To report clinicopathologic features, radiologic findings, and treatment outcomes of isolated, orbital aspergillosis.
Multicenter, retrospective case series.
setting : Multicenter. participants : There were 8 lesions in 8 eyes of 8 patients with isolated, orbital aspergillosis. procedure : Review of medical records and histopathology slides. main outcome measures : Disease control.
Of 34 patients with orbital aspergillosis, 8 (23.5%) had isolated orbital involvement at presentation. The mean age at presentation was 34.5 years (median, 43 years: range, 0.5–72 years). Gradually progressive proptosis and eyelid swelling were the most common presenting features (each 4/8). Proptosis ranged from 4 mm to 9 mm (median, 5.5 mm; mean, 5.75 mm). Restriction of ocular motility was seen in all 8 patients. Other examination findings included palpable mass (2/8), conjunctival chemosis (2/8), hyperglobus (1/8), hypoglobus (1/8), and resistance to retropulsion (1/8). Microbial culture results were available in 1 patient and showed Aspergillus fumigatus . Two patients were treated with complete surgical excision alone while 6 were treated with antifungal medications. Complete resolution of proptosis and restoration of ocular motility were seen in all patients following treatment. Visual disturbances present in 1 were corrected following treatment. Recurrence was observed in 1 patient.
Isolated orbital aspergillosis, though rare, should be considered in the differential diagnosis of a patient presenting with a gradually progressive orbital mass, especially in Asian individuals. Early recognition will help reduce the morbidity and mortality associated with this disease.
Aspergillosis is a multifaceted disease caused by fungi of the genus Aspergillus . Aspergillus spp. are ubiquitous, spore-forming, dichotomously branching fungi often found in dampened soil, humid areas, agricultural environments, and decaying or decomposing matter. The spectrum of aspergillosis is wide, ranging from mere colonization (Aspergilloma) to disseminated infection. Aspergillus spores are commensals of the respiratory tract and external auditory canal. Understandably, the lungs and paranasal sinuses are the most commonly affected sites in human beings. Orbital involvement is uncommon and often a result of contiguous spread from the oropharynx or paranasal sinuses. Isolated orbital aspergillosis is extremely rare. Equally rare is its occurrence in immunocompetent, otherwise healthy individuals. We report on 8 cases of isolated, orbital aspergillosis in immunocompetent patients and also review the literature on this disease.
Materials and Methods
This was a retrospective, clinicopathologic study of 8 consecutive patients with isolated orbital aspergillosis treated at 6 centers; 5 of these were in India (Centre For Sight, Hyderabad, Delhi, and Jaipur, Vasan Eye Care Hospitals and Drishti Eye Care, Hyderabad) and 1 in Singapore (National University Health System, Singapore). This study was approved by the Institutional Review Board of each of the aforementioned institutes and was performed in accordance with the tenets of the 1964 Declaration of Helsinki. Informed consent was obtained from the patients. A retrospective chart review of all histopathologically or microbiologically proven cases of orbital aspergillosis was performed. Only those patients who had isolated orbital involvement at presentation and fungal elements with characteristics of aspergillosis on histopathologic examination of the orbital biopsy were included in the study. Exclusion criteria included incomplete data, unavailability of tissue material for histopathologic review, and follow-up less than 3 months. No cases were excluded. Patient folders were analyzed for demographic details, clinical features, imaging findings, treatment, and outcome. Patient survival with complete resolution of the lesion at 3 month follow-up was considered as treatment success. Histopathology slides were reviewed in all cases.
Thirty-four patients had histologically or microbiologically proven orbital aspergillosis at the 6 centers in the past 33 months (January 2013 to September 2015). Of these, 8 (23.5%) had an isolated orbital involvement at presentation.
Demographic details, clinical features, and imaging findings of all 8 patients with isolated orbital aspergillosis are shown in the Table . Common clinical and radiologic features are shown in Figures 1–3 .
|Case No.||Age (y)||Sex||Laterality||Duration of Symptoms (mo)||Presenting Features||Examination Findings||Primary Management||Medical Management||Recurrence|
|1||44||Male||Left||2||Lower eyelid swelling||Hypoglobus mass, proptosis, ROM (vertical gaze)||Incision biopsy||Itraconazole (200 mg BD orally for 3 months)||Yes|
|2||72||Female||Right||3||Upper eyelid swelling||ROM (vertical gaze), erythema and tenderness of upper eyelid||Complete excision||None||No|
|3||0.5||Male||Right||0.5||Upper and lower eyelid swelling||ROM (all gazes), hyperglobus, chemosis||Incision biopsy||IV amphotericin B (0.25 mg/kg for 3 weeks) followed by voriconazole (50 mg BD orally for 6 weeks)||No|
|4||13||Female||Right||6||Lower eyelid swelling, anterior orbital mass, diplopia||ROM (vertical gaze); firm, noncompressible mass||Complete excision||None||No|
|5||12||Female||Left||4||Gradually progressive proptosis, transient blurring of vision||ROM (vertical gaze), proptosis, resistance to retropulsion||Incision biopsy||Voriconazole (4 mg/kg IV for 6 weeks followed by 200 mg orally for 3 months)||No|
|6||42||Male||Left||18||Gradually progressive proptosis, diplopia, ptosis||ROM (all gazes), proptosis||Incision biopsy||Voriconazole (oral; 400 mg BD for 3 days followed by bolus 400 mg IV and then 200 mg orally BD for 6 months)||No|
|7||48||Female||Right||9||Gradually progressive proptosis||ROM (all gazes), chemosis, proptosis, periocular swelling||Incision biopsy||Itraconazole (200 mg TID for 3 days followed by 200 mg BD for 2 months)||No|
|8||45||Male||Left||3||Gradually progressive proptosis||ROM (all gazes), proptosis||Incision biopsy||Voriconazole (200 mg TID for 3 days followed by 200 mg BD for 2 months)||No|
Mean age at the time of first presentation to the clinic was 34.5 years (median, 43 years; range, 6 months to 72 years). One patient presented during infancy. No sex predilection was observed. There were 4 male and 4 female patients. Six patients were of Indian origin; 1 was a Myanmarese, and 1 was from the Middle East, both residing in Singapore for a considerable period. Orbital involvement was unilateral in all patients (8/8) with no predilection for any side (right, 4/8; left, 4/8). The mean duration of symptoms was 5.7 months (median, 3.5 months; range, 0.5–18 months). Gradually increasing proptosis ( Figure 1 , Top left, and Figure 2 , Top left) and eyelid fullness ( Figure 2 , Middle left and Bottom left, and Figure 3 , Top left) each occurred in 4 of 8 patients. Other symptoms included mass (2/8), diplopia (2/8), and intermittent and transient blurring of vision (1/8).
