Implications of Enlarged Infraorbital Nerve in Idiopathic Orbital Inﬂammatory Disease Ka Hyun Lee,1,2 Sun Hyup Han,3 Jin Sook Yoon1

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Downloaded from http://bjo.bmj.com/ on August 30, 2016 - Published by group.bmj.com Clinical science Implications of enlarged infraorbital nerve in idiopathic orbital inﬂammatory disease Ka Hyun Lee,1,2 Sun Hyup Han,3 Jin Sook Yoon1

1Department of ABSTRACT METHODS Ophthalmology, Institute of Purpose To investigate the clinical characteristics of Patients with IOI were selected from our database Vision Research, Yonsei fl University College of Medicine, idiopathic orbital in ammatory (IOI) disease with (Severance Hospital, Seoul, Korea). A retrospective Seoul, Korea infraorbital nerve (ION) enlargement. review of the medical records, laboratory results, 2Department of Design Retrospective, comparative case series. and radiological and histopathological findings was Ophthalmology, KonYang Methods Participants: Consecutive patients who were performed. Only the patients first diagnosed with University College of Medicine, diagnosed with IOI between January 2009 and IOI in our hospital whose medical and radiological Daejon, Korea fi 3Yonsei University College of December 2013 were identi ed. The study included results were available and whose follow-up period Medicine, Seoul, Korea patients whose medical and radiological data at was longer than 12 months after treatment were diagnosis were available and whose follow-up period included in the study. We divided the patients with Correspondence to was more than 12 months after treatment. The patients IOI into two groups, patients with and without Professor Jin Sook Yoon, fi Department of Ophthalmology, were divided into two groups according to ION enlargement. ION enlargement was de ned Institute of Vision Research, accompaniment of ION enlargement and were with orbital CT scan, which was taken at initial Yonsei University College of compared. Main outcome measures: clinical evaluation. We compared clinical manifestations, Medicine, 50 Yonsei-ro, manifestation, radiology and treatment outcome. radiological and histopathological results, and treat- Seodaemun-ku, 120-752 Results Among 89 patients with IOI, 12 (13.5%) were ment outcomes between the two groups. This study Seoul, Korea; [email protected] identified to have ION enlargement. The ION-enlarged was approved by the institutional review board of Received 1 June 2015 group showed a higher percentage of the patients with Yonsei University College of Medicine (Seoul, Revised 3 November 2015 diffuse inflammation (66.7%, p<0.001). 91.7% of the Korea) and was in accordance with the ethics Accepted 28 November 2015 ION-enlarged group showed inferiorly located guidelines of the Declaration of Helsinki. Published Online First fl 30 December 2015 in ammation. Patients with ION enlargement showed a Orbital CT was used to determine the location significantly higher incidence rate of proptosis and extension of the orbital inflammation, and the (p=0.013), pain (p=0.004) and altered sensation size of the ION and ION canal. Clinical manifesta- (p<0.001). The recurrence rate was significantly higher tions and radiological and histopathological results in the ION-enlarged group (83.3%) than in the other were identified and used as primary outcome mea- group (33.8%) (p=0.001). Repetitive inflammation sures. According to the coronal imaging, the diam- (recurrence ≥3) with steroid dependency was found only eter of the ION canal greater than that of the optic in 19.5% patients without ION enlargement but in nerve was considered enlarged ION and ION 66.7% patients with ION enlargement. canal.4 Conclusions Patients with ION-enlarged IOI showed Histopathology was performed if the patient distinct clinical and radiological characteristics. As IOI underwent orbital biopsy. If the specimen revealed accompanied by ION enlargement showed significantly the presence of characteristic histological features higher steroid dependency and recurrence rate, a more of IgG4-related disease such as dense lymphoplas- careful follow-up of patients during steroid tapering macytic infiltrate, fibrosis, usually storiform in might be helpful to prevent recurrence of IOI. character and obliterative phlebitis,5 immunohistochemical analysis was performed to evaluate IgG and IgG4 expression levels. The cut-off value for INTRODUCTION IgG4-related disease was set, with >40% of the Idiopathic orbital inflammation (IOI), also called IgG-positive plasma cells being IgG4 positive or orbital inflammatory pseudotumour, had been >100 IgG4-positive plasma cells per high-power – known as a benign, non-infectious inflammatory field.5 7 condition with heterogeneous clinical and histo- The treatment outcome of IOI and the recurrence pathological characteristics. Recently, enlargement rate following treatment were used as the secondary of the infraorbital nerve (ION) with subsequent outcome measures. Three patients were excluded expansion of the ION canal was reported to be from the steroid treatment regimen as they were associated with IgG4-related orbital inflammation, suspected of neoplasm and received complete exci- one of the well-known causes of IOI.12Hardy sion of the lesion. The rest of the patients received et al3 described 14 patients with ION canal high-dose per oral (po) prednisolone (1 mg/kg) enlargement who all had a reactive lymphoid with a weekly tapering schedule. Steroid treatment hyperplasia. Seven of these patients were diagnosed was repeated for relapsed patients with careful mon- with an IgG4-related inflammatory disease. itoring of complications. In cases with repetitive In the present study, we conducted a novel inves- inflammation, orbital radiotherapy (a total dose of tigation in which clinical manifestations, radio- 20 Gy divided into 2 Gy fractions) or immunosup- To cite: Lee KH, Han SH, logical and histological findings, and treatment pressive therapy was applied. Yoon JS. Br J Ophthalmol outcomes were compared between patients who Statistical analyses were performed using SPSS – 2016;100:1295 1300. had IOI with and without ION enlargement. software, V.19.0 (SPSS, Chicago, Illinois, USA).

