t e r i o r c h a m b e r i n t r a o c u l a r l e n s i m p l a n t a t i o n e x a m i n e d at our i n s t i tution b e t w e e n 1 9 7 9 a n d 1 9 8 9 , four o r g a n i s m s in this c h r o n i c c a t e g o r y w e r e i s o l a t e d : P. acnes, C. parapsilosis, S. epidermidis, and Corynebacte rium s p e c i e s . T h i s s p e c t r u m o f i n f e c t i n g or g a n i s m s in the d e l a y e d - o n s e t p s e u d o p h a k i c e n d o p h t h a l m i t i s c a t e g o r y differs from a p r e v i ously p u b l i s h e d r e p o r t from our i n s t i t u t i o n , which reviewed primarily acute postoperative pseudophakic endophthalmitis." Even though S. epidermidis was s e e n in b o t h c a t e g o r i e s . Staphylococcus s p e c i e s ( i n c l u d i n g S. aureus), streptococci, and gram-negative organisms w e r e m o r e f r e q u e n t l y o b s e r v e d in the a c u t e p o s t o p e r a t i v e category.'•"'•"·" A syndrome of delayed-onset pseudophakic endophthalmitis manifesting with a white p l a q u e , m o d e r a t e visual l o s s , a n d often g r a n u l o m a t o u s i n f l a m m a t i o n after e x t r a c a p s u l a r cat a r a c t e x t r a c t i o n c a u s e d by P. acnes was d e s c r i b e d by M e i s l e r a n d a s s o c i a t e s ^ in 1 9 8 6 . F u r t h e r r e p o r t s have d e s c r i b e d the m a n a g e m e n t o p t i o n s a n d final v i s u a l r e s u l t s o f t h i s syndrome.'" Semel and a s s o c i a t e s " reported g r o w t h of P. acnes from the i n t r a o c u l a r l e n s in four o f 12 p a t i e n t s in w h o m the i n t r a o c u l a r lenses were removed during routine keratoplas ty for p s e u d o p h a k i c b u l l o u s k e r a t o p a t h y . A l t h o u g h this r e p o r t did n o t i d e n t i f y P. acnes as an e t i o l o g i c a g e n t in p s e u d o p h a k i c b u l l o u s k e r a t o p a t h y , it d o e s s u g g e s t that this o r g a n i s m c a n r e m a i n v i a b l e in the p s e u d o p h a k i c e y e for an extended time. Even t h o u g h Propionibacterium s p e c i e s , S. epidermidis, a n d C. parapsilosis are now wellrecognized ocular pathogens, Corynebacterium s p e c i e s have often b e e n r e g a r d e d as n o n p a t h o g e n i c c o n t a m i n a n t s o f the h u m a n e x t e r n a l e y e . However, ocular infections caused by Coryne bacterium s p e c i e s , i n c l u d i n g i n d o l e n t keratitis^" and endophthalmitis,^' have been reported. E n d o p h t h a l m i t i s o c c u r r i n g m o n t h s or y e a r s after s u r g e r y is a w e l l - r e c o g n i z e d c o m p l i c a t i o n of c o n j u n c t i v a l filtering blebs.^^ P a t i e n t s w i t h bleb-associated endophthalmitis, however, t y p i c a l l y have the a c u t e o n s e t o f i n f l a m m a t i o n a n d are u s u a l l y d i s t i n g u i s h e d from t h e s e p a tients with delayed-onset pseudophakic en d o p h t h a l m i t i s b y the p r e s e n c e of an o b v i o u s l y i n f e c t e d filtering b l e b . F u r t h e r m o r e , b l e b - a s sociated infections are generally caused by
February, 1991
more virulent organisms, including either Streptococcus s p e c i e s or Haemophilus s p e c i e s , in 8 0 % o f r e p o r t e d c u l t u r e - p o s i t i v e cases.^^ E n d o p h t h a l m i t i s c a s e s o c c u r r i n g five a n d n i n e m o n t h s after s c l e r a l b u c k l i n g s u r g e r y h a v e b e e n reported.^" V i s i b l e i n t r u s i o n o f the b u c k ling e l e m e n t w a s s u s p e c t e d to b e the a c c e s s site of the i n f e c t i o n . V i t r e o u s c u l t u r e s p e r f o r m e d at the t i m e of s c l e r a l b u c k l e r e m o v a l w e r e p o s i t i v e for Proteus mirabilis in b o t h c a s e s . L a t e - o n s e t e n d o p h t h a l m i t i s o c c u r r i n g m o n t h s after r e t i n a l detachment surgery caused by such a virulent o r g a n i s m c l e a r l y r e p r e s e n t s a different e n t i t y c o m p a r e d to d e l a y e d - o n s e t p s e u d o p h a k i c e n d o p h t h a l m i t i s in our s e r i e s o f p a t i e n t s . T h e s e patients with delayed-onset pseudo p h a k i c e n d o p h t h a l m i t i s h a d s e v e r a l specific c l i n i c a l f e a t u r e s , w h i c h m a y h e l p to d i s t i n g u i s h b e t w e e n the different i n f e c t i n g o r g a n i s m s . A white intracapsular plaque, representing se q u e s t e r e d o r g a n i s m s w i t h i n the c a p s u l e , was s e e n in all 12 o f the p a t i e n t s w i t h Propionibacte rium s p e c i e s i n f e c t i o n . In o n e p a t i e n t w i t h C. parapsilosis e n d o p h t h a l m i t i s a n d the p a t i e n t with Corynebacterium species infection, howev er, a w h i t e i n t r a c a p s u l a r p l a q u e w a s a l s o o b s e r v e d . G r a n u l o m a t o u s i n f l a m m a t i o n as m a n i fested by large k e r a t i c p r e c i p i t a t e s was a l s o s e e n in six o f the 12 p a t i e n t s w i t h Propionibac terium s p e c i e s i n f e c t i o n . B e a d e d fibrin s t r a n d s e x t e n d i n g a c r o s s to the a n t e r i o r c h a m b e r w e r e s e e n in t w o o f the 12 p a t i e n t s w i t h Propionibac terium s p e c i e s i n f e c t i o n . S t r i n g y w h i t e infil t r a t e s in the a n t e r i o r v i t r e o u s a d j a c e n t to the c a p s u l a r r e m n a n t s o c c u r r e d in all t h r e e o f the p a t i e n t s w i t h C. parapsilosis infection. Dense v i t r e i t i s c a u s i n g a p o o r v i e w o f fundus d e t a i l s w a s n o t e d in all t h r e e p a t i e n t s w i t h S. epider midis e n d o p h t h a l m i t i s a n d the p a t i e n t w i t h Corynebacterium s p e c i e s i n f e c t i o n . N o n e of the p a t i e n t s with fungal o r P. acnes i n f e c t i o n h a d a diffuse, d e n s e v i t r e i t i s , e v e n t h o u g h a m i l d c e l l u l a r r e a c t i o n in the v i t r e o u s w a s o b s e r v e d in all o f t h e s e p a t i e n t s . In t h e s e p a t i e n t s w i t h d e l a y e d - o n s e t p s e u d o p h a k i c e n d o p h t h a l m i t i s , the s p e c t r u m o f or g a n i s m s a n d the p o t e n t i a l difficulty e n c o u n tered in a c h i e v i n g a p o s i t i v e c u l t u r e r e s u l t e m p h a s i z e the n e e d for effective c u l t u r e t e c h niques. Anterior chamber and vitreous speci m e n s from t h e s e c a s e s c a n b e p l a c e d o n a n a e r o bic p l a t e s a n d t h i o g l y c o l a t e b r o t h ( i d e a l for P. acnes), S a b o u r a u d ' s m e d i a ( i d e a l for f u n g i ) , a n d b l o o d a g a r a n d c h o c o l a t e p l a t e s ( i d e a l for S. epidermidis a n d Corynebacterium species). The u s e of b l o o d c u l t u r e b o t t l e s , a t e c h n i q u e a l l o w -
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Delayed-Onset Pseudophakie Endophthalmitis
ing direct i n o c u l a t i o n of u n f i l t e r e d v i t r e c t o m y specimens,^" was a l s o s u c c e s s f u l in a c h i e v i n g a p o s i t i v e c u l t u r e r e s u l t in four o f t h e s i x p a t i e n t s in w h o m t h e y w e r e u s e d . In all c u l t u r e m e t h ods, c u l t u r e m e d i a s h o u l d b e o b s e r v e d for at least two w e e k s b e c a u s e o f t h e s l o w g r o w t h o f b o t h P. flcnes' a n d Corynebacterium species.^' Patients with delayed-onset Pseudophakie endophthalmitis had better posttreatment visu al acuity w h e n c o m p a r e d to a c u t e p o s t o p e r a t i v e P s e u d o p h a k i e e n d o p h t h a l m i t i s . " " " ' * O f 19 p a t i e n t s , 16 h a d final v i s u a l a c u i t y o f 2 0 / 4 0 0 or better. O f the three patients with visual acuity w o r s e t h a n 2 0 / 4 0 0 , two p a t i e n t s h a d signifi cant preexisting diseases (optic atrophy, n e o vaseular glaucoma, and proliferative diabetic r e t i n o p a t h y in t h e p a t i e n t in C a s e 2 a n d a d v a n c e d o p e n - a n g l e g l a u c o m a in t h e p a t i e n t in Case 17). The patient with Corynebacterium species infection developed chronic hypotony a n d refused further t r e a t m e n t . B e c a u s e of t h e v a r i a b l e m a n i f e s t a t i o n s a n d l i m i t e d t r e a t m e n t e x p e r i e n c e w i t h this c a t e g o r y of d e l a y e d - o n s e t P s e u d o p h a k i e e n d o p h t h a l m i tis, t h e i d e a l t r e a t m e n t r e m a i n s c o n t r o v e r s i a l . ^ S e v e r a l different a p p r o a c h e s w e r e s e l e c t e d b y the s u r g e o n s o f different s u b s p e c i a l i t i e s w h o t r e a t e d t h e s e p a t i e n t s . In t h e five p a t i e n t s w i t h P. acnes i n f e c t i o n t r e a t e d i n i t i a l l y w i t h i n j e c tion o f i n t r a o c u l a r a n t i b i o t i c s w i t h o u t v i t r e c tomy, r e c u r r e n t i n f e c t i o n o c c u r r e d in four p a tients. S u b s e q u e n t pars plana vitrectomy, central capsulectomy, and repeat intraocular a n t i b i o t i c i n j e c t i o n w e r e p e r f o r m e d in t h r e e patients, and complete capsule removal with i n t r a o c u l a r l e n s e x c h a n g e w a s p e r f o r m e d in one patient. Despite apparent initial cure with pars p l a n a v i t r e c t o m y a n d i n j e c t i o n o f i n t r a o c u lar a n t i b i o t i c s or a n t i f u n g a l a g e n t s , i n i t i a l t r e a t m e n t failures a l s o o c c u r r e d in five o f t h e 1 3 p a t i e n t s t r e a t e d b y this a p p r o a c h . S t e r n , E n g e l , a n d Driebe^' h a v e d e s c r i b e d s i m i l a r p a t i e n t s with r e c u r r e n t e n d o p h t h a l m i t i s w h o h a v e r e quired r e p e a t e d i n j e c t i o n s o f i n t r a o c u l a r a n t i b i o t i c s w i t h p a r s p l a n a v i t r e c t o m y to a c h i e v e a clinical cure. A l t e r n a t i v e m e t h o d s o f t r e a t m e n t for p a t i e n t s w i t h Propionibacterium species infection have been reported. Brady, Cohen, and Fischer' re ported successful therapy with topical and sys t e m i c a n t i b i o t i c s for o n e p a t i e n t w i t h P. acnes. T e s s l e r , O w e n s , a n d Deutsch^^ r e p o r t e d the a p p r o a c h o f i n t r a c a p s u l a r i n j e c t i o n o f 0 . 2 ml o f c l i n d a m y c i n (2 m g ) , w h i c h w a s p e r f o r m e d on an o u t p a t i e n t b a s i s e v e r y o t h e r day for a t o t a l o f three treatments. The n u m b e r of patients with
