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�BBB�BBB......����A Review of Orbital Involvement in Patients with Primary Paranasal Sinus Space Occupying Lesions in a South-East Asian Tertiary Centre
Shantha Amrith1, FRCS.,  Ko Ko Lin1, M.Med., JK Gangadhara Sundar1, FRCS., Chao Siew Shuen2, FRCS
Department of Ophthalmology, National University Hospital, Singapore.
Department of Otolaryngology and Head and Neck Surgery, National University Hospital, Singapore

Corresponding Author:
Shantha Amrith
Senior Consultant 
Department of Ophthalmology
National University Hospital
5 Lower Kent Ridge Road Singapore 119074
Tel: (65) 98217402
Fax: (65) 6777 7161
Email: HYPERLINK "mailto:ophv14@nus.edu.sg"ophv14@nus.edu.sg

Financial support and disclosure: None


Key words: Diplopia, Mucocele, Neoplasm paranasal sinus, Ophthalmoplegia, Proptosis, Visual disability


Abstract
Objective: To study the ophthalmic symptoms, signs and the outcomes after therapeutic intervention in patients with various space occupying lesions (SOL) of paranasal sinuses in a tertiary referral centre in South-East Asia.
Patients and Methods: Retrospective review of all the cases with primary sinus SOL presenting with orbital involvement seen at the ophthalmic plastic service between January 1, 2000 and December 31, 2011.
Results: There were a total of 22 cases.  Mean age was 51.5 years and male to female ratio was 2:1. Presenting ophthalmic signs were proptosis (77.3%), palpable mass (63.6%), ophthalmoplegia (54.6%), pain (36.4%) and poor vision (13.6%). All cases were co-managed by Eye and ENT surgeons, with 15 cases first detected by ophthalmologists and 7cases by otolaryngologists. Of the 22 cases, 10 (45.5%) cases were neoplasms, 9 (40.9%) were paranasal sinus mucoceles and 3 cases were dysplastic lesions. Mean follow up period was 23 months (3 months to 69 months). 
Conclusion: Sinus SOL cases can present with ophthalmic signs and symptoms to the ophthalmologists and often may be the first presentation. Proper referral and team management are important. The outcome largely depends upon the primary etiology of the sinus lesion and efficacy of the multi-disciplinary approach.