Proptosis ranged from 4 to 9 mm (median, 5.5 mm; mean, 5.75 mm). While variable degree (mild to severe) of ocular movement restriction ( Figure 1 , Middle and Bottom panels) was seen in all patients, a nontender, nonreducible, and noncompressible mass ( Figure 3 , Top left) was palpable in 2 patients (Cases 1 and 4). Visual acuity, colored vision, and papillary reactions (both direct and consensual) were normal in all patients. Fungal granuloma was suspected in only 1 patient (Case 7) at the time of clinical examination. Differential diagnoses on clinical examination included idiopathic orbital inflammation (5/8), ocular adnexal lymphoma (3/8), rhabdomyosarcoma (1/8), and lacrimal gland tumor (1/7). Intraoperatively, the mass was firm to gritty in all cases.
Computed tomography (CT) and magnetic resonance imaging (MRI) were performed in 6 and 2 patients, respectively. CT scan showed an ill-defined, infiltrative, homogenous, and hyperdense mass limited to the orbit in 4 patients (Cases 1, 6, 7, and 8) and was well-defined, homogenous, and hyperdense in 2 (Cases 2 and 4). MRI in 2 patients (Cases 3 and 5) showed the mass to be isointense to the extraocular muscle on T1-weighted images and hypointense to the muscle on T2-weighted images. Contrast enhancement was mild to moderate and patchy in 7 patients (Cases 1, 2, and 4–8). In the infant (Case 3), a diffuse, intense, and homogenous enhancement with gadolinium was observed. The mass was extraconal in 6 (Cases 1–5 and 8) and both intra- and extraconal in 2 (Cases 6 and 7). In 3 patients (Cases 6, 7, and 8), the disease extended posteriorly to involve the apex ( Figure 2 , Top right). Bone remodeling secondary to pressure effect ( Figure 2 , Middle right) was seen in 3 patients (Cases 1, 6, and 8). In 1 patient (Case 6), the mass was inseparable from the medial rectus and closely approximated to the optic nerve ( Figure 2 , Top right). The paranasal sinuses and nasal cavity were normal in all.
Histopathologic and Microbiologic Findings
An incision biopsy was performed in 5 patients (Cases 1 and 5–8), complete excision in 2 (Cases 2 and 4), and debulking in 1 (Case 3). Light microscopy, in all cases, showed noncaseating, epithelioid cell granulomas with multinucleate giant cells and lymphoplasmacytic infiltrate in a densely fibrotic stroma ( Figure 4 , Top panel). Thin-walled, septate fungal hyphae that were relatively uniform in size and branching dichotomously at 45 degrees were identified in all ( Figure 4 , Bottom panel). These were characteristic of Aspergillus and stained positively with Gomori methanamine silver ( Figure 4 , Bottom left) and periodic acid–Schiff stains ( Figure 4 , Bottom right). Variable numbers of eosinophils were present in all patients. A fungal etiology was suspected in only 1 case (Case 7) on clinical examination. The tissue in this case grew Aspergillus fumigatus on Sabouraud dextrose agar. In the remaining 7, fungal granuloma not being an initial suspicion, tissue was not preserved for microbiologic examination.
Complete blood count was normal and human immunodeficiency virus (HIV) serology negative in all patients.
Treatment and Outcome
Six patients were treated with antifungal drugs ( Table ): 2 of these (Cases 1 and 7) with oral itraconazole, 1 (Case 3) with a combination of intravenous (IV) amphotericin B and voriconazole followed by oral voriconazole, and 3 (Cases 5, 6, and 8) with a combination of IV and oral voriconazole. Two patients (Cases 2 and 4) underwent a complete excision of the mass and had no systemic lesion, as a result of which they did not receive any further treatment. Post-treatment, a complete resolution of proptosis and restoration of ocular motility was observed in all. Visual disturbances observed in 1 (Case 5) were also corrected after completion of treatment. Follow-up duration ranged from 6 to 28 months (mean, 12.5 months). One patient (Case 1) developed recurrence 6 months after surgery, this time with involvement of the ethmoid sinus, and was lost to follow-up before any further treatment could be initiated. The remaining 7 patients were disease-free at the time of last follow-up.