REVIEW

CURRENT
OPINION Ocular rosacea
Travis K. Redd a,b and Gerami D. Seitzman a,b

Purpose of review
To revisit ocular rosacea as an underappreciated condition which can cause permanent blindness if
inadequately treated, and to review data supporting improved diagnostic and treatment strategies.
Recent findings
Ocular rosacea has an underrecognized prevalence in children and individuals with darker skin tone.
Rosacea has several associations with other significant systemic diseases. Variations in local and systemic
microbiome, including demodex infestation, may play a role in pathogenesis, severity, and in explaining
the different phenotypes of rosacea. The National Rosacea Society Expert Committee established an
updated classification system of rosacea in 2017. New treatment algorithms based on these clinical
subtypes are suggested.
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Summary
With continued advancements in the understanding of the epidemiology and pathogenesis of rosacea,
randomized controlled trials specific for ocular rosacea remain lacking. There is overall consensus that
rosacea and ocular rosacea require chronic maintenance treatment strategies involving combination topical
and systemic therapies.
Keywords
demodex, microbiome, ocular rosacea, rosacea

INTRODUCTION transition from a classification based on subtypes

Acne rosacea is a common, chronic, inflammatory
cutaneous disorder with multifactorial causes which
affects the skin of the cheeks, nose, chin, forehead,
and eyelids. The disease typically follows a relapsing
and remitting course, with exacerbations that can be
triggered by exposure to heat, spicy foods, or ultra-
violet radiation [1]. The ocular manifestations of
rosacea are often overlooked by ophthalmologists
managing patients with chronic external ocular
inflammation, but this disease can have significant
psychosocial impact on patients and can be poten-
tially blinding if left untreated [2,3]. The last review
of this condition in Current Opinion was in 2004 [4].
of disease to a multifaceted phenotypic classifica-
tion system recognizing the significant clinical over-
lap of these syndromes. Rosacea is now diagnosed
based on the presence of at least one ‘diagnostic
phenotype’ (centrofacial erythema with periodic
intensification or phymatous changes) or at least
two ‘major phenotypes’ (papules and pustules,
flushing, telangiectasia, or ocular rosacea). It should
be noted these are not distinct classification strata
and likely represent a spectrum of clinical manifes-
tations of the same underlying inflammatory pro-
cess, evidenced by the fact that individuals can
transition from one phenotype to another over time
&&

Herein we provide an interval update, emphasizing [5 ]. An additional potential subtype termed ‘neu-
developments in the epidemiology, pathophysiol- rogenic rosacea’ has been described, though its role
ogy, and treatment of this condition. in the current classification system is unclear [6].

CLINICAL MANIFESTATIONS
Rosacea has traditionally been categorized into four
discrete subtypes: erythemato-telangiectatic, papu-
lopustular, phymatous, and ocular rosacea. How-
ever, significant overlap existed between these
groups, prompting the National Rosacea Society
to convene an Expert Committee in 2017 to revise
&&
this classification system [5 ]. This resulted in a
a
Francis I. Proctor Foundation and bDepartment of Ophthalmology,
University of California, San Francisco, San Francisco, California, USA
Correspondence to Gerami D. Seitzman, MD, Francis I. Proctor Foun-
dation; Department of Ophthalmology, University of California,
San Francisco, 95 Kirkham Street, San Francisco, California, USA.
E-mail: gerami.seitzman@ucsf.edu
Curr Opin Ophthalmol 2020, 31:503–507
DOI:10.1097/ICU.0000000000000706

