Intraorbital Injection of Triamcinolone Acetonide in Patients With Idiopathic Orbital Inflammation FREE

Idiopathic orbital inflammation (IOI) refers to benign noninfective inflammatory conditions of the orbit without identifiable local or systemic cause.¹ Onset is generally acute or subacute and may be focal (myositis, dacryoadenitis, anterior, or apical) or diffuse. Histopathologic analysis usually reveals a nonspecific, chronic, polymorphic inflammatory infiltrate, but sclerosing and nonspecific granulomatous variants may also be seen.^{2 - 3} Though IOI is usually exquisitely sensitive to corticosteroid therapy, a large percentage of patients may not demonstrate this rapid response or may require long-term maintenance therapy,^{1 ,4} exposing them to the considerable adverse effects of systemic corticosteroid therapy. Local corticosteroid injections are an attractive alternative, especially because ophthalmologists are familiar with the procedure. While periocular corticosteroid injections are an established treatment for intraocular inflammation, to our knowledge, there are few reports in the literature about their use in orbital inflammatory conditions.^{5 - 8} We describe the successful treatment of biopsy-proved IOI with intraorbital corticosteroid injections.

The study group included all patients with clinically, radiologically, and histologically confirmed IOI and an anterior inflammatory mass treated with intraorbital injection of 40 mg/mL of triamcinolone acetonide at the Royal Adelaide Hospital, Adelaide, South Australia, from January 1, 2002, through October 31, 2006. Patients with a blind contralateral eye, glaucoma, ocular hypertension, or bilateral orbital inflammation were excluded from the study. Patients with posteriorly located orbital inflammation were excluded because of the small number of cases (<10% of IOI cases at our center) and because these patients were treated empirically with corticosteroids in the first instance owing to the possible morbidity associated with biopsy. This study was approved by the institutional review board, and all patients gave written informed consent before treatment.

Data collected in the study group included initial clinical signs and symptoms, findings at physical examination and at computed tomography or magnetic resonance imaging, and final outcome. Patients were assessed for local and systemic complications of corticosteroid injection including visual acuity, fundus examination, intraocular pressure, systemic blood pressure, and serum glucose levels. Follow-up examination was performed at 1 and 4 weeks after each orbital corticosteroid injection.

Twenty to 40 mg/mL of triamcinolone acetonide was injected intraorbitally (intralesionally or perilesionally) using a 27- or 25-gauge needle. Follow-up visits were at 1 and 4 weeks. The decision to repeat the injection at 4 weeks was based on the clinical response and signs of an active inflammatory process. If no response was noted 4 weeks after the injection, the treatment was not repeated.

The demographic data and clinical characteristics of the 10 patients are given in the Table. There were 5 men and 5 women, with a mean age of 49.8 years (age range, 25-82 years). In most patients, onset of IOI was subacute. Eyelid edema, ptosis, mild proptosis, globe displacement, and impairment of motility were common findings. At imaging, the disease process was found to involve the lacrimal gland in 4 patients, the lacrimal gland and superior rectus muscle in 2 patients (Figure 1), the superior rectus muscle in 2 patients, the lateral rectus muscle in 1 patient (Figure 2), and the inferomedial orbit in 1 patient. Histologic analysis revealed nonspecific, nongranulomatous, chronic inflammation in 5 patients, sclerosing inflammation in 3 patients, and nonspecific granulomatous inflammation in 2 patients.

Intralesional or perilesional triamcinolone acetonide was injected in all 10 patients. Based on clinical findings, repeated injections were given in 4 patients, all of whom demonstrated an excellent response. Five patients had complete resolution of symptoms after a single injection. One patient did not respond to the first injection and refused further treatment. There were no signs of recurrence over a mean follow-up of 9.8 months (range, 3-24 months) in the 9 patients who responded to the corticosteroid injections.

The only complication noted was an isolated episode of nausea and vomiting that developed a few hours following the injection in 1 patient. None of the patients demonstrated increased intraocular pressure or any systemic complications as a result of corticosteroid treatment. None of the patients had diabetes mellitus.

Idiopathic orbital inflammation was treated with intraorbital injection of triamcinolone acetonide in 10 patients in our unit during a 5-year period. Intraorbital injection of corticosteroids (sub-Tenon space or orbital floor injection) is well established in the treatment of intraocular inflammation. Similarly, intralesional injection of corticosteroids has been used to treat periorbital conditions such as capillary hemangioma,⁹ chalazia,¹⁰ cutaneous sarcoidosis,¹¹ and vernal keratoconjunctivitis.¹² Intralesional corticosteroid injections are the most commonly used treatment of periorbital capillary hemangiomas.¹³ The use of intraorbital corticosteroid injections to treat orbital diseases, however, has not been widely reported, with only isolated series documenting its use in thyroid ophthalmopathy,⁵ orbital xanthogranuloma,⁶ dacryoadenitis,⁸ and orbital capillary hemangioma.¹⁴ Elner et al⁶ treated 6 patients with orbital xanthogranuloma with intralesional triamcinolone acetonide injection (dose range, 20-120 mg). Local control was obtained in all patients; however, 4 patients required repeated injections (22 injections in 1 patient). Mohammad⁸ described a series of 5 patients with acute dacryoadenitis who were treated with intralesional betamethasone injection (dose range, 14-28 mg). All patients had complete resolution of disease after a single injection, and no recurrence was noted over a minimum follow-up of 8 months.

