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Orbital Infections
Allan E. Wulc
Brenda C. Edmonson
Orbital and periorbital infections are the most common causes of acute orbital
inflammation and are distinguished clinically by anatomic location. Preseptal cellulitis
and periorbital cellulitis are synonymous terms that refer to superficial spreading
cellulitis without associated spread to the postseptal tissues. Orbital cellulitis, in contrast,
is an infection of the postseptal orbital tissues sometimes associated with superficial
spreading cellulitis. Both conditions are more commonly seen in children and young
adults.1,2,3,4,5,6,7 In Schramm's series of 303 cases of orbital cellulitis, 68% of patients
were younger than 9 years of age, and only 17% were older than 15 years of age.8
Interestingly, there seems to be an unexplained preponderance of left-sided orbital
infections as compared with right-sided infections.8,9,10
In the preantibiotic era, Gamble11 reported a mortality rate of 17% in patients with
orbital cellulitis. An additional 20% of survivors had loss of vision. Even now, with the
ubiquitous use of modern imaging techniques and new antibiotics, the relative ease and
rapidity of spread of contiguous infection to the cavernous sinus and the brain renders
complications associated with misdiagnosis or inappropriate therapy life threatening.
Estimates of the case fatality rate in one series suggest an improvement from 9.4% to
2%, but this mortality rate is unacceptably high, particularly in newborns in which the
mortality rate approaches 11%.11
Although these alarming figures are 10-fold less in patients with preseptal cellulitis rather
than with orbital cellulitis, preseptal cellulitis can be associated with sepsis and bacterial
meningitis and therefore is not necessarily a benign process.12,13
The discussion in this chapter focuses on the differential diagnosis, symptoms and signs,
radiologic diagnosis, and microbiology of preseptal and orbital cellulitis. Over the past
decade, the management of sinusitis has evolved. New vaccines, better imaging and new
antibiotics along with refined methods of surgery all have improved the diagnosis and
treatment of sinusitis and as a consequence, the diagnosis and treatment of periorbital
and orbital cellulitis. A rational approach to the evaluation and management of these
conditions, as well as their sequelae, is provided.
SYSTEMS OF CLASSIFICATION
Preseptal and orbital cellulitis are two distinct conditions that have different anatomic
problems at their source but often present with a similar clinical picture.
Preseptal cellulitis usually occurs in either of four clinical settings. These settings include:
(a) sinusitis, (b) bacteremia, (c) upper respiratory infection, or (d) local cutaneous
infection.14,15,16 In the latter setting, preseptal cellulitis can arise from spread of a
contiguous anterior eyelid infection such as a chalazion, local trauma resulting in
infection such as an insect bite, or a foreign body.(Fig. 1)
Fig. 1. Preseptal cellulitis in a 32-year-old woman. Swelling developed over 3 days.
Motility was preserved.
Prior to the Haemophilus influenzae type b (Hib) vaccine, the most common clinical
presentation was of a child younger than the age of 36 months with a history of
antecedent upper respiratory tract infection, otitis media, and bacteremia and usually
resulted from infection with Hib.4 However, since the introduction of the Hib vaccine,
the incidence of Hib induced preseptal cellulitis has declined dramatically with some
studies reporting up to a 90% reduction.15
Orbital cellulitis, in contrast, usually arises from spread of infection from the paranasal
sinuses. Orbital involvement occurs in 0.5% to 3% of patients with acute sinusitis.14 In a
large series of patients with orbital cellulitis, sinusitis was responsible for orbital infection
in 75% to 90% of cases.8,18,19 The ethmoid sinus is the most commonly implicated sinus
in infections that spread to the orbit in children; the frontal and sphenoidal sinuses do
not develop until age 7.20 In adults, pansinusitis often is associated with orbital cellulitis
and spread is believed to occur through the ethmoid or frontal sinuses.
