s u r v e y o f o p h t h a l m o l o g y 6 3 ( 2 0 1 8 ) 5 3 4 e5 5 3

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Major review

Orbital cellulitis

Theodora Tsirouki, MD, PhDa, Anna I. Dastiridou, MD, PhDa,

Nuria Ibánez flores, MDb, Johnny Castellar Cerpa, MDb,
Marilita M. Moschos, MD, PhDc, Periklis Brazitikos, MD, PhDd,
Sofia Androudi, MD, PhDa,*
a
Department of Ophthalmology, University of Thessaly, Larissa, Greece
b
Institut Català de Retina, Barcelona, Spain
c
Department of Ophthalmology, University of Athens, Athens, Greece
d
2nd Department of Ophthalmology, Aristotle University, Thessaloniki, Greece

article info abstract

Article history: Orbital cellulitis (OC) is an inflammatory process that involves the tissues located posterior
Received 23 December 2016 to the orbital septum within the bony orbit, but the term generally is used to describe
Received in revised form 22 infectious inflammation. It manifests with erythema and edema of the eyelids, vision loss,
November 2017 fever, headache, proptosis, chemosis, and diplopia. OC usually originates from sinus
Accepted 7 December 2017 infection, infection of the eyelids or face, and even hematogenous spread from distant
Available online 15 December 2017 locations. OC is an uncommon condition that can affect all age groups but is more frequent
in the pediatric population. Morbidity and mortality associated with the condition have
Keywords: declined with advances in diagnostic and therapeutic options; however, OC can still lead to
orbital cellulitis serious sight- and life-threatening complications in the modern antibiotics era. Therefore,
intracranial abscess prompt diagnosis and treatment remain crucial. Antibiotic coverage, computed tomo-
orbital abscess graphy imaging, and surgical intervention when needed have benefitted patients and
vision loss changed the disease prognosis. We review the worldwide characteristics of OC, predis-
antibiotics posing factors, current evaluation strategies, and management of the disease.
diagnosis ª 2017 Elsevier Inc. All rights reserved.
management

1. Introduction pediatric population, with an incidence of 1.6 per 100,000 and

Orbital cellulitis (OC) is an inflammatory process that involves
the tissues located posteriorly to the orbital septum within the
bony orbit, but the term generally is used to describe infec-
tious inflammation. It is not as common as preseptal cellulitis
that affects tissues anterior to the orbital septum. OC is
encountered at all age groups but more frequently affects the
0.1 per 100,000 in children and adults, respectively.129
Morbidity and mortality of OC have declined with improve-
ment in diagnosis and therapy32; however, since it may still
have serious complications, prompt diagnosis and treatment
are crucial.108,158,196 We review the worldwide characteristics
of OC, predisposing factors, infectious causes, and current
evaluation and management of the disease.

* Corresponding author: Sofia Androudi, MD, PhD, Department of Ophthalmology, University of Thessaly, Larissa 412 22, Greece.
E-mail address: androudi@otenet.gr (S. Androudi).
0039-6257/$ e see front matter ª 2017 Elsevier Inc. All rights reserved.
https://doi.org/10.1016/j.survophthal.2017.12.001

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 s u r v e y o f o p h t h a l m o l o g y 6 3 ( 2 0 1 8 ) 5 3 4 e5 5 3 535

of OC compared to sinusitis in the age group 6e16 years.11 In

2. Predisposing factors
The most frequent predisposing factor in all age groups is
secondary infection extending from the paranasal sinuses. This
is established in studies in both the Western and the devel-
oping world.32,34,85,188,191 Specifically, it has been determined
that 1.3%e5.6% of sinusitis results in OC, and 0.3%e5.1%
develop orbital or subperiosteal abscess.6,151 OC most
commonly originates from the ethmoid sinuses, with a re-
ported frequency of 43%22,61,68,76,82,113,127 to as high as 94.7% of
cases in a study from Canada53 and 100% in another study from
Massachusetts.8 The infection proceeds from the sinuses to the
orbit, assisted by specific anatomical characteristics such as the
thin medial orbital wall, lack of lymphatics, valveless veins of
the orbit, and foramina of the orbital bones.104
Surveys that detect sinusitis radiologically find up to 91% of
cases of sinus-related OC originate from the ethmoid and
maxillary sinus.30,58 In a 10-year retrospective analysis from
Taiwan, however, children aged 3e18 years diagnosed with
OC underwent computed tomography (CT) scans, and the
involved sinuses, in the order of frequency, were maxillary,
ethmoid, frontal, and sphenoid.83 In fact, childhood OC in-
volves more than 1 sinus in up to 38% of cases.34,62 In a study
from Canada, pansinusitis was observed in 15.7% of cases in
children.58 In adults, OC may be related to frontal sinus
infection,75,84,120 whereas multiple sinus involvement does
not exceed 11%.34,62
Spread of the infection from the upper respiratory tract to
the orbit is also a major cause of OC.35,38,103,176 The affinity of
OC with infections arising from the sinuses and the upper
respiratory tract reflects the seasonal distribution of the dis-
ease, with peak occurrence in winter to early spring.34,62 This
is proportional to the seasonal distribution of infections
initiating in the aforementioned anatomical locations.32
Reported etiological factors of OC also differ between
Western and developing countries. Trauma or surgery is a
common cause of OC in developing countries.14,32,62,90 OC
follows either direct inoculation from a penetrating injury or
develops secondarily to orbital fracture that allows comm-
unication between the sinuses and the orbit.104 In a study
from Pakistan, trauma was reported as a more common cause
India, injury was associated with OC in 24% of cases132 and
was usually linked to the presence of a foreign body.108,195
Foreign body OC is caused either by organic materials or
by metal objects (Fig. 1). Usually children and young males
are affected because injuries are caused during playing or at
work.49 Organic foreign bodies usually involve wood.
Wooden foreign bodies carry a large amount of bacteria, and
if not promptly removed, they lead to severe infections.179
These injuries are associated with a high risk of OC and
complications such as recurrent cellulitis, cutaneous fistula,
restrictive myopathy, periorbital abscess, and even pan-
ophthalmitis.164 Identification of the wooden foreign bodies
with CT can be difficult. During the first days after the injury,
wooden foreign bodies appear as low-density signal on CT
scan and may be misdiagnosed as air. After a few months the
wooden material presents the same density as the sur-
rounding tissues, making it difficult to diagnose.105 In certain
cases, additional imaging with magnetic resonance imaging
(MRI) and especially T1-weighted images may further
enhance the ability to identify a wooden or vegetable foreign
body.179 Timely removal of these foreign bodies leads to
resolution of inflammation and associated signs.110 Metal
objects are more easily identified and surgically removed
from the orbit; however, most metals are inert and,
depending on their location in the orbit, may be treated
conservatively without removal.83 Iron, copper, and lead,
however, may cause serious complications, and gunshot
injuries usually lead to severe ocular injury.28
In Nigeria, upper respiratory tract infections and facial and
globe injuries were reported as the major predisposing factors
for OC.14 Additionally, in children, insect bite (10%), hordeo-
lum, and molluscum contagiosum of the lid with secondary
bacterial infection were common predisposing factors.141
In developed countries, OC is not common after ophthalmic
surgery; however, there are rare reports of OC after strabismus
surgery,4,19,48 blepharoplasty,93 canaliculitis surgery,80 cataract
surgery,101 peribulbar injection,5,84,108,120,189 sub-Tenon anes-
thesia,111 hydroxyapatite35 and polyethylene98 orbital sockets,
implanted aqueous drainage devices, keratoprosthesis, and
silicone-sponge scleral buckle implants for rhegmatogenous
retinal detachment.3,132

Fig. 1 e Foreign body causing endophthalmitis and orbital cellulitis. A: Photo of a patient with an intraocular foreign body of
the left eye and B: axial CT scan of the orbits. A metal intraocular foreign body with the entry wound in the medial
conjunctiva is causing endophthalmitis and orbital cellulitis of the left orbit. Although removal of metallic foreign bodies is
not always necessary, the foreign body in this case must be removed. CT, computed tomography.

