REVIEW
Use of Topical Steroids in Conjunctivitis: A Review of the
Evidence
Edward J. Holland, MD,* Murray Fingeret, OD,† and Francis S. Mah, MD‡
Downloaded from https://journals.lww.com/corneajrnl by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3StWKv21BgeybUtZ48IxSMDNrCJ7coa15Dh9s2A1hikkvKGKqgjq8eA== on 04/13/2020
Purpose: Conjunctivitis, or inflammation of the conjunctiva, is
a common condition that can be caused by infectious (eg, bacterial or
viral infections) and noninfectious (eg, allergy) etiologies. Treatment
involves diagnosis of the underlying cause and use of appropriate
therapies. A broad-spectrum therapy that can address multiple
etiologies, and also the accompanying inflammation, would be very
useful. In this review, we discuss the usefulness of topical
ophthalmic corticosteroids and ophthalmic formulations that com-
bine corticosteroids with anti-infectives/antibiotics for treating acute
infectious conjunctivitis.
Methods: A review of the published literature and relevant
treatment guidelines.
Results: Topical corticosteroids are useful in treating ocular
inflammation, but most treatment guidelines recommend steroid
use generally in severe cases of conjunctivitis. This is partly due to
risks associated with steroid use. These risks include potential for
prolonging adenoviral infections and potentiating/worsening herpes
simplex virus infections, increased intraocular pressure, glaucoma,
and cataracts. Most of these perceived risks are not, however,
supported by high-quality clinical data. They are also associated with
Received for publication October 23, 2018; revision received March 13,
2019; accepted March 15, 2019. Published online ahead of print May 3,
2019.
From the *Cincinnati Eye Institute, Edgewood, KY; †Department of Veterans
Affairs, New York Harbor Health Care System, Brooklyn, NY; and
‡Departments of Cornea and External Diseases, Scripps Clinic Torrey
Pines, La Jolla, CA.
E. J. Holland has been a consultant for Alcon, Allergan, Bausch + Lomb,
Kala, Mati, Omeros, PRN, RPS, Senju, Shire (a Takeda company),
TearLab, and TearScience and has received research support from Alcon,
Allergan, Mati, Omeros, PRN, and Senju. M. Fingeret has been
a consultant for Aerie, Allergan, Bausch + Lomb, Novartis, and Shire
(a Takeda company). F. S. Mah has been a consultant for Abbott Medical
Optics, Inc., Alcon, Aerie, Allergan, Avedro, Avellino, Bausch + Lomb,
CoDa, EyePoint, inVirsa, iView, Kala, Mallinckrodt, NovaBay, Novartis,
Ocular Science, Ocular Therapeutix, Okogen, Omeros, PolyActiva,
RxSight, Shire (a Takeda company), Slack Publishing, Sun, Sydnexis,
and TearLab; has received research support from Abbott Medical Optics,
Inc., Ocular Therapeutix, and Senju; is an investor in Ocular Science,
Okogen, and Sydnexis; holds a patent/royalty in Slack Publishing; and
has received lecture fees from Abbott Medical Optics, Inc., Alcon,
Bausch + Lomb, Novartis, Shire (a Takeda company), and Sun.
Correspondence: Edward J. Holland, MD, Cincinnati Eye Institute, 580 S
Loop Rd Ste 200, Edgewood, KY 41017 (e-mail: eholland@holprovision.
com).
Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc.
This is an open-access article distributed under the terms of the Creative
Commons Attribution-Non Commercial-No Derivatives License 4.0
(CCBY-NC-ND), where it is permissible to download and share the
work provided it is properly cited. The work cannot be changed in any
way or used commercially without permission from the journal.
1062 | www.corneajrnl.com
long-term steroid uses that are dissimilar to applications for
infectious conjunctivitis. Clinical data show that ophthalmic
formulations that combine corticosteroids with broad-spectrum
anti-infectives could be effective and well tolerated when used for
short-term treatment (#2 weeks).
