CENTRAL MACULAR THICKNESS IN 6.5-YEAR-OLD CHILDREN BORN EXTREMELY PRETERM IS STRONGLY ASSOCIATED WITH GESTATIONAL AGE EVEN WHEN ADJUSTED FOR RISK FACTORS.

PURPOSE: To assess the macular thickness in 6.5-year-old children born extremely preterm (EPT) in comparison with children born at term and to investigate risk factors associated with the macular thickness in the preterm group. METHODS: A population-based study of 6.5-year-old children born before the gestational age of 27 weeks and age-matched control subjects. Macular assessments with optical coherence tomography were performed, and the results were compared with neonatal risk factors and sex. RESULTS: Adequate optical coherence tomography measurements were obtained from 134 children born EPT (mean gestational age of 25 weeks [range 23-26]) and 145 control subjects. The mean (range) of central macula thickness was significantly increased (P < 0.001) in the EPT group (right eyes: 282 µm [238-356], left eyes: 283 µm [229-351]), compared with the control group (right eyes: 249 µm [208-293], left eyes: 248 µm [207-290]). A multiple linear mixed model analysis of the EPT group revealed gestational age, retinopathy of prematurity, and male gender as important risk factors for an increased macular thickness. The macular thickness decreased by 3.9 µm per gestational week, when adjusted for retinopathy of prematurity and sex. CONCLUSION: Extremely preterm birth constitutes a substantial risk factor for a thick central macula, even when adjusted for retinopathy of prematurity and male gender.

Macular function measured by binocular mfERG and compared with macular structure in healthy children.

PURPOSE: To create normative data in children from binocular multifocal ERG (mfERG) recordings and compare results with the macular thickness. METHODS: Forty-nine 5- to 15-year-old healthy, full-term children were examined with Espion Multifocal System, using DTL electrodes. The stimulus matrix consisted of 37 hexagonal elements. Amplitudes, implicit times and response densities (presented in three rings) of the first-order component P1 were analyzed. Measurements of macular thickness were performed with spectral-domain Cirrus OCT. RESULTS: There were no significant differences between right and left eyes regarding mfERG recordings. Median P1 implicit times of Rings 1-3 of the 46 right eyes were 30.0, 30.0 and 30.8 ms and response densities 20.5, 10.9 and 7.6 nV/deg(2), respectively. Implicit time was longer in boys than in girls (p = 0.009, 0.039, 0.005 in Rings 1-3) and was correlated with age (r s = 0.417, 0.316, 0.274 in Rings 1-3). Implicit time in Ring 1 correlated significantly with the inner circle of the OCT measurements (p = 0.014). CONCLUSION: Binocular mfERG with DTL electrodes is a reliable test of the central macular function in children and correlates with macular structure. As previously not shown, there was a significant difference in implicit time between boys and girls.

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.

Reduction of Rod and Cone Function in 6.5-Year-Old Children Born Extremely Preterm.

Importance: The function of rods and cones in children born extremely preterm has not yet been fully investigated. Objective: To compare retinal function via full-field electroretinographic (ffERG) recordings in 6.5-year-old children born extremely preterm with children born at term. Design, Setting, and Participants: A subcohort study was conducted from July 1, 2010, to January 15, 2014, of the national Extremely Preterm Infants in Sweden Study, including preterm children (<27 weeks' gestational age) and children born at term, at 6.5 years of age and living in the Uppsala health care region in Sweden. Full-field electroretinography was performed binocularly, using DTL electrodes and electroretinographic (ERG) protocols with flash strengths of 0.009, 0.17, 3.0, and 12.0 candelas (cd)/s/m2, together with 30-Hz flicker and 3.0 cd/s/m2 single-cone flash. Main Outcomes and Measures: The ffERG recordings were analyzed, and their associations with gestational age and retinopathy of prematurity were examined. Results: Adequate ffERG recordings were obtained from 52 preterm children (19 girls and 33 boys; mean [SD] age at examination, 6.6 [0.1] years) and 45 children born at term (22 girls and 23 boys; mean [SD] age at examination, 6.6 [0.1] years). Lower amplitudes of the combined rod and cone responses (the a-wave of the dark-adapted ERG protocol of 3.0 cd/s/m2: mean difference, -48.9 µV [95% CI, -80.0 to -17.9 µV]; P=.003; the a-wave of the dark-adapted ERG protocol of 12.0 cd/s/m2: mean difference, -55.7 µV [95% CI, -92.5 to -18.8 µV]; P = .004), as well as of the isolated cone response (30-Hz flicker ERG: mean difference, -12.1 µV [95% CI, -22.5 to -1.6 µV]; P = .03), were found in the preterm group in comparison with the group born at term. The implicit time of the combined rod and cone responses (the a-wave of the dark-adapted ERG protocol of 12.0 cd/s/m2) was longer (mean difference, 1.2 milliseconds [95% CI, 0.3-2.0 milliseconds]; P = .01) in the preterm group, as were the isolated cone responses (30-Hz flicker ERG: mean difference, 1.2 milliseconds [95% CI, 0.5-1.8 milliseconds]; P < .001), than in the group born at term. No association was found between the ffERG recordings and gestational age or retinopathy of prematurity in the preterm group. Conclusions and Relevance: Both rod function and cone function were reduced in children born extremely preterm when compared with children born at term. There was no association with retinopathy of prematurity in the preterm group, which suggests that being born extremely preterm may be one of the main reasons for a general retinal dysfunction.