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536 s u r v e y o f o p h t h a l m o l o g y 6 3 ( 2 0 1 8 ) 5 3 4 e5 5 3
Other etiological factors of OC include dacryocystitis, dental
infections from spread through the maxillary sinus,45,46
endophthalmitis, panophthalmitis,142 untreated preseptal
cellulitis, and hematogenous spread in the setting of bacter-
emia from distant sources.5,30e32,34,39,62,63,65,108,125,138 In a study
from Saudi Arabia, intraocular or orbital tumorsdspecifically
retinoblastoma, rhabdomyosarcoma, and melanomadwere
the underlying cause in 3.7% of patients with OC.34,128
Finally, there are also case reports of OC from rare
causes.101 In a study from Malaysia, swimming was consid-
ered a possible predisposing factor because the symptoms
worsened following this activity.176 In a study from Saudi
Arabia, the allergic reaction to topical neomycin drops was
reported as the cause of OC in 2 cases,34 whereas Kim and
colleagues reported a case of a 67-year-old Korean man diag-
nosed with epidemic keratoconjunctivitis than supposedly led
to orbital inflammation.100
3. Epidemiology
OC is not a common condition. Incidence of the disease has
been calculated as 1.6 per 100,000 in the pediatric population
and 0.1 per 100,000 in adults129; however, a retrospective study
from Nigeria found that 6.2% of ocular emergency admissions
during a 3-year study period were for OC.14
Although etiological factors of OC differ considerably be-
tween patients in the Western and developing world, there are
no documented ethnicity differences in epidemiology.121
Average age at presentation has been reported from 19.92 to
25.7 years.34,139 OC commonly affects children and early ad-
olescents, likely because until the age of 15 years the immu-
nologic system is immature.14,32,34,139 In a report from India,141
however, 57% of cases were adults and 42% were children,
with a mean age of 45 years in the adult group and 4 years in
the pediatric group. In pediatric studies, the mean age varies
from 6.1 to 8 years, with a range of 0.5e17 years.1,58,65,103,176 A
study from Texas examined children with OC before the age of
12 months. Average age at presentation was 3.8 months, with
a range of 1e9 months.123
Gender distribution is usually equal32,58,176; however, in the
studies from Iran, India, and Nigeria, males are affected more
often (66.7%e70.6%). This male preponderance in the devel-
oping countries may be attributable to the prevalence of work
accidents as an etiological factor.13,14,32,65 Some studies from
the developed world have also exhibited male predominance,
such as a pediatric study from the United States in which 73%
were males130 and a study from Canada in which 74% of OC
cases were males.107
Seasonal presentation of OC in late winter-early spring has
been observed in Western studies, directly associated with the
occurrence of sinus and upper respiratory infections.32,34,107 A
seasonal distribution, however, was not observed in children
younger than 9 years of age.58 Another pediatric study from
the United States also failed to demonstrate any obvious
seasonality.130
Increased ocular morbidity in the developing countries is
associated with late seeking of medical care and concurrent
sinus infection, with 9.1% of eyes presenting with no light
perception.141 In a retrospective study from Nigeria, only 29.4%
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presented within 3 days of disease onset.14 The average re-
ported duration of symptoms was 5.2e10.6 days, and average
hospital stay was 9e13.7 days in the developing countries, with
57.6% of cases presenting a prolonged hospital stay of more
than 10 days.14,65,139,141 In contrast, in the Western countries,
the average duration of symptoms was 4.4 days, and the
average hospital stay was 5.8e6.2 days.58,62,130
Finally, right and left orbits are almost equally affected,
with the right orbit being involved in 51% of children in a study
from Israel65 and 50.5% in a study from Saudi Arabia.34
4. Microbiology
The causative organisms associated with OC are difficult to
identify because of the normal flora of the area, previous
antibiotic therapy, and the multiple agents that are usually
contributing to the infections.108 Blood cultures are rarely
positive in patients with OC.58,68,87,139,141 Cultures from nasal
swabs, throat swabs, and ocular secretions are generally more
effective, but cultures of material recovered from orbital ab-
scesses and sinus aspirates are the most reliable.25,108,113,141
While it is commonly understood that these invasive surgi-
cal techniques are more likely to achieve a positive culture
result, their routine use is not generally recommended.119
Moreover, Ferguson and McNab found different results
between cultures of conjunctival swabs and cultures of
abscesses material from patients with positive cultures,62
whereas Oxford and McClay found that all patients with
positive surgical and blood cultures had the same culture
results.138
The majority of studies performed in developed countries
find Staphylococcus aureus13,22,27,32,41,68,72,82,87,108,113,115,123,135,141,180
and Streptococcus species32,68,82,87,108,141,143,153,155,160 as the most
common causative organisms. Most recent studies from both
developed and developing countries underline an increasing
trend of OC cases caused by methicillin-resistant Staphyloccocus
aureus (MRSA).58,108,118,119,160 The incidence of MRSA in such in-
fections varies from 21% to 72%.20,112,119,194 Community-acquired
MRSA is increasing in various countries.21,29,124,141 The limited
number of effective antibiotics in treating MRSA renders the
increasing prevalence of this microorganism a major public
health concern. A study from California underlines the
increasing incidence and resistance among the pediatric popu-
lation, reporting a significant danger of neonatal infection with
MRSA.7 Peña and colleagues investigated the prevalence and
antibiotic resistance patterns of pathogens associated with
orbital complications from acute sinusitis after the widespread
use of 7-valent pneumococcal conjugate vaccine (PCV7) vacci-
nation and emphasized the significant increase in S. aureus OC,
with a concurrent increase of MRSA.146
Streptococcal infection is age related, with younger chil-
dren more likely to present with infection from Streptococcus
pneumoniae and older children from group A streptococcus.10
Additionally, Streptococcus milleri,138 Streptococcus viridians,87
and Streptococcus anginosus160 are the most commonly iden-
tified organisms. Peña and colleagues observed a decline in
the incidence of S. pneumoniae as an etiologic pathogen.146
Other frequently associated microorganisms in various
studies over the world are coagulase-negative
 s u r v e y o f o p h t h a l m o l o g y 6 3 ( 2 0 1 8 ) 5 3 4 e5 5 3 537

