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.

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.

Management of presumed trematode-induced granulomatous intermediate uveitis.

PURPOSE: To describe the surgical management of presumed trematode-induced granulomatous intermediate uveitis (PTIGIU) not responding to medical treatment in controlling the inflammation. METHODS: A prospective, interventional, single-center study in which patients with a history of fresh canal water contact and PTIGIU were enrolled. All patients underwent lensectomy-pars plana vitrectomy (PPV) and post-operative control of inflammation, functional and anatomical outcomes were assessed. RESULTS: Fifteen eyes of 12 patients were included in the study with median age of 11.6 ± 4 yrs. Six months following lensectomy-PPV, inflammation was well controlled in all patients. The eyes were divided into two groups: Group A: 10 patients with an attached retina while Group B: 5 patients who were in the cicatricial stage with tractional retinal detachment. All patients in group A had CDVA of 20/40 or better, unlike patients in group B who failed to achieve a CDVA better than 20/70 throughout their follow-up. In group B, final anatomical success was achieved in only 40% with hypotony occurring in 20%. CONCLUSION: PTIGIU is associated with the presence of ciliary body granuloma which, if left untreated, can lead to drastic outcomes. Early lensectomy-PPV represents a viable management option in cases resistant to medical treatment, with a favorable outcome.

Retinal vascular assessment in psoriatic patients with and without metabolic syndrome using optical coherence tomography angiography.

To evaluate the retinal vasculature in psoriasis patients and detect if metabolic syndrome is an additional risk factor. This cross-sectional analytic study was carried out on 80 eyes of 80 subjects; 28 eyes with psoriasis only (PS group), 12 eyes with additional metabolic syndrome to psoriasis (PMS group) and 40 eyes healthy controls (HS). The retinal capillary plexuses were evaluated by OCTA. The disease activity was evaluated by the Psoriasis Area and Severity Index (PASI) score and extent. The superficial capillary plexus (SCP) vascular density was significantly lower in PS group than HS while in PMS it was significantly lower only in whole image and superior and temporal perifoveal areas (p-value = 0.020, 0.030, 0.001 respectively). The changes correlated with the disease duration. The vascular density of the deep capillary plexus (DCP) was significantly lower in both PS and PMS groups (p-value < 0.001). Psoriatic patients are at a higher risk of developing retinal vascular complications even without evident clinical ocular disease. It was noted that the presence of metabolic syndrome contributes as an additional risk factor in possible visual loss secondary to ischemic changes that are likely to start in the DCP and progress to involve all levels.

Combined nasal goniotomy - temporal trabeculotomy (NGTT) for circumferential angle surgery in primary congenital glaucoma.

PURPOSE: To assess the safety and efficacy of combining nasal goniotomy with temporal trabeculotomy in the management of primary congenital glaucoma. DESIGN: Case series. METHODS: Fifteen eyes of eleven children (3-12 months old at presentation) were enrolled in this study after the establishment of PCG diagnosis based on the criteria placed by the World Glaucoma Association. Combined nasal goniotomy and temporal trabeculotomy were done on each eye in an attempt to perform almost 360 degrees circumferential angle surgery without disturbing the superior 180 degrees of conjunctiva to preserve it for future filtering glaucoma surgeries. RESULTS: By first month, average IOP was 10.5 ± 4.3 mmHg with a 65.3% reduction from average pre-operative IOP. Almost the same percentage of reduction was maintained at 3rd,6th and 12th months postoperative visits with average IOP of 11.9 ± 4.65, 11.8 ± 2.77 and 13 ± 2.82 mmHg (60.7%, 61.1% and 57.2% reduction from pre-operative average). According to success rates, complete success has been achieved in all eyes but one (93.3%), with minor complications in 4 out of 15 eyes (26.6%) that did not affect IOP outcome. Nine out of fifteen eyes completed 18 months post-operative follow-up visits with a successfully, maintained target average IOP of 13.3 ± 3.0 mmHg (57.2% reduction). All of the mean IOP readings during post-operative follow-up period were significantly lower when compared to pre-operative IOP (p < 0.0001). Only one eye had persistently elevated IOP of 26 mmHg at 1st and 3rd months post-operatively that necessitated a subsequent subscleral trabeculectomy which succeeded in controlling the pressure bringing it down to 15 mmHg on topical medications. CONCLUSION: Nasal goniotomy - temporal trabeculotomy (NGTT) is the combination of two well established surgeries that exploits the advantages of circumferential angle surgery while sparing the superior conjunctiva completely for future surgeries if needed. This new procedure was safe and effective in lowering IOP by an average of 60% from pre-operative IOP with a sustained effect till 18 months post-operatively. We believe that this surgery might be added to the armentarium of the surgical management of infantile glaucomas with other circumferential angle surgeries.

