survey of ophthalmology 63 (2018) 534e553

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Major review Orbital cellulitis

Theodora Tsirouki, MD, PhDa, Anna I. Dastiridou, MD, PhDa, Nuria Iba´nez 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 Catala` 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 0.1 per 100,000 in children and adults, respectively.129 Orbital cellulitis (OC) is an inflammatory process that involves Morbidity and mortality of OC have declined with improve- the tissues located posteriorly to the orbital septum within the ment in diagnosis and therapy32; however, since it may still bony orbit, but the term generally is used to describe infec- have serious complications, prompt diagnosis and treatment tious inflammation. It is not as common as preseptal cellulitis are crucial.108,158,196 We review the worldwide characteristics that affects tissues anterior to the orbital septum. OC is of OC, predisposing factors, infectious causes, and current encountered at all age groups but more frequently affects the 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: [email protected] (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 survey of ophthalmology 63 (2018) 534e553 535

of OC compared to sinusitis in the age group 6e16 years.11 In 2. Predisposing factors India, injury was associated with OC in 24% of cases132 and was usually linked to the presence of a foreign body.108,195 The most frequent predisposing factor in all age groups is Foreign body OC is caused either by organic materials or secondary infection extending from the paranasal sinuses. This by metal objects (Fig. 1). Usually children and young males is established in studies in both the Western and the devel- are affected because injuries are caused during playing or at 32,34,85,188,191 oping world. Specifically, it has been determined work.49 Organic foreign bodies usually involve wood. e e that 1.3% 5.6% of sinusitis results in OC, and 0.3% 5.1% Wooden foreign bodies carry a large amount of bacteria, and 6,151 develop orbital or subperiosteal abscess. OC most if not promptly removed, they lead to severe infections.179 commonly originates from the ethmoid sinuses, with a re- These injuries are associated with a high risk of OC and 22,61,68,76,82,113,127 ported frequency of 43% to as high as 94.7% of complications such as recurrent cellulitis, cutaneous fistula, 53 cases in a study from Canada and 100% in another study from restrictive myopathy, periorbital abscess, and even pan- 8 Massachusetts. The infection proceeds from the sinuses to the ophthalmitis.164 Identification of the wooden foreign bodies orbit, assisted by specific anatomical characteristics such as the with CT can be difficult. During the first days after the injury, thin medial orbital wall, lack of lymphatics, valveless veins of wooden foreign bodies appear as low-density signal on CT 104 the orbit, and foramina of the orbital bones. scan and may be misdiagnosed as air. After a few months the Surveys that detect sinusitis radiologically find up to 91% of wooden material presents the same density as the sur- cases of sinus-related OC originate from the ethmoid and rounding tissues, making it difficult to diagnose.105 In certain 30,58 maxillary sinus. In a 10-year retrospective analysis from cases, additional imaging with magnetic resonance imaging e Taiwan, however, children aged 3 18 years diagnosed with (MRI) and especially T1-weighted images may further OC underwent computed tomography (CT) scans, and the enhance the ability to identify a wooden or vegetable foreign involved sinuses, in the order of frequency, were maxillary, body.179 Timely removal of these foreign bodies leads to 83 ethmoid, frontal, and sphenoid. In fact, childhood OC in- resolution of inflammation and associated signs.110 Metal 34,62 volves more than 1 sinus in up to 38% of cases. In a study objects are more easily identified and surgically removed from Canada, pansinusitis was observed in 15.7% of cases in from the orbit; however, most metals are inert and, 58 children. In adults, OC may be related to frontal sinus depending on their location in the orbit, may be treated 75,84,120 infection, whereas multiple sinus involvement does conservatively without removal.83 Iron, copper, and lead, 34,62 not exceed 11%. however, may cause serious complications, and gunshot Spread of the infection from the upper respiratory tract to injuries usually lead to severe ocular injury.28 the orbit is also a major cause of OC.35,38,103,176 The affinity of In Nigeria, upper respiratory tract infections and facial and OC with infections arising from the sinuses and the upper globe injuries were reported as the major predisposing factors respiratory tract reflects the seasonal distribution of the dis- for OC.14 Additionally, in children, insect bite (10%), hordeo- 34,62 ease, with peak occurrence in winter to early spring. This lum, and molluscum contagiosum of the lid with secondary is proportional to the seasonal distribution of infections bacterial infection were common predisposing factors.141 initiating in the aforementioned anatomical locations.32 In developed countries, OC is not common after ophthalmic Reported etiological factors of OC also differ between surgery; however, there are rare reports of OC after strabismus Western and developing countries. Trauma or surgery is a surgery,4,19,48 blepharoplasty,93 canaliculitis surgery,80 cataract common cause of OC in developing countries.14,32,62,90 OC surgery,101 peribulbar injection,5,84,108,120,189 sub-Tenon anes- follows either direct inoculation from a penetrating injury or thesia,111 hydroxyapatite35 and polyethylene98 orbital sockets, develops secondarily to orbital fracture that allows comm- implanted aqueous drainage devices, keratoprosthesis, and unication between the sinuses and the orbit.104 In a study silicone-sponge scleral buckle implants for rhegmatogenous from Pakistan, trauma was reported as a more common cause 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. 536 survey of ophthalmology 63 (2018) 534e553

