Long-Term Outcomes of IgG4-Related Ophthalmic Disease in a Chinese IgG4-Related Disease Cohort

Purpose: To define the treatment response and long-term outcomes of a large IgG4-related ophthalmic disease (IgG4-ROD) cohort.Methods: A total of 132 patients with a minimum follow-up of 1 year were included in this study. Demographic, clinical, and laboratory data were collected. Treatment response was assessed by the IgG4-RD responder index (IgG4-RD RI). Risk factors for relapse were analyzed with the multivariate Cox regression analysis.Results: The median follow-up time was 39 months. Lacrimal gland involvement was detected in 87.9% of cases. Extraocular muscles, the trigeminal nerve, and other soft tissue were affected in 25.8, 6.1, and 18.2% of patients. The relapse rate of watchful waiting, glucocorticoid monotherapy, immunosuppressant monotherapy, and combination therapy was 50.0, 51.7, 50.0, and 26.7% (p = 0.038), respectively. The combination therapy group exhibited shorter glucocorticoids therapy duration (36 vs. 48 months, p = 0.009) and maintenance period (24 vs. 42 months, p = 0.003). At the 6th month, the median IgG4-RD RI declined from 12 to 1 and 105 (79.5%) patients achieved complete response (CR). Relapse occurred in 49 (37.1%) patients. The multivariate Cox regression analysis exhibited that CR at the 6th month was an independent protective factor for relapse. Patients with multiple ocular lesions suffered from a higher risk of relapse. No patient had severe adverse reactions to the treatment in this study.Conclusion: Relapse was common in patients with IgG4-ROD. Patients receiving combination therapy showed a lower relapse rate and a shorter glucocorticoids therapy period. The presence of multiple ocular lesions was associated with a higher risk of relapse. CR at the 6th month might be a predictor for a better prognosis in IgG4-ROD. Thus, a more aggressive regimen should be prescribed for patients with a poor initial response.

Investigating the causes of stimulus-evoked changes in cone reflectance using a combined adaptive optics SLO-OCT system

In vivo functional imaging of human photoreceptors is an emerging field, with compelling potential applications in basic science, translational research, and clinical management of ophthalmic disease. Measurements of light-evoked changes in the photoreceptors has been successfully demonstrated using adaptive optics (AO) coherent flood illumination (CFI), AO scanning light ophthalmoscopy (SLO), AO optical coherence tomography (OCT), and full-field OCT with digital AO (dAO). While the optical principles and data processing of these systems differ greatly, and while these differences manifest in the resulting measurements, we believe that the underlying physiological processes involved in each of those techniques are likely the same. AO CFI and AOSLO systems are more widely used than OCT systems. However, those systems produce only two-dimensional images and so, less can be said about the anatomical and physiological origins of the observed signal. OCT signal, on the other hand, provides 3D imaging but at a cost of high volume of data, making it impractical to clinical purposes. In light of this, we employed a combined AO OCT SLO system with point for point correspondence between the OCT and SLO images to measure functional responses simultaneously with both and investigate SLO retinal functional biomarkers based on OCT response. The resulting SLO images reveal reflectance changes in the cones which are consistent with those previously reported using AO CFI and AO SLO. The resulting OCT volumes show phase changes in the cone outer segment (OS) consistent with those previously reported by us and others. We recapitulate a model of the cone OS previously proposed to explain AO-CFI reflectance changes, and show how this model can be used to predict the signal in AO SLO. The limitations of the model is also discussed in this manuscript.

A Hybrid Method to Enhance Thick and Thin Vessels for Blood Vessel Segmentation

Retinal blood vessels have been presented to contribute confirmation with regard to tortuosity, branching angles, or change in diameter as a result of ophthalmic disease. Although many enhancement filters are extensively utilized, the Jerman filter responds quite effectively at vessels, edges, and bifurcations and improves the visualization of structures. In contrast, curvelet transform is specifically designed to associate scale with orientation and can be used to recover from noisy data by curvelet shrinkage. This paper describes a method to improve the performance of curvelet transform further. A distinctive fusion of curvelet transform and the Jerman filter is presented for retinal blood vessel segmentation. Mean-C thresholding is employed for the segmentation purpose. The suggested method achieves average accuracies of 0.9600 and 0.9559 for DRIVE and CHASE_DB1, respectively. Simulation results establish a better performance and faster implementation of the suggested scheme in comparison with similar approaches seen in the literature.

Deep Learning for Ultra-Widefield Imaging: A Scoping Review

Purpose: This article is a scoping review of published and peer-reviewed articles using deep-learning (DL) applied to ultra-widefield (UWF) imaging. This study provides an overview of the published uses of DL and UWF imaging for the detection of ophthalmic and systemic diseases, generative image synthesis, quality assessment of images, and segmentation and localization of ophthalmic image features. Methods: A literature search was performed up to August 31st, 20201 using PubMed, Embase, Cochrane Library, and Google Scholar. The inclusion criteria were as follows: (1) Deep Learning, (2) Ultra-Widefield Imaging. The exclusion criteria were as follows: (1) articles published in any language other than English, (2) articles not peer-reviewed (usually preprints) (3) no full-text availability (4) articles using machine learning algorithms other than deep learning. No study design was excluded from consideration.Results: A total of 36 studies were included. 23 studies discussed ophthalmic disease detection and classification, 5 discussed segmentation and localization of UWF images, 3 discussed generative image synthesis, 3 discussed ophthalmic image quality assessment, and 2 discussed detecting systemic diseases via UWFI.Conclusion: The application of DL to UWFI has demonstrated significant effectiveness in the diagnosis and detection of ophthalmic diseases including diabetic retinopathy, retinal detachment, and glaucoma. DL has been used with UWFI to also diagnose systemic diseases like Alzheimer’s, and also applied in the generation of synthetic ophthalmic images. This scoping review highlights and discusses the current uses of DL with UWFI, and the future of DL applications in this field.