Conclusions: Corticosteroids, in combination with anti-infectives,
could be a promising treatment option for acute conjunctivitis
subject to development of further evidence on their effectiveness
and safety in conjunctivitis treatment.
Key Words: conjunctivitis, dexamethasone, inflammation,
povidone–iodine, topical corticosteroids
(Cornea 2019;38:1062–1067)
C onjunctivitis, or conjunctival inflammation, is a common
eye condition that accounts for ;1% of all primary care
visits in the United States.1,2 It carries a significant burden of
symptoms and imposes a considerable economic burden.3,4
Conjunctivitis can be infectious or noninfectious5:
1. Infectious: viral or bacterial;
2. Noninfectious: allergic, mechanical, toxic, immune
mediated, and neoplastic.
Adenoviral conjunctivitis is a major cause of acute
infectious conjunctivitis cases among adults.5 Infections are
generally self-limited and do not require antibiotic treatment.
There is no approved treatment, but topical corticosteroids may
be helpful in alleviating symptoms of adenoviral conjunctivitis
and may prevent scarring in severe cases. It should be noted,
however, that treatment guidelines suggest caution in the use of
corticosteroids because they can potentially prolong infection.5
Bacterial conjunctivitis is responsible for the majority of cases
among children.6 Mild bacterial conjunctivitis typically re-
solves spontaneously, but topical antibacterial therapy is
generally preferred as it is associated with a shorter infectious
period and earlier resolution of clinical signs and symptoms.5
Allergic conjunctivitis is typically treated with antihistamines
and mast cell stabilizers, but if the symptoms persist, therapy
may be supplemented with topical corticosteroids.5
Corticosteroids are extensively used to treat ocular
inflammatory conditions and are among the most prescribed
class of drugs in ophthalmology. In this article, we will review
evidence for and against the use of corticosteroids in patients
with conjunctivitis and discuss the potential for ophthalmic
formulations of corticosteroid and anti-infective combinations
to treat acute infectious conjunctivitis in adults and children.
Cornea  Volume 38, Number 8, August 2019
Cornea  Volume 38, Number 8, August 2019
CHALLENGES OF CONJUNCTIVITIS DIAGNOSIS
AND MANAGEMENT
Early detection and use of appropriate therapies is the
key to expeditious resolution of the disease and helps
minimize potential harmful effects or transmission of
untreated conjunctivitis. Accurate diagnosis of conjunctivitis
and identification of the etiology (eg, bacterial, viral, or
allergic) require focused ocular examination and, in some
cases, laboratory investigation. According to the American
Academy of Ophthalmology guidelines, ocular examination
should include comprehensive slit-lamp biomicroscopy eval-
uation.5 However, most patients with conjunctivitis are seen
at primary care and urgent care clinics, where ocular
examination does not include a slit lamp.7 Distinguishing
between the different forms of conjunctivitis (bacterial, viral,
or allergic) can therefore be challenging. Primary or urgent
care physicians may prescribe antibiotics without making an
informed differential diagnosis. Misdiagnosis of viral etiolo-
gies as bacterial conjunctivitis and the resulting inappropriate
use of antibiotics can occur in as much as 50% of cases.8
It is important to note that irrespective of the underlying
etiology, conjunctivitis is characterized by inflammation of
the conjunctiva.5 Inflammation is caused by an ocular
immune response against the underlying etiology (eg, bacte-
rial, viral, allergic, etc). Treatment of conjunctivitis should
therefore recognize this inflammation and, in severe cases of
conjunctivitis, aim to manage this inflammation. Cortico-
steroids are well known to be effective and fast-acting anti-
inflammatory agents that ameliorate symptoms of pain and
swelling.9 However, the use of a corticosteroid alone can
reactivate and potentiate herpes simplex virus (HSV) infec-
tion,5 which makes some primary urgent care physicians
reluctant to prescribe it. A combination of a corticosteroid
(eg, dexamethasone) and an antiseptic (eg, povidone–iodine
[PVP-I]) that has the potential to treat both inflammatory and
infectious components of conjunctivitis might be very useful.
