THE EFFECT OF CORTICOSTEROIDS IN THE TREATMENT OF

EXPERIMENTAL BACTERIAL ENDOPHTHALMITIS

JULES L. BAUM, M.D., MICHAEL BARZA, M.D., JOHN LUGAR, A.B.,
AND PHILIP ONIGMAN, A.B.
Boston, Massachusetts

The role of corticosteroids in the treat­ against bacterial invasion during cortico­
ment of bacterial endophthalmitis is still steroid therapy.
controversial. The problems in assessing the We examined the effects of retrobulbar
value of corticosteroids arise from variations administration of dexamethasone or pred-
in the severity of the initial disease, the nisolone, together with pencillin G, on the
promptness with which it is recognized, and outcome of staphylococcal -endophthalmitis
the adequacy of antimicrobial therapy in in rabbits.
terms of drug, dose, and route. The use of
an experimental model helps to control many MATERIALS AND METHODS
of the variables.
We used albino rabbits, 1.5 to 2.0 kg,
Few investigators have examined the ef­
of either sex. An endophthalmitis was pro­
fects of corticosteroid therapy on the out­
duced in both eyes of each rabbit (day 0)
come of experimental bacterial endophthal­
by injecting 0.1 ml of a 10"7 dilution of an
mitis. Maylath and Leopold1 demonstrated
overnight growth of a penicillin G-sensitive
that the addition of subconjunctival cortisone
strain of Staphylococcus aureus into the
to therapy with penicillin G or chlorampheni-
vitreous cavity through the pars plana. The
col improved the results of therapy in staphy-
inoculum was standardized by using a Gil­
lococcal endophthalmitis in rabbits. This was
ford photometer and contained approxi­
true, however, only when the corticosteroid
mately six colony-forming units. Treatment
was given within four hours of the initiation
was initiated 24 hours after infection (day
of infection; a delay of 12 hours yielded a
1) and was administered each day for ten
poor outcome regardless of therapy. More­
consecutive days. The following treatment
over, the results were only assessed four days
groups were studied: in Group A, 50 eyes
after the onset of therapy.
received 100 mg of penicillin G (0.32 ml) ;
Peters and associates2 demonstrated the
in Group B, 74 eyes received 100 mg of
mobilization of leukocytes from blood to a
penicillin G (0.32 ml), and 25 mg of pred-
skin chamber to be slightly inhibited by pred-
nisplone sodium succinate (Meticortelone
nisone and increased by dexamethasone.
soluble) (1 ml); in Group C, 74 eyes re­
They suggested that the difference in the
ceived 100 mg of penicillin G (0.32 ml),
effect of the two corticosteroids might be
and 4 mg of dexamethasone sodium phos­
relevant in situations where granulocyte
phate (Decadron phosphate) (1 ml); and
migration was important in defending
in Group D, 20 eyes received a normal saline
From the Department of Ophthalmology (Dr. control (1 ml).
Baum and Mr. Lugar and Mr. Onigman) and the In addition, four animals with normal
Department of Medicine, Infectious Disease Section
(Dr. Barza), New England Medical Center Hos­ eyes were treated; two received penicillin
pital and Tufts University School of Medicine, Bos­ and dexamethasone and two received penicil­
ton, Massachusetts. This study was Supported in
part by training grant EY00054 and research grant lin and prednisolone as above.
EY00493 from the National Eye Institute, and a Retrobulbar injections were performed
grant from Eli Lilly. through the conjunctiva with a 1-ml dis­
Reprint requests to Jules L. Baum, M.D., Depart­ posable tuberculin syringe and a 25-gauge
ment of Ophthalmology, New England Medical
Center Hospital, 171 Harrison Ave., Boston, MA ^-inch needle. Each drug was injected sepa­
02111. rately. The left and right eyes of each animal
513
514 AMERICAN JOURNAL OF OPHTHALMOLOGY
received the same treatment. In Group A, a
retrobulbar injection of 1 ml of saline was
given in place of the corticosteroid.
All eyes were normal before the experi­
ment. Each was examined daily for the first
ten days as well as on days 30 and 60. Ani­
mals dying before day 5 were not included
in the study results. The experiment was
terminated at day 60. All eyes were dilated
for the first ten days with 1% atropine eye-
drops and the atropine was maintained until
the eyes whitened. Examination consisted
of penlight and slit-lamp observation, and
direct ophthalmoscopy. Changes in eyelids
and all ocular tissues were recorded. We used
the following grades to evaluate changes in
the vitreous cavities and retinas: 0, normal
vitreous and retina or a few cells in the
vitreous; 1, excellent red reflex with hazy
f undus details; 2, good red reflex and f undus
not visible; 3, poor red reflex; and 4, no red
reflex.
All animals were weighed periodically
throughout the experiment. At the conclusion
of the experiment eyes with opaque media
were sectioned horizontally and examined
with a dissecting microscope. We examined
multiple histopathologic sections, stained
with hemotoxylin and eosin.
Statistical analysis of the data was per­
formed by x2 tests of independence.
RESULTS
Initially, there were 113 rabbits but by
day 60, only 59 animals were alive. Most
died during three summer months when epi­
demic diarrhea of unexplained etiology was
prevalent in the animal quarters. The death
rates for the various treatment groups dur­
ing the epidemic diarrhea were Group A
(penicillin G), 6 of 10 ( 6 0 % ) ; Groups B
and C (penicillin G and corticosteroid),
28 of 38 (74%) ; and Group D (saline con­
trol), 2 of 4 (50%). Fifteen other animals
died during the experiment, some with diar­
rhea, others for no apparent cause. In addi­
tion, 21 eyes were excluded from the analysis
for reasons other than death. Corneal ulcers
SEPTEMBER, 1975
developed in 14 eyes precluding visualization
of the posterior segment; all occurred in the
corticosteroid-treated groups. The other
seven eyes were eliminated because they
never exhibited signs of infection; five of
these occurred in the groups receiving corti-
costeroids, one in the group receiving peni­
cillin G alone, and one in the saline control
group.
Figure 1 depicts the distribution of oph-
thalmoscopic findings during the first four
days. To simplify the analysis, we pooled
data for the two corticosteroid-treated
groups, and combined the injuries of grades
2 to 4. During the first 24 hours after infec­
tion, most eyes in each group exhibited only
trivial abnormalities. By 48 hours, however,
severe changes were evident in all groups and
persisted through day 4. Chi-square tests
of independence showed no significant dif­
ferences in lesion distribution among these
three groups at day 1. In contrast, animals
receiving penicillin G exhibited significantly
more severe injuries than those receiving
pencillin G and a corticosteroid on day 2
( P = .005), day 3 ( P = .025), and day 4
( P = .05). Neither group differed signifi­
cantly from the saline-treated animals during
days 1 to 4.
By day 10, eyes comprised grades 0, 1,
and 2 in the following manner: penicillin G
and corticosteroids—19, 32, and 4 1 % ; peni­
cillin G—8, 32, and 60% ; and saline—7,
7, and 86%. While the penicillin G and cor­
ticosteroid-treated group did not differ sig­
nificantly from the penicillin G-treated
animals, both exhibited better results than
the saline controls ( P < .05).
On day 60 (Fig. 2 ) , we noted a significant
difference between eyes treated with penicil­
lin G and corticosteroids and those receiving
only penicillin G. The fundi were not visible
in 61.1% of eyes treated with antibiotic
alone, in contrast to 35.8% of eyes receiving
corticosteroids ( P < .025). There was no
significant difference when the results of
the group receiving prednisolone were com­
pared with the dexamethasone results. Thus,
VOL. 80, NO. 3, PART II BACTERIAL ENDOPHTHALMITIS SIS