Primary paranasal sinus space occupying lesions (PNS SOL) often have orbital involvement which calls for the co-management between ophthalmologist and otolaryngologist. Secondary orbital tumors involve the orbit by direct extension from the adjacent structures including the paranasal sinuses.1 More than 50% of the patients with sinus and nasal tumors have the signs and symptoms related to the eye or orbit.2 Sometimes the ophthalmic signs and symptoms may be the first presenting features of PNS SOL. PNS SOL involving the orbit can be benign or malignant. 
	Orbit is at risk because it shares three thin, bony walls with the nasal cavity and sinuses: the roof, medial wall and floor. Rootman et al3  stated that neoplasms of the sinus and nasopharynx account for 5% of orbital tumors. Tumors may invade the orbit via preformed
pathways, such as neurovascular bundles, or by direct extension through bone. Tumor extension into the orbit occurs particularly in ethmoidal tumors, because of the thin lamina papyracea separating the 2 structures.4 Su�rez  et al4  stated that the periorbitum is a barrier against invasion, but once the tumor has transgressed this robust periosteum it gains access to a space that lacks barriers to check local tumor spread.
Koukoulomatis et al5 reported that the most common presenting symptoms of PNS SOL with orbital invasion were proptosis, diplopia, visual loss, nasal obstruction and/or discharge. Fronto ethmoidal mucocele with orbital extension causes globe displacement, proptosis, ocular motility disturbances with diplopia, visual loss and headache6. 
 Advanced imaging techniques and the expanded use of CT scanning and MR imaging allow clinicians to view with increasing detail the normal and pathologic structures of the orbit. Bilaniuk and Zimmerman7 reported in their study that in 43% of patients with primary PNS SOL CT scan could demonstrate the extent of orbital involvement. Detailed radiographic images not only delineate the extent of the tumor invasion to the orbit but also show the nature of the pathologic process, thereby enabling the clinician to narrow down the differential diagnosis and build an appropriate treatment plan.8
Primary sinus SOL involving orbit are notorious for recurrence;1 therefore, careful therapeutic intervention and long term follow up is mandatory in such cases. This study aims to evaluate the ophthalmic symptoms,  signs and the outcomes after therapeutic intervention in patients with various PNS SOLs in a tertiary referral center in South-East Asia. We would like to emphasize the importance of recognizing the orbital signs and symptoms as the presenting features of primary PNS SOL and also the importance of radiographic imaging and team management for the best outcomes.
Methods
This is a retrospective, descriptive case study of primary PNS SOL with orbital involvement presenting to the Departments of Otolaryngology and Ophthalmology at the National University Hospital, Singapore from January 1, 2000 to December 31, 2011. The study followed the tenets of Helsinki Declaration and an institutional review board�s approval was obtained. Case notes and medical records were reviewed and necessary information was collected. Only cases with primary sinus space occupying lesions, with secondary orbital extensions (confirmed on CT-scans and/or histopathological reports) with ophthalmic manifestations were included in the study. Cases of orbital cellulitis or abscesses secondary to acute or chronic sinusitis, and those that had lesions confined to PNS were excluded from the study.
Patient profile data included demographic details, presenting symptoms and signs, and findings on imaging and investigations. The modes of management, follow-up period and outcomes of the treatments were also recorded. The outcome measures were improvement of ophthalmic and nasal symptoms and signs, recurrence of the lesions, adverse effects of the treatment and patient survival after the treatment.
Results
	During the 11 year period, 22 cases with primary PNS SOL affecting the orbit were identified. Males to females ratio was 2.1:1 (15 males and 7 females). The mean age was 51.5(range 4-83) years. Fifteen patients (68.2%) first presented to ophthalmologists and 7 patients (31.8%) to otolaryngologists. The details are described in Table-1.
The most common presenting features to the ophthalmologists were proptosis, dystopia (globe displacement) and localized swelling in and around the orbit and the cheek. Most patients had more than one clinical feature.  (Table -2)
	To support the clinical judgments in getting the diagnoses, CT-scans were done in all and MRI scans in 10 patients (45.4%). For definitive tissue diagnoses, incision or excision biopsies were also done for 21 cases (95.4%). According to imaging and histopathological records, mucoceles were the most common benign cause of sinus SOL (Figure-1 and 2), affecting the orbit in 9 patients (40.9% of the cases). Ten patients (45.5%) had neoplastic disease (Figure-3 and 4) and 3 others (13.6%) were diagnosed as dysplastic disease (Table-2).
The odds ratio for different signs and symptoms is described in Table-3. From the table it is evident that patients with ophthalmic involvement in PNS SOL have the highest risk of developing diplopia and ophthalmoplegia. 
Patients were co-managed by multidisciplinary teams of ophthalmologists, otolaryngologists, radiologists, pathologists, medical and radiation oncologists. Eighteen patients (81.8%) were treated surgically. All cases of sinus mucocele (Figure-2) were treated with Functional Endoscopic Sinus Surgery (FESS).The patient with cemento-ossifying fibroma of right maxilla underwent medial maxillectomy and the two fibro-osseous lesions patients were observed without any intervention, one of whom had a confirmatory biopsy. The case of right frontal sinus squamous metaplasia was treated with debridement of frontal air cells and orbital decompression. The details of management of all PNS SOL are described in Table 4. 