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P. acnes t r e a t e d b y t h e s e a l t e r n a t i v e t e c h n i q u e s has been limited. B a s e d on our e x p e r i e n c e w i t h t h e s e 1 9 p a t i e n t s , we r e c o m m e n d t h e f o l l o w i n g t r e a t m e n t a p p r o a c h in c a s e s o f d e l a y e d - o n s e t P s e u d o p h a kie e n d o p h t h a l m i t i s . In all c a s e s , i n t r a o c u l a r cultures should be performed, and pars plana v i t r e c t o m y is o u r p r e f e r r e d m e t h o d for o b t a i n ing t h e s p e c i m e n . W e r e c o m m e n d a l a r g e c e n tral c a p s u l e c t o m y w i t h s e l e c t i v e r e m o v a l o f t h e a r e a o f w h i t e p l a q u e at t h e t i m e o f t h e p a r s p l a n a v i t r e c t o m y . L i k e w i s e , d e n s e v i t r e o u s in filtrates should b e r e m o v e d during the pars plana vitrectomy. A more complete three-port p a r s p l a n a v i t r e c t o m y is p r e f e r r e d i f a s a t i s f a c tory v i e w o f t h e p o s t e r i o r s e g m e n t is p o s s i b l e . I n t r a v i t r e a l v a n c o m y c i n h y d r o c h l o r i d e , 1.0 m g , is o u r r e c o m m e n d e d a n t i b i o t i c in p a t i e n t s w i t h suspected bacterial infection, because vanco m y c i n h y d r o c h l o r i d e h a s b e e n p r o v e n effective a g a i n s t P. acnes a n d S. epidermidis infections.*" T h e Corynebacterium species isolates (Case 16) w e r e a l s o s e n s i t i v e to v a n c o m y c i n h y d r o c h l o r ide. A n i m a l s t u d i e s h a v e s h o w n t h a t this d o s e o f i n t r a v i t r e a l v a n c o m y c i n h y d r o c h l o r i d e is well tolerated with no signs o f retinal toxicity.^' Although methicillin sodium and the cephalo s p o r i n s m a y b e effective, t h e i n c r e a s i n g r e s i s t a n c e o f S. epidermidis to methicillin sodium gives vancomycin hydrochloride a distinct ad v a n t a g e in t h e s e c a s e s . S i n c e P. acnes s h o w s relative resistance to a m i n o g l y c o s i d e anti b i o t i c s , w e do n o t r e c o m m e n d t h e i n i t i a l u s e of this c l a s s o f a n t i b i o t i c s for s u s p e c t e d P. acnes endophthalmitis. The use of intraocular corti c o s t e r o i d s ( d e x a m e t h a s o n e , 0 . 4 m g ) is o p t i o n a l b u t s h o u l d b e c o n s i d e r e d in e y e s w i t h m o r e a d v a n c e d inflammation.^"'^' T h e r o l e o f i n t r a v e n o u s a n t i b i o t i c t h e r a p y in cases of endophthalmitis remains controver sial. Brady, C o h e n , and Fischer' described one p a t i e n t w i t h P. acnes e n d o p h t h a l m i t i s w h o w a s treated with prolonged intravenous, oral, and topical antibiotic therapy and regained 2 0 / 2 0 visual acuity. O'Day and associates'^ reported the successful use of subconjunctival, topical, and intravenous antibiotics without intravitreal a n t i b i o t i c s in p a t i e n t s w i t h S. epidermidis en dophthalmitis. However, subtherapeutic intra vitreal concentrations o f vancomycin hydro c h l o r i d e w e r e a c h i e v e d in a n i m a l s t u d i e s , ' ' ' ^ a n d s y s t e m i c c o m p l i c a t i o n s , s u c h as p e r i p h l e b i tis, a l l e r g i c r e a c t i o n s , a n d n e p h r o t o x i c i t y , h a v e b e e n r e p o r t e d in p a t i e n t s r e c e i v i n g i n t r a v e n o u s vancomycin hydrochloride. Intravenous anti b i o t i c s w e r e u s e d d u r i n g t h e b r i e f h o s p i t a l stay
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AMERICAN JOURNAL OF OPHTHALMOLOGY
of o n l y o n e o f our 19 p a t i e n t s w i t h d e l a y e d onset endophthalmitis (Case 1 ) . Because of the r e t r o s p e c t i v e n a t u r e of t h e p r e s e n t s e r i e s w i t h out r a n d o m i z a t i o n of t r e a t m e n t , w e are u n a b l e to draw any c o n c l u s i o n s a b o u t t h e e f f e c t i v e n e s s of i n t r a v e n o u s a n t i b i o t i c s in t h i s c a t e g o r y o f endophthalmitis. W h e n c h a r a c t e r i s t i c s t r i n g y , w h i t e infiltrates are s e e n in t h e v i t r e o u s or c u l t u r e s a r e p o s i t i v e for fungal e l e m e n t s , w e r e c o m m e n d i n t r a v i t r e a l i n j e c t i o n o f a m p h o t e r i c i n B, 5 μg. Brod a n d associates'*^ r e p o r t e d s u c c e s s f u l t r e a t m e n t o f e n d o g e n o u s Candida species endophthalmitis w i t h o u t i n t r a v e n o u s a m p h o t e r i c i n B . To avoid t h e s y s t e m i c t o x i c i t y a s s o c i a t e d w i t h its u s e , s y s t e m i c a m p h o t e r i c i n Β was n o t u s e d in o u r p a t i e n t s w i t h Candida s p e c i e s e n d o p h t h a l m i t i s . T r e a t m e n t w i t h o r a l i m i d a z o l e s , s u c h as k e t o c o n a z o l e or fluconazole, c o u l d b e c o n s i d e r e d in p a t i e n t s w i t h fungal i n f e c t i o n . T h e d e t e r m i n a t i o n of a c l i n i c a l cure w a s diffi cult in t h e s e p a t i e n t s w i t h d e l a y e d - o n s e t P s e u d o p h a k i e e n d o p h t h a l m i t i s b e c a u s e 12 p a t i e n t s h a d r e c u r r e n c e o f m a r k e d i n f l a m m a t i o n a n d ten o f t h e s e p a t i e n t s h a d p o s i t i v e c u l t u r e r e s u l t s on r e p e a t e x a m i n a t i o n o f i n t r a o c u l a r fluids d e s p i t e an a p p a r e n t i n i t i a l c u r e ( T a b l e 3 ) . N i n e p a t i e n t s required long-term use of topical corticoste roids p o s t o p e r a t i v e l y to s u p p r e s s l o w - g r a d e in flammation or e p i s o d e s o f a c u t e - o n s e t a n t e r i o r uveitis. Despite these features, delayed-onset P s e u d o p h a k i e e n d o p h t h a l m i t i s h a s a m o r e fa v o r a b l e v i s u a l p r o g n o s i s , c o m p a r e d to o t h e r c a t e g o r i e s of e n d o p h t h a l m i t i s .
References 1. Picker, L., Meredith, T. Α., Wilson, L. Α., Kap lan, H. J . , and Kozarsky, A. M.: Chronic bacterial endophthalmitis. Am. J. Ophthalmol. 103:745, 1987. 2. Friedman, E., Peyman, G. Α., and May, D. R.: Endophthalmitis caused by Propionibacterium acnes. Can. J. Ophthalmol. 13:50, 1978. 3. Meisler, D. M., Palestine, A. G., Vastine, D. W., Demartini, D. R., Murphy, B. F., Reinhart, W. J., Zakov, Z. N., McMahon, J. T., and CUffel, T. P.: Chronic Propionibacterium endophthalmitis after ex tracapsular cataract extraction and intraocular lens implantation. Am. J. Ophthalmol. 102:733, 1 9 8 6 . 4. Jaffe, G. J . , Whitcher, J. P., Biswell, R., and Ir vine, A. R.: Propionibacterium acnes endophthalmitis seven months after extracapsular cataract extraction and intraocular lens implantation. Ophthalmic Surg. 17:791, 1986. 5. Zambrano, W., Flynn, H. W„ Jr., Pflugfelder, S. C , Roussel, Τ. J., Culbertson, W. W., Holland, S.,
February, 1991
and Miller, D.: Management options for Propionibac terium acnes endophthalmitis. Ophthalmology 96:1100, 1989. 6. Roussel, T. J . , Culbertson, W. W., and Jaffe, N. S.: Chronic postoperative endophthalmitis associ ated with Propionibacterium acnes. Arch. Ophthal mol. 105:1199, 1987. 7. Brady, S. E., Cohen, E. J . , and Fischer, D, H.: Diagnosis and treatment of chronic postoperative bacterial endophthalmitis. Ophthalmic Surg. 19:580, 1988. 8. Forster, R. K., Abbott, R. L., and Gelender, H.: Management of infectious endophthalmitis. Oph thalmology 87:313, 1980. 9. Forster, R. K.: Etiology and diagnosis of bacteri al postoperative endophthalmitis. Ophthalmology 85:320, 1978. 10. Forster, R. K., Zachary, 1. G., Cottingham, A. J., Jr., and Norton, E. W. D.: Further observations on the diagnosis, cause, and treatment of endoph thalmitis. Am. J. Ophthalmol. 81:52, 1 9 7 6 . 11. Walker, J., Dangel, M. £., Makley, T. Α., and Opremeak, E. M.: Postoperative Propionibacterium granulosum endophthalmitis. Arch. Ophthalmol. 108:1073, 1990. 12. Seedor, J. Α., Koplin, R. S., Shah, Μ., Almdeda, Ε. Ε., Jr., and Perry, Η. D.: Chronic postopera tive endophthalmitis from Staphylococcus aureus. J. Cataract Refract. Surg. 16:512, 1990. 13. Puliafito, C. Α., Baker, A. S., Haaf, J., and Foster, C. S.: Infectious endophthalmitis. Review of 36 cases. Ophthalmology 8 9 : 9 2 1 , 1982. 14. Stern, W. H., Tamura, E., Jacobs, R. Α., Pons, V. G., Stone, R. D., O'Day, D. M., and Irvine, A. R.: Epidemic postsurgical Candida parapsilosis endoph thalmitis, clinical findings and management of 15 consecutive cases. Ophthalmology 9 2 : 1 7 0 1 , 1 9 8 5 . 15. Pflugfelder, S. C , Flynn, Η. W., Jr., Zwiekey, T. Α., Forster, R. Κ., Tsiügianni, Α., Culbertson, W. W., and Mandelbaum, S.: Exogenous fungal en dophthalmitis. Ophthalmology 95:19, 1988. 16. Roussel, Τ. J . , Stern, W. H., Goodman, D. F., and Whitcher, J. P.: Postoperative mycobacterial en dophthalmitis. Am. J. Ophthalmol. 107:403, 1 9 8 9 . 17. Driebe, W. T., Mandelbaum, S., Forster, R. Κ., Schwartz, L. Κ., and Culbertson, W. W.: Pseudopha kie endophthalmitis. Diagnosis and management. Ophthalmology 93:442, 1 9 8 6 . 18. Olson, J. C , Flynn, H. W., Jr., Forster, R. K., and Culbertson, W. W.: Results in the treatment of postoperative endophthalmitis. Ophthalmology 90:692, 1983. 19. Semel, J., Nobe, J., Bowe, B., Finegold, S., and Smith, R. E.: Propionibacterium acnes isolated from explanted intraocular lens in Pseudophakie bullous keratopathy. Cornea 8:259, 1989. 20. Rubinfeld, R. S., Cohen, E. J . , Arentsen, J. J . , and Laibson, P. R.: Diphtheroids as ocular patho gens. Am. J. Ophthalmol. 108:251, 1989. 2 1 . MeManaway, J. W., Weinberg, R. S., and Coudron, P. E.: Coryneform endophthalmitis. Two case reports. Arch. Ophthalmol. 108:942, 1 9 9 0 .