Lee KH, et al. Br J Ophthalmol 2016;100:1295–1300. doi:10.1136/bjophthalmol-2015-307232 1295 Downloaded from http://bjo.bmj.com/ on August 30, 2016 - Published by group.bmj.com Clinical science

Demographic variables were calculated as frequency/rate (per- showed a significantly higher rate of proptosis (66.7% in centage), range, mean and median values. Sex, age and group 1 and 26.0% in group 2, p=0.013), pain in the affected symptom duration were tested using the Mann–Whitney U test. eye (66.7% in group 1 and 22.1% in group 2, p=0.004) and Bilaterality, location, laboratory and histological findings, and alteration of sensation in the ipsilateral cheek area (25.0% and the treatments and outcomes of inflammation were tested using 0% in groups 1 and 2, respectively, p<0.001) (figure 1). the χ2 test. A p value <0.05 was considered to indicate a statis- Review of the CT scan results revealed that there is a statistical tically significant result. significance to the location of the IOI lesion for both groups. Diffuse involvement of retrobulbar fat was most common in RESULTS group 1 (8 of 12 patients, 66.7%), and the lacrimal gland Of 152 patients diagnosed with IOI between January 2009 and involvement was most common in group 2 (34 of 77 patients, December 2013, 89 patients were included in the study. Patient 44.2%). Eleven (91.7%) patients with ION enlargement had follow-up period ranged from 12 to 144 months (median, inferiorly located inflammation with extension of the inflamma- 14.0 months; mean, 25.5 months). Twelve patients (7 males and tion into the maxillary sinus (table 2). 5 females) had ION enlargement with the initial CT findings We performed a biopsy of the inflamed lesion when it (group 1), and 77 patients (38 males and 39 females) did not recurred after tapering of the steroid therapy, or to differentiate (group 2). The median patient age was 46.5 years (mean, 49.8; the lesion from an orbital tumour (eg, for the presence of a lym- range, 35–71) in group 1 and 46.5 years (mean, 44.9; range, phoproliferative disorder). Pathological confirmation was per- 10–80) in group 2. Three of the 12 patients in group 1 formed in 7 (58.3%) patients in group 1. For all specimens, the (25.0%) and 13 of the 77 (16.9%) patients in group 2 had results revealed the presence of dense fibrosis from chronic bilateral disease presentation. Sex, age, symptom duration and inflammation. Sclerosing change, which was defined as collage- bilaterality of the inflammation were not different between the nous replacement of majority of the normal anatomical struc- two groups. The results for patient characteristics are presented ture,8 was present in 4 (33.3%) cases. Among the 77 patients in in table 1. group 2, 22 patients underwent biopsy of the orbital lesion, and The most frequent symptom present at the initial diagnosis 8 patients showed sclerosis of the inflammatory lesion (10.4%). was eyelid swelling (66.7% in group 1 and 59.7% in group 2, The ratio of sclerosing disease was higher in group 1 than in p=0.889) for both groups. Group 1, compared with group 2, group 2 (p=0.015).

