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Orbital aspergillosis in immunocompetent patients
  1. Kruti H Mody1,
  2. Mohammad Javed Ali1,
  3. Geeta K Vemuganti2,
  4. Suma Nalamada3,
  5. Milind N Naik1,
  6. Santosh G Honavar1
  1. 1Division of Ophthalmic Plastic Surgery, L.V. Prasad Eye Institute, Hyderabad, India
  2. 2Ophthalmic Pathology Service, L.V. Prasad Eye Institute, Hyderabad, India
  3. 3Jhaveri Microbiology Laboratory, L.V. Prasad Eye Institute, Hyderabad, India
  1. Correspondence to Dr Kruti H Mody, Division of Ophthalmic Plastics Surgery, L.V. Prasad Eye Institute, Hyderabad, India; krutimody{at}


Purpose To describe clinical, ultrasonographic, radiological and histopathological features of orbital aspergillosis in immunocompetent patients.

Methods Medical records of immunocompetant individuals with orbital aspergillosis between November 1995 and November 2010 were reviewed.

Results Thirty-five cases (27 males, 8 females) were reviewed. Mean age at presentation was 37.63 (8–73) years and mean duration of symptoms was 12.03 (0.5–84) months. Proptosis (22.63%) and mass lesion (13.37%) were the commonest presenting complaints. Presenting visual acuity was better than 6/9 in 21 (60%) and no perception of light in 3 (8%). Ocular motility restriction was noted in 25 (71%). The commonest clinical differential diagnosis was non-specific orbital inflammatory disease (NSOID) (10.29%) followed by malignancy (7.20%). CT showed infiltrative lesions with bone destruction in 22 (63%), contiguous paranasal sinus involvement in 22 (63%) and intracranial extension in 10 (29%). Diagnosis was by histopathology and microbiological evaluation. Fungal cultures revealed Aspergillus flavus in 30 (86%) and Aspergillus fumigatus in 5 (14%). Treatment included conservative medical management in 18 (51%) and surgical debulking in 17 (49%). Average follow-up was 37.6 (3–183) months, and patient survival was 33/35 (94%).

Conclusions Though orbital aspergillosis is commonly seen in immunocompromised patients, it should be suspected in young immunocompetent individuals presenting with proptosis of insidious onset and infiltrating lesions involving the paranasal sinuses. Definitive diagnosis is achieved by histopathological and microbiological evaluation. Systemic steroids should be avoided prior to definitive diagnosis. Prolonged systemic antifungal therapy with an option of additional debulking of lesions provides good disease control with improved survival.

  • Orbit
  • Infection
  • Pathology
  • Microbiology
  • Imaging

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Aspergillus is an asexual spore-forming, highly aerobic, dichotomously branching fungus that commonly affects the aero-digestive tract of individuals with impaired immune status. Classically, it is classified into an invasive or non-invasive type depending on the tissue involvement. Orbital involvement of aspersillosis is uncommon.1–3

Orbital aspergillosis affection in immunocompetent individuals is even rarer, and till date only 22 cases have been reported.4–18 In this article, we discuss our experience with 35 cases of orbital aspergillosis seen in immunocompetent individuals over the last 15 years. Further, common presenting features, investigations, differential diagnosis, histopathological and microbiological features, treatment modalities and their outcomes are elaborated upon. These are compared with the previously reported cases to enable better understanding of the disease process.


A retrospective chart review of all histopathologically and microbiologically proven cases of aspergillosis at a tertiary eye care centre from November 1995 to November 2010 was conducted. We excluded immunocompromised patients. For the purpose of this retrospective study, immune-compromised status was defined as presence of one of the following: granulocyte count in peripheral smear of <500/μL, treatment with supraphysiologic dose of adrenal glucocorticoids, and a history of treatment with other immunosuppressive drugs such as cyclosporine. We also excluded patients with ELISA test positive for HIV, and diagnosed cases of diabetes mellitus.

Data collected included demographics, presenting symptoms, ocular examination, clinical diagnosis, investigations, associated systemic diseases, investigations and treatment. Ocular examination included external examination, Snellen visual acuity, ocular motility, Hertels exophthalmometry, slit lamp evaluation, applanation tonometry and fundus evaluation. Investigations included ultrasonography (USG), CT scan and a biopsy.

Histopathological diagnosis of orbital aspergillosis was based on the uniformly sized septate hyphae with dichotomous branching, presence of inflammatory background, multinucleated giant cells and epitheloid granulomas. Gomori methanamine staining was performed in all cases.

