Orbital Cellulitis

Background

Orbital cellulitis and preseptal cellulitis are the major infections of the ocular adnexal and orbital tissues. Orbital cellulitis is an infection of the soft tissues of the orbit posterior to the orbital septum. Preseptal cellulitis is an infection of the soft tissue of the eyelids and periocular region anterior to the orbital septum. (See Presentation.) Orbital cellulitis and preseptal cellulitis can sometimes be a continuum.

Orbital cellulitis has various causes and may be associated with serious complications. As many as 11% of cases of orbital cellulitis result in visual loss. Prompt diagnosis and proper management are essential for curing the patient with orbital cellulitis (see the images below). (See Etiology, Prognosis, Presentation, Workup, Treatment, and Medication.)

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A male patient with orbital cellulitis with proptosis, ophthalmoplegia, and edema and erythema of the eyelids. The patient also exhibited pain on eye ....

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A male patient with orbital cellulitis who demonstrated proptosis, ophthalmoplegia, and edema and erythema of the eyelids. The patient also exhibited ....

Anatomy

The orbital septum is a layer of fascia extending vertically from the periosteum of the orbital rim to the levator aponeurosis in the upper eyelid and to the inferior border of the tarsal plate in the lower eyelid.

Patient education

For patient education information, see the Diabetes Center, as well as Cellulitis.

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Etiology

Orbital cellulitis occurs in the following 3 situations^[1] :

• Extension of an infection from the paranasal sinuses or other periorbital structures such as the face, globe, or lacrimal sac
• Direct inoculation of the orbit from trauma or surgery
• Hematogenous spread from bacteremia

Extension of infection

Orbital cellulitis is commonly associated with sinus infection and can be caused by direct extension of infection from the globe, eyelids, ocular adnexum, and other periocular tissues. Orbital cellulitis may follow dacryocystitis, osteomyelitis of the orbital bones, phlebitis of the facial veins, and dental infections.

Orbital cellulitis is caused most commonly in all age groups by ethmoid sinusitis, accounting for more than 90% of all cases; aerobic, non-spore–forming bacteria are the organisms that are most frequently responsible. The process involves edema of the sinus mucosa, which leads to narrowing of the ostia and subsequent reduction or cessation of normal sinus drainage. Microflora indigenous to the sinuses and upper respiratory tract proliferate and invade the edematous mucosa, resulting in suppuration. It is enhanced by the reduced oxygen tension within the obstructed sinus cavity.

The organisms gain access to the orbit through thin bones of the orbital walls, venous channels, foramina, and dehiscences. Then, subperiorbital and intraorbital abscesses may occur. The resulting elevation of intraorbital pressure results in the typical signs of proptosis, ophthalmoplegia, and chemosis.

Orbital cellulitis resulting from infection of the maxillary sinus secondary to dental infections can be caused by microorganisms indigenous to the mouth, including anaerobes, commonly Bacteroides species.

Those cases stemming from dacryocystitis most commonly are caused by S aureus, S pneumoniae, Streptococcus pyogenes, and nontypeable H influenzae. Infections spreading from the soft tissues of the eyelids and face are due most commonly to staphylococci and S pyogenes. The initial antibiotic regimen can be modified if the response is inadequate or if the cultures dictate otherwise.

Traumatic causes

Infectious material may be introduced into the orbit directly through accidental (eg, orbital fracture) or surgical trauma. Indeed, orbital cellulitis may be caused by any injury perforating the orbital septum. Orbital inflammation^[2] may be noted within 48-72 hours after injury, or, in the case of a retained orbital foreign body, it may be delayed for several months.

Surgical procedures, including orbital decompression, dacryocystorhinostomy, eyelid surgery,^[3] strabismus surgery, retinal surgery, and intraocular surgery, have been reported as the precipitating cause of orbital cellulitis. Postoperative endophthalmitis can extend to the orbital soft tissues.