Table 1 Clinical manifestations in patients with idiopathic orbital inflammation Patients with ION Patients without ION enlargement (12 patients) enlargement (77 patients) p Value

Sex (M:F) 7:5 38:39 0.788 Age (years, mean) 49.8 44.9 0.281 Symptom duration (months, mean) 7.2 7.3 0.991 Total follow-up (months, mean) 36.5 23.8 0.053 Unilateral:bilateral 9:3 64:13 0.630 Initial symptom Eyelid swelling 8 (66.7%) 46 (59.7%) 0.889 Proptosis 8 (66.7%) 20 (26.0%) 0.013 Palpable mass 1 (8.3%) 12 (15.6%) 0.824 Eyeball pain 8 (66.7%) 17 (22.1%) 0.004 Blurred vision 2 (16.7%) 4 (5.2%) 0.090 Alteration of sensation or pain of cheek area 3 (25.0%) 0 <0.001 Diplopia 4 (33.3%) 18 (23.4%) 0.701 Location Lacrimal gland 2 (16.7%) 34 (44.2%) 0.137 Intraocular muscle 5 (41.7%) 22 (28.6%) 0.562 Diffuse infiltration of retrobulbar fat 8 (66.7%) 9 (11.7%) <0.001 Other 3 (25.0%) 6 (7.8%) 0.185 Inferiorly located inflammation 11 (91.7%) 6 (7.8%) <0.001 Other medical history 3 (25.0%) 13 (16.9%) 0.782 Sclerosing disease (pathology) 4/7 8/22 0.015

IgG4-related disease 5/8 9/25 0.363 Treatment Only systemic steroid 6 (50.0%) 67 (87.0%) 0.007 + Additional immunosuppressants* 3 (25.0%) 3 (3.9%) 0.036 + Radiation 5 (41.7%) 5 (6.5%) 0.002 Complete excision without steroid 0 3 (3.9%) 0.870 Outcome Recurrence 0/1/2/≥3 2/2/0/8 51/5/6/15 0.001 Bold values denote significant p values. p Values <0.05 are considered to be statistically significant. *Per oral methotrexate, azathioprine and ciclosporin in addition to systemic steroid. ION, infraorbital nerve.

1296 Lee KH, et al. Br J Ophthalmol 2016;100:1295–1300. doi:10.1136/bjophthalmol-2015-307232 Downloaded from http://bjo.bmj.com/ on August 30, 2016 - Published by group.bmj.com Clinical science