Visual acuities at presentation in 15 patients (68.2%) were good (e"6/12) and the remaining 7 patients (31.8%) had poor vision (<6/60). After treatment, 22.7% became blind either due to exenteration for malignant sinus tumors, or due to surgery related complication (central retinal artery occlusion in the contralateral eye). One patient (4.5%) with poor vision due to right frontal sinus squamous metaplasia improved to 6/9 after orbital decompression and debridement of isolated air cells in the frontal sinus. All others maintained pre-operative vision (Figure 5)
Four patients (18.2%) were treated without surgical intervention and 6 patients (27.2%) (two mucoceles, two squamous cell carcinomas (SCCs), one cement-ossifying fibroma and one squamous metaplasia) underwent more than one surgical intervention; three of which were due to recurrences of the original disease.
Mean follow up period was 23 months (range 3 months-5 years 9 months). Four patients passed away during follow up period, but one of them died due to causes unrelated to the sinus pathology. All 3 (13.6%) disease related deaths happened within a year of diagnosis and all were due to SCC.
Discussion
	In this study, the only the space occupying lesions arising from paranasal sinuses were reviewed, so pattern of presentation is different from other studies which include other kinds of sino-nasal lesions such as infections. The lesions occurred in all age groups with a male preponderance, supporting the findings of Malik at el9 which revealed that there was clear male preponderance.
The ophthalmic features of mucoceles are mostly as a result of mass effect to the orbits. Nearly 90% of patients have significant pressure effect  which indicate that the sinus lesions had been there for a considerable period before presentation. On the other hand, malignant epithelial tumors cause ophthalmic symptoms as a result of infiltration. Rootman and Katz10  stated that the clinical hallmark of secondary malignant epithelial tumors is nonaxial globe displacement associated with infiltration of orbital and paraorbital structures, leading to pain, paresthesia, decreased vision, and reduced extraocular movements. The frequency and severity of ocular and orbital symptoms attest to the relatively silent origin and late stage of presentation.10
Although the lesions arise from paranasal sinuses, about three quarters of the patients presented first to ophthalmologists. Proptosis was seen in majority of the patients indicating the importance of nasal examination and neuro-imaging in all patients presenting with proptosis1. Because CT scan accurately delineates bone and soft-tissue structures, it is indispensable in the planning of treatment and post therapy evaluation of sinus tumors.4  MRI scans are done only when the soft tissue delineation of the lesions is necessary. Signal characteristics of the paranasal sinus mass are different from the inflammatory process, which help in differentiating the two conditions.9
Our study showed that mucoceles are the commonest benign cause of PNS SOL, affecting the orbit. The frontal and ethmoidal sinuses are the most commonly involved, which reflect the predisposition for their small sinus openings to be damaged during sinus surgery or trauma or by repeated infections with subsequent obstruction and mucocele formation.11
All our cases of sinus mucocele were treated with FESS.  Khong et al11 confirmed our view that FESS is effective in improving ophthalmic symptoms and signs due to paranasal sinus mucocele. In our study, seven patients with mucoceles were found to be symptom free after treatment. One of the two cases which required a second surgery became stable after the second surgery, although the patient had poor vision due to orbital apex involvement. Another young boy with cystic fibrosis had recurrence of mucocele involving all paranasal sinuses after repeat surgery, indicating high rate of recurrence of mucocele in these patients. Cystic fibrosis is a chronic disease�of mucociliary transport, and even after successful surgery,�infection, obstruction, and polyposis can recur.12
Another half of the cases in our study were sinus neoplasia. SCC is the most common epithelial tumor secondarily invading the orbit from the sinuses.13
		The role of exenteration in surgical treatment of sinonasal malignancies has been addressed by many authors.14-16 Malignant sinonasal tumors usually present as advanced disease because early diagnosis is difficult.4 In treating advanced malignant maxillary sinus tumors, Nishimo et al15 felt that with aggressive therapy, including total maxillectomy with orbital exenteration and irradiation, the 5-year local recurrence-free survival was 59.2%. Orbital involvement is associated with a significant reduction in survival both in ethmoidal and maxillary sinus tumors4 which is clearly evident in our series. Two of the 4 patients who underwent orbital exenteration for malignant tumors in our study died of malignancy during follow up. Although it is desirable to save all uninvolved structures during surgical resection of malignancies, it is more important that this does not compromise the life of the patient.15
		Patients with adenocarcinoma have a better disease-free survival and recurrence-free survival than those with SCC.4 Lymphomas usually respond well to treatment as our case with large B cell lymphoma. 
		In our series, 3 patients had fibro-osseous lesions of the PNS. The orbital bones, some of which are membranous, and not preformed from cartilage, develop a small number of relatively common and distinctive tumors such as  osteoma, fibro-osseous lesions, and ossifying fibroma.17 Lane et al17 also described that tumors may begin in the bones associated with the sinuses and thereafter secondarily encroach on to the orbit.