Bacterial causes

Streptococcus species, Staphylococcus aureus, and Haemophilus influenzae type B are the most common bacterial causes of orbital cellulitis. Pseudomonas, Klebsiella, Eikenella, and Enterococcus are less common culprits. Polymicrobial infections with aerobic and anaerobic bacteria are more common in patients aged 16 years or older.

Fungal causes

Fungal causes of orbital cellulitis are most commonly Mucor and Aspergillus species. Fungi can enter the orbit. Orbital cellulitis due to fungal infections carries a high mortality rate in patients who are immunosuppressed.

Zygomycosis (also known as mucormycosis or phycomycosis)^{[4, 5, 6]} has a wide distribution, while aspergillosis more commonly is seen in warm, humid climates. Mucormycosis can cause rapid-onset thrombosing vasculitis (1-7 days), while some forms of aspergillosis can be chronic and indolent (months to years).

Aspergillosis initially results in chronic proptosis and decreased vision, while mucormycosis gives rise to the orbital apex syndrome (involving cranial nerves II, III, IV, V-1, and VI, and orbital sympathetics). More commonly, mucormycosis presents with pain, lid edema, proptosis, and visual loss. While aspergillosis and mucormycosis may each result in nasal and palatal necrosis, mucormycosis also may lead to thrombosing arteritis and ischemic necrosis, while aspergillosis gives rise to chronic fibrosis and a nonnecrotizing granulomatous process.

Path of infection

The medial orbital wall is thin and is perforated not only by numerous valveless blood vessels and nerves but also by numerous defects (lamina papyracea/Zuckerkandl dehiscences). This combination of thin bone, foramina for neurovascular passage, and naturally occurring defects in the bone allows for easy communication of infectious material between the ethmoidal air cells and the subperiorbital space in the medial aspect of the orbit. The most common location of a subperiorbital abscess is along the medial orbital wall. The periorbita is adherent relatively loosely to the bone of the medial orbital wall, which allows abscess material to easily move laterally, superiorly, and inferiorly within the subperiorbital space.

In addition, the lateral extensions of the sheaths of the extraocular muscles, the intermuscular septa, extend from one rectus muscle to the next and from the insertions of the muscles to their origins at the annulus of Zinn, posteriorly. Posteriorly in the orbit, the fascia between the rectus muscles is thin and often incomplete, allowing easy extension between the extraconal and intraconal orbital spaces.

Venous drainage from the middle third of the face, including the paranasal sinuses, is mainly via the orbital veins, which are without valves, allowing the passage of infection anterograde and retrograde.

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Epidemiology

An increased incidence of orbital cellulitis occurs in the winter nationally and internationally, because of the increased incidence of sinusitis in cold weather.

In the United States, an increase has been noted in the frequency of orbital cellulitis due to community-acquired methicillin-resistant S aureus infections.^{[7, 8, 9, 10, 11, 12, 13]}

Sex- and age-related demographics

In children, orbital cellulitis has been reported as twice as common in males as in females. In adults, however, no difference in the frequency of orbital cellulitis exists between the sexes, except for cases caused by methicillin-resistant Saureus, which are more common in females than in males by a ratio of 4:1.

Orbital cellulitis, in general, is more common in children than in adults.^[14] The median age range of children hospitalized with orbital cellulitis is 7-12 years.

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Prognosis

Prior to the availability of antibiotics, patients with orbital cellulitis had a mortality rate of 17%, and 20% of survivors were blind in the affected eye. As a result of prompt diagnosis and the appropriate use of antibiotics, however, this rate has been reduced significantly, although blindness still occurs in up to 11% of cases. Orbital cellulitis due to methicillin-resistant S aureus can lead to blindness despite antibiotic treatment.

Morbidity and mortality

Orbital cellulitis can result in orbital and intracranial complications. Subperiosteal or orbital abscess formation may occur (7-9%), while permanent vision loss may result from corneal damage secondary to exposure or neurotrophic keratitis, destruction of intraocular tissues, secondary glaucoma, optic neuritis, or central retinal artery occlusion. Blindness also may occur secondary to elevated intraorbital pressure or the direct extension of infection to the optic nerve from the sphenoid sinus.