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22. Mandelbaum, S., Forster, R. Κ., Gelender, Η., and Culbertson, W. W.: Late onset endophthalmitis associated with filtering blebs. Ophthalmology 92:964, 1 9 8 5 . 23. Duker, J. S., and Belmont, J. B.: Late bacterial endophthalmitis following retinal detachment sur gery. Retina 9:263, 1989. 24. Joondeph, B. C „ Flynn, H. W., Jr., Miller, D., and Joondeph, H. C.: A new culture method for infectious endophthalmitis. Arch. Ophthalmol. 107:1334, 1989. 25. Stern, G. Α., Engel, Η. Μ., and Driebe, W. Τ., Jr.: Recurrent postoperative endophthalmitis. Cornea 9:102, 1990. 26. Tessler, H. H., Owens, S. L., and Deutsch, Τ. Α.: Intracapsular bag diagnosis and treatment of Propionibacterium acnes endophthalmitis. Ophthal mology 96:118, 1989. 27. Smith, M. Α., Sorenson, J. Α., Lowy, F. D., Shakin, J. L., Harrison, W., and Jakobiec, F. Α.: Treat ment of experimental methicillin-resistant Staphylo coccus epidermidis endophthalmitis with intravitreal vancomycin. Ophthalmology 9 3 : 1 3 2 8 , 1986. 28. Pflugfelder, S. C., Hernandez, Ε., Fliesler, S. J., Alvarez, J . , Pflugfelder, Μ. Ε., and Forster, R. Κ.: Intravitreal vancomycin. Retinal toxicity, clearance, and interaction with gentamicin. Arch. Ophthalmol. 105:831, 1987. 29. Davis, J. L., Koidou Tsiligianni, Α., Pflug
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felder, S. C , Miller, D., Flynn, H. W., Jr., and Forster, R. K.: Coagulase negative staphylococcal endoph thalmitis. Increase in antimicrobial resistance. Oph thalmology 9 5 : 1 4 0 4 , 1 9 8 8 . 30. Peyman, G. Α., and Herbst, R.: Bacterial en dophthalmitis. Treatment with intraocular injection of gentamicin and dexamethasone. Arch. Ophthal mol. 9 1 : 4 1 6 , 1 9 7 4 . 3 1 . Graham, R. O., and Peyman, G. Α.: Intravitre al injection of dexamethasone. Treatment of experirnentally induced endophthalmitis. Arch. Ophthal mol. 9 2 : 1 4 9 , 1 9 7 4 . 32. O'Day, D. M., Jones, D. B., Patrinely, J., and Elliott, J. H.: Staphylococcus epidermidis endophthal mitis. Visual outcome following non-invasive thera py. Ophthalmology 89:354, 1 9 8 2 . 33. Pryor, J. G., Apt, L., and Leopold, 1. H.: Intra ocular jserietration of vancomycin. Arch. Ophthal mol. 67:608, 1962. 3 4 . Barza, M., Kane, Α., and Baum, J . : Intraocular penetration of gentamicin after subconjunctival and retrobulbar injection. Am. J. Ophthalmol. 8 5 : 5 4 1 , 1978. 35. Brod, R. D., Flynn, H. W., Jr., Clarkson, J. G., Pflugfelder, S. C , Culbertson, W. W., and Miller, D.: Endogenous Candida endophthalmitis management without intravenous amphotericin B. Ophthalmolo gy 97:666, 1 9 9 0 .
OPHTHALMIC MINIATURE After the war he i n t e n d e d to go b a c k to London, w h e r e o n e could s e e o n e ' s own oculist. For Oliver's oculist had disappeared into the Army at the beginning of the war and he had c h a n c e d upon a very unlovable g e n t l e m a n w h o s e attitude towards his patients was that if his glasses did not suit them, something must be wrong with their eyes and it was entirely their own fault. Angela Thirkell, Marling Hall New York, Carroll & Graf Publishers, Inc., 1 9 9 0 , p. 6 6
Gregory Μ . Fox, M.D., Brian C. Joondeph, M . D . , Harry W. Flynn, Jr., M.D., Stephen C. Pflugfelder, M . D , , and Thomas J. Roussel, M . D .
We r e v i e w e d 1 9 c a s e s o f d e l a y e d - o n s e t P s e u dophakie e n d o p h t h a l m i t i s in which diagnos tic c u l t u r e s w e r e p e r f o r m e d a t o n e m o n t h o r more after cataract extraction with posterior chamber intraocular lens implantation. We i s o l a t e d f o u r different o r g a n i s m s i n t h e s e 1 9 c a s e s : 12 Propionibacterium s p e c i e s (63%), t h r e e Candida parapsilosis (16%), t h r e e Staph ylococcus epidermidis (16%), a n d o n e Corynebacterium s p e c i e s (5%). B e c a u s e o f t h e u n u s u al delayed-onset features of these cases a n d the retrospective nature of this study, a varie t y of t r e a t m e n t r e g i m e n s w e r e u s e d . T w e l v e p a t i e n t s h a d r e c u r r e n c e of m a r k e d i n f l a m m a tion despite an apparent initial cure, a n d ten of t h e s e p a t i e n t s h a d p o s i t i v e c u l t u r e r e s u l t s on r e p e a t e x a m i n a t i o n of i n t r a o c u l a r fluids. Nine patients continued to be treated with topical corticosteroids postoperatively to sup press low-grade inflammation. Of the 19 p a t i e n t s , 16 h a d final v i s u a l a c u i t y o f 2 0 / 4 0 0 o r better, Delayed-onset Pseudophakie endoph thalmitis had a more favorable visual progno sis, c o m p a r e d t o a c u t e - o n s e t e n d o p h t h a l m i t i s .
I N F E C T I O U S E N D O P H T H A L M I T I S is a n
uncommon
c o m p l i c a t i o n after c a t a r a c t s u r g e r y a n d i n t r a o c ular l e n s i m p l a n t a t i o n . A l t h o u g h t h i s c o n d i t i o n t y p i c a l l y o c c u r s in t h e e a r l y p o s t o p e r a t i v e p e r i od, a l e s s c o m m o n m a n i f e s t a t i o n o f p o s t o p e r a tive e n d o p h t h a l m i t i s h a s a c h r o n i c c o u r s e w i t h recurrent low-grade inflammation and has been called chronic bacterial endophthalmitis.' Even t h o u g h Propionibacterium acnes i s a f r e q u e n t e t i o l o g i c a g e n t in t h i s c a t e g o r y o f p o s t o p e r a t i v e
Accepted for publication Sept. 18, 1990. From the Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami School of Medicine, Miami, Florida. This study was supported in part by Fight For Sight, Inc. This study was presented in part at the 23rd Annual Meeting of the Retina Society, Key Largo, Florida, Oct. 5, 1990. Reprint requests to Harry W. Flynn, Jr., M.D., Bascom Palmer Eye Institute, P.O. Box 016880, Miami, FL 33101.
endophthalmitis,^"* d e l a y e d - o n s e t P s e u d o p h a kie e n d o p h t h a l m i t i s i s n o t a l w a y s c a u s e d b y P. acnes. I n 1 9 c u l t u r e - p r o v e n c a s e s o f d e l a y e d onset Pseudophakie endophthalmitis, we stud ied the spectrum o f organisms and the distin guishing clinical features o f these infections. B a s e d u p o n o u r e x p e r i e n c e in t h e m a n a g e m e n t of t h e s e e a s e s , specific t r e a t m e n t o p t i o n s a r e discussed.
