Abstract: An intestinal dysbiosis is connected to a number of inflammatory diseases through various mechanisms relating to its effect on immune cell function and differentiation. This is a review of the literature summarizing our current understanding of intestinal microbial contributions to non-infectious uveitis and strategies to target the intestinal microbiome to treat uveitis. Several groups have demonstrated an intestinal dysbiosis associated with certain types of non-infectious uveitis. Additionally, approaches to treat uveitis by modifying the intestinal microbiota, such as oral antibiotics or administration of oral short chain fatty acids (SCFAs), which are intestinal bacterial metabolites produced by fermentation of dietary fiber, can successfully treat uveitis in mouse models. This reduction in severity of ocular inflammation occurs via the following mechanisms: enhancement of regulatory T cells, decreasing intestinal permeability, and/or affecting T cell trafficking between the intestines and the spleen. Other strategies that are directed at the intestinal microbiota that might be effective to treat uveitis include dietary changes, probiotics, or fecal microbial transplantation. The commensal gut bacteria are influential in systemic and intestinal mucosal immunity and thus contribute to the development of extraintestinal inflammation like uveitis. Targeting the intestinal microbiome thus has the potential to be a successful strategy to treat non-infectious uveitis.

Abstract: Optical coherence tomography (OCT) is a technology that is widely used to assess structural abnormalities in the retina for a variety of pediatric conditions. The introduction of this instrument has allowed for widespread access to minimally invasive standardized, reproducible quantified structural assessments of the optic nerve and retina. This has had important implications in pediatric optic neuropathies, populations in whom monitoring of disease activity is essential to making treatment decisions. OCT has had particular relevance for inflammatory optic neuropathies, as onset of an inflammatory optic neuropathy may herald the onset of a chronic inflammatory disorder of the central nervous system (CNS) such as multiple sclerosis, neuromyelitis optica spectrum disorder (aquaporin 4 antibody positive), and myelin oligodendrocyte glycoprotein (MOG) associated disorders. This paper will focus on the application of OCT technology to this group of disorders in pediatrics. After reviewing pediatric-specific anatomic and practical issues pertinent to OCT, we will review knowledge related to the use of OCT in inflammatory pediatric optic neuropathies, with a focus on structural outcomes and their correlation with functional outcome metrics.

Abstract: Focal intraretinal alterations have been studied to advance our understanding of the pathology of neurodegenerative diseases. The current literature involving focal alterations in the intraretinal layers was reviewed through PubMed using the search terms “focal alteration”, “region of interest”, “optical coherence tomography”, “glaucoma”, “multiple sclerosis”, “Alzheimer’s disease”, “Parkinson disease”, “neurodegenerative diseases” and other related items. It was found that focal alterations of intraretinal layers were different in various neurodegenerative diseases. The typical focal thinning might help differentiate various ocular and cerebral diseases, track disease progression, and evaluate the outcome of clinical trials. Advanced exploration of focal intraretinal alterations will help to further validate their clinical and research utility.

Abstract: Statins are used widely to treat hypercholesterolemia and atherosclerotic cardiovascular disease. They have inflammatory and immunomodulatory effects potentially useful for managing systemic autoimmune diseases such as rheumatoid arthritis, lupus erythematosus and multiple sclerosis. Statins also have anti-oxidative and large-vessel endothelial supportive properties that occur independent of their lipid-lowering effects. Additionally, statins can suppress macrophage and microglial activation responsible for initiating inflammatory cytokine release. More than forty percent of adults aged 65 years or older use statins in the United States and Australia, a prevalence that increases with age. The effects of statin usage on ophthalmic practice are probably underrecognized. Cardiovascular disease and age-related macular degeneration (AMD) share common risk factors, consistent with the “vascular model” of AMD pathogenesis that implicates impaired choroidal circulation in Bruch’s membrane lipoprotein accumulation. AMD has a complex multifactorial pathogenesis involving oxidative stress, choroidal vascular dysfunction, dysregulated complement-cascade-mediated inflammation and pro-inflammatory and pro-angiogenic growth factors. Many of these components are hypothetically amenable to the primary (cholesterol lowering) and secondary (anti-inflammatory, anti-oxidative, anti-vasculopathy) effects of statin use. Experimental studies have been promising, epidemiological trails have produced conflicting results and three prospective clinical trials have been inconclusive at demonstrating the value of statin therapy for delaying or preventing AMD. Cumulative evidence to date has failed to prove conclusively that statins are beneficial for preventing or treating AMD.

