Brain MRI findings and their association with visual impairment in young adolescents born very preterm.

PURPOSE: Very preterm birth increases risk for neonatal white matter injury, but there is limited data on to what extent this persists into adolescence and how this relates to ophthalmological outcomes. The aim of this study was to assess brain MRI findings in 12-year-old children born very preterm compared to controls and their association with concurrent ophthalmological outcomes. METHODS: We included 47 children born very preterm and 22 full-term controls (gestational age <32 and >37 weeks, respectively). Brain MRI findings were studied in association with concurrent ophthalmological outcomes at 12-year follow-up. RESULTS: Evans index (0.27 vs 0.25, p<0.001) and a proposed "posterior ventricle index" (0.47 vs 0.45, p=0.018) were increased in children born very preterm. Higher gestational age associated with larger corpus callosum area (ß=10.7, 95%CI 0.59-20.8). Focal white matter lesions were observed in 15 (32%) of very preterm children and in 1 (5%) of full-term controls. Increased posterior ventricle index increased risk for visual acuity ≤1.0 (OR=1.07×1011, 95%CI=7.78-1.48×1021) and contrast sensitivity <0.5 (OR=2.6×1027, 95%CI=1.9×108-3.5×1046). Decreased peritrigonal white matter thickness associated with impaired visual acuity (ß=0.04, 95%CI 0.002-0.07). CONCLUSION: More white matter lesions and evidence of lower white matter volume were found in children born very preterm compared with full-term controls at 12-year follow-up. The association between larger posterior ventricle index and reduced visual acuity and contrast sensitivity suggests disturbances of the posterior visual pathway due to diffuse white matter lesions.

Strabismus and refraction in non-syndromic craniosynostosis - A longitudinal study up to 5 years of age.

PURPOSE: To evaluate the refractive outcome and strabismus at 5 years of age, in children operated for various types of non-syndromic craniosynostosis, and further analyse the refractive and strabismic development over time. METHODS: Eighty-nine children, who had undergone operations for non-syndromic craniosynostosis, were examined at 5 years of age. These children also underwent ophthalmological examination preoperatively and up to 1 year after the operation. An age-matched control group including 32 healthy children was also recruited. Strabismus and eye motility were registered. Refraction was measured in cycloplegia. RESULTS: There was a difference regarding the refractive outcome between the different types of craniosynostosis. Higher values of hypermetropia were found in the metopic craniosynostosis group on both eyes. In the unicoronal craniosynostosis group, high values of hypermetropia and a higher degree of astigmatism were found on the side contralateral to the craniosynostosis. Strabismus was found in 11/88 children of whom 10/11 had unicoronal craniosynostosis. A vertical deviation on the side ipsilateral to the fused suture was highly prevalent (6/10 cases). Ophthalmological dysfunctions were rare in children operated for sagittal craniosynostosis. CONCLUSION: Ocular manifestations such as strabismus, astigmatism and anisometropia were highly prevalent in children operated for unilateral coronal craniosynostosis. Children operated for metopic craniosynostosis had higher rates of hypermetropia. The screening and follow-up protocols need to be tailored with regard to the type of craniosynostosis.

Central macular morphology and optic nerve fibre layer thickness in young adults born premature and screened for retinopathy of prematurity.

PURPOSE: To investigate central retinal morphology and optic retinal nerve fibre layer (RNFL) in prematurely born young adults and compare to term born controls. MATERIALS AND METHODS: The participants were 59 prematurely born individuals, with a birthweight ≤1.500 g, and 44 term born controls, all 25-29 years of age. Visual acuity (VA) and contrast sensitivity (CS) were assessed. The retinal macular thickness, ganglion cell-inner plexiform layer (GC-IPL) thickness and RNFL thickness were assessed with Cirrus optical coherence tomography (OCT). RESULTS: Central macular thickness was increased (mean 26.7 µm) in prematurely born individuals compared to controls. The macular GC-IPL was thinner (mean 3.84 µm), also when excluding those with previous retinopathy of prematurity (ROP) and those with neurological complications. Gestational age at birth and previous treatment of ROP were risk factors for a thicker macula, however, not for reduced GC-IPL. The average peripapillary RNFL was thinner (mean 4.61 µm) in the prematurely born individuals, also when excluding those with previous ROP and/or neurological complications. Within the prematurely born group, treated ROP was correlated with increased average RNFL. Further, both better VA and CS were associated with thinner optic nerve RNFL and thicker average GC-IPL. CONCLUSION: Macular and optic nerve morphology were influenced by premature birth as assessed with OCT in adult individuals. Gestational age at birth and treatment for ROP seemed to affect central macular thickness, and treated ROP affected the peripapillary RNFL. Thus, retinal sequelae remained in adulthood.