Patients and Methods We reviewed the microbiology laboratory files a n d c o r r e s p o n d i n g c l i n i c a l r e c o r d s o f 1 8 7 patients who had culture-proven endophthal m i t i s after e x t r a c a p s u l a r c a t a r a c t e x t r a c t i o n with placement of a posterior c h a m b e r intraoc u l a r l e n s . A l l p a t i e n t s w e r e e x a m i n e d at o u r institution between November 1 9 7 9 and June 1 9 8 9 . C h a r t s w e r e r e v i e w e d for t h e t i m i n g o f the onset of symptoms, previous topical antibi otic or corticosteroid treatment, a n d initial clin ical m a n i f e s t a t i o n . F o l l o w - u p i n f o r m a t i o n after t r e a t m e n t w a s o b t a i n e d t h r o u g h M a y 1 9 9 0 from t h e m e d i c a l r e c o r d s o r from t h e r e f e r r i n g p h y s i c i a n s a n d i n c l u d e d final v i s u a l a c u i t y , i n t r a o c u lar p r e s s u r e , a n d a n y o b s e r v e d c o m p l i c a t i o n s . Of the 1 8 7 patients with Pseudophakie en d o p h t h a l m i t i s in t h i s t e n - y e a r p e r i o d , 1 2 7 h a d d i a g n o s t i c c u l t u r e s p e r f o r m e d in t h e first f o u r w e e k s after c a t a r a c t e x t r a c t i o n . O f t h e s e 1 2 7 patients, 1 2 0 had positive cultures of intraocu lar s p e c i m e n s o b t a i n e d d u r i n g t h e first t w o weeks. S e v e n patients underwent vitreous tap d u r i n g t h e third w e e k after c a t a r a c t s u r g e r y , a n d in t w o p a t i e n t s t h e s e i n f e c t i o n s w e r e a s s o ciated with suture removal or vitreous wick syndrome. Of the 1 8 7 patients, 6 0 h a d the initial diag n o s t i c p r o c e d u r e p e r f o r m e d o n e m o n t h after extracapsular cataract surgery. O n e month was s e l e c t e d as a d i v i d i n g l i n e b e t w e e n e a r l y a n d delayed-onset Pseudophakie endophthalmitis. Of the 6 0 patients with delayed-onset Pseudo phakie endophthalmitis, we excluded 2 6 pa-
©AMERICAN JOURNAL OF OPHTHALMOLOGY 111:163-173, FEBRUARY, 1991
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tients with acute bleb-associated endophthal m i t i s , six p a t i e n t s w i t h r e c e n t p o s t o p e r a t i v e s u t u r e r e m o v a l , six p a t i e n t s w i t h t r a u m a t i c w o u n d d e h i s c e n c e s , a n d o n e c r i t i c a l l y ill p a tient w i t h s e p t i c e m i a w h o d e v e l o p e d e n d o g e n o u s b a c t e r i a l e n d o p h t h a l m i t i s . Two o f t h e s e 60 patients with positive intraocular cultures p e r f o r m e d in o u r m i c r o b i o l o g y l a b o r a t o r y w e r e t r e a t e d b y p h y s i c i a n s at a n o t h e r h o s p i t a l a n d were excluded because of inadequate informa tion regarding their clinical course and treat m e n t . In o n e of t h e s e two p a t i e n t s , b o t h Actino myces israelii a n d P. acnes w e r e c u l t u r e d from the v i t r e o u s , a n d this p a t i e n t a t t a i n e d final visual acuity of counting fingers. Propionibacte rium acnes w a s c u l t u r e d from the a q u e o u s s p e c i m e n o f the o t h e r p a t i e n t . T h i s s e c o n d p a t i e n t , d e s c r i b e d b y B r a d y , C o h e n , a n d F i s c h e r , ' at t a i n e d final visual a c u i t y o f 2 0 / 2 0 w i t h f o l l o w up at a n o t h e r h o s p i t a l . T h e r e m a i n i n g 19 p a t i e n t s w i t h c l i n i c a l e n d o p h t h a l m i t i s a n d di agnostic intraocular cultures performed one m o n t h after e x t r a c a p s u l a r c a t a r a c t e x t r a c t i o n and posterior chamber intraocular lens implan t a t i o n m e t our c r i t e r i a for d e l a y e d - o n s e t p s e u d o p h a k i c e n d o p h t h a l m i t i s . O f t h e s e 19 p a t i e n t s , four ( C a s e s 1, 7, 1 1 , a n d 1 2 ; T a b l e 1 ) have b e e n p r e v i o u s l y d e s c r i b e d by Z a m b r a n o a n d associates.^ I n t r a o c u l a r s p e c i m e n s w e r e o b t a i n e d from all patients and were inoculated into appropriate c u l t u r e media.*'" O u r c r i t e r i a for a p o s i t i v e c u l t u r e were the f o l l o w i n g : g r o w t h o f the s a m e o r g a n i s m on t w o or m o r e m e d i a ; or s e m i c o n fluent g r o w t h on o n e s o l i d m e d i u m ; o r g r o w t h at the i n o c u l a t i o n site on a m e d i u m a n d c o n firmed by o r g a n i s m s s e e n on G r a m s t a i n or histologic examination of intraocular tissues. All p a t i e n t s m e t t h e s e c r i t e r i a for p o s i t i v e c u l ture, e x c e p t for t h r e e p a t i e n t s in w h o m Propi onibacterium s p e c i e s g r e w from t h i o g l y c o l a t e m e d i u m o n l y b u t w h o h a d the t y p i c a l c l i n i c a l features o f P. acnes e n d o p h t h a l m i t i s ' ( C a s e s 8, 10, and 1 1 ; Table 1).
Results The s p e c t r u m o f c a u s a t i v e o r g a n i s m s in t h e s e patients with delayed-onset p s e u d o p h a k i c en d o p h t h a l m i t i s is s h o w n in T a b l e 1. T h e c u l t u r e r e p o r t s i n d i c a t e d that of the 19 c a s e s , 12 ( 6 3 % ) w e r e c a u s e d b y Propionibacterium species (one b y P. arachnia a n d 11 b y P. acnes); t h r e e c a s e s ( 1 6 % ) w e r e c a u s e d b y Candida parapsilosis;
February, 1991
three cases ( 1 6 % ) were caused by Staphylococ cus epidermidis; a n d the r e m a i n i n g c a s e ( 5 % ) w a s c a u s e d by a Corynebacterium species. T h e v i t r e o u s w a s c u l t u r e - p o s i t i v e in all 1 9 p a t i e n t s . T h e a n t e r i o r c h a m b e r fluid w a s c u l t u r e d in six p a t i e n t s a n d w a s p o s i t i v e in five o f t h e s e p a t i e n t s . G r a m s t a i n s of t h e initial i n t r a o c u l a r s p e c i m e n w e r e p o s i t i v e in o n l y o n e o f 12 p a t i e n t s w i t h Propionibacterium species infec t i o n , in o n e o f t h r e e p a t i e n t s w i t h C. para psilosis i n f e c t i o n , in t w o o f t h r e e p a t i e n t s w i t h S. epidermidis e n d o p h t h a l m i t i s , a n d in the p a t i e n t w i t h Corynebacterium species endophthal mitis. R e v i e w o f the c l i n i c a l c o u r s e o f t h e s e 19 patients showed that recurrent episodes of p o s t o p e r a t i v e i n f l a m m a t i o n w e r e t y p i c a l o f all p a t i e n t s . In the p a t i e n t s w i t h Propionibacterium s p e c i e s i n f e c t i o n , the t i m e o f d i a g n o s i s by p o s i tive c u l t u r e o f i n t r a o c u l a r fluid a v e r a g e d e i g h t m o n t h s a n d r a n g e d from six w e e k s to 3 6 m o n t h s after s u r g e r y . T h e o t h e r c a s e s w e r e c o n f i r m e d by p o s i t i v e c u l t u r e s at v a r i a b l e t i m e s after c a t a r a c t s u r g e r y (C. parapsilosis, one m o n t h to 2 3 m o n t h s ; S. epidermidis, o n e to t h r e e m o n t h s ; a n d Corynebacterium species, two m o n t h s ) . All p a t i e n t s w e r e r e f e r r e d b y a n t e r i o r s e g m e n t s u r g e o n s for t r e a t m e n t . M a n y o f t h e s e p a t i e n t s w e r e n o t e d to have c o r t i c o s t e r o i d - r e s p o n s i v e iritis, v i t r e i t i s , or b o t h , b e f o r e t h e i r referral. C o n t i n u e d t o p i c a l c o r t i c o s t e r o i d t r e a t m e n t of p r e s u m e d s t e r i l e i n t r a o c u l a r i n f l a m m a tion d e l a y e d the d i a g n o s i s in 15 o f 19 p a t i e n t s . Ten o f 12 p a t i e n t s w i t h Propionibacterium spe c i e s i n f e c t i o n (all e x c e p t C a s e s 1 a n d 1 0 ) , all t h r e e p a t i e n t s w i t h S. epidermidis infection, and the p a t i e n t w i t h Corynebacterium endophthal m i t i s h a d r e d u c e d or s t a b l e i n t r a o c u l a r inflam m a t i o n for a v a r i a b l e l e n g t h o f t i m e w h i l e taking topical corticosteroids. However, only o n e o f the t h r e e p a t i e n t s w i t h fungal e n d o p h thalmitis (Case 19) clinically improved while taking topical corticosteroids. All 12 p a t i e n t s w i t h Propionibacterium spe cies e n d o p h t h a l m i t i s d e m o n s t r a t e d a p r o m i n e n t w h i t e p l a q u e w i t h i n the c a p s u l e (Fig. 1) and vitreitis (Table 1). C h r o n i c granulomatous inflammation and keratic precipitates were not ed in six o f the 12 p a t i e n t s . B e a d e d fibrin strands extending across the anterior c h a m b e r w e r e s e e n in two p a t i e n t s ( C a s e s 1 0 a n d 1 1 ) . E i g h t p a t i e n t s w i t h Propionibacterium species endophthalmitis had initial visual acuity of 2 0 / 2 0 0 or b e t t e r . A s u b s e t o f two p a t i e n t s (Cases 2 and 5 ) , however, initially had more
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TABLE 1
CLINICAL FEATURES ON INITIAL EXAMINATION TIME FROM CATARACT EXTRACTION TO
INITIAL
INITIAL INFLAMMATION
CASE NO..
ORGANISM
ONSET OF
DIAGNOSTIC
VISUAL
IMPROVED OR STABILIZED WITH
AGE (YRS). SEX
CULTURED
SYMPTOMS
CULTURE
ACUITY*
20/200 White plaque, hypopyon, vitreitis LP White plaque, hypopyon, vitreitis 20/30 White plaque, keratic precipitates, vitreitis 20/200 White plaque, keratic precipitates, vitreitis HM White plaque, keratic precipitates, hypopyon, vitreitis 20/200 White plaque, vitreitis 20/100 White plaque, hypopyon, vitreitis 20/70 White plaque, keratic precipitates, vitreitis 20/200 White plaque, fibrin in anterior chamber, vitreitis HM White plaque, keratic precipitates, beaded strands, vitreitis, central retinal vein occlusion HM White plaque, keratic precipitates, beaded strands, vitreitis, central retinal vein occlusion 20/100 White plaque, vitreitis 1/200 Fibrin in anterior chamber, dense vitreitis 3/200 Hypopyon, keratic precipi tates, dense vitreitis LP Keratic precipitates, fibrin in anterior chamber, dense vitreitis LP White plaque, hypopyon, dense vitreitis 20/300 Keratic precipitates, iso lated vitreous infiltrates, vitreitis 20/60 Keratic precipitates, Iso lated vitreous infiltrates, vitreitis 20/25 White plaque, keratic precip itates. Isolated vitreous infiltrates, vitreitis
1, 63, Ft
P. acnes
6 wks
6 wks
2, 73, Μ
p. acnes
4 mos
11 mos
3, 77, F
P. acnes
4 mos
13 mos
4, 75, Μ
P. acnes
2 wks
4 mos
5, 75, F
P. arachnia
6 wks
3 mos
6, 62, Μ 7, 74, W
P. acnes P. acnes
4 mos 8 mos
21 mos 36 mos
8, 57, Μ
P. acnes*
2 mos
5 mos
9, 76, Μ
P. acnes
2 wks
6 wks
10, 76, F
P. acnes*
2 mos
12 mos
11, 81, Mt
P. acnes*
2 mos
24 mos
12, 68, Mt P. acnes 13, 75, F S. epidermidis
2 wks 5 days
4 mos 6 wks
14, 71. Μ
S. epidermidis
1 mo
3 mos
15, 78, Μ
S. epidermidis
2 days
1 mo
16, 91, F
Corynebacterium
6 wks
2 mos
17, 81, Μ
C. parapsilosis
3 days
2 mos
18, 76, Μ
C. parapsilosis
3 days
1 mo
19, 66, Μ
C. parapsilosis
2 mos
23 mos
CLINICAL FEATURES
• LP indicates light perception and HM indicates hand motions. t Cases have been reported previously in reference 5 (Cases 1, 7, 11, and 12). * Equivocal culture grovrth found in Cases 8, 10, and 11.
TOPICAL CORTICOSTEROIDS
No Yes Yes Yes Yes
Yes Yes Yes Yes
Not given
Yes
Yes Yes Yes Yes Yes No Not given Yes
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Fig. 1 (FOX and associates). Case 4. Propionibacteri um acnes endoplithalmitis on initial examination demonstrating a prominent white plaque within the capsule and inferior keratic precipitates.