Several combinations of dexamethasone and PVP-I are
currently under development.
TREATMENT GUIDELINES AND PUBLISHED LIT-
ERATURE ON TOPICAL CORTICOSTEROID USE
The American Academy of Ophthalmology guidelines
on treatment of conjunctivitis list corticosteroids as a treatment
option, but suggest caution in their use5:
1. Indiscriminate use should be avoided due to the
potential for prolonging adenoviral infections and
worsening HSV infections;
2. Patients who are prescribed corticosteroids for a long
term should be periodically monitored for increases in
intraocular pressure (IOP) and evaluated for glaucoma
and cataract formation;
3. Steroids should be avoided if HSV conjunctivitis is
suspected due to their ability to potentiate
the infection.
The United Kingdom College of Optometrists lists cortico-
steroids as a predisposing factor for bacterial conjunctivitis.10
Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc.
Topical Steroids in Conjunctivitis: Review
A review of literature on adverse outcomes associated
with the short- and long-term use of topical corticosteroids
shows that the majority of adverse outcomes are related to an
increase in IOP. However, in most cases, the observed
increase in IOP was not related to the short-term use of
corticosteroids for conjunctivitis. Increases in IOP tend to be
associated with a longer duration of treatment—typically
more than 2 weeks.11–13 A #2-weeks treatment course of
corticosteroids is unlikely to affect IOP. Other common
adverse outcomes of corticosteroid therapy include risk of
cataract formation and glaucoma,14,15 which are also associ-
ated with long-term steroid use.14,15
When used alone, topical steroid use is associated with
prolonged periods of viral shedding and infection.16–18 The
anti-inflammatory and immunosuppressive effect of cortico-
steroids is thought to inhibit normal viral clearance by the
immune system. However, when used in combination with
anti-infectives, corticosteroids such as dexamethasone have
been shown to be well tolerated19–22 and efficacious in
treating inflammatory conditions associated with viral and
bacterial infections.18,21,22
Topical ophthalmic steroids are contraindicated in
epithelial herpes simplex keratitis.14,23 However, the use of
topical steroids is also associated with the perceived risk of
reactivating latent HSV in the absence of active epithelial
disease. HSV is a less frequent cause of acute conjunctivitis
of infectious etiology and may be indistinguishable from
adenoviral conjunctivitis without further diagnostic test-
ing.24,25 In settings where such testing is not feasible,
physicians could be reluctant to prescribe steroids. However,
the risk of HSV reactivation by topical steroids in the absence
of active epithelial disease is not entirely supported by the
published literature. Experimental studies and limited clinical
evidence have shown no increased production of HSV after
steroid administration.24,26–28 In addition, a randomized
placebo-controlled study of dexamethasone 0.1% for the
treatment of acute follicular (presumed viral) conjunctivitis
showed significantly improved response with no harm or
serious complications and no signs of HSV.29 It should be
noted that although data from small clinical trials indicate that
steroids may be well tolerated, larger randomized clinical
trials are needed to further confirm safety.
