Diagnosis and treatment of a red, swollen eye

Abstract

Unilateral eye swelling, redness, and pain may represent a diagnostic challenge to many clinicians. The differential diagnosis is broad and includes both nonemergent and emergent diagnoses. While the emergent diagnoses must be made and treatment initiated immediately, the nonemergent differential also includes life- and vision-threatening entities. The diagnosis of idiopathic orbital inflammatory syndrome (IOIS) is characterized by acute-onset, typically unilateral periorbital swelling, chemosis, and proptosis. It can be differentiated from other entities by radiologic findings and rapid response to corticosteroids; however, it is often a diagnosis of exclusion. We report a case-based discussion including distinguishing features, diagnostic modalities, and treatment of similar entities involving periorbital/orbital edema and conjunctival injection complicated by a past medical history of breast cancer.

CASE STUDY

A 59-year-old Nigerian woman with hypertension, hyperlipidemia, and left breast cancer treated with mastectomy and chemotherapy in 2005, as well as a recent history of “strep” throat treated with amoxicillin, presented to an outside hospital after experiencing left eye swelling and pain with eye movement for 3 days. Two days before her symptoms appeared, she had an ocular exam at Wal-Mart for eye discomfort and was given a new glasses prescription. She was seen at three different outside facilities for worsening swelling before being transferred to Baylor University Medical Center at Dallas (BUMC) for a higher level of care. On admission, the patient reported unilateral eye pain with eye movement, redness, and excessive tearing. The patient denied blurred vision, diplopia, headache, sinus pain, epistaxis, fevers, chills, weight loss, and night sweats. The remainder of the review of symptoms was negative or noncontributory. She did not wear contact lenses and recalled no trauma to the eye.

At the time of admission, she was taking lisinopril, hydrochlorothiazide, and pravastatin daily and had no drug allergies. She denied recent alcohol or any tobacco or recreational drug use. She had moved to Texas from Nigeria 1 year earlier, and while she was currently unemployed, she had worked as a nurse in Nigeria.

Physical examination revealed hypertension (144/64 mm Hg), a pulse of 67 beats per minute, a respiration rate of 18 breaths per minute, a temperature of 98.7°F, and oxygen saturation of 100% on room air. She was a thin, African woman in no acute distress. She had a 2/6 systolic ejection murmur with radiation to the axilla heard best at the mitral valve position. The patient had a well-healed left mastectomy scar without palpable nodules, tenderness, drainage, or exudates. The right breast had no palpable nodules, tenderness, or nipple discharge, and there was no palpable cervical, supraclavicular, or axillary lymphadenopathy. The remainder of the physical exam was within normal limits with exception of the ophthalmic exam.

The ophthalmic exam revealed a white and quiet sclera of the right eye, with a deep anterior chamber and no obvious abnormalities of the lids or lashes or any obvious external disease. The left eye had a partial ophthalmoplegia with a partial lateral rectus palsy, ptosis, proptosis, chemosis, and periorbital edema. There was no afferent pupillary defect, and the pupillary exam was within normal limits bilaterally. The funduscopic exam was unremarkable. Visual acuity without correction was 20/25 in both eyes, which was the patient's baseline. Visual fields were grossly intact. The patient was initially admitted to the general medicine unit and placed on broad-spectrum antibiotics for possible orbital cellulitis.

Admission laboratory values were as follows: white blood count, 10.9 K/μL with normal differential and 0% bands; hemoglobin, 11.1 g/dL; hematocrit, 33.3%; platelets, 381 K/μL; mean corpuscular volume, 87.2 fL; sodium, 133 mEq/L; potassium, 4 mEq/L; chloride, 95 mEq/L; bicarbonate, 30 mEq/L; and calcium, 9.2 mg/dL. Both renal function and liver function tests were within normal limits. Her globulin level was elevated at 6.8 g/dL, her total protein level was elevated at 9.8 g/dL, and her thyroid-stimulating hormone level was low at <0.01, both at her presentation to the outside hospital and at BUMC. Two sets of blood cultures had no growth after 5 days.

