Childhood Chronic Idiopathic Uveitis in a Multicentre International Cohort.

IMPORTANCE: Idiopathic uveitis makes up around 50% of non-infectious uveitis but the clinical characteristics in children are poorly understood. OBJECTIVE: To report the demographic, clinical characteristics, and outcomes of children with idiopathic non-infectious uveitis (iNIU) in a multicentric retrospective study. RESULTS: There were 126 (61 female) children with iNIU. The median age at diagnosis was 9.3 years (3-16 years) . Uveitis was bilateral in 106 patients and anterior in 68.At onset,impaired visual acuity and blindness in the worse eye were reported, in 24.4% and 15.1% patients but at 3 years of follow-up, there was a significant improvement in visual acuity (mean 0.11 SD ±0.50 vs 0.42 SD ± 0.59 p < .001). CONCLUSIONS AND RELEVANCE: There is a high rate of visual impairment at presentation in children with idiopathic uveitis. The majority of patients have a significant improvement in vision, but 1 in 6 had impaired vision or blindness in their worse eye at 3 years.

This is a large retrospective study of children with chronic idiopathic uveitis,There is a high rate of visual impairment at presentation in children with idiopathic uveitis. Although visual acuity improves during follow-up, one in six still had impaired vision or blindness in their worse eye at 3 years.At 3 years, more than half of patients were on immunosuppression and one-third were on a biologic agent.

Efficacy of a Cationic Emulsion of Cyclosporine in Moderate Vernal Keratoconjunctivitis.

PURPOSE: The aim of this study was to demonstrate the efficacy of cyclosporine A 0.1% cationic emulsion (CsA CE) eye drops 4 times a day in pediatric patients affected by a moderate form of vernal keratoconjunctivitis (VKC). METHODS: This was a prospective study of pediatric patients, aged 5-16 years, with an active moderate form of VKC who were poor responders to topical antihistamines treatment and were treated 4 times a day with CsA CE. The clinical signs were graded for analysis as follows: hyperemia, tarsal papillae, and limbal papillae. RESULTS: Twenty-eight patients (22 males and 6 females) with a minimum follow-up period of 3 months were included in the analysis. Statistical analysis excluded tarsal papillae because of the very low baseline value. The clinical score of hyperemia and limbal papillae improved from the first evaluation and was maintained over the follow-up. No side effects were noted. CONCLUSION: CsA CE has been proposed as a treatment for severe forms of VKC. This study has shown that administration 4 times a day is also effective in the treatment of moderate forms of VKC in children.

Laser Flare Photometry to Monitor Childhood Chronic Uveitis: A Preliminary Report of a Monocentric Italian Experience.

Background: Childhood chronic non-infectious uveitis (cNIU) is a challenging disease that needs close monitoring. Slit lamp evaluation (SLE) is the cornerstone of ophthalmological evaluation for uveitis, but it is affected by interobserver variability and may be problematic in children. Laser flare photometry (LFP), a novel and objective technique, might be used in children with uveitis. Aim: The aim of this study was to attempt the use of LFP in cNIU clinical practice. Methods: Children, attending the Rheumatology Unit and who were scheduled to receive ophthalmological evaluation, were prospectively enrolled to concomitantly receive SLE and LFP. SLE was performed blind to LFP measure. Demographic, laboratory, clinical, and ophthalmology data were collected. Results: A total of 29 children (58 eyes) were enrolled, including 3 with juvenile idiopathic arthritis without uveitis (JIA-no-U), 15 with JIA-associated uveitis (JIA-U), and 11 with idiopathic chronic uveitis (ICU). We observed significantly higher LFP values in the eyes of children with uveitis compared to the others (10.1 IQR 7.1-13.6 versus 6.2 IQR 5.8-6.9, p = 0.007). Accordance between the SLE and LFP measures, at baseline (ρ.498, p < 0.001) and during the follow-up (LFP II ρ 0.460, p < 0.001, LFP III ρ 0.631, p < 0.001, LFP IV ρ 0.547, p = 0.006, LFP V ρ 0.767, p = 0.001), was detected. We evaluated significant correlation between LFP values and the presence of complications (ρ 0.538, p < 0.001), especially with cataract formation (ρ 0.542, p < 0.001). Conclusions: In this cohort, LFP measurements showed a good correlation with SLE. LFP values showed a positive correlation with the presence of complications. LFP might be considered as a reliable objective modality to monitor intraocular inflammation in cNIU.