staphylococcus,68,87,119,141 Klebsiella pneumoniae,87,141 Asper-
gillus,141 Moraxella catarrhalis,143 and Haemophilus influenzae.85
Rare etiologic factors for OC include Pseudomonas species,34
Neisseria, Eikenella corrodens, Corynebacterium, Prevotella melani-
nogenica, Morganella morganii, Acinetobacter,87 Bacillus anthra-
cis,141 Escherichia coli, Actinobacter species, Enterobacter species,
and various anaerobes such as Propionibacterium acnes,
Peptococcus species, Peptostreptococcus species, Veillonella species,
Prevotella, Porphyromonas, Fusobacterium bacteroides, and
Clostridium bifermentans.20,22e24,34,62,112,119
Specific pathogens have been identified in certain situa-
tions. In posttraumatic cases, S. aureus and S. pyogenes are the
main pathogens.108 Microbiology of odontogenic origin mainly
includes mixed aerobic and anaerobic bacteria.23,24 Lee and
colleagues reported that nonespore-forming anaerobic bac-
teria usually cause OC after human or animal bites.108
Age has also been shown to influence bacteriology of OC. A
considerable number of studies present anaerobes34,67 as
common pathogens of pediatric OC. It is generally accepted
that OC in children younger than 10 years is caused by single
aerobic pathogens as compared to older children, who often
present more complex infections by multiple aerobic and
anaerobic pathogens.2,34,79 With age, the ostia of the sinus
cavities narrows, creating convenient conditions for the
development of anaerobic pathogens (Fig. 2). This is probably
an explanation why responsiveness to antimicrobial therapy
appears to be age related,51,79 since in younger children
treatment with medical therapy alone is adequate, whereas in
older children, the combination of medical and surgical
intervention is often necessary.78 Harris and colleagues found
that 43.2% of children with OC between the ages of 9e14 years
present complex infections, more often with polymicrobial
infections, and anaerobes were found in all cases.79 Anaerobic
OC is much less common in adults.62
Up to the early 1990s, H. influenzae was one of the most
frequent pathogens associated with OC in children.8,51,141 H.
influenzae was extremely aggressive, with bacteremia and
meningitis.18,51,109,119 After the introduction of H. influenzae
type B vaccine in 1985, there was a significant decline in OC
caused by H. influenzae type B.8,34,62,108,134,154,162,188 Pandian
and colleagues attributed this decline to additional factors
such as the introduction and wide use of more effective an-
tibiotics.141 In developing countries where vaccines are not
accessible, H. influenzae remains a common cause of OC.108,143
Orbital organic foreign bodies usually carry a large amount
of bacteria. Previous studies have not shown a predominant
organism. Similarly, fungal organisms have not been found
commonly in cases of orbital wooden foreign bodies. In a
recent review of 32 cases with orbital wooden foreign bodies,
Staphylococcus epidermidis, S. aureus, Enterobacter agglomerans,
and Clostridium perfringens were identified.179
A high rate of suspicion for fungal OC should arise in high-
risk patients, such as immunocompromised patients, patients
with diabetes mellitus, or patients under chronic steroids or
antibiotic treatment.60,91 Both Mucormycosis and Aspergillosis,
the most common fungal rhinoorbital infections, often lead to
severe complications such as ophthalmic vascular thrombosis,
optic atrophy, palsies, meningoencephalitis, brain abscess,
thrombosis of the cavernous sinus, subdural, or intracerebral
hemorrhages, presenting finally a high mortality rate.181
Streptococcus infection can lead to a dangerous necro-
tizing lid disease, necrotizing fasciitis.32,37,117,163,165 This is a
condition that may cause systemic complications and prog-
ress to multiorgan failure37,117 through the production of in-
flammatory proteins and exotoxins.32 Ng and colleagues
presented a case of necrotizing OC with rapid development of
severe systemic toxicity, extensive soft tissue necrosis, and
formation of abscess leading to severe complications
including panophthalmitis requiring evisceration.133
5. Classification
Historically, Chandler’s classification of orbital complications
of acute sinusitis has been used, based on their location and
severity.
Group 1: Preseptal cellulitis
Group 2: Orbital cellulitis
Group 3: Subperiosteal abscess
Group 4: Intraorbital abscess
Group 5: Cavernous sinus thrombosis (CST)
Group I comprises preseptal cellulitis, in which the in-
flammatory process is limited anteriorly to the orbital septum
and does not invade the intraorbital structures. In group II
(OC), the orbital tissues are affected. Group III includes the
formation of a subperiosteal abscess, in which purulent

Fig. 2 e Imaging of paranasal sinuses in various age groups. Coronal CT scan of the paranasal sinuses of A: a 6-year-old
child, B: 14-year-old child with mucosal thickening of the paranasal sinuses and C: a 19 year-old child. With age, the ostia of
the sinus cavities narrow, creating convenient conditions for the development of anaerobic pathogens. This is probably an
explanation why in children younger than 10 years, treatment with medical therapy alone is adequate, whereas in older
children, the combination of medical and surgical intervention is often necessary. CT, computed tomography.

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538 s u r v e y o f o p h t h a l m o l o g y 6 3 ( 2 0 1 8 ) 5 3 4 e5 5 3
material collects periorbitally, between the bony walls of the
orbit and the periorbita. In group IVeorbital abscessethere is a
purulent collection inside the orbit. In group VeCSTethere is
an extension of orbital inflammation into the cavernous sinus
that can lead to involvement of the third, fifth, and sixth
cranial nerves.30
Jain and Rubin recently simplified the classification system
as follows:89
1. Preseptal cellulitis
2. OC (with or without intracranial complications)
3. Orbital abscess (with or without intracranial
complications)
a. Intraorbital abscess, which may arise from collection of
purulent material in an OC
b. Subperiosteal abscess, which may lead to true infection
of orbital soft tissues
6. Clinical manifestations
OC presents with classical signs. Since it can potentially lead
to severe visual and life-threatening complications and
progress rapidly, prompt diagnosis and treatment are
essential.108 The prevalence of signs is similar in developing and
developed countries. OC begins with general signs and symp-
toms such as severe eyelid redness and edema (71.5%e100%),
ptosis (10.6%e33.3%), conjunctival chemosis (32%e45.3%),
discharge (16.7%), erythema of periorbital tissues, and periocular
pain or pain with eye movement (39.2%e63%; Fig. 3).108,158,196 As
the infection progresses, there are signs that can help differen-
tiate between more superficial infections and OC,33 such as
proptosis and globe displacement (46.9%e100%), decreased
vision (12.5%e37%), afferent pupillary defect (5.5%e16.7%),
impaired color vision (16.7%), and limited ocular motility
(39.1%e84.6%).1,12,32,58,62,65,70,76,87,113,176
Fig. 3 e Orbital cellulitis. A: Photo of a patient with orbital
cellulitis of the left eye. The eyelid edema and redness are
obvious. Additional signs are ptosis, mild proptosis,
redness, and chemosis of the conjunctiva; B: photo of the
patient after treatment.
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Additionally, constitutional signs develop, such as fever
(32%e81.2%), leukocytosis (47%), headache (10.1%), general
malaise, and loss of appetite.75,92 Generally, a history of acute
sinusitis or upper respiratory tract infection during the days
preceding should be sought.108
Clinical signs and symptoms at presentation may also
differ according to age. In a study from the United States,
clinical characteristics were compared in children younger
and older than 7 years. The younger group presented higher
white blood cell counts and decreased frequency of proptosis
and ophthalmoplegia.130 In children younger than 1 year, OC
may present with fever, periorbital edema, periorbital ery-
thema, reduced appetite, and lethargy.42,123
7. Complications
OC may be associated with severe visual and life-threatening
complications, including optic neuropathy, the formation of
an orbital abscess, meningoencephalitis, intracranial ab-
scesses, CST, and sepsis.56,108,109,158,159,196 Children are sus-
ceptible to serious complications such as optic neuropathy,
endophthalmitis, meningitis, and brain abscess because of
their immature immune system.123 Patients with sinusitis and
OC in developing countries often seek treatment later in the
course of their disease and develop complications more
frequently compared to patients in Western countries.32
Involvement of the optic nerve or the vasculature of the
orbit and the eye are among the eye-threatening complica-
tions that may develop. The optic nerve can be affected by
inflammatory infiltration, mechanical compression, or
compression of the feeding arteries with resultant
ischemia.2,50 This can lead to disc swelling or neuritis with
rapid progression to optic atrophy and blindness. Other usual
causes of loss of vision include ischemia from thrombophle-
bitis of the orbital veins and ischemia by compression and
occlusion of the central retinal artery. Vascular causes usually
lead to permanent visual loss, whereas compressive optic
neuropathy may respond to treatment with antibiotics or
surgical drainage.32 Before the broad use of antibiotics,
permanent loss of vision occurred in over 20% of OC90 but has
significantly fallen since.52,144 Up to 11% of cases resulted in
visual loss until the late 80s.104,126,144 In recent years, the vi-
sual morbidity of OC has minimized in the developed coun-
tries and has significantly dropped in the developing world.32
Other ocular complications of OC include exposure kerat-
opathy resulting in corneal ulceration; infarction of the sclera,
choroid, or the retina136,150; septic uveitis; iridocyclitis, cho-
roiditis, or panophthalmitis, retinal detachment; and glau-
coma with rapid elevation of intraocular pressure.32,34,43,61
One report refers to OC complicated with combined retinal
and choroidal detachments.59
A complication of OC that may potentially lead to irre-
versible visual loss is the development of an abscess.185 A
subperiosteal abscess usually occurs as a complication of
bacterial sinusitis30,32,79 and is commonly located adjacent to
opacified paranasal sinuses, specifically at the medial orbital
wall and the orbital floor.108 A subperiosteal abscess is the
result of the accumulation of purulent material between the
periorbita and the orbital bone (Fig. 4). Specifically, the
 s u r v e y o f o p h t h a l m o l o g y 6 3 ( 2 0 1 8 ) 5 3 4 e5 5 3 539