Fig. 2 (Fox and associates). Case 18. Candida parapsilosis endophthalmitis on initial examination dem onstrating stringy, isolated, white infiltrates in the anterior vitreous adjacent to capsular remnants.
advanced intraocular inflammation, including hypopyon, vitreitis, and visual acuity of hand motions or worse. The remaining two patients with p o o r i n i t i a l v i s u a l a c u i t y ( C a s e s 1 0 a n d 1 1 ) h a d diffuse i n t r a r e t i n a l h e m o r r h a g e s r e s e m b l i n g a c e n t r a l r e t i n a l vein o c c l u s i o n at the t i m e of the initial d i a g n o s i s . All p a t i e n t s with i n f e c t i o n s c a u s e d by S. epi dermidis h a d m a r k e d a n t e r i o r c h a m b e r inflam m a t i o n , but o n l y o n e p a t i e n t h a d h y p o p y o n formation (Case 1 4 ) . A white intracapsular p l a q u e was n o t o b s e r v e d in a n y o f t h e s e pa t i e n t s , but d e n s e v i t r e i t i s was n o t e d in all t h r e e p a t i e n t s . In t h e s e t h r e e p a t i e n t s , i n i t i a l v i s u a l a c u i t y varied from light p e r c e p t i o n to 3 / 2 0 0 . s p e c i e s in T h e p a t i e n t with Corynebacterium fection ( C a s e 1 6 ) i n i t i a l l y h a d m a r k e d a n t e r i o r chamber inflammation, hypopyon, and dense v i t r e i t i s . A w h i t e p l a q u e a d j a c e n t to t h e p o s t e r i or c a p s u l e was a l s o n o t e d . I n i t i a l v i s u a l a c u i t y was light p e r c e p t i o n . S i m i l a r to the p a t i e n t s with Propionibacteri um s p e c i e s i n f e c t i o n , all p a t i e n t s w i t h c h r o n i c fungal e n d o p h t h a l m i t i s h a d a v a r i a b l e d e c r e a s e o f v i s u a l a c u i t y r a n g i n g from 2 0 / 2 5 to 2 0 / 3 0 0 on initial m a n i f e s t a t i o n . T h e s e i n f e c t i o n s w e r e c h a r a c t e r i z e d at s o m e p o i n t d u r i n g their c l i n i cal c o u r s e by l o c a l i z e d w h i t e infiltrates in the a n t e r i o r v i t r e o u s a d j a c e n t to the c a p s u l e (Fig. 2 ) . A w h i t e p l a q u e i n s i d e the p o s t e r i o r c a p s u l e , r e s e m b l i n g t h o s e s e e n in Propionibacterium s p e c i e s e n d o p h t h a l m i t i s , w a s o b s e r v e d in o n e of t h r e e p a t i e n t s ( C a s e 1 9 ) . G r a n u l o m a t o u s anterior segment inflammation was seen ini tially in o n l y two o f the t h r e e p a t i e n t s ( C a s e s 17 a n d 1 8 ) , a n d the third p a t i e n t ( C a s e 1 9 )
d e v e l o p e d g r a n u l o m a t o u s i n f l a m m a t i o n later during recurrent episodes of infection. Five p a t i e n t s w i t h Propionibacterium species infection were treated initially with intraocular a n t i b i o t i c s a l o n e ( C a s e s 1, 4 , 7, 8, a n d 1 2 ; T a b l e 2). Because of suspected recurrent infection, four o f t h e s e five p a t i e n t s h a d f u r t h e r s u r g e r y . T h r e e p a t i e n t s h a d pars p l a n a v i t r e c t o m y a n d c e n t r a l c a p s u l e c t o m y , i n c l u d i n g r e m o v a l o f the a r e a o f the w h i t e p l a q u e a n d r e p e a t i n j e c t i o n o f i n t r a o c u l a r a n t i b i o t i c s d u r i n g the f o l l o w - u p course. T h e fourth patient had complete cap sule removal and intraocular lens exchange. V i t r e o u s s p e c i m e n s t a k e n d u r i n g the s e c o n d o p e r a t i v e p r o c e d u r e in t h e s e four p a t i e n t s w e r e still p o s i t i v e for Propionibacterium species de spite p r e v i o u s t r e a t m e n t . All five o f t h e s e p a t i e n t s a t t a i n e d final v i s u a l a c u i t y o f 2 0 / 4 0 0 or better. O f the 1 2 p a t i e n t s w i t h Propionibacterium s p e c i e s i n f e c t i o n s , six ( C a s e s 2, 3 , 5, 6 , 9 , a n d 10; Table 2) were initially treated with a stan dard three-port vitrectomy, central capsulecto my with s e l e c t i v e r e m o v a l o f the a r e a o f w h i t e plaque, and injection of intraocular antibiotics. O n e o f t h e s e six p a t i e n t s ( C a s e 3 ) h a d r e c u r r e n t inflammation and documented recurrent infec t i o n . An a n t e r i o r v i t r e c t o m y , c o m p l e t e c a p s u l e removal using alpha-chymotrypsin, and intra o c u l a r l e n s e x c h a n g e with r e p e a t i n t r a v i t r e a l a n t i b i o t i c s w e r e p e r f o r m e d in this p a t i e n t . T h e cultures of removed capsular remnants were p o s i t i v e for P. acnes. O f the six p a t i e n t s w i t h Propionibacterium species infection treated with initial v i t r e c t o m y , five o f six a t t a i n e d final v i s u a l a c u i t y o f 2 0 / 4 0 0 or b e t t e r . O n e p a t i e n t
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TABLE 2
TREATMENT AND FINAL VISUAL RESULTS INITIAL TREATMENT
CASE NO., ORGANISM
INTRAOCULAR ANTIBIOTICS* (INTRAOCULAR CORTICOSTEROIDS)
2, P. acnes
Vancomycin, tobra mycin (No) Vancomycin (No)
3, P. acnes
Vancomycin (Yes)
4, P. acnes
Vancomycin (Yes)
5, P. arachnia
Vancomycin (No)
6, P. acnes
None (No)
7, P. acnes
Vancomycin, tobra mycin (No)
8, P. acnes
1, P. acnes
SURGERY
FOLLOW-UP TREATMENT INTRAOCULAR ANTIBIOTICS* (INTRAOCULAR CORTICOSTEROIDS)
SURGERY
FINAL VISUAL ACUITY'
FOLLOW-UP (MOS)
6
Vitreous aspiration
None
None
20/40
Pars plana vitrec tomy, central capsulectomy Pars plana vitrec tomy, central capsulectomy Vitreous tap
None
None
LP
Vancomycin (No)
20/60
6
20/100
4
None
Anterior vitrectomy, intraocular lens exctiange Pars plana vitrec tomy, central capsu lectomy None
20/30
15
Vancomycin (No)
10
Pars plana vitrec tomy, central capsulectomy Pars plana vitrec tomy, intraocular lens exctiange Vitreous tap
None
None
20/20
13
Cefazolln (No)
20/30
16
Vancomycin, tobra mycin (No)
Vitreous tap
Vancomycin (No)
20/20
10
9, P. acnes
Vancomycin (No)
None
20/40
18
10, P. acnes
Vancomycin (No)
None
None
20/400
12
11, P. acnes
Vancomycin, tobra mycin (No)
Pars plana vitrec tomy, central capsulectomy Pars plana vitrec tomy, central capsulectomy Two-port subtotal pars plana vitrectomy
Pars plana vitrec tomy, central capsu lectomy Pars plana vitrec tomy, central capsu lectomy None
20/100
48
12, P. acnes
Cefazolln, gentamicin (No)
20/30
36
None
20/40
9
None
20/70
3
Three-port pars plana vitrectomy, central capsu lectomy
20/25
7
13, S. epidermidis
14, S. epidermidis
15, S. epidermidis
Vancomycin, genta- Ttiree-portmore micin (Yes) complete pars plana vitrectomy, central capsulectomy Intraocular lens No Intraocular exctiange antibiotics
Vitreous aspiration, pars plana vitrectomy, central capsulectomy None Vancomycin (No) Pars plana vitrec tomy, central capsulectomy None Vancomycin (No) Pars plana vitrec tomy, central capsulectomy Vancomycin (Yes) Vancomycin, genta- Two-port subtotal micin (No) pars plana vitrectomy
Contir)ued on pg 1 6 8
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TABLE 2 {continued) TREATMENT AND FINAL VISUAL RESULTS INITIAL TREATMENT
CASE NO., ORGANISM
INTRAOCULAR ANTIBIOTICS* (INTRAOCULAR CORTICOSTEROIDS)
FOLLOW-UP TREATMENT
SURGERY
INTRAOCULAR ANTIBIOTICS* (INTRAOCULAR CORTICOSTEROIDS)
16, Corynebacterium
Cefazolin, gentamicin (No)
Vitreous aspiration
Vancomycin (No)
17, C. parapsilosis
Amphotericin Β (No)
Amphotericin Β x2 (No)
18, C. parapsilosis
Amphotericin Β (No)
19, C. parapsilosis
Amphotericin Β (No)
Pars plana vitrec tomy, central capsulectomy Pars plana vitrec tomy, central capsulectomy Pars plana vitrec tomy, central capsulectomy
Amphotericin Β (No) Amphotericin Β x2 (No)
SURGERY
Pars plana vitrec tomy, central capsulectomy Pars plana vitrec tomy, central capsulectomy (x2) None
Pars plana vitrec tomy, capsulectomy, and intraocular lens removal
FINAL VISUAL ACUITY'
FOLLOW-UP (MOS)
HM
4
HM
12
20/70
60
20/25
7
*Dose of intraocular antibiotic or antifungal agents: vancomycin, 1 mg; cefazolin, 2.25 mg; gentamicin, 0.1 mg; tobramycin, 0.1 mg; and amptiotericin B, 5 μς. 'LP indicates light perception and HM indicates hand motions.
( C a s e 2 ) h a d final v i s u a l a c u i t y o f l i g h t p e r c e p tion because of optic atrophy, neovascular glau coma, and proliferative diabetic retinopathy. O n e p a t i e n t w i t h Propionibacterium species infection (Case 1 1 , Table 2) was treated initially w i t h a s u b t o t a l t w o - p o r t v i t r e c t o m y with i n j e c tion of intraocular antibiotics. Because of recur rent inflammation, a more complete three-port vitrectomy, central capsulectomy, and repeat injection of intraocular antibiotics were per f o r m e d . Propionibacterium acnes w a s a g a i n c u l t u r e d from t h e v i t r e c t o m y s p e c i m e n . T h i s p a t i e n t a t t a i n e d final v i s u a l a c u i t y o f 2 0 / 1 0 0 . Because of the high rate of recurrent infec tion, the determination o f a clinical cure was difficult in t h e s e p a t i e n t s w i t h Propionibacteri um s p e c i e s i n f e c t i o n ( T a b l e 3 ) . In t o t a l , six o f 1 2 p a t i e n t s c o n t i n u e d to u s e t o p i c a l c o r t i c o s t e r o i d s on l o n g - t e r m f o l l o w - u p ( C a s e s 2 t h r o u g h 5, 8, a n d 9 ) . D e s p i t e t h e r e c u r r e n c e s o f i n f l a m m a t i o n in t h e p a t i e n t s w i t h Propionibacterium s p e c i e s i n f e c t i o n , 11 of 1 2 p a t i e n t s a t t a i n e d final v i s u a l a c u i t y of 2 0 / 4 0 0 or b e t t e r . S e v e n o f 12 p a t i e n t s h a d v i s u a l a c u i t y o f 2 0 / 5 0 or b e t t e r . B e c a u s e o f t h e d e n s e v i t r e o u s infiltrates at t h e i n i t i a l e x a m i n a t i o n , all t h r e e p a t i e n t s w i t h S. epidermidis infection were treated by pars plana v i t r e c t o m y a n d i n j e c t i o n of i n t r a o c u l a r a n t i b i o t i c s . W i t h f o l l o w - u p o f t h r e e to n i n e m o n t h s .
