Retinal detachment following retinopathy of prematurity in France: Screening and treatment pathways.

AIM: Preterm children are highly vulnerable to sensorial impairments through Retinopathy Of Prematurity (ROP). The objective was to determine whether some cases of ROP requiring surgery could be secondary to deficiencies in care pathways. METHODS: Descriptive study of neonatal characteristics and the screening/treatment pathways of children treated for stage ≥4A ROP from 2009 to 2020 in a referral unit in France. RESULTS: Twenty-five preterm children (44 eyes) were included: median gestational age was 25 weeks, and median birthweight was 700 grams. Eighty-four per cent had received at least one fundus examination, 50% of which were completed on time. At the time of retinal detachment diagnosis, only 36% of the children had received laser or anti-vascular endothelial growth factor (VEGF) intra-vitreal injection. ROP stage was only reported in 8%, and the zone or type was reported in 16% of the files. CONCLUSION: The risk of blindness and the effectiveness of laser or anti-VEGF treatment highlight the need to enhance screening and treatment practices in France.

EPHA2 biallelic disruption causes syndromic complex microphthalmia with iris hypoplasia.

Disruption of any of the ocular development steps can result in ocular defects such as microphthalmia, coloboma and anterior segment dysgeneses including aniridia and cataract. All of these anomalies can be isolated or seen in association with each other. Except for aniridia (almost exclusively due to PAX6 mutations), most of these congenital ocular malformations are related to a wide genetic heterogeneity, as hundreds of genes are implied in ocular development. Here we describe a patient presenting with bilateral microphthalmia, congenital cataract, corneal dystrophy and iris hypoplasia, associated with extra-ocular features, who underwent an analysis of 119 ocular development related genes. Genetic testing revealed the presence of two truncating variants in the EPHA2 gene. While EPHA2 mutations are mainly known to be responsible for isolated dominant congenital cataract, we report here the first case of complex anterior segment dysgenesis caused by a biallelic EPHA2 mutation. This gene should be screened in case of aniridia with a negative PAX6 testing, as the ocular features of our patient clearly mimic those of PAX6 mutated patients. This observation enlarges the phenotype associated with EPHA2 variations and rise the insight of a possible PAX6-EPHA2 interaction that needs further investigations. Moreover, despite a great variability in ocular and extra-ocular phenotypes, mutations type and inheritance pattern, a possible genotype-phenotype correlation can also be drawn for this gene.

Ophthalmological Impairments at Five and a Half Years after Preterm Birth: EPIPAGE-2 Cohort Study.

We report the 51/2 year prevalence of visual and oculomotor impairments in preterm children born at 24−34 weeks' gestation (WG) using the population-based cohort study EPIPAGE-2, set in France, 2011. The main outcomes were imputed prevalence of refractive errors (REs), strabismus, and binocular visual acuity (VA). Children were clinically assessed by specially trained pediatricians. The population was also analyzed in terms of cerebral palsy at 51/2 years (no CP, stage 1, stage 2, or stage 3−5) and retinopathy of prematurity in the neonatal period (no ROP, stage 1 or 2, or severe ROP). Among the 4441 children included, 2718 (weighted percentage 58.7%) were clinically assessed. REs were reported in 43.1% (95% confidence interval 37.6−48.4), 35.2% (32.7−37.6), and 28.4% (25.0−31.8) of children born at 24−26, 27−31, and 32−34 WG (p < 0.01), respectively; strabismus rates were 19.5% (14.6−24.4), 14.8% (12.9−16.7), and 8.3% (6.2−10.4) (p < 0.001), respectively. Moderate/severe visual deficiencies (VA < 3.2/10) were present in 1.7% (0.2−3.3) of children born at 24−26 WG, and in less than 1% in other groups. A suboptimal VA 5/10−6.3/10 was measured in 40.6% (35.3−45.8) of children born at 24−26 WG, 35.8% (33.5−38.1) at 27−31 WG, and 33.7% (30.4−37.0) at 32−34 WG. CP and ROP were associated with strabismus and RE. The association between CP and VA was strong, while it was not observed for ROP. In this large cohort of preterm-born children, we found a high prevalence of RE and strabismus regardless of WG, supporting the need for specific attention in this population. High prevalence of suboptimal VA could be challenging for these children at the age of reading and writing acquisition.

Congenital cataract surgery: long-term refractive outcomes of a new intraocular lens power correction formula.