ethmoidal sinuses are separated from the orbit by the lamina
papyracea, the thinnest bone in the orbit. Additionally, the
orbital floor that lies on above part of the maxillary sinus is
also thin. In these areas, the periosteum in the orbit (the
periorbita) is not firmly attached to the bone and can be
elevated by an accumulation of purulent material, thus lead-
ing to the formation of a subperiosteal abscess.85,167,172
An orbital abscess, the accumulation of pus within the
orbital elements, results from the organization of the orbital
inflammatory progress or the rupture of a subperiosteal ab-
scess. It may lead to severe consequences, such as proptosis,
ophthalmoplegia, and loss of vision.44,89,177 Orbital abscesses
have led to devastating results in the past,85 even in cases
receiving medical and surgical treatment. A study from 1969
refers to a percentage of 7.1%e23.6% of patients with orbital
abscess experiencing permanent visual loss.90 Few cases of
acute visual loss as a result to orbital abscess are reported in the
recent literature, especially in developed countries, whereas in
developing countries, many patients with OC still exhibit severe
complications, mainly as a result of delayed treatment.32,53
The incidence of abscess formation has declined signifi-
cantly, especially in developed countries. Among series with
reported orbital complications of sinus disease, the incidence
of subperiosteal abscess reached 79%69,127,193 in older studies
and is estimated to be around 42% in more recent studies.138 In
a 10-year retrospective study in Wisconsin of 228 patients
with OC, 53 (23.8%) had CT-confirmed subperiosteal ab-
scesses, whereas the majority of patients with subperiosteal
abscesses belonged to the older children or adult group144,153;
lately, there are reports suggesting that adults were less likely
than children to present with abscesses.55 Ferguson and
McNab present incidences of 29% of inflammatory changes,
62% subperiosteal abscess, and 9% orbital abscess in the
children group, compared to 72%, 5%, and 22%, respectively, in
the adult group.62
Intracranial complications of OC include meningitis, em-
pyema or abscess of the epidural or subdural space, intrace-
rebral abscess, Pott’s puffy tumor, CST, and ischemic brain
infarction.2,14,15,32,147,166 These are considered rare (4% of
hospitalized patients with sinusitis) and are a grave danger to
life.2,23 The aforementioned complications result from sinus-
itis or cellulitis by direct extension, hematogenous spread, or
retrograde thrombophlebitis through the valveless venous
system that interconnects the sinus or orbital veins with the
intracranial venous system.23,153 Sinus infection is considered
the major etiologic factor for intracranial abscesses, with
frontal sinus involvement being the most common, followed
by ethmoid and maxillary sinuses.32 When neurological signs
are present in a patient with OC, intracranial extension must
be suspected. Symptoms are not always present in patients
with intracranial abscess, or they can be minimal, especially
in children. The usual symptoms are nausea, vomiting, sei-
zures, fever, and change in mental status.108,153
Epidural and subdural empyemas are the 2 most common
intracranial complications of sinusitis-related OC.2,138,184
Meningitis was considered the most common intracranial
complication in a study from 1984,32 along with epidural,
subdural, and brain parenchymal abscess.16 A retrospective
study that reviewed the complications of acute sinusitis from
a tertiary care children’s hospital in Texas between 1995 and
2002 found orbital abscesses in 42.3% of patients, epidural
empyema in 6.7%, subdural empyema in 5.8%, Pott’s puffy
tumor in 2.9%, intracerebral abscess in 1.9%, meningitis in
1.9%, and CST in 1.0%.138
CST represents one of the most severe complications of OC.
CST should be suspected clinically when there is severe loss of
visual acuity. Orbital pain, chemosis, eyelid edema, and limi-
tation of globe motility are also marked and progress rapidly.
There is retinal venous engorgement. Involvement of the III,
IV, V, or VI cranial nerves adds a strong clinical suspicion for
CST. Systematic deterioration is rapid, with general prostra-
tion, high fever, meningitis, and sepsis. The rate of blindness
and death is up to 20%.138,183,187 Without prompt treatment,
CST is a fatal situation. Morbidity in these cases is related to
the contents of the cavernous sinus, cranial nerves III, IV, V1,
V2, and VI, and internal carotid artery. Thrombosed
ophthalmic veins and retinal infarction are other possible
complications, whereas the thrombus from the cavernous
sinus may lead to petrosal sinus, sigmoid sinus, or internal
jugular vein thrombosis.23
The most common pathogens leading to these intracranial
complications are anaerobes,153 and infections are often pol-
ymicrobial.21,32 S. milleri2,138,183 and S. aureus4 have been
described as the most common pathogens, whereas Strepto-
coccus, Stapylococcus, Bacteroides, and Fusobacterium species are
also significant etiologic factors.32
Various researchers have studied the long-term symptoms
and signs of intracranial involvement. Oxford and Mc Clay in

Fig. 4 e Subperiosteal abscess. A: Photo of a patient with a subperiosteal abscess of the right orbit, B: sagittal CT scan of the
orbits, and C: coronal CT scan of the orbits. The abscess is the result of the accumulation of purulent material between the
periorbita and the orbital bone. It is located at the orbital roof. The right frontal sinus appears opacified and full of purulent
material. CT, computed tomography.

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540 s u r v e y o f o p h t h a l m o l o g y 6 3 ( 2 0 1 8 ) 5 3 4 e5 5 3

2005 reported palsies of cranial nerves II, III, IV, and VI as a
result of CST with facial nerve paresis, hemiparesis, unilateral
lower extremity paresis, generalized motor weakness, apha-
sia, and altered level of consciousness.138 Others have re-
ported ophthalmoplegia, blindness, aphasia, and motor
deficits4; hearing loss187; cranial nerve palsies183; and hemi-
paresis,2 probably from infarction of the internal capsule, and
Kabre and colleagues reported no long-term neurological
sequelae in 2 cases with intracranial abscesses.94
In the preantibiotic era, intracranial complications resulted
to death in a significant proportion of patients. A study per-
formed between 1907 and 1930 reported a 19% mortality rate
among 275 cases of OC.52 Over 50 years later in a study from
1989, 19 children had intracranial abscesses secondary to
nasal, sinus, and orbital infection. A subdural abscess, repre-
senting the most dangerous intracranial complication,
developed in 7 patients, with 3 of them eventually dying.115
The overall mortality rate in this series was 21% (4 out of 19
patients with intracranial abscess) despite aggressive treat-
ment and specialist consultation.
The broad use of more effective antibiotics also led to sig-
nificant decline in the incidence of meningitis. Studies from
the preantibiotic era on the orbital complications of sinusitis
reported death from meningitis in 17% of cases, whereas only
1.9% of patients in recent times developed meningitis.30,169
adenocarcinoma and urothelial carcinoma,114 neuroblas-
tomas,20 adenocarcinoma of the rectum,71 and lung
carcinoma.36
Rheumatologic diseases such as granulomatosis with
angiitis, polyarteritis nodosa, and giant cell arteritis can mimic
an infectious process.72,104 Other rare conditions that may
mimic OC and must be kept in mind when treating such pa-
tients are traumatic or spontaneous carotid cavernous fistula
(Fig. 6),148 sickle cell disease, facial bone infarctions,47
ethmoidal bone fracture,168 hemorrhagic cysts, aneurysmal
bone cysts, nasal foreign bodies,190 hemorrhagic infarct of the
orbital bones,20 ossifying fibroma,41 pseudoaneurysm of orbital
bones, cranioorbital cerebrospinal fluid leak,182 Langerhans cell
histiocytosis,97 dacryops infection,106 idiopathic orbital in-
flammatory disease,140 thyroid ophthalmopathy, sarcoid-
osis,104 cat scratch disease,64 and even posterior scleritis.156
In a retrospective study from Germany, 49 children with
orbital swelling were reviewed.192 In 20 (40.8%), the signs were
unrelated to OC and were attributed to atheroma, inflamed
insect stings, dental abscesses, conjunctivitis, Herpes simplex
infection, and an orbital tumor.
9. Imaging

CT scan is the imaging modality of choice in the diagnosis and

8. Differential diagnosis
Various conditions can mimic OC, with the characteristics of
proptosis, chemosis, and periorbital swelling. In order to
ascertain the correct diagnosis, a thorough history, physical
examination, laboratory, and imaging information are
indispensible.108
The differential diagnosis is quite extensive.20,73 A primary
neoplasm, most commonly rhabdomyosarcoma88 or retino-
blastoma,186 or even a malignant melanoma, can mimic OC.131
Additionally, various types of leukemia and lymphomas are
included in the differential diagnosis, such as acute leuke-
mia,12 ocular adnexal T-cell lymphoma,175 extranodal and
natural killer/T-cell lymphoma (Fig. 5).99 Metastatic neo-
plasms to the orbit may mimic OC, such as esophageal
monitoring of patients with OC. Cases with periorbital inflam-
mation, severe eyelid edema, proptosis, ophthalmoplegia, and
deteriorating visual acuity or color vision must be subjected to
an orbital CT scan.32,81,157 Additional indications include the
presence of central nervous system signs, no improvement or
deterioration of the patient’s condition within 24 hours, and
nonresolving pyrexia over 36 hours.86
CT provides imaging data of the anatomic elements of the
orbit, such as the orbital walls, extraocular muscles, optic
nerve, adipose tissue, and paranasal sinuses (Fig. 7). There-
fore, orbital infections and lesions can be recognized, espe-
cially in cases where clinical examination is not adequate for
the diagnosis.157 Additionally, CT provides information on the
extension of the inflammatory changes in the orbital struc-
tures, identification of potential sources of the infection such
as sinus disease, and the presence of a foreign body.107,108 CT

Fig. 5 e Natural killer lymphoma. A: Photo of a patient with natural killer lymphoma of the left orbit and B: coronal CT scan of
the orbits. A correct approach to the differential diagnosis of orbital cellulitis is very important for the patient’s life. Imaging
guides the diagnosis and shows a large mass that molds to the globe and is not subperiosteal in location. CT, computed
tomography.

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 s u r v e y o f o p h t h a l m o l o g y 6 3 ( 2 0 1 8 ) 5 3 4 e5 5 3
Fig. 6 e Carotid cavernous fistula. A, B: Photos of a patient
with right carotid cavernous fistula. Chemosis,
conjunctival hyperemia, proptosis, and ophthalmoplegia
are present. C: Axial CT scan of the orbits. The superior
ophthalmic vein appears enlarged. CT, computed
tomography.
is also essential in monitoring the efficacy of treatment.44 In a
10-year retrospective review of 101 pediatric cases of OC, CT
increased the prediction accuracy of cases needing surgical
intervention.107
Moreover, CT scanning provides evidence for the identifi-
cation of an orbital abscess and defines its size and location.
The recognition of subperiosteal abscesses is more accurate
with the use of CT than clinically.32 Detection of an abscess
can be difficult even with CT, however, especially at an early
stage, and should not be excluded if suspected clinically.44
Initially, the abscess appears as a density of the soft tissues,
usually at the medial orbital wall, in combination with a fluid-
filled paranasal sinus. A larger abscess appears as a fluid
collection with enhancement of its rim.44,157 Contrast media
may be used for the differentiation between an abscess and
inflammatory procedure of the orbit, as the walls of the ab-
scess enhance.107,108
Imaging studies are also essential when neurological signs
are present to exclude intracranial extension of the inflam-
mation, such as a brain abscess or CST.44
MRI is also a useful tool in the identification of the orbital
infection, especially when the CT findings are unclear. MRI
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541
Fig. 7 e CT of orbital cellulitis. Axial CT scan of the orbits of
a patient with orbital cellulitis of the right eye.
Inflammatory process in the retrobulbar fat and proptosis
of the right globe are noticed. CT, computed tomography.
provides superior resolution of orbital soft tissues compared
to CT.161 Fat-saturated T2-weighted MRI and diffusion-
weighted imaging MRI sequences are preferred96,161 because
they are sensitive in the detection of OC and help differentiate
from pathological entities that provide similar images, such as
orbital inflammatory disease or lymphoid lesions.44 Sub-
periosteal and orbital abscesses and intracranial involvement
are also better identified with MRI compared to CT. Finally,
follow-up is safer with the use of MRI, as it does not expose the
patient to radiation.161 Increased scanning time compared to
standard CT, and decreased availability of MRI, often renders
urgent imaging of the orbit impossible and are disadvantages
of this technique.108,161
Finally, ultrasonography of the orbit has been used for the
identification of orbital abnormalities; however, ultrasonog-
raphy does not have a major role in diagnosing OC.77,95 Ul-
trasonography can be useful for the detection of orbital
abscesses, especially of the anterior orbit or medial wall,
although an acute abscess is not clearly delineated.32
Generally, ultrasonography lacks sensitivity in orbital imag-
ing as compared to CT and MRI and is mostly used as an in-
office screening procedure.44
10. Treatment
10.1. Medical management
Rapid diagnosis of OC and initiation of the treatment scheme
are mandatory in order to minimize complications. Hence,
almost all patients require admission, especially when the
following signs are present: periorbital swelling, diplopia,
reduced visual acuity, abnormal light reflexes, proptosis,
ophthalmoplegia, drowsiness, vomiting, headache, and sei-
zures.86 Medical management focuses primarily on aggressive
antibiotic therapy and concurrent therapy of underlying pre-
disposing factors such as sinusitis.108 Duration of antibiotic
treatment varies from 1 to 2 weeks intravenously, followed by
oral treatment in order to complete a 4-week regimen
(Table 1).104 Clinical signs should be assessed at least twice
daily along with frequent laboratory and imaging investiga-
tion (Fig. 8). In case a complication is suspected, hourly eval-
uation of the patient should be performed.86 On discharge
 542
Table 1 e Summary table of the largest studies on orbital cellulitis during the last 18 years
Study Year, Total Mean age Duration of Number of Commonest Commonest Three major Main Number of Imaging
group country number of (years) hospital patients symptoms predisposing organisms intravenous patients method
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orbital orbital/ used surgery (%)

cellulitis subperiosteal
abscess (%)

Ferguson 1999, Pediatric 3 months 6.2 32.4 Proptosis Sinus disease Streptococcus Third- 73.5 CT
and Australia group: 34 e16 years Ophthalmoplegia viridans generation
McNab61 Fever >37.5
C Staphylococcus cephalosporin
Leukocytosis aureus Flucloxacillin
Decreased visual acuity Anaerobic bacteria Metronidazole
Chemosis
Ferguson 1999, Adult group: 18 17 6.4 22.2 Ophthalmoplegia Sinus disease S. aureus Third- 33.3 CT

s u r v e y o f o p h t h a l m o l o g y 6 3 ( 2 0 1 8 ) 5 3 4 e5 5 3
and Australia e86 years Proptosis Dacyrocystitis Staphylococcus generation
McNab61 Leukocytosis Retained metallic epidermidis cephalosporin
Decreased visual acuity foreign body Staphylococcus Flucloxacillin
Chemosis Uveitis leading to coagulase (e) Metronidazole
Fever >37.5
C panophthalmitis Vancomycin
Secondary infected Amoxicillin/
nasal penicillin
neuroblastoma
Oxford and 2005, USA 95 7.3 5.9 46.3 Restricted ocular Sinusitis Streptococcus 37.5 CT
McClay136 motility milleri
Visual loss Hemolytic
Nonreactive pupil Streptococcus
Neurological deficits Staphylococcus
Seizures aureus
Nageswaran 2006, USA 41 7.5  5.0 5.8  2.9 83 Proptosis Sinusitis (ethmoid Nonhemolytic Ampicillin- 71 CT
et al.128 Fever sinusitis in 98%) streptococcus sulbactam
Ophthalmoplegia Group A Nafcillin þ third-
White blood cell count -hemolytic generation
increase Streptococcus cephalosporin
Peptostreptococcus Clindamycin þ
third-generation
cephalosporin
Liu et al.112 2006, Sum: 27 41.5 (3 29.6 Erythematous swelling Sinusitis First-generation 18.5 CT
Taiwan e83 years) Ophthalmoplegia Upper respiratory cephalosporin þ
Chemosis infection aminoglycoside
Proptosis Tumor
CRP elevation Diabetes
Fever Hypertension
Blurred vision Dacryoadenitis
Headache/drowsiness Dental abscess
Leukocytosis Dacryocystitis
Diplopia Endophthalmitis
Discharge/tearing Malignancy
Abnormal pupillary Bacteremia
 reflex Open wound
Entropion/ectropion Foreign body
ESR elevation Postevisceration
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hemorrhage
Liu et al.112 2006, Pediatric 11.4 S aureus Oxacillin
Taiwan group: 8 S. coagulase() First-generation
cephalosporin
Aminoglycoside
Liu et al.112 2006, Adult group: 19 13.8 S. aureus Aminoglycoside
Taiwan Pseudomonas First-generation
aeruginosa cephalosporin
S. viridans Vancomycin
Uy and 2007, 35 17.1  18.6 17  22 11.4 Lid swelling Lid infection Staphylococcus Cloxacillin 63 CT
Tuano182 Philippines Ophthalmoplegia Sinusitis spp. Penicillin þ

s u r v e y o f o p h t h a l m o l o g y 6 3 ( 2 0 1 8 ) 5 3 4 e5 5 3
Chemosis Dental abscess Alcaligenes spp. chloramphenicol
Proptosis Respiratory tract Escherichia spp. Cloxacillin þ
Decreased vision Infection Enterococcus spp. chloramphenicol
Fever Eyelid trauma Peptococcus spp.
Neurological changes Panophthalmitis Serratia spp.
Fundus changes Systemic illness Streptococcus spp.
Afferent pupil defect
Resistance to
retrodisplacement,
exposure keratopathy,
intraocular pressure
rise
Chaudhry 2007, Saudi 218 25.7 8.9 53.2 Swelling Sinusitis Staphylococcus Cephalosporins 72.9 CT
et al.34 Arabia Proptosis Trauma spp. Aminoglycosides
Restricted motility Endophthalmitis Streptococcus spp. Flucloxacillin
Pain Orbital implants Propionibacterium Vancomycin
Decreased visual acuity Dacryocystitis acnes
Ptosis Dental infection
Headache Retained foreign
Diplopia body
RAPD Scleral buckle
Sinusitis and
trauma
Tumors
McKinley 2007, USA 38 6.8 (1 week S. aureus, S. 60.5 CT
et al.117 e16 years) coagulase ()
S. pneumoniae
Botting 2008, New 35 7.5 5.9 Proptosis Sinus infection S. aureus Cefuroxime 23 CT
et al.22 Zealand Fever Trauma Streptococcus co-amoxicillin/
Diplopia pyogenes clavulanic acid
Vomiting
Ophthalmoplegia
Vision affected

543
(continued on next page)
 544
Table 1 e (continued )
Study Year, Total Mean age Duration of Number of Commonest Commonest Three major Main Number of Imaging
group country number of (years) hospital patients symptoms predisposing organisms intravenous patients method
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orbital orbital/ used surgery (%)

cellulitis subperiosteal
abscess (%)

Fanella 2011, 38 7.5 (1 7.0  2.7 42.1 Eye swelling Sinusitis (ethmoid S. pyogenes Cefuroxime 21.1 CT
et al.57 Canada e16 years) Fever sinusitis and S. aureus Clindamycin þ
Eye pain Pansinusitis) S. viridans cephalosporin
Coryza Cloxacillin þ
Proptosis cefotaxime
Abnormal extraocular
movements

s u r v e y o f o p h t h a l m o l o g y 6 3 ( 2 0 1 8 ) 5 3 4 e5 5 3
Headache
Cough
Huang 2011, 64 6.95  5.37 12 days (e6 56.2 Diplopia Sinusitis S. aureus Amoxicillin- 46.9 CT
et al.86 Taiwan (12 days years: 9.16 Vision S. viridans clavulanate
e18 years) and for 7e18 Proptosis S. coagulase () Cefuroxime þ
years: 13.17) Chemosis gentamicin
Purulent rhinorrhea Oxacillin þ
Fever gentamicin
Increase of WBCs
Increase of C-reactive
protein
Pandian 2011, India Sum: 33 13.69  9.76 Visual acuity Injury Methicillin- Gentamicin CT
et al.139 deterioration Sinusitis resistant Penicillin
Staphylococcus Cloxacillin
aureus
S. coagulase (), S.
pyogenes
Pandian 2011, India Pediatric 4 10.5
et al.139 group: 19
Pandian 2011, India Adult group: 14 45 7.1
et al.139
Bagheri 2012, Iran 39 27.4  23.9 6.3  3.8 46.2 Lid redness Sinusitis S. aureus Ceftazidime 48.7 CT/MRI
et al.13 (6 months Lid edema Periocular surgery Streptococcus b Cloxacillin
e48 years) Ophthalmoplegia Trauma ehemolytic Gentamicin
Periocular pain Klebsiella Cephalothin
Proptosis Ceftriaxone
Clinical abscess Vancomycin
Reduced vision
Ptosis
Ozkurt 2014, 19 18.79  10.05  3.93 (5 78.9 Periorbital erythema Sinusitis Ceftriaxone 63.2 CT
et al.137 Turkey 18.01 (2 e18) and edema Oornidazole
e62 years) Limited eye Clindamycin
movements
Proptosis
Visual loss
 Sharma 2015, 101 7.1  4.0 6.1  2.9 71.3 Sinusitis S. pyogenes 29.7 CT
et al160 Canada S. Coagulase ()
Haemophilus
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influenzae
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Friling 2014, Israel 51 6.1 (0.5 39.2 Fever (>38
C) Sinusitis S. pneumoniae Ceftriaxone þ 19.6 CT
et al.64 e17 years) RAPD (ethmoidal, Anaerobic clindamycin
Proptosis maxillary sinuses, bacteria Cefazolin
Extraocular motility frontal sinuses) S. aureus Cefuroxime
restriction
Ocular pain
Marchiano USA, 2016 14,149 28.0 þ 26.0 3.7 þ 3.4 Diplopia Sinusitis 12.1
et al.116 Conjunctival edema
Exophthalmos
Crosbie Scotland, 30 76.7 Sinusitis S. pyogenes Cefotaxime þ 83.3 CT/MRI
et al.40 2016 Streptococcus flucloxacillin

s u r v e y o f o p h t h a l m o l o g y 6 3 ( 2 0 1 8 ) 5 3 4 e5 5 3
anginosus
H. influenzae
Elshafei Egypt, 2017 102 25.56 þ 6.76  2.58 15.7 Proptosis Paranasal sinusitis Vancomycin þ 19.6 CT
et al.54 18.87 (2 Periorbital edema Orbital trauma ceftazidime
e70 years) Tenderness Panophthalmitis Clindamycin
Restriction of ocular secondary to Metronidazole
motility extension of
Fever infection from the
RAPD globe
Fever Dental abscess
Punctate keratitis

CT, computed tomography; MRI, magnetic resonance imaging; CRP, C reactive protein, ESR, erythrocyte sedimentation rate; RAPD, relative afferent pupillary defect; WBC, white blood cells.

545
546 s u r v e y o f o p h t h a l m o l o g y 6 3 ( 2 0 1 8 ) 5 3 4 e5 5 3

Ophthalmic and systemic examinaon

Imaging if:

Periorbital Edema Fever

Proptosis Headache • Periorbital inflammaon
Ophthalmoplegia + Drowsiness • Severe eyelid edema
Visual acuity Voming • Proptosis
Color vision • Ophthalmoplegia
Pupillary reflex • Deteriorang visual acuity
• Deteriorang color vision
+
Admission when suspected Chandler II, III, IV, V • Central nervous system signs
• No improvement/deterioraon within 24 hours
• Non-resolving pyrexia within 36 hours

Medical Management Laboratory check

• Prompt empirical IV anbioc • Culture and sensivity

CT scan/ MRI
administraon • Full blood count
(Third-generaon Cephalosporin +
Flucloxacillin) • Extent of Orbital inflammaon
• When culture and sensivity results are • Sinus assessment
available change accordingly if necessary • Brain MRI (when brain infecon is suspected)
• Systemic steroids
• Nasal Hygiene

No abscess Subperiosteal/Orbital abscess Intracranial complicaon

• Systemic examinaon every 4 hours

• Ophthalmological examinaon every 12 hours • Retained foreign body
• Laboratory check every 24 hours • Paranasal or frontal sinus infecon
• If a complicaon is suspected: Hourly ophthalmological and systemic • Dental source of the infecon
assessment is indicated • Intracranial complicaons
• Large dimensions of the abscess

Clinical Improvement No Clinical improvement or No Yes

deterioraon within 24-36
hours

Connue with Medical Expectant Emergent Surgical

Management observaon Surgical Management Management
treatment and checks
Repeat CT

+
• Close clinical monitoring
Consider adding Metronidazole or Clindamycin • Repeat Orbital CT scan

Fig. 8 e General guidelines for the management of orbital cellulitis. Laboratory check, indications for imaging, medical and
surgical treatment plan, ophthalmological, and systemic examinations are presented. CT, computed tomography; MRI,
medical resonance imaging.

from the hospital, patients usually continue treatment with
oral antibiotics for varying periods of time.32
Initiation of intravenous antibiotics must be immedi-
ate.86,108 The mainstay of therapy for OC is empiric coverage
with broad-spectrum antibiotics against the most common
pathogens; however, cultures should be obtained, and when
needed, treatment is altered accordingly. Empiric treatment
depends on the incidence of pathogens producing OC in each
geographic area and the age of the patient.
The regimens described in the literature have been incon-
sistent because the pathogens leading to OC vary among
different geographic locations.86 Generally, antibiotic protocol
depends on local microbiological sensitivities. A well-accepted
proposed treatment scheme includes a broad-spectrum anti-
biotic, specifically a third-generation cephalosporin such as
ceftriaxone with flucloxacillin. This scheme is effective against
most usual bacteria, both gram-positive and gram-negative
bacteria. Coverage for anaerobic bacteria is initiated in cases
where there is no clinical improvement or in case of pyrexia
after 24e36 hours after initiation of treatment. Metronidazole
or clindamycin is preferred.40,108 As previously mentioned,
children younger than 9 years present simpler infections,
usually caused by a single aerobic pathogen, that respond easily
to medical treatment. Older children and adults present more
often with infections caused by multiple aerobic and anaerobic
organisms, which may necessitate both medical and surgical
treatment.34,74 In cases that MRSA is suspected, vancomycin is
administered.86
Various studies worldwide advocate treatment regimens
used in their centers. The American Academy of Pediatrics
advises that empiric treatment should target against the most
common pathogens (S. pneumoniae, H. influenzae, and M.
catarrhalis).9 Based on this, Lee and colleagues prefer empiric
coverage against gram-positive organisms, since Staphylo-
coccus and Streptococcus species are the most common patho-
gens.108 Specifically, empiric use of vancomycin is
recommended, based on the reported increased incidence of
Community-acquired MRSA infections. They also advocate
the use of cefotaxime and metronidazole or clindamycin to
provide concurrent coverage against gram-negative and
anaerobic organisms. Empiric antibiotic treatment should in
general cover against sinus pathogens, prevent b-lactamase
resistance, and penetrate cerebrospinal fluid.137 In a study
from the United Kingdom, contemporary empiric treatment
with cefuroxime and metronidazole is advocated.86 Chaudhry
and colleagues in a center in Saudi Arabia use a combination
of a third-generation cephalosporin and flucloxacillin for the
coverage against Staphylococcus, Streptococcus, and Haemophilus
species.32 Friling and colleagues from Israel treat OC with
ceftriaxone and clindamycin, which cover against penicillin-
resistant S. pneumoniae, anaerobic bacteria, and S. aureus.65
Abdouramani and colleagues in Cameroon treat with

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 s u r v e y o f o p h t h a l m o l o g y 6 3 ( 2 0 1 8 ) 5 3 4 e5 5 3
ceftriaxone, gentamicin, and metronidazole for concurrent
coverage against aerobic and anaerobic organisms.2
Aggressive intervention is required in cases of intracra-
nial complications, with a multidisciplinary approach of
oculoplastic surgeons, otolaryngologists, neurosurgeons,
and experts in infectious diseases.32 Medical treatment of
intracranial complications includes wide-spectrum antibi-
otics that exhibit anaerobic coverage and central nervous
system penetration.67,153 In early stages of cerebritis, when
the brain abscess is not yet formed, aggressive antimicrobial
treatment may prevent abscess formation. Penicillin, chlor-
amphenicol, third-generation cephalosporins, and metroni-
dazole penetrate well into the intracranial space and
combined are effective against most responsible patho-
gens.17 After the brain abscess has formed, the surgical
treatment is combined with a long course of antibiotics
(4e8 weeks). Mannitol, hyperventilation, and steroids are
also used for the increased intracranial pressure.23
CST is generally treated with broad-spectrum antibiotics
that cover against aerobic and anaerobic organisms (vanco-
mycin, cephalosporin, and metronidazole).170 Anticoagulants
are additionally used to prevent further thrombosis and to
dissolve the clot; however, treatment with anticoagulants in
these cases is still controversial.149,174 Steroids are used to
reduce edema and inflammatory process.149,170 Prompt sur-
gical intervention is essential in cases with CST.174
Adjunctive use of corticosteroids is considered favorable
together with the appropriate antibiotics, in the management
of OC particularly after clinical improvement is noted. Intra-
venous corticosteroids moderate the inflammatory process
and decrease the levels of inflammatory cytokines.66,197 Ste-
roids, however, are contraindicated in cases of fungal OC or in
immunocompromised individuals because of their immuno-
suppressive effects and the potential risk of delaying or pre-
venting the resolution of the primary infection. Steroid use for
the control of cerebral edema can present disadvantages.
Steroids retard the encapsulation of the abscess, reduce the
antibiotic potency, and influence CT scans. Hence, their use in
these cases should be cautious,23 and each case must be
carefully evaluated before steroids are administered.108
Antifungals should be considered in cases that do not
respond to first-line therapy, especially at high-risk pop-
ulations. In cases of fungal infection, treatment focuses on
fixing the underlying metabolic abnormalities, along with
intravenous antifungal therapy and surgical debridement of
the affected tissues. Orbital exenteration may be necessary in
nonresponding cases of fungal infections in order to avoid
fatal complications.60,91,181
Finally, it is important that simultaneous sinusitis is
treated, along with medical treatment of OC, with aggressive
nasal hygiene, decongestants, saline nasal irrigation, and
intranasal corticosteroids.26,108
10.2. Surgical management
Surgical management in cases of OC includes drainage of
orbital abscesses, sinus surgery and treatment of intracranial
complications.
Orbital abscesses, apart from aggressive antibiotic treat-
ment, often require prompt drainage; however, the necessity
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547
of surgical treatment of a subperiosteal or orbital abscess is
not clearly defined.86,173 Delayed drainage is likely to lead to
serious complications and poor visual outcomes. On the other
hand, an abscess may resolve with medical therapy alone,
avoiding the likelihood of complications from surgery such as
infection seeding.79,86,152
There are reports that propose surgery in high-risk cases
such as children over the age of 10 years in whom complex
infections are more common, the presence of anaerobes is
more frequent, and extension of the abscesses more
likely.75,79,108 Patients younger than 10 years with OC are more
likely to respond to medical therapy without surgical
drainage.26,72 Harris and colleagues consider that, with this
approach, the formation of an orbital abscess or the intra-
cranial extension of the infection can be prevented.79 Addi-
tionally, medial or inferior abscesses are more likely to
respond to medical treatment,26,67,79,86,152 whereas cases of a
superior abscess or an abscess at the orbital apex may require
surgical drainage.108 Other factors considered for surgical
treatment include the presence of severe signs such as
compromised vision, pupillary changes, raised intraocular
pressure, proptosis of over 5 mm, and failure to respond to
medical therapy.102 Patients with optic nerve or retinal
compromise from compression by the abscess also require
emergent drainage.72
The presence of a retained foreign body, a concurrent
paranasal or frontal sinus infection, an identified dental
source of the infection, the presence of intracranial compli-
cations, and the large abscesses also constitute high-risk
factors that may require surgical treatment.34,67,72,86,89,108,171
Iatrogenic foreign bodies that lead to orbital infection, such
as scleral buckles and glaucoma drainage devices, require
urgent removal.108 Organic foreign bodies must be immedi-
ately surgically removed, as they carry a high risk of severe
infections and complications. The treatment approach is
empiric antibiotic therapy, immediate removal of the foreign
body, simultaneous removal of the necrotic tissue, acquisition
of cultures during surgery, and change of antibiotic therapy
according to culture results.179 Usually, the entrance of the
surgical incision for the foreign body removal is the original
wound, as less injury is caused. If the wound has healed, the
surgical approach depends on the location of the injury and
the size of the foreign body. Finally, caution is required during
removal of wooden foreign bodies because they tend to break
into multiple pieces.110
An individualized treatment scheme is generally recom-
mended.32 Jain and Rubin suggested the following categori-
zation to guide the choice of the treatment modality in cases
with orbital abscesses: patients requiring emergent drainage,
patients who may need urgent drainage, and patients sub-
jected in expectant observation.72,89 Close clinical monitoring
is indicated, including careful evaluation of the optic nerve
function, the pupillary reflexes, visual acuity and the level of
consciousness, along with repeated orbital CT scans, so that
surgical intervention can be offered when needed.32
There are different techniques for surgical removal of
subperiosteal and orbital abscesses.178 The traditional
external method for medial abscesses is performed through
Lynch incision, which offers adequate visibility and effective
drainage but leaves a visible scar, unpleasant in the pediatric
548 s u r v e y o f o p h t h a l m o l o g y 6 3 ( 2 0 1 8 ) 5 3 4 e5 5 3
population. This indicates why transnasal endoscopic surgery
represents a great advance. Factors that guide the surgical
approach of choice include location of the abscess and
radiographic findings. Successful transnasal endoscopic sur-
gery is reported in patients with medial-based subperiosteal
orbital abscesses, whereas superolateral extension requires
an external approach.152,178 Migirov and colleagues have
suggested endoscopic sinus surgery in the treatment of
medial orbital abscesses.121,122 Another report from the
United States suggests a combined endoscopic and trans-
caruncular surgical approach to medial orbital subperiosteal
abscesses for an effective and cosmetically superior
outcome.145
In cases with intracranial complications, surgical treat-
ment is indicated and should be planned promptly after
diagnosis, given that a delay in surgical drainage and
decompression of brain abscesses is related to high
morbidity and mortality.23 Cases of OC with concurrent
frontal sinusitis and complex infections with anaerobes are
candidates for surgical management because of the
increased risk of intracranial extension.32 Surgical drainage
of the concomitant sinus infection and any orbital or other
adjacent abscesses, such as a periodontal abscess, should
also be performed concomitantly.168 A study from New York
that reviewed pediatric cases of intracranial infections
associated with sinusitis and OC concluded that all patients
with intracranial extension of the infection require surgical
intervention. Over 90% of patients were subjected to a
combination of 2 or more surgical procedures such as
craniotomy, orbital surgery, and sinus surgery.153 In cases
with CST, surgery should be performed promptly after
diagnosis. Surgical intervention is also indicated in the
treatment of the bacterial sinusitis that precipitates CST,
such as endoscopic sinus surgery.170
11. Conclusion
Morbidity and mortality from OC have decreased over the
past decades; however, OC still may lead to serious
ophthalmic, neurologic, and even fatal complications. Early
diagnosis and management are crucial for the preservation
of vision and diminution of complications. Ongoing research
into new antibiotic agents may further benefit the care of
patients presenting with the disease. Future studies may
also help better define prognostic criteria based on imaging
to stratify risk and identify cases that require early inter-
vention. Comprehension of clinical manifestations, predis-
posing factors, microbiology, and management of the
disease is necessary. A multidisciplinary approach is indis-
pensable for responsible monitoring and management of the
disease.
11.1. Literature search
An extensive literature research has been performed in the
MEDLINE database (PubMed) and included surveys published
until 2016. The below key words were used: Orbital cellulitis
AND predisposing factors, age, sinusitis, epidemiology,
microbiology, classification, differential diagnosis, imaging
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and management. Articles that reported the possible causa-
tive organisms, and their correlation to geographic distribu-
tion were thoroughly studied. There was no language
restriction. References cited in the articles were also studied.
In the present review, 197 studies were evaluated, which
were published from the year 1948 to 2017. The included
studies comprise data of OC coming from various geographic
locations (North and South America, Europe, Africa, Australia,
and Asia), and regarding different age groups (childhood,
young adults, patients over 60 years), etiologic factors, clinical
manifestations, complications, and treatment modalities of
cellulitis.
12. Disclosure
There was no funding for this study. The authors report no
proprietary or commercial interest in any product mentioned
or concept discussed in this article.
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