Background: Children with atopic dermatitis (AD) appear to have higher skin permeation, which may increase the risk of systemic adverse events following administration of potent topical corticosteroids, such as clobetasol propionate (CP). However, the assessment of dermal absorption in a controlled clinical trial in children is not feasible. Using model-based approaches, this study aimed to characterise stratum corneum (SC) and systemic exposure to CP following topical application of the cream formulation, and to investigate its effects on circulating cortisol levels and growth velocity in children with AD. Methods: Physiologically-based pharmacokinetic (PBPK) and pharmacokinetic-pharmacodynamic (PKPD) modelling were utilised to describe the dermal absorption of CP in a virtual cohort of paediatric patients (1 - < 18 years old). Based on a skin impairment model for lesional and non-lesional skin, CP concentrations in the SC and in plasma were described over time. Simulation scenarios were then implemented to evaluate the effect of varying treatment conditions on the systemic exposure to CP, cortisol levels and growth velocity. Subsequently, clinical case scenarios were simulated to illustrate typical cases of AD in the paediatric population. Results: Surface area had the largest impact on the local and systemic concentrations of CP, while body site and age had a minor effect. When comparing similar surface areas and site of application, the dose, dosing regimen (o.d. vs. b.i.d.) and occlusion had no clinically relevant effect on the local and systemic exposure. Assuming a uniform application (1.2 mg/cm2), CP cream can be applied on up to 20% of the body surface area in children with AD over a period of 2 weeks. The short-term use of CP cream had no effect on the growth velocity of children with AD. Discussion: Surface area affected by AD should be considered when assessing the risk of systemic side effects. CP can be applied up to 20% of the BSA of a child (> 1 year old) without clinically relevant changes to circulating cortisol levels. In contrast to the systemic effects of oral corticosteroids, the short-term use of CP has no impact the growth velocity of paediatric subjects with AD.

Background: Children with atopic dermatitis (AD) appear to have higher skin permeation, which may increase the risk of systemic adverse events following administration of potent topical corticosteroids, such as clobetasol propionate (CP). However, the assessment of dermal absorption in a controlled clinical trial in children is not feasible. Using model-based approaches, this study aimed to characterise stratum corneum (SC) and systemic exposure to CP following topical application of the cream formulation, and to investigate its effects on circulating cortisol levels and growth velocity in children with AD. Methods: Physiologically-based pharmacokinetic (PBPK) and pharmacokinetic-pharmacodynamic (PKPD) modelling were utilised to describe the dermal absorption of CP in a virtual cohort of paediatric patients (1 - < 18 years old). Based on a skin impairment model for lesional and non-lesional skin, CP concentrations in the SC and in plasma were described over time. Simulation scenarios were then implemented to evaluate the effect of varying treatment conditions on the systemic exposure to CP, cortisol levels and growth velocity. Subsequently, clinical case scenarios were simulated to illustrate typical cases of AD in the paediatric population. Results: Surface area had the largest impact on the local and systemic concentrations of CP, while body site and age had a minor effect. When comparing similar surface areas and site of application, the dose, dosing regimen (o.d. vs. b.i.d.) and occlusion had no clinically relevant effect on the local and systemic exposure. Assuming a uniform application (1.2 mg/cm2), CP cream can be applied on up to 20% of the body surface area in children with AD over a period of 2 weeks. The short-term use of CP cream had no effect on the growth velocity of children with AD. Discussion: Surface area affected by AD should be considered when assessing the risk of systemic side effects. CP can be applied up to 20% of the BSA of a child (> 1 year old) without clinically relevant changes to circulating cortisol levels. In contrast to the systemic effects of oral corticosteroids, the short-term use of CP has no impact the growth velocity of paediatric subjects with AD.