Other etiological factors of OC include dacryocystitis, dental presented within 3 days of disease onset.14 The average re- infections from spread through the maxillary sinus,45,46 ported duration of symptoms was 5.2e10.6 days, and average endophthalmitis, panophthalmitis,142 untreated preseptal hospital stay was 9e13.7 days in the developing countries, with cellulitis, and hematogenous spread in the setting of bacter- 57.6% of cases presenting a prolonged hospital stay of more e emia from distant sources.5,30 32,34,39,62,63,65,108,125,138 In a study than 10 days.14,65,139,141 In contrast, in the Western countries, from Saudi Arabia, intraocular or orbital tumorsdspecifically the average duration of symptoms was 4.4 days, and the retinoblastoma, rhabdomyosarcoma, and melanomadwere average hospital stay was 5.8e6.2 days.58,62,130 the underlying cause in 3.7% of patients with OC.34,128 Finally, right and left orbits are almost equally affected, Finally, there are also case reports of OC from rare with the right orbit being involved in 51% of children in a study causes.101 In a study from Malaysia, swimming was consid- from Israel65 and 50.5% in a study from Saudi Arabia.34 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 4. Microbiology 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- The causative organisms associated with OC are difficult to nosed with epidemic keratoconjunctivitis than supposedly led identify because of the normal flora of the area, previous to orbital inflammation.100 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 3. Epidemiology swabs, throat swabs, and ocular secretions are generally more effective, but cultures of material recovered from orbital ab- OC is not a common condition. Incidence of the disease has scesses and sinus aspirates are the most reliable.25,108,113,141 been calculated as 1.6 per 100,000 in the pediatric population While it is commonly understood that these invasive surgi- and 0.1 per 100,000 in adults129; however, a retrospective study cal techniques are more likely to achieve a positive culture from Nigeria found that 6.2% of ocular emergency admissions result, their routine use is not generally recommended.119 during a 3-year study period were for OC.14 Moreover, Ferguson and McNab found different results Although etiological factors of OC differ considerably be- between cultures of conjunctival swabs and cultures of tween patients in the Western and developing world, there are abscesses material from patients with positive cultures,62 no documented ethnicity differences in epidemiology.121 whereas Oxford and McClay found that all patients with Average age at presentation has been reported from 19.92 to positive surgical and blood cultures had the same culture 25.7 years.34,139 OC commonly affects children and early ad- results.138 olescents, likely because until the age of 15 years the immu- The majority of studies performed in developed countries nologic system is immature.14,32,34,139 In a report from India,141 find Staphylococcus aureus13,22,27,32,41,68,72,82,87,108,113,115,123,135,141,180 however, 57% of cases were adults and 42% were children, and Streptococcus species32,68,82,87,108,141,143,153,155,160 as the most with a mean age of 45 years in the adult group and 4 years in common causative organisms. Most recent studies from both the pediatric group. In pediatric studies, the mean age varies developed and developing countries underline an increasing from 6.1 to 8 years, with a range of 0.5e17 years.1,58,65,103,176 A trend of OC cases caused by methicillin-resistant Staphyloccocus study from Texas examined children with OC before the age of aureus (MRSA).58,108,118,119,160 The incidence of MRSA in such in- 12 months. Average age at presentation was 3.8 months, with fections varies from 21% to 72%.20,112,119,194 Community-acquired a range of 1e9 months.123 MRSA is increasing in various countries.21,29,124,141 The limited Gender distribution is usually equal32,58,176; however, in the number of effective antibiotics in treating MRSA renders the studies from Iran, India, and Nigeria, males are affected more increasing prevalence of this microorganism a major public often (66.7%e70.6%). This male preponderance in the devel- health concern. A study from California underlines the oping countries may be attributable to the prevalence of work increasing incidence and resistance among the pediatric popu- accidents as an etiological factor.13,14,32,65 Some studies from lation, reporting a significant danger of neonatal infection with the developed world have also exhibited male predominance, MRSA.7 Pen˜ a and colleagues investigated the prevalence and such as a pediatric study from the United States in which 73% antibiotic resistance patterns of pathogens associated with were males130 and a study from Canada in which 74% of OC orbital complications from acute sinusitis after the widespread cases were males.107 use of 7-valent pneumococcal conjugate vaccine (PCV7) vacci- Seasonal presentation of OC in late winter-early spring has nation and emphasized the significant increase in S. aureus OC, been observed in Western studies, directly associated with the with a concurrent increase of MRSA.146 occurrence of sinus