Silver Nitrate Ophthalmic Solution and Chemical

Conjunctivitis

Hiroshi Nishida, M.D., F.A.A.P., and Herman M. Risemberg, M.D., F.A.A.P.

From the Division ofNeonatotogy, Baltimore City Hospitals, and the Department ofPedlatrics, Johns Hopkins
University School of Medicine. Baltimore, Maryland

ABSTRACT. The current status of nursery routines of chloride which may be more irritating. Still
prophylaxis against ophthalmia neonatorum were surveyed
others9 recommend no rinsing at all.
by mail questionnaire to 100 leading maternity hospitaLs.
More than 20% of the respondents were not using silver
As chemical conjunctivitis is the main reason
nitrate, mainly because of chemical conjunctivitis. The for withholding this valuable agent from routine
clinical significance and incidence of chemical conjunctivitis use, these studies were undertaken to evaluate the
were studied in 1,000 newborns whose eyes were handled clinical significance of chemical conjunctivitis
differently. Rinsing after instillation of silver nitrate does not
and to determine the most efficient method of the
reduce the conjunctival irritation. Although 90% of the
infants had conjunctivitis in the first six hours of life, the
application of silver nitrate.
majority cleared within 24 hours. Chemical conjunctivitis
did not increase secondary infection, did it mask neither
METHOD
bacterial infection. Silver nitrate in vitro against
is effective Study 1: Survey of the Current Status of
Neisseria gonorrhoeae and Staphylococcus aureus in a
Nursenj Routines of Prophylaxis of Ophthalmia
concentration of 0.1% and against Escherichia coil in a
concentration of 0.01%. PediatriCs, 56:368-373, 1975, Neonatorum-In February 1973 a mail question-
OPHTHALMIA NEONATORUM PROPHYLAXIS, SILVER NiTRATE, naire was sent to 100 major maternity hospitals in
CHEMICAL CONJUNCTIViTIS. the United States.
Question: (1) Are you using silver nitrate oph-
thalmic solution?
(2) If yes, do you rinse after instilla-
tion?
(3) How often do you see chemical
conjunctivitis?
(4) What procedure do you follow
In spite of nearly 100 years of experience with
when an infant has eye discharge in
silver nitrate prophylaxis of ophthalmia neonato-
the first 24 hours of life?
rum, dating back to Dr. Cred#{233}’shistorical work in
Study 2: Incidence and Clinical Significance of
December 1879 at Leipzig Lying-In Hospital,1’2
Chemical Conjunctivitis of Silver Nitrate-From
there are still many controversial aspects to its
use.
Many publications, including current leading
textbooks,36 state that rinsing eyes with isotonic
saline after instillation reduces the incidence of
chemical conjunctivitis by neutralizing silver
ions, which are thought to cause conjunctival (Received May 17; revision accepted for publication
December 17, 1974.)
irritation. On the contrary, others7’8 (including
ADDRESS FOR REPRINTS: (H.N.) Pediatrics, Kitasato
the manufacturer’s package inserts), state that University, School of Medicine, 1-Asamizodai, Sagamthara,
rinsing with isotonic saline precipitates silver Kanagawaken, Japan.

368 PEDIATRICS Vol. from

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January 1973 to February 1974, 1,000 newborns TABLE I
at Baltimore city hospitals were studied. All Q UESTIONAIRE RESULTS OF CURRENT STATUS OF

infants were admitted within 10 to 20 minutes PROPHYLAXIS AGAINST OPHTHALMIA NEONATORUM

after birth to the transitional nursery where eye Hospitals

care was given by one of several specially ---

assigned nurses as follows: Any blood and mucus Nursery Procedure No. %
around the eye was cleaned with a cotton ball Nature of agent used