PURPOSE: The final refraction after intraocular lens (IOL) implantation remains a challenge in the management of paediatric cataracts. No consensual guidelines exist for the choice of IOL power. The aim of this study was to validate a method of IOL power calculation by evaluating the final refractive error in all patients with IOL implantation operated at our institution. METHODS: We retrospectively studied all children under 7 years of age who underwent cataract surgery with IOL implantation at our institution between 2010 and 2015. Intraocular lens (IOL) power was calculated as follows: After B-scan determination of the emmetropic IOL power, a reduction of 40%, 35%, 30%, 25%, 20%, 15%, 10% and 5% was applied to children 0-3, 3-6, 6-12, 12-18, 18-24, 24-30, 30-36, 36-48 months, respectively. The following data were collected: follow-up, age at surgery, uni- or bilaterality, implanted IOL power and final refraction. RESULTS: During this period, 81 children (125 eyes) met the inclusion criteria with a median follow-up of 60 months (36-97). The median age at surgery was 6.61 months (0.76-48). We included 52 children with bilateral cataract (96 eyes) and 29 children with unilateral cataract (29 eyes). The mean implanted IOL power was 23.3 ± 4.6 diopters (D). The mean spherical equivalent at last follow-up was 0.07 ± 3.5 D. CONCLUSION: Our undercorrection formula for IOL implantation after congenital cataract surgery leads to long-term refractive results globally close to emmetropia.

Evaluation and modification of French screening guidelines for retinopathy of prematurity.

PURPOSE: To evaluate the current French screening guidelines for retinopathy of prematurity (ROP) and to suggest modifications to it. METHODS: In this multicentric retrospective, noncomparative, interventional case series we included infants with a gestational age (GA) ≤32 weeks who were screened for ROP by fundus examination between 2011 and 2018. Main Outcome Measures were the presence of ROP and the need for treatment. RESULTS: A total of 2246 children with a mean GA of 28.9 ± 2.0 weeks and mean birth weight (BW) of 1141.1 ± 332.0 g were screened. Retinopathy of prematurity (ROP) was found in 683 infants (30.4%), of whom 145 (6.5%) had type 2 ROP and 58 (2.6%) had type 1 ROP. Mean GA of infants with type 1 ROP needing treatment was 25.9 + 1.5 weeks (range: 23.6-30) and mean BW was 774.1 ± 173.7 g (range: 540-1400). Both GA and BW had an impact on the development of type 1 and 2 ROP. None of the infants needing treatment had a GA of 31 weeks or more. None of the children needed treatment before 33 weeks of postmenstrual age (PMA) or 6 weeks of postnatal age (PNA). CONCLUSION: It seems possible to decrease the screening of premature infants to ≤31 weeks of GA and to start screening at 31 weeks PMA for infants having a GA < 26 weeks and at 6 weeks PNA for more mature children.

Screening for Retinopathy of Prematurity in Very Preterm Children: The EPIPAGE-2 Cohort Study.

INTRODUCTION: Retinopathy of prematurity (ROP) is a blinding disease that requires screening by retinal examination. Screening practices are rarely evaluated. We aimed to determine the prevalence of ROP screening in very preterm infants and individual- and center-related factors associated with ROP screening. METHODS: Data were extracted from the EPIPAGE-2 cohort, a French prospective population-based study of premature births in 2011. Children born before 32 weeks' gestation (WG) without severe malformation and alive at the recommended time for ROP screening were included. Outcome measures were achievement of ROP screening and compliance with recommended screening timeline. Individual- and center-related factors associated with both measures were studied using mixed models. RESULTS: Among 3,077 eligible infants, 2,169 (70.5%) had a ROP screening, ranging from 96% at 24 WG to 50% at 31 WG. Large variability among units was observed. Individual characteristics associated with screening were low gestational age, low birth weight, severe bronchopulmonary dysplasia or neurological lesions, and transfer between neonatal units during the screening period. Odds of screening were higher in neonatal units using wide-angle imaging (odds ratio 2.65 [95% confidence interval 1.17-6.01]) but decreased in units without a local protocol for ROP screening (0.03 [0.01-0.09]). Among screened children, 1,641/2,169 (75.7%) were screened according to recommended timeline. Delayed screening was associated with low gestational age, severe bronchopulmonary dysplasia or necrotizing enterocolitis, and absence of local protocol for ROP screening. DISCUSSION/CONCLUSIONS: In this large cohort study of infants born very preterm, almost one-third were not screened for ROP. Children most at risk for ROP were the best screened but often with delay. The higher compliance of neonatal units using wide-angle imaging systems supports its use.