and upper respiratory infections.32,34,107 A Streptococcal infection is age related, with younger chil- seasonal distribution, however, was not observed in children dren more likely to present with infection from Streptococcus younger than 9 years of age.58 Another pediatric study from pneumoniae and older children from group A streptococcus.10 the United States also failed to demonstrate any obvious Additionally, Streptococcus milleri,138 Streptococcus viridians,87 seasonality.130 and Streptococcus anginosus160 are the most commonly iden- Increased ocular morbidity in the developing countries is tified organisms. Pen˜ a and colleagues observed a decline in associated with late seeking of medical care and concurrent the incidence of S. pneumoniae as an etiologic pathogen.146 sinus infection, with 9.1% of eyes presenting with no light Other frequently associated microorganisms in various perception.141 In a retrospective study from Nigeria, only 29.4% studies over the world are coagulase-negative survey of ophthalmology 63 (2018) 534e553 537

staphylococcus,68,87,119,141 Klebsiella pneumoniae,87,141 Asper- Orbital organic foreign bodies usually carry a large amount gillus,141 Moraxella catarrhalis,143 and Haemophilus influenzae.85 of bacteria. Previous studies have not shown a predominant Rare etiologic factors for OC include Pseudomonas species,34 organism. Similarly, fungal organisms have not been found Neisseria, Eikenella corrodens, Corynebacterium,Prevotellamelani- commonly in cases of orbital wooden foreign bodies. In a nogenica, Morganella morganii, Acinetobacter,87 Bacillus anthra- recent review of 32 cases with orbital wooden foreign bodies, cis,141 Escherichia coli, Actinobacter species, Enterobacter species, Staphylococcus epidermidis, S. aureus, Enterobacter agglomerans, and various anaerobes such as Propionibacterium acnes, and Clostridium perfringens were identified.179 Peptococcus species, Peptostreptococcus species, Veillonella species, A high rate of suspicion for fungal OC should arise in high- Prevotella, Porphyromonas, Fusobacterium bacteroides,and risk patients, such as immunocompromised patients, patients e Clostridium bifermentans.20,22 24,34,62,112,119 with diabetes mellitus, or patients under chronic steroids or Specific pathogens have been identified in certain situa- antibiotic treatment.60,91 Both Mucormycosis and Aspergillosis, tions. In posttraumatic cases, S. aureus and S. pyogenes are the the most common fungal rhinoorbital infections, often lead to main pathogens.108 Microbiology of odontogenic origin mainly severe complications such as ophthalmic vascular thrombosis, includes mixed aerobic and anaerobic bacteria.23,24 Lee and optic atrophy, palsies, meningoencephalitis, brain abscess, colleagues reported that nonespore-forming anaerobic bac- thrombosis of the cavernous sinus, subdural, or intracerebral teria usually cause OC after human or animal bites.108 hemorrhages, presenting finally a high mortality rate.181 Age has also been shown to influence bacteriology of OC. A Streptococcus infection can lead to a dangerous necro- considerable number of studies present anaerobes34,67 as tizing lid disease, necrotizing fasciitis.32,37,117,163,165 This is a common pathogens of pediatric OC. It is generally accepted condition that may cause systemic complications and prog- that OC in children younger than 10 years is caused by single ress to multiorgan failure37,117 through the production of in- aerobic pathogens as compared to older children, who often flammatory proteins and exotoxins.32 Ng and colleagues present more complex infections by multiple aerobic and presented a case of necrotizing OC with rapid development of anaerobic pathogens.2,34,79 With age, the ostia of the sinus severe systemic toxicity, extensive soft tissue necrosis, and cavities narrows, creating convenient conditions for the formation of abscess leading to severe complications development of anaerobic pathogens (Fig. 2). This is probably including panophthalmitis requiring evisceration.133 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 5. Classification older children, the combination of medical and surgical intervention is often necessary.78 Harris and colleagues found Historically, Chandler’s classification of orbital complications that 43.2% of children with OC between the ages of 9e14 years of acute sinusitis has been used, based on their location and present complex infections, more often with polymicrobial severity. infections, and anaerobes were found in all cases.79 Anaerobic OC is much less common in adults.62 Group 1: Preseptal cellulitis Up to the early 1990s, H. influenzae was one of the most Group 2: Orbital cellulitis frequent pathogens associated with OC in children.8,51,141 H. Group 3: Subperiosteal abscess influenzae was extremely aggressive, with bacteremia and Group 4: Intraorbital abscess meningitis.18,51,109,119 After the introduction of H. influenzae Group 5: Cavernous sinus thrombosis (CST) 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 Group I comprises preseptal cellulitis, in which the in- and colleagues attributed this decline to additional factors flammatory process is limited anteriorly to the orbital septum such as the introduction and wide use of more effective an- and does not invade the intraorbital structures. In group II tibiotics.141 In developing countries where vaccines are not (OC), the orbital tissues are affected. Group III includes the accessible, H. influenzae remains a common cause of OC.108,143 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. 538 survey of ophthalmology 63 (2018) 534e553