Further testing for abnormalities revealed a T₃ level of 4.0 pg/mL and free T₄ of 2.0 ng/dL, consistent with hyperthyroidism; however, results for antithyroglobulin, antimicrosomal, and antithyrotropin receptor antibodies were negative. Workup for normocytic anemia revealed normal B12 and folate levels, and iron studies were consistent with iron deficiency anemia and anemia of chronic disease. Evaluation of elevated globulin and total protein revealed an absence of HIV, and a hepatitis panel was remarkable for previous hepatitis B exposure. Antinuclear antibody was positive at 1:320 in a nucleolar pattern. Anti-dsDNA, HLA-B27, and angiotension-converting enzyme testing was negative.

Magnetic resonance imaging (MRI) of the orbits with and without contrast (Figure) revealed marked lateral rectus muscle enlargement with abnormal homogeneous enhancement resulting in a decreased volume and diameter of the posterior orbit and apex, with proptosis. The left lacrimal gland was also involved, with surrounding intraconal and extraconal inflammatory changes including subtle thickening and enhancement of the left posterior globe consistent with periscleritis. No ring-enhancing focus was present.

Figure.

MRI of the head showing inflammatory changes of the left orbit with isolated involvement of the left lateral rectus muscle.

DISCUSSION

The differential diagnosis in this case includes cellulitis, particularly preseptal or orbital cellulitis, sarcoidosis, thyroid ophthalmopathy, rheumatologic disorders, idiopathic orbital inflammatory syndrome (IOIS) (also known as orbital pseudotumor), metastatic disease (particularly with the patient's history of breast cancer), and tumors, including neuroblastoma, rhabdomyosarcoma, lymphangioma, liposarcoma, and lymphoma. Trauma could be ruled out by her history.

The key diagnosis to rule out emergently is orbital cellulitis, which is an eye- and vision-threatening emergency. Orbital cellulitis typically presents with unilateral severe pain of acute onset. Key signs include limited ocular mobility (ophthalmoplegia), fever, elevated white blood cell count, and decreased vision. Imaging typically reveals a decreased signal of orbital fat, sinus disease, bony erosion, and/or venous thrombosis. Preseptal cellulitis can be differentiated from the more emergent orbital cellulitis by the limitation of infection to the soft tissues of the eyelids and periorbital tissues anterior to the orbital septum. Orbital cellulitis involves extension beyond the orbital septum and presents with the findings listed above. The treatment of orbital cellulitis is parenteral broad-spectrum antibiotics until the pathogen is identified. Coverage of the most likely organisms, which include Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus pyogenes, is essential; in pediatric cases, one must also consider Haemophilus influenza. Consensus recommendations suggest that coverage should include gram-positive, gram-negative, and anaerobic organisms. Treatment should begin promptly, as the risk for cavernous sinus thrombosis, meningitis, and brain abscesses is significant. Otolaryngologic evaluation should be obtained in cases of mucoceles or sinusitis. If the patient is immunocompromised or has diabetes mellitus, particularly with ketoacidosis, mucormycosis must be considered, which requires immediate surgical debridement and antifungal therapy.

Thyroid eye disease often presents with proptosis and can be accompanied by a red eye; however, thyroid eye disease is more commonly bilateral and has a more gradual onset. Thyroid function testing as well as antithyroglobulin, antimicrosomal, and antithyrotropin receptor antibody testing can be used to exclude this diagnosis. Common signs and symptoms include upper eyelid retraction, lid lag with infraduction, widened palpebral fissure during fixation, and lagophthalmos. Tearing, redness, and chemosis can result due to prolonged corneal exposure. Pain is not a typical symptom; however, periorbital swelling due to inflammation can be observed. The inferior rectus muscle is most commonly involved, leading to vertical diplopia on upgaze. In severe cases, the optic nerve can be compressed due to enlargement of the extraocular muscles at the orbital apex. Involvement of the tendinous insertion of the muscle distinguishes IOIS muscle enlargement from that of thyroid-associated orbitopathy, in which the tendinous insertion point is spared. This can lead to loss of visual acuity, field defects, afferent pupillary defect, and loss of color saturation. These extreme cases constitute a surgical emergency (1).