Development and Implementation of the AIDA International Registry for Patients with Non-Infectious Uveitis.

INTRODUCTION: The aim of this paper is to point out the design, development and deployment of the AutoInflammatory Disease Alliance (AIDA) International Registry for paediatric and adult patients with non-infectious uveitis (NIU). METHODS: This is a physician-driven, population- and electronic-based registry implemented for both retrospective and prospective collection of real-world demographics, clinical, laboratory, instrumental and socioeconomic data of patients with uveitis and other non-infectious inflammatory ocular diseases recruited through the AIDA Network. Data recruitment, based on the Research Electronic Data Capture (REDCap) tool, is thought to collect standardised information for real-life research and has been developed to change over time according to future scientific acquisitions and potentially communicate with other similar instruments. Security, data quality and data governance are cornerstones of this platform. RESULTS: Ninety-five centres have been involved from 19 countries and four continents from 24 March to 16 November 2021. Forty-eight out of 95 have already obtained the approval from their local ethics committees. At present, the platform counts 259 users (95 principal investigators, 160 site investigators, 2 lead investigators, and 2 data managers). The AIDA Registry collects baseline and follow-up data using 3943 fields organised into 13 instruments, including patient's demographics, history, symptoms, trigger/risk factors, therapies and healthcare utilization for patients with NIU. CONCLUSIONS: The development of the AIDA Registry for patients with NIU will facilitate the collection of standardised data leading to real-world evidence and enabling international multicentre collaborative research through inclusion of patients and their families worldwide.

Development and Implementation of the AIDA International Registry for Patients with Non-Infectious Scleritis.

INTRODUCTION: This article points out the design, methods, development and deployment of the international registry promoted by the AutoInflammatory Disease Alliance (AIDA) Network with the aim to define and assess paediatric and adult patients with immune-mediated scleritis. METHODS: This registry collects both retrospective and prospective real-world data from patients with non-infectious scleritis through the Research Electronic Data Capture (REDCap) tool and aims to promote knowledge and real-life evidence from patients enrolled worldwide; the registry also allows the collection of standardised data, ensuring the highest levels of security and anonymity of patients' data and flexibility to change according to scientific acquisitions over time. The communication with other similar registries has been also ensured in order to pursue the sustainability of the project with respect to the adaptation of collected data to the most diverse research projects. RESULTS: Since the launch of the registry, 99 centres have been involved from 20 countries and four continents. Forty-eight of the centres have already obtained a formal approval from their local ethics committees. At present, the platform counts 259 users (95 principal investigators, 160 site investigators, 2 lead investigators, and 2 data managers); the platform collects baseline and follow-up data using 3683 fields organised into 13 instruments, including patient's demographics, history, symptoms, trigger or risk factors, therapies and healthcare utilization. CONCLUSIONS: The development of the AIDA International Registry for patients with non-infectious scleritis will allow solid research on this rare condition. Real-world evidence resulting from standardised real-life data will lead to the optimisation of routine clinical and therapeutic management, which are currently limited by the rarity of this ocular inflammatory condition.