Orbital Apex Syndrome in a Patient with Sphenoethmoidal Fungal Rhinosinusitis

Thanikachalam Subramanyan1, Rakesh Singh2, Karunanidhi Manickam1, Jagadeeswaran Vadivel Udayakumaran1, Neeta pal1*, Namrata Pal3 and Govind Pal4 1Indira Gandhi Government General Hospital and Postgraduate Institute, Pondicherry, India 2Jawaharlal Institute of Medical Education and Research, Pondicherry, India 3Vivekanand Education Society’s Institute of Technology, Mumbai, India 4Miraj Medical College, Miraj, India

A 65 years old lady presented with right visual loss after 7 day history of complete drooping of Right Eye (RE) upper lid. Her physical examination details: Conscious, cooperative well oriented to time, place and person. Blood pressure was 110/60 mmHg, right arm sitting posture. Pulse was 90 beats per minute, feeble and regular low volume. Body temperature was 37°C. Systemic examination: Cardiovascular system: S1, S2 Heard, No murmurs. Respiratory System: Right side: Basal crepts and Rhonchi present, Left side: Within normal limits. Per / Abdomen: Soft, non-tender, no organomegaly. Central nervous system: conscious, co-operative and well-oriented to time, place and person, Higher functions: Normal, Involuntary movements absent. No gross motor abnormalities were detected. Cranial nerve examination showed multiple nerve palsies which included 2 nd , 3 rd , 4 th , 5 th (ophthalmic and maxillary division) and 6 th nerve palsies of right eye. Blood tests: Hemoglobin: 11 g/dl, White Blood Cells: 11,000 cells/cu.mm, Differential count: Neutrophils: 74%, Eosinophils: 4%, Lymphocytes: 22%, Blood urea: 30 mg/dl, Serum creatinine: 1.2 mg/dl, Blood sugar: 382 mg/dl, Erythrocyte Sedimentation Rate: 15 mm/hr. Liver Function Tests: Total rotein:6.9 g/dl, Serum Total bilirubin: 0.6 mg/dl, Serum Direct bilirubin: NIL, Serum albumin: 3.4 g/dl, Serum globulin: 3.5 g/ dl, S.G.O.T.: 19 IU/L, S.G.P.T.: 34 IU/L, Alkaline phosphatase: 92 IU/L. ELISA: Negative, HbsAg: Negative Patient had a 2-yr history of poorly controlled type II diabetes mellitus and 10 yr history of bronchial asthma on irregular treatment for the same. The initial blood sugar measured was 382 mg/dL. Her visual acuity in the RE was PL negative and it was 20/200 in the Left Eye (LE). Her RE examination revealed loss of pupillary light reflex with an afferent defect grade 2, normal anterior chamber, intraocular pressure and fundus. It also showed complete ptosis, mild congestion and total ophthalmoplegia (Figure 1a and 1b). There was no evidence of proptosis. The sensations over forehead, cheek, angle of mouth were absent, RE corneal sensations were absent. E.N.T. examination: Right side: 1 st pass: Crusts over middle and superior turbinate, congestion of middle turbinate; 2 nd pass: Normal osteomeatal complex; 3 rd pass: mucopurulent discharge from the sphenoethmoidal recess of the right side above and behind eustachian tube orifice. Endoscopic examination detected edematous mucosa and mucopurulent discharge from the sphenoethmoidal recess of the right side. The ophthalmological and nasal examinations of the left side showed no abnormal findings. Hence clinical diagnosis was Orbital Apex Syndrome (OAS). Further radiological investigations were conducted to confirm this diagnosis.
C.T. showed bilateral sphenoid and right ethmoidal sinusitis with no orbital invasion (Figure 2a and 2b). Most of the orbital lesions were located at the retrobulbar area and the orbital apex, with surrounding soft tissue thickening. There was no evidence of intracranial extension. Increased signal intensities were noted at the same regions on brain MRI (Figure 2c) with gadolinium enhancement. The initial clinical diagnosis of OAS due to noninvasive fungal sinusitis was confirmed. Initial treatment: The patient was started on intravenous cefoperazone with sulbactam 1 gm b.i.d., Flagyl 500 mg t.i.d., systemic antifungal Tab., Fluconazole 150 mg b.i.d and insulin therapy to control blood sugar. The blood sugar levels were fluctuating throughout the therapy. However, there was no improvement in signs and symptoms after medical management.
Improved treatment: Elective surgery, Functional Endoscopic Sinus Surgery (FESS) was performed under local anesthesia on the 7th hospital day. Thick mucus and yellowish-colored matted fungal balls were found in sphenoid sinus during the surgery. All fungal materials were removed using curettes and sinus irrigation. These were sent to the Department of Pathology and Microbiology for detailed evaluation.
Result of FESS: By the 4th PostOperative Day (POD), there was no improvement in visual acuity but ptosis and extraocular movements resolved completely. The culture of tissue from the sinus biopsy on Sabouraud glucose agar yielded multiple colonies of mold with satellite smaller colonies at periphery. The histopathological report confirmed conidiobolus without evidence of tissue invasion (Figure 3). Therefore, corticosteroid therapy was started with prednisolone (40 mg for first 7 days followed by 20 mg for next 7 days and 10 mg for next 7 days) on 4 th POD. With the exception of the visual acuity, the ptotic upper eyelid completely recovered and the extraocular movements improved by the day of discharge (the 30 th POD). The patient's blood sugar was not well controlled with fluctuations being noted during the hospitalization. By 2 nd month, the right visual acuity was PL negative and the extraocular muscle movement was completely normalized.