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Ocular manifestations of systemic disease
KEY POINTS
 Ocular rosacea is a common condition that can be
blinding if inadequately treated.
 The prevalence of ocular rosacea is underrecognized in
populations with darker skin tone.
 Ocular rosacea is often more difficult to diagnose in
children, but is critically important due to increased
disease severity in this demographic.
 The local and systemic microbiome likely play a role in
the pathogenesis of ocular rosacea,
particularly demodex.
 Significant equipoise exists with regard to effective
management strategies for ocular rosacea,
necessitating additional investigation.
Greater than 50% of patients with cutaneous
&&
rosacea also have ocular rosacea [7 ]. Ocular rosacea
can occur with severe, mild, or even absent cutane-
ous manifestations. The severity of ocular and cuta-
neous rosacea may be discrepant. Lid margin
telangiectases (Fig. 1), conjunctival injection, evap-
orative tear loss due to meibomian gland inspissa-
tion, chalazia, lid margin thickening with irregular
contour (tylosis), and anterior displacement of the
‘Marx line’ along the eyelid margin, as noted with
diagnostic dyes such as fluorescein and lissamine
&&
green, are common manifestations [5 ,8]. Vascular-
ized, ‘spade-shaped’, sterile corneal inflammation
(Fig. 2), sclerokeratitis, and cicatricial conjunctivitis
can also develop, and are the primary causes of
vision loss from this disorder [9].
FIGURE 1. Slit lamp photograph of a 36-year-old male with
cutaneous and ocular rosacea. The eyelid margin
demonstrates classic findings of inspissated meibmonian
glands and lid margin telangiectasis.
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FIGURE 2. This slit lamp photograph demonstrates marked
meibomian gland inspissation, lid margin telengiectasias,
circumferential corneal neovascularization, and an inferior
pericentral area of corneal infiltrate with surrounding edema.
EPIDEMIOLOGY
Acne rosacea has classically been described as a
condition primarily affecting white individuals in
Western Europe and North America, where its prev-
&&
alence is estimated to be 10% or higher [5 ]. How-
ever, in recent years the disease has become
increasingly recognized in populations with darker
&
skin tones [10,11 ]. It is generally underdiagnosed in
these demographics because erythema and telangi-
ectatic changes are less pronounced, often requiring
the presence of papulopustular or phymatous
changes to be readily detectable. Rosacea is generally
more common in women, and the onset of disease is
typically after age 30 [12]. The prevalence of ocular
rosacea in children is generally underappreciated,
despite the fact that it is one of the primary causes of
sterile keratitis in this population and can result in
permanent vision loss due to corneal scarring and
&&
even corneal perforation (Fig. 3) [9,13,14 ,15]. The
diagnosis in this demographic is made more difficult
by the tendency for ocular findings to occur in the
absence of clear cutaneous manifestations of rosacea
[15]. One case series of 16 pediatric patients with
ocular rosacea demonstrated that the majority had a
delay in diagnosis, with the average delay being
&&
greater than 1 year [14 ]. Earlier detection and
prompt treatment, coupled with an appreciation
for the importance of chronic suppressive therapy,
may prevent long-term vision loss from rosacea
keratitis in children.
Volume 31  Number 6  November 2020