t h e t h r e e p a t i e n t s a t t a i n e d v i s u a l a c u i t y of 2 0 / 2 5 , 2 0 / 4 0 , a n d 2 0 / 7 0 , r e s p e c t i v e l y . O n e of these patients (Case 15, Table 2) had marked recurrent inflammation, including vitreitis, anterior uveitis, hypopyon, and visual acuity of h a n d m o t i o n s , o n e m o n t h after i n i t i a l p r e sumed successful treatment with a subtotal vitrectomy without capsulectomy and injection of i n t r a o c u l a r a n t i b i o t i c s . A m o r e c o m p l e t e three-port pars plana vitrectomy with central capsulectomy and repeat injection of intraocu lar a n t i b i o t i c s a n d c o r t i c o s t e r o i d s w a s p e r formed. The repeat cultures of the vitreous s p e c i m e n w e r e n e g a t i v e . F i n a l v i s u a l a c u i t y in this patient was 2 0 / 2 5 . T h e p a t i e n t w i t h Corynebacterium species in f e c t i o n w a s i n i t i a l l y t r e a t e d w i t h v i t r e o u s tap and intraocular antibiotics. Visual acuity re mained hand motions because of persistent media opacities. W h e n visual acuity decreased to l i g h t p e r c e p t i o n o n l y a n d i n t r a o c u l a r p r e s sure b y a p p l a n a t i o n t o n o m e t r y d e c r e a s e d to 1 m m Hg, a pars plana vitrectomy was performed two m o n t h s after t h e i n i t i a l t r e a t m e n t . T h e e y e developed increasing inflammation six m o n t h s after v i t r e c t o m y , a n d r e p e a t v i t r e o u s tap w a s recommended. The patient refused further treatment, and visual acuity remained hand motions with hypotony.
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TABLE 3 ENDOPHTHALMITIS RECURRENCES CASE
NO. OF EPISODES OF
REPEAT CULTURE
LONG-TERM TOPICAL
NO.
RECURRENCE
RESULT*
CORTICOSTEROIDS
1 2 3
0 0 1
None None Positive
No Yes Yes
4
1
Positive
Yes
5
1
Not performed
Yes
6 7 8 9 10 11
0 1 1 0 0 1
None Positive Positive None None Positive
No No Yes Yes No No
12 13 14 15 16
1 0 0 1 2
Positive None None Negative Positive botti times
No No No Yes Yes
17
2
Positive twtti times
No
18 19
1 2
Positive Positive both times
No Yes
COMMENTS
No recurrent inflammation Proliferative diabetic retinopathy, neovascular glaucoma Recurred after pars plana vitrectomy, capsulectomy, and intraocular antibiotics Recurred after vitreous tap and intraocular antibiotics; age-related macular degeneration Recurrent anterior uveitis treated with topical corticosteroids No recurrent inflammation Recurred after vitreous tap and intraocular antibiotics Recurred after vitreous tap and intraocular antibiotics Intermittent episodes of intraocular inflammation Central retinal vein occlusion Recurred after subtotal pars plana vitrectomy and intraocular antibiotics; central retinal vein occlusion Recurred after vitreous tap and intraocular antibiotics No recurrent inflammation Macular hole Culture negative recurrence 1 month after apparent cure Recurred after vitreous tap and intraocular antibiotics; suspected recurrence after pars plana vitrectomy; patient refused further treatment Recurred after two pars plana vitrectomies; endstage chronic open-angle glaucoma Recurred after pars plana vitrectomy Recurred after two pars plana vitrectomies; required intraocular lens removal
* Repeat positive culture results were the same organism as initially cultured in all cases.
All t h r e e p a t i e n t s v^rith e n d o p h t h a l m i t i s c a u s e d b y C. parapsilosis had recurrent posttreatment inflammation and repeat culturep r o v e n p e r s i s t e n t i n f e c t i o n after i n i t i a l a p p a r ent cure with vitrectomy and intraocular am photericin B. One patient (Case 17) received a r e p e a t a m p h o t e r i c i n Β i n j e c t i o n (5 μ g ) , at t h e t i m e of the s e c o n d v i t r e c t o m y p r o c e d u r e . Five m o n t h s after t h e t h i r d v i t r e c t o m y p r o c e d u r e , the p a t i e n t r e q u i r e d filtering s u r g e r y a n d h a d final v i s u a l a c u i t y o f h a n d m o t i o n s b e c a u s e o f endstage glaucoma. Another patient (Case 18) had two vitrectomy procedures (each including 5 μ g o f a m p h o t e r i c i n B) a n d a t t a i n e d v i s u a l a c u i t y o f 2 0 / 7 0 , w i t h five y e a r s o f f o l l o w - u p after t h e s e c o n d v i t r e c t o m y . O n e p a t i e n t ( C a s e 19) required pars plana vitrectomy twice and intraocular amphotericin Β injection three times. Despite these procedures, this patient h a d i n c r e a s i n g i n f l a m m a t i o n in t h e v i t r e o u s
base region, which necessitated intraocular lens removal and complete capsulectomy using a l p h a - c h y m o t r y p s i n . T h i s p a t i e n t ( C a s e 1 9 ) at t a i n e d final v i s u a l a c u i t y o f 2 0 / 2 5 w i t h s e v e n m o n t h s o f f o l l o w - u p s i n c e t h e last s u r g i c a l treatment.
Discussion C a s e r e p o r t s or s m a l l s e r i e s o f p a t i e n t s w i t h delayed-onset postoperative endophthalmitis c a u s e d b y a v a r i e t y o f o r g a n i s m s , i n c l u d i n g P. acnes,^-^ P. granulosum,^^ S. aureus,^^ S. epider midis,^ Achromobacter species,' Cephalosporium s p e c i e s , ' ^ C. parapsilosis,^^ Acremonium spe cies,'^ Paecilomyces species,'^ and Aspergillus species'^ h a v e b e e n d e s c r i b e d . We h a v e a l s o previously reported a case of endophthalmitis
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m a n i f e s t i n g s e v e n weelcs after s e c o n d a r y i n t r a o c u l a r l e n s i m p l a n t a t i o n in w h i c h Mycobacteri um chelonae was isolated.'* In o u r p a t i e n t s w i t h c u l t u r e - p r o v e n i n f e c t i o n after e x t r a c a p s u l a r cataract e x t r a c t i o n a n d p o s t e r i o r c h a m b e r i n t r a o c u l a r l e n s i m p l a n t a t i o n e x a m i n e d at our i n s t i tution b e t w e e n 1 9 7 9 a n d 1 9 8 9 , four o r g a n i s m s in this c h r o n i c c a t e g o r y w e r e i s o l a t e d : P. acnes, C. parapsilosis, S. epidermidis, and Corynebacte rium s p e c i e s . T h i s s p e c t r u m o f i n f e c t i n g or g a n i s m s in the d e l a y e d - o n s e t p s e u d o p h a k i c e n d o p h t h a l m i t i s c a t e g o r y differs from a p r e v i ously p u b l i s h e d r e p o r t from our i n s t i t u t i o n , which reviewed primarily acute postoperative pseudophakic endophthalmitis." Even though S. epidermidis was s e e n in b o t h c a t e g o r i e s . Staphylococcus s p e c i e s ( i n c l u d i n g S. aureus), streptococci, and gram-negative organisms w e r e m o r e f r e q u e n t l y o b s e r v e d in the a c u t e p o s t o p e r a t i v e category.'•"'•"·" A syndrome of delayed-onset pseudophakic endophthalmitis manifesting with a white p l a q u e , m o d e r a t e visual l o s s , a n d often g r a n u l o m a t o u s i n f l a m m a t i o n after e x t r a c a p s u l a r cat a r a c t e x t r a c t i o n c a u s e d by P. acnes was d e s c r i b e d by M e i s l e r a n d a s s o c i a t e s ^ in 1 9 8 6 . F u r t h e r r e p o r t s have d e s c r i b e d the m a n a g e m e n t o p t i o n s a n d final v i s u a l r e s u l t s o f t h i s syndrome.'" Semel and a s s o c i a t e s " reported g r o w t h of P. acnes from the i n t r a o c u l a r l e n s in four o f 12 p a t i e n t s in w h o m the i n t r a o c u l a r lenses were removed during routine keratoplas ty for p s e u d o p h a k i c b u l l o u s k e r a t o p a t h y . A l t h o u g h this r e p o r t did n o t i d e n t i f y P. acnes as an e t i o l o g i c a g e n t in p s e u d o p h a k i c b u l l o u s k e r a t o p a t h y , it d o e s s u g g e s t that this o r g a n i s m c a n r e m a i n v i a b l e in the p s e u d o p h a k i c e y e for an extended time. Even t h o u g h Propionibacterium s p e c i e s , S. epidermidis, a n d C. parapsilosis are now wellrecognized ocular pathogens, Corynebacterium s p e c i e s have often b e e n r e g a r d e d as n o n p a t h o g e n i c c o n t a m i n a n t s o f the h u m a n e x t e r n a l e y e . However, ocular infections caused by Coryne bacterium s p e c i e s , i n c l u d i n g i n d o l e n t keratitis^" and endophthalmitis,^' have been reported. E n d o p h t h a l m i t i s o c c u r r i n g m o n t h s or y e a r s after s u r g e r y is a w e l l - r e c o g n i z e d c o m p l i c a t i o n of c o n j u n c t i v a l filtering blebs.^^ P a t i e n t s w i t h bleb-associated endophthalmitis, however, t y p i c a l l y have the a c u t e o n s e t o f i n f l a m m a t i o n a n d are u s u a l l y d i s t i n g u i s h e d from t h e s e p a tients with delayed-onset pseudophakic en d o p h t h a l m i t i s b y the p r e s e n c e of an o b v i o u s l y i n f e c t e d filtering b l e b . F u r t h e r m o r e , b l e b - a s sociated infections are generally caused by
February, 1991
more virulent organisms, including either Streptococcus s p e c i e s or Haemophilus s p e c i e s , in 8 0 % o f r e p o r t e d c u l t u r e - p o s i t i v e cases.^^ E n d o p h t h a l m i t i s c a s e s o c c u r r i n g five a n d n i n e m o n t h s after s c l e r a l b u c k l i n g s u r g e r y h a v e b e e n reported.^" V i s i b l e i n t r u s i o n o f the b u c k ling e l e m e n t w a s s u s p e c t e d to b e the a c c e s s site of the i n f e c t i o n . V i t r e o u s c u l t u r e s p e r f o r m e d at the t i m e of s c l e r a l b u c k l e r e m o v a l w e r e p o s i t i v e for Proteus mirabilis in b o t h c a s e s . L a t e - o n s e t e n d o p h t h a l m i t i s o c c u r r i n g m o n t h s after r e t i n a l detachment surgery caused by such a virulent o r g a n i s m c l e a r l y r e p r e s e n t s a different e n t i t y c o m p a r e d to d e l a y e d - o n s e t p s e u d o p h a k i c e n d o p h t h a l m i t i s in our s e r i e s o f p a t i e n t s . T h e s e patients with delayed-onset pseudo p h a k i c e n d o p h t h a l m i t i s h a d s e v e r a l specific c l i n i c a l f e a t u r e s , w h i c h m a y h e l p to d i s t i n g u i s h b e t w e e n the different i n f e c t i n g o r g a n i s m s . A white intracapsular plaque, representing se q u e s t e r e d o r g a n i s m s w i t h i n the c a p s u l e , was s e e n in all 12 o f the p a t i e n t s w i t h Propionibacte rium s p e c i e s i n f e c t i o n . In o n e p a t i e n t w i t h C. parapsilosis e n d o p h t h a l m i t i s a n d the p a t i e n t with Corynebacterium species infection, howev er, a w h i t e i n t r a c a p s u l a r p l a q u e w a s a l s o o b s e r v e d . G r a n u l o m a t o u s i n f l a m m a t i o n as m a n i fested by large k e r a t i c p r e c i p i t a t e s was a l s o s e e n in six o f the 12 p a t i e n t s w i t h Propionibac terium s p e c i e s i n f e c t i o n . B e a d e d fibrin s t r a n d s e x t e n d i n g a c r o s s to the a n t e r i o r c h a m b e r w e r e s e e n in t w o o f the 12 p a t i e n t s w i t h Propionibac terium s p e c i e s i n f e c t i o n . S t r i n g y w h i t e infil t r a t e s in the a n t e r i o r v i t r e o u s a d j a c e n t to the c a p s u l a r r e m n a n t s o c c u r r e d in all t h r e e o f the p a t i e n t s w i t h C. parapsilosis infection. Dense v i t r e i t i s c a u s i n g a p o o r v i e w o f fundus d e t a i l s w a s n o t e d in all t h r e e p a t i e n t s w i t h S. epider midis e n d o p h t h a l m i t i s a n d the p a t i e n t w i t h Corynebacterium s p e c i e s i n f e c t i o n . N o n e of the p a t i e n t s with fungal o r P. acnes i n f e c t i o n h a d a diffuse, d e n s e v i t r e i t i s , e v e n t h o u g h a m i l d c e l l u l a r r e a c t i o n in the v i t r e o u s w a s o b s e r v e d in all o f t h e s e p a t i e n t s . In t h e s e p a t i e n t s w i t h d e l a y e d - o n s e t p s e u d o p h a k i c e n d o p h t h a l m i t i s , the s p e c t r u m o f or g a n i s m s a n d the p o t e n t i a l difficulty e n c o u n tered in a c h i e v i n g a p o s i t i v e c u l t u r e r e s u l t e m p h a s i z e the n e e d for effective c u l t u r e t e c h niques. Anterior chamber and vitreous speci m e n s from t h e s e c a s e s c a n b e p l a c e d o n a n a e r o bic p l a t e s a n d t h i o g l y c o l a t e b r o t h ( i d e a l for P. acnes), S a b o u r a u d ' s m e d i a ( i d e a l for f u n g i ) , a n d b l o o d a g a r a n d c h o c o l a t e p l a t e s ( i d e a l for S. epidermidis a n d Corynebacterium species). The u s e of b l o o d c u l t u r e b o t t l e s , a t e c h n i q u e a l l o w -