moistened with tap water. Two drops of 1% silver Silver nitrate 56 78.9
Topically applied antiobiotics#{176} 15 21.1
nitrate ophthalmic solution sealed in a wax
ampoule were put into the lower cul-du-sac at the Procedure after silver nitrate instillation
Norinsingatall 7 12.5
angle of the nasal bridge and eyes. Eyelids were
Rinsing with isotonic saline 22 39.3
forced open with two fingers to allow silver Rinsing with sterile water 27 48.2
nitrate to run across the whole conjunctival sac.
Management of eye discharge in
Excess silver nitrate around the eye was wiped off first 24 hours
with a wet sponge to prevent darkening of the No bacteriologic study 37 52.5
skin. Smear and/or culture (treatment
In the first 100 infants, one eye was rinsed with dependent on result) 34 47.9
isotonic saline after instillation of silver nitrate, #{176}Neosporin, 6; tetracycline, 3; Achromycin, 2; ery-
while the other was not rinsed at all. The next 900 thromycin, 2; chlortetracycline, 1; and penicillin, 1.
infants were divided into three equal groups. One
group had no rinsing of either eye and the other
RESULTS
groups were rinsed either with isotonic saline or
Study 1
distilled water. All infants were examined by the
authors at least twice each day until discharge, Out of the 100 hospitals, 71 responded to the
usually after three days. If eye discharge was questionnaire. The results are summarized in
noticed in the first 24 hours of life, the eyes were Table I. More than 20% of the hospitals were not
irrigated with warm isotonic saline and observed. using silver nitrate and three hospitals using silver
When eye discharge persisted for over 24 hours, nitrate were considering a change to topically
eye cultures were taken with a dry cotton swab applied antibiotics because of chemical conjunc-
from the conjunctiva, not touching the outer skin. tivitis. On the other hand, three hospitals
The specimen was immediately plated on 5% previously using topically applied antibiotics had
human blood agar, desoxy agar, and chocolate recently switched to silver nitrate because of
agar and incubated at 36 to 37 C for 24 to 48 increasing failure of prophylaxis against gono-
hours. (Chocolate plates were put in a CO2 coccal ophthalmia, encountering resistant organ-
chamber). If bacterial growth was observed, the isms, and an increasing incidence of late-onset
material was sent to the bacteriology laboratory conjunctivitis.
for identification. Nearly 90% of the hosptials using silver nitrate
Study 3: Antibacterial Effect of Silver Nitrate: were rinsing after its instillation with the objec-
Part 1-A 1% silver nitrate ophthalmic solution live of lessening the chemical irritation. However,
(Parke-Davis Co.) was diluted from 1:1 to 1:200 one hospital recently stopped rinsing because the
with isotonic saline or distilled water. Pure excessive rinsing was thought to be one of the
cultures of NeLiseria gonorrhoeae, Staphylococcus causes of prophylactic failure.
aureus, and Escherichia coli obtained from the Chemical conjunctivitis was seen more com-
bacteriology laboratory were plated on 5% monly with silver nitrate prophylaxis (10% to
human blood agar, desoxy agar, and chocolate 100%) than with topically applied antibiotics (less
agar. Then two drops of diluted silver nitrate than 10%).
solution were added to each plate and incubated Although discharge from the eye in the first 24
as before. hours of life is mostly due to chemical conjunctiv-
Part 2-N. gonorrhoeae, S. aureus, and E. coli itis, nearly one half of the hospitals were doing
were plated as before and then 0.1 ml of 1% silver bacteriological work-ups for this and 10% of them
nitrate ophthalmic solution was dropped on each even initiated treatment with topically applied
culture plate. At 15 seconds and at 120 seconds antibiotics.
after application, silver nitrate was rinsed off with
Study 2
5 to 60 times its volume of isotonic saline or
distilled water. After this the plates were incu- The clinical picture was divided into the
bated as before. following three groups: (1) Within normal limits

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ARTICLES 369
 SILVER NITRATE OPHTHALMIC SOLUTION 6
CHEMICAL CONJUNCTIVITIS

INCIDENCE OF
CONJUNCTIVITIS
I 0/
‘ 10

I00

90

80

70

60

50

40

30

20

10

abc abc abc abc abc abc abc abc abc abc
AGE 0 .-.‘ 3 6 -‘ I2 ‘e-l 8 *- 24 -‘ 30 **36E-’42*-’48 *-72
(HOURS)
( a: NO RINSING, b’RINSEDWITHDISTILLEDWATER,
C: RINSED WITH NORMAL SALINE
C OBVIOUS CONJUNCTIVITIS, ‘ 1 MILD CONJUNCTIVITIS

FIG. 1. Silver nitrate ophthalmic solution and chemical conjunctivitis.