material collects periorbitally, between the bony walls of the Additionally, constitutional signs develop, such as fever orbit and the periorbita. In group IVeorbital abscessethere is a (32%e81.2%), leukocytosis (47%), headache (10.1%), general purulent collection inside the orbit. In group VeCSTethere is malaise, and loss of appetite.75,92 Generally, a history of acute an extension of orbital inflammation into the cavernous sinus sinusitis or upper respiratory tract infection during the days that can lead to involvement of the third, fifth, and sixth preceding should be sought.108 cranial nerves.30 Clinical signs and symptoms at presentation may also Jain and Rubin recently simplified the classification system differ according to age. In a study from the United States, as follows:89 clinical characteristics were compared in children younger and older than 7 years. The younger group presented higher 1. Preseptal cellulitis white blood cell counts and decreased frequency of proptosis 2. OC (with or without intracranial complications) and ophthalmoplegia.130 In children younger than 1 year, OC 3. Orbital abscess (with or without intracranial may present with fever, periorbital edema, periorbital ery- complications) thema, reduced appetite, and lethargy.42,123 a. Intraorbital abscess, which may arise from collection of purulent material in an OC b. Subperiosteal abscess, which may lead to true infection 7. Complications of orbital soft tissues OC may be associated with severe visual and life-threatening complications, including optic neuropathy, the formation of 6. Clinical manifestations an orbital abscess, meningoencephalitis, intracranial ab- scesses, CST, and sepsis.56,108,109,158,159,196 Children are sus- OC presents with classical signs. Since it can potentially lead ceptible to serious complications such as optic neuropathy, to severe visual and life-threatening complications and endophthalmitis, meningitis, and brain abscess because of progress rapidly, prompt diagnosis and treatment are their immature immune system.123 Patients with sinusitis and essential.108 The prevalence of signs is similar in developing and OC in developing countries often seek treatment later in the developed countries. OC begins with general signs and symp- course of their disease and develop complications more toms such as severe eyelid redness and edema (71.5%e100%), frequently compared to patients in Western countries.32 ptosis (10.6%e33.3%), conjunctival chemosis (32%e45.3%), Involvement of the optic nerve or the vasculature of the discharge (16.7%), erythema of periorbital tissues, and periocular orbit and the eye are among the eye-threatening complica- pain or pain with eye movement (39.2%e63%; Fig. 3).108,158,196 As tions that may develop. The optic nerve can be affected by the infection progresses, there are signs that can help differen- inflammatory infiltration, mechanical compression, or tiate between more superficial infections and OC,33 such as compression of the feeding arteries with resultant proptosis and globe displacement (46.9%e100%), decreased ischemia.2,50 This can lead to disc swelling or neuritis with vision (12.5%e37%), afferent pupillary defect (5.5%e16.7%), rapid progression to optic atrophy and blindness. Other usual impaired color vision (16.7%), and limited ocular motility causes of loss of vision include ischemia from thrombophle- (39.1%e84.6%).1,12,32,58,62,65,70,76,87,113,176 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 Fig. 3 e Orbital cellulitis. A: Photo of a patient with orbital bacterial sinusitis30,32,79 and is commonly located adjacent to cellulitis of the left eye. The eyelid edema and redness are opacified paranasal sinuses, specifically at the medial orbital obvious. Additional signs are ptosis, mild proptosis, wall and the orbital floor.108 A subperiosteal abscess is the redness, and chemosis of the conjunctiva; B: photo of the result of the accumulation of purulent material between the patient after treatment. periorbita and the orbital bone (Fig. 4). Specifically, the survey of ophthalmology 63 (2018) 534e553 539

ethmoidal sinuses are separated from the orbit by the lamina intracranial venous system.23,153 Sinus infection is considered papyracea, the thinnest bone in the orbit. Additionally, the the major etiologic factor for intracranial abscesses, with orbital floor that lies on above part of the maxillary sinus is frontal sinus involvement being the most common, followed also thin. In these areas, the periosteum in the orbit (the by ethmoid and maxillary sinuses.32 When neurological signs periorbita) is not firmly attached to the bone and can be are present in a patient with OC, intracranial extension must elevated by an accumulation of purulent material, thus lead- be suspected. Symptoms are not always present in patients ing to the formation of a subperiosteal abscess.85,167,172 with intracranial abscess, or they can be minimal, especially An orbital abscess, the accumulation of pus within the in children. The usual symptoms are nausea, vomiting, sei- orbital elements, results from the organization of the orbital zures, fever, and change in mental status.108,153 inflammatory progress or the rupture of a subperiosteal ab- Epidural and subdural empyemas are the 2 most common scess. It may lead to severe consequences, such as proptosis, intracranial complications of sinusitis-related OC.2,138,184 ophthalmoplegia, and loss of vision.44,89,177 Orbital abscesses Meningitis was considered the most common intracranial have led to devastating results in the past,85 even in cases complication in a study from 1984,32 along with epidural, receiving medical and surgical treatment. A study from 