Microbiological work-up included cultures in Sabourauds dextrose agar media. Aspergillus was identified in all cases by septate hyphae, unbranched conidiophores arising from specialised foot cell and conidiophores enlarging at the tip forming vesicles which were partly or completely covered by phialides forming round or rough conidia. Aspergillus flavus were identified by velvety yellow to green/brown colonies with rough, pitted, spiny conidiophores. Their phialides were uniseriated or biseriated covering the entire vesicle pointing out in all directions (figure 1A). Aspergillus fumigatus formed velvety or powdery colonies that were initially white and later became dark green to grey. Their conidiophores were short with phialides usually covering the upper two-thirds of vesicles and parallel to the axis of coniophores (figure 1B).

Figure 1

Microbiology and histopathology. (A) Cultures of Aspergillus Flavus, (B) Cultures of Aspergillus Fumigatus, (C) Histopathology slide with periodic acid Schiff stain at ×400 showing fungus filaments (arrow), (D) histopathology slide with Gomori methanamine silver stain at ×400 showing fungus filaments (arrow) with giant cell reaction (rectangle).

Outcome measures included disease recurrence, visual acuity and patient survival at the last follow-up (>3 months). Unfavourable visual outcomes were defined as deterioration of visual acuity by ≥2 lines on Snellen visual acuity chart. Since visual acuity did not always correlate with the extent or progression of disease, treatment success was defined as patient survival with resolution of the lesion and no recurrence at the last follow-up (>3 months).


Thirty-five cases of orbital aspergillosis in healthy and immunocompetent patients were seen. There were 27 males and 8 females. The mean age at presentation was 37.63 years (range: 8–73 years). The duration of symptoms ranged from 0.5 to 84 months (mean: 12.03 months).

Chronic progressive proptosis was the most common presenting feature noted in 22 of 35 (63%) cases (figure 2C). Thirteen (37%) cases presented with periocular swelling (figure 2B) and 7 (17%) with pain (figure 2D).

Figure 2

Clinical presentation. (A) Squint (exotropia), (B) swelling, (C) proptosis, (D) chart showing all the presenting complaints, (E) restricted extraocular movements.

Presenting visual acuity was 6/9 or better in 21 (60%) cases, 6/9–6/18 in 9 (26%) cases, 6/18 perception of light (PL), in 2 (6%) cases, and no PL in 3 (8%) cases. Mean proptosis (compared with the fellow eye) was 2.93 mm (range 1–11 mm). Ocular motility restriction was noted in 25 (71%) cases (figure 2E). Other ocular findings included ptosis in 4 (11%), papilloedema in 5 (14%), raised intra-ocular pressure in 2 (6%), and choroidal folds in 2 (6%) cases.

Clinically, a fungal granuloma was suspected in 18 cases (51%). Common differential diagnosis included non-specific orbital inflammatory disease (NSOID) in 10 (29%) cases and paranasal sinus malignancy in 7 (20%) cases. Lymphoma was the differential diagnosis in 4 (11%), and orbital cellulitis in 2 (6%) cases (figure 3).

Figure 3

Chart showing the differential diagnosis.

USG reports were available for 8 cases. It revealed an irregular mass lesion with low regular internal reflectivity with multiple high reflective spots with acoustic shadowing suggesting calcification in six cases, and two other cases showed irregular mass lesion and thickened recti muscles.

CT scans were available in all 35 cases, and showed an irregular mass lesion, isodense to extraocular muscles. The mass was sino-orbital in 30 cases, and purely orbital in five cases. Maxillary sinus was the most commonly involved sinus (figure 4A), seen in 21 of 35 (60%) cases. Ethmoidal sinus was involved in 15 (43%), sphenoid in eight (23%) and frontal in five (14%). The details of sinus involvement were not documented in two cases. Intracranial extension was seen in 10 (29%) cases (figure 4); four (11%) showed thickened recti muscles.

Figure 4

Extension in surrounding structures. (A) CT scan showing the lesion involving the maxillary sinus, (B) CT scan showing intracranial extension, (C) chart showing extension into surrounding structures.

Diagnostic incisional biopsy was performed in all cases, and fresh tissue samples were sent for histopathological and microbiological evaluation. Histopathological findings were similar in all cases, and showed granulomatous inflammation with multinucleated giant cells and few eosinophils. Gomori methanamine silver staining showed elongated, regular, narrow septate, acutely branching fungal filaments suggestive of aspergillus in the background as well as in the cytoplasm of giant cells (figure 1). Fungal cultures revealed A flavus in 30 (86%) and A fumigatus in five (14%) cases.