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Delayed-Onset Pseudophakie Endophthalmitis
ing direct i n o c u l a t i o n of u n f i l t e r e d v i t r e c t o m y specimens,^" was a l s o s u c c e s s f u l in a c h i e v i n g a p o s i t i v e c u l t u r e r e s u l t in four o f t h e s i x p a t i e n t s in w h o m t h e y w e r e u s e d . In all c u l t u r e m e t h ods, c u l t u r e m e d i a s h o u l d b e o b s e r v e d for at least two w e e k s b e c a u s e o f t h e s l o w g r o w t h o f b o t h P. flcnes' a n d Corynebacterium species.^' Patients with delayed-onset Pseudophakie endophthalmitis had better posttreatment visu al acuity w h e n c o m p a r e d to a c u t e p o s t o p e r a t i v e P s e u d o p h a k i e e n d o p h t h a l m i t i s . " " " ' * O f 19 p a t i e n t s , 16 h a d final v i s u a l a c u i t y o f 2 0 / 4 0 0 or better. O f the three patients with visual acuity w o r s e t h a n 2 0 / 4 0 0 , two p a t i e n t s h a d signifi cant preexisting diseases (optic atrophy, n e o vaseular glaucoma, and proliferative diabetic r e t i n o p a t h y in t h e p a t i e n t in C a s e 2 a n d a d v a n c e d o p e n - a n g l e g l a u c o m a in t h e p a t i e n t in Case 17). The patient with Corynebacterium species infection developed chronic hypotony a n d refused further t r e a t m e n t . B e c a u s e of t h e v a r i a b l e m a n i f e s t a t i o n s a n d l i m i t e d t r e a t m e n t e x p e r i e n c e w i t h this c a t e g o r y of d e l a y e d - o n s e t P s e u d o p h a k i e e n d o p h t h a l m i tis, t h e i d e a l t r e a t m e n t r e m a i n s c o n t r o v e r s i a l . ^ S e v e r a l different a p p r o a c h e s w e r e s e l e c t e d b y the s u r g e o n s o f different s u b s p e c i a l i t i e s w h o t r e a t e d t h e s e p a t i e n t s . In t h e five p a t i e n t s w i t h P. acnes i n f e c t i o n t r e a t e d i n i t i a l l y w i t h i n j e c tion o f i n t r a o c u l a r a n t i b i o t i c s w i t h o u t v i t r e c tomy, r e c u r r e n t i n f e c t i o n o c c u r r e d in four p a tients. S u b s e q u e n t pars plana vitrectomy, central capsulectomy, and repeat intraocular a n t i b i o t i c i n j e c t i o n w e r e p e r f o r m e d in t h r e e patients, and complete capsule removal with i n t r a o c u l a r l e n s e x c h a n g e w a s p e r f o r m e d in one patient. Despite apparent initial cure with pars p l a n a v i t r e c t o m y a n d i n j e c t i o n o f i n t r a o c u lar a n t i b i o t i c s or a n t i f u n g a l a g e n t s , i n i t i a l t r e a t m e n t failures a l s o o c c u r r e d in five o f t h e 1 3 p a t i e n t s t r e a t e d b y this a p p r o a c h . S t e r n , E n g e l , a n d Driebe^' h a v e d e s c r i b e d s i m i l a r p a t i e n t s with r e c u r r e n t e n d o p h t h a l m i t i s w h o h a v e r e quired r e p e a t e d i n j e c t i o n s o f i n t r a o c u l a r a n t i b i o t i c s w i t h p a r s p l a n a v i t r e c t o m y to a c h i e v e a clinical cure. A l t e r n a t i v e m e t h o d s o f t r e a t m e n t for p a t i e n t s w i t h Propionibacterium species infection have been reported. Brady, Cohen, and Fischer' re ported successful therapy with topical and sys t e m i c a n t i b i o t i c s for o n e p a t i e n t w i t h P. acnes. T e s s l e r , O w e n s , a n d Deutsch^^ r e p o r t e d the a p p r o a c h o f i n t r a c a p s u l a r i n j e c t i o n o f 0 . 2 ml o f c l i n d a m y c i n (2 m g ) , w h i c h w a s p e r f o r m e d on an o u t p a t i e n t b a s i s e v e r y o t h e r day for a t o t a l o f three treatments. The n u m b e r of patients with
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P. acnes t r e a t e d b y t h e s e a l t e r n a t i v e t e c h n i q u e s has been limited. B a s e d on our e x p e r i e n c e w i t h t h e s e 1 9 p a t i e n t s , we r e c o m m e n d t h e f o l l o w i n g t r e a t m e n t a p p r o a c h in c a s e s o f d e l a y e d - o n s e t P s e u d o p h a kie e n d o p h t h a l m i t i s . In all c a s e s , i n t r a o c u l a r cultures should be performed, and pars plana v i t r e c t o m y is o u r p r e f e r r e d m e t h o d for o b t a i n ing t h e s p e c i m e n . W e r e c o m m e n d a l a r g e c e n tral c a p s u l e c t o m y w i t h s e l e c t i v e r e m o v a l o f t h e a r e a o f w h i t e p l a q u e at t h e t i m e o f t h e p a r s p l a n a v i t r e c t o m y . L i k e w i s e , d e n s e v i t r e o u s in filtrates should b e r e m o v e d during the pars plana vitrectomy. A more complete three-port p a r s p l a n a v i t r e c t o m y is p r e f e r r e d i f a s a t i s f a c tory v i e w o f t h e p o s t e r i o r s e g m e n t is p o s s i b l e . I n t r a v i t r e a l v a n c o m y c i n h y d r o c h l o r i d e , 1.0 m g , is o u r r e c o m m e n d e d a n t i b i o t i c in p a t i e n t s w i t h suspected bacterial infection, because vanco m y c i n h y d r o c h l o r i d e h a s b e e n p r o v e n effective a g a i n s t P. acnes a n d S. epidermidis infections.*" T h e Corynebacterium species isolates (Case 16) w e r e a l s o s e n s i t i v e to v a n c o m y c i n h y d r o c h l o r ide. A n i m a l s t u d i e s h a v e s h o w n t h a t this d o s e o f i n t r a v i t r e a l v a n c o m y c i n h y d r o c h l o r i d e is well tolerated with no signs o f retinal toxicity.^' Although methicillin sodium and the cephalo s p o r i n s m a y b e effective, t h e i n c r e a s i n g r e s i s t a n c e o f S. epidermidis to methicillin sodium gives vancomycin hydrochloride a distinct ad v a n t a g e in t h e s e c a s e s . S i n c e P. acnes s h o w s relative resistance to a m i n o g l y c o s i d e anti b i o t i c s , w e do n o t r e c o m m e n d t h e i n i t i a l u s e of this c l a s s o f a n t i b i o t i c s for s u s p e c t e d P. acnes endophthalmitis. The use of intraocular corti c o s t e r o i d s ( d e x a m e t h a s o n e , 0 . 4 m g ) is o p t i o n a l b u t s h o u l d b e c o n s i d e r e d in e y e s w i t h m o r e a d v a n c e d inflammation.^"'^' T h e r o l e o f i n t r a v e n o u s a n t i b i o t i c t h e r a p y in cases of endophthalmitis remains controver sial. Brady, C o h e n , and Fischer' described one p a t i e n t w i t h P. acnes e n d o p h t h a l m i t i s w h o w a s treated with prolonged intravenous, oral, and topical antibiotic therapy and regained 2 0 / 2 0 visual acuity. O'Day and associates'^ reported the successful use of subconjunctival, topical, and intravenous antibiotics without intravitreal a n t i b i o t i c s in p a t i e n t s w i t h S. epidermidis en dophthalmitis. However, subtherapeutic intra vitreal concentrations o f vancomycin hydro c h l o r i d e w e r e a c h i e v e d in a n i m a l s t u d i e s , ' ' ' ^ a n d s y s t e m i c c o m p l i c a t i o n s , s u c h as p e r i p h l e b i tis, a l l e r g i c r e a c t i o n s , a n d n e p h r o t o x i c i t y , h a v e b e e n r e p o r t e d in p a t i e n t s r e c e i v i n g i n t r a v e n o u s vancomycin hydrochloride. Intravenous anti b i o t i c s w e r e u s e d d u r i n g t h e b r i e f h o s p i t a l stay
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of o n l y o n e o f our 19 p a t i e n t s w i t h d e l a y e d onset endophthalmitis (Case 1 ) . Because of the r e t r o s p e c t i v e n a t u r e of t h e p r e s e n t s e r i e s w i t h out r a n d o m i z a t i o n of t r e a t m e n t , w e are u n a b l e to draw any c o n c l u s i o n s a b o u t t h e e f f e c t i v e n e s s of i n t r a v e n o u s a n t i b i o t i c s in t h i s c a t e g o r y o f endophthalmitis. W h e n c h a r a c t e r i s t i c s t r i n g y , w h i t e infiltrates are s e e n in t h e v i t r e o u s or c u l t u r e s a r e p o s i t i v e for fungal e l e m e n t s , w e r e c o m m e n d i n t r a v i t r e a l i n j e c t i o n o f a m p h o t e r i c i n B, 5 μg. Brod a n d associates'*^ r e p o r t e d s u c c e s s f u l t r e a t m e n t o f e n d o g e n o u s Candida species endophthalmitis w i t h o u t i n t r a v e n o u s a m p h o t e r i c i n B . To avoid t h e s y s t e m i c t o x i c i t y a s s o c i a t e d w i t h its u s e , s y s t e m i c a m p h o t e r i c i n Β was n o t u s e d in o u r p a t i e n t s w i t h Candida s p e c i e s e n d o p h t h a l m i t i s . T r e a t m e n t w i t h o r a l i m i d a z o l e s , s u c h as k e t o c o n a z o l e or fluconazole, c o u l d b e c o n s i d e r e d in p a t i e n t s w i t h fungal i n f e c t i o n . T h e d e t e r m i n a t i o n of a c l i n i c a l cure w a s diffi cult in t h e s e p a t i e n t s w i t h d e l a y e d - o n s e t P s e u d o p h a k i e e n d o p h t h a l m i t i s b e c a u s e 12 p a t i e n t s h a d r e c u r r e n c e o f m a r k e d i n f l a m m a t i o n a n d ten o f t h e s e p a t i e n t s h a d p o s i t i v e c u l t u r e r e s u l t s on r e p e a t e x a m i n a t i o n o f i n t r a o c u l a r fluids d e s p i t e an a p p a r e n t i n i t i a l c u r e ( T a b l e 3 ) . N i n e p a t i e n t s required long-term use of topical corticoste roids p o s t o p e r a t i v e l y to s u p p r e s s l o w - g r a d e in flammation or e p i s o d e s o f a c u t e - o n s e t a n t e r i o r uveitis. Despite these features, delayed-onset P s e u d o p h a k i e e n d o p h t h a l m i t i s h a s a m o r e fa v o r a b l e v i s u a l p r o g n o s i s , c o m p a r e d to o t h e r c a t e g o r i e s of e n d o p h t h a l m i t i s .