Challenges and management of childhood noninfectious chronic uveitis.

INTRODUCTION: Childhood uveitis is a sight-threatening condition, because if not properly recognized and treated can lead to several ocular complications and blindness. It represents a real challenge not only from an etiologic/diagnostic point of view, but also for management and therapy. AREAS COVERED: In this review we will discuss the main etiologies, the diagnostic approach, risk factors associated to childhood noninfectious uveitis (cNIU), and the difficulties in eye examination in childhood. Moreover, we will discuss the treatment of cNIU in terms of therapeutic choice, timing of initiation, and withdrawal. EXPERT OPINION: Identification of specific diagnosis is mandatory to prevent severe complications, thus a thorough differential diagnosis is essential. Pediatric eye examination may be extremely challenging due to the scarce collaboration, but novel techniques and biomarkers will help in identifying low grade of inflammation, eventually modifying long-term outcomes. Once identified the appropriate diagnosis, recognition of children who may benefit of a systemic treatment is crucial. What, When, and how long are the key questions to address in this field. Current evidence and future results of ongoing clinical trials will help in driving treatment. A proper ocular screening, not only in the context of systemic disease, should be discussed by experts.

Acute Rejection Following COVID-19 Vaccination in Penetrating Keratoplasty in a Young Male - A Case Report and Review of Literature.

PURPOSE: To report a case of a boy with acute keratoplasty rejection manifesting 12 days after receiving BNT162b2 messenger RNA (mRNA) vaccine for COVID-19. STUDY DESIGN: A case report. RESULTS: A 15-year-old boy with a history of penetrating keratoplasty due to acanthamoeba keratitis developed corneal decompensation 12 days after BNT162b2 messenger RNA vaccine for COVID-19 disease. One-week treatment with topical Dexamethasone 2% eye drops resulted in a complete resolution of corneal edema. CONCLUSIONS: This case suggests that BNT162b2 messenger RNA (mRNA) vaccine can be associated with acute keratoplasty rejection in children, which responds completely to topical steroids. Ophthalmologists should be aware of this risk of cornea decompensation after COVID-19 vaccine in children who received a cornea transplant.

Impact of screen exposure on pediatric vernal Keratoconjunctivitis: a survey during the COVID-19 pandemic in Italy.

BACKGROUND: The SARS-CoV-2 outbreak pushed the Italian government to start a strict lockdown, replacing school attendance with long-distance learning. This caused reduced exposure to sunlight but increased exposure to screens. Vernal keratoconjunctivitis (VKC) is a chronic inflammatory ocular condition in which exposure to light plays a cardinal role. We conducted an online survey to evaluate the impact of screen exposure on children with VKC during the COVID-19 lockdown. METHODS: We performed a survey-based observational study, asking patients followed at the Allergology clinics of Meyer Children's University Hospital in Florence and of Policlinico Umberto I in Rome to provide grading on 6 subjective ocular clinical manifestations presented during the lockdown and to give an estimate of their hours/day of screen exposure. RESULTS: Mean scores of signs and symptoms increased homogeneously when studying patients exposed to longer screen time. When comparing scores collected in 2019 to those in 2020, there was not a significant reduction in clinical manifestations, although the situation differed between the two centers due to geographical differences in sunlight exposure. CONCLUSION: During the lockdown, there was a reduction in sunlight exposure but conversely an increase in the time spent in front of screens that correlated with the worsening of VKC signs and symptoms in direct proportion to the hours/day of screen exposure. Our results also showed a statistically significant difference in the relative impact of long-distance learning on VKC clinical manifestations in the different Italian regions.