1969 subdural, and brain parenchymal abscess.16 A retrospective refers to a percentage of 7.1%e23.6% of patients with orbital study that reviewed the complications of acute sinusitis from abscess experiencing permanent visual loss.90 Few cases of a tertiary care children’s hospital in Texas between 1995 and acute visual loss as a result to orbital abscess are reported in the 2002 found orbital abscesses in 42.3% of patients, epidural recent literature, especially in developed countries, whereas in empyema in 6.7%, subdural empyema in 5.8%, Pott’s puffy developing countries, many patients with OC still exhibit severe tumor in 2.9%, intracerebral abscess in 1.9%, meningitis in complications, mainly as a result of delayed treatment.32,53 1.9%, and CST in 1.0%.138 The incidence of abscess formation has declined signifi- CST represents one of the most severe complications of OC. cantly, especially in developed countries. Among series with CST should be suspected clinically when there is severe loss of reported orbital complications of sinus disease, the incidence visual acuity. Orbital pain, chemosis, eyelid edema, and limi- of subperiosteal abscess reached 79%69,127,193 in older studies tation of globe motility are also marked and progress rapidly. and is estimated to be around 42% in more recent studies.138 In There is retinal venous engorgement. Involvement of the III, a 10-year retrospective study in Wisconsin of 228 patients IV, V, or VI cranial nerves adds a strong clinical suspicion for with OC, 53 (23.8%) had CT-confirmed subperiosteal ab- CST. Systematic deterioration is rapid, with general prostra- scesses, whereas the majority of patients with subperiosteal tion, high fever, meningitis, and sepsis. The rate of blindness abscesses belonged to the older children or adult group144,153; and death is up to 20%.138,183,187 Without prompt treatment, lately, there are reports suggesting that adults were less likely CST is a fatal situation. Morbidity in these cases is related to than children to present with abscesses.55 Ferguson and the contents of the cavernous sinus, cranial nerves III, IV, V1, McNab present incidences of 29% of inflammatory changes, V2, and VI, and internal carotid artery. Thrombosed 62% subperiosteal abscess, and 9% orbital abscess in the ophthalmic veins and retinal infarction are other possible children group, compared to 72%, 5%, and 22%, respectively, in complications, whereas the thrombus from the cavernous the adult group.62 sinus may lead to petrosal sinus, sigmoid sinus, or internal Intracranial complications of OC include meningitis, em- jugular vein thrombosis.23 pyema or abscess of the epidural or subdural space, intrace- The most common pathogens leading to these intracranial rebral abscess, Pott’s puffy tumor, CST, and ischemic brain complications are anaerobes,153 and infections are often pol- infarction.2,14,15,32,147,166 These are considered rare (4% of ymicrobial.21,32 S. milleri2,138,183 and S. aureus4 have been hospitalized patients with sinusitis) and are a grave danger to described as the most common pathogens, whereas Strepto- life.2,23 The aforementioned complications result from sinus- coccus, Stapylococcus, Bacteroides, and Fusobacterium species are itis or cellulitis by direct extension, hematogenous spread, or also significant etiologic factors.32 retrograde thrombophlebitis through the valveless venous Various researchers have studied the long-term symptoms system that interconnects the sinus or orbital veins with the 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. 540 survey of ophthalmology 63 (2018) 534e553

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

CT scan is the imaging modality of choice in the diagnosis and monitoring of patients with OC. Cases with periorbital inflam- 8. Differential diagnosis mation, severe eyelid edema, proptosis, ophthalmoplegia, and deteriorating visual acuity or color vision must be subjected to Various conditions can mimic OC, with the characteristics of an orbital CT scan.32,81,157 Additional indications include the proptosis, chemosis, and periorbital swelling. In order to presence of central nervous system signs, no improvement or ascertain the correct diagnosis, a thorough history, physical deterioration of the patient’s condition within 24 hours, and examination, laboratory, and imaging information are nonresolving pyrexia over 36 hours.86 indispensible.108 CT provides imaging data of the anatomic elements of the The differential diagnosis is quite extensive.20,73 A primary orbit, such as the orbital walls, extraocular muscles, optic neoplasm, most commonly rhabdomyosarcoma88 or retino- nerve, adipose tissue, and paranasal sinuses (Fig. 7). There- blastoma,186 or even a malignant melanoma, can mimic OC.131 fore, orbital infections and lesions can be recognized, espe- Additionally, various types of leukemia and lymphomas are cially in cases where clinical examination is not adequate for included in the differential diagnosis, such as acute leuke- the diagnosis.157 Additionally, CT provides information on the mia,12 ocular adnexal T-cell lymphoma,175 extranodal and extension of the inflammatory changes in the orbital struc- natural killer/T-cell lymphoma (Fig. 5).99 Metastatic neo- tures, identification of potential sources of the infection such plasms to the orbit may mimic OC, such as esophageal 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. survey of ophthalmology 63 (2018) 534e553 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 108,161 Fig. 6 e Carotid cavernous fistula. A, B: Photos of a patient of this technique. with right carotid cavernous fistula. Chemosis, Finally, ultrasonography of the orbit has been used for the conjunctival hyperemia, proptosis, and ophthalmoplegia identification of orbital abnormalities; however, ultrasonog- 77,95 are present. C: Axial CT scan of the orbits. The superior raphy does not have a major role in diagnosing OC. Ul- ophthalmic vein appears enlarged. CT, computed trasonography can be useful for the detection of orbital tomography. 