Development of astigmatism and anisometropia in preterm children during the first 10 years of life: a population-based study.

OBJECTIVE: To assess the development of astigmatism and anisometropia to 10 years of age in preterm children, previously included in a population-based study on the incidence of retinopathy of prematurity. METHODS: Cycloplegic retinoscopies were performed in 198 preterm children at 6 months, 2(1/2) years, and 10 years of age. We analyzed the development of astigmatism of 1 diopter (D) or more and anisometropia of 1 D or more. RESULTS: The amount and prevalence of astigmatism declined between 6 months and 2(1/2) years of age and then remained stable. We found no difference in the course of astigmatism at different ages with regard to stage of retinopathy of prematurity. The amount of anisometropia increased, but its prevalence remained unchanged. Multiple regression analyses showed that astigmatism of 1 D or more at 2(1/2) years of age and cryotreated severe retinopathy of prematurity were risk factors for astigmatism at 10 years of age, and that anisometropia of 2 D or more at 2(1/2) years of age was a risk factor for anisometropia at 10 years of age. CONCLUSIONS: The development of astigmatism and anisometropia showed a similar course, regardless of stage of retinopathy of prematurity. The retinoscopy findings at 6 months of age were of no value in predicting astigmatism and anisometropia at 10 years of age, but the refraction at 2(1/2) years of age was. Retinoscopy at about 2(1/2) years of age in all preterm children may be useful for detecting astigmatism and anisometropia that will persist in children of school age.

Development of spherical equivalent refraction in prematurely born children during the first 10 years of life: a population-based study.

OBJECTIVE: To evaluate the development of refraction, expressed as spherical equivalents, in prematurely born children during the first 10 years of life. METHODS: Retinoscopy in cycloplegia was performed at 6 months, 2.5 years, and 10 years of age in 198 prematurely born children from a previous population-based study on the incidence of retinopathy of prematurity. Spherical equivalents were calculated. Myopia was defined as a spherical equivalent of less than 0 diopters (D), clinically significant myopia at 10 years of age as -1 D or less, and moderate or high myopia as less than -3D. Hypermetropia greater than +3 D was regarded as significant. RESULTS: There were no significant differences during the refractive development between the various subgroups of retinopathy of prematurity. Cryotreated eyes had a wider distribution of refractive errors. A multiple regression analysis revealed that the spherical equivalents at 2.5 years of age predicted clinically significant myopia (

A population-based study on the visual outcome in 10-year-old preterm and full-term children.

OBJECTIVES: To report the visual outcome in prematurely born and full-term children at the age of 10 years and to evaluate the effects of prematurity per se, retinopathy of prematurity (ROP), and cryotreatment on visual acuity. METHODS: The study included 216 prematurely born children and 217 children born at term from the same geographical area and study period. Best-corrected distance and near visual acuities were assessed with linear letter logarithm of the minimum angle of resolution charts. Crowding was evaluated. RESULTS: Prematurely born children had reduced distance and near visual acuities compared with full-term children, even when children who had retinopathy of prematurity and neurologic disorders were excluded (P<.001). Children who had been treated with cryotherapy had the highest risk of a reduced visual acuity. Two percent of the prematurely born children were visually impaired (<20/60). CONCLUSIONS: Although we found an overall good visual outcome in the prematurely born cohort, the risk of reduced visual acuity was greater than in full-term children. Children who had been treated with cryotherapy had the highest risk, but prematurity per se was also associated with reduced visual acuity.

A population-based study of the refractive outcome in 10-year-old preterm and full-term children.