Tocilizumab and Abatacept for the Treatment of Childhood Chronic Uveitis: A Monocentric Comparison Experience.

Background: Our study aimed to evaluate the efficacy of Tocilizumab and Abatacept for treating Childhood Chronic non-infectious Uveitis (CCU), resistant to anti-tumor necrosis factor (anti-TNF) treatment. Methods: This is a monocentric retrospective charts review study (January 2010-April 2021) recruiting CCU, refractory to anti-TNF. To be included, children should have active uveitis at the time of Tocilizumab (8 mg/kg, every 4 weeks) or Abatacept (10 mg/kg, every 4 weeks). The main outcome was the achievement of ocular remission on treatment defined as the absence of flares for ≥ 6 months. Results: In this study, 18 patients with CCU (14 F), previously treated with Methotrexate and Adalimumab, were enrolled: 15 had juvenile idiopathic arthritis (JIA) (83.3%), 2 idiopathic (11.1%), and 1 Behçet (5.6%). Furthermore, ten patients received Abatacept and 8 patients received Tocilizumab. The mean duration of treatment on Abatacept was 31.6 months (SD ± 30.8), on Tocilizumab 25.25 months (SD ± 17.8). In total, 13 children (72.2%) achieved remission, with a better remission rate for the Tocilizumab group (8/8) compared to the Abatacept group (5/10) (χ2 5.53, p = 0.019). No difference was evaluated between the two groups in the proportion of patients who showed flares during the treatment (2/6 Abatacept vs. 1/8 Tocilizumab). A significant difference was evaluated in the proportion of patients who flared after treatment discontinuation: 3/3 Abatacept vs. 0/3 Tocilizumab (χ2 3.8, p = 0.025). Conclusion: Even though this is a monocentric retrospective study, in a relatively small group, our study suggests a superior efficacy of Tocilizumab over Abatacept for treating anti-TNF refractory CCU.

A case of unilateral acute hypertensive uveitis in a child.

A 6-year-old boy was referred to our hospital for sudden blurring vision in the left eye. An ophthalmological evaluation showed white endothelial keratic precipitates and increased intra-ocular pressure. To our knowledge, this is the first reported case of hypertensive uveitis in children under 10 years of age and we also discuss the role of Epstein-Barr virus as a possible infectious trigger.

Long-Term Safety and Efficacy of Tacrolimus 0.1% in Severe Pediatric Vernal Keratoconjunctivitis.

PURPOSE: The aim of this study was to evaluate the safety and efficacy of tacrolimus 0.1% eye drops in a large population of pediatric patients affected by a severe form of vernal keratoconjunctivitis (VKC) who responded poorly to cyclosporine eye drops. METHODS: This is a retrospective study based on standardized clinical charts and data collection of consecutive patients affected by severe VKC who responded poorly to cyclosporine eye drops topical treatment but treated with tacrolimus 0.1% eye drops with a follow-up of 18 months. Four clinical signs were graded for analysis: hyperemia, tarsal papillae, giant papillae, and limbal papillae. The blood tests for kidney and liver function and the tacrolimus level were studied. Visits were scheduled at baseline and at 3, 6, 12, and 18 months. Patients received tacrolimus 0.1% eye drops in both eyes 2 times daily. RESULTS: Four hundred thirty-one patients were included. Three hundred twenty-five patients were affected by a seasonal form, whereas the remaining 106 by a perennial form. Statistical analysis on each single score showed a positive relevance (P < 0.001) from baseline to all other visits. No local or systemic complications were recorded. CONCLUSIONS: Tacrolimus has been proposed as a treatment for severe forms of VKC. This study has confirmed the safety and efficacy of tacrolimus 0.1% eye drops in a large pediatric population of patients affected by a severe form of VKC who responded poorly to cyclosporine eye drops.

Increased Lacrimal Fluid Level of HMGB1 in Vernal Keratoconjunctivitis.

