IgG4-related Ophthalmic Disease Research Articles

Clinical characteristics and treatment outcomes of patients with IgG4-positive ocular adnexal marginal zone B-cell lymphoma.

To explore the clinicopathological characteristics of immunoglobulin G4 (IgG4)-positive ocular adnexal marginal zone B-cell lymphoma (OAML) and associated patient treatment outcomes. Medical records from patients diagnosed with IgG4-positive OAML treated at the West China Hospital between January 2016 and August 2023 were retrospectively analyzed. This study included data from 22 patients (11 males, 11 females), aged between 36 and 83 years, with disease durations from 1 month to 30 years. Sixteen cases exhibited unilateral ocular involvement (ten left eyes, six right eyes), while six exhibited bilateral involvement. Common clinical symptoms included ocular masses, eyelid swelling, and proptosis, with the orbit and lacrimal gland being the most commonly impacted sites. Among the 22 patients, 13 who were clinically suspected of having IgG4-related ophthalmic disease (IgG4-ROD) underwent serum IgG4 testing pre-operatively, revealing elevated IgG4 levels in 11 of these patients. The use of computed tomography and magnetic resonance imaging facilitated the evaluation of the location and size of lesions. All 22 patients received surgical treatment. Subsequently, 14 of these patients underwent local radiotherapy, five received post-operative chemotherapy, and three were closely observed. The follow-up period of patients in this study was 3-77 months, with an average follow-up time of 36 months. Except for one patient who died of disease progression, all others showed favorable prognoses with significant improvements. These results support the classification of IgG4-positive OAML as a distinct OAML sub-type with clinical features that partially overlap with IgG4-ROD. Therefore, accurate differentiation between OAML and IgG4-ROD is imperative, necessitating timely surgical intervention and precise pathological diagnosis to prevent diagnostic errors and inappropriate treatment. Currently, no standardized treatments for IgG4-positive OAML exist, but our results suggest that standard OAML therapies are generally efficacious.

Artificial intelligence-based differential diagnosis of orbital MALT lymphoma and IgG4 related ophthalmic disease using hematoxylin-eosin images.

To investigate the possibility of distinguishing between IgG4-related ophthalmic disease (IgG4-ROD) and orbital MALT lymphoma using artificial intelligence (AI) and hematoxylin-eosin (HE) images. After identifying a total of 127 patients from whom we were able to procure tissue blocks with IgG4-ROD and orbital MALT lymphoma, we performed histological and molecular genetic analyses, such as gene rearrangement. Subsequently, pathological HE images were collected from these patients followed by the cutting out of 10 different image patches from the HE image of each patient. A total of 970 image patches from the 97 patients were used to construct nine different models of deep learning, and the 300 image patches from the remaining 30 patients were used to evaluate the diagnostic performance of the models. Area under the curve (AUC) and accuracy (ACC) were used for the performance evaluation of the deep learning models. In addition, four ophthalmologists performed the binary classification between IgG4-ROD and orbital MALT lymphoma. EVA, which is a vision-centric foundation model to explore the limits of visual representation, was the best deep learning model among the nine models. The results of EVA were ACC = 73.3% and AUC = 0.807. The ACC of the four ophthalmologists ranged from 40 to 60%. It was possible to construct an AI software based on deep learning that was able to distinguish between IgG4-ROD and orbital MALT. This AI model may be useful as an initial screening tool to direct further ancillary investigations.

Infraorbital nerve involvement as a pathognomonic sign of IgG4-related ophthalmic disease

Infraorbital nerve involvement as a pathognomonic sign of IgG4-related ophthalmic disease