Treatment for retinopathy of prematurity in Sweden 2008-2021: Reduced gestational age of treated infants and remaining differences in treatment type and recurrence rates between hospitals.

PURPOSE: This study aimed to investigate various aspects of treatment for retinopathy of prematurity (ROP) in Sweden over the past 14 years, nationally and at a hospital level. METHODS: Data on screening and treatment for ROP in infants born in Sweden from 2008 to 2021 were extracted from the national ROP register, SWEDROP. During this period, Swedish screening guidelines were reduced from gestational age (GA) < 32 weeks to <31 weeks in 2012 and to <30 weeks in 2020. RESULTS: Altogether, 10 959 infants were screened and 600 infants treated for ROP during the study period. Parallel to changed guidelines, the number of screened infants decreased (p < 0.000) and the incidence of ROP and frequency of treatment increased (p < 0.001), while both remained similar in infants with a GA below 30 weeks. Among treated infants, GA and BW were reduced over the years (p < 0.001). Laser treatment (85.2% of primary treatments) became less common and anti-VEGF injections (13.6%) became more common over time (p < 0.001). Altogether 16 eyes were treated with the encircling band and 13 with vitrectomy. The total frequency of retreatment (32.7% of treated eyes) remained similar over time but was more common after primary anti-VEGF injection (67.7%) than laser treatment (27.2%). There were differences between the seven university hospitals regarding type of treatment and number of retreatments (p < 0.001). CONCLUSION: The frequency of treatment and retreatment for ROP remained similar over time, but the type of treatment changed and anti-VEGF injections became more common. Differences between treating hospitals emphasize the importance of centralizing the most severe cases.

Prognostic Value of Parenteral Nutrition Duration on Risk of Retinopathy of Prematurity: Development and Validation of the Revised DIGIROP Clinical Decision Support Tool.

Importance: The prognostic impact of parenteral nutrition duration (PND) on retinopathy of prematurity (ROP) is not well studied. Safe prediction models can help optimize ROP screening by effectively discriminating high-risk from low-risk infants. Objective: To evaluate the prognostic value of PND on ROP; to update and validate the Digital ROP (DIGIROP) 2.0 birth into prescreen and screen prediction models to include all ROP-screened infants regardless of gestational age (GA) and incorporate PND; and to compare the DIGIROP model with the Weight, IGF-1, Neonatal, and ROP (WINROP) and Postnatal Growth and ROP (G-ROP) models. Design, Setting, and Participants: This retrospective study included 11 139 prematurely born infants from 2007 to 2020 from the Swedish National Registry for ROP. Extended Poisson and logistic models were applied. Data were analyzed from August 2022 to February 2023. Main Outcomes and Measures: Any ROP and ROP requiring treatment were studied in relation to PND. ROP treatment was the outcome in DIGIROP models. Sensitivity, specificity, area under the receiver operating characteristic curve, and adjusted OR (aOR) with 95% CI were the main measures. Internal and external validations were performed. Results: Of 11 139 screened infants, 5071 (45.5%) were girls, and the mean (SD) gestational age was 28.5 (2.4) weeks. ROP developed in 3179 infants (29%), treatment was given in 599 (5%), 7228 (65%) had PND less than 14 days, 2308 (21%) had PND for 14 days or more, and 1603 (14%) had unknown PND. PND was significantly correlated with ROP severity (Spearman r = 0.45; P < .001). Infants with 14 days or more of PND vs less than 14 days had faster progression from any ROP to ROP treatment (adjusted mean difference, -0.9 weeks; 95% CI, -1.5 to -0.3; P = .004). Infants with PND for 14 days or more vs less than 14 days had higher odds of any ROP (aOR, 1.84; 95% CI, 1.62-2.10; P < .001) and of severe ROP requiring treatment (aOR, 2.20; 95% CI, 1.73-2.80; P < .001). Among all 11 139 infants, the DIGIROP 2.0 models had 100% sensitivity (95% CI, 99.4-100). The specificity was 46.6% (95% CI, 45.6-47.5) for the prescreen model and 76.9% (95% CI, 76.1-77.7) for the screen model. G-ROP as well as the DIGIROP 2.0 prescreen and screen models showed 100% sensitivity on a validation subset (G-ROP: sensitivity, 100%; 95% CI, 93-100; DIGIROP prescreen: sensitivity, 100%; 95% CI, 93-100; DIGIROP screen: sensitivity, 100%; 95% CI, 93-100), whereas WINROP showed 89% sensitivity (95% CI, 77-96). Specificity for each prediction model was 29% (95% CI, 22-36) for G-ROP, 38% (95% CI, 32-46) for DIGIROP prescreen, 53% (95% CI, 46-60) for DIGIROP screen at 10 weeks, and 46% (95% CI, 39-53) for WINROP. Conclusion and Relevance: Based on more than 11 000 ROP-screened infants born in Sweden, PND of 14 days or more corresponded to a significantly higher risk of having any ROP and receiving ROP treatment. These findings provide evidence to support consideration of using the updated DIGIROP 2.0 models instead of the WINROP or G-ROP models in the management of ROP.