In group 1, 10 of the 12 (83.3%) patients had one or more relapse, and 8 (66.7%) patients experienced repetitive inflammation (recurrence ≥3) with steroid dependency (figure 2). Three (25.0%) of the patients with repetitive inflammation received other immunosuppressive agents such as methotrexate, azathioprine and ciclosporin in addition to systemic steroid, and five (47.1%) received orbital radiotherapy. Two patients received both additional immunosuppressive therapy and orbital radiotherapy. In group 2, 74 of the 77 patients received po steroid therapy. Fifty-one (66.2%) patients in group 2 did not experi- ence any recurrence, and only 15 (19.5%) patients experienced repetitive inflammation (recurrence ≥3) with steroid dependency. Five (6.5%) of the patients with recurrent inflammation received radiotherapy, and three patients (3.9%) required additional immunosuppressive agents. One patient received both Figure 1 Distribution of patients with and without infraorbital nerve (ION) enlargement according to initial symptoms of idiopathic orbital additional immunosuppressive therapy and orbital radiotherapy. inflammation (*p<0.05). All patients maintained without recurrence with additional treatment. Group 1 showed a significantly higher inflammation recurrence rate (p=0.001) than group 2. Thirty-three (37.1%) patients received serological and histo- We further analysed the recurrence rate in patients with or pathological tests for IgG4-related disease (8 in group 1 and 25 without diffuse inflammation. In patients with diffuse inflamma- in group 2), and 14 patients (5 in group 1 and 9 in group 2) sat- tion (17 patients, ION-enlarged group of 8 and non-ION- isfied the diagnostic criteria for IgG4-related disease. The ratio enlarged group of 9), five patients (62.5%) with ION of IgG4-related disease was not different between the two enlargement experienced recurrence as opposed to one recur- groups (p=0.363). rence (11.1%) in non-ION-enlarged patients. The recurrence Suspected of a benign neoplasm of the lacrimal gland, three rate was significantly higher in the ION-enlarged group patients (3.4%) underwent complete excision of the lesion. The (p=0.029) in the patients with diffuse inflammation. In the pathology results for the three patients indicated chronic scleros- localised inflammation group (72 patients, ION-enlarged group ing inflammation of the lacrimal gland. None showed ION of 4 and non-ION-enlarged group of 68), the recurrence rate in enlargement and were included in group 2. They remained ION enlargement group (75%) was significantly higher than symptom free without steroid treatment during the follow-up that in non-ION enlarged (20.6%) (p=0.004). period. Except for the three patients in group 2, all patients We subanalysed the rate of repetitive inflammation in patients received po steroid therapy. according to whether their diagnosis was based on pathological

Table 2 Clinical manifestations at the initial visit in patients with ION enlargement Radiological finding Symptom duration ION Follow-up Case Sex/age Ocular signs and symptoms (months) Location of inflammation enlargement (months)

1* M/54 Eyelid swelling, pain (OU) 4 Diffuse infiltration of retrobulbar fat, both Bilateral 40 Maxillary sinus, both 2*† F/35 Eyelid swelling, pain, proptosis (OD) 1 Inferior orbit, right Ipsilateral 12 Altered sensation at ipsilateral cheek area, right Maxillary sinus, right 3* F/41 Eyelid swelling, pain (OS) 12 Inferior orbit, left Ipsilateral 35 Diplopia 4 F/36 Eyelid swelling, proptosis, pain (OD) 3 Diffuse infiltration of retrobulbar fat, right Ipsilateral 96 Blurred vision(OD) 5 M/48 Eyelid swelling, proptosis, pain (OS) 3 Diffuse infiltration of retrobulbar fat, left Ipsilateral 60 Blurred vision (OS) Maxillary sinus, left 6 M/40 Proptosis (OD) 1.5 Intraocular muscle/retrobulbar fat, right Ipsilateral 40 Altered sensation at ipsilateral cheek area, right 7 M/71 Proptosis, pain (OS) 12 Lacrimal gland/intraocular muscle/retrobulbar fat, Bilateral 27 left/maxillary sinus, left 8 M/57 Eyelid swelling, proptosis, pain (OS) 0.5 Intraocular muscle/retrobulbar fat, left Ipsilateral 12 9 F/59 Eyelid swelling (OD) 1 Intraocular muscle/retrobulbar fat, right Ipsilateral 12 Diplopia Maxillary sinus, right 10 M/40 Pain (OS) 0.5 Intraocular muscle/inferior orbit, left Ipsilateral 20 Altered sensation at ipsilateral cheek area (OS) Maxillary sinus, left 11* F/57 Proptosis (OU), palpable mass (OU) 12 Lacrimal gland, both Bilateral 72 12* M/60 Eyelid swelling, proptosis (OU) 36 Diffuse infiltration of retrobulbar fat, both Bilateral 12 Diplopia Maxillary sinus, both

*Cases diagnosed as IgG4-related disorder. †Illustrations for radiological and histochemical analyses of case 2 are provided in figure 3. ION, infraorbital nerve; OD, right eye; OS, left eye; OU, both eyes.