In addition to anatomic proximity, several other factors predispose the orbit to the
spread of contiguous sinus infection. Dehiscences often are present in the orbital walls,
particularly in the thin-walled lamina papyracea.21,22,23 As a consequence, pus or
transudate may rupture through the thin-walled lamina into the orbit and result in
subperiosteal abscess formation. This theoretical mechanism is consistent with the
observation that most abscesses occur in the medial orbit, adjacent to the ethmoidal
sinuses.24,25,26 Posteriorly, the optic nerve within the optic canal is adjacent to the
lateral wall of the sphenoidal sinus. Dehiscences can also be present in the lateral wall of
the sphenoidal sinus along the optic canal, in approximately 6% of cases.27
Another factor predisposing the orbit to the spread of adjacent sinus infection is the free
vascular communication between the orbit and the sinuses. The orbital veins are
valveless, and flow occurs in either direction28 through the anterior and posterior
ethmoidal foramina. Increased pressure within the sinuses caused by obstruction to
mucus outflow in sinusitis may hamper venous drainage and manifest as the eyelid
edema that accompanies acute sinus inflammation. Septic thrombophlebitis can also
occur within these vessels and allow bacterial spread into the orbit.29,30,31,32,33
However, all orbital cellulitis resulting from sinus disease is not secondary to acute
sinusitis. Orbital fracture can spread existing chronic sinus infection into the orbit (Fig.
2).25,31,32,33 Mucoceles, slowly enlarging mucus-filled cysts within the sinuses that
enlarge by pressure erosion of adjacent orbital and intracranial structures, can become
infected and result in mucopyoceles that cause both cellulitis and abscess
formation.34,35,36,37
Fig. 2. Orbital cellulitis following repair of an orbital floor fracture in a 14-year-old patient
with a history of stuffy nose. There was progressive onset of diplopia, pain, and
extraocular movement limitation 2 days after surgery to the left orbit. A. Primary
position. B. Downgaze.
Fig. 3. Neonatal dacryocystitis. Untreated lacrimal sac infection may result in orbital
cellulitis. In addition to antibiotics, probing and irrigation are required.
Fig. 4. A. Orbital cellulitis from a dacryocystitis. The dacryocystitis developed in this 43-
year-old woman who sustained multiple orbital fractures after facial trauma. B. The axial
computed tomogram shows dacryocystitis and orbital inflammation. The patient was
treated with intravenous antibiotics and a dacryocystorhinostomy.
Fig. 5. A. Orbital cellulitis from a foreign body in a 45-year-old patient who 4 days earlier
fell off a ladder and sustained a right nasal laceration. The cellulitis was treated with
intravenous antibiotics with no improvement. All imaging scans were negative. B. At
surgery, these wooden foreign bodies were removed from the right orbit.
Regardless of its anatomic site of origin, edema develops as the orbital infection spreads
within the connective tissues. Septic thrombophlebitis may ensue and increase both
edema and orbital pressure as blood flow is impeded. Congestive signs such as chemosis,
intraocular pressure, and proptosis increase. The infection may consolidate to form an
abscess. The infection, in turn, may spread through the vascular emissaries into the
cavernous sinus or intracranially, causing cavernous sinus thrombosis, meningitis, carotid
occlusion, and subdural, epidural, or brain abscess.
A spectrum of progressive infectious changes in orbital cellulitis initially was described by
Hubert30 and modified by Smith and Spencer43 and later by Chandler,29 and is useful to
the understanding of the nature of the evolution of orbital cellulitis, in classifying the
severity of infection and defining progression and management.
Stage 1 inflammation represents preseptal cellulitis. All changes that are seen on
examination are confined to the anterior eyelid tissues. Occasionally, edema may spread
secondarily posterior to the septum but does not represent the spread of cellulitis
posteriorly. Chemosis may be present, and it may even cause minimal limitation of
ocular movement.
Stage 2 inflammation represents orbital cellulitis, with leukocytosis, and often fever,
proptosis, extraocular movement limitation, and the congestive signs discussed earlier
(Fig. 6).
Fig. 6. A. Orbital cellulitis presenting in a 27-year-old man with normal visual acuity. B.
Chemosis and limitation of abduction. C. Computed tomography shows ethmoid sinusitis
on the left side.
With stage 3 inflammation, subperiosteal orbital abscess formation occurs. The globe is
often displaced and limited in the field of gaze of the abscess, which occurs concomitant
with the signs of orbital cellulitis seen in stage 2.
