Enlargement of the Infraorbital Nerve: An Important Sign Associated with Orbital Reactive Lymphoid Hyperplasia or Immunoglobulin G4–Related Disease

doi:10.1016/j.ophtha.2013.12.028

Ophthalmology

Volume 121, Issue 6, June 2014, Pages 1297-1303

https://doi.org/10.1016/j.ophtha.2013.12.028 Get rights and content

Objective

To describe the clinical, histopathologic, and radiologic features of a recently identified cause for enlargement of the infraorbital canal.

Design

Retrospective, noncomparative case series.

Participants

Consecutive patients were identified from the orbital databases at Moorfields Eye Hospital, London, England, and the Royal Victorian Eye and Ear Hospital, Melbourne, Australia.

Methods

A retrospective, noncomparative review of the clinical case notes, radiology, and histopathology was performed. The English-language medical literature was reviewed for reports of enlargement of the infraorbital canal or nerve.

Main Outcome Measures

Extent of clinical and radiologic changes in patients with enlargement of the infraorbital canal.

Results

A total of 14 patients (10 male) presented between the ages of 29 and 76 years with proptosis, eyelid swelling or a mass (10/14 cases), and periocular ache (5/14 cases). Clinical evidence of bilateral involvement was present in 6 of 14 patients. None had impairment of visual functions or facial sensation, but 4 of 14 patients had some reduction in ocular motility. Imaging showed a focal orbital mass in 10 of 14 patients (16/28 orbits), and all patients (22/28 orbits) had enlargement of some extraocular muscles. The infraorbital canal was enlarged in 20 of the 28 orbits, with associated ipsilateral orbital changes in 19 of 20 (all 14 patients) and ipsilateral maxillary sinus changes in 12 of 20 (11 patients). Biopsy-proven chronic orbital inflammation was present in all patients; this resembled reactive lymphoid hyperplasia (RLH) in 7 patients and immunoglobulin (Ig) G4–related sclerosing inflammation in 7 patients. When tested, serum IgG4 was elevated in 6 of 7 patients. Clinical or histologically proven enlargement of cervical lymph nodes was present in 7 of 14 patients. All patients responded well to systemic corticosteroid therapy, although some had a relapse upon withdrawal. One patient developed diffuse large B-cell lymphoma and subsequently leukemia, of which he later died 20 years after presentation.

Conclusions

Enlargement of the infraorbital nerve and canal is rare and strongly suggests a diagnosis of RLH or IgG4-related disease, especially in the presence of ipsilateral extraocular muscle enlargement, sinus disease, or focal orbital disease.

Section snippets

Methods

Consecutive patients with expansion of the ION or canal were identified from 2 orbital databases (Moorfields Eye Hospital, London, England, and the Royal Victorian Eye and Ear Hospital, Melbourne, Australia), and a retrospective review of the clinical case notes, radiology, and histopathology was performed. The nerve or canal was regarded as expanded where the diameter on coronal imaging exceeded that of the optic nerve.¹⁰ Institutional review board/ethics committee approval was obtained for

Results

Fourteen consecutive patients with ION enlargement were identified from the authors' databases: 5 from Moorfields Eye Hospital and 9 from the Royal Victorian Eye and Ear Hospital. Their initial presentations ranged from 1991 to 2005. We describe the details of 3 of these patients and summarize the findings.

Discussion

The clinical, radiologic, and histologic findings in patients with ION enlargement have been described. Although ION enlargement has been recently described as being almost pathognomonic¹⁰ or suggestive14, 15 of IgG4 disease in some patient groups, our series suggests that this process can occur with other diseases, namely, RLH. Approximately half our cases were categorized as IgG4-RD on histologic review. All of our patients had sinus disease and enlarged extraocular muscles, and two thirds

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A total of 115 (94%) of the 122 patients in our cohort had preoperative orbital images (computed tomography=105, magnetic resonance imaging=40). Among them, 103/115 (90%) showed enlarged lacrimal glands, and 91 (88%) were bilateral. Nerve enlargement was observed: infraorbital in 31/115 (27%) patients and frontal in 17/115 (15%), 10 and 9 being bilateral, respectively. At least 1 or more extraocular muscle (EOM) enlargement was found in 41/115 (37%) patients, bilaterally in 20. Lateral rectus occurred in 30 (73%) of these 41 EOM patients and inferior rectus in 28 (68%). Two adjacent EOMs (inferior and lateral recti in 11 patients, inferior and medial recti in 7 patients) or multiple EOMs (at least 3) were enlarged in 23/41 (56%) and 13/41 (32%) of the patients, respectively. Intraconal lesions (67% vs 11%, P<0.05), infraorbital (83% vs 23%, P<0.005), or frontal (50% vs 15%, P<0.05) nerve enlargement was significantly associated with IgG4-RON (6 patients) by univariate analyses. Asymmetric lacrimal gland enlargement and discrete orbital mass (both P<0.05) were associated with IgG4-ROL (9 patients) by multivariate analyses.
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: Supplementary material available at www.aaojournal.org

: Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

: Funding: G.E.R. receives partial funding from the Department of Health's NIHR Biomedical Research Centre for Ophthalmology at Moorfields Eye Hospital and UCL Institute of Ophthalmology.

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Original articleEnlargement of the Infraorbital Nerve: An Important Sign Associated with Orbital Reactive Lymphoid Hyperplasia or Immunoglobulin G4–Related Disease

Objective

Design

Participants

Methods

Main Outcome Measures

Results

Conclusions

Section snippets

Methods

Results

Discussion

Ophthalmology

Am J Ophthalmol

Ophthalmology

Am J Ophthalmol

Ophthalmology

Mayo Clin Proc

Mod Pathol

Mod Pathol

Am J Pathol

Blood

Ophthalmology

Mod Pathol

Hum Pathol

Semin Diagn Pathol

Ocular adnexal lymphoproliferative disease: a series of 73 cases

Clin Experiment Ophthalmol

IgG4-related perineural disease

Int J Rheumatol [serial online]

The usefulness of infraorbital nerve enlargement on MRI imaging in clinical diagnosis of IgG4-related orbital disease

Jpn J Ophthalmol

IgG4-positive plasma cells specifically infiltrate various organs in autoimmune pancreatitis [letter]

Pancreas

Ocular adnexal IgG4-related disease has uniform clinicopathology

Pathol Int

Pathological findings of infraorbital nerve enlargement in IgG4-related ophthalmic disease

Jpn J Ophthalmol

Clinical aspects of IgG4-related orbital inflammation in a case series of ocular adnexal lymphoproliferative disorders

Int J Rheumatol [serial online]

MR imaging of IgG4-related disease in the head and neck and brain

AJNR Am J Neuroradiol

Reactive lymphoid hyperplasia

An overview of ocular adnexal lymphoid tumors

Trans Am Ophthalmol Soc

Orbital lymphoproliferative tumors: analysis of clinical features and systemic involvement in 160 cases

Ophthalmology

Malignant lymphomas in autoimmunity and inflammation: a review of risks, risk factors, and lymphoma characteristics

Cancer Epidemiol Biomarkers Prev

Population-based study of autoimmune conditions and the risk of specific lymphoid malignancies

Int J Cancer

Differential risk of non-Hodgkin's lymphoma in Italian patients with primary Sjogren's syndrome

J Rheumatol

Lacrimal gland orbital lobe cysts associated with MALT lymphoma and primary Sjogren's syndrome

Orbit

Lymphoid neogenesis: de novo formation of lymphoid tissue in chronic inflammation through expression of homing chemokines

J Leukoc Biol

Disease activity and risk of lymphoma in patients with rheumatoid arthritis: nested case-control study

BMJ

Original article
Enlargement of the Infraorbital Nerve: An Important Sign Associated with Orbital Reactive Lymphoid Hyperplasia or Immunoglobulin G4–Related Disease