		Fibro-osseous lesions are rare after the age of 15, and the disease may stabilize at puberty, and in children treatment should be delayed, if possible, until after puberty.  We observed two fibro-osseous lesions in patients, aged 55 and 72, who never had any intervention for their condition that remained stable until one of them died of other systemic condition. Complete local excision is frequently impossible, and conservative surgical excision is the preferred treatment and is indicated only in cases with compromise of function, progression of deformity, pain, associated pathologic fracture(s), or the development of a malignancy.17
Ossifying fibroma is a more aggressive lesion, which typically develops in younger individuals.18 It is currently believed that the best management of juvenile ossifying fibromas is surgical excision. Because these tumors can recur after incomplete excision, every attempt should be made to remove the mass completely.18 In our study, one patient with cemento-ossifying fibroma of right maxilla who had undergone medial maxillectomy, found new bony expansion of the remnant right maxillary walls which indicated possible recurrence after 10 months.
The case of squamous metaplasia of right frontal sinus case in our study behaved like a malignant neoplasm as it recurred after orbital decompression and debridement of the isolated frontal air cell. The vision improved to near normal after more aggressive second time surgery. 
Conclusion
	Paranasal sinus space occupying lesions frequently present to ophthalmologists with signs and symptoms similar to orbital mass lesions, which can be benign or malignant. Although some lesions like mucoceles can be cured and some other malignant conditions such as lymphoma and adenoid cystic carcinoma have favorable prognosis, some diseases, SCC in particular, respond poorly to treatment and patients decease even after aggressive surgical procedures. Any non-axial proptosis should be promptly investigated for sinus lesions and effectively managed with other disciplines to achieve the best outcomes.
References
1. Ben Simon GJ, Volpe NJ, Albert DM : Metastatic and Secondary Orbital Tumors. In Albert DM ,ed. Principles and Practice of Ophthalmology, Philadelphia: Saunders Elsevier; 2008 : 3073-3110
2. Myers LL , Oxford LE, Differential diagnosis and treatment options in paranasal sinus cancers. Surg Oncol Clin N Am 2004; 13:167-186
3. Rootman J, Chang W, Jones D: Distribution and differential diagnosis of orbital disease. In: Rootman J, ed. Diseases of orbit. A multidisciplinary approach, Philadelphia: Lippincott Williams & Wilkins; 2003: 53-84
4. Su�rez  C,FerlitoA,Lund VJ, et.al. Management of the orbit in malignantsinonasal tumors.HEAD & NECK�DOI 10.1002/hedFebruary 2008, 242-250.
5. Koukoulomatis P, Charakidas A, Papakrivopoulos A, Giotakis I : Ethmoidal sinus adenocarcinoma with orbital invasion. International Ophthalmology 2001; 24: 259-261
6. Lai PC, Liao SL , Jou JR, Hou PK: Transcaruncular approach for the management of frontoethmoida mucoceles. Br J Ophthalmol 2003; 87: 699-703
7. Bilaniuk LT, Zimmerman RA: Computer assisted tomography; Sinus lesion with orbital involvement. Head and Neck surgery 1980; 2:293-301
8. Eisen M, Yousem DM, Loevner LA , et al : Preoperative imaging to predict orbital invasion by tumor. Head Neck 2000; 22:456-462
9. Malik TG, Rashid A, Farooq K: Paranasal sinus and nasal cavity; the notorious neighbours of orbit : Professional Med J Mar 2011; 18 (1) : 154-159
10. Rootman J, Katz  SE. Secondary tumors of the orbit. In:  Diseases of the orbit, 2nd  Edition. Philadelphia: Lippincott Williams & Wilkins, 2003: 304-329.
11. Khong JJ, Malhotra R, Wormald PJ, Selva D: Endoscopic sinus surgery for paranasal sinus mucocele with orbital involvement. Eye 2004; 18; 877-881
12. Rickert S, Banuchi VE, Germana JD, et al. Cystic Fibrosis and Endoscopic Sinus Surgery: Relationship Between Nasal Polyposis and Likelihood of Revision Endoscopic Sinus Surgery in Patients With Cystic Fibrosis. Arch Otolaryngol Head Neck Surg.�2010; 136(10):988-992.
13. Skuta GL, Cantor LB, Weiss JS. Orbital Neoplasms. In: Orbit, Eyelids and Lacrimal System, Basic and Clinical Science Course, San Francisco: American Academy of Ophthalmology, 2011-2012; 63-93.
14. Imola MJ, Schramm VL Jr : Orbital preservation in surgical management of sinonasal malignancy. Laryngoscope 2002; 112: 1357-1365
15. Nishino H, Ichimura K, Tanaka H et al: Results of orbital preservation for advanced malignant maxillary sinus tumors. Laryangoscopy2003; 113:1064-1069
16. McCary WS, Levine PA, Cantrell RW. Preservation of the eye in the treatment of sinonasal malignant neoplasms with orbital involvement. Arch Otolaryngol Head Neck Surg 1996; m122:657-659.
17. Lane KA, Bilyk JR, Jakobiec FA. Mesenchymal, Fibroosseous and Cartilaginous Orbital Tumors. In: Albert & Jakobiec's Principles & Practice of Ophthalmology, 3 Edition. Oculoplastics.�Elsevier�Inc 2012
18. Shields JA, Peyster RG, Handler S, et al. Massive juvenile ossifying fibroma of maxillary sinus with orbital involvement.  British Journal of Ophthalmology, 1985, 69, 392-395.

Figure Legends:
Figure 1:
Pre and post-operative visual acuity of 16 out of 18 patients with PNS-SOL treated surgically (data incomplete for 2 patients)
Figure 2: 
Patient with left Ethmoidal SCC, presented with sudden onset diplopia. 
Figure 3:
CT scan of the same patient as in figure 2, showing infiltration in the left orbital apex.
Figure 4: 
Patient presenting with painless left non-axial proptosis.
Figure 5:
CT scan of the same patient as in figure 4, showing fronto-ethmoidal mucocele. 










	

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