In stage 4 inflammation, a true orbital abscess develops. These patients have severe
proptosis, chemosis, ophthalmoplegia, and, often, visual loss.
Stage 5 inflammation represents retro-orbital spread of infection into the cavernous
sinus. In these instances, orbital signs may occur in the fellow eye and other central
nervous system signs supervene.29
SYMPTOMS AND SIGNS
PRESEPTAL CELLULITIS
Patients with preseptal cellulitis often present with a short history of painless swelling of
the eyelids. A history of previous upper respiratory tract infection, trauma, insect or
animal bite, conjunctivitis, or chalazion may be elicited.
Fever is an inconstant feature but may be present in approximately 62% of cases.12 The
eyelid characteristically is erythematous and edematous and may show signs of the
trauma, bite, or chalazion that initiated the cellulitis (see Fig. 1). The eyelid may be
painful to palpation. The superficial spreading cellulitis is confined to the eyelid and
delimited by the attachments of the orbital septum to the arcus marginalis of the orbital
rim so that infection will extend to this area and not beyond.
Rarely, the etiology of the eyelid infection may be diagnosed clinically. Necrotizing eyelid
cellulitis may be caused by erysipelas, an infection with a group A ?-hemolytic
Streptococcus, and can give rise to lid necrosis (Fig. 7).44,45 H. influenzae produces a
characteristic nonsuppurative preseptal cellulitis with a purplish discoloration of the
eyelids.46 Staphylococcal species may cause a suppurative cellulitis with abscess
formation.
Chemosis and extraocular motility deficits are seen only occasionally and are presumed
to result from anterior edema rather than spread of infection. Vision and pupillary
examination are always unaffected by preseptal cellulitis, and proptosis and globe
displacement never are present. Therefore, in the examination of patients with
presumed preseptal cellulitis, vision, proptosis, and extraocular movements are key
distinguishing points.
ORBITAL CELLULITIS
Orbital cellulitis presents as pain, proptosis, globe displacement, double vision, and/or
vision loss (Figs. 6 and 8). Patients often have accompanying headache and malaise. In
children fever occurs with equal incidence as in preseptal cellulitis (62%),12 whereas in
adults it may be absent 66% of the time.47
Antecedent and significant past medical history may include a history of headache,
rhinitis, sinusitis, polyposis, nasal discharge, anosmia, or recent upper respiratory tract
infection. The patient may give a history of prior orbital fracture or orbital fracture
surgery with implantation of alloplastic materials. Scleral buckling procedures and
strabismus surgery have been noted to cause orbital cellulitis; thus, the patient should be
queried regarding prior ophthalmic surgery.38,39,40 The patient may also give a history
of recent dental work, specifically dental extractions.42 The patient may have had prior
surgery of the eyelids or of the facial skeleton with insertion of wires, rigid internal
fixation (miniplates), alloplastic plates, or nondissolving suture material.34
Pain is not invariably present. It is notably absent in approximately 40% of cases, even
those presenting with abscess.25
Fever is a nonspecific sign. In the presence of purulent sinusitis, pain may be present
when the affected sinus is palpated; and with ethmoid sinusitis, pain may be elicited with
pressure on the inner canthus. The sinus may not transilluminate. Mucopurulent
rhinorrhea may be present, and the ophthalmologist when possible should look in the
nose or seek the opinion of an otorhinolaryngologist.
Proptosis, chemosis, and extraocular motility deficit are the clinical hallmarks of orbital
cellulitis (see Fig. 6). Visual acuity decrease, pupillary signs, and vision loss may occur
rapidly. Rarely, if sphenoid sinusitis occurs in isolation, the patient may present with
atypical optic neuritis without proptosis or with little in the way of superficial cellulitis.48
Optic neuropathy, with the associated pupillary finding of a relative afferent pupillary
defect and optic nerve head findings such as optic disc edema, may be observed. As
orbital pressure increases, patients can show signs of retinal and choroidal arterial and
venous stasis with congestion and a picture resembling chronic vein occlusion or central
retinal artery occlusion. Hypesthesia of the nasociliary or frontal nerves is rarely seen.