Purpose: The aim of the present prospective study was to evaluate the lacrimal fluid concentration of HMGB1 in young patients affected by Vernal Keratoconjunctivitis (VKC) compared to a control group of healthy subjects of same age. Methods: Tear fluids was collected in a group of VKC patients and compared to a control group of healthy subjects. HMGB1 concentration was measured using the HMGB1 ELISA II test both in VCK and control subjects. Results: The mean concentration of HMGB1 in tear fluids of 45 VKC patients was 0,977 ± 0,72 ng/ml whereas in the control group was 0,24 ± 0,25 ng/ml and the difference was statistically significant (p = 0,000106) Conclusion: The concentration of HMGB1 in VCK patients was found to be significantly increased, suggesting a possible role of this protein in the inflammatory mechanism of VKC.

Propranolol eye drops in patients with corneal neovascularization.

RATIONALE: Studies performed in animal models of corneal neovascularization suggested the possible efficacy of a treatment with propranolol. Corneal neovascularization is one of the most feared complications of Stevens-Johnson syndrome that frequently involves ocular surface. We report the first 2 patients with severe ocular neo-vascularization treated with different degrees of success, with propranolol eye drops. PATIENT CONCERNS: Two patients with corneal neovascularization complicating the Stevens-Johnson syndrome, not responsive to steroids and cyclosporine, were treated with propranolol eye drops. DIAGNOSES: Corneal neovascularization was detected by ophthalmoscopic evaluation. INTERVENTIONS: Topical treatment with propranolol eye drops at different concentrations. OUTCOMES: Both patients reported dramatic subjective benefits (reduction of photophobia and discomfort) without adverse effects, and in the patient with a less advanced disease, an objective reduction of neovascularization and an improved visual acuity was observed. LESSONS: This experience suggests that propranolol might be an inexpensive, safe and effective treatment in counteracting the progression of corneal neovascularization.

Longterm Safety and Efficacy of Adalimumab and Infliximab for Uveitis Associated with Juvenile Idiopathic Arthritis.

OBJECTIVE: Anti-TNF-α agents have significantly changed the management of juvenile idiopathic arthritis (JIA). We evaluated the safety and efficacy of adalimumab (ADA) and infliximab (IFX) for the treatment of JIA-associated uveitis in patients treated for ≥ 2 years. METHODS: Patients with JIA-associated uveitis treated with IFX and ADA were managed by a standardized protocol and data were entered in the ORCHIDEA registry. At baseline, all patients were refractory to standard immunosuppressive treatment or were corticosteroid-dependent. Data recorded every 3 months were uveitis course, number/type of ocular flares and complications, drug-related adverse events (AE), and treatment switch or withdrawal. Data of patients treated for ≥ 2 years were analyzed by descriptive statistics. RESULTS: Up to December 2014, 154 patients with ≥ 24 months followup were included in the study. Fifty-nine patients were treated with IFX and 95 with ADA. Clinical remission, defined as the absence of flares for > 6 months on treatment, was achieved in 69 patients (44.8%), with a better remission rate for ADA (60.0%) as compared to IFX (20.3%; p < 0.001). A significant reduction of flares was observed in all patients without difference between the 2 treatment modalities. The number of new ocular complications decreased in both groups but was lower for ADA (p = 0.015). No serious AE were recorded; 16.4% of patients experienced 35 minor AE and the incidence rate was lower with ADA than with IFX. CONCLUSION: At the 2-year followup, ADA showed a better efficacy and safety profile than IFX for the treatment of refractory JIA-associated uveitis.

Predictors of Relapse after Discontinuing Systemic Treatment in Childhood Autoimmune Chronic Uveitis.