Ophthalmological outcome of 6.5 years children treated for retinopathy of prematurity: a Swedish register study.

AIMS: To determine the ophthalmological outcome at 6.5 years of age in children treated for retinopathy of prematurity (ROP), and registered in the national Swedish National Register for ROP register. METHODS: Data on ROP, treatment and ophthalmological outcome were retrieved from the register. Visual acuity (VA), refractive errors and strabismus, together with visual impairment (VI) and any significant eye problem, defined as VA >0.5 logarithm of the minimal angle of resolution (logMAR) and/or strabismus and/or any refractive error were analysed. Risk factors such as sex, gestational age (GA), birth weight SD score, number of treatments and retreatments, postnatal age and postmenstrual age at first treatment were analysed. RESULTS: Follow-up data were available in 232 of 270 children born between 2007 and 2014 who had been treated for ROP. VI (VA >0.5 logMAR) was found in 32 (14%), strabismus in 82 (38%), refractive errors in 114 (52%) and significant eye problem in 143 (65%) children. Retreatment was a risk factor for VI and refractive errors. Male sex and neonatal brain lesion were risk factors for strabismus. An additional week of GA at birth reduced the risk for refractive errors, strabismus and significant eye problems. CONCLUSION: The results of the present study revealed a high number of eye problems in children treated for ROP, emphasising the need for long-term follow-up. Retreatment of ROP was a risk factor for VI, and emphasises the importance of an accurate first treatment for the long-term ophthalmological outcome.

Validation of DIGIROP models and decision support tool for prediction of treatment for retinopathy of prematurity on a contemporary Swedish cohort.