OBJECTIVE: To evaluate the refractive outcome in 10-year-old prematurely born children and in full-term control children. METHODS: Retinoscopy during cycloplegia was performed in 213 prematurely born children from a previous population-based study on the incidence of retinopathy of prematurity and in 217 children born at term. The spherical equivalent, astigmatism, anisometropia, and significant refractive errors (defined as hypermetropia >3 diopters [D], myopia < or =-1 D, astigmatism > or =1 D in 1 or both eyes, and/or anisometropia > or =1 D) were analyzed. RESULTS: Significant refractive errors were found in 29.6% of the prematurely born and in 7.8% of the full-term children. Prematurely born children had higher prevalences of hypermetropia of more than 3 D, myopia of -1 D or less, astigmatism of 1 D or more, and anisometropia of 1 D or more than those born at term. In the preterm group, the cryotreated children had the greatest risk of refractive errors (16 [64%] of 25 children), with higher prevalences of myopia (<0, < or =-1, or <-3 D), astigmatism (> or =1 D), and anisometropia (> or =1 D). CONCLUSIONS: Significant refractive errors were 4 times more common in 10-year-old prematurely born children than in full-term controls. Cryotreated children had the highest risk, but prematurity per se was also associated with refractive errors. Ophthalmological follow-up of prematurely born children should, therefore, also include children without retinopathy of prematurity in the neonatal period.

Ophthalmologic outcome at 30 months' corrected age of a prospective Swedish cohort of children born before 27 weeks of gestation: the extremely preterm infants in sweden study.

IMPORTANCE: Follow-up at 30 months' corrected age reveals eye and visual problems in one-third of children born extremely prematurely (<27 weeks' gestation). OBJECTIVE: To investigate the ophthalmologic outcome of extremely preterm children at 30 months' corrected age. DESIGN, SETTING, AND PARTICIPANTS A prospective, population-based follow-up study (Extremely Preterm Infants in Sweden Study [EXPRESS]) was conducted in Sweden. The population included extremely preterm infants (<27 weeks' gestation) born in Sweden between 2004 and 2007, of whom 491 survived until age 2.5 years. Screening for retinopathy of prematurity (ROP) was performed in the neonatal period. At 30 months' corrected age, an ophthalmologic assessment was performed in 411 of 491 children (83.7%). MAIN OUTCOMES AND MEASURES: Visual acuity, manifest strabismus, and refractive errors were evaluated. RESULTS: Visual impairment was identified in 3.1% of the children, and 1.0% were blind. Refractive errors, defined as myopia less than -3 diopters (D), hypermetropia greater than +3 D, astigmatism 2 D or more, and/or anisometropia 2 D or more, were found in 25.6% of the children, and 14.1% had manifest strabismus. There were significant associations between visual impairment and treated ROP (P = .02), cognitive disability (P < .001), and birth weight (P = .02). Multiple regression analyses revealed significant associations between strabismus and treated ROP (P < .001), cognitive disability (P < .01), and cerebral palsy (P = .02). Refractive errors were significantly correlated with severity of ROP (right eye, P < .001; left eye, P < .01). Children who had been treated for ROP had the highest frequency (69.0%) of eye and visual abnormalities. CONCLUSIONS AND RELEVANCE: One-third of the extremely prematurely born children in this study had some kind of eye or visual problems, such as visual impairment, strabismus, or major refractive error. Despite being born extremely preterm, the present cohort has a similar prevalence of blindness and visual impairment as in previous Swedish cohorts of children born less prematurely.

Swedish national register for retinopathy of prematurity (SWEDROP) and the evaluation of screening in Sweden.

OBJECTIVES: To evaluate screening for retinopathy of prematurity (ROP) in Sweden and to investigate possible modifications of the present screening guidelines. METHODS: Infants in Sweden with a gestational age (GA) of 31 weeks + 6 days or less are screened for ROP. Data from the Swedish national register for ROP (SWEDROP) during 2008 and 2009 were extracted and compared with a national perinatal quality register. RESULTS: In SWEDROP, there were 1791 infants born before a GA of 32 weeks from January 1, 2008, through December 31, 2009. Another 70 infants were registered in the perinatal quality register but not in SWEDROP (dropout rate, 3.8% [70 of 1861 infants]). Seven infants died before termination of screening. In the final study cohort (1784 infants), 15.6% had mild ROP and 8.5% had severe ROP. Treatment was performed in 4.4% of the infants, none of whom had a GA at birth of more than 28 weeks. Nine infants with a GA of more than 28 weeks at birth developed stage 3 ROP, which regressed spontaneously. The total number of examinations was 9286 (964 in infants with a GA of 31 weeks), and the mean (range) number of examinations of each infant was 5.2 (1-30). CONCLUSIONS: The SWEDROP, a quality register for ROP, has a national coverage (ie, participation) of 96%. Data from 2008 to 2009 show that it seems possible to reduce the upper limit for screening in Sweden by 1 week, including only infants with a GA of 30 weeks + 6 days or less. However, such a change should be combined with a strong recommendation to neonatologists to refer also severely ill and more "mature" infants.

Screening for retinopathy of prematurity in infants born before 27 weeks' gestation in Sweden.