Direct involvement of the ocular motor nerves or the extraocular muscles may lead to decreased ocular motility.

Intracranial complications include meningitis (2%), cavernous sinus thrombosis (1%), and intracranial, epidural, or subdural abscess formation. Cavernous sinus thrombosis has a mortality rate of 50% or higher, but it has become relatively rare in industrialized countries with proper treatment. Cavernous sinus thrombosis should be considered in any patient with orbital cellulitis and should be suspected in the presence of rapid progression of the clinical signs (eg, increasing proptosis, mydriasis, dilation of retinal veins, decreasing visual acuity, development of an afferent pupillary defect).

Intracranial abscess formation is suggested by altered consciousness, signs of central nervous system disturbance, persistent fever despite adequate antibiotic therapy, and resolution of the sinusitis and orbital cellulitis components of the disease.

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History

A thorough history and physical examination are critical in establishing a diagnosis of orbital cellulitis. Patients with orbital cellulitis frequently complain of fever, malaise, and a history of recent sinusitis or upper respiratory tract infection. Questioning the patient about any recent facial trauma or surgery, dental work,^[15] or infection elsewhere in the body is important.

Diverse conditions such as sickle cell orbitopathy, bisphosphonate use, and cosmetic fillers can cause orbital inflammation that can be mistaken for infection.

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Physical Examination

Proptosis and ophthalmoplegia are the cardinal signs of orbital cellulitis. The symptoms and signs of orbital cellulitis can advance at an alarming rate and eventually lead to prostration. (See the images below.)

View Image

A male patient with orbital cellulitis with proptosis, ophthalmoplegia, and edema and erythema of the eyelids. The patient also exhibited pain on eye ....

View Image

A male patient with orbital cellulitis who demonstrated proptosis, ophthalmoplegia, and edema and erythema of the eyelids. The patient also exhibited ....

Proptosis and ophthalmoplegia may be accompanied by the following:

• Decreased vision, dyschromatopsia, and relative afferent pupillary defect
• Elevated intraocular pressure
• Pain on eye movement
• Conjunctival chemosis
• Orbital pain and tenderness - Are present early
• Dark red discoloration of the eyelids, chemosis, hyperemia of the conjunctiva, and resistance to retropulsion of the globe may be present
• Purulent nasal discharge may be present

Vision may be normal early, but it may become difficult to evaluate in very ill children with marked edema.

The above signs may be accompanied by the following:

• Fever
• Headache
• Lid edema
• Rhinorrhea
• Increasing malaise

Methicillin-resistant Staphylococcus aureus (MRSA) should be considered in the setting of multiple orbital abscesses and lacrimal gland abscess.

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Laboratory Studies

Laboratory evaluation should include the following (needle aspiration of the orbit is contraindicated):

• Complete blood count (CBC) - Leukocytosis greater than 15,000 with a shift to the left commonly is seen.
• Blood cultures - Obtain blood cultures prior to the administration of any antibiotics, although they are unlikely to reveal the responsible organism
• Purulent material assessment - Collect purulent material from the nose with a cotton or calcium alginate swab, smear for Gram stain, and culture on aerobic and anaerobic media; assess any material obtained from the sinuses or directly from an orbital abscess in the same manner

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Imaging Studies

High-resolution contrast CT scanning of the orbit with axial and coronal views is very helpful. Axial views should include low, narrow cuts of the frontal lobes to rule out peridural and parenchymal brain abscess formation. Coronal views are helpful in determining the presence and extent of any subperiorbital abscesses. Orbital fat stranding suggests orbital cellulitis. Globe tenting is an adverse prognostic sign, particularly in adults.^[17]

MRI may be helpful in defining orbital abscesses and in evaluating the possibility of cavernous sinus disease.