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- is also essential in monitoring the efficacy of treatment.44 In a office screening procedure.44 10-year retrospective review of 101 pediatric cases of OC, CT increased the prediction accuracy of cases needing surgical intervention.107 10. Treatment Moreover, CT scanning provides evidence for the identifi- cation of an orbital abscess and defines its size and location. 10.1. Medical management The recognition of subperiosteal abscesses is more accurate with the use of CT than clinically.32 Detection of an abscess Rapid diagnosis of OC and initiation of the treatment scheme can be difficult even with CT, however, especially at an early are mandatory in order to minimize complications. Hence, stage, and should not be excluded if suspected clinically.44 almost all patients require admission, especially when the Initially, the abscess appears as a density of the soft tissues, following signs are present: periorbital swelling, diplopia, usually at the medial orbital wall, in combination with a fluid- reduced visual acuity, abnormal light reflexes, proptosis, filled paranasal sinus. A larger abscess appears as a fluid ophthalmoplegia, drowsiness, vomiting, headache, and sei- collection with enhancement of its rim.44,157 Contrast media zures.86 Medical management focuses primarily on aggressive may be used for the differentiation between an abscess and antibiotic therapy and concurrent therapy of underlying pre- inflammatory procedure of the orbit, as the walls of the ab- disposing factors such as sinusitis.108 Duration of antibiotic scess enhance.107,108 treatment varies from 1 to 2 weeks intravenously, followed by Imaging studies are also essential when neurological signs oral treatment in order to complete a 4-week regimen are present to exclude intracranial extension of the inflam- (Table 1).104 Clinical signs should be assessed at least twice mation, such as a brain abscess or CST.44 daily along with frequent laboratory and imaging investiga- MRI is also a useful tool in the identification of the orbital tion (Fig. 8). In case a complication is suspected, hourly eval- infection, especially when the CT findings are unclear. MRI 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 patients with stay (days) presenting described factors involved antibiotics submitted in 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 >37.5C 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 534 (2018) 63 ophthalmology of survey 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 >37.5C 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 e 553 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 Ecchymosis/ 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 182 þ

Tuano Philippines Ophthalmoplegia Sinusitis spp. Penicillin 534 (2018) 63 ophthalmology of survey 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 e Headache Retained foreign 553 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 patients with stay (days) presenting described factors involved antibiotics submitted in 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 534 (2018) 63 ophthalmology of survey 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 e 553 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 influenzae Friling 2014, Israel 51 6.1 (0.5 39.2 Fever (>38C) 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 40

et al. 2016 Streptococcus flucloxacillin 534 (2018) 63 ophthalmology of survey 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. e 553 545 546 survey of ophthalmology 63 (2018) 534e553

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 treatment.34,74 In cases that MRSA is suspected, vancomycin is oral antibiotics for varying periods of time.32 administered.86 Initiation of intravenous antibiotics must be immedi- Various studies worldwide advocate treatment regimens ate.86,108 The mainstay of therapy for OC is empiric coverage used in their centers. The American Academy of Pediatrics with broad-spectrum antibiotics against the most common advises that empiric treatment should target against the most pathogens; however, cultures should be obtained, and when common pathogens (S. pneumoniae, H. influenzae, and M. needed, treatment is altered accordingly. Empiric treatment catarrhalis).9 Based on this, Lee and colleagues prefer empiric depends on the incidence of pathogens producing OC in each coverage against gram-positive organisms, since Staphylo- geographic area and the age of the patient. coccus and Streptococcus species are the most common patho- The regimens described in the literature have been incon- gens.108 Specifically, empiric use of vancomycin is sistent because the pathogens leading to OC vary among recommended, based on the reported increased incidence of different geographic locations.86 Generally, antibiotic protocol Community-acquired MRSA infections. They also advocate depends on local microbiological sensitivities. A well-accepted the use of cefotaxime and metronidazole or clindamycin to proposed treatment scheme includes a broad-spectrum anti- provide concurrent coverage against gram-negative and biotic, specifically a third-generation cephalosporin such as anaerobic organisms. Empiric antibiotic treatment should