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

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

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

Myopie de l’enfant

La myopie est une anomalie réfractive, enjeu mondial de santé publique, essentiellement due à une augmentation de longueur axiale du globe oculaire. La myopie est en forte augmentation dans le monde, revêtant un aspect « d’épidémie mondiale de la myopie ». Chez les enfants de moins de 6 ans, 20 % présentent des anomalies dont les plus fréquentes sont essentiellement les anomalies réfractives, suivies par le strabisme et l’amblyopie. La myopie présente des risques majeurs de complications, corrélée à sa sévérité, comme le décollement de rétine, les néovaisseaux rétiniens, la cataracte précoce et le glaucome. Une myopie syndromique doit être recherchée devant toute myopie forte. Il est essentiel de dépister précocement et de reconnaître la myopie évolutive de façon à mettre en place des stratégies de freination. Les traitements les plus prometteurs incluent les activités d’extérieur, les verres correcteurs ou les lentilles de contact défocalisants, l’orthokératologie et les traitements pharmacologiques par atropine faiblement dosée

Prise en charge du glaucome dans le syndrome de Sturge-Weber-Krabbe

Le syndrome de Sturge-Weber-Krabbe est une atteinte rare (1/50000). Le glaucome est présent dans environ 30 % des cas. (glaucomes congénitaux :60%, glaucomes juvéniles ou de l adulte jeunes : 40%). La prise en charge est affaire d école. Notre étude a pour but l évaluation de notre prise en charge et une revue de la littérature sur les différents modes de prise en charge de l hypertonie (médicaux et chirurgicaux). Afin de pouvoir donner un arbre décisionnel. Matériel et méthodes : Nous présentons une étude pro et rétrospective de 14 patients suivis de 1991 à 2009, à l hôpital Robert Debré (6 patients) et au CHU d Amiens (8 patients). Ont été collectées : l âge de prise en charge, la présentation clinique, les traitements entrepris et leur durée d action, lesdonnées biométriques oculaires. Résultats : 8 personnes avaient une atteinte bi symptomatique (oculaire et cutanée), et 6 une atteinte trisymptomatique (oculaire, cutanée, neurologique). 9 glaucomes congénitaux secondaires (avant 2 ans), 3 glaucomes juvéniles (après 2 ans), 1 glaucome de l adulte jeune et une personne indemne de glaucome. 7 patients ont bénéficié d une prise en charge initiale chirurgicale avec adjonction d hypotonisant locaux, 6 ont bénéficié d une prise en charge uniquement médical (3 par b-bloquant, 1 par analogue des prostaglandine associé un alpha-agoniste, 1 par analogue des prostaglandine seule, un par alpha-agoniste et b-bloquant) dont 2 ont nécessité une intervention, 1 d un suivi simple. 7 patients furent traités par trabéculectomie avec un taux de réussite de 100% à 6 mois, et de 75% à 12 mois. Dans les patients traités par trabéculectomies, 4 nécessitèrent un retraitement (2 patients une nouvelle trabéculectomie, un patient 4 trabéculectomies dont deux avec antimitotique. Une sclérectomie profonde après échec du traitement médicamenteux. La tension intra-oculaire pré-opératoire est de 24,4 mmHg, la post-opératoire à 14,7 mmHg. La pachymétrie moyenne est de 644 . L acuité visuelle finale est retrouvée à 4/10, mais réduite à 3/10 chez les glaucomes congénitaux et infantiles. Les longueurs axiales comparées aux courbes de croissance bien que plus élevées sont parallèles aux normales après équilibre tensionnel. Conclusion : La prise en charge précoce du glaucome congénital est indispensable dans le Sturge-Weber-Krabbe. Le suivi doit être étroit et aidé de l anesthésie générale pour les enfants jeunes. Les traitements médicaux sont débutés en première intention sauf devant une buphtalmie majeure associée à un œdème cornéen imposant la chirurgie filtrante. En première intention, un b- bloquant sera prescrit. S il est insuffisant une intervention sera réalisée. En cas d échappement du contrôle tensionnel malgré la chirurgie une adjonction de collyre hypotonisant par un b- bloquant sera débutée, associée à un inhibiteur de l anhydrase carbonique en cas d insuffisance. L ajout des analogues des prostaglandines n est réservé qu au glaucome juvénile. L intervention de première intention, est la trabéculectomie, pour sa facilité de réalisation et son efficacité. Les chirurgies non perforantes doivent être réservées aux glaucomes juvéniles et de l adulte jeune. Les antimitotiques, les dispositifs de drainage et la cyclodestruction sont indiqués aux glaucomes réfractaires. L intégration des différentes données biométriques doit être réalisées pour pouvoir juger de l efficacité du traitement ainsi que de son adaptation.AMIENS-BU Santé (800212102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Chirurgie de l'oblique inférieur (indications et résultats à court et moyen terme)

Plusieurs techniques chirurgicales pour le traitement du strabisme avec élévation en adduction sont utilisées. L objectif de cette étude a été d évaluer les indications et les résultats à court et moyen terme après chirurgie de l oblique inférieur. Notre étude rétrospective a porté sur 56 patients opérés au CHU d Amiens présentant une déviation verticale et traités par antéroposition du muscle oblique inférieur. Les patients ont été suivis à J1, puis de 0 à 6 mois, de 7 à 12 mois et au-delà de 1 an. L âge moyen des patients était de 19,1 ans. Les étiologies de l élévation en adduction étaient les paralysies de l oblique supérieur, l élévation primaire en adduction et les étiologies d origine inconnue. Les patients présentaient un torticolis pour 60,7% des patients et une diplopie pour 25% d entre eux. La réalisation d une antéroposition a entrainé une diminution de l hypertropie en moyenne en position primaire de 10,5+ /-6,3 dioptries prismatiques(DP) à 3,4+/-2,8DP. La diminution de l hyperaction de l oblique inférieur a été de 2,6+/-0,7 à 0,5 +/-0,8. Le torticolis a été amélioré dans 68% des cas et la diplopie a disparu dans 57% des cas. L antéroposition de l oblique inférieur a montré des résultats postopératoires très satisfaisants sur l hypertropie et l hyperaction de l oblique inférieur et des résultats satisfaisants sur les signes fonctionnels que sont le torticolis et la diplopie. Une analyse bibliographique a comparé les résultats de notre étude et celles de la littérature en fonction des techniques chirurgicales utilisées. Notre étude a montré l efficacité de cette technique chirurgicale dans le traitement des élévations en adduction.AMIENS-BU Santé (800212102) / SudocSudocFranceF