Early postnatal growth variables are related to morphologic and functional ophthalmologic outcome in children born preterm.

AIM: To evaluