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Major review

Orbital cellulitis

Theodora Tsirouki, MD, PhDa, Anna I. Dastiridou, MD, PhDa,Nuria Ibanez flores, MDb, Johnny Castellar Cerpa, MDb,Marilita M. Moschos, MD, PhDc, Periklis Brazitikos, MD, PhDd,Sofia Androudi, MD, PhDa,*aDepartment of Ophthalmology, University of Thessaly, Larissa, Greeceb Institut Catala de Retina, Barcelona, SpaincDepartment of Ophthalmology, University of Athens, Athens, Greeced2nd Department of Ophthalmology, Aristotle University, Thessaloniki, Greece

a r t i c l e i n f o

Article history:

Received 23 December 2016

Received in revised form 22

November 2017

Accepted 7 December 2017

Available online 15 December 2017

Keywords:

orbital cellulitis

intracranial abscess

orbital abscess

vision loss

antibiotics

diagnosis

management

* Corresponding author: Sofia Androudi, ME-mail address: androudi@otenet.gr (S. A

0039-6257/$ e see front matter ª 2017 Elsevhttps://doi.org/10.1016/j.survophthal.2017.12

a b s t r a c t

Orbital cellulitis (OC) is an inflammatory process that involves the tissues located posterior

to the orbital septum within the bony orbit, but the term generally is used to describe

infectious inflammation. It manifests with erythema and edema of the eyelids, vision loss,

fever, headache, proptosis, chemosis, and diplopia. OC usually originates from sinus

infection, infection of the eyelids or face, and even hematogenous spread from distant

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

declined with advances in diagnostic and therapeutic options; however, OC can still lead to

serious sight- and life-threatening complications in the modern antibiotics era. Therefore,

prompt diagnosis and treatment remain crucial. Antibiotic coverage, computed tomo-

graphy imaging, and surgical intervention when needed have benefitted patients and

changed the disease prognosis. We review the worldwide characteristics of OC, predis-

posing factors, current evaluation strategies, and management of the disease.

ª 2017 Elsevier Inc. All rights reserved.

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 septumwithin 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

D, PhD, Department of Ondroudi).ier Inc. All rights reserved.001

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.

phthalmology, University of Thessaly, Larissa 412 22, Greece.

.

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

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 fromCanada53 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, traumawas reported as amore common cause

Fig. 1 e Foreign body causing endophthalmitis and orbital celluli

the left eye and B: axial CT scan of the orbits. A metal intraocu

conjunctiva is causing endophthalmitis and orbital cellulitis of t

not always necessary, the foreign body in this case must be rem

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

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 andmay bemisdiagnosed as air. After a fewmonths 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 themajor 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

tis. A: Photo of a patient with an intraocular foreign body of

lar foreign body with the entry wound in the medial

he left orbit. Although removal of metallic foreign bodies is

oved. CT, computed tomography.

s u r v e y o f o p h t h a lmo l o g y 6 3 ( 2 0 1 8 ) 5 3 4e5 5 3536

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-

nosedwith 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 theWestern and developingworld, 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 fromTexas examined childrenwith 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 inWestern studies, directly associatedwith 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%

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 generallymore

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-

fectionsvaries from21%to72%.20,112,119,194Community-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 Pena 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. Pena 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 lm o l o g y 6 3 ( 2 0 1 8 ) 5 3 4e5 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 originmainly

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 withmedical 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

Fig. 2 e Imaging of paranasal sinuses in various age groups. Co

child, B: 14-year-old child with mucosal thickening of the parana

the sinus cavities narrow, creating convenient conditions for th

explanation why in children younger than 10 years, treatment

children, the combination of medical and surgical intervention

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

ronal CT scan of the paranasal sinuses of A: a 6-year-old

sal sinuses and C: a 19 year-old child. With age, the ostia of

e development of anaerobic pathogens. This is probably an

with medical therapy alone is adequate, whereas in older

is often necessary. CT, computed tomography.

s u r v e y o f o p h t h a lmo l o g y 6 3 ( 2 0 1 8 ) 5 3 4e5 5 3538

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%), erythemaof periorbital tissues, andperiocular

pain or pain with eyemovement (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.

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 Patientswith 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 lm o l o g y 6 3 ( 2 0 1 8 ) 5 3 4e5 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,manypatientswithOC 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% inmore 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

Fig. 4 e Subperiosteal abscess. A: Photo of a patient with a subp

orbits, and C: coronal CT scan of the orbits. The abscess is the r

periorbita and the orbital bone. It is located at the orbital roof. T

material. CT, computed tomography.

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 themost 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

eriosteal abscess of the right orbit, B: sagittal CT scan of the

esult of the accumulation of purulent material between the

he right frontal sinus appears opacified and full of purulent

s u r v e y o f o p h t h a lmo l o g y 6 3 ( 2 0 1 8 ) 5 3 4e5 5 3540

2005 reported palsies of cranial nerves II, III, IV, and VI as a

result of CSTwith 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

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 amalignantmelanoma, canmimic 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

Fig. 5 eNatural killer lymphoma. A: Photo of a patient with natur

the orbits. A correct approach to the differential diagnosis of orb

guides the diagnosis and shows a large mass that molds to the

tomography.

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

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

al killer lymphoma of the left orbit and B: coronal CT scan of

ital cellulitis is very important for the patient’s life. Imaging

globe and is not subperiosteal in location. CT, computed

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.

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.

s u r v e y o f o p h t h a lm o l o g y 6 3 ( 2 0 1 8 ) 5 3 4e5 5 3 541

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 themedial 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

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

frompathological 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 saferwith the use ofMRI, 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

Table 1 e Summary table of the largest studies on orbital cellulitis during the last 18 years

Studygroup

Year,country

Totalnumber of

patients withorbitalcellulitis

Mean age(years)

Duration ofhospital

stay (days)

Number ofpatients

presentingorbital/

subperiostealabscess (%)

Commonestsymptomsdescribed

Commonestpredisposing

factors

Three majororganismsinvolved

Mainintravenousantibiotics

used

Number ofpatients

submitted insurgery (%)

Imagingmethod

Ferguson

and

McNab61

1999,

Australia

Pediatric

group: 34

3 months

e16 years

6.2 32.4 Proptosis

Ophthalmoplegia

Fever >37.5�CLeukocytosis

Decreased visual acuity

Chemosis

Sinus disease Streptococcus

viridans

Staphylococcus

aureus

Anaerobic bacteria

Third-

generation

cephalosporin

Flucloxacillin

Metronidazole

73.5 CT

Ferguson

and

McNab61

1999,

Australia

Adult group: 18 17

e86 years

6.4 22.2 Ophthalmoplegia

Proptosis

Leukocytosis

Decreased visual acuity

Chemosis

Fever >37.5�C

Sinus disease

Dacyrocystitis

Retained metallic

foreign body

Uveitis leading to

panophthalmitis

Secondary infected

nasal

neuroblastoma

S. aureus

Staphylococcus

epidermidis

Staphylococcus

coagulase (e)

Third-

generation

cephalosporin

Flucloxacillin

Metronidazole

Vancomycin

Amoxicillin/

penicillin

33.3 CT

Oxford and

McClay1362005, USA 95 7.3 5.9 46.3 Restricted ocular

motility

Visual loss

Nonreactive pupil

Neurological deficits

Seizures

Sinusitis Streptococcus

milleri

Hemolytic

Streptococcus

Staphylococcus

aureus

37.5 CT

Nageswaran

et al.1282006, USA 41 7.5 � 5.0 5.8 � 2.9 83 Proptosis

Fever

Ophthalmoplegia

White blood cell count

increase

Sinusitis (ethmoid

sinusitis in 98%)

Nonhemolytic

streptococcus

Group A

-hemolytic

Streptococcus

Peptostreptococcus

Ampicillin-

sulbactam

Nafcillin þ third-

generation

cephalosporin

Clindamycin þthird-generation

cephalosporin

71 CT

Liu et al.112 2006,

Taiwan

Sum: 27 41.5 (3

e83 years)

29.6 Erythematous swelling

Ophthalmoplegia

Chemosis

Proptosis

CRP elevation

Fever

Blurred vision

Headache/drowsiness

Leukocytosis

Diplopia

Discharge/tearing

Abnormal pupillary

Sinusitis

Upper respiratory

infection

Tumor

Diabetes

Hypertension

Dacryoadenitis

Dental abscess

Dacryocystitis

Endophthalmitis

Malignancy

Bacteremia

First-generation

cephalosporin þaminoglycoside

18.5 CT

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542

reflex

Entropion/ectropion

ESR elevation

Ecchymosis/

hemorrhage

Open wound

Foreign body

Postevisceration

Liu et al.112 2006,

Taiwan

Pediatric

group: 8

11.4 S aureus

S. coagulase(�)

Oxacillin

First-generation

cephalosporin

Aminoglycoside

Liu et al.112 2006,

Taiwan

Adult group: 19 13.8 S. aureus

Pseudomonas

aeruginosa

S. viridans

Aminoglycoside

First-generation

cephalosporin

Vancomycin

Uy and

Tuano182

2007,

Philippines

35 17.1 � 18.6 17 � 22 11.4 Lid swelling

Ophthalmoplegia

Chemosis

Proptosis

Decreased vision

Fever

Neurological changes

Fundus changes

Afferent pupil defect

Resistance to

retrodisplacement,

exposure keratopathy,

intraocular pressure

rise

Lid infection

Sinusitis

Dental abscess

Respiratory tract

Infection

Eyelid trauma

Panophthalmitis

Systemic illness

Staphylococcus

spp.

Alcaligenes spp.

Escherichia spp.

Enterococcus spp.

Peptococcus spp.

Serratia spp.

Streptococcus spp.

Cloxacillin

Penicillin þchloramphenicol

Cloxacillin þchloramphenicol

63 CT

Chaudhry

et al.342007, Saudi

Arabia

218 25.7 8.9 53.2 Swelling

Proptosis

Restricted motility

Pain

Decreased visual acuity

Ptosis

Headache

Diplopia

RAPD

Sinusitis

Trauma

Endophthalmitis

Orbital implants

Dacryocystitis

Dental infection

Retained foreign

body

Scleral buckle

Sinusitis and

trauma

Tumors

Staphylococcus

spp.

Streptococcus spp.

Propionibacterium

acnes

Cephalosporins

Aminoglycosides

Flucloxacillin

Vancomycin

72.9 CT

McKinley

et al.1172007, USA 38 6.8 (1 week

e16 years)

S. aureus, S.

coagulase (�)

S. pneumoniae

60.5 CT

Botting

et al.222008, New

Zealand

35 7.5 5.9 Proptosis

Fever

Diplopia

Vomiting

Ophthalmoplegia

Vision affected

Sinus infection

Trauma

S. aureus

Streptococcus

pyogenes

Cefuroxime

co-amoxicillin/

clavulanic acid

23 CT

(continued on next page)

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Table 1 e (continued )

Studygroup

Year,country

Totalnumber of

patients withorbitalcellulitis

Mean age(years)

Duration ofhospital

stay (days)

Number ofpatients

presentingorbital/

subperiostealabscess (%)

Commonestsymptomsdescribed

Commonestpredisposing

factors

Three majororganismsinvolved

Mainintravenousantibiotics

used

Number ofpatients

submitted insurgery (%)

Imagingmethod

Fanella

et al.572011,

Canada

38 7.5 (1

e16 years)

7.0 � 2.7 42.1 Eye swelling

Fever

Eye pain

Coryza

Proptosis

Abnormal extraocular

movements

Headache

Cough

Sinusitis (ethmoid

sinusitis and

Pansinusitis)

S. pyogenes

S. aureus

S. viridans

Cefuroxime

Clindamycin þcephalosporin

Cloxacillin þcefotaxime

21.1 CT

Huang

et al.862011,

Taiwan

64 6.95 � 5.37

(12 days

e18 years)

12 days (e6

years: 9.16

and for 7e18

years: 13.17)

56.2 Diplopia

Vision

Proptosis

Chemosis

Purulent rhinorrhea

Fever

Increase of WBCs

Increase of C-reactive

protein

Sinusitis S. aureus

S. viridans

S. coagulase (�)

Amoxicillin-

clavulanate

Cefuroxime þgentamicin

Oxacillin þgentamicin

46.9 CT

Pandian

et al.1392011, India Sum: 33 13.69 � 9.76 Visual acuity

deterioration

Injury

Sinusitis

Methicillin-

resistant

Staphylococcus

aureus

S. coagulase (�), S.

pyogenes

Gentamicin

Penicillin

Cloxacillin

CT

Pandian

et al.1392011, India Pediatric

group: 19

4 10.5

Pandian

et al.1392011, India Adult group: 14 45 7.1

Bagheri

et al.132012, Iran 39 27.4 � 23.9

(6 months

e48 years)

6.3 � 3.8 46.2 Lid redness

Lid edema

Ophthalmoplegia

Periocular pain

Proptosis

Clinical abscess

Reduced vision

Ptosis

Sinusitis

Periocular surgery

Trauma

S. aureus

Streptococcus b

ehemolytic

Klebsiella

Ceftazidime

Cloxacillin

Gentamicin

Cephalothin

Ceftriaxone

Vancomycin

48.7 CT/MRI

Ozkurt

et al.1372014,

Turkey

19 18.79 �18.01 (2

e62 years)

10.05 � 3.93 (5

e18)

78.9 Periorbital erythema

and edema

Limited eye

movements

Proptosis

Visual loss

Sinusitis Ceftriaxone

Oornidazole

Clindamycin

63.2 CT

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Sharma

et al1602015,

Canada

101 7.1 � 4.0 6.1 � 2.9 71.3 Sinusitis S. pyogenes

S. Coagulase (�)

Haemophilus

influenzae

29.7 CT

Friling

et al.642014, Israel 51 6.1 (0.5

e17 years)

39.2 Fever (>38�C)RAPD

Proptosis

Extraocular motility

restriction

Ocular pain

Sinusitis

(ethmoidal,

maxillary sinuses,

frontal sinuses)

S. pneumoniae

Anaerobic

bacteria

S. aureus

Ceftriaxone þclindamycin

Cefazolin

Cefuroxime

19.6 CT

Marchiano

et al.116USA, 2016 14,149 28.0 þ 26.0 3.7 þ 3.4 Diplopia

Conjunctival edema

Exophthalmos

Sinusitis 12.1

Crosbie

et al.40Scotland,

2016

30 76.7 Sinusitis S. pyogenes

Streptococcus

anginosus

H. influenzae

Cefotaxime þflucloxacillin

83.3 CT/MRI

Elshafei

et al.54Egypt, 2017 102 25.56 þ

18.87 (2

e70 years)

6.76 � 2.58 15.7 Proptosis

Periorbital edema

Tenderness

Restriction of ocular

motility

Fever

RAPD

Fever

Punctate keratitis

Paranasal sinusitis

Orbital trauma

Panophthalmitis

secondary to

extension of

infection from the

globe

Dental abscess

Vancomycin þceftazidime

Clindamycin

Metronidazole

19.6 CT

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

survey

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545

Ophthalmic and systemic examina�on

Periorbital EdemaProptosis

OphthalmoplegiaVisual acuityColor vision

Pupillary reflex

FeverHeadache

DrowsinessVomi�ng

Admission when suspected Chandler II, III, IV, V

Laboratory check

Culture and sensi�vityFull blood count

CT scan/ MRI

Extent of Orbital inflamma�onSinus assessmentBrain MRI (when brain infec�on is suspected)

+

No abscess Subperiosteal/Orbital abscess Intracranial complica�on

Expectant observa�on

Emergent Surgical Management

Close clinical monitoringRepeat Orbital CT scan

Retained foreign bodyParanasal or frontal sinus infec�onDental source of the infec�onIntracranial complica�onsLarge dimensions of the abscess

Surgical Management

Medical Management

Prompt empirical IV an�bio�c administra�on(Third-genera�on Cephalosporin + Flucloxacillin)When culture and sensi�vity results are available change accordingly if necessarySystemic steroidsNasal Hygiene

Medical Management

Systemic examina�on every 4 hoursOphthalmological examina�on every 12 hoursLaboratory check every 24 hoursIf a complica�on is suspected: Hourly ophthalmological and systemic assessment is indicated

Clinical Improvement No Clinical improvement or deteriora�on within 24-36

hours

Consider adding Metronidazole or Clindamycin

+

Repeat CT

Imaging if:

Periorbital inflamma�onSevere eyelid edemaProptosisOphthalmoplegiaDeteriora�ng visual acuityDeteriora�ng color visionCentral nervous system signs No improvement/deteriora�on within 24 hoursNon-resolving pyrexia within 36 hours

Con�nue with treatment and checks

+

YesNo

• ••

•••••••••

•••

•••••

••

•

••

••••

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.

s u r v e y o f o p h t h a lmo l o g y 6 3 ( 2 0 1 8 ) 5 3 4e5 5 3546

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 causedby 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 themost

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 andmetronidazole 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, andHaemophilus

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

s u r v e y o f o p h t h a lm o l o g y 6 3 ( 2 0 1 8 ) 5 3 4e5 5 3 547

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

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 aremore

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

s u r v e y o f o p h t h a lmo l o g y 6 3 ( 2 0 1 8 ) 5 3 4e5 5 3548

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 andmanagement 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

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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