in ceftriaxone with flucloxacillin. This scheme is effective against general cover against sinus pathogens, prevent b-lactamase most usual bacteria, both gram-positive and gram-negative resistance, and penetrate cerebrospinal fluid.137 In a study bacteria. Coverage for anaerobic bacteria is initiated in cases from the United Kingdom, contemporary empiric treatment where there is no clinical improvement or in case of pyrexia with cefuroxime and metronidazole is advocated.86 Chaudhry after 24e36 hours after initiation of treatment. Metronidazole and colleagues in a center in Saudi Arabia use a combination or clindamycin is preferred.40,108 As previously mentioned, of a third-generation cephalosporin and flucloxacillin for the children younger than 9 years present simpler infections, coverage against Staphylococcus, Streptococcus, and Haemophilus usually caused by a single aerobic pathogen, that respond easily species.32 Friling and colleagues from Israel treat OC with to medical treatment. Older children and adults present more ceftriaxone and clindamycin, which cover against penicillin- often with infections caused by multiple aerobic and anaerobic resistant S. pneumoniae, anaerobic bacteria, and S. aureus.65 organisms, which may necessitate both medical and surgical Abdouramani and colleagues in Cameroon treat with survey of ophthalmology 63 (2018) 534e553 547

ceftriaxone, gentamicin, and metronidazole for concurrent of surgical treatment of a subperiosteal or orbital abscess is coverage against aerobic and anaerobic organisms.2 not clearly defined.86,173 Delayed drainage is likely to lead to Aggressive intervention is required in cases of intracra- serious complications and poor visual outcomes. On the other nial complications, with a multidisciplinary approach of hand, an abscess may resolve with medical therapy alone, oculoplastic surgeons, otolaryngologists, neurosurgeons, avoiding the likelihood of complications from surgery such as and experts in infectious diseases.32 Medical treatment of infection seeding.79,86,152 intracranial complications includes wide-spectrum antibi- There are reports that propose surgery in high-risk cases otics that exhibit anaerobic coverage and central nervous such as children over the age of 10 years in whom complex system penetration.67,153 In early stages of cerebritis, when infections are more common, the presence of anaerobes is the brain abscess is not yet formed, aggressive antimicrobial more frequent, and extension of the abscesses more treatment may prevent abscess formation. Penicillin, chlor- likely.75,79,108 Patients younger than 10 years with OC are more amphenicol, third-generation cephalosporins, and metroni- likely to respond to medical therapy without surgical dazole penetrate well into the intracranial space and drainage.26,72 Harris and colleagues consider that, with this combined are effective against most responsible patho- approach, the formation of an orbital abscess or the intra- gens.17 After the brain abscess has formed, the surgical cranial extension of the infection can be prevented.79 Addi- treatment is combined with a long course of antibiotics tionally, medial or inferior abscesses are more likely to (4e8 weeks). Mannitol, hyperventilation, and steroids are respond to medical treatment,26,67,79,86,152 whereas cases of a also used for the increased intracranial pressure.23 superior abscess or an abscess at the orbital apex may require CST is generally treated with broad-spectrum antibiotics surgical drainage.108 Other factors considered for surgical that cover against aerobic and anaerobic organisms (vanco- treatment include the presence of severe signs such as mycin, cephalosporin, and metronidazole).170 Anticoagulants compromised vision, pupillary changes, raised intraocular are additionally used to prevent further thrombosis and to pressure, proptosis of over 5 mm, and failure to respond to dissolve the clot; however, treatment with anticoagulants in medical therapy.102 Patients with optic nerve or retinal these cases is still controversial.149,174 Steroids are used to compromise from compression by the abscess also require reduce edema and inflammatory process.149,170 Prompt sur- emergent drainage.72 gical intervention is essential in cases with CST.174 The presence of a retained foreign body, a concurrent Adjunctive use of corticosteroids is considered favorable paranasal or frontal sinus infection, an identified dental together with the appropriate antibiotics, in the management source of the infection, the presence of intracranial compli- of OC particularly after clinical improvement is noted. Intra- cations, and the large abscesses also constitute high-risk venous corticosteroids moderate the inflammatory process factors that may require surgical treatment.34,67,72,86,89,108,171 and decrease the levels of inflammatory cytokines.66,197 Ste- Iatrogenic foreign bodies that lead to orbital infection, such roids, however, are contraindicated in cases of fungal OC or in as scleral buckles and glaucoma drainage devices, require immunocompromised individuals because of their immuno- urgent removal.108 Organic foreign bodies must be immedi- suppressive effects and the potential risk of delaying or pre- ately surgically removed, as they carry a high risk of severe venting the resolution of the primary infection. Steroid use for infections and complications. The treatment approach is the control of cerebral edema can present disadvantages. empiric antibiotic therapy, immediate removal of the foreign Steroids retard the encapsulation of the abscess, reduce the body, simultaneous removal of the necrotic tissue, acquisition