Lee KH, et al. Br J Ophthalmol 2016;100:1295–1300. doi:10.1136/bjophthalmol-2015-307232 1297 Downloaded from http://bjo.bmj.com/ on August 30, 2016 - Published by group.bmj.com Clinical science

Figure 2 Treatment and outcome ﬂow chart for patients with orbital inﬂammatory disease.

examination of IOI. In patients with histopathological results IgG4-positive plasma cells were present, which suggests that (29 patients, ION-enlarged group of 7, non-ION-enlarged ION enlargement during IgG4-related disease results from group of 22), five patients (71.4%) with ION enlargement inflammation involving the epineurium of the ION.9 Our radio- experienced repetitive inflammation as opposed to five (22.7%) logical and immunochemical findings suggested similar results in patients with non-ION enlargement. The rate of repetitive (figure 3). In a case with IOI-associated ION enlargement inflammation was significantly higher among the patients with (case 2, see table 2), immunohistochemical analyses revealed ION enlargement (p=0.018, Fisher’s exact test) when their diffuse infiltration of inflammatory cells and IgG4-positive diagnoses were confirmed by histopathological results. In the plasma cells in the inflammatory region (figure 3C, D). The sig- patients without histopathological results (60 patients, nificant correlation between IgG4-related disease and ION ION-enlarged group of 5 and non-ION-enlarged group of 55), enlargement had been previously published in multiple – the rate of repetitive inflammation in ION enlargement group studies.13 15 However, contrary to the general understanding, (3 patients, 60%) was significantly higher than that in non-ION both groups in this study showed the same ratio of patients with enlarged (10 patients, 18.1%) (p=0.03, Fisher’s exact test). IgG4-related disease. There was no statistical correlation between IgG4-related disease and accompanied ION enlarge- DISCUSSION ment. Such discrepancy could be due to the fact that group 1 This was the first report to compare the clinical and histological had a small sample size and might have lacked sufficient statis- characteristics of IOI according to ION enlargement. ION tical power, and that other unidentified mechanisms might have enlargement was found in 13.5% of patients in our study, the played a role in ION enlargement. percentage of which is similar to those of previous studies The previously reported common symptoms of IOI included – – ranging from 12.7% to 33%.2912 Proptosis, ocular pain or proptosis, pain, lid swelling and presence of a mass.10 12 Similar altered sensation of the ipsilateral cheek area was more common to the results of previous studies, eyelid swelling or a mass, in patients with ION enlargement. Most patients with ION proptosis and pain were common in patients with IOI in this enlargement had inferiorly located inflammation with extension study. However, the ratio of patients with proptosis and pain of the inflammatory lesion into the maxillary sinus. The number was significantly higher in the patients with ION enlargement. of patients who showed steroid dependency and recurrence was This result may be related to the anatomical difference of loca- higher in patients with ION enlargement, signifying a poorer tion of inflammation; in group 1, there were more patients with IOI treatment outcome. diffuse infiltrative inflammation of retrobulbar space and in Enlargement of the ION during IOI had been previously group 2, more patients had inflammation of anterior soft tissue reported in several articles, but the exact pathogenesis had been (eg, lacrimal gland). still unknown. Watanabe et al2 suggested that the cause of ION Three patients in the ION-enlarged group presented with enlargement in IOI may be associated with the inflammatory changes in sensation around the ipsilateral cheek area. Sensory process that occurs during IgG4-related disease. Sogabe et al changes around the cheek area could be related to the inflamma- performed an excisional biopsy of the infraorbital canal in a tion of ION. Katsura et al14 described a patient with ION patient diagnosed with IgG4-related disease with bilateral ION enlargement who presented with left-sided facial numbness. enlargement. Histopathological assessment revealed the pres- While IOI had been classically associated with pain and numer- ence of a massive infiltration of small lymphocytes, plasma cells ous other symptoms in the affected area of the face, in the and scattered eosinophils in the epineurium of the ION. present study, the location of the symptoms coincided with the Immunohistostain results indicated that a large number of area of face innervated by ION, including lower eyelids and

1298 Lee KH, et al. Br J Ophthalmol 2016;100:1295–1300. doi:10.1136/bjophthalmol-2015-307232 Downloaded from http://bjo.bmj.com/ on August 30, 2016 - Published by group.bmj.com Clinical science

