Ocular Manifestations in Juvenile Behçet's Disease: A Registry-Based Analysis from the AIDA Network.

INTRODUCTION: This study aims to characterize ocular manifestations of juvenile Behçet's disease (jBD). METHODS: This was a registry-based observational prospective study. All subjects with jBD from the Autoinflammatory Diseases Alliance (AIDA) Network BD Registry showing ocular manifestations before 18 years were enrolled. RESULTS: We included 27 of 1000 subjects enrolled in the registry (66.7% male patients, 45 affected eyes). The median (interquartile range [IQR]) age at ocular involvement was 14.2 (4.7) years. Uveitis affected 91.1% of eyes (anterior 11.1%, posterior 40.0%, panuveitis 40.0%), retinal vasculitis 37.8% and other manifestations 19.8%. Later onset (p = 0.01) and male predominance (p = 0.04) characterized posterior involvement. Ocular complications occurred in 51.1% of eyes. Patients with complications had earlier onset (p < 0.01), more relapses (p = 0.02) and more prolonged steroidal treatment (p = 0.02). The mean (standard deviation [SD]) central macular thickness (CMT) at the enrolment and last visit was 302.2 (58.4) and 293.3 (78.2) µm, respectively. Fluorescein angiography was pathological in 63.2% of procedures, with a mean (SD) Angiography Scoring for Uveitis Working Group (ASUWOG) of 17.9 (15.5). At the last visit, ocular damage according to the BD Overall Damage Index (BODI) was documented in 73.3% of eyes. The final mean (SD) best corrected visual acuity (BCVA) logMAR was 0.17 (0.47) and blindness (BCVA logMAR < 1.00 or central visual field ≤ 10°) occurred in 15.6% of eyes. At multivariate regression analysis, human leukocyte antigen (HLA)-B51 + independently predicted a + 0.35 change in the final BCVA logMAR (p = 0.01), while a higher BCVA logMAR at the first assessment (odds ratio [OR] 5.80; p = 0.02) independently predicted blindness. CONCLUSIONS: The results of this study may be leveraged to guide clinical practice and future research on this rare sight-threatening condition.

Effectiveness and Safety of Biosimilars in Pediatric Non-infectious Uveitis: Real-Life Data from the International AIDA Network Uveitis Registry.

INTRODUCTION: Since many biological drug patents have expired, biosimilar agents (BIOs) have been developed; however, there are still some reservations in their use, especially in childhood. The aim of the current study is to evaluate the efficacy and safety of tumor necrosis factor (TNF) inhibitors BIOs as treatment for pediatric non-infectious uveitis (NIU). METHODS: Data from pediatric patients with NIU treated with TNF inhibitors BIOs were drawn from the international AutoInflammatory Disease Alliance (AIDA) registries dedicated to uveitis and Behçet's disease. The effectiveness and safety of BIOs were assessed in terms of frequency of relapses, risk for developing ocular flares, best-corrected visual acuity (BCVA), glucocorticoids (GCs)-sparing effect, drug survival, frequency of ocular complications, and adverse drug event (AE). RESULTS: Forty-seven patients (77 affected eyes) were enrolled. The BIOs employed were adalimumab (ADA) (89.4%), etanercept (ETA) (5.3%), and infliximab (IFX) (5.3%). The number of relapses 12 months prior to BIOs and at last follow-up was 282.14 and 52.43 per 100 patients/year. The relative risk of developing ocular flares before BIOs introduction compared to the period following the start of BIOs was 4.49 (95% confidence interval [CI] 3.38-5.98, p = 0.004). The number needed to treat (NNT) for ocular flares was 3.53. Median BCVA was maintained during the whole BIOs treatment (p = 0.92). A significant GCs-sparing effect was observed throughout the treatment period (p = 0.002). The estimated drug retention rate (DRR) at 12-, 24-, and 36-month follow-up were 92.7, 83.3, and 70.8%, respectively. The risk rate for developing structural ocular complications was 89.9/100 patients/year before starting BIOs and 12.7/100 patients/year during BIOs treatment, with a risk ratio of new ocular complications without BIOs of 7.1 (CI 3.4-14.9, p = 0.0003). Three minor AEs were reported. CONCLUSIONS: TNF inhibitors BIOs are effective in reducing the number of ocular uveitis relapses, preserving visual acuity, allowing a significant GCs-sparing effect, and preventing structural ocular complications. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT05200715.