Several topical corticosteroids are commonly pre-
scribed for ophthalmic conditions. Table 1 lists ophthalmic
steroids used to treat ocular inflammation. Several different
ophthalmic formulations that combine antimicrobials/anti-
infectives and corticosteroids are also available for treatment
of eye infections and ocular inflammation (Table 2). These
include loteprednol etabonate and prednisolone formula-
tions, as well as various dexamethasone formulations that
are discussed in the next section. Loteprednol etabonate
0.5%/tobramycin 0.3% (Zylet; Bausch + Lomb, Bridge-
water, NJ)30 has been in clinical use since 2004 and is
approved for use in steroid-responsive inflammatory ocular
conditions, for which a corticosteroid is indicated and where
superficial bacterial ocular infection or a risk of bacterial
ocular infection exists. Prednisolone 0.2%/sulfacetamide
10% (Blephamide; Allergan, Irvine, CA)31 is a combination
of a corticosteroid and an anti-infective that has been in
www.corneajrnl.com | 1063
Holland et al Cornea  Volume 38, Number 8, August 2019

TABLE 1. Corticosteroids Typically Used for Ocular Inflammation

Corticosteroid Trade Name
Dexamethasone Maxidex (Alcon Laboratories, Inc., Fort Worth, TX)
Prednisolone Pred Forte (Allergan USA, Inc., Madison, NJ), Pred
Mild (Allergan USA, Inc., Madison, NJ), and others
Fluorometholone Efflumidex (Allergan Pharmaceuticals Ireland, Mayo,
Ireland), Flucon (Novartis Pharmaceuticals Australia,
Macquarie Park, New South Wales, Australia), FML
(Allergan USA, Inc., Madison, NJ), Flarex (Eyevance
Pharmaceuticals, Fort Worth, TX), FML Forte
(Allergan USA, Inc., Madison, NJ), and others
Loteprednol etabonate Alrex (Bausch + Lomb, Bridgewater, NJ)
Lotemax (Bausch + Lomb, Bridgewater, NJ)
Rimexolone Vexol (Alcon Laboratories, Inc., Fort Worth, TX)
Difluprednate Durezol (Alcon Laboratories, Inc., Fort Worth, TX)
Indication
Steroid-responsive ocular inflammation of the anterior
eye
Steroid-responsive ocular inflammation of the anterior
eye
Steroid-responsive ocular inflammation of the anterior
eye
Allergic conjunctivitis
Postoperative inflammation and pain after ocular surgery
Postoperative inflammation after ocular surgery and
anterior uveitis
Inflammation and pain associated with ocular surgery

clinical use since the 1980s. It is typically used to treat eye used for a short course. Most warnings and contraindica-
infections and ocular inflammation. tions, particularly in product monographs, typically relate to
long-term use. For example, the package insert of an
ophthalmic dexamethasone product warns that the pro-
DEXAMETHASONE FORMULATIONS longed use of topical dexamethasone can lead to ocular
FOR CONJUNCTIVITIS hypertension and/or glaucoma, posterior subcapsular cata-
Topical ophthalmic dexamethasone is routinely used ract formation, and suppression of the immune response,
to treat ocular inflammation. It is the most widely used with the consequent risk of secondary ocular infections.14
corticosteroid in ophthalmology and has been studied Published data have demonstrated that when used in
extensively.22 Published adverse event data21,22,32–34 pro- combination with antibiotics or antiseptics, for #7 days,
vide evidence on the topical use of dexamethasone when dexamethasone was well tolerated,21,22 with no significant
increase in IOP33 and with no observed trend toward
increase in viral shedding or viral titers.32,34 Moreover,
TABLE 2. Ophthalmic Anti-infective/Corticosteroid
when preservative-free dexamethasone 0.01% was used and
Combination Products in Clinical Use or Under Investigation follow-up conducted 4 to 60 months later, none of the
patients had IOP elevation of .5 mm Hg above baseline,
Corticosteroid Combination
Product Indication/Status suggesting that the short-term use of low-dose dexametha-
sone may be well tolerated.35
Tobramycin 0.3%, dexamethasone Prescribed for steroid-responsive
0.1% (TobraDex; Alcon inflammatory ocular conditions for
Various formulations of dexamethasone in combination
Laboratories, Inc., Fort Worth, which a corticosteroid is indicated with antibiotics or anti-infectives are in clinical use and/or
TX)36 and where superficial bacterial under clinical investigation (Table 2). Examples include
ocular infection or a risk of combinations of tobramycin and dexamethasone, and differ-
bacterial ocular infection exists ent combinations of PVP-I and dexamethasone.