Hypotony, choroidal folds, and anterior segment inflammation with hypopyon can occur
and imply intraocular spread. A dilated nonreactive pupil implies third nerve
involvement. Patients may show signs of third, fourth, or sixth nerve involvement when
the infection extends into the orbital apex.
Subperiosteal abscess formation most often is diagnosed on neuroimaging and is
indistinguishable clinically from orbital cellulitis. Signs of an abscess include displacement
of the globe away from the affected sinus and limitation of abduction and adduction,24
but these signs can occur with orbital cellulitis as well. Intraorbital abscess formation can
present in the patient who has been partially treated for an orbital infection and may
present as proptosis or globe displacement without any infectious signs or as orbital
cellulitis.25
If infection spreads posteriorly through the superior orbital fissure to involve the
cavernous sinus, additional signs may supervene. Signs of cavernous sinus thrombosis
include headache, ipsilateral hypesthesia from involvement of the ophthalmic and
maxillary division of the trigeminal nerve; third, fourth, and sixth cranial nerve palsies;
and mental status changes from confusion to obtundation. The contralateral side may
develop cranial nerve signs, periorbital edema, or cellulitis (Fig. 9).
Fig. 9. Cavernous sinus thrombosis in a 74-year-old patient with 2-day history of right
orbital cellulitis with rapidly developed obtundation and left-sided orbital changes. A.
Primary position. B. Upgaze.
DIFFERENTIAL DIAGNOSIS
Several conditions can mimic orbital and periorbital cellulitis. Most of these present as
the same constellation of symptoms and signs and often can have a similar appearance
on neuroimaging.
PRESEPTAL CELLULITIS
Conditions that may masquerade as preseptal cellulitis include allergic edema of the
eyelids, severe blepharoconjunctivitis, dacryoadenitis (Fig. 10), trauma, thyroid eye
disease (Fig. 11), leukemic infiltrates,49 blepharochalasis syndrome, and autoimmune
inflammatory disorders such as lupus.
Fig. 10. A. Bacterial dacryoadenitis. B. Computed tomography shows a mass in the left
lacrimal gland.
Fig. 11. A. Inflammatory thyroid eye disease; note bilateral eyelid retraction and
proptosis. B. Malar festoons and right eyelid retraction.
ORBITAL CELLULITIS
Conditions that may mimic orbital cellulitis include thyroid eye disease, idiopathic
inflammatory orbital pseudotumor (Fig. 12), orbital myositis,50 orbital abscess,51
ruptured dermoid cyst, necrotic intraocular melanoma or retinoblastoma,52,53 orbital
trauma, orbital foreign body, orbital vasculitis, Wegener's granulomatosis, herpes
simplex or zoster (Fig. 13), and carotid cavernous fistula. Acute-onset proptosis with
inflammatory signs in a child always should alert the clinician to the possibility of
rhabdomyosarcoma (Fig. 14).
Fig. 12. A. Idiopathic inflammatory orbital pseudotumor. Note chemosis and limitation of
abduction. There was no evidence of anterior cellulitis. B. Computed tomography
demonstrates enlargement of right medial rectus muscle.
Fig. 13. A. Herpes zoster affecting the V1 nerve and causing upper eyelid edema and
erythema.
Fig. 14. Acute-onset proptosis in 12-year-old child caused by pseudocellulitis resulting
from rhabdomyosarcoma.
Fig. 15. Computed tomography showing preseptal cellulitis of left eye. Note that all
swelling is anterior to the orbital septum.
An extraconal or intraconal mass may be present in orbital cellulitis. Proptosis also may
be visible. In particular, with intraconal involvement, proptosis is seen with obliteration
of the normal soft tissue shadows. “Patchy enhancement” of the intraconal fat in orbital
cellulitis has been described.59 The rectus muscles, particularly the medial rectus, and
the optic nerve may be thickened.58
CT is particularly useful for imaging orbital and subperiosteal abscesses. Because the
periorbit is not adherent to the orbital walls except at the suture lines, an abscess lifts
the periorbit, creating a convexity in the orbital periosteum (Fig. 16). Usually
subperiosteal abscess formation occurs adjacent to the involved sinus,25,64 but
occasionally it occurs at a remote location such as the superolateral orbit.65 Gas may be
found within a subperiosteal abscess or within the orbit, arising either from gas-forming
bacilli or free communication with sinus air or from prior trauma (Fig. 17). 57,66 CT
cannot accurately predict whether a subperiosteal mass represents exudate,
inflammatory transudate, or hematoma.67,68
Fig. 16. Computed tomography showing subperiosteal abscess formation. Note elevation
of orbital periosteum and convexity as pus elevates periorbit from the medial orbital
wall.
Fig. 17. Intraorbital gas in a 58-year-old patient with orbital cellulitis from a left frontal
sinus mucocele. Gas appears as an area of complete radiolucency on this computed
tomographic image.
Fig. 19. Magnetic resonance image of preseptal cellulitis with anterior abscess formation.
MRI is superior to CT in the diagnosis of cavernous sinus thrombosis. T2- and proton-
weighted images show high signal luminal narrowing as well as absent flow or localized
parenchymal infarcts (Fig. 20).72 Absent flow can be demonstrated as well in the
superior ophthalmic vein in cases of carotid or cavernous sinus thrombosis.72 MRI with
gadolinium can help define these abnormalities and can detect dural invasion.
Fig. 20. Cavernous sinus thrombosis. Axial T1 image shows cavernous carotid luminal
narrowing on right and enlargement of right cavernous sinus. Note extensive sinus
disease.
Alternatively, the disease can present in the healthy host in a noninvasive form as sinus
mycetoma or allergic fungal sinusitis.106 A colony of organisms forms a mycetoma in a
sinus and gives rise to a chronic sinusitis. This type of aspergillosis is more common in
hot humid climates. These patients present with nasal congestion, postnasal drip, and
chronic sinus pain, along with frequent bouts of acute sinusitis. A mass is seen that
originates from an adjacent sinus that may have sclerotic margins and can produce an
adjacent inflammatory reaction within the orbit. This form responds well to surgical
debridement with restoration of normal sinus drainage and does not require intravenous
antifungal therapy.114 Allergic fungal sinusitis is an allergic reaction to aerosolized
environmental fungi and causes patients to suffer from headaches and nasal stuffiness.
Patients may also present with proptosis and extraocular muscle entrapment. Treatment
consists of surgical debridement and steroids without antifungals.106,109,112
Computed tomographic findings in patients with both forms of the disease demonstrate
areas that are almost metallic in density. These foci of irregularly calcified bone on CT
may be pathognomonic (Fig. 22). On MRI, these areas appeared bright on T1-weighted
imaging and have decreased signal on T2-weighted images, which may be related to the
presence of ferromagnetic materials such as iron and manganese within the fungal
concretions.115
Fig. 22. Aspergillosis. Computed tomography shows areas of extreme density of the
ethmoidal bones.
Biopsy of tissue within the orbit shows invasion of the mucosa, submucosa, and bone in
cases of invasive fungal sinusitis or a granulomatous reaction without mucosal or bone
invasion in the noninvasive form. The material within the sinuses may be yellowish,
black, or friable. Hyphae are not seen within the mucosa or bone of patients with the
noninvasive form but can be seen on routine stains of mucus. Multiple specimens should
be examined116 in a search for septate fungal hyphae of relatively uniform width that
are apparent on hematoxylin and eosin staining.
The most common effects on the orbit are cellulitis, proptosis, ptosis, and diplopia.
Invasion in both forms may produce pain. Optic nerve involvement is rare. The orbit may
be affected by contiguous spread from the sinuses, usually the ethmoid.
The treatment for aspergillosis in the immunosuppressed patient is both medical and
surgical, with antifungal agents (usually amphotericin B) and radical debridement and
sinus surgery.106,107,111 Flucytosine and rifampin with amphotericin B may be more
effective than amphotericin alone.117,118,119
Conservative debridement, intravenous amphotericin, and local amphotericin irrigation
have been described as an alternative to radical surgery.99 Five milliliters of
amphotericin B is placed in sterile water, creating a concentration of 0.25 mg/mL.
Irrigation is performed two times a day directly into the orbit through a site of entry into
the orbit or sinus.116
MUCORMYCOSIS
Mucormycosis is a fungal infection with the organisms from the genera Mucor, Absidia,
and Rhizopus100,101,102 that normally are present in air, soil, vegetable matter, skin
body orifices, manure, and bread mold.120
Most patients who develop mucormycosis have a predisposing systemic disease:
Typically the infection occurs in the diabetic patient with ketoacidosis, but it can occur in
patients with renal failure, gastroenteritis, or in those who are immunosuppressed.121
Rarely, it can occur in the normal host.124,125 An association between deferoxamine
therapy for iron or aluminum excess and mucormycosis has also been described in
hemodialysis patients with chronic renal failure, as well as in a variety of hematologic
disorders.126 It is possible that the fungus uses the iron that is mobilized by
deferoxamine to proliferate, thus facilitating invasive infection.126
Rhinocerebral mucormycosis originates as a rhinitis, parapharyngitis, or sinusitis, and
spreads by invasion of blood vessel walls, causing a necrotizing vasculitis with thrombosis
of the vascular lumina and resultant infarction. The patient typically presents with
unilateral orbital apex syndrome, including severe pain, visual loss, total
ophthalmoplegia, corneal anesthesia, and multiple cranial nerve palsies.127 Orbital
cellulitis presenting with early visual loss is one of the hallmarks of mucormycosis.72
Gangrene may occur of external periorbital tissues as well as of the hard palate and nose,
and eschar-like crusting may be observed within the nose or on the hard palate (Fig. 23).
Obstruction of the central retinal artery, ciliary arteries, and choroidal circulation can
also be seen.124,125 Brain damage may occur because of spread of infection or
infarction or occlusion of affected intracranial vessels.72
Fig. 23. Mucormycosis of the right ethmoidal sinus, with right orbital subperiosteal
abscess formation. A. T1-weighted axial image. B. T2-weighted image. Note brain
abscess.
CT shows sinusitis with or without bone destruction and is indistinguishable from other
causes of orbital cellulitis.128 MRI may show carotid narrowing, occlusion, and absent
flow in the superior ophthalmic vein (Fig. 24).72
Fig. 24. Mucormycosis. A. A 72-year-old patient with acute myelogenous leukemia and
invasive fungal sinusitis presented with orbital cellulitis. B. Involvement of hard palate
with eschar. C. Fungi in the posterior ciliary artery.
Diagnosis is made by having a large index of suspicion and obtaining specimens of nasal
turbinate, sinus, or infected orbital tissue. Large, branching nonseptate hyphae are
readily apparent on hematoxylin and eosin staining or with methenamine silver staining
(see Fig. 23). These hyphae can be grown on fungal culture.
The treatment of mucormycosis involves the control of ketoacidosis or other systemic
disease. Sinus drainage must be restored, and intravenous amphotericin B in doses of up
to 1 mg/kg per day can be administered up to a total dose of 2 to 4 g. Radical and
aggressive surgical debridement of infected tissue is advocated by most authors,
including exeneration if necessary. Surgical debridement is important because local
thrombosis caused by fungal invasion prevents amphotericin from reaching necrotic and
infected tissue.
In the patient with known infection and preserved vision, the need for exenteration and
radical surgery is more controversial, particularly if orbital biopsy does not show orbital
invasion with fungal elements. Successful outcomes have been achieved with
debridement of infected tissue without exenteration.128 In one series intravenous
amphotericin has been used successfully in conjunction with local irrigation of orbital
and sinus tissues with amphotericin B.129 Hyperbaric oxygen has been used as an
adjunctive therapy for rhinocerebral mucormycosis by treating patients with 100%
oxygen at 2.5 atm for 90 minutes for approximately 6 weeks.130
In untreated patients, rhinocerebral mucormycosis is associated with a 14% survival rate.
With amphotericin B and surgery, the survival rate improves to 57%.121 This implies
nonetheless that a significant number of patients will die of this disease and emphasizes
the need for early diagnosis and aggressive management.
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94:785, 1976
3. Hawkins DB, Clark RW: Orbital involvement in acute sinusitis. Clin Pediatr 16:464, 1977