Knowledge and Current Practices in Monogenic Uveitis: An International Survey by IUSG and AIDA Network.

INTRODUCTION: This study aims to explore awareness, knowledge, and diagnostic/therapeutic practices in monogenic uveitis (mU) among uveitis experts. METHODS: This is an explorative, cross-sectional survey study. An anonymous, semi-structured, electronic survey was delivered to uveitis experts from the Autoinflammatory Diseases Alliance (AIDA) Network and International Uveitis Study Group (IUSG). We included respondents answering ≥ 50% of the survey. RESULTS: Seventy-seven participants rated their knowledge of mU as proficient (3.9%), adequate (15.6%), sufficient (16.9%), or poor (63.6%). When asked about the first mU gene they thought of, 60.4% mentioned NOD2, 3.9% mentioned NLRP3 or MEFV, and 49.4% provided incorrect or no answers. Success rates in clinical scenarios varied from 15.6% to 55.8% and were higher for ophthalmologists working in multidisciplinary teams (p < 0.01). Genetic testing was ordered for suspected mU by 41.6% of physicians. The availability of molecular techniques did not significantly differ based on geography (p > 0.05). The public healthcare system ensured a higher percentage of tests prescribed were obtained by patients compared to private insurances (p < 0.00). In terms of disease-modifying anti-rheumatic drugs (DMARDs), tumor necrosis factor-α inhibitors were the most familiar to uveitis experts. The difficulties with off-label therapy procedures were the primary barrier to DMARDs prescription for patients with mU and correlated inversely with the obtained/prescribed drug ratio for interleukin-1 (p < 0.01) and interleukin-6 (p < 0.01) inhibitors. CONCLUSIONS: This survey identifies proficiency areas, gaps, and opportunities for targeted improvements in patients care. The comprehensive outputs may inform evidence-based guidelines, empowering clinicians with standardized approaches, and drive an AIDA Network-IUSG unified effort to advance scientific knowledge and clinical practice.

A patient-driven registry on Behçet's disease: the AIDA for patients pilot project.

Introduction: This paper describes the creation and preliminary results of a patient-driven registry for the collection of patient-reported outcomes (PROs) and patient-reported experiences (PREs) in Behçet's disease (BD). Methods: The project was coordinated by the University of Siena and the Italian patient advocacy organization SIMBA (Associazione Italiana Sindrome e Malattia di Behçet), in the context of the AIDA (AutoInflammatory Diseases Alliance) Network programme. Quality of life, fatigue, socioeconomic impact of the disease and therapeutic adherence were selected as core domains to include in the registry. Results: Respondents were reached via SIMBA communication channels in 167 cases (83.5%) and the AIDA Network affiliated clinical centers in 33 cases (16.5%). The median value of the Behçet's Disease Quality of Life (BDQoL) score was 14 (IQR 11, range 0-30), indicating a medium quality of life, and the median Global Fatigue Index (GFI) was 38.7 (IQR 10.9, range 1-50), expressing a significant level of fatigue. The mean Beliefs about Medicines Questionnaire (BMQ) necessity-concern differential was 0.9 ± 1.1 (range - 1.8-4), showing that the registry participants prioritized necessity belief over concerns to a limited extent. As for the socioeconomic impact of BD, in 104 out of 187 cases (55.6%), patients had to pay from their own pocket for medical exams required to reach the diagnosis. The low family socioeconomic status (p < 0.001), the presence of any major organ involvement (p < 0.031), the presence of gastro-intestinal (p < 0.001), neurological (p = 0.012) and musculoskeletal (p = 0.022) symptoms, recurrent fever (p = 0.002), and headache (p < 0.001) were associated to a higher number of accesses to the healthcare system. Multiple linear regression showed that the BDQoL score could significantly predict the global socioeconomic impact of BD (F = 14.519, OR 1.162 [CI 0.557-1.766], p < 0.001). Discussion: Preliminary results from the AIDA for Patients BD registry were consistent with data available in the literature, confirming that PROs and PREs could be easily provided by the patient remotely to integrate physician-driven registries with complementary and reliable information.