BACKGROUND/AIMS: Retinopathy of prematurity (ROP) is currently diagnosed through repeated eye examinations to find the low percentage of infants that fulfil treatment criteria to reduce vision loss. A prediction model for severe ROP requiring treatment that might sensitively and specifically identify infants that develop severe ROP, DIGIROP-Birth, was developed using birth characteristics. DIGIROP-Screen additionally incorporates first signs of ROP in different models over time. The aim was to validate DIGIROP-Birth, DIGIROP-Screen and their decision support tool on a contemporary Swedish cohort. METHODS: Data were retrieved from the Swedish national registry for ROP (2018-2019) and two Swedish regions (2020), including 1082 infants born at gestational age (GA) 24 to <31 weeks. The predictors were GA at birth, sex, standardised birth weight and age at the first sign of ROP. The outcome was ROP treatment. Sensitivity, specificity and area under the receiver operating characteristic curve (AUC) with 95% CI were described. RESULTS: For DIGIROP-Birth, the AUC was 0.93 (95% CI 0.90 to 0.95); for DIGIROP-Screen, it ranged between 0.93 and 0.97. The specificity was 49.9% (95% CI 46.7 to 53.0) and the sensitivity was 96.5% (95% CI 87.9 to 99.6) for the tool applied at birth. For DIGIROP-Screen, the cumulative specificity ranged between 50.0% and 78.7%. One infant with Beckwith-Wiedemann syndrome who fulfilled criteria for ROP treatment and had no missed/incomplete examinations was incorrectly flagged as not needing screening. CONCLUSIONS: DIGIROP-Birth and DIGIROP-Screen showed high predictive ability in a contemporary Swedish cohort. At birth, 50% of the infants born at 24 to <31 weeks of gestation were predicted to have low risk of severe ROP and could potentially be released from ROP screening examinations. All routinely screened treated infants, excluding those screened for clinical indications of severe illness, were correctly flagged as needing ROP screening.

Retrospective evaluation of ophthalmological and neurological outcomes for infants born before 24 weeks gestational age in a Swedish cohort.

OBJECTIVES: To retrospectively evaluate ophthalmological and neurological outcomes in a Swedish cohort of infants born before 24 weeks gestational age (GA) and explore risk factors for visual impairment. SETTING: Eye and paediatric clinics in Sweden. PARTICIPANTS: Infants screened for retinopathy of prematurity (ROP) (n=399), born before 24 weeks GA, 2007-2018. Cases were excluded if ophthalmological follow-up records could not be traced. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes were ophthalmological, including visual acuity (VA), refractive error, strabismus, nystagmus and cerebral visual impairment (CVI). Secondary outcomes comprised neonatal and neurological morbidities. Data were retrospectively retrieved from medical records. RESULTS: The 355 assessed children had a median GA of 23 weeks and 2 days and a median birth weight of 565 g. At the last available ophthalmological examination, the median age was 4.8 years (range 0.5-13.2 years). Nystagmus was recorded in 21.1%, strabismus in 34.8%, and 51.0% wore spectacles. Seventy-three of 333 (21.9%) were visually impaired, defined as being referred to a low vision clinic and/or having a VA less than 20/60 at 3.5 years of age or older. ROP treatment was a significant risk factor for visual impairment (OR 2.244, p=0.003). Visually impaired children, compared with children without visual impairment, more often had neurological deficits such as intellectual disability 63.8% versus 33.3% (p<0.001), epilepsy 21.1% versus 7.5% (p=0.001) and autism spectrum disorders 32.8% versus 20.9% (p=0.043). Nine of the 355 children had been diagnosed with CVI. CONCLUSIONS: Children born before 24 weeks GA frequently had visual impairment in association with neurological deficits. CVI was rarely diagnosed. A multidisciplinary approach for the evaluation and habilitation of these vulnerable infants is warranted. National follow-up guidelines need to be developed and implemented.

National cohort of infants born before 24 gestational weeks showed increased survival rates but no improvement in neonatal morbidity.

AIM: To describe survival and neonatal morbidities in infants born before 24 weeks of gestation during a 12-year period. METHODS: Data were retrieved from national registries and validated in medical files of infants born before 24 weeks of gestation 2007-2018 in Sweden. Temporal changes were evaluated. RESULTS: In 2007-2018, 282 live births were recorded at 22 weeks and 460 at 23 weeks of gestation. Survival to discharge from hospital of infants born alive at 22 and 23 weeks increased from 20% to 38% (p = 0.006) and from 45% to 67% (p < 0.001) respectively. Caesarean section increased from 12% to 22% (p = 0.038) for infants born at 22 weeks. Neonatal morbidity rates in infants alive at 40 weeks of postmenstrual age (n = 399) were unchanged except for an increase in necrotising enterocolitis from 0 to 33% (p = 0.017) in infants born at 22 weeks of gestation. Bronchopulmonary dysplasia was more common in boys than girls, 90% versus 82% (p = 0.044). The number of infants surviving to 40 weeks doubled over time. CONCLUSION: Increased survival of infants born before 24 weeks of gestation resulted in increasing numbers of very immature infants with severe neonatal morbidities likely to have a negative impact on long-term outcome.

