Gene therapies in pediatric ophthalmology

Genetic pediatric eye disease frequently leads to severe vision impairment or blindness. Voretigene neparvovec is the first approved gene therapy for an inherited retinal dystrophy (IRD). Voretigene neparvovec has been shown to be well tolerated and safe, with encouraging results in terms of efficacy, mainly when administered early in childhood. While we assisted at the first gene therapy available in clinical practice for an IRD, some questions remain unanswered, especially when gene therapy is delivered in young children. We review here the most recent reports and promising ongoing studies concerning various approaches on gene therapy in pediatric ophthalmology

Novel Insights in the Management of Vernal Keratoconjunctivitis (VKC): European Expert Consensus Using a Modified Nominal Group Technique

Introduction: Vernal keratoconjunctivitis (VKC) is a rare, severe allergic ocular disease, typically occurring in children and adolescents, that can have a significant impact on quality of life and lead to visual impairment. Long-term treatment may be necessary to tackle chronic inflammation and topical corticosteroid dependency must be minimised due to the risk of complications. There is a need for unified clinical guidance to aid the assessment, diagnosis and management of VKC across Europe. The aim of this expert panel (the EUR-VKC Group) was to provide clear guidance for primary care physicians and general ophthalmologists involved in the diagnosis and management of VKC. Methods: An expert group of seven European ophthalmologists was convened and a modified nominal group technique used to develop key recommendations on VKC management. The recommendations were subject to up to two rounds of voting using a 5-point Likert scale to ascertain consensus and the strength of each recommendation. Consensus was set at a predetermined threshold of ≥ 75.0% of experts selecting 'Strongly agree' or 'Agree'. Results: A total of 47 recommendations were developed relating to the assessment of key of VKC, guidance on who and when to refer, as well as treatment-escalation pathways, long-term follow-up, and supportive care and education. All recommendations reached consensus after two rounds. The group emphasise how timely diagnosis and treatment initiation that is appropriate to disease severity are crucial to benefit patients with VKC. Patients with signs ('red flags') indicating severe VKC, or persistent mild-to-moderate VKC that is non-responsive following 2-4 weeks of treatment, should be referred to a sub-specialist. Conclusion: The EUR-VKC Group provides recommendations on the assessment, diagnosis, management, referral and follow-up of patients with VKC. It also provides a framework to facilitate collaboration between primary care physicians, general ophthalmologists and sub-specialists to improve the outcomes for patients with VKC.info:eu-repo/semantics/publishedVersio

A Randomized, Controlled Trial of Cyclosporine A Cationic Emulsion in Pediatric Vernal Keratoconjunctivitis: The VEKTIS Study

Purpose Vernal keratoconjunctivitis (VKC) is a chronic, allergic, and potentially severe ocular disease affecting children and adolescents that can lead to impaired quality of life (QoL) and loss of vision. This study evaluated the efficacy and safety of an investigational therapy for severe VKC, cyclosporine A (CsA) cationic emulsion (CE), an oil-in-water emulsion with increased bioavailability versus conventional CsA formulations. Design The VErnal KeratoconjunctiviTIs Study (VEKTIS) is a phase 3, multicenter, double-masked, vehicle-controlled trial. Participants Pediatric patients (4 to younger than 18 years) with active severe VKC (grade of 3 or 4 on the Bonini severity scale) and severe keratitis (corneal fluorescein staining [CFS] score of 4 or 5 on the modified Oxford scale). Methods One hundred sixty-nine patients were randomized to CsA CE 0.1% (1 mg/ml) eye drops 4 times daily (high dose), CsA CE twice daily (low dose) plus vehicle twice daily, or vehicle 4 times daily for 4 months. Main Outcome Measures The primary end point was a mean composite score that reflected CFS, rescue medication use (dexamethasone 0.1% 4 times daily), and corneal ulceration over the 4 months. Results Differences in least-squares means versus vehicle for the primary end point were statistically significant for both the high-dose (0.76; P = 0.007) and the low-dose (0.67; P = 0.010) groups, with treatment effect mainly driven by CFS score. Significant differences were found between both active treatment groups and vehicle for use of rescue medication. Vernal keratoconjunctivitis symptoms and patient QoL (assessed by visual analog scale and the Quality of Life in Children with Vernal Keratoconjunctivitis questionnaire) improved in all 3 groups, with significant improvements for high-dose CsA CE versus vehicle. Conclusions The efficacy of high-dose CsA CE in improving keratitis, symptoms, and QoL for those with severe VKC was demonstrated in these study patients. In addition, in this study cohort, CsA CE was well tolerated