Co-Expression of Podoplanin and CD44 in Proliferative Vitreoretinopathy Epiretinal Membranes.

Epiretinal membranes (ERMs) are sheets of tissue that pathologically develop in the vitreoretinal interface leading to progressive vision loss. They are formed by different cell types and by an exuberant deposition of extracellular matrix proteins. Recently, we reviewed ERMs' extracellular matrix components to better understand molecular dysfunctions that trigger and fuel the onset and development of this disease. The bioinformatics approach we applied delineated a comprehensive overview on this fibrocellular tissue and on critical proteins that could really impact ERM physiopathology. Our interactomic analysis proposed the hyaluronic-acid-receptor cluster of differentiation 44 (CD44) as a central regulator of ERM aberrant dynamics and progression. Interestingly, the interaction between CD44 and podoplanin (PDPN) was shown to promote directional migration in epithelial cells. PDPN is a glycoprotein overexpressed in various cancers and a growing body of evidence indicates its relevant function in several fibrotic and inflammatory pathologies. The binding of PDPN to partner proteins and/or its ligand results in the modulation of signaling pathways regulating proliferation, contractility, migration, epithelial-mesenchymal transition, and extracellular matrix remodeling, all processes that are vital in ERM formation. In this context, the understanding of the PDPN role can help to modulate signaling during fibrosis, hence opening a new line of therapy.

Efficacy and Safety of Adalimumab in Pediatric Non-infectious Non-anterior Uveitis: Real-life Experience From the International AIDA Network Uveitis Registry.

INTRODUCTION: Scientific evidence of the effectiveness of the tumor necrosis factor inhibitor adalimumab (ADA) in pediatric patients with non-infectious non-anterior uveitis is still limited. The aim of this study is to investigate the therapeutic role of ADA in a cohort of pediatric patients with non-anterior uveitis. METHODS: This is an international multicenter study analyzing real-life data referred to pediatric patients treated with ADA for intermediate uveitis/pars planitis, posterior uveitis and panuveitis. Data were drawn from the AutoInflammatory Disease Alliance (AIDA) registry for patients with uveitis. RESULTS: Twenty-one patients (36 affected eyes) were enrolled, and all patients benefited from ADA administration. In detail, 11 patients (19 affected eyes) did not experience further ocular inflammation after ADA introduction; 10 cases (17 affected eyes) showed a significant clinical improvement consisting of a decrease in severity and/or frequency of ocular relapses. The number of ocular flares dropped from 3.91 to 1.1 events/patient/year after ADA introduction (p = 0.0009); macular edema and retinal vasculitis were respectively observed in 18 eyes and 20 eyes at the start of ADA and in 4 eyes and 2 eyes at the last assessment. The mean daily glucocorticoid dosage significantly decreased from 26.8 ± 16.8 mg/day at the start of ADA to 6.25 ± 6.35 mg/day at the last assessment (p = 0.002). Intermediate uveitis/pars planitis (p = 0.01) and posterior uveitis (p = 0.03) were more frequently observed in patients with full response to ADA; panuveitis (p = 0.001) was significantly more frequent among patients continuing to experience uveitic flares. This could be related to a higher use of systemic glucocorticoids (p = 0.002) and conventional immunosuppressants (p = 0.007) at the start of ADA when treating intermediate uveitis/pars planitis. Regarding the safety profile, only one adverse event was reported during ADA treatment, consisting of the development of generalized adenopathy. CONCLUSIONS: ADA proved to have an effective therapeutic role in all pediatric patients with non-anterior uveitis enrolled in the study. An overall glucocorticoid-sparing effect was observed despite the severity of cases enrolled. A more aggressive treatment of panuveitis and posterior uveitis at start of ADA could increase the likelihood of full response to therapy.

