Editorials

Etiology and management of idiopathic orbital inflammation

To investigate the utility of intravoxel incoherent motion diffusion-weighted MRI (IVIM-DWI) derived diffusion and perfusion parameters in differentiating ocular adnexal lymphoma (OAL) from idiopathic orbital inflammation (IOI), and to assess whether IVIM-DWI provides improved diagnostic performance for the distinction.

Twenty-one patients with OAL and 24 patients with IOI underwent IVIM-DWI. Apparent diffusion coefficient (ADC) and IVIM-DWI parameters including true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f) were measured in lesions by two independent radiologists. The MRI parameter differences between OAL and IOI were tested using two-sample t-test. The receiver operating characteristic (ROC) analysis curves were used to determine the diagnostic performance of significant parameters for differentiation between OAL and IOI.

The ADC, D, and f were lower in OAL than those in IOI (ADC = 0.78 ± 0.12 vs. 0.99 ± 0.16 × 10⁻³ mm²/s, P < 0.001; D = 0.34 ± 0.15 vs. 0.76 ± 0.25 × 10⁻³ mm²/s, P < 0.001; f = 0.31 ± 0.06 vs. 0.41 ± 0.08 × 100 %, P < 0.001). There was no significant difference in D* between OAL and IOI (P = 0.235). The optimal cut-off values of ADC, D, and f in differentiating OAL from IOI were 0.83 × 10^-3 mm²/s, 0.56 × 10^-3 mm²/s, and 0.36 × 100 %, respectively. No significant differences were found in areas under the curve (AUCs) among ADC, D and f (all P > 0.05). The combination of D and f provided significantly higher AUC than ADC (AUC = 0.984 vs. 0.838, Z = 2.128, P = 0.033), and had higher sensitivity of 95.24 %, specificity of 95.83 %, and accuracy of 95.56 %.

IVIM-DWI is valuable in differentiating OAL from IOI, and D combined f can improve the performance of differential diagnosis.

A large array of pathologies must be considered in the etiologic differential diagnosis of diseases affecting the ocular tissues. Understanding the most common pathologies that explain symptoms in the eye or threaten life or vision even without symptoms, knowledge of the nomenclature and its nuances used to communicate findings, and recognizing challenging differential diagnoses are key to the accurate diagnosis and treatment of ocular diseases. This chapter describes the major causes of neoplastic ocular diseases, the histopathological findings, and major differential diagnoses. This chapter is divided into three sections. The first section describes the most common benign and malignant pathologies of the conjunctiva, some of which may be challenging lesions encountered in surgical pathology practice. The second section is dedicated to pathological processes affecting the orbital tissues and lacrimal gland, providing an overview of the most common diagnoses, the differential diagnoses, and options of treatment for mass lesions that may lead to decreased vision or worse. The third section describes the most common intraocular tumors including metastasis, uveal melanoma, and retinoblastoma. A discussion on the normal histopathology of the ocular tissues in each section will allow the reader to better understand the various pathological processes. The goal of the chapter is to determine the role of pathology in informing treatment strategies for eye diseases, and to illuminate the collaboration between the pathologist and ophthalmologist.

Biopsies and ANCA testing for limited forms of granulomatosis with polyangiitis (GPA) are frequently non-diagnostic. We characterized gene expression in GPA and other causes of orbital inflammation. We tested the hypothesis that a sub-set of patients with non-specific orbital inflammation (NSOI, also known as pseudotumor) mimics a limited form of GPA. Formalin-fixed, paraffin-embedded orbital biopsies were obtained from controls (n = 20) and patients with GPA (n = 6), NSOI (n = 25), sarcoidosis (n = 7), or thyroid eye disease (TED) (n = 20) and were divided into discovery and validation sets. Transcripts in the tissues were quantified using Affymetrix U133 Plus 2.0 microarrays.

Distinct gene expression profiles for controls and subjects with GPA, TED, or sarcoidosis were evident by principal coordinate analyses. Compared with healthy controls, 285 probe sets had elevated signals in subjects with GPA and 1472 were decreased (> 1.5-fold difference, false discovery rate adjusted p < 0.05). The immunoglobulin family of genes had the most dramatic increase in expression. Although gene expression in GPA could be readily distinguished from gene expression in TED, sarcoidosis, or controls, a comparison of gene expression in GPA versus NSOI found no statistically significant differences.

Thus, forms of orbital inflammation can be distinguished based on gene expression. NSOI/pseudotumor is heterogeneous but often may be an unrecognized, localized form of GPA.

L’inflammation orbitaire est un terme générique regroupant les pathologies inflammatoires affectant toutes les structures situées à l’intérieur de l’orbite : forme antérieure (atteinte localisée jusqu’à la partie postérieure du globe), diffuse (atteinte de la graisse orbitaire intra et/ou extraconique), apicale (atteinte de la partie postérieure de l’orbite), myosite (atteinte uniquement des muscles orbitaires), dacryoadénite (atteinte de la glande lacrymale). On distingue les inflammations spécifiques des inflammations non spécifiques appelées plus communément inflammations idiopathiques. Les inflammations orbitaires spécifiques correspondent à la localisation secondaire d’une maladie « générale » (maladie systémique ou auto-immune). Les inflammations orbitaires idiopathiques correspondent à une atteinte inflammatoire uniquement orbitaire sans maladie générale retrouvée et donc d’étiologie inconnue. Au premier rang des diagnostics différentiels des inflammations orbitaires spécifiques ou idiopathiques, se situent les affections tumorales malignes, dominées chez l’adulte par les syndromes lympho-prolifératifs et les métastases. Le traitement des inflammations orbitaires spécifiques est d’abord le traitement de la maladie causale. Pour les inflammations orbitaires idiopathiques un traitement (le plus souvent corticothérapie) est indiqué surtout en cas d’altération visuelle par neuropathie optique, en présence d’une douleur ou d’une paralysie oculomotrice.

Orbital inflammation is a generic term encompassing inflammatory pathologies affecting all structures within the orbit : anterior (involvement up to the posterior aspect of the globe), diffuse (involvement of intra- and/or extraconal fat), apical (involvement of the posterior orbit), myositis (involvement of only the extraocular muscles), dacryoadenitis (involvement of the lacrimal gland). We distinguish between specific inflammation and non-specific inflammation, commonly referred to as idiopathic inflammation. Specific orbital inflammation corresponds to a secondary localization of a “generalized” disease (systemic or auto-immune). Idiopathic orbital inflammation corresponds to uniquely orbital inflammation without generalized disease, and thus an unknown etiology. At the top of the differential diagnosis for specific or idiopathic orbital inflammation are malignant tumors, represented most commonly in the adult by lympho-proliferative syndromes and metastases. Treatment of specific orbital inflammation begins with treatment of the underlying disease. For idiopathic orbital inflammation, treatment (most often corticosteroids) is indicated above all in cases of visual loss due to optic neuropathy, in the presence of pain or oculomotor palsy.

Les myosites aiguës représentent la deuxième entité la plus fréquente des inflammations orbitaires non spécifiques. Nous décrirons leurs caractéristiques cliniques et évolutives. Il s’agit d’une étude rétrospective de dix cas. Le diagnostic de myosite aiguë était posé sur des arguments cliniques et d’imagerie. Notre étude porte sur cinq hommes et cinq femmes. L’âge moyen était de 35,8 ans (17–59 ans). Les signes cliniques étaient : douleur majorée à la mobilisation du globe (10/10), diplopie (4/10), exophtalmie (6/10), baisse d’acuité visuelle (3/10), œdème palpébral (6/10), hyperémie conjonctivale (7/10), sclérite antérieure (2/10), épisclérite (2/10), chémosis (4/10), rétraction palpébrale supérieure (1/10), limitation de l’oculomotricité (3/10), signes au fond d’œil (2/10). L’imagerie montrait un épaississement d’un ou plusieurs muscles oculomoteurs (10/10). La récupération était totale sous traitement anti-inflammatoire pour six patients. Trois patients ont présenté une récidive. Un patient a présenté un rebond lors de la décroissance du traitement. Les myosites aiguës se définissent par une douleur à la mobilisation du globe oculaire, des signes inflammatoires et un épaississement musculaire à l’imagerie. Devant un tableau typique, il est possible de surseoir à l’analyse histopathologique. Celle-ci reste indiquée en cas de mauvaise réponse au traitement, de passage à la chronicité ou de suspicion d’infiltration tumorale. Le diagnostic de myosite aiguë peut être suspecté dès l’examen clinique devant des signes constants et bien définis. Une inflammation de contiguïté est souvent associée. La thérapeutique repose sur un traitement anti-inflammatoire stéroïdien ou non stéroïdien, administré isolément ou successivement. Les récidives sont fréquentes sans altérer le pronostic final.

Acute myositis is the second most common component of non-specific orbital inflammation. We will describe its clinical features and natural history. This is a retrospective study of 10 cases. The diagnosis of acute myositis was based on clinical and imaging criteria. Our study includes five men and five women. The average age was 35.8 years (17–59 years). Clinical symptoms were: pain increased on eye movement (10/10), diplopia (4/10), proptosis (6/10), visual loss (3/10), lid edema (6/10), conjunctival hyperemia (7/10), anterior scleritis (2/10), episcleritis (2/10), chemosis (4/10), upper lid retraction (1/10), limitation of eye movement (3/10), fundus abnormalities (2/10). Imaging showed thickening of one or more extraocular muscles (10/10). Recovery was complete with anti-inflammatory therapy in six patients. Three patients experienced recurrence, and one patient had a clinical rebound upon tapering the treatment. Acute myositis can be defined by pain on eye movement, signs of inflammation, and extraocular muscle thickening on imaging. If the clinical presentation is typical, histopathological analysis can be deferred but remains necessary in cases of poor response to treatment, chronic duration or suspicion of tumor infiltration. The diagnosis of acute myositis may be suspected in the presence of consistent, well-defined clinical signs. Contiguous inflammation is often associated. Treatment is based on steroids or non-steroidal treatment anti-inflammatory therapy, administered alone or consecutively. Recurrences are frequent but do not alter the final prognosis.