The average time from presentation to definite diagnosis was 3 weeks (range: 1–8 weeks), and the average time from initiation of symptoms to definite diagnosis was 50 weeks (4–340 weeks). Of the 35 patients, 18 were treated conservatively after incision biopsy, and 17 underwent surgical intervention in the form of debulking or exenteration. For analysis of treatment outcomes, we excluded patients who had less than 3 months of follow-up. Of the 35 patients, 32 had sufficient follow-up (mean: 37.6 months; range: 3–183 months). Of the 32 patients, 17 had received medical management and 15 were treated surgically.

Medical management included intravenous amphotericin-B, 0.5 mg/kg body weight followed by oral antifungals (Voriconazole or Itraconazole) for an average of 6.34 months (range 6–12 months) under the care of an internist. Of the 17 that underwent surgical debulking before systemic medications, two underwent exenteration as the first surgery and the other 15 underwent debulking.

The decision on conservative or surgical management was based on surgeons’ discretion. In general, more extensive and/or accessible lesions were debulked during the initial intervention followed by medical management. Others received medical treatment immediately after the diagnosis. At 6 weeks follow-up, lesions which worsened underwent a second surgical intervention.

Of the 35 cases, one patient died within 6 weeks of initial presentation. Of the 32 patients with adequate follow-up, 22 (69%) patients were stable or had improvement in vision, and 10 (31%) patients had visual deterioration. Confounding factors like other ocular causes of visual deterioration (eg, cataract, etc) were not considered. The final visual acuity was 6/9 or better in 19 patients (59%), 6/9–6/18 in 3 patients (9%), 6/18– PL in 6 patients (19%) and no PL in 4 patients (13%). Six out of 32 (19%) patients recurred following initial improvement. Of the six cases with recurrence, four required further surgical debulking along with medical management, one required an exenteration followed by medical management, and one received debulking via transcranial and transnasal approach followed by antifungal treatment. The latter died within 4 months. All the four patients who underwent debulking had received only medical treatment initially. The patient in whom exenteration was done had an initial disease involving only the orbit. There was involvement on the orbital apex at presentation. A debulking was done followed by medical management. Disease recurrence was noted at the orbital apex. The patient, who required a transcranial and transnasal debulking, had presented as a sino-orbital disease involving unilateral orbit and bilateral ethmoid and sphenoid sinus. A debulking was done during the initial intervention, which was followed by medical management. After initial improvement, disease recurrence was noted with intracranial extension. Thus, recurrence was noted in 4 of 17 (23%) patients who received medical management, and 2 of 15 (13%) patients with surgical management. Our overall success rate was 81%.

Disease mortality was seen in 2 of 35 patients (6%), both having had intracranial extension at some stage of the course of the disease. Of the 10 patients with intracranial extension at presentation, mortality was noted in only one (10%, p=0.62).


Aspergillous is commonly found in soil, various types of organic debris, water, indoor environment, and so on, and thrives in aerobic environment. Its spores are virtually present in the entire environment but, because of the body defence mechanism, infection by aspergillosis is infrequent in healthy individuals. Immunocompromised individuals are more often affected. Affection in uncontrolled diabetics is also common.1–3

There are over 700 species of Aspergillus identified. Among them, infection by A fumigatus is the most common infection. Other commonly isolated species include A flavus, Aspergillus niger, Aspergillus nidulans, Aspergillus terreus. Aspergillosis commonly affects the lungs and paranasal sinuses. Gastrointestinal tract and skin are relatively less commonly affected sites.19–21

Aspergillosis has two forms of presentation: invasive and non-invasive. The non-invasive form presents either as a fungal ball—mycetoma or as allergic fungal sinusitis. In this form, it does not cause tissue invasion or necrosis. Though, it can cause local tissue destruction including mucosal and bony destruction. The invasive form essentially crosses the tissue planes and causes necrosis of tissues. It can be localised or fulminant. The localised form causes invasion of adjoining structures, vascular invasion, thrombosis and tissue necrosis. The fulminant form causes embolisation, distant organ involvement and even death. The invasive form is known to have higher mortality. The non-invasive infections are known to be more common in immunocompetent individuals, and invasive form in immunocompromised individuals. Though, both the forms have been reported in immunocompetent patients.3

Orbital involvement of aspergillosis can be primarily orbital, sino-orbital, or with central nervous system involvement. It may be caused by either non-invasive or invasive form.3

Presentation of orbital aspergillosis varies, ranging from an isolated mass lesion, squint, nasolacrimal duct obstruction, to even optic neuropathy. Imaging is essential for diagnosis and for documentation of the extent of the lesion. It may closely resemble affection by other fungal organisms like mucormycosis and so on.4 Differentiation is essentially on microbiological and pathological work-up. Management is essentially medical management with or without surgical debulking.