Refraction and its development in young adults born prematurely and screened for retinopathy of prematurity.

PURPOSE: To evaluate refraction and its development in young adults born prematurely, screened for retinopathy of prematurity, and to compare with individuals of the same age born at term. MATERIALS AND METHODS: The participants were 59 preterms, with a birthweight of ≤ 1500 g, and 43 term-born controls, all born during 1988-1990. The refraction was measured in cycloplegia, and the spherical equivalent (SE) was calculated. The axial length (AL), anterior chamber depth and corneal radius (CR) were measured, and the AL/CR ratio was calculated. RESULTS: The mean SE was -0.5 dioptres (D) (SD 2.5) in right eyes (REs) and -0.4 D (SD 2.3) in left eyes (LEs) of preterms, and -0.2 D (SD 1.5) in REs and -0.2 D (SD 1.5) in LEs of controls. The distribution of refraction was wider in the preterm group compared to the control group. In the preterm group, 12% had a SE ≥ 1.5 D, but none of the controls. Ten preterms, but none of the controls, had anisometropia ≥ 1.0 D. The prevalence of astigmatism ≥ 1.0 D was higher in preterms than controls. The SE decreased around 1 D in both preterms and controls from 10 to 25 years of age. The AL and CR were shorter in the preterms; however, the AL/CR ratio was similar in both groups. Within the preterm group, cryotherapy was correlated with astigmatism, but not with SE and anisometropia at this age. CONCLUSION: Prematurely born individuals had higher prevalence of refractive errors in young adulthood compared to term-born controls.

Development and validation of a new clinical decision support tool to optimize screening for retinopathy of prematurity.

BACKGROUND/AIMS: Prematurely born infants undergo costly, stressful eye examinations to uncover the small fraction with retinopathy of prematurity (ROP) that needs treatment to prevent blindness. The aim was to develop a prediction tool (DIGIROP-Screen) with 100% sensitivity and high specificity to safely reduce screening of those infants not needing treatment. DIGIROP-Screen was compared with four other ROP models based on longitudinal weights. METHODS: Data, including infants born at 24-30 weeks of gestational age (GA), for DIGIROP-Screen development (DevGroup, N=6991) originate from the Swedish National Registry for ROP. Three international cohorts comprised the external validation groups (ValGroups, N=1241). Multivariable logistic regressions, over postnatal ages (PNAs) 6-14 weeks, were validated. Predictors were birth characteristics, status and age at first diagnosed ROP and essential interactions. RESULTS: ROP treatment was required in 287 (4.1%)/6991 infants in DevGroup and 49 (3.9%)/1241 in ValGroups. To allow 100% sensitivity in DevGroup, specificity at birth was 53.1% and cumulatively 60.5% at PNA 8 weeks. Applying the same cut-offs in ValGroups, specificities were similar (46.3% and 53.5%). One infant with severe malformations in ValGroups was incorrectly classified as not needing screening. For all other infants, at PNA 6-14 weeks, sensitivity was 100%. In other published models, sensitivity ranged from 88.5% to 100% and specificity ranged from 9.6% to 45.2%. CONCLUSIONS: DIGIROP-Screen, a clinical decision support tool using readily available birth and ROP screening data for infants born GA 24-30 weeks, in the European and North American populations tested can safely identify infants not needing ROP screening. DIGIROP-Screen had equal or higher sensitivity and specificity compared with other models. DIGIROP-Screen should be tested in any new cohort for validation and if not validated it can be modified using the same statistical approaches applied to a specific clinical setting.

Antenatal steroids and neurodevelopment in 12-year-old children born extremely preterm.