Introduction: Accommodative esotropia (AET) is characterized by an esodeviation of the eyes due to uncorrected hyperopia, deficient fusional divergence, or high accommodative convergence. Decreasing hyperopia would reduce accommodative convergence and strabismus. We sought to review the existing evidence regarding the outcomes of refractive surgery in patients with AET. Methods: A four-database search (Pubmed, ISI Web of Science, Cochrane, and Scopus) was performed from inception to March 2021 using the MeSH terms: ("Refractive Surgical Procedures" OR "Keratomileusis, Laser In Situ" OR "Photorefractive Keratectomy" OR "Lens Implantation, Intraocular") AND ("Esotropia" OR "Accommodative Esotropia" OR "Refractive Esotropia” OR "Accommodative Strabismus"). No meta-analysis was performed due to studies’ heterogeneity. Results: Twenty-eight studies including 22 case series enrolling 378 patients and 6 case reports enrolling 8 patients were selected among 185 original abstracts. In the case series, a total of 378 patients (726 eyes) were recruited with an age range of 8-52 years. All studies reported mean follow-up periods of at least 12 months. Photorefractive keratectomy was performed in 7 studies, laser-assisted in situ keratomileusis in 9 studies, laser-assisted sub-epithelial keratectomy was reported in 1 study and 3 studies implanted IOL lenses, including iris-fixated and collamer. Considering the adult patients with a preoperative corrected esodeviation ≤10PD (n=129), all but five (3.9%) presented orthophoria or ≤10PD after refractive surgery. All children but 4 (4.5%) ended up with an esodeviation ≤10PD after surgery with those exceptions being in the range of 11 to 15PD. Six case reports were included in this review, comprising a total of 8 patients (16 eyes) with an age range of 7 to 34 years and a follow-up range of 4 to 48 months.Six case reports were included in this review, comprising a total of 8 patients (16 eyes) with an age range of 7 to 34 years and a follow-up range of 4 to 48 months. Discussion/Conclusion: Evidence produced so far points out that refractive surgery may be an alternative for spectacle correction for adults with accommodative esotropia ≤10PD. There is not enough evidence to recommend its use for patients under 18 years. The safety and predictability of these procedures for this purpose remains unclear as the selection criteria used for these patients are much different than the usual indications and there are no studies with long-term follow-up.

Introduction: Accommodative esotropia (AET) is characterized by an esodeviation of the eyes due to uncorrected hyperopia, deficient fusional divergence, or high accommodative convergence. Decreasing hyperopia would reduce accommodative convergence and strabismus. We sought to review the existing evidence regarding the outcomes of refractive surgery in patients with AET. Methods: A four-database search (Pubmed, ISI Web of Science, Cochrane, and Scopus) was performed from inception to March 2021 using the MeSH terms: ("Refractive Surgical Procedures" OR "Keratomileusis, Laser In Situ" OR "Photorefractive Keratectomy" OR "Lens Implantation, Intraocular") AND ("Esotropia" OR "Accommodative Esotropia" OR "Refractive Esotropia” OR "Accommodative Strabismus"). No meta-analysis was performed due to studies’ heterogeneity. Results: Twenty-eight studies including 22 case series enrolling 378 patients and 6 case reports enrolling 8 patients were selected among 185 original abstracts. In the case series, a total of 378 patients (726 eyes) were recruited with an age range of 8-52 years. All studies reported mean follow-up periods of at least 12 months. Photorefractive keratectomy was performed in 7 studies, laser-assisted in situ keratomileusis in 9 studies, laser-assisted sub-epithelial keratectomy was reported in 1 study and 3 studies implanted IOL lenses, including iris-fixated and collamer. Considering the adult patients with a preoperative corrected esodeviation ≤10PD (n=129), all but five (3.9%) presented orthophoria or ≤10PD after refractive surgery. All children but 4 (4.5%) ended up with an esodeviation ≤10PD after surgery with those exceptions being in the range of 11 to 15PD. Six case reports were included in this review, comprising a total of 8 patients (16 eyes) with an age range of 7 to 34 years and a follow-up range of 4 to 48 months.Six case reports were included in this review, comprising a total of 8 patients (16 eyes) with an age range of 7 to 34 years and a follow-up range of 4 to 48 months. Discussion/Conclusion: Evidence produced so far points out that refractive surgery may be an alternative for spectacle correction for adults with accommodative esotropia ≤10PD. There is not enough evidence to recommend its use for patients under 18 years. The safety and predictability of these procedures for this purpose remains unclear as the selection criteria used for these patients are much different than the usual indications and there are no studies with long-term follow-up.