Tobramycin 0.3%, loteprednol Tobramycin 0.3% (antibiotic) and dexamethasone 0.1%
etabonate 0.5% (Zylet)30
ophthalmic suspension (TobraDex) is indicated for steroid-
Netilmicin 0.3%/dexamethasone
0.1% (Netildex; Knight responsive inflammatory ocular conditions for which a corti-
Therapeutics, Inc., Montreal, costeroid is indicated and where superficial bacterial ocular
Quebec, Canada)22 infection or a risk of bacterial ocular infection exists.36
Neomycin, polymyxin B sulfates, PVP-I is a disinfectant and antiseptic agent with broad-
dexamethasone (Maxitrol; Alcon spectrum antimicrobial activity against various viruses,
Laboratories, Inc., Fort Worth,
TX)23
bacteria, and fungi. It is routinely used in ophthalmic
Sulfacetamide, prednisolone
surgery.37 Advantages of PVP-I include low documented
(Blephamide)31 antibiotic resistance and effect on multiple pathogens
PVP-I 0.4%, dexamethasone 0.1% Tested for acute viral conjunctivitis33 in vitro.38 The combination of PVP-I and dexamethasone
(FST-100) has the potential to treat both viral and bacterial conjunctivitis
PVP-I 0.6%, dexamethasone 0.1% Ongoing phase 3 trials for treatment and also to address the inflammatory component of infectious
(SHP640) of bacterial and adenoviral conjunctivitis. Various combinations of PVP-I/dexamethasone
conjunctivitis41–43 have been studied or are currently under investigation for the
PVP-I 1.0%, dexamethasone 0.1% Tested for treatment of adenoviral treatment of inflammatory conditions associated with ocular
keratoconjunctivitis18
infections.

1064 | www.corneajrnl.com Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc.
Cornea  Volume 38, Number 8, August 2019
1. PVP-I 0.4%/dexamethasone 0.1% suspension: Preclin-
ical data in rabbit eyes showed that it reduced
symptoms of adenovirus infection and was effective
in reducing viral titers and the duration of viral
shedding.39 In vitro studies showed that it was effective
in killing all bacterial, Candida, and Fusarium isolates
within 60 seconds of exposure.40 In an open-label,
single-arm, descriptive phase 2 study in presumed viral
conjunctivitis, 8 of 9 eyes achieved clinical resolution
by days 3/4, and no adverse events or increased
duration of viral shedding were observed.32 In a ran-
domized, masked, controlled study in acute viral
conjunctivitis, the formulation shortened the disease
duration, and no prolonged viral shedding or differ-
ences in IOP versus artificial tears were observed.33
2. PVP-I 1.0%/dexamethasone 0.1%: In a randomized con-
trolled trial, it reduced symptoms and expedited recovery
among patients with adenoviral keratoconjunctivitis.18
3. PVP-I 0.6%/dexamethasone 0.1% (SHP640): In a ran-
domized, placebo-controlled, phase 2 trial, SHP640
improved clinical resolution and adenoviral eradication
in patients with acute adenoviral conjunctivitis.34
Ongoing phase 3, randomized, double-masked, con-
trolled studies will further evaluate its efficacy and
safety in adenoviral conjunctivitis (ClinicalTrials.gov
identifiers: NCT0299855441 and NCT0299854142) and
bacterial conjunctivitis (NCT03004924).43
Ophthalmic formulations of PVP-I/dexamethasone are
promising treatment options for acute conjunctivitis and are
currently under investigation. By addressing both infectious
and inflammatory components of infectious conjunctivitis,
they would simplify diagnosis and treatment. Moreover, they
have the potential to treat adenoviral conjunctivitis that does
not currently have any approved treatment options.
CORTICOSTEROIDS FOR CONJUNCTIVITIS IN
THE PEDIATRIC POPULATION
Published data do not show a clear difference in
corticosteroid response between the pediatric and adult
populations, but pediatricians have been trained to avoid
ocular steroid use because of the risk of potentiation of latent
HSV infection and a lack of slit lamps to detect HSV keratitis,
which is a contraindication for topical steroid use. Neverthe-
less, several ophthalmic corticosteroids have been approved
for treatment in pediatric populations. For example, FML
(fluorometholone 0.1%)44 and TobraDex36 are approved for
use in children aged .2 years.