OBJECTIVE: To identify clinical predictors of relapse in childhood autoimmune chronic uveitis after stopping systemic treatment. METHODS: A retrospective, multicenter, cohort study. RESULTS: Ninety-four children in remission, receiving no treatments and with at least a 6-month followup, were enrolled. A higher probability of maintaining remission after discontinuing treatment was shown in idiopathic compared with juvenile idiopathic arthritis uveitis (Mantel-Cox chi-square = 23.21) if inactivity had been obtained within 6 months from starting systemic treatment (Mantel-Cox chi-square = 24.17) and by antitumor necrosis factor-α treatment (Mantel-Cox chi-square = 6.43). CONCLUSION: Type of disease, time, and type of systemic therapy to achieve inactivity predict different duration of uveitis remission after treatment withdrawal.

Retinal capillaritis in a CRB1-associated retinal dystrophy.

PURPOSE: To report a case of CRB1-associated retinal dystrophy characterized by vitritis, retinal capillaritis, and cystoid macular edema (CME). METHODS: A case report. RESULTS: An 8-year-old boy was diagnosed with intermediate uveitis and treated with corticosteroids. He was subsequently diagnosed with retinal dystrophy and found to have two CRB1 mutations. CONCLUSIONS: Retinal capillaritis, vitritis, and CME could be inflammatory features of CRB1 retinal dystrophy in our young patient.

Very Low Prevalence of Keratoconus in a Large Series of Vernal Keratoconjunctivitis Patients.

PURPOSE: To evaluate the prevalence of keratoconus (KC) and other corneal abnormalities by means of videokeratography and tomography in a large series of patients affected by vernal keratoconjunctivitis (VKC). DESIGN: Cross-sectional study. METHODS: Setting: Single-center children's hospital. STUDY POPULATION: A total of 651 consecutive patients with VKC and a control group of 500 were prospectively recruited between May 1, 2012 and September 30, 2013, with a minimum follow-up of 12 months. OBSERVATION PROCEDURE: All patients were evaluated by means of a Scheimpflug camera combined with a Placido corneal topographer. Keratoconus, suspected keratoconus, or its absence were determined in each patient. The corneal symmetry index of front (SIf) and back curvature (SIb), shape indices, and thicknesses were compared between the 2 groups. MAIN OUTCOME MEASURES: Prevalence of keratoconus and corneal indices modifications. RESULTS: Five out of 651 patients (0.77%) demonstrated topographic signs of KC. Two of them were bilateral. All patients were older than 7 years of age, and the mean age was 11.54 years. Four other patients (0.61%) were classified as KC suspects by the screening program. Of 304 patients older than 11 years (mean age 14.4 years), 4 (1.32%) were found to have KCN, and 4 (1.32%) were KC suspects. The corneal indices of patients in the VKC group were extremely similar to those in the control group. (P > .05). CONCLUSIONS: The prevalence of KC in our patient population, compared with previous reports in the literature, is much lower. The similar corneal indices in both groups suggest the absence of permanent corneal deformation due to VKC.

Long-term efficacy of abatacept in pediatric patients with idiopathic uveitis: a case series.

BACKGROUND: Non-infectious uveitis represents one of the most common causes of blindness, even at pediatric age; in particular, idiopathic chronic uveitis can pose significant difficulties during treatment, due to a partial response to TNF-α antagonists. To date, very few case series exist describing the treatment of idiopathic uveitis not adequately controlled by TNF-α antagonists. The aim of our study is to describe the role of abatacept in achieving remission in patients with idiopathic uveitis previously treated with TNF-α antagonists, and to assess how long abatacept efficacy is maintained during follow-up. The treatment's safety profile and tolerability were also specifically investigated. METHODS: Three patients affected with chronic idiopathic uveitis, who have been treated with abatacept due to loss of efficacy of TNF-α antagonists, were reviewed. Details of the demographic and clinical characteristics were recorded, and a summary of the medical history was obtained. Patients were regularly reviewed in the ophthalmology and rheumatology clinics. Assessment of their ocular condition was characterized according to the Standardization of Uveitis Nomenclature (SUN) group. RESULTS: In our patients, abatacept was able to induce remission and to discontinue systemic corticosteroids after a mean of 30 weeks; the drug maintained its efficacy through a long follow-up period (42, 33, and 18 months respectively), with an excellent safety profile. CONCLUSION: Our small case series seems to suggest abatacept to be a promising therapy in children affected with chronic idiopathic uveitis not adequately controlled by TNF-α antagonists.