References 1. Picker, L., Meredith, T. Α., Wilson, L. Α., Kap lan, H. J . , and Kozarsky, A. M.: Chronic bacterial endophthalmitis. Am. J. Ophthalmol. 103:745, 1987. 2. Friedman, E., Peyman, G. Α., and May, D. R.: Endophthalmitis caused by Propionibacterium acnes. Can. J. Ophthalmol. 13:50, 1978. 3. Meisler, D. M., Palestine, A. G., Vastine, D. W., Demartini, D. R., Murphy, B. F., Reinhart, W. J., Zakov, Z. N., McMahon, J. T., and CUffel, T. P.: Chronic Propionibacterium endophthalmitis after ex tracapsular cataract extraction and intraocular lens implantation. Am. J. Ophthalmol. 102:733, 1 9 8 6 . 4. Jaffe, G. J . , Whitcher, J. P., Biswell, R., and Ir vine, A. R.: Propionibacterium acnes endophthalmitis seven months after extracapsular cataract extraction and intraocular lens implantation. Ophthalmic Surg. 17:791, 1986. 5. Zambrano, W., Flynn, H. W„ Jr., Pflugfelder, S. C , Roussel, Τ. J., Culbertson, W. W., Holland, S.,
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and Miller, D.: Management options for Propionibac terium acnes endophthalmitis. Ophthalmology 96:1100, 1989. 6. Roussel, T. J . , Culbertson, W. W., and Jaffe, N. S.: Chronic postoperative endophthalmitis associ ated with Propionibacterium acnes. Arch. Ophthal mol. 105:1199, 1987. 7. Brady, S. E., Cohen, E. J . , and Fischer, D, H.: Diagnosis and treatment of chronic postoperative bacterial endophthalmitis. Ophthalmic Surg. 19:580, 1988. 8. Forster, R. K., Abbott, R. L., and Gelender, H.: Management of infectious endophthalmitis. Oph thalmology 87:313, 1980. 9. Forster, R. K.: Etiology and diagnosis of bacteri al postoperative endophthalmitis. Ophthalmology 85:320, 1978. 10. Forster, R. K., Zachary, 1. G., Cottingham, A. J., Jr., and Norton, E. W. D.: Further observations on the diagnosis, cause, and treatment of endoph thalmitis. Am. J. Ophthalmol. 81:52, 1 9 7 6 . 11. Walker, J., Dangel, M. £., Makley, T. Α., and Opremeak, E. M.: Postoperative Propionibacterium granulosum endophthalmitis. Arch. Ophthalmol. 108:1073, 1990. 12. Seedor, J. Α., Koplin, R. S., Shah, Μ., Almdeda, Ε. Ε., Jr., and Perry, Η. D.: Chronic postopera tive endophthalmitis from Staphylococcus aureus. J. Cataract Refract. Surg. 16:512, 1990. 13. Puliafito, C. Α., Baker, A. S., Haaf, J., and Foster, C. S.: Infectious endophthalmitis. Review of 36 cases. Ophthalmology 8 9 : 9 2 1 , 1982. 14. Stern, W. H., Tamura, E., Jacobs, R. Α., Pons, V. G., Stone, R. D., O'Day, D. M., and Irvine, A. R.: Epidemic postsurgical Candida parapsilosis endoph thalmitis, clinical findings and management of 15 consecutive cases. Ophthalmology 9 2 : 1 7 0 1 , 1 9 8 5 . 15. Pflugfelder, S. C , Flynn, Η. W., Jr., Zwiekey, T. Α., Forster, R. Κ., Tsiügianni, Α., Culbertson, W. W., and Mandelbaum, S.: Exogenous fungal en dophthalmitis. Ophthalmology 95:19, 1988. 16. Roussel, Τ. J . , Stern, W. H., Goodman, D. F., and Whitcher, J. P.: Postoperative mycobacterial en dophthalmitis. Am. J. Ophthalmol. 107:403, 1 9 8 9 . 17. Driebe, W. T., Mandelbaum, S., Forster, R. Κ., Schwartz, L. Κ., and Culbertson, W. W.: Pseudopha kie endophthalmitis. Diagnosis and management. Ophthalmology 93:442, 1 9 8 6 . 18. Olson, J. C , Flynn, H. W., Jr., Forster, R. K., and Culbertson, W. W.: Results in the treatment of postoperative endophthalmitis. Ophthalmology 90:692, 1983. 19. Semel, J., Nobe, J., Bowe, B., Finegold, S., and Smith, R. E.: Propionibacterium acnes isolated from explanted intraocular lens in Pseudophakie bullous keratopathy. Cornea 8:259, 1989. 20. Rubinfeld, R. S., Cohen, E. J . , Arentsen, J. J . , and Laibson, P. R.: Diphtheroids as ocular patho gens. Am. J. Ophthalmol. 108:251, 1989. 2 1 . MeManaway, J. W., Weinberg, R. S., and Coudron, P. E.: Coryneform endophthalmitis. Two case reports. Arch. Ophthalmol. 108:942, 1 9 9 0 .
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22. Mandelbaum, S., Forster, R. Κ., Gelender, Η., and Culbertson, W. W.: Late onset endophthalmitis associated with filtering blebs. Ophthalmology 92:964, 1 9 8 5 . 23. Duker, J. S., and Belmont, J. B.: Late bacterial endophthalmitis following retinal detachment sur gery. Retina 9:263, 1989. 24. Joondeph, B. C „ Flynn, H. W., Jr., Miller, D., and Joondeph, H. C.: A new culture method for infectious endophthalmitis. Arch. Ophthalmol. 107:1334, 1989. 25. Stern, G. Α., Engel, Η. Μ., and Driebe, W. Τ., Jr.: Recurrent postoperative endophthalmitis. Cornea 9:102, 1990. 26. Tessler, H. H., Owens, S. L., and Deutsch, Τ. Α.: Intracapsular bag diagnosis and treatment of Propionibacterium acnes endophthalmitis. Ophthal mology 96:118, 1989. 27. Smith, M. Α., Sorenson, J. Α., Lowy, F. D., Shakin, J. L., Harrison, W., and Jakobiec, F. Α.: Treat ment of experimental methicillin-resistant Staphylo coccus epidermidis endophthalmitis with intravitreal vancomycin. Ophthalmology 9 3 : 1 3 2 8 , 1986. 28. Pflugfelder, S. C., Hernandez, Ε., Fliesler, S. J., Alvarez, J . , Pflugfelder, Μ. Ε., and Forster, R. Κ.: Intravitreal vancomycin. Retinal toxicity, clearance, and interaction with gentamicin. Arch. Ophthalmol. 105:831, 1987. 29. Davis, J. L., Koidou Tsiligianni, Α., Pflug
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felder, S. C , Miller, D., Flynn, H. W., Jr., and Forster, R. K.: Coagulase negative staphylococcal endoph thalmitis. Increase in antimicrobial resistance. Oph thalmology 9 5 : 1 4 0 4 , 1 9 8 8 . 30. Peyman, G. Α., and Herbst, R.: Bacterial en dophthalmitis. Treatment with intraocular injection of gentamicin and dexamethasone. Arch. Ophthal mol. 9 1 : 4 1 6 , 1 9 7 4 . 3 1 . Graham, R. O., and Peyman, G. Α.: Intravitre al injection of dexamethasone. Treatment of experirnentally induced endophthalmitis. Arch. Ophthal mol. 9 2 : 1 4 9 , 1 9 7 4 . 32. O'Day, D. M., Jones, D. B., Patrinely, J., and Elliott, J. H.: Staphylococcus epidermidis endophthal mitis. Visual outcome following non-invasive thera py. Ophthalmology 89:354, 1 9 8 2 . 33. Pryor, J. G., Apt, L., and Leopold, 1. H.: Intra ocular jserietration of vancomycin. Arch. Ophthal mol. 67:608, 1962. 3 4 . Barza, M., Kane, Α., and Baum, J . : Intraocular penetration of gentamicin after subconjunctival and retrobulbar injection. Am. J. Ophthalmol. 8 5 : 5 4 1 , 1978. 35. Brod, R. D., Flynn, H. W., Jr., Clarkson, J. G., Pflugfelder, S. C , Culbertson, W. W., and Miller, D.: Endogenous Candida endophthalmitis management without intravenous amphotericin B. Ophthalmolo gy 97:666, 1 9 9 0 .
OPHTHALMIC MINIATURE After the war he i n t e n d e d to go b a c k to London, w h e r e o n e could s e e o n e ' s own oculist. For Oliver's oculist had disappeared into the Army at the beginning of the war and he had c h a n c e d upon a very unlovable g e n t l e m a n w h o s e attitude towards his patients was that if his glasses did not suit them, something must be wrong with their eyes and it was entirely their own fault. Angela Thirkell, Marling Hall New York, Carroll & Graf Publishers, Inc., 1 9 9 0 , p. 6 6