(mild redness and/or mild swelling only); (2) mild (31%) showed S. albus, and 4 (10%) showed other
conjunctivitis (moderate-to-severe redness and/or S. aureus (coagulase-negative), 6 -Streptococcus,
swelling without discharge, mild discharge with! Hemophilus influenzae type b, and Aspergillus.
without mild-to-moderate redness and/or swell- Four additional infants, whose eyes were initially
ing); (3) obvious conjunctivitis (moderate-to- normal, developed conjunctivitis between the
severe discharge with/without redness and/or fifth and tenth days while in the nursery. All
swelling, mild discharge with severe redness and! cultures and smears were negative for pathogenic
or swelling). bacteria. They were diagnosed as having inclusion
Of the 100 infants who had each eye handled conjunctivitis and successfully treated with topi-
differently, 24 had more conjunctivitis in the cally applied sulfonamides. Only one infant out of
rinsed eye, 13 had more in the unnnsed eye, and 1,000 studied infants had bacterial conjunctivitis
63 had the same degree of conjunctivitis. (H. influenzae) clinically severe enough to require
Among the three groups of infants who had antibiotic treatment.
both eyes handled differently, there was also no
Study 3
definite difference in the eye findings. Between 3
to 6 hours of age, nearly 90% of infants in all three As low a concentration of silver nitrate as 0.1%
groups had conjunctivitis, but after 24 hours only inhibited growth of N. gonorrhoeae and S. aureus
7% had obvious conjunctivitis and after 48 hours and 0.01% was effective against E. coli. Silver
even mild conjunctivitis was rarely observed (Fig. nitrate was less effective when diluted with
1). isotonic saline than with distilled water.
Eye cultures were taken from 41 infants who The time interval between instillation and
had obvious eye discharge after 24 hours of life. rinsing did not alter the effectiveness of silver
Twenty-four (59%) of these were negative, 13 nitrate. Although rinsing of the newborn’s eyes

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370 CHEMICAL CONJUNCTIVITIS
and of culture plates are not the same, it appears TABLE II
that excessive rinsing, especially with isotonic ANTIBACTERIAL EFFECT OF SILVER NITRATE

saline, may reduce the effectiveness of silver

Dilution of Silver Nitrate With Distilled Water or
nitrate (Table II).
Isotonic Saline
DISCUSSION Culture Resnlts
N. gonorrheae S. aureus E. coli
The recent almost pandemic increase of gono- Dilution ___f_____

coccal infection, especially among young women (1% SN:DW/IS) DW IS DW IS DW IS

of child-bearing age,’#{176}3 has reemphasized the 1:8 - - - - - -

importance of prophylaxis of gonococcal ophthal- 1:10 - - - ± - -

mia neonatorum.’5 1:12 ± ± - ± - -

1:14 ± ± + - -
Although silver nitrate has been the most
1:16 + + +
extensively studied and the most widely used 1:18 + + + +
agent for this purpose, for various reasons it has 1:40 + + + +
not been accepted universally. 1:60 + + + + - +
The safety of silver nitrate has aroused concern 1:100 + + + + - +
1:200 + + + + + +
because blindness caused by accidental instilla-
tion of high concentrations has been reported.’617 Rinsing After Application of 1% Silver
Nitrate (0.1 ml)
But, since silver nitrate sealed in a wax ampoule
N.
has been used to prevent the solution’s concentra-
. gonorrheae S. aureus E. coli
tion from becoming higher following evaporation Amount Time After
of water,’8 eye damage caused by prophylactic (ml) Application DW IS DW IS DW IS

use has been almost negligible.’92’ The quality of 0.Sml l5sec

wax, which tends to convert silver nitrate into l2Osec
1.Oml l5sec
nitric acid, has also been improved22 and the
l2Osec
current solution retains its concentration and pH 2.OmI l5sec - ± - - - -

for 30 months at room temperature as long as the l2Osec - ± - - - -

ampoules are intact (Parke, Davis & Co., personal 4.Oml l5sec - ± - ± - -

communication). l2Osec - ± - ± - -

6.Oml l5sec - + - ± - -
Its effectiveness has also been seriously ques-
l2Osec ± + - ± - -