In immunocompetent individuals, presentation is usually chronic and indolent. Most of them present with pain as the chief complaint. Lesions are more often localised, as an allergic mycetoma. Imaging is an important tool in diagnosis. On CT scan, these appear as isodense, heterogeneous, irregular lesions; commonly affecting paranasal sinuses; with associated bony erosion.22 Incision biopsy with microbiological and histopathological work-up is essential for diagnosis. Microbiological review helps to differentiate the species. Treatment is similar to that in immunocompromised patients. Systemic amphotericin B, followed by itraconazole/voriconazole is most often followed. Surgical debulking aids in reducing the infection load and improving response to medical treatment. Irrigation with amphotericin B after debulking has been advocated by few authors. Overall outcomes of orbital aspergillosis depends on the extent of lesion at presentation. Survival rates documented in literature are poor in spite of treatment.

Table 1 shows a comparison of our data with previous studies. In the present series, proptosis was the most common presenting symptom and the common differential diagnoses were NSOID and malignancy. Contrarily, pain was the most common presenting symptom in the previously reported cases, and the differential diagnosis most often was temporal arteritis.4–6 ,8 ,16 Temporal arteritis is a less common disease in India and was rarely considered as a differential diagnosis in our series.

Table 1

A comparison of our data with previous studies

In our series, all patients underwent an incision biopsy for diagnosis and none of them required a repeat biopsy. Among the previously reported cases, five of 22 cases needed a repeat biopsy.4–5 ,11 ,17 Also, some authors have advocated fine needle aspiration cytology (FNAC) for diagnosis, as a more conservative approach.5 We believe that an incision biopsy with adequate tissue sample is preferable for accurate diagnosis.

In the present study, favourable visual outcomes were seen in 62.5% of patients. Of the four patients with no PL as the final visual acuity, three had an initial disease involving only the orbit (2 of 3 patients with involvement of orbital apex) and one had an initial sino-orbital disease (involving the orbit and ethmoid sinus). The final visual acuity of no PL was noted to be more common in patients with only orbital disease (3/5, 60%, p=0.0013). This could be attributed to early optic nerve compression.

In the present study, patient mortality did not correlate with intracranial extension of disease at presentation. Patient survival was significantly better than that reported in the previous studies. This difference can be attributed to multiple factors. With advancement in medical management over the years, an overall improvement in disease control and survival rates in patients with orbital aspergillosis has been noted. Our patient population included those presenting between 1995 and 2010, when compared to the previous reports in which 11 out of 22 presented prior to 1995. There was also a difference in the demographics. Our patients were younger, with a mean age of presentation being 38 years in contrast with the mean age of presentation of 62 years in previously reported cases, and this could also have contributed to better outcomes in our study.

In our series, A flavus was isolated in 30 of 35, patients and A fumigatus was isolated in the remaining five. We did not have any cases affected with Aspergillus terreus or other species. Although, we are not aware of the species isolated in most of the previous reports, A terreus has been isolated in one.18 A difference in species involved could have also contributed to this difference in outcomes.

Among the previously reported cases, systemic steroids, prior to diagnosis, was used in 11 of 22 cases. None of our cases received steroids. Oral steroids could have aggravated the disease and resulted in poorer outcomes.

Being retrospective in nature, the current study has a few limitations with 3/35 (9%) of our patients lost to follow-up soon after initiation of treatment. There was inadequate documentation that would enable classification into invasive and non-invasive forms. Also, being an ophthalmology set-up, systemic evaluation and management of systemic complications to antifungal treatment was done by a physician, details of which are not mentioned. However, since this is a rare disease, our series with clinical examination, histopathology, cytology and imaging has demonstrated the spectrum of presentation of orbital aspergillosis.

In summary, invasive orbital aspergillosis can occur in immunocompetent individuals, and most often mimics an NSOID or a malignancy. High index of suspicion, radiologic investigations, and incision biopsy may be worthwhile before starting systemic steroids in suspected cases of orbital aspergillosis. A multidisciplinary approach involving oculoplastic surgeons, ear, nose and throat (ENT) and neurosurgeons is very much needed in the management.


Dr Anita Peddi.



  • Collaborators Anita Peddi.

  • Contributors KHM: concept, data collection, data evaluation, manuscript write-up. MJA: data evaluation, manuscript review. Vemuganti G: data collection, manuscript evaluation. SN: data collection, manuscript review. MNN: concept, manuscript review. SGH: concept.

  • Competing interests None.

  • Patient consent Obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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