Figure 3 Case 2. Orbital CT and histopathological findings in a patient who visited our clinic with a 1-month history of pain in the right eye, and diplopia. (A) Initial CT results revealed infiltration of the right inferior orbital area with enlargement of the ipsilateral infraorbital nerve (ION) and ION canal. (B) The follow-up CT taken after steroid treatment indicated a reduction in the size of the ION and in the ION canal and in inflammation of the inferior orbital area. (C) Low-power H&E photomicrography of the inflammatory lesion indicated the presence of chronic active inflammation with diffuse lymphohistiocytic and plasma cell infiltration and sclerosis (40×). (D) Immunohistochemistry stain for IgG4-positive plasma cells (54 IgG4+ cells per high power field).

cheeks. The symptom profile was significantly increased when type of inflammation might be the determining factor for IOI is accompanied by ION enlargement. response to steroid treatment, instead of the presence of ION Most of patients with ION enlargement (11/12, 91.7%) had enlargement. A higher rate of recurrence was observed in the inferiorly located inflammation with extension of the inflamma- ION enlargement group, but there were also a higher percent- tory lesion into the maxillary sinus. Only one patient in group 1 age of patients with diffuse infiltrative type of inflammation had inflammation around bilateral lacrimal gland without with sinus inflammation compared with the group without infiltration around inferior orbit and was diagnosed with enlargement. McNicholas et al22 published a study suggesting IgG4-related disease after pathological confirmation (case 11, diffuse inflammation as a bad prognostic factor. However, the see table 2). change in recurrence rate depending on the extensiveness of IOI Traditional first-line treatment for IOI had been steroid has not been thoroughly researched and still requires much to therapy. The response rate of systemic therapy had been 80%– be explored. There has not been a consensus on whether the 90%, but roughly one-half of patients experienced relapse of diffuse IOI increases the recurrence rate and interestingly, we – the inflammation.16 18 In our study, 36 of the 89 (40.4%) found that in patients with and without diffuse inflammation, patients experienced relapse of the inflammation, which was the recurrence rate was higher in patients with ION enlargement similar to the results of previous studies. However, the rate of than in patients without ION enlargement. (p=0.029 and recurrence was significantly higher in patients with ION enlarge- p=0.004). In addition, the number of patients with dacryoade- ment. A higher percentage (66.7%) of patients with ION nitis was lower for the enlarged group compared with the group enlargement experienced repetitive inflammation more than without enlargement. Dacryoadenitis had generally shown dra- three times after discontinuation of steroid therapy, compared matic response to steroid treatment and this might be the case with 19.5% of the patients without ION enlargement. in yielding better treatment outcome in the latter group. The The cause of greater steroid dependency in patients with ION presence of such confounding variables could have skewed the enlargement was not clear, but we could propose several alter- data and further analysis would be necessary to rule out alterna- native hypotheses to explain such a phenomenon. First, the tive hypotheses. Third, the ION enlargement might itself be an ratio of sclerosing disease was higher in group 1 (33.3%) com- indicator of severe local or systemic inflammation. pared with group 2 (10.4%, p=0.015). The presence of scleros- Clinically, we diagnosed cases of IOI with typical clinical ing disease was indicated when dense fibrous connective tissue manifestation, imaging studies of patients and dramatic response with hardening of the normal tissue is the predominant compo- to systemic steroid, which can be viewed as pathognomonic for nent of the specimen. Sclerosis suggested the histopathological IOI. Biopsy of lesion was performed in patients with persistent end stage of IOI19 20 or a unique disease entity.21 In either case, or recurrent disease or in cases suspicious of tumour. Only 29 sclerosing disease often indicated the presence of a more aggres- patients (7 in group 1 and 22 in group 2) underwent histopatho- sive disease process with a poorer therapeutic outcome, com- logical examination, which might cause bias towards more pared with the non-sclerosing forms of the disease. Second, the sclerosing lesion in this subgroup of biopsied patients. The