tioned,’7’2326 but discontinuation of the prophy-

#{176}No
growth, -; partial growth, ± ; growth, +.
lactic use of silver nitrate resulted in a significant
rise of gonococcal ophthalmia neonatorum in
high-risk populations, clearly indicating its
prophylactic effectiveness.273#{176} effective and safe for the prophylaxis of
Many topically applied antibiotics (penicil- ophthalmia neonatorum, more than 20% of the
lin,3133 erythromycin,34 bacitracin,35 tetracy- hospitals are still reluctant to use it, mainly
chine,36 oxytetracycline,37 aureomycin38), sulface- because of the high incidence of chemical
tamide,28 and parenteral penicillin in the conjunctivitis associated with its use.
newborn2933; (and the latter in the mother32’39) To minimize chemical irritation, 1% silver
have been used for the prophylaxis of ophthalmia nitrate has been used instead of the 2% advocated
neonatorum. Comparative studies with silver by Cred#{233}’s original method. But there are no data
nitrate have shown that all of these antibiotics are showing that silver nitrate must be 1% in order to
as effective as silver nitrate, but with no super- have an adequate effect with the least irritation.
iority except in the lower incidence of chemical Study 3 showed that a concentration of silver
conjunctivitis. Moreover, several disadvantages of nitrate as low as 0.1% inhibits the growth of N.
topically applied antibiotics have been reported gonorrhoeae, S. aureus, and E. coli in vitro. Two
as follows: (1) sensitization of infants40; (2) ineffec- drops of silver nitrate (about 0.08 to 0.1 ml) is not
tiveness against many gram-negative organisms greatly diluted by tears after instillation because
which are also causative of ophthalmia neonato- the newborn has limited tear production. (The
rum443; (3) selection of resistant organisms which authors could collect a total of no more than 0.1
may induce a nursery epidemic44’45; (4) they may ml of tears from ten vigorously crying infants on
require multiple instillations since most are bacte- several occasions.) Therefore, the concentration
riostatic31; and (5) more frequent incidence of of silver nitrate ophthalmic solution could be less
late-onset conjunctivitis.3’ than 1% and still have the same prophylactic
In spite of the evidence that silver nitrate is effect.

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ARTICLES 371
 Rinsing the eyes after instillation of silver junctivitis with silver nitrate is seen in as many as
nitrate to reduce chemical irritation has been 90% of infants in the first 24 hours of life, obvious
widely practiced. However, there was no differ- conjunctivitis with eye discharge is rare after this
ence in the incidence of chemical conjunctivitis period. Furthermore, chemical conjunctivitis nei-
among groups of infants whose eyes were not ther masks nor increases the likeithood of bacte-
rinsed at all, were rinsed with distilled water, or rial infection, if properly handled. Bacteriological
rinsed with isotonic saline. Rinsing either imme- work-up of eye discharge in the first 24 hours of
diately or two minutes after instillation did not life is not necessary, unless prenatal infection is
change the antibacterial effect in vitro, although strongly suspected.
publications recommend waiting for 156 to 120 There is no difference in the incidence of
seconds,4 before rinsing. chemical conjunctivitis when rinsing is done with
Silver ions kill the bacteria by binding with isotonic saline or distilled water, or even without
their surface protein and at the same time irritate rinsing at all after instillation of silver nitrate
the conjunctiva by reacting with the protein of its ophthalmic solution. Although the time interval
epithelial cells. They also combine with chloride between instillation and rinsing does not alter the
to precipitate silver chloride. (The tears of effectiveness of silver nitrate, excessive rinsing
newborn infants contain 145 to 155 mEq/liter of may reduce its effect. Therefore, it would be
chloride [Nishida and Risemberg, unpublished advisable not to rinse after instillation of silver
data].) These reactions are almost instantaneous nitrate.
and therefore rinsing even soon after instillation Silver nitrate maintains its antibacterial effect
alters neither its effectiveness nor the degree of against N. gonorrhoeae and S. aureus in concen-
irritation. trations of 0.1% and against E. coli in a concen-
Regardless of the technique, chemical conjunc- tration of 0.01%.
tivitis is much more common with silver nitrate
prophylaxis than with topically applied antibiot- REFERENCES
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ARTICLES 373
 Silver Nitrate Ophthalmic Solution and Chemical Conjunctivitis
Hiroshi Nishida and Herman M. Risemberg
Pediatrics 1975;56;368

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 Silver Nitrate Ophthalmic Solution and Chemical Conjunctivitis
Hiroshi Nishida and Herman M. Risemberg
Pediatrics 1975;56;368

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