PenicillinG a Steriod Penicillin G Saline

(136 EYES) (46 EYES) (18 EYES)

85.3 88.9
80 76.1
60 -
DAYI
40
21.7
20 11.8 II .1
W7A 29 7777\
84.8
80

1 1
61.1
60 532
DAY 2
40

i
<n 33.3
ui 27.9
Ml
U.
O
n
20 - 16.9 10.9 ^M
r-—i
5.6
88.8
* 80 70.6
60
0AY3
40
20
■nmm

1
4.3 4.3 ^ | 5.6 ^ |
88.8
80 69.9
60
DAY 4
40
20
i
5.6
i trim
^B
_^^m
Fig. 1 (Baum and associates). Response of eyes on days 1 to 4. Gear bars indicate
grade 0; striped bars, grade 1; and black bars, grades 2 to 4. See text for explana­
tion of grading.

62% of eyes treated with penicillin G and
prednisolone, and 65% of eyes treated with
penicillin G and dexamethasone had grades
0 or 1 injuries. The four animals with nor-
mal eyes who received antibiotics and cor-
ticosteroids exhibited no signs of ocular
inflammation.
Ophthalmoscopic examination performed
at day 60 on eyes in grades 0 and 1 revealed
small white retinal patches in most eyes,
These patches were usually smaller than 1
disk diameter and one to four patches were
typically seen in each eye. Large, white
patches rarely occupied as much as a quad-
rant of the retina. However, most of the
retina in eyes in grades 0 and 1 appeared
grossly normal. Eyes with opaque media,
when opened and examined with a dissecting
microscope, invariably revealed organized
vitreous humor.
516 AMERICAN JOURNAL OF OPHTHALMOLOGY SEPTEMBER. 197S