antibiotic potency, and influence CT scans. Hence, their use in of cultures during surgery, and change of antibiotic therapy these cases should be cautious,23 and each case must be according to culture results.179 Usually, the entrance of the carefully evaluated before steroids are administered.108 surgical incision for the foreign body removal is the original Antifungals should be considered in cases that do not wound, as less injury is caused. If the wound has healed, the respond to first-line therapy, especially at high-risk pop- surgical approach depends on the location of the injury and ulations. In cases of fungal infection, treatment focuses on the size of the foreign body. Finally, caution is required during fixing the underlying metabolic abnormalities, along with removal of wooden foreign bodies because they tend to break intravenous antifungal therapy and surgical debridement of into multiple pieces.110 the affected tissues. Orbital exenteration may be necessary in An individualized treatment scheme is generally recom- nonresponding cases of fungal infections in order to avoid mended.32 Jain and Rubin suggested the following categori- fatal complications.60,91,181 zation to guide the choice of the treatment modality in cases Finally, it is important that simultaneous sinusitis is with orbital abscesses: patients requiring emergent drainage, treated, along with medical treatment of OC, with aggressive patients who may need urgent drainage, and patients sub- nasal hygiene, decongestants, saline nasal irrigation, and jected in expectant observation.72,89 Close clinical monitoring intranasal corticosteroids.26,108 is indicated, including careful evaluation of the optic nerve function, the pupillary reflexes, visual acuity and the level of 10.2. Surgical management consciousness, along with repeated orbital CT scans, so that surgical intervention can be offered when needed.32 Surgical management in cases of OC includes drainage of There are different techniques for surgical removal of orbital abscesses, sinus surgery and treatment of intracranial subperiosteal and orbital abscesses.178 The traditional complications. external method for medial abscesses is performed through Orbital abscesses, apart from aggressive antibiotic treat- Lynch incision, which offers adequate visibility and effective ment, often require prompt drainage; however, the necessity drainage but leaves a visible scar, unpleasant in the pediatric 548 survey of ophthalmology 63 (2018) 534e553

population. This indicates why transnasal endoscopic surgery and management. Articles that reported the possible causa- represents a great advance. Factors that guide the surgical tive organisms, and their correlation to geographic distribu- approach of choice include location of the abscess and tion were thoroughly studied. There was no language radiographic findings. Successful transnasal endoscopic sur- restriction. References cited in the articles were also studied. gery is reported in patients with medial-based subperiosteal In the present review, 197 studies were evaluated, which orbital abscesses, whereas superolateral extension requires were published from the year 1948 to 2017. The included an external approach.152,178 Migirov and colleagues have studies comprise data of OC coming from various geographic suggested endoscopic sinus surgery in the treatment of locations (North and South America, Europe, Africa, Australia, medial orbital abscesses.121,122 Another report from the and Asia), and regarding different age groups (childhood, United States suggests a combined endoscopic and trans- young adults, patients over 60 years), etiologic factors, clinical caruncular surgical approach to medial orbital subperiosteal manifestations, complications, and treatment modalities of abscesses for an effective and cosmetically superior cellulitis. 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 12. Disclosure decompression of brain abscesses is related to high morbidity and mortality.23 Cases of OC with concurrent There was no funding for this study. The authors report no frontal sinusitis and complex infections with anaerobes are proprietary or commercial interest in any product mentioned candidates for surgical management because of the or concept discussed in this article. 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 references 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 1. Aabideen KK, Munshi V, Kumar VB, Dean F. Orbital cellulitis with intracranial extension of the infection require surgical in children: a review of 17 cases in the UK. Eur J Pediatr. intervention. Over 90% of patients were subjected to a 2007;166(11):1193e4 combination of 2 or more surgical procedures such as 2. Abdouramani O, Nguefack S, Dohvoma V, et al. Bilateral intraorbital abscesses with intracranial complications in a craniotomy, orbital surgery, and sinus surgery.153 In cases young Cameroonian girl: a case report. Clin Ophthalmol. with CST, surgery should be performed promptly after 2012;6:1429e32 diagnosis. Surgical intervention is also indicated in the 3. Abdullah AS, Jan S, Qureshi MS, Khan MT, Khan MD. treatment of the bacterial sinusitis that precipitates CST, Complications of conventional scleral buckling occuring such as endoscopic sinus surgery.170 during and after treatment of rhegmatogenous retinal detachment. J Coll Physicians Surg Pak. 2010;20(5):321e6 4. Ailal F, Bousfiha A, Jouhadi Z, Bennani M, Abid A. Orbital cellulitis in children: a retrospective study of 33. Med Trop 11. Conclusion (Mars). 2004;64(4):359e62, French. 5. Allen MV, Cohen KL, Grimson BS. 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