Lee KH, et al. Br J Ophthalmol 2016;100:1295–1300. doi:10.1136/bjophthalmol-2015-307232 1299 Downloaded from http://bjo.bmj.com/ on August 30, 2016 - Published by group.bmj.com Clinical science diagnosis of IOI was made clinically similar to ours in other 3 Hardy TG, McNab A, Rose GE. Enlargement of the infraorbital nerve: an important – reports.12 23 25 Interestingly, in both groups of patients evalu- sign associated with orbital reactive lymphoid hyperplasia or immunoglobulin G4-related disease. Ophthalmology 2014;121:1297–303. ated separately according to either clinical trial of steroid or 4 Inoue D, Zen Y, Sato Y, et al. IgG4-related perineural disease. Int J Rheumatol pathological confirmation, the rate of repetitive inflammation 2012;2012;401890. was higher in patients with ION enlargement than in patients 5 Deshpande V, Zen Y, Chan JK, et al. Consensus statement on the pathology of without ION enlargement (p=0.018 in biopsied group and IgG4-related disease. Mod Pathol 2012;25:1181–92. p=0.03 in non-biopsied group). The small sample size of 6 Umehara H, Okazaki K, Masaki Y, et al. A novel clinical entity, IgG4-related disease (IgG4RD): general concept and details. Mod Rheumatol 2012;22:1–14. biopsy-proven patients may be a limitation to this study, but we 7 Plaza JA, Garrity JA, Dogan A, et al. Orbital inflammation with IgG4-positive believe that it did not affect the primary conclusion of our plasma cells: manifestation of IgG4 systemic disease. Arch Ophthalmol research. A further prospective study with much larger number 2011;129:421–8. of cases with histopathological examination in all cases espe- 8 Paul A, Brannan, A review of sclerosing idiopathic orbital inflammation. Curr Opin fi Ophthalmol 2007;18:402–4. cially with IgG4 evaluation would be bene cial. 9 Sogabe Y, Miyatani K, Goto R, et al. Pathological findings of infraorbital nerve In conclusion, patients with ION-enlarged IOI showed enlargement in IgG4-related ophthalmic disease. Jpn J Ophthalmol 2012;56:511–4. unique clinical and radiological characteristics. Symptoms 10 Swamy BN, McCluskey P, Nemet A, et al. Idiopathic orbital inflammatory syndrome: including proptosis, ocular pain and altered sensation of the clinical features and treatment outcomes. Br J Ophthalmol 2007;91:1667–70. 11 Mendenhall WM, Lessner AM. Orbital pseudotumor. Am J Clin Oncol ipsilateral cheek area were more common. Signs of sclerosis and – fi fl 2010;33:304 6. diffuse in ltrative in ammatory process were frequently 12 Yuen SJ, Rubin PA. Idiopathic orbital inflammation: distribution, clinical features, observed in pathological specimens. Steroid dependency and and treatment outcome. Arch Ophthalmol 2003;121:491–9. recurrence rate of inflammation were significantly higher as 13 Ohshima K, Sogabe Y, Sato Y. The usefulness of infraorbital nerve enlargement on well. Therefore, a more careful treatment plan of steroid taper- MRI imaging in clinical diagnosis of IgG4-related orbital disease. Jpn J Ophthalmol 2012;56:380–2. ing with more frequent follow-up is necessary in IOI patients 14 Katsura M, Morita A, Horiuchi H, et al. IgG4-related inflammatory pseudotumor of with ION enlargement. the trigeminal nerve: another component of IgG4-related sclerosing disease? AJNR Am J Neuroradiol 2011;32:E150–2. Acknowledgements The authors thank Dong Soo Chang for his significant 15 Siqueira GB, Jain A, Chahud F, et al. Bilateral infraorbital nerve involvement in contribution in illustration and design of data figures. idiopathic orbital myositis. Ophthal Plast Reconstr Surg 2002;18:474–8. Contributors Conception and design: KHL and JSY; acquisition of data: KHL; 16 Mombaerts I, Schlingemann RO, Goldschmeding R, et al. 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1300 Lee KH, et al. Br J Ophthalmol 2016;100:1295–1300. doi:10.1136/bjophthalmol-2015-307232 Downloaded from http://bjo.bmj.com/ on August 30, 2016 - Published by group.bmj.com

Implications of enlarged infraorbital nerve in idiopathic orbital inflammatory disease

Ka Hyun Lee, Sun Hyup Han and Jin Sook Yoon

Br J Ophthalmol 2016 100: 1295-1300 originally published online December 30, 2015 doi: 10.1136/bjophthalmol-2015-307232

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