VEXAS syndrome: a new paradigm for adult-onset monogenic autoinflammatory diseases.

VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is a recently described pathological entity. It is an acquired monogenic autoinflammatory disease caused by somatic mutations of the UBA1 gene in blood cells precursors; the gene encodes one of the two E1 enzyme isoforms that initiates ubiquitylation in cell's cytoplasm. VEXAS syndrome leads to systemic inflammation, with all organs and tissues potentially involved. The clinical picture may be extremely heterogenous, mimicking different other systemic rheumatologic entities coexisting with haematological disorders, especially myelodysplastic syndrome. This new disease represents a very intriguing clinical condition in several respects: it accounts for the paradigm of adult-onset monogenic autoinflammatory diseases determined by a genetic mosaicism resulting in the development of a challenging multiorgan inflammatory condition. Moreover, VEXAS syndrome is perhaps not an exceptionally rare condition and represents an example of a systemic genetic autoinflammatory disease drawing its origin in bone marrow disorders. VEXAS syndrome should be strongly considered in each adult patient with an unexplained systemic inflammatory condition, especially when recurrent fevers, neutrophilic dermatosis, relapsing polychondritis, ocular inflammation and other systemic inflammatory symptoms accompanying myelodysplastic syndrome or other haematological disorders. The syndrome deserves a multidisciplinary approach to reach the diagnosis and ensure the best management of a potentially very challenging condition. To quickly describe the clinical course, long-term outcomes, and the optimal management of this new syndrome it is essential to join forces internationally. To this end, the international AutoInflammatory Disease Alliance (AIDA) registry dedicated to VEXAS syndrome has been developed and is already active.

Comparing biologic options for the management of Behcet's disease-related uveitis.

INTRODUCTION: Behçet's disease (BD) associated uveitis occurs in approximately 50-70% of the patients. Ocular involvement in BD may induce a severe affection of visual function, leading to a considerable decrease in patients' quality of life. The risk for severe visual loss increases when the ocular posterior segment is involved and in patients with no adequate treatment. AREAS COVERED: Monoclonal tumor necrosis factor (TNF) biotechnological inhibitors represent a relatively recent milestone for the treatment of non-infectious uveitis (NIU) also in BD patients. In addition to TNF inhibitors, further biologic agents have been increasingly proposed for multi-recalcitrant cases, as for interleukin (IL)-1 and IL-6 inhibitors. However, evidence on these new opportunities requires to be widened in the next future. EXPERT OPINION: Joining the forces for scientific efforts is essential to quickly obtain solid acquisitions useful for the everyday clinical practice. To this end, the Auto-Inflammatory Disease Alliance (AIDA) Network has recently supported the development of an international registry dedicated to NIU and other inflammatory ocular involvement observed in BD patients. This will be essential to resolve current and future unmet needs burdening the everyday clinical practice.

Exogenous Endophthalmitis.

PURPOSE: Exogenous endophthalmitis (ExE) results from microbial infection as a complication of ocular surgery, penetrating ocular trauma, and intraocular foreign bodies. We herein review the classification of ExE, etiological agents, differential diagnosis and therapeutic challenges. METHODS: Narrative Literature Review. RESULTS: Identification of the causative agent through ocular fluid analysis is central in the diagnostic work-up of ExE. Prompt intravitreal antimicrobial therapy is key to successful management of ExE and vitrectomy is essential in severe cases. In culture-negative cases, and in the presence of specific features, a diagnosis of sterile intraocular inflammation or toxic syndrome should be suspected. CONCLUSION: Strict adherence to treatment guidelines may improve outcomes of ExE, however the ultimate prognosis, especially in severe cases, may depend more on the virulence of the causative organism and associated ocular complications. Accurate differential diagnosis and effective treatment are crucial elements in the management and prognosis of non-infectious masquerades of ExE.

