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.

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.

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.