FIGURE 3. Slit lamp photograph of the right eye of a
17-year-old male with rosacea keratitis characterized by a
nasal fascicle of neovascularization extending to the central
cornea. The visual acuity in this eye is 20/200 due to
central corneal scarring and irregular astigmatism.
The diagnosis of acne rosacea is made all the
more important by its association with a number of
systemic conditions including cardiovascular dis-
ease, inflammatory bowel disease, diabetes, Parkin-
son’s disease, and various forms of cancer
&& &
[5 ,16 ,17]. It can also have significant psychosocial
effects and has been specifically associated with an
increased prevalence of anxiety and depression, as
well as chronic sleep disruption [2,18].
PATHOPHYSIOLOGY
Rosacea has long been recognized as an inflamma-
tory disease resulting from a complex interaction of
abnormalities of the innate immune system, the
adaptive immune system, mast cell dysfunction,
&&
and/or neurovascular compromise [5 ]. However,
the exact mechanisms and roles of these different
components of the pathophysiology remain
obscure. More recently, the importance of the local
microbiome in the pathogenesis of this disease has
become increasingly clear [19,20]. One case –con-
trol study found an increased prevalence of Cuti-
bacterium acnes (formerly known as
Propionibacterium acnes) and Serratia marcescens
on the facial skin of rosacea patients compared
with controls and those with acne vulgaris [21].
Another case– control study identified a relative
depletion of Roseomonas mucosa and an increased
prevalence of Campylobacter ureolyticus, Corynebac-
terium kroppenstedtii, and Prevotella intermedia in
participants with rosacea compared with controls
[22]. Several theories have been espoused to
explain the mechanisms by which the cutaneous
microbiome may promote inflammation in
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Ocular rosacea Redd and Seitzman
rosacea. Increased expression of Toll-like receptor
2 has been demonstrated in the affected cutaneous
zones in rosacea patients, which may promote local
activation of the innate immune system [23]. Over-
expression of the antimicrobial peptide cathelici-
din and matrix metalloproteinases have also been
described, both of which may independently pro-
mote inflammation [24]. Alternative evidence sug-
gests disruption to the barrier function of the skin
may be a mechanism of disease, or perhaps alter-
ations in local gene expression [25,26]. A patho-
logic role of the cutaneous microbiome may also
explain the efficacy of oral antibiotics in the treat-
ment of rosacea, though the evidence for this
mechanism remains preliminary [27]. Signifi-
cantly, alterations in the gut microbiome have also
been described in rosacea patients, particularly the
presence of Helicobacter pylori [23].
DEMODEX
It is well established that demodex mite density is
increased in the skin and eyelids/eyelashes of people
with rosacea. The role demodex plays, both com-
mensal and/or pathogenic, is not fully understood
[28]. Skin biopsies of facial rosacea and discoid
lupus, which can mimic rosacea clinically and is
also associated with increased demodex load, sug-
gest the density of mites correlates with increased
inflammatory changes [29]. Methods for consistent
objective evaluation of eyelash demodex load have
not been established. Clinical evaluation for circum-
ferential sleeve debris (Fig. 4), epilation with micro-
scopic evaluation, and confocal microscopy have all
been utilized [30,31].
FIGURE 4. Slit lamp photograph demonstrating
circumferential sleeves at the base of numerous eyelashes,
indicative of demodex infestation.
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Ocular manifestations of systemic disease
TREATMENT
With regard to rosacea treatment, there are two
main considerations. The first is the differentiation
of episodic versus chronic treatment for both cuta-
neous and ocular rosacea. The second is the lack of
established treatment guidelines, and marked clini-
cal equipoise with specific regard to ocular rosacea
treatment. According to a 2015 Cochrane review of
randomized control trials (RCTs) for the treatment
of cutaneous rosacea, there was high-quality data
supporting the effective use of the topical agents
azelaic acid, ivermectin, and brimonidine and sys-
temic treatment with doxycycline and isotretinoin
[32]. This extensive review found only low-quality
evidence supporting oral minocycline, intense
pulsed light, or any ocular rosacea treatment includ-
ing the use of cyclosporine drops. The final conclu-
sion recommended the need for further rosacea
RCTs in particular for ocular rosacea. In 2016, the
American Academy of Ophthalmology similarly
concluded, though oral antibiotics are commonly
used for treatment of meibomian gland dysfunc-
tion, a cardinal sign of ocular rosacea, no level 1
evidence exist to definitely guide selection of oral
antibiotic or specific dose or length of treatment
[33]. Also in 2016, the global ROSacea COnsensus
(ROSCO) panel incorporated the 2015 Cochrane
review to include clinical experience recommenda-
tions from an international panel consisting of 17
dermatologists and three ophthalmologists [34].
Here, recommendations were made based on the
more recent stratified rosacea phenotypes. The over-
all consensus was that moderate to severe presenta-
tions of rosacea, including ocular rosacea, require a
combination of oral and topical treatments simul-
taneously. Doxycycline was the preferred systemic
tetracycline. Here, topical steroids are recom-
mended for severe ocular rosacea. Treatment
requires sufficient time for efficacy, no clear consen-
sus regarding length of initial therapy is concluded,
though 6–12 weeks is suggested. Long-term main-
tenance treatment is required for control of the
disease. However, the favored maintenance treat-
ment regimen is not well defined and more studies
to better determine time needed to respond,
response duration and maintenance therapy are
needed. This consensus statement acknowledges
the role patient preferences and values have in
therapy selection. In 2019, the National Rosacea
Society Expert Committee similarly refined manage-
ment recommendations based on rosacea pheno-
&&
types [7 ]. Again, this consensus statement
emphasizes there is no cure for rosacea, this is a
chronic remitting relapsing process and chronic
combination topical and systemic medications are
required for control.
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CONCLUSION
With specific regard to ocular rosacea treatments,
few RCTs exist to guide treatment choices. The
overall consensus, similar to the summary state-
ments above, parallel that ocular rosacea, like cuta-
neous rosacea, is chronic with recurrent flares. Some
combination of topical and systemic therapy is
likely necessary for initial control, and some selec-
tion of therapy (topical and/or systemic) is likely to
be required for chronic maintenance. Topical ther-
apy includes nonmedicated warm compresses, and
lid scrubs with antibiotic ointments or other solu-
tions. However, with inflamed eyelid margins,
mechanical irritation of eyelids may not always be
indicated. The Cochrane review does not support
high-level evidence for the use of topical cyclo-
sporin, though practice patterns may differ [32].
For severe ocular inflammatory disease, especially
with keratitis and very often in children with ocular
rosacea, topical steroids are required to calm and
often maintain ocular surface inflammation. In
these instances, the lowest potency, lowest fre-
quency topical steroid is selected, with careful repeat
monitoring of eye pressure. Topical ivermectin may
also have a role in ocular surface inflammatory
control [35,36]. With regard to systemic treatment
for ocular rosacea, some tetracycline is often used,
with doxycycline being common and azithromycin
and minocycline selected by some.
In the last decade, we now recognize ocular
rosacea as a disease that affects all skin types. We
have increasing awareness of the overall frequency
of the occurrence of ocular rosacea especially in eyes
with chronic recurrent ocular surface inflammation.
We continue to recognize the severity of ocular
rosacea as a vision limiting process, especially in
the pediatric population. We recognize treatment
strategies vary per rosacea subtype and with severity
of presentation. There is consensus that treatment
combinations of topical and systemic therapies are
likely required. However, data currently do not
guide the selection of specific treatment agents in
each of these categories.
Acknowledgements
This work was made possible, in part, by NEI P30
EY002162 - Core Grant for Vision Research, and by
an unrestricted grant from Research to Prevent Blindness,
New York, NY.
Financial support and sponsorship
None.
Conflicts of interest
There are no conflicts of interest.
Volume 31  Number 6  November 2020

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