The diagnostic role of pathergy test in patients with Behçet's disease from the Western Europe.

The aim of the study is to evaluate the frequency and features of positive pathergy test (PPT) in Italy, its role in the diagnosis of Behçet's disease (BD), and any association with other BD-related manifestations. 52 BD patients, 52 patients with axial spondyloarthritis (ax-SpA), and 26 healthy controls (HCs) underwent intradermal injection of normal saline and intradermal needle soaked with fresh self-saliva. The results of pathergy tests were statistically analysed in the light of demographic, clinical, and therapeutic features of subjects enrolled. Pathergy test performed with saline resulted always negative in all groups. Skin prick test using self-saliva resulted in the occurrence of a papule in 3 (5.8%) BD patients and in 1 (1.9%) patient with ax-SpA. A ≥ 15 mm erythematous area surrounding the needle prick site was observed in 22 (42.3%) BD patients, 5 (9.6%) patients with ax-SpA, and 2 (7.7%) HCs (p = 0.00002). The frequency of skin erythema was significantly more frequent in patients with BD than those with ax-SpA (p < 0.0001) and HCs (p = 0.003). No statistically significant differences were observed between ax-SpA patients and HCs (p = 1.000). The occurrence of skin erythema at pathergy test was not associated with any BD-related clinical manifestation. Erythema at self-saliva prick test presented a sensitivity of 42.31% (CI 28.73-56.80%) and a specificity of 91.03% (CI 82.38-96.32%). The development of a ≥ 15 mm erythematous area at self-saliva prick test could be sufficient to unveil the hyper-reactivity of the innate immune system in BD patients from Western Europe, where the development of skin erythema shows good sensitivity and specificity toward the diagnosis of BD.

Risk of Intraocular Pressure Increase With Intravitreal Injections of Vascular Endothelial Growth Factor Inhibitors: A Cohort Study.

PURPOSE: Intraocular pressure increase (IOPi) after intravitreal injections of vascular endothelial growth factor inhibitors (VEGFis) might be different among different VEGFis (bevacizumab, aflibercept, ranibizumab). The purpose of this study was to evaluate the risk of IOPi among new users of bevacizumab, ranibizumab, and aflibercept in nondiabetic patients in Tuscany, Italy. DESIGN: Retrospective cohort study. METHODS: Tuscan regional administrative database was used to identify subjects with a first VEGFi intravitreal injection between 2011 and 2020, followed to first incidence of IOPi. Diabetic subjects, those with pre-existing IOPi, or previous use of dexamethasone implants were excluded. Multivariable Cox regression analyses (intention-to-treat and as treated) were conducted to evaluate risk of IOPi among aflibercept, bevacizumab, and ranibizumab, adjusting for potential confounding variables. IOPi was defined as the first record of International Classification of Diseases, Ninth Revision (ICD-9-CM) code 365 or use of 2 glaucoma drugs dispensations within 180 days of each other. RESULTS: We identified 6585 new users of VEGFis: 1749 aflibercept, 1112 bevacizumab, and 3724 ranibizumab. Women made up 60% of the cohort, with a mean age of 73.6 years. In the intention-to-treat analysis, the adjusted hazard ratio (HR) for incident IOPi, compared with aflibercept, was higher for bevacizumab (HR = 2.20, 95% CI = 1.64-2.95) and ranibizumab users (HR = 1.88, 95% CI = 1.46-2.42), respectively. The HRs remained robust after exclusion of patients with proxy of retinal vascular occlusion. As treated analysis confirmed such results (bevacizumab: HR = 3.76, 95% CI = 2.30-6.17; ranibizumab: HR = 2.49, 95% CI = 1.62-3.82). CONCLUSIONS: This study found an increased risk of IOPi among nondiabetic patients with ranibizumab and bevacizumab compared with aflibercept. Future studies are needed to validate these findings.

Dimerization of the C-type lectin-like receptor CD93 promotes its binding to Multimerin-2 in endothelial cells.