12-Month Results of Cyclosporine A Cationic Emulsion in a Randomized, Study in Patients With Pediatric Vernal Keratoconjunctivitis

Abstract Purpose To assess the safety and efficacy of cyclosporine A cationic emulsion (CsA CE) 0.1% eye drops in pediatric patients with severe active vernal keratoconjunctivitis (VKC). Design Multicenter, double-masked, randomized control trial 8-month safety analysis Methods Of 169 patients (age range, 4-17 years) initially randomized in the 4-month VEKTIS study, 142 entered the 8-month follow-up period during which CsA CE patients remained on their original regimen (CsA CE four times daily [QID, high-dose] or CsA CE twice daily [BID, low-dose] + vehicle BID) and vehicle patients were allocated to one of these 2 active regimens. Main outcome measures were safety, including treatment-emergent adverse events, and efficacy, including corneal fluorescein staining (CFS) score. Results Improvements in CFS score, rescue medication use, key VKC symptoms (photophobia, tearing, itching, and mucous discharge), and quality of life (QoL) assessed by QUICK questionnaire observed with CsA CE compared with vehicle during the 4-month evaluation period remained stable during the 8-month follow-up period, with the high-dose regimen continuing to provide greater benefits in most efficacy measures. CsA CE was well tolerated. Treatment-related treatment-emergent adverse events during the 12-month study were reported in 15 (20.8%) and 11 (15.7%) of the CsA CE high-dose and low-dose patients, respectively, most commonly instillation site pain (13.9% and 7.1%), respectively). Laboratory data, vital signs, slit lamp examination, best-corrected distance visual acuity, and intraocular pressure raised no safety concerns. Conclusions Improvements in keratitis, symptoms, and QoL achieved after CsA CE treatment for 4 months remained stable over the 8-month follow-up period. CsA continued to maintain a favorable safety profile

The FLURESP European commission project. cost-effectiveness assessment of ten public health measures against influenza in Italy. is there an interest in COVID-19 pandemic?

Background: The FLURESP project is a public health research funded by the European Commission, with the objective to design a methodological framework to assess the cost-effectiveness of existing public health measures against human influenza pandemics. A dataset has been specifically collected in the frame of the Italian health system. As most of interventions against human influenza are relavant against other respiratory diseases pandemics, potential interests in COVID-19 are discussed. Methods: Ten public health measures against human influenza pandemics pandemic were selected to be also relevant to other respiratory virus pandemics such as COVID 19: individual (hand washing, using masks), border control (quarantine, fever screening, border closure), community infection (school closure, class dismissal, social distancing, limitation of public transport), reduction of secondary infections (implementation of antibiotic therapy guidelines), pneumococcal vaccination for at-risk people, development of Intensive Care Unit (ICU) capacity, implementation of life support equipments in ICU, screening interventions, vaccination programs targeting health professional and targeting general population. Results: Using mortality reduction as effectiveness criteria, the most cost-effective strategies are "reduction of secondary infections" and "implementation of life support equipment in ICU". The least cost-effective option whatever the level of pandemic events are screening interventions and mass vaccination. Conclusions: A number of intervention strategies against human influenza pandemics appears relevant against every respiratory virus, including the COVID-19 event. Measures against pandemics should be considered according to their expected effectiveness but also their costs for the society because they impose substantial burden to the population, confirming the interest of considering cost-effectiveness of public health measures to enlighten decision making