AIM: To investigate neurodevelopmental outcome in 12-year-old children born very preterm in relation to perinatal, neonatal and socioeconomic variables. To examine whether previously described positive effects of antenatal steroids on cognition persist at 12 years. METHODS: Prospective cohort, 78 children with gestational ages 22.7-31.9 weeks, born in 2004-2007 and examined at 12 years of age with cognitive, motor and visual motor integration tasks and compared to an age-matched control group (n = 50). Two preterm subgroups were studied: very preterm children (28-31 gestational weeks, n = 53) and extremely preterm children (22-27 gestational weeks, n = 25). RESULTS: The preterm children had significantly lower scores on all cognitive, motor and visual motor integration tasks than the controls. Gestational age and maternal education influenced associations differently in the two preterm subgroups. Also, severe retinopathy of prematurity demonstrated strong associations to outcome. In the extremely preterm group, administration of antenatal steroids was associated with better cognition, basic attention, word generation and motor skills. CONCLUSION: At 12 years of age, very preterm children born in the 2000s still have deficits across several neurodevelopmental domains compared to term-born peers. Administration of antenatal steroids has long-lasting associations to cognition and motor skills in extremely preterm-born children.

Strabismus, stereoacuity, accommodation and convergence in young adults born premature and screened for retinopathy of prematurity.

PURPOSE: The aim of the study was to evaluate strabismus, stereoacuity, accommodation and convergence in prematurely born young adults; screened for retinopathy of prematurity in the neonatal period and compare with term-born individuals of the same age. MATERIALS AND METHODS: The study participants included 59 prematurely born individuals with a birthweight of ≤1,500 grams and 44 term-born controls, all born during 1988-1990 in Stockholm County, Sweden. Ocular alignment was assessed with a cover test, stereoacuity with the TNO stereo test and the amplitude of accommodation and the near point of convergence with the Royal Air Force Rule. RESULTS: Seven of 59 (12%) preterms had manifest strabismus, 4/59 (7%) had esotropia and 3/59 (5%) exotropia. One of 44 (2%) controls had esotropia; no other controls had manifest strabismus. Stereoacuity was within normal limits in 38/59 (64%) preterms and 43/44 (98%) controls, p < 0.01; the difference remained after excluding those with strabismus. A neurological complication at 2.5 years of age was the strongest risk factor for subnormal stereoacuity within the preterm group after excluding those with strabismus. The mean amplitude of accommodation was poorer in the preterms than the controls in better (p < 0.05) and worse eyes (p < 0.05). The preterms were more likely to have an amplitude of accommodation below the minimum, according to Hofstetter's equation. There were no differences between the groups regarding the near point of convergence. CONCLUSION: Prematurely born young adults had a higher prevalence of strabismus, reduced stereoacuity and worse amplitude of accommodation than term-born controls.

Visual tracking at 4 months in preterm infants predicts 6.5-year cognition and attention.

BACKGROUND: Visual tracking of moving objects requires sustained attention and prediction of the object's trajectory. We tested the hypothesis that measures of eye-head tracking of moving objects are associated to long-term neurodevelopment in very preterm infants. METHODS: Visual tracking performance was assessed at 4 month's corrected age in 57 infants with gestational age <32 weeks. An object moved in front of the infant with sinusoidal or triangular (i.e. abrupt) turns of the direction. Gaze gain, smooth pursuit gain, and timing of gaze to object motion were analyzed. At 6.5 years the Wechsler Intelligence Scale for Children (WISC-IV), the Brown Attention Deficit Disorder (Brown ADD), and visual examination were performed. RESULTS: Gaze gain and smooth pursuit gain at 4 months were strongly related to all WISC-IV parameters at 6.5 years. Gaze gain for the triangular and sinusoidal motion patterns related similarly to the cognitive scores. For the sinusoidal motion pattern, timing related to most Brown ADD parameters. There were no statistically significant differences in associations dependent on motion pattern. Visual function did not influence the results. CONCLUSION: The ability to attend to and smoothly track a moving object in infancy is an early marker of cognition and attention at 6.5 years. IMPACT: Potential long-term implications of infant visual tracking of moving objects for school-age neurodevelopment has not been previously studied in very preterm infants. Early coordination of eye and head movements in gaze gain, smooth pursuit, and timing of gaze to object motion are closely associated with cognition and attention at 6.5 years. As related functions at 6.5 years include perceptual and verbal skills, working memory, processing speed and attention, predictive elements in gaze tracking of moving objects might be a suitable target for future intervention studies.

International Classification of Retinopathy of Prematurity, Third Edition.