Blocking the signaling activated by the plasma membrane receptor CD93 has recently been demonstrated a useful tool in antiangiogenic treatment and oncotherapy. In the proliferating endothelium, CD93 regulates cell adhesion, migration, and vascular maturation, yet it is unclear how CD93 interacts with the extracellular matrix activating signaling pathways involved in the vascular remodeling. Here for the first time we show that in endothelial cells CD93 is structured as a dimer and that this oligomeric form is physiologically instrumental for the binding of CD93 to its ligand Multimerin-2. Crystallographic X-ray analysis of recombinant CD93 reveals the crucial role played by the C-type lectin-like and sushi-like domains in arranging as an antiparallel dimer to achieve a functional binding state, providing key information for the future design of new drugs able to hamper CD93 function in neovascular pathologies.

Purtscher-like retinopathy in a patient with systemic tacrolimus vasculopathy.

INTRODUCTION: Purtscher-like retinopathy is a rare occlusive retinal microangiopathy, whose pathogenesis has not been totally defined yet. Most frequent cause of Purtscher-like retinopathy is acute pancreatitis, but it may be triggered by other systemic or toxic conditions. We report herein a case of Purtscher-like retinopathy in the context of systemic tacrolimus vasculopathy. CASE REPORT: A 56-years old male with history of kidney transplant was referred to local emergency room because of a global worsening of health conditions, with fatigue, muscular pain and diuresis contraction. During hospitalization the patient came to our attention for sudden and severe visual acuity impairment in both eyes. Extensive ophthalmological assessment, optical coherence tomography (OCT) and fluorescein angiography (FA) were performed disclosing a marked drop in best corrected visual acuity (BCVA) (20/200 in the right eye and 10/400 in the left eye) caused by a bilateral severe occlusive retinal microangiopathy complicated by diffuse retinal ischaemia and neovascular glaucoma. Muscular biopsy showed a necrotizing myopathy with autoimmune features, as indicated by conspicuous upregulation of MHC-I complex and microangiopathic changes, consistent with tacrolimus toxicity. Tacrolimus administration was interrupted, and intravenous glucocorticoids were administered. The large areas of retinal ischemia and neovascular glaucoma were treated with pan-retinal photocoagulation and intravitreal injections of bevacizumab with complete regression of iris neovascolarization. BCVA measured 20/200 in both eyes at last follow-up visit, 20 months after symptoms onset. CONCLUSIONS: Purtscher-like retinopathy should be suspected in patients under treatment with calcineurin inhibitors especially in case of sudden and severe bilateral visual impairment.

Color Doppler Eye Ultrasonography in giant cell arteritis: differential diagnosis between arteritic and non-arteritic sudden blindness.

PURPOSE: Temporal (TA) and axillary (AXA) arteries Color Doppler Ultrasonography (CDUS) is the most reliable diagnostic technique for the diagnosis of giant cell arteritis (GCA), displaying high sensitivity and specificity. Nevertheless, CDUS is still poorly performed in the common clinical practice, being employed only by rheumatologists with a relevant expertise in this field. Color Doppler Eye Ultrasound (CDEUS) is a procedure variously employed in ophthalmology and preliminary findings have displayed a possible role also in the diagnostic work-up of GCA. Aim of this study was to assess whether CDEUS may play a role in the differential diagnosis between arteritic and non-arteritic blindness. METHODS: We prospectively included all patients evaluated since September 2021 to May 2022 by our Ophthalmology Unit for sudden blindness and referred to our Vasculitis Clinic in the suspicion of GCA. All patients underwent complete ophthalmological evaluation, routine blood tests, AxA and TA CDUS and CDEUS. According to the definite diagnosis, patients were divided in the following subgroups: (A) patients suffering from arteritic central retinal artery occlusion (CRAO), (B) patients suffering from non-arteritic CRAO, (C) patients suffering from arteritic anterior ischemic optic neuropathy (AION), (D) patients suffering from non-arteritic AION. RESULTS: During the observational period, we included a total of 25 patients suffering from sudden blindness and referred to Vasculitis Clinic for ruling out GCA. Patients belonging to group A showed no flow or reduced flow within the territory of central retinal artery (CRA), no "spot sign" and positive TA CDUS; on the other hand, patients from group B presented normal TA CDUS, no flow or reduced flow within the territory of CRA and the presence of "spot sign". Conversely, no relevant difference was evidenced at CDEUS in patients with and without arteritic AION. CONCLUSION: Our preliminary data displayed a good reliability of CDEUS in distinguishing between arteritic and non-arteritic CRAO, while no difference was assessed between arteritic and non-arteritic AION. Since AION represents the most common presentation of cranial GCA, CDEUS does not seem a reliable procedure in the diagnostic work-up of GCA and should be restricted only to the exclusion of thrombo-embolic occlusions within the territory of central retinal artery.