Penicillin G Penicillin G 6 Steroid permanent tissue destruction, cicatrization,

and organization.
Therapy was instituted 24 hours after the
14* 43 initiation of infection at a time when most
(38.9%) (64.2%) eyes were still clinically normal. By day 2,
we categorized more than 80% of the eyes
in each group in grades 1 to 4. This persisted
through day 10. The extent of damage did
not differ among the treated groups on day
22 24
10. By day 60, however, there was a sig­
(61.1%) (35.8%)
nificant difference among animals receiving
various forms of therapy.
Penicillin G alone produced good results
—grades 0 and 1—in approximately 40%
Fig. 2 (Baum and associates). Comparison of of eyes, while the addition of corticosteroids
results of treatment with penicillin G or penicillin increased this proportion to 64%. The differ­
G and corticosteroids at day 60. Good indicates
grades 0 and 1; bad, grades 2 to 4; asterisk, eyes. ence was significant by a x2 test (P < .025).
Only 59 of 113 rabbits remained in the
experiment on day 60. Deaths during the ex­
Histopathologic examination of diseased periment were equally distributed among the
eyes in grades 2 to 4 examined after day 60 different treatment and control groups. De­
revealed marked diffuse retinal destruction. velopment of corneal ulcers eliminated 14
Eyes in grades 0 and 1 had infrequent small additional eyes from the study. Only eyes
areas of atrophic retina. These atrophic receiving corticosteroid therapy developed
areas probably correspond to the white ret­ such ulcers, possibly because corticosteroids
inal patches seen ophthalmoscopically at day increase the susceptibility of the cornea to
60. infection.
Peters and associates2 suggested that the
DISCUSSION difference in mobilizing polymorphonuclear
The results indicate the retrobulbar ad­ leukocytes between prednisone and dexa­
ministration of corticosteroids exerts a methasone may be relevant when extravascu-
beneficial effect on the outcome of experi­ lar granulocytes are important in defense
mental bacterial endophthalmitis when used against bacterial invasion. The response to
in combination with effective antibiotic ther­ these two corticosteroids was almost identi­
apy. cal in our study.
Our grading on the severity of the ocular
lesions is admittedly arbitrary, but a counter­ SUMMARY
part exists in human disease. The degree of
resolution of bacterial endophthalmitis in man We evaluated the effects of the addition
is measured in terms of vitreous opacities, of corticosteroids to antibiotic therapy in
retinal damage, and loss of vision. While the treatment of staphylococcal endophthal­
we could not evaluate the last criterion, the mitis in rabbits. Twenty-four hours after
first two were easily assessed. Because pro­ the induction of infection with Staphylo-
longed observation may be necessary to es­ coccus aureus, penicillin G, penicillin G and
tablish the extent of residual damage, final dexamethasone or prednisolone, or saline
grading was performed after 60 days. This was injected retrobulbarly for ten days.
interval is presumably sufficient to distin­ Afterward, there was no ophthalmoscopic
guish temporary infiltrative lesions from difference between the penicillin and cortico-
VOL. 80, NO. 3, PART II BACTERIAL ENDOPHTHALMITIS 517

steroid-treated group and those animals re­
ceiving only penicillin G. At day 60, how­
ever, the fundus was visible in 64% of eyes
treated with penicillin G with corticosteroids
in contrast to 39% of those eyes treated only
with penicillin G ( P < .025). The results
between dexamethasone and prednisolone
use were not significant. Retrobulbar cortico­
steroids in combination with effective anti­
biotic therapy effectively treated experi­
mental bacterial endophthalmitis.
REFERENCES
1. Maylath, F. R., and Leopold, I. H.: Study of
experimental intraocular infection. Am. J. Oph-
thalmol. 40:86, 1955.
2. Peters, W. P., Holland, J. F., Senn, H., and
Banejee, T.: Corticosteroid administration and local­
ized leukocyte mobilization in man. N. Engl. J.
Med. 282:342, 1972.

OPHTHALMIC MINIATURE

And thus ends all that I doubt I shall ever be able to do with my own
eyes in the keeping of my Journal, I being not able to do it any longer,
having done now so long as to undo my eyes almost every time that I
take a pen in my hand; and, therefore, whatever comes of it, I must
forbear: and, therefore, resolve, from this time forward, to have it kept
by my people in long-hand, and must therefore be contented to set down
no more than is fit for them and all the world to know; or, if there be
anything, which cannot be much, now my amours to Deb. are past, and
my eyes hindering me in almost all other pleasures, I must endeavour to
keep a margin in my book open, to add here and there, a note in short­
hand with my own hand.
An4 so I betake myself to that course, which is almost as much as to
see myself go into my grave: for which, and all the discomforts that will
accompany my being blind, the good God prepare me!
Diary of Samuel Pepys
May 31, 1669