A 1980 Israeli study investigated IOP response in
children (aged 4–19 years) treated with dexamethasone for
6 weeks. They found that the steroid-associated increase in
IOP among children was similar to that in adults.45 A 1991
Japanese study reported that dexamethasone 0.1% temporar-
ily raised IOP among children aged ,10 years after 1 to 2
weeks of treatment, but not among children aged $10
years.46 A 1997 study among Chinese children aged ,10
years reported that topical dexamethasone increased IOP
more frequently, more severely, and more rapidly among
Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc.
Topical Steroids in Conjunctivitis: Review
children compared with what was previously reported for
adults.47 Most children (89%) in this study achieved peak IOP
within 8 days after dexamethasone treatment.
Later studies showed that this ocular hypertensive
response to dexamethasone may be dose and age dependent
in children.48–50 Ng et al48 reported that among children aged
2 to 10 years, peak IOP and net increase in IOP were higher
among those receiving topical dexamethasone 4 times daily
versus twice daily. Lam et al49 also reported a greater net
increase in IOP with topical dexamethasone doses of 4 times
daily versus twice daily among children aged 3 to 10 years.
Patients in both studies were treated with dexamethasone for
4 weeks. Lee et al50 examined age dependence of IOP
response to topical dexamethasone among children aged 3 to
13 years. They reported that peak IOP and net increase in IOP
were significantly higher in children aged #5 years compared
with those aged .5 years.
It should be noted that accurately identifying the type of
conjunctivitis and proper follow-up present greater challenges
in the pediatric population compared with the adult popula-
tion. The short-term use of PVP-I/dexamethasone, currently
under investigation, may be useful for shortening disease
duration and reducing inappropriate antibiotic prescriptions.
Isenberg et al51 investigated the efficacy of PVP-I versus
neomycin–polymyxin B–gramicidin for treatment of infec-
tious conjunctivitis in children aged 7 months to 21 years
(mean age, 6.6 years). Their data showed that PVP-I was as
effective as the antibiotic for treating bacterial conjunctivitis
and is somewhat more effective against chlamydia. Bacterial
conjunctivitis constitutes a majority of conjunctivitis cases
among children,6 but survey data show that very few primary
care physicians are able to discriminate between viral and
bacterial etiologies.6,8 This can lead to inappropriate antibi-
otic prescriptions and risk of antibiotic resistance. PVP-I has
the potential to circumvent these risks, and it may also be
a useful option in conditions when antibiotics are unavailable/
costly. Further, in vitro studies show that PVP-I has
significant virucidal activity against a range of viruses that
include HSV.52,53 Although clinical trials would be needed to
evaluate the efficacy and safety of PVP-I/dexamethasone in
HSV conjunctivitis cases, or cases where an HSV etiology
cannot be ruled out, the virucidal activity of PVP-I in
conjunction with the anti-inflammatory activity of steroids
has the potential to make these combination agents effective
treatment options.
CONCLUSIONS
Corticosteroids, in combination with anti-infectives/
antiseptics, have the potential to address both infectious and
inflammatory components of acute infectious conjunctivitis.
Some of these combination products could reduce the need
for differential diagnosis of bacterial or adenoviral conjunc-
tivitis, and available data show that they may be appropriate
for use in both adult and pediatric populations. Perceived
risks associated with corticosteroid use (eg, increased IOP,
prolonged viral shedding, and HSV reactivation) are not
supported by high-quality evidence in the literature, at least in
some situations (eg, short-term use). In fact, a review of the
www.corneajrnl.com | 1065
Holland et al
literature indicates that topical corticosteroids have been
shown to be efficacious and well tolerated when used for
short periods, in combination with antibiotics, antiseptics, or
anti-infectives. Future randomized clinical trials to investigate
the effectiveness and safety of steroids in conjunctivitis
treatment are needed.
ACKNOWLEDGMENTS
The authors thank Ira Probodh, PhD, of Excel Medical
Affairs, who provided medical writing assistance funded by
Shire, a member of the Takeda group of companies.
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