Pediatric Scleritis: An Update.

Posterior idiopathic scleritis is the most common type of scleritis observed in childhood. Nevertheless, anterior and even necrotizing inflammatory scleritis may occur as well. Although less frequently than in the adult population, scleral inflammation can be associated with systemic disorders, which should be promptly recognized and treated to avoid both ocular and systemic complications. Hence, a multidisciplinary diagnostic work-up should be performed to rule out primarily infectious and autoimmune causes, such as viral and bacterial infections, anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis, pediatric sarcoidosis, Behçet's disease and HLA-B27-associated diseases. Treatment of scleritis should aim to control ocular inflammation, relieve symptoms and prevent relapses, to avoid complications, preserve visual acuity and improve the child's quality of life. It should be tailored to the patient, considering the type and severity of scleritis, the possible identification of an infectious cause or the presence of an associated rheumatologic condition.

Untangling the Extracellular Matrix of Idiopathic Epiretinal Membrane: A Path Winding among Structure, Interactomics and Translational Medicine.

Idiopathic epiretinal membranes (iERMs) are fibrocellular sheets of tissue that develop at the vitreoretinal interface. The iERMs consist of cells and an extracellular matrix (ECM) formed by a complex array of structural proteins and a large number of proteins that regulate cell-matrix interaction, matrix deposition and remodelling. Many components of the ECM tend to produce a layered pattern that can influence the tractional properties of the membranes. We applied a bioinformatics approach on a list of proteins previously identified with an MS-based proteomic analysis on samples of iERM to report the interactome of some key proteins. The performed pathway analysis highlights interactions occurring among ECM molecules, their cell receptors and intra- or extracellular proteins that may play a role in matrix biology in this special context. In particular, integrin ß1, cathepsin B, epidermal growth factor receptor, protein-glutamine gamma-glutamyltransferase 2 and prolow-density lipoprotein receptor-related protein 1 are key hubs in the outlined protein-protein cross-talks. A section on the biomarkers that can be found in the vitreous humor of patients affected by iERM and that can modulate matrix deposition is also presented. Finally, translational medicine in iERM treatment has been summed up taking stock of the techniques that have been proposed for pharmacologic vitreolysis.

The Role of Biologic Agents in the Management of Pediatric-Onset Noninfectious Posterior Scleritis.

Registry-based observational prospective study aimed at describing the use of biologic drugs in pediatric-onset scleritis. Data were collected at baseline, at 3-, 6-, 12-month follow-up and at last assessment. Scleral inflammation was graded according to Sen classification. Five patients (9 eyes) treated with adalimumab, infliximab, abatacept and secukinumab were included. All patients were previously treated with conventional immunosuppressors and glucocorticoids. Median biologic treatment duration was 28 (IQR = 118) months. At 6-months, scleritis resolved in all eyes. At 12-months, complete disease control was observed in 7/9 eyes (77.8%). The number of relapses 12 months before and after treatment initiation was 17 and 2, respectively. Mean BCVA was 0.83 (range 0.3-1.0) at baseline and 1.0 for all eyes after 12 months. Glucocorticoids had been withdrawn in 4/5 patients.In conclusion, biological agents proved to be effective in pediatric-onset scleritis, allowing a noticeable steroid-sparing effect and preserving visual function and bulbar integrity.