Treatment outside the Recommended Guidelines for Retinopathy of Prematurity (ROP): Prevalence, Characteristics, and Issues.

This study aims to assess the prevalence and characteristics of preterm infants with retinopathy of prematurity (ROP) treated outside the recommended guidelines. In this retrospective monocentric cohort, we included all premature children treated in our department for ROP by laser photoablation or anti-VEGF intravitreal injection. The main outcome was treatment of both eyes for ROP less severe than pre-threshold type 1, treated outside ETROP guidelines. A total of 114 children received treatment for ROP in our department, among whom 32 (28.1%) children received treatment for indications outside the ETROP guidelines for both eyes. The indications outside the guidelines were persistent stage 2 or 3 ROP that showed no evidence of regression after 41 weeks of corrected gestational age (11 children; 34.4%), pre-plus stage (11; 34.4%), difficulties in disease staging (7; 21.9%), type 2 ROP with plus disease (2; 6.2%), and treatment due to logistical difficulties (1; 3.1%; hospitalized in neonatal units hundreds of miles away from our department, with no fundus examination possible in the neonatal unit). To resume, in our cohort, 28.1% of children received treatment for ROP less severe than pre-threshold type 1 both eyes. The main indications for off-label treatment were the persistence of active ROP during follow-up and the presence of pre-plus-stage disease. Our data suggest the need to update ROP treatment criteria to reflect real-life practices. Additional studies are required in order to evaluate the long-term benefits and side effects of treatments outside the recommended indications, and to establish revised treatment guidelines.

Cataract Surgery with Primary Lens Implantation in Children with Chronic Uveitis.

PURPOSE: To evaluate the evolution of chronic uveitis in children undergoing cataract surgery with primary intraocular lens (IOL) implantation. METHODS: Twelve children with chronic uveitis underwent cataract surgery with primary posterior chamber intraocular lens (IOL) implantation. RESULTS: Fourteen eyes were implanted with a foldable hydrophobic acrylic IOL. The mean follow-up was 35.39 months (8.72-69.57). The mean BCDVA before surgery and at the end of follow-up was 1.11 (0.40-2.30; SD: 0.57) and 0.48 (0-3; SD: 0.77; p=0.007) respectively. The mean oral corticosteroids dosage after surgery and at the end of follow-up was 0.80 mg/kg/day (SD: 0.37) and 0.17 mg/kg/day (SD: 0.24; p=0.001) respectively. All patients except one were treated with methotrexate. Four patients (5 eyes) were additionally treated with anti-tumor necrosis factor agent. CONCLUSIONS: Cataract surgery with primary posterior chamber hydrophobic IOL implantation is possible and leads to a good visual recovery in cases of pediatric chronic uveitis. This surgery requires aggressive anti-inflammatory management with immunosuppressive drugs to control inflammation and reduce the corticosteroids dosage.

Combination of 5% phenylephrine and 0.5% tropicamide eyedrops for pupil dilation in neonates is twice as effective as 0.5% tropicamide eyedrops alone.

PURPOSE: Comparison of the efficacy of tropicamide eyedrops to the combination of 0.5% tropicamide and 5% phenylephrine eyedrops in order to achieve a proper dilation in premature infants undergoing screening for retinopathy of prematurity. METHODS: A prospective, randomized, double-blind study was conducted to compare the efficacy of two mydriatic regimens: one regimen consisting of three drops of 0.5% tropicamide (TTT regimen), the other regimen consisting of one drop of 5% phenylephrine and two drops of 0.5% tropicamide (PTT regimen). Thirty premature infants were enrolled and received both mydriatic regimens: one regimen in each eye. Outcomes were pupil dilation evaluated by the percentage of pupil diameter over cornea diameter, the percentage of pupil surface over cornea surface and the quality of the eye fundus examination. RESULTS: The percentage of pupil diameter over cornea diameter was 47.3% (±8.7) with the TTT regimen and 65.9% (±8.8) with the PTT regimen (p < 0.0001). The percentage of pupil surface over cornea surface was 23.1% (±8.3) with the TTT regimen and 43.8% (±7.3) with the PTT regimen (p < 0.0001). Thus, the pupil surface area was 1.9 times greater with the PTT than with the TTT regimen. Visualization of the retinal periphery was possible for 30 of 30 eyes dilated with the PTT regimen and for 16 of 30 eyes dilated with the TTT regimen (p < 0.0001). CONCLUSION: The dilated pupil surface area for the combination of 5% phenylephrine and 0.5% tropicamide was almost twice that for 0.5% tropicamide eyedrops alone and provided significantly superior quality of the eye fundus examination.