The use of intraorbital corticosteroid injections in thyroid ophthalmopathy has a long history but does not seem to be widely used.^{15 - 16} Recently, Ebner et al⁵ reported the beneficial effects of periocular triamcinolone injection in diplopia and extraocular muscle size in 20 patients. In that study, a series of 4 weekly injections of 20 mg of triamcinolone acetonide were given in the inferolateral quadrant of each orbit. No complications were observed.

Harris¹⁷ has suggested that intraoperative local injection with triamcinolone is useful, especially in sclerosing inflammation. In our series, 2 of the 3 patients with sclerosing inflammation showed a response to triamcinolone injection.

Triamcinolone acetonide has been most commonly used for periocular injections, though betamethasone and methylprednisolone have also been used.^{8 ,18} The elimination rate of these corticosteroid boluses from the injection site has not been well documented, but active corticosteroid has been found 13 months after triamcinolone injection.¹⁹ The dose equivalent between systemic and periocular corticosteroid is also unknown; though Goldberg⁷ has suggested that a 40-mg injection is equivalent to a 20-mg/d dose of orally administered prednisone.⁷ As with oral corticosteroids, periocular injections may also need to be repeated several times before the desired therapeutic effect is achieved. However, inasmuch as the injections are not given daily, the total systemic dose is substantially smaller with periocular corticosteroids.

Although the injection of orbital corticosteroids is usually safe, potential risks include skin depigmentation,⁷ methyl cellulose–initiated granuloma,⁷ intractable elevated intraocular pressure,²⁰ ptosis,²¹ globe perforation,²² corneoscleral or conjunctival melting,²³ retinal artery occlusion from embolization or pressure-induced optic nerve compression,^{24 - 25} proptosis,²⁶ and fat atrophy.^{27 - 28} Increased intraocular pressure is a well-recognized adverse effect of periocular corticosteroid injection and in intractable cases may necessitate surgical removal of the corticosteroid bolus.¹⁹ Ptosis is a complication after injection into the posterior sub-Tenon space but seems to occur exclusively after triamcinolone injection and may reflect the myotoxic effect of this drug.^{18 ,29} As Goldberg⁷ noted, however, most of these complications have been reported after injection into the posterior sub-Tenon space, and it is conceivable that anteriorly placed intraorbital injections would substantially decrease the complication rate

The most dreaded complication of periorbital corticosteroid injection is central retinal artery occlusion²⁶ ; however, this seems to be a rare complication and is primarily associated with injections into capillary hemangiomas.^{13 ,30} Systemic effects are uncommon, though adrenal suppression has been reported after periocular corticosteroid injection.³¹ The decreased risk of systemic adverse effects with local injection compared with systemic use makes this a good option in patients who demonstrate a good response to corticosteroid therapy but are intolerant of the systemic adverse effects. Complications may be minimized with attention to the injection technique and use of the smallest volume necessary (≤1 mL of a 40-mg/mL triamcinolone injection). Imaging studies should be used to localize the quadrant of injection, and injection away from the globe into the anterior orbit may minimize complications. At least a 27-gauge needle and preferably a 25-gauge needle should be used because smaller needles offer greater resistance to corticosteroid flow and increase injection pressure.³² The plunger must be withdrawn before injection as a safeguard against intravascular injection. The corticosteroid should then be injected slowly with the patient's eyes open to detect any blurring of vision during the treatment. The fundus may be monitored during the injection with indirect ophthalmoscopy or with an immediate postinjection fundus examination.

As with systemic corticosteroid therapy, some patients are resistant to periocular corticosteroid treatment. In our opinion, it is unlikely that patients with a localized disease process who do not respond to corticosteroid injection will respond to systemic corticosteroid therapy. However, because the dose equivalent between corticosteroid injections and systemic corticosteroid therapy is unknown, a trial of high-dose systemic corticosteroid therapy may be considered before other therapies such as immunosuppressive agents or radiotherapy.¹⁷

Our findings demonstrate that intraorbital corticosteroid injections may be at least as efficacious as systemic corticosteroid therapy in the treatment of anterior IOI, with minimal systemic adverse effects. Larger studies will be required to further assess the local safety issues with the use of corticosteroid injections in the context of IOI. The risk of local adverse effects perhaps may be minimized by giving close attention to the technique, placing the corticosteroid bolus in the anterior orbit, using a 25-gauge needle, and using the smallest volume necessary of corticosteroid. Biopsy is recommended in all cases to confirm the diagnosis and to exclude malignant neoplasm. A substantial number of patients may require repeated injections to achieve a therapeutic response. Although further investigation is required to delineate the safety profile, intraorbital corticosteroid injections may have a role as first-line therapy in the treatment of anteriorly located IOI and in patients with IOI who are corticosteroid responsive but corticosteroid intolerant.

Correspondence: Venkatesh C. Prabhakaran, MS, MRCOphth, Oculoplastic and Orbital Division, Department of Ophthalmology and Visual Sciences, Royal Adelaide Hospital, University of Adelaide, North Terrace, Adelaide 5000, South Australia (eye@health.sa.gov.au).

Submitted for Publication: April 29, 2007; final revision received July 4, 2007; accepted July 15, 2007.

Author Contributions: Drs Leibovitch, Prabhakaran, and Selva had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Leibovitch and Selva. Acquisition of data: Davis and Selva. Analysis and interpretation of data: Prabhakaran and Selva. Drafting of the manuscript: Leibovitch and Prabhakaran. Critical revision of the manuscript for important intellectual content: Davis and Selva. Administrative, technical, and material support: Selva. Study supervision: Leibovitch, Davis, and Selva.

Financial Disclosure: None reported.