PURPOSE: The International Classification of Retinopathy of Prematurity is a consensus statement that creates a standard nomenclature for classification of retinopathy of prematurity (ROP). It was initially published in 1984, expanded in 1987, and revisited in 2005. This article presents a third revision, the International Classification of Retinopathy of Prematurity, Third Edition (ICROP3), which is now required because of challenges such as: (1) concerns about subjectivity in critical elements of disease classification; (2) innovations in ophthalmic imaging; (3) novel pharmacologic therapies (e.g., anti-vascular endothelial growth factor agents) with unique regression and reactivation features after treatment compared with ablative therapies; and (4) recognition that patterns of ROP in some regions of the world do not fit neatly into the current classification system. DESIGN: Review of evidence-based literature, along with expert consensus opinion. PARTICIPANTS: International ROP expert committee assembled in March 2019 representing 17 countries and comprising 14 pediatric ophthalmologists and 20 retinal specialists, as well as 12 women and 22 men. METHODS: The committee was initially divided into 3 subcommittees-acute phase, regression or reactivation, and imaging-each of which used iterative videoconferences and an online message board to identify key challenges and approaches. Subsequently, the entire committee used iterative videoconferences, 2 in-person multiday meetings, and an online message board to develop consensus on classification. MAIN OUTCOME MEASURES: Consensus statement. RESULTS: The ICROP3 retains current definitions such as zone (location of disease), stage (appearance of disease at the avascular-vascular junction), and circumferential extent of disease. Major updates in the ICROP3 include refined classification metrics (e.g., posterior zone II, notch, subcategorization of stage 5, and recognition that a continuous spectrum of vascular abnormality exists from normal to plus disease). Updates also include the definition of aggressive ROP to replace aggressive-posterior ROP because of increasing recognition that aggressive disease may occur in larger preterm infants and beyond the posterior retina, particularly in regions of the world with limited resources. ROP regression and reactivation are described in detail, with additional description of long-term sequelae. CONCLUSIONS: These principles may improve the quality and standardization of ROP care worldwide and may provide a foundation to improve research and clinical care.

Ophthalmological findings in children with non-syndromic craniosynostosis: preoperatively and postoperatively up to 12 months after surgery.

AIMS: Craniosynostosis is a congenital condition characterised by premature fusion of one or more cranial sutures. The aim of this study was to analyse ophthalmic function before and after cranial surgery, in children with various types of non-syndromic craniosynostosis. METHODS: Children referred to Uppsala University Hospital for surgery of non-syndromic craniosynostosis were examined preoperatively. Visual acuity was measured with Preferential Looking tests or observation of fixation and following. Strabismus and eye motility were noted. Refraction was measured in cycloplegia and funduscopy was performed. Follow-up examinations were performed 6-12 months postoperatively at the children's local hospitals. RESULTS: One hundred twenty-two children with mean age 6.2 months were examined preoperatively. Refractive values were similar between the different subtypes of craniosynostosis, except for astigmatism anisometropia which was more common in unicoronal craniosynostosis. Strabismus was found in seven children, of which four had unicoronal craniosynostosis.Postoperatively, 113 children were examined, at mean age 15.9 months. The refractive values decreased, except for astigmatism and anisometropia in unicoronal craniosynostosis. Strabismus remained in unicoronal craniosynostosis. Two new cases with strabismus developed in unicoronal craniosynostosis and one in metopic, all operated with fronto-orbital techniques. No child had disc oedema or pale discs preoperatively or postoperatively. CONCLUSION: Ophthalmic dysfunctions were not frequent in children with sagittal craniosynostosis and preoperative ophthalmological evaluation may not be imperative. Children with unicoronal craniosynostosis had the highest prevalence of strabismus and anisometropia. Fronto-orbital techniques used to address skull deformity may be related to a higher prevalence of strabismus postoperatively.

High rate and large intercentre variability in retreatment of retinopathy of prematurity in infants born <24 gestational weeks.