Abstract: Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease of childhood, and juvenile idiopathic associated uveitis (JIA-U) is the most frequently noted extra-articular manifestation. JIA-U can present asymptomatically and lead to ocular complications, so regular screening and monitoring are needed to prevent potentially sight-threatening sequelae. Topical glucocorticoids such as prednisolone acetate are usually the first line of treatment for anterior uveitis associated with JIA-U, but long-term use may be associated with cataract, ocular hypertension and glaucoma. Disease modifying anti-rheumatic drugs (DMARDs) such as methotrexate allow tapering of the corticosteroids to prevent long-term complications. Biologic therapies have been increasingly used as targeted therapies for JIA-U, particularly monoclonal antibodies targeting the proinflammatory cytokine TNF-α such as adalimumab and infliximab. One recent, multicenter, prospective, randomized clinical trial provided evidence of the efficacy of adalimumab with methotrexate for JIA-U compared to methotrexate alone. Another clinical trial studying the interleukin-6 inhibitor tocilizumab for JIA-U showed promise in tapering topical corticosteroids. Additionally, JAK inhibitors are emerging biologic therapies for JIA-U in patients refractory to TNF-α inhibitors, with a clinical trial assessing the efficacy of baricitinib for JIA-U underway. While clinical trials on these novel biologics are limited, further investigation of these agents may provide additional therapeutic options for JIA-U.

Abstract: The rare disease of chronic infantile neurological cutaneous and articular (CINCA) syndrome, is caused by the over-secretion of interleukin (IL)-1β due to a gain-of-function NLRP3 gene mutation in the autosomal chromosome which often involves in eyes. In this report, we studied a 9-year-old girl with CINCA. The eyes were also involved and presented bilateral papilledema. Genetic testing revealed that the symptoms were caused by a novel gene mutation site (c.913G>A, p. D305N) in conservative domain exon-3 of NLRP3 which is gain-function gene of CINCA. The patient had the characteristic facial features, frontal fossa and saddle nose, manifested the generalized urticaria-like skin rash at two weeks after birth, periodic fever 6 months after birth, sensorineural deafness at 7 years old, and bilateral papilledema, aseptic meningitis and knee arthropathy at 9 years old. White cell counts, C-reactive protein increased and intracranial pressure raised to 300 mmH2O. The meningeal thickening enhanced by gadolinium in magnetic resonance imaging (MRI). Based on clinical features and genetic test, the girl was diagnosed bilateral papilledema secondary to CINCA and administered prednisone and lowered intracranial pressure medicine to resolve symptoms. With 3-year follow-up, patient had no inflammatory flare-up with visual acuity improvement. The finding of novel genetic mutation site (p. D305N) in NLRP3 gene expanded genotype spectrum associated with CINCA. This case also expanded the cause spectrum of papilledema and it highlighted systemic disease history for patients with bilateral papilledema.

Abstract: Red eye is common in our daily practice. It ranges from non-inflammatory to inflammatory causes. An extended course of disease should prompt suspicion and the possibility of diagnosis revision. A prolonged conjunctivitis mimicking nodular episcleritis can be presented as a manifestation of granulomatosis with polyangiitis (GPA). A 57-year-old woman complained of eye redness and tearing for two weeks which partially resolved with antibiotics. She was subsequently commenced on topical and oral non-steroidal anti-inflammatory drugs (NSAIDs) and topical anti-allergic. However, in the following reviews she developed cornea thinning and her systemic examination revealed an injected uvula with absence of upper respiratory tract infection. She was investigated for connective tissue disease and found to have raised anti-inflammatory markers and her antinuclear antibody and C-ANCA tests were positive. She was diagnosed with GPA. Her conditions improved followed by the commencement of topical corticosteroid with high dose of systemic corticosteroid, which followed by a tapering regime with oral corticosteroid. Although red eye is common, it is associated with a variety of diseases. GPA manifestation can be as subtle as a red eye. Any prolonged partially treated red eye should prompt suspicion of a more sinister cause. Sensitive detection of other subtle systemic signs is very important.