Tumors, both primary and metastatic, can be more challenging to rule in or out. Particularly in this case, with the patient's history of breast cancer, we were concerned about a metastatic lesion. Cases have described patients presenting with orbital inflammation associated with metastatic breast cancer lesions; however, other discrete lesions, such as a unilateral choroidal mass, were present as well (2). Indeed, the most common site of metastasis in breast cancer is the choroid (3). Additionally, ocular metastasis from breast cancer is typically preceded by metastasis to other organs, most commonly the lungs (4). Unilateral eye swelling with or without redness, pain, and ophthalmoplegia can be the result of liposarcoma, lymphoma, neuroblastoma, rhabdomyosarcoma, or lymphangioma. Imaging was helpful but not diagnostic. The diagnostic standard is to obtain a tissue diagnosis with biopsy, with or without immunohistochemical staining, when metastatic disease is thought to be likely.

IOIS is the most common diagnosis in adult patients presenting with a painful orbital mass (1); however, it is often a diagnosis of exclusion (5). Presentation is typically unilateral, although children may present with bilateral findings (6); it is also acute, with ocular pain, photophobia, proptosis, periorbital edema, chemosis, conjunctival injection, and occasionally diplopia. Vision loss is rare, and patients typically respond quickly and dramatically to high doses of glucocorticoids (5), allowing differentiation from other diagnostic entities. MRI often reveals mass lesions that are hypointense to orbital fat on T1 and isointense or minimally hyperintense to fat on T2 (7). The pathophysiology is thought to be autoimmune, mediated by both T cells and B cells, but the exact mechanisms are unknown (8). Biopsy typically reveals a mixed cellular infiltrate, and while biopsy is not usually indicated and may exacerbate the swelling and inflammation, it may be helpful in challenging cases (9). Workup to exclude other entities such as sarcoidosis and the above diagnoses should be pursued.

Based on the history, physical examination, and imaging (Table), the presumptive diagnosis of IOIS was made in our patient. Importantly, a biopsy was not obtained, and thus close follow up will be required to ensure the lesion was not an occult malignancy or metastatic lesion. The patient was treated with 60 mg of oral prednisone with a taper over 3 months. The patient had a dramatic response to the first dose of prednisone within 24 hours, further exemplifying this feature of IOIS. The patient has been followed closely by an ophthalmologist and is free of any symptoms at the time of this writing.

Table.

Focused differential diagnosis with exam findings, symptoms, distinguishing features, and treatment

	Idiopathic orbital inflammatory syndrome (orbital pseudotumor)	Orbital cellulitis	Thyroid eye disease	Metastatic or primary malignancy
Exam findings	Proptosis, periorbital edema, chemosis, conjunctival injection	Ophthalmoplegia, decreased visual acuity, afferent papillary defect	Upper eyelid retraction, lid lag with infraduction, widened palpebral fissure during fixation, lagophthalmos	Variable depending on type; typically unilateral mass effect
Symptoms	Ocular pain, photophobia	Fever, chills	Dry eye symptoms, tearing, vertical diplopia on upgaze	Variable depending on type
Distinguishing features	Rapid response to steroids within 24 to 48 hours; diagnosis of exclusion	Elevated white blood cell count, decreased signal of orbital fat on imaging, sinus disease	Thyroid function tests: thyroid-stimulating hormone; free T4; antithyroglobulin, antimicro-somal, and antithyrotropin receptor testing	History, magnetic resonance imaging findings, tissue diagnosis with or without biopsy, immunohistochemical staining
Treatment	High-dose steroids with taper	Intravenous antibiotics (initially broad-spectrum) covering Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus pyogenes	Antithyroid medications, surgery if needed, thyroid hormone replacement	Variable based on primary tumor and extent of metastasis