Discussion
Most infections with Conidiobolus have been described in immunocompetent patients, typically men, working in agriculture or in the forest in subtropical and tropical regions [1,2]. Patients suffer from a local chronic, indolent infection involving facial and subcutaneous tissues as well as the paranasal sinuses, leading to swelling of the infected tissues and chronic sinusitis [2]. C. coronatus is the most common species identified. Disseminated infections due to Conidiobolus are extremely rare [1][2][3]. Patients with Diabetes Mellitus (DM) are known to be prone to infection [4]. Orbital apex syndrome is common in poorly controlled diabetics. The most frequent fungal agent that causes rhinosinusitis is Aspergillus [5]. Orbital apex syndrome due to mucormycosis [6], aspergillosis [6] have been reported earlier. It is also common in immunocompromised patients. In the immunocompromised patient, there has been an increased incidence of invasive aspergillosis in the last 20 years [7]. Zygomycosis of upper respiratory tract, caused by Conidiobolus coronatus, in eight Bengali males and one female is described [8]. But there was no involvement of orbital apex.  Conidiobolus causing orbital apex syndrome is extremely rare. It is known to cause upper respiratory tract infections. But fungal balls were removed from the sphenoid sinus during FESS. A fungal ball is defined as the non-invasive accumulation of dense fungal hyphae in the sinus cavity [9]. Various terms, such as mycetoma, aspergilloma, and chronic noninvasive granuloma have been used interchangeably in the literature to designate sinus fungal ball [9]. Interestingly, the disease has been found more commonly in middle-aged and elderly females, in contrast to all forms of invasive and chronic aspergillosis, which are more common in males [10]. Fungi remain non-invasive in the context of a fungal ball, however, and rarely could become invasive after substantial immunosuppression, such as renal transplantation [11]. In addition, some patients develop allergic mucin surrounding the fungal balls when corticosteroids are tapered [9,12]. Dhong et al. showed that all fungal balls have a characteristic gritty matted gross appearance to the surgeon, whereas the majority, but not all, had C.T. characteristics that included radiographic heterogeneity [13].
The biopsy of specimen obtained from FESS showed spherical conidia with hair-like appendages (villae) and prominent papillae characteristic of Conidiobolus coronatus (Figure 3). Although we did not perform orbital apex biopsy, we considered the orbital apex lesion to be non-invasive disease for the following reasons: 1) the lack of response to systemic antibiotics and antifungal agents and 2) the dramatic improvement after surgical drainage and systemic corticosteroid treatment.
The prognosis of OAS secondary to fungal infection is poor, and neurological sequelae and fatal outcomes have been reported in the majority of the cases [9,14,15]. This is probably the first reported case from India. The changing characteristics and clinical behavior of fungal infection should be closely monitored to select the optimal therapeutic modalities. A future study on the proper clinical tools to identify a residual fungal infection after treatment is needed to help save the vision and often the life of patients who suffer with OAS secondary to fungal infection.