A Review of the Impact of Alterations in Gut Microbiome on the Immunopathogenesis of Ocular Diseases

Recent studies have highlighted the association between ocular diseases and microbiota profiles of the host intestinal tract and oral cavity. There is mounting evidence supporting the existence of a ‘gut–eye axis’, whereby changes in gut microbiome alter host immunity, with consequential implications for ocular health and disease. In this review, we examined recent published findings on the association between gut microbiome and ocular morbidity, based on 25 original articles published between 2011 to 2020. The review included both clinical and in vivo animal studies, with particular focus on the influence of the microbiome on host immunity and metabolism. Significant associations between altered intestinal microbiome and specific ocular diseases and pathological processes, including Behçet’s syndrome, autoimmune uveitis, age-related macular degeneration, choroidal neovascularization, bacterial keratitis, and Sjögren-like lacrimal keratoconjunctivitis have been demonstrated. Furthermore, alterations in the gut microbiome resulted in quantifiable changes in the host immune response, suggesting immunopathogenesis as the basis for the link between intestinal dysbiosis and ocular disease. We also examined and compared different techniques used in the identification and quantification of gut microorganisms. With our enhanced understanding of the potential role of gut commensals in ophthalmic disease, the stage is set for further studies on the underlying mechanisms linking the gut microbiome, the host immune response, and the pathogenesis of ophthalmic disease.

P33 A female with a drooping eyelid and positive autoantibodies: mystery solved?

Case report - Introduction The presence of autoantibodies in IgG4-related disease (IgG4-RD) can lead to confusion and we present a case to highlight the diagnostic difficulty in this condition. Case report - Case description A 63-year-old Indian female presented with progressive ptosis and swelling of the left eyelid for 2 months. She was referred to the stroke clinic where she was found to have left ptosis with associated swelling. An MRI of the orbit revealed an enlarged left lacrimal gland and mucosal thickening in paranasal sinuses. Her ESR was 20, CRP 2, 15% peripheral eosinophils and IgG 17.55 g/L (6-16). A referral was made to rheumatology due to an abnormal immunological profile: cANCA +, MPO ANCA positive 32 IU/ml (0-3.5) and a strongly positive anti-Ro antibody >600 U/ml (0-10). Differential diagnosis considered: ANCA associated vasculitis (AAV), Primary Sjögren’s syndrome (SS), and IgG4-related orbital disease. She was assessed by the ENT surgeon and there was no sinusitis or evidence of vasculitis. Chest X-ray and CT scan of chest were normal. A left lacrimal gland biopsy revealed reactive lymphoid hyperplasia with numerous plasma cells and eosinophils. Immunohistochemistry revealed over 50% of plasma cells to be IgG4-positive (approximately 100/HPF) suggestive of IgG4-RD. There was no evidence of granuloma formation or malignancy. Serum IgG4 was raised 6.82 g/l (<1.3). A review by ophthalmology revealed no objective evidence of dry eyes. She was treated as IgG4-RD and demonstrated a marked improvement following treatment with oral steroids and azathioprine. Case report - Discussion IgG4-RD is an immune-mediated systemic fibro inflammatory disease characterised by tumefactive lesions with abundant IgG4-positive plasma cells infiltrating into multiple organs. Isolated IgG4-related ophthalmic disease is present in 23% of patients with IgG4-RD, in whom the lacrimal gland is the most commonly involved structure, followed by orbital fat and extraocular muscles. IgG4-related ophthalmic disease is rare and we need to exclude commoner causes of orbital inflammation (such as thyroid ophthalmopathy, granulomatosis with poly-angiitis, sarcoidosis, and tuberculosis) or malignancy. Case report - Key learning points The diagnosis of IgG4-RD is often challenging. It is well recognised that small vessel vasculitis can increase the number of IgG4-positive plasma cells in tissue biopsies. Additionally, literature reveals biopsy-proven IgG4-RD can have ANCA positivity with and without concomitant presence of ANCA-associated vasculitis and there are case reports of patients who fulfil criteria for both Sjogren’s syndrome and IgG4-RD. As such, diagnosis requires careful correlation of clinical, radiologic and histological features due to the overlapping features in differential diagnoses.

Malignancies in Immunoglobulin G4-Related Ophthalmic Disease

Purpose: Clinical phenotypes in Immunoglobulin G4-related disease (IgG4-RD) according to the affected organs affected have different risks of malignancies. We attempt to determine the association of malignances with IgG4-related ophthalmic disease (IgG4-ROD). Design: Retrospective cohort study. Methods: Review of medical records, orbital images and histopathology reports in a territory-wide cohort of patients fulfilling the “probable” or “definite” comprehensive diagnostic criteria of IgG4-RD from 2005-2019. Findings: 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), 16 (13%) 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 extraorbital malignancy was similar. The SIR 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 when diagnosed of IgG4-ROD (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 pattern of extraorbital involvement was similar among patients with or without malignancies. Conclusion: 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.