Pseudo-accommodation in non-amblyopic children after bilateral cataract surgery and implantation with a monofocal intraocular lens: prevalence and possible mechanisms.

BACKGROUND: Some pseudophakic patients implanted with a monofocal intraocular lens (IOL) have good near visual acuity (VA) with their distance correction. The objective was to evaluate the prevalence of pseudo-accommodation in children after bilateral cataract surgery, without amblyopia, and to define its mechanisms. METHODS: Observational study that took place in a pediatric ophthalmology department, Paris, France. A total of 68 eyes were included, 40 from 23 children and 28 from 14 adults, with a corrected distance VA above 20/25 and a normal near VA (20/25) with +3 addition. Pseudo-accommodation was defined as a near VA better than 20/50 with the distance correction and without addition. Prevalence of pseudo-accommodation was calculated in each group. In order to determine the possible mechanisms of pseudo-accommodation in children, we compared children with pseudo-accommodation and adults without pseudo-accommodation regarding several parameters: refraction, axial length, corneal topography, aberrometry, pupillary diameter and IOL shift after cyclopentolate instillation. RESULTS: Among the children group, 36 (90 %) had pseudo-accommodation versus 2 (7 %) in the adult group. We found that spherical equivalent, implant power, corneal multifocality and corneal higher-order aberrations (mainly coma and trefoil) were significantly higher in the pseudo-accommodation group, while pupil diameter and implant shift were not significantly different. CONCLUSIONS: Pseudo-accommodation has a high prevalence among non-amblyopic pseudophakic children. Several possible mechanisms have been found to explain pseudo-accommodation in children: a high power of the IOL and a small axial length, maximizing the effect of the IOL shift, corneal multifocality and corneal higher-order aberrations.

Ectopia lentis associated with primary congenital glaucoma.

PURPOSE: To describe 3 cases of ectopia lentis (EL) associated with primary congenital glaucoma (PCG) and differentiate between primary and secondary EL regarding pathogenesis. METHODS: We reviewed the clinical charts of 3 children previously diagnosed with congenital glaucoma who developed secondary EL. The following points were noted: medical and surgical history, refraction, keratometry, corneal diameter, axial length (AL), intraocular pressure, and cup/disc ratio. RESULTS: The 3 patients were respectively aged 12, 3, and 4 months. A trabeculectomy was performed in both eyes at 1-week interval in all cases. The EL was noted during follow-up controls. Lensectomy/vitrectomy was performed in 2 patients, in case of high astigmatism (>5.00 D) and/or the lens border visible in the pupillary area. Postoperative refraction was hyperopic. CONCLUSIONS: Ectopia lentis secondary to PCG should be differentiated from primary EL regarding pathogenesis. Anterior segment distension appears to be the principal mechanism in these cases. Postoperative hyperopia is observed despite the increased AL secondary to PCG. These biometric results are due to global distension of the globe, which also flattens the cornea with consequently lower refractive effect.

A new VCAN/versican splice acceptor site mutation in a French Wagner family associated with vascular and inflammatory ocular features.

PURPOSE: To detail the highly variable ocular phenotypes of a French family affected with an autosomal dominantly inherited vitreoretinopathy and to identify the disease gene. METHODS: Sixteen family members with ten affected individuals underwent detailed ophthalmic evaluation. Genetic linkage analysis and gene screening were undertaken for genes known to be involved in degenerative and exudative vitreoretinopathies. Qualitative reverse transcriptase-PCR analysis of the versiscan (VCAN) transcripts was performed after mutation detection in the VCAN gene. RESULTS: The first index patient of this French family was referred to us because of a chronic uveitis since infancy; this uveitis was associated with exudative retinal detachment in the context of a severe uncharacterized familial vitreoretinopathy. Genetic linkage was obtained to the VCAN locus, and we further identified a new pathogenic mutation at the highly conserved splice acceptor site in intron 7 of the VCAN gene (c.4004-2A>T), which produced aberrantly spliced VCAN transcripts. CONCLUSIONS: Extensive molecular investigation allowed us to classify this familial vitreoretinopathy as Wagner syndrome. This study illustrates the need to confirm clinical diagnosis by molecular genetic testing and adds new ocular phenotypes to the Wagner syndrome, such as vascular and inflammatory features.