OBJECTIVE: Prematurity is a major risk factor for retinopathy of prematurity (ROP). We aimed to elucidate ROP prevalence, treatment and retreatment in infants born before 24 gestational age (GA) weeks in a Swedish cohort. METHODS AND ANALYSIS: Infants with completed ROP screening, born at <24 GA weeks, 2007-2018 in Sweden were included. Data of GA, birth weight (BW), sex, neonatal morbidities, maximal ROP stage, aggressive posterior ROP (APROP), ROP treatments, treatment modality and treatment centre were retrieved. RESULTS: In total, 399 infants, with a mean GA of 23.2 weeks (range 21.9-23.9) and a mean BW of 567 g (range 340-874), were included. ROP was detected in 365 (91.5%) infants, 173 (43.4%) were treated for ROP and 68 of 173 (39.3%) were treated more than once. As the first treatment, 142 (82.0%) received laser and 29 (16.1%) received intravitreal injection of antivascular endothelial growth factor (anti-VEGF). Retreatment was performed after first laser in 46 of 142 (32.4%) and in 20 of 29 (69.0%) after first anti-VEGF treatment. Retreatment rate was not associated with GA, BW or sex but with APROP, treatment method (anti-VEGF) and treatment centre where the laser was performed (p<0.001). Twenty eyes progressed to retinal detachment, and two infants developed unilateral endophthalmitis after anti-VEGF treatment. CONCLUSION: Infants, born at <24 weeks' GA, had high rates of treatment-warranting ROP and retreatments. Treatment centre highly influenced the retreatment rate after laser indicating that laser treatment could be improved in some settings.

Analysis of Brain Injury Biomarker Neurofilament Light and Neurodevelopmental Outcomes and Retinopathy of Prematurity Among Preterm Infants.

Importance: Circulating levels of neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) are important in the course of brain injury in adults, but longitudinal postnatal circulating levels in preterm infants have not been investigated. Objectives: To examine postnatal longitudinal serum levels of NfL and GFAP in preterm infants during the first 15 weeks of life and to explore possible associations between these biomarkers, neonatal morbidities, and neurodevelopmental outcomes at 2 years. Design, Setting, and Participants: This cohort study used data from 3 clinical studies, including 221 infants born before 32 weeks gestational age (GA) from 1999 to 2015; neurodevelopmental outcomes were evaluated in 120 infants. Data were collected at tertiary-level neonatal intensive care units in Gothenburg, Lund, and Uppsala, Sweden. Data analysis was conducted from January to October 2020. Exposure: Preterm birth. Main Outcomes and Measures: Serum NfL and GFAP levels, retinopathy of prematurity (ROP), intraventricular hemorrhage, and Bayley Scales of Infant Development II and III at 2 years of age, analyzed by multivariate logistic regression measured by odds ratio (OR), and receiver operating characteristic curve (ROC) analysis. Area under the curve (AUC) was also measured. Results: The 221 included infants (108 [48.9%] girls) had a mean (SD) GA at birth of 26.5 (2.1) weeks and a mean (SD) birth weight of 896 (301) grams. NfL levels increased after birth, remaining high during the first 4 weeks of life before declining to continuously low levels by postnatal age 12 weeks (median [range] NfL level at birth: 58.8 [11.5-1371.3] ng/L; 1 wk: 83.5 [14.1-952.2] ng/L; 4 wk: 24.4 [7.0-306.0] ng/L; 12 wk: 9.1 [3.7-57.0] ng/L). In a binary logistic regression model adjusted for GA at birth, birth weight SD score, Apgar status at 5 minutes, and mode of delivery, the NfL AUC at weeks 2 to 4 was independently associated with any ROP (OR, 4.79; 95% CI, 2.17-10.56; P < .001). In an exploratory analysis adjusted for GA at birth and sex, NfL AUC at weeks 2 to 4 was independently associated with unfavorable neurodevelopmental outcomes at 2 years corrected age (OR per 10-unit NfL increase, 1.07; 95% CI, 1.02-1.13; P = .01). Longitudinal GFAP levels were not significantly associated with neonatal morbidity or neurodevelopmental outcome. Conclusions and Relevance: In this study, high NfL levels during the first weeks of life were associated with ROP and poor neurodevelopmental outcomes at 2 years of age. Associations between NfL and later neurovascular development in infants born prematurely should be investigated further.