IgG4-related uveitis. A French cohort and literature review

IntroductionIgG4-related disease (IgG4-RD) is a fibro-inflammatory disorder that can affect almost any organ. IgG4-related ophthalmic disease is a protean condition involving the orbit and ocular adnexa. Although a few cases of uveitis have been reported, the exact pattern of IgG4-related intraocular manifestations remains unclear. Here, we report on a nationwide French multicenter cohort of patients with IgG4-RD and uveitis and conducted a literature review. MethodsPatients with uveitis and a concomitant definite diagnosis of IgG4-RD (Revised Comprehensive Diagnostic criteria, American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-RD, International Consensus Diagnostic Criteria for auto-immune pancreatitis, or diagnostic criteria for IgG4-related hypophysitis), were screened from our national IgG4-RD and systemic fibrosis database. Concomitantly, we conducted a PubMed literature review and selected cases of definite IgG4-RD with uveitis. ResultsWe reported on 16 patients (8 from our database and 8 from the literature) and a total of 30 episodes of uveitis. Uveitis cases represented 3 % of total IgG4-RD patients in the national database on IgG4-RD and systemic fibrosis. Uveitis was inaugural in IgG4-RD in 4/16 cases (25 %) (appearing before any other IgG4-related symptom, at a median of 9 months), occurred concurrently to other IgG4-related symptoms in 9/16 cases (56 %) (at a median of 15 months before IgG4-RD diagnosis), and appeared during follow up in 3/16 patients (19 %) (at a median of 57 months after first IgG4-related symptoms). When uveitis occurred during follow up, it was associated with IgG4-RD manifestations in other organs in 6/9 patients (67 %). Uveitis was bilateral in 8/16 cases (50 %) and granulomatous in 5/10 cases (50 %). It was anterior in 8/13 (62 %), intermediate in 3/13 (23 %), and global (panuveitis) in 4/13 patients (31 %). Median serum IgG4 at diagnosis was 3.2 g/L. Median follow up time was of 6 years, during which 8/16 patients (50 %) experienced at least one relapse of uveitis. Treatment data was available for 29/30 uveitis flares. Steroids were used in 28/29 episodes of uveitis (97 %), leading to remission of uveitis in 16/28 cases (57 %). Methotrexate and rituximab (in combination with systemic steroids) were administered as second- or third-line therapy in 6/29 (21 %) and 5/29 (17 %) episodes of uveitis, respectively, and led to remission of uveitis in 4/6 cases (67 %) and 4/5 cases (80 %), respectively. One third of uveitides required at least two different lines of treatment for remission induction (mainly a combination of both systemic steroids and methotrexate or rituximab). Discussion and conclusionsUveitis may be one of the initial symptoms of IgG4-RD, and IgG4-RD should be considered in the diagnostic workup of uveitis. Its early onset in IgG4-RD may help with early diagnosis and treatment of the disease. Steroid monotherapy may be sufficient to treat IgG4-related uveitis, yet relapses were frequent (50 %) and ultimately a third of patients required at least two lines of treatment. Hence, steroid-sparing agents can be considered at early stages of the disease, particularly for patients with a high risk of relapse or steroid-related complications.

Successful remission induction of IgG4-related ophthalmic disease by obinutuzumab therapy: a retrospective study of 8 patients.

To evaluate the therapeutic efficacy and safety of obinutuzumab in remission induction for IgG4-related ophthalmic disease (IgG4-ROD) patients. Eight IgG4-ROD patients were retrospectively enrolled. They were intravenously administered 1000 mg obinutuzumab at baseline and examined for changes in physical signs, orbital structure imaging parameters, IgG4-related disease responder index (IgG4-RD RI), serological index, and adverse events during treatment. The number of treatment sessions was based on treatment response. The mean IgG4-RD RI scores of all patients at baseline (7.75 ± 2.92) and after treatment (2.00 ± 0.76) were highly significantly different (P < 0.001). Six patients achieved complete remission (CR) (75%) and two patients achieved partial remission (25%). The mean serum IgG4 levels at baseline (9.45 ± 6.95 g/L) and after treatment (1.55 ± 1.09 g/L) showed a mean decrease of 83% (P = 0.0079). The serum IgG4 level correlated well with IgG4-RD RI at baseline and that after each treatment (r = 0.852, P < 0.01; r = 0.78, P < 0.001). In patients with CR, the serum IgG4 levels at baseline correlated positively with dose numbers required for CR (r = 0.86, P < 0.05). Five patients (62.5%) experienced infusion-related reactions (IRRs) during the first obinutuzumab infusion, while only one (12.5%) experienced IRRs during all subsequent eight infusions. Obinutuzumab is a safe and promising therapeutic option for IgG4-ROD. It rapidly reduces ocular inflammation and serum IgG4 levels to avoid excessive corticosteroid usage and reduce potential risk of adverse events.

IgG4-Related Ophthalmic Disease following COVID-19 Infection: Is it Associated or Incidental?

IgG4-Related Ophthalmic Disease following COVID-19 Infection: Is it Associated or Incidental?

Ocular Surface Evaluation in Immunoglobulin G4–Related Ophthalmic Disease

To evaluate the functional and structural changes of the meibomian glands and ocular surface in immunoglobulin G4-related ophthalmic disease (IgG4-ROD) patients. Cross-sectional, matched case-control comparison study. This study included 64 patients with biopsy-proven IgG4-ROD (aged 63.4 ± 12.2 years, 39 male) and 64 sex- and age-matched healthy controls. Patients were managed by hospitals covering the publicly funded ophthalmology service in Hong Kong. Outcome measures included anterior segment examination and keratographic and meibographic imagings. A total of 64 worst-affected eyes of the 64 IgG4-ROD patients were analyzed. Corneal fluorescein staining (P=.0187), lid margin telangiectasia (P=.0360), lid-parallel conjunctival folds (P=.0112), papillae (P=.0393), meibomian gland plugging (P=.0001), meibomian gland expressibility (P=.0001), and meibum quality (P=.0001) were more significant in IgG4-ROD patients compared with healthy controls. Both upper and lower meibomian gland dropouts (P=.001 and .0003), and tear meniscus height (P=.0001) were higher in IgG4-ROD patients. Non-invasive tear break-up time (NITBUT) (P=.0166) and Schirmer test results (P=.0243) were lower in IgG4-ROD patients. Upper (r=0.336, P=.0140) meibomian gland dropouts and NITBUT (r=-0.293, P=.0497) were positively and negatively correlated with the IgG4-ROD onset age, respectively. The number of extraocular organ involvement was negatively correlated with the Schirmer test(r=-0.341, P=.0167). Lower NITBUT was found in IgG4-ROD eyes with lacrimal gland enlargement than in IgG4-ROD eyes without lacrimal gland enlargement radiologically (P < .0001). IgG4-ROD patients showed features of both aqueous tear deficiency and evaporative dry eye disease. We recommend ocular surface evaluation to all patients newly diagnosed with IgG4-ROD. Further studies are warranted to clarify the mechanism of IgG4-related dry eye disease.

Radiomics analysis of T1WI and T2WI magnetic resonance images to differentiate between IgG4-related ophthalmic disease and orbital MALT lymphoma

BackgroundPreoperative differentiation between IgG4-related orbital disease (IgG4-ROD) and orbital mucosa-associated lymphoid tissue (MALT) lymphoma has a significant impact on clinical decision-making. Our research aims to construct and evaluate a magnetic resonance imaging (MRI)-based radiomics model to assist clinicians to better identify IgG4-ROD and orbital MALT lymphoma and make better preoperative medical decisions.MethodsMR images and clinical data from 20 IgG4-ROD patients and 30 orbital MALT lymphoma patients were classified into a training (21 MALT; 14 IgG4-ROD) or validation set (nine MALT; six IgG4-ROD). Radiomics features were collected from T1-weighted (T1WI) and T2-weighted images (T2WI). Student’s t-test, the least absolute shrinkage and selection operator (LASSO) and principal component analysis (PCA) were conducted to screen and select the radiomics features. Support vector machine (SVM) classifiers developed from the selected radiomic features for T1WI, T2WI and combined T1WI and T2WI were trained and tested on the training and validation set via five-fold cross-validation, respectively. Diagnostic performance of the classifiers were evaluated with area under the curve (AUC) readings of the receiver operating characteristic (ROC) curve, and readouts for precision, accuracy, recall and F1 score.ResultsAmong 12 statistically significant features from T1WI, four were selected for SVM modelling after LASSO analysis. For T2WI, eight of 51 statistically significant features were analyzed by LASSO followed by PCA, with five features finally used for SVM. Combined analysis of T1WI and T2WI features selected two and four, respectively, for SVM. The AUC values for T1WI and T2WI classifiers separately were 0.722 ± 0.037 and 0.744 ± 0.027, respectively, while combined analysis of T1WI and T2WI classifiers further enhanced the classification performances with AUC values ranging from 0.727 to 0.821.ConclusionThe radiomics model based on features from both T1WI and T2WI images is effective and promising for the differential diagnosis of IgG4-ROD and MALT lymphoma. More detailed radiomics features and advanced techniques should be considered to further explore the differences between these diseases.

Efficacy and safety of intravenous glucocorticoid therapy for IgG4-related ophthalmic disease.

To evaluate and compare the efficacy and safety of intravenous (IV) glucocorticoid therapy with those of oral glucocorticoids as a first-line treatment for IgG4-related ophthalmic disease (IgG4-ROD). We retrospectively reviewed the medical records of patients who underwent systemic glucocorticoid therapy for biopsy-proven IgG4-ROD from June 2012 to June 2022. Glucocorticoids were given either oral prednisolone at an initial dose of 0.6 mg/kg/day for four weeks with subsequent tapering or once weekly IV methylprednisolone (500 mg for six weeks, then 250 mg for six weeks), according to the date of treatment. Clinicoserological features, initial response, relapse during follow-ups, cumulative doses of glucocorticoids, and adverse effects of glucocorticoids were compared for the IV and oral steroid groups. Sixty one eyes of 35 patients were evaluated over a median follow-up period of 32.9 months. The complete response rate was significantly higher in the IV steroid group (n = 30 eyes) than in the oral steroid group (n = 31 eyes) (66.7% vs. 38.7%, p = 0.041). Kaplan-Meier analysis showed that the 2-year relapse-free survival was 71.5% (95% confidence interval: 51.6-91.4) and 21.5% (95% confidence interval: 4.5-38.5) in the IV steroid and oral steroid group, respectively (p < 0.001). Although the cumulative dose of glucocorticoids was significantly higher in the IV steroid group than in the oral steroid group (7.8 g vs. 4.9 g, p = 0.012), systemic and ophthalmic adverse effects were not significantly different between the two groups throughout follow-ups (all p > 0.05). As a first-line treatment for IgG4-ROD, IV glucocorticoid therapy was well-tolerated, led to better clinical remission and more effectively prevented inflammatory relapse than oral steroids. Further research is needed to establish guidelines on dosage regimens.

IgG4-related ophthalmic disease masquerading as ciliary body tumors and scleritis in both eyes: a case report

BackgroundTo report a rare case of IgG4-related ophthalmic disease (IgG4-ROD) manifesting as intraocular masses and scleritis in both eyes in a 61-year-old male and to investigate the changes in multimodal imaging features of the lesion sites and helper T-cell type 1 (Th 1)/Th 2/Th 17 cytokine levels in the aqueous humor.Case presentationA patient with IgG4-ROD seemingly manifested with an intraocular tumor in the left eye and sequentially, with an inflammatory mass in the ciliary body and scleritis in the right eye. The patient complained of vision loss of 6 months duration in the left eye at his first visit. With a preliminary diagnosis of an intraocular tumor, enucleation of the left eyeball and histopathological examination were performed. Approximately 3 months later, the patient started to experience headache, eye pain, and declining vision in the right eye. Ophthalmic imaging revealed a ciliary mass and scleritis. Th 1/Th 2/Th 17 cytokine levels and multimodal imaging findings were analyzed before and after corticosteroid treatment. Histopathological examination and immunohistochemistry (IHC) of the enucleated left eye demonstrated lymphoplasmacytic infiltration with an IgG4+/IgG+ cell ratio of approximately 40%, pointing to the diagnosis of probable IgG4-ROD. Long-term treatment with corticosteroids led to significant improvement in the signs and symptoms of the left eye. Th 1/Th 2/Th 17 cytokine profile monitoring of the aqueous humor and multimodal imaging of the right eye showed gradual regression of the mass and attenuation of ocular inflammation during treatment.ConclusionsPatients with an atypical presentation of IgG4-ROD, such as intraocular masses and scleritis, are likely to experience a significant delay in diagnosis. This case demonstrates the significance of IgG4-ROD in the differential diagnosis of intraocular tumors and ocular inflammation. IgG4-RD is a newly diagnosed disease with multi-organ involvement and little is known about its pathogenesis, particularly in the eye. The present case will open new challenges in the clinico-pathological diagnosis and research of this disease. Combined investigations of multimodal imaging and cytokine level detection of intraocular fluid provide a new and effective way to monitor disease progression.

Immunoglobulin G4-related ophthalmic disease presenting as a steroid-resistant choroidal mass: a case report

Immunoglobulin G4-related ophthalmic disease presenting as a steroid-resistant choroidal mass: a case report

Long-Term Follow-Up in IgG4-Related Ophthalmic Disease: Serum IgG4 Levels and Their Clinical Relevance.

(1) Background: To analyze the association between long-term changes in serum IgG4 levels and the clinical course of patients with IgG4-related ophthalmic disease (IgG4-ROD). (2) Methods: Retrospective analysis of 25 patients with IgG4-ROD. (3) Results: Mean age at diagnosis was 60.68 years. Fifty-six percent of patients had bilateral ocular involvement and 32% had systemic associations. The ocular structures involved were the lacrimal gland (76%), orbital soft tissue (36%), extraocular muscle (20%) and infraorbital nerve (20%). According to last follow-up, 9 (36%) patients had normalized IgG4 levels, and 16 (64%) patients had elevated IgG4 levels. Patients with normalized IgG4 levels had better response to initial steroid treatment and attained a significantly lower IgG4 level after treatment (p = 0.002). The highest IgG4 levels were at baseline and disease recurrence, and lowest after initial treatment. At final follow-up, IgG4 levels differed in patients with remission (mean 326.25 mg/dL) and stable disease (mean 699.55 mg/dL). Subgroup analysis was performed in patients with remission, categorized according to whether IgG4 levels were normalized (9 patients) or elevated (10 patients) on last follow up. The elevated group had a higher percentage of bilateral disease, lacrimal gland involvement and recurrence. (4) Conclusions: IgG4-ROD patients with a greater response to initial steroid therapy were more inclined to have normalized IgG4 levels in the long term. Some patients remained in remission despite persistently elevated IgG4 levels, and had regular follow-up without treatment.

Treatment outcomes and their determinants of IgG4-related ophthalmic disease: a territory-wide cohort study

BackgroundOral corticosteroid remains the first-line treatment of IgG4-related ophthalmic disease, but steroid-dependence is common and serious. Factors associated with steroid dependence and relapse have to be further explored.Study populationA city-wide,...

Local recurrence as extraocular muscle lymphoma after 6 years of chronic myositis: a case report

BackgroundExtraocular muscle is usually affected by thyroid disease or inflammatory pseudotumor, but seldom by neoplastic process. Primary malignant lymphoma involving isolated extraocular muscle is very rare, especially after 6 years of chronic myositis.Case presentationA middle-aged female presented with swelling of the lower lid of the right eye for 2 months. Magnetic resonance imaging showed significant enlargement of the right inferior rectus muscle belly. The patient first presented 6 years prior with upper eyelid swelling. A total of 5 surgical biopsies of the right eye were performed during 6 years with the following successive findings: inflammatory pseudotumor, chronic inflammation, inflammatory lesions, IgG4-related ophthalmic disease, and lastly, extraocular muscle extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma).ConclusionMALT lymphoma may have occurred as a result of chronic extraocular myositis. Malignancy should be considered in patients with recurrent painless extraocular muscle hypertrophy. Differential diagnosis can rule out thyroid-associated ophthalmopathy (TAO), whose symptoms are similar. Diagnosis confirmation by biopsy is warranted if necessary.

Lacrimal Gland and Orbital Lesions in LatY136F Knock-in Mice, a Model for Human IgG4-Related Ophthalmic Disease

Purpose LatY136F knock-in mice were recently proposed as an animal model for immunoglobulin G4 (IgG4)-related disease. In this study, we investigated whether LatY136F knock-in mice exhibit ophthalmic lesions, specifically in the lacrimal and Harderian glands. Methods Lacrimal glands, Harderian glands, and adherent lymphoid follicle lesions were dissected from LatY136F knock-in mice and wild type (WT) C57BL/6 mice between 6 and 24 weeks of age. Tissues were stained with hematoxylin-eosin, immunoglobulin G (IgG), and anti-IgG1, a homologue of human IgG4, for histopathological analysis. Results In LatY136F knock-in mice, IgG1-positive cells infiltrated the space between the lacrimal gland acinar cells at 6, 9, 12, and 20 weeks or order, and the number of IgG1-positive cells did not differ significantly between these age groups. Infiltration of IgG1-positive inflammatory cell was also observed in the Harderian glands of LatY136F knock-in mice at all ages. The ratio of IgG1/IgG-positive cells averaged 80 and 67% in the lacrimal and Harderian glands, respectively. Dense IgG1-positive lesions were also seen in tissues adjacent to the lacrimal and Harderian glands in some LatY136F knock-in mice. In contrast, there were almost no IgG1-positive cell infiltrates in the lacrimal and Harderian glands of WT mice. Conclusion IgG1-positive cells infiltrate the lacrimal and Harderian glands of LatY136F knock-in mice, indicating that LatY136F knock-in mice could be a representative animal model for IgG4-related ophthalmic disease.

Radiological Determinants of Complicated Immunoglobulin G4-Related Ophthalmic Disease: A Territory-Wide Cohort Study.

To evaluate the presenting radiological features of immunoglobulin G4-related ophthalmic disease (IgG4-ROD) and their associations with IgG4-related optic neuropathy (IgG4-RON), and IgG4-related ocular adnexal lymphoma (IgG4-ROL). A territory-wide, biopsy-proven, Chinese cohort. Masked review of orbital images, medical records, and histopathology reports. 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. In this IgG4-ROD cohort, most patients had bilateral enlarged lacrimal glands, and the lateral rectus is the most frequently involved EOM. For the first time, unique radiological patterns associated with the development of IgG4-RON and IgG4-ROL are found.

A Case of Choroidal Folds in a Patient with Immunoglobulin G4-related Ophthalmic Disease

Purpose: To report a case of choroidal folds caused by enlargement of the extraocular muscles (EOM) and orbital fat in a patient with immunoglobulin (Ig) G4-related ophthalmic disease. A full recovery was achieved after steroid administration.Case summary: A 56-year-old male received intravenous high-dose steroids to treat IgG4-related ophthalmic disease presenting with bilateral eyelid edema, hypertrophy of all EOM, and mild exophthalmos. After 3 months, only slight improvement was observed and azathioprine was initiated. The patient exhibited only a minimal response over the next 2 months; all medications were therefore stopped. One month later, the patient presented with aggravation of the swelling (both eyelids), exophthalmos, and visual impairment of the left eye. The corrected vision was 1.0 in the right eye and 0.2 in the left eye; choroid folds were observed in the posterior pole of the left eye. Intravenous steroid (500 mg) was given once and oral steroids prescribed as maintenance therapy. After 2 weeks, the corrected visual acuity recovered to 1.0 in both eyes, the eyelid edema and exophthalmos improved and the choroidal folds resolved completely.Conclusions: Choroidal folds associated with enlargement of EOM and orbital fat tissue can cause visual impairment in patients with IgG4-related ophthalmic disease. Steroids are effective in the acute phases and prevent irreversible visual impairment.

Malignancies in Immunoglobulin G4-related ophthalmic disease.

Clinical phenotypes in Immunoglobulin G4-related disease (IgG4-RD) according to the patterns of affecting organs have different risks of malignancies. We attempt to determine the association of malignancies with IgG4-related ophthalmic disease (IgG4-ROD). Retrospective cohort study. Review of medical records, orbital images and histopathology reports in a territory-wide cohort of biopsy proven IgG4-ROD patients from 2005-2019. Among 122 patients who had biopsies taken from adnexal lesions including lacrimal glands (n = 108), orbital mass (n = 30), infiltrated orbital fat (n = 10), conjunctiva (n = 2) or extraocular muscles (n = 3), 13% (16/122) developed malignancies over 73 ± 48months' follow-up. There were 9 cases of ocular adnexal lymphoma (OAL) and 7 extra-orbital malignancies. Compared with the general population, the incidence of OAL was significantly higher (standardized incidence ratios, SIRs = 10.0, 95%CI = 4.5-17.6) while that of extra-orbital malignancies was similar. The SIRs was highest within the first year (SIR = 46.7, 95%CI = 18.5-87.6) when 7 OAL were concomitantly diagnosed. Patients who developed OAL or extra-orbital malignancies were older than other patients at IgG4-ROD diagnosis (64.9 ± 7.1, 68.3 ± 8.5 versus 55.2 ± 15.0 years, P < 0.05). Asymmetric lacrimal gland enlargement (78% versus 13%), lack of frontal (0% versus 12%) or infraorbital nerve enlargement (0% versus 36%) were associated with OAL (all P < 0.05). Pre-treatment serum IgG4 level or extra-orbital IgG4-RD involvement was similar among patients with or without malignancies. In this biopsy-proven IgG4-ROD cohort, 7% developed OAL which was 10 times higher than the general population. Patients with asymmetric lacrimal gland enlargement or without trigeminal nerves involvement radiologically were associated with OAL.

Re: "Clinical Outcomes of IgG4-Related Ophthalmic Disease and Idiopathic Sclerosing Orbital Inflammation".

The authors have no financial or conflicts of interest to disclose. Address correspondence and reprint requests to Bulent Yazici, M.D., Department of Ophthalmology, Uludag University, Bursa 16059, Turkey. E-mail: [email protected].

Reply Re: "Clinical Outcomes of IgG4-Related Ophthalmic Disease and Idiopathic Sclerosing Orbital Inflammation".

Reply Re: "Clinical Outcomes of IgG4-Related Ophthalmic Disease and Idiopathic Sclerosing Orbital Inflammation".