COVID-19 outbreak and increased risk of amblyopia and epidemic myopia: Insights from EUROCOVCAT group

The most common cause of vision impairment in children is amblyopia. It is defined as impaired visual acuity in one or both eyes that is present with no demonstrable abnormality of the visual pathway and is not immediately resolved by wearing glasses. After the World Health Organization (WHO) recognized COVID-19 as a global pandemic on March 11, 2020, widespread changes and restrictions to social and sanitary practices have presented significant issues in access to eye care during the COVID-19 pandemic. A reduction of more than 80% in pediatric eye care volume up to its total cessation has been observed in different departments. In this scenario, reduced or absent eyesight, due to delay in timely treatment of amblyopic conditions, could create major, long-lasting effects on all aspects of life, including daily personal activities, interacting with the community, school and work opportunities and the ability to access public services. Processes coming out of lockdown should be gradually easing restrictions giving priority to ophthalmology and eye care facilities so that amblyopia does not remain unattended and irreversible as in adults due to lack of timely treatments. If not reversible, this process could lead to a dramatic increase in disability and unsustainable social costs for many governments

COVID-19 outbreak and increased risk of amblyopia and epidemic myopia: Insights from EUROCOVCAT group

The most common cause of vision impairment in children is amblyopia. It is defined as impaired visual acuity in one or both eyes that is present with no demonstrable abnormality of the visual pathway and is not immediately resolved by wearing glasses. After the World Health Organization (WHO) recognized COVID-19 as a global pandemic on March 11, 2020, widespread changes and restrictions to social and sanitary practices have presented significant issues in access to eye care during the COVID-19 pandemic. A reduction of more than 80% in pediatric eye care volume up to its total cessation has been observed in different departments. In this scenario, reduced or absent eyesight, due to delay in timely treatment of amblyopic conditions, could create major, long-lasting effects on all aspects of life, including daily personal activities, interacting with the community, school and work opportunities and the ability to access public services. Processes coming out of lockdown should be gradually easing restrictions giving priority to ophthalmology and eye care facilities so that amblyopia does not remain unattended and irreversible as in adults due to lack of timely treatments. If not reversible, this process could lead to a dramatic increase in disability and unsustainable social costs for many governments

COVID-19 outbreak and increased risk of amblyopia and epidemic myopia: Insights from EUROCOVCAT group

The most common cause of vision impairment in children is amblyopia. It is defined as impaired visual acuity in one or both eyes that is present with no demonstrable abnormality of the visual pathway and is not immediately resolved by wearing glasses. After the World Health Organization (WHO) recognized COVID-19 as a global pandemic on March 11, 2020, widespread changes and restrictions to social and sanitary practices have presented significant issues in access to eye care during the COVID-19 pandemic. A reduction of more than 80% in pediatric eye care volume up to its total cessation has been observed in different departments. In this scenario, reduced or absent eyesight, due to delay in timely treatment of amblyopic conditions, could create major, long-lasting effects on all aspects of life, including daily personal activities, interacting with the community, school and work opportunities and the ability to access public services. Processes coming out of lockdown should be gradually easing restrictions giving priority to ophthalmology and eye care facilities so that amblyopia does not remain unattended and irreversible as in adults due to lack of timely treatments. If not reversible, this process could lead to a dramatic increase in disability and unsustainable social costs for many governments

Future directions in managing aniridia-associated keratopathy

Congenital aniridia is a panocular disorder that is typically characterized by iris hypoplasia and aniridia-associated keratopathy (AAK). AAK results in the progressive loss of corneal transparency and thereby loss of vision. Currently, there is no approved therapy to delay or prevent its progression, and clinical management is challenging because of phenotypic variability and high risk of complications after interventions; however, new insights into the molecular pathogenesis of AAK may help improve its management. Here, we review the current understanding about the pathogenesis and management of AAK. We highlight the biological mechanisms involved in AAK development with the aim to develop future treatment options, including surgical, pharmacological, cell therapies, and gene therapies