OBJECTIVE: To analyze screening for retinopathy of prematurity (ROP) during a 3-year period in a national cohort of infants born before 27 weeks' gestation. METHODS: A national prospective study of neonatal morbidity in extremely preterm infants was performed in Sweden between April 1, 2004, and March 31, 2007. Screening for ROP was to start in the fifth postnatal week and to continue weekly until complete vascularization of the retina or until regression of ROP. RESULTS: The first eye examination was performed no later than the sixth postnatal week in 84.8% of 506 infants, and the last examination was performed at postmenstrual age (PMA) of 38 weeks or later in 96.2% of infants. The mean and median numbers of days between examinations in the total cohort were 8.6 and 7.9 days, respectively (range, 1-27.8 days), and the mean and median numbers of examinations were 12 and 10, respectively. Most infants were treated during a limited period (eg, at PMA of 39 weeks, 75.0% of infants had been treated). CONCLUSIONS: The objective of screening for ROP is timely detection of ROP before reaching treatment of criteria, ie, type 1 ROP, according to the Early Treatment for ROP recommendations. In our population of infants born before 27 weeks' gestation, the first examination could safely be postponed until PMA of 31 weeks because the onset of ROP stage 3 did not occur before then and criteria for treatment were not reached before PMA of 32 weeks. Gestational age at birth and PMA at the time of examination should be considered when deciding when and where the next examination should be performed.

Natural history of retinopathy of prematurity in infants born before 27 weeks' gestation in Sweden.

OBJECTIVE: To investigate the natural history of retinopathy of prematurity (ROP) in 506 extremely preterm infants born before 27 weeks' gestation in Sweden during a 3-year period. METHODS: A national population-based study was performed in Sweden from April 1, 2004, to March 31, 2007. According to the study protocol, initial eye examinations were to be performed at postnatal week 5, and examinations were repeated until the retina was completely vascularized or until criteria for treatment were met. The examinations were to be performed weekly, enabling study of the course and severity of ROP. In infants without ROP or with mild ROP without progression during the latest examinations, further examinations were performed weekly or every other week from postmenstrual age 35 weeks. RESULTS: During the study, 368 infants (72.7%) developed ROP. Postmenstrual age at onset of ROP was significantly related to severity of ROP, even when controlling for gestational age (ie, the earlier the onset of ROP, the higher the risk of developing severe ROP). Site of onset of ROP was significantly related to gestational age at birth. The risk of nasal onset was almost doubled for every week of decrease in gestational age at birth. Nasal onset was associated with severe ROP, even after adjusting for gestational age at birth. CONCLUSION: This population-based study confirms results of the Cryotherapy for Retinopathy of Prematurity study and shows new correlations regarding time and site of onset of ROP, both of which are associated with disease severity.

Treatment for retinopathy of prematurity in infants born before 27 weeks of gestation in Sweden.

AIMS: To study various aspects of treatment for retinopathy of prematurity (ROP) in a Swedish population of extremely preterm infants born before 27 weeks of gestation. METHODS: A national, prospective and population-based study was performed in Sweden from 1 April 2004 to 31 March 2007. The criteria for the treatment of ROP accorded with the recommendations of the Early Treatment for Retinopathy of Prematurity Cooperative Group. RESULTS: Twenty per cent of the infants (99/506) were treated for ROP. The likelihood of reaching treatment criteria nearly doubled for each week of reduction in gestational age at birth. The first treatment was performed at an earlier postmenstrual age in the most immature infants. One third of the infants had more than one session of laser treatment. CONCLUSIONS: A high percentage of these extremely preterm infants required treatment for ROP. The likelihood of reaching treatment criteria increased with a decline in gestational age at birth. Although only a few infants progressed to ROP stages 4 and 5, the findings of this study indicate a potential for improvement in the treatment routines, both regarding the timing and number of laser spots at the first treatment.

Incidence of retinopathy of prematurity in infants born before 27 weeks' gestation in Sweden.

OBJECTIVE: To determine the incidence of retinopathy of prematurity (ROP) in extremely preterm infants born before 27 weeks' gestation in Sweden during a 3-year period. METHODS: A national, prospective, population-based study was performed in Sweden from April 1, 2004, to March 31, 2007. The ophthalmologic part of the study was separately organized, and screening for ROP was performed beginning postnatal week 5. The criteria for the treatment of ROP agreed with the recommendations of the Early Treatment for Retinopathy of Prematurity Cooperative Group. RESULTS: During the study, 506 of 707 live-born infants survived until the first eye examination. Of these, 368 (72.7%) had ROP: 37.9% had mild ROP and 34.8% had severe ROP. Ninety-nine infants (19.6%) were treated. Gestational age at birth was a stronger predictor of ROP than was birth weight. A log-linear relationship between severe ROP and gestational age at birth was found in the present cohort, and the risk of ROP was reduced by 50% for each week of increase in gestational age at birth. CONCLUSIONS: Today, extremely preterm infants are surviving, and this population-based study with ROP as a primary outcome shows a higher incidence of this condition than in previously reported national cohorts.