Tacrolimus vs. cyclosporine eyedrops in severe cyclosporine-resistant vernal keratoconjunctivitis: A randomized, comparative, double-blind, crossover study.

BACKGROUND: Vernal keratoconjunctivitis (VKC) is a chronic sight-threatening ocular disease. Topical cyclosporine A (Cyc) has been widely administered as a steroid-sparing drug, although in about 7-10% of cases, it has been ineffective. The purpose of this study was to evaluate the efficacy of 0.1% topical tacrolimus (Tcr) in patients with severe VKC who failed to respond to 1% Cyc eyedrops. METHODS: Consecutive patients with severe, Cyc-resistant VKC were enrolled in a double-blind, comparative, crossover (DBCO) trial; all patients were treated with 1% Cyc in one eye and 0.1% Tcr in the other eye for 3 wk. After a washout period of 7 days, patients were instructed to cross over the medications for three additional weeks. Objective ocular score, subjective score, and quality-of-life questionnaires (QoLQ) were collected during the trial. Blood samples were drawn to assess several safety parameters. RESULTS: Thirty patients have been enrolled (mean age 9.05 ± 2.12 yr). In each of the two phases of the DBCO trial, a significant improvement in objective and subjective scores was observed in the eyes treated with 0.1% Tcr (p < 0.001). Likewise, the quality of life significantly improved despite only half the eyes being successfully treated. Serum creatinine and blood parameters were constantly within the normal range, and both blood Cyc and Tcr concentrations remained below the lowest detectable levels. CONCLUSIONS: Topical Tcr is very effective and safe in the short term for patients suffering from severe VKC resistant to topical Cyc.

Increased prevalence of growth hormone deficiency in patients with vernal keratoconjuntivitis; an interesting new association.

INTRODUCTION: Vernal keratoconjunctivitis (VKC) is a chronic conjunctivitis that mainly affects children living in temperate areas. The notable difference between genders and VKC's resolution with puberty have persistently suggested a role of hormonal factors in VKC development. OBJECTIVE: To describe six cases of males with VKC and growth hormone deficiency (GHD) reported as a long-term follow-up during rhGH treatment. METHODS: Six consecutive male patients (median age at GHD diagnosis 9.7, range 7.9 to 13.1 years) with VKC, were recruited from July 2005 to July 2013 at the Paediatric Endocrinology Unit of Anna Meyer Children's Hospital in Florence, Italy. In these patients, anthropometric data were collected periodically. In three of these patients, data were collected to near-adult or adult height. RESULTS: Familial history was uneventful for all patients. The target height was normal, ranging from 0.65 standard deviation scores (SDS) to 2.01 SDS. The patients showed a normal birth-weight (from -1.21 to 1.35 SDS) and birth-length (from -0.93 to 1.21 SDS). At GHD diagnosis, all of the patients exhibited demonstrated important growth retardation (from -2.05 to -2.78 SDS). Plasmatic concentrations of IGF-1 and IGFBP-3 were low (from -1.85 to -3 SDS and from -1.81 to -2.76 SDS, respectively). GH stimulation tests showed classic GHD symptoms in all of the patients. Pubertal onset was normal. All of the patients treated with rhGH responded well to rhGH treatment. Adult height, evaluated in three patients, was in accordance with their target height. CONCLUSIONS: To our current knowledge, we have described for the first time six patients affected by VKC with GH deficiency, in some of whom we performed a long-term follow-up to adult height. Further studies will be needed to establish whether GHD may be a common feature of VKC patients. Nevertheless, it appears to be useful to carefully follow statural growth of VKC patients, while the possibility of a GH deficiency must to be taken into account in the presence of growth failure.