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Procedures

Lumbar puncture is advisable if cerebral or meningeal signs develop.

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Approach Considerations

The patient with orbital cellulitis should be promptly hospitalized for treatment, with hospitalization continuing until the patient is afebrile and has clearly improved clinically. Historically, the presence of subperiosteal or intraorbital abscess was an indication for surgical drainage in addition to antibiotic therapy. However, medical management alone can be successful in select patients without visual loss, especially those with small (< 500 mm³), medially located, pediatric subperiosteal abscess.^{[18, 19, 20]}

Surgery

Canthotomy and cantholysis should be performed on an emergency basis if an orbital compartment syndrome is diagnosed. In patients with corneal exposure, continued lubrication is important.

Consider surgical drainage if the response to appropriate antibiotic therapy has been poor within 24-48 hours, if the CT scan shows the sinuses to be completely opacified, if the patient has an intraorbital abscess, or if there is a large subperiosteal abscess, especially in an adult. The drains should be left in place for several days. Repeat surgical drainage may be required. In cases of fungal infection, surgical debridement of the orbit is indicated and may require exenteration of the orbit and the sinuses.

Consultations

Ear, nose, and throat (ENT) consultation is required for cases of orbital cellulitis arising from sinus disease. Consult other specialists such as pediatricians, infectious disease specialists, and radiologists, as indicated. Neurosurgical consultation is indicated if brain abscesses appear.

Transfer

If necessary, the patient may be transferred for further diagnostic evaluation or for surgical intervention.

Deterrence/prevention

No foolproof method for the prevention of orbital cellulitis exists; however, proper treatment of conditions that may precipitate orbital cellulitis (eg, preseptal cellulitis, sinusitis, dental disease) is the best deterrent.

Diet

No special dietary requirements are indicated other than adequate hydration of the patient.

Follow-up

Patients with severe orbital cellulitis often follow a protracted course, and repeat surgery may be required. Patients are ideally monitored by an ophthalmologist, ENT specialist, and infectious disease specialist until symptoms, fever, WBC count, and imaging confirm that antibiotics can be discontinued.

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Inpatient Care

Closely monitor the patient at least daily, with vision reevaluated by standardized vision testing, preferably by the same examiner, as appropriate. The extent of erythema can be marked with a marking pen. Evaluate the antibiotic coverage daily and change it as needed, depending on the results of cultures and the patient's clinical course.^[21] Repeat CT scans if the patient's condition worsens or does not respond to appropriate antibiotics.

Once the patient is clearly improving and has been afebrile for at least 48 hours, he or she can be changed from IV antibiotics to oral antibiotics (eg, amoxicillin clavulanate, ampicillin, cefpodoxime, cefuroxime, cefprozil) for aerobic infections or to metronidazole for anaerobic infections.

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Pharmacologic Therapy

Medical care of orbital cellulitis consists of the proper use of the appropriate antibiotics. Broad-spectrum IV antibiotics should be started immediately and continued until the choice of antibiotics can be tailored for specifically identified pathogens identified on cultures. Typically, IV antibiotic therapy should be continued for 1-2 weeks and then followed by oral antibiotics for an additional 2-3 weeks. Fungal infection requires IV antifungal therapy along with surgical debridement.

Regarding pediatric care, a study by Emmett et al found that the length of IV therapy associated with successful nonsurgical management of children with subperiosteal abscess was considerably shorter than the length of time normally recommended in pediatric infectious disease literature. This result suggested that clinical judgment regarding each patient’s initial CT scan findings and evolving signs, symptoms, and laboratory profile should be taken into account when scheduling IV intervals.^[22]

Traditionally systemic steroids are not initiated until the patient improves with antibiotic or surgical intervention. One pediatric orbital cellulitis study suggests intravenous steroids with antibiotics upon hospital admission.^[23]

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Indications for Surgical Drainage

Surgical drainage of an orbital abscess is indicated in any of the following instances:

• A decrease in vision occurs
• An afferent pupillary defect develops
• Proptosis progresses despite appropriate antibiotic therapy
• The size of the abscess does not reduce on CT scan within 48-72 hours after appropriate antibiotics have been administered; if brain abscesses develop and do not respond to antibiotic therapy, craniotomy is indicated.
• The presence of a drainable fluid collection is evident on CT scan in patients older than 16 years

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Medication Summary

Prompt administration of appropriate antibiotics is key to successful treatment of orbital cellulitis. Most cases of orbital cellulitis result from ethmoid sinusitis; in such cases, the initial antibiotics are chosen based on the most likely sinus pathogens, primarily Streptococcus pneumoniae and other streptococci, S aureus, H influenzae, and non-spore–forming anaerobes.

The occurrence of methicillin-resistant S aureus in orbital cellulitis is increasing, and empiric antimicrobial therapy should be directed against this organism if it is prevalent in the community. Infection due to methicillin-resistant S aureus is best treated with vancomycin and clindamycin.

Fungal orbital cellulitis also occurs and is primarily due to Mucor and Aspergillus species. Fungal infection requires antifungals, such as amphotericin.

Corticosteroids may be helpful, but they should not be started until after any surgery is performed and until the patient has been on appropriate antibiotics for 2-3 days.

If glaucoma develops secondary to orbital cellulitis, ocular antihypertensives should be administered promptly. In cases of posttraumatic orbital cellulitis, tetanus prophylaxis should be given according to standard protocol.

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Vancomycin

• Dosing, Interactions, etc.

Clinical Context:  Vancomycin is a tricyclic glycopeptide antibiotic for IV administration. It is indicated for the treatment of susceptible strains of methicillin-resistant (beta-lactam resistant) staphylococci in penicillin-allergic patients.

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Clindamycin (Cleocin)

• Dosing, Interactions, etc.

Clinical Context:  Clindamycin inhibits bacterial protein synthesis at the bacterial ribosomal lever, binding with preference to the 50S ribosomal subunit and affecting the peptide chain initiation process.

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Nafcillin

• Dosing, Interactions, etc.

Clinical Context:  Nafcillin is a semisynthetic penicillin that is effective against a wide gram-positive spectrum, including Staphylococcus, pneumococci, and group A beta-hemolytic streptococci.

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Ceftazidime (Fortaz, Tazicef)

• Dosing, Interactions, etc.

Clinical Context:  Ceftazidime is a semisynthetic, broad-spectrum, beta-lactam antibiotic for parenteral injection. It has a broad spectrum of effectiveness against gram-negative aerobes, such as H influenzae; gram-positive aerobes, such as S aureus (including penicillinase and non-penicillinase-producing strains) and S pyogenes; and anaerobes, including Bacteroides species.

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Chloramphenicol

• Dosing, Interactions, etc.

Clinical Context:  Chloramphenicol exerts a bacteriostatic effect on a wide range of gram-negative and gram-positive bacteria and is particularly effective against H influenzae.

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Ticarcillin and clavulanate potassium (Timentin)

• Dosing, Interactions, etc.

Clinical Context:  Ticarcillin is a semisynthetic, injectable penicillin that is bactericidal against gram-positive and gram-negative organisms, including H influenzae, S aureus (non-penicillinase producing), beta-hemolytic streptococci (group A), S pneumoniae, and anaerobic organisms, such as Bacteroides and Clostridium species. Clavulanate potassium is a beta-lactamase inhibitor that protects against resistance by beta-lactamase producing enzymes.

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Cefazolin

• Dosing, Interactions, etc.

Clinical Context:  Cefazolin is a semisynthetic cephalosporin for intramuscular (IM) or IV administration. It has a bactericidal effect against S aureus (including penicillinase-producing strains), group A beta-hemolytic streptococci, and H influenzae.

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Trimethoprim and sulfamethoxazole (Bactrim, Bactrim DS, Septra DS, Sulfatrim)

• Dosing, Interactions, etc.

Clinical Context:  Trimethoprim/sulfamethoxazole inhibits bacterial growth by inhibiting the synthesis of dihydrofolic acid. The antibacterial activity of trimethoprim/sulfamethoxazole includes common urinary tract pathogens, except Pseudomonas aeruginosa.

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Class Summary

Appropriate antibiotics may include nafcillin (for Staphylococcus and Streptococcus species) and metronidazole (for anaerobes).

Ticarcillin-clavulanate would cover most gram-positive and gram-negative organisms and most anaerobes. Nafcillin in combination with ceftazidime is also appropriate, although chloramphenicol may be substituted for ceftazidime. Cefazolin can be used in place of nafcillin in cases of mild allergy to penicillin and vancomycin can be used in cases of severe penicillin allergy.

Vancomycin, clindamycin, and trimethoprim/sulfamethoxazole double-strength would be appropriate for susceptible penicillinase- and non-penicillinase-producing strains of methicillin-resistant S aureus.

It is prudent to consult with an infectious disease specialist for the latest antibiotic recommendations if in doubt.

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Amphotericin B deoxycholate (AmBisome)

• Dosing, Interactions, etc.

Clinical Context:  This is a lipid preparation consisting of amphotericin B within unilamellar liposomes. It delivers higher concentrations of the drug, with a theoretical increase in therapeutic potential and decreased nephrotoxicity.

Amphotericin is the antifungal medication of choice in the treatment of fungal orbital cellulitis. It is administered intravenously and, in cases of severe infection, may be appropriately provided before laboratory confirmation of fungal infection.

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Class Summary

Fungal orbital cellulitis is a potentially lethal condition, and the principal organisms involved, Mucor and Aspergillus, require the use of antifungals.

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Phenylephrine nasal (Neo-Synephrine, Nasal Decongestant, Sudogest PE, Sudafed PE)

• Dosing, Interactions, etc.

Clinical Context:  This agent is beneficial in the treatment of nasal congestion that may cause blockage of the ostia of the sinus, interfering with sinus drainage.

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Oxymetazoline (Afrin 12 Hour, Afrin Sinus, Neo-Synephrine 12 Hour Spray, QlearQuil, Dristan Spray)

• Dosing, Interactions, etc.

Clinical Context:  Oxymetazoline is applied directly to mucous membranes, where it stimulates alpha-adrenergic receptors and causes vasoconstriction. Decongestion occurs without drastic changes in blood pressure, vascular redistribution, or cardiac stimulation.

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Class Summary

Nasal decongestants may help to open the sinus ostia and aid with drainage in cases of orbital cellulitis secondary to sinusitis.

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Acetazolamide (Diamox Sequels)

• Dosing, Interactions, etc.

Clinical Context:  Acetazolamide inhibits the enzyme carbonic anhydrase, reducing IOP by reducing the rate of aqueous humor formation. It is used for the adjunctive treatment of chronic simple (open-angle) glaucoma and secondary glaucoma and is employed preoperatively in acute angle-closure glaucoma when there is a desire to delay surgery in order to lower IOP.

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Class Summary

These agents reduce intraocular pressure (IOP).

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Prednisone (Rayos, Deltasone)

• Dosing, Interactions, etc.

Clinical Context:  Prednisone inhibits phagocytosis of platelets and may improve RBC survival.

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Prednisolone (Orapred ODT, Prelone, Millipred)

• Dosing, Interactions, etc.

Clinical Context:  Prednisolone decreases autoimmune reactions, possibly by suppressing key components of the immune system. This agent does not need to undergo hepatic metabolism.

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Class Summary

Corticosteroids have anti-inflammatory properties and cause profound and varied metabolic effects. These agents modify the body's immune response to diverse stimuli. Corticosteroids may be helpful, but they should not be started until after any surgery is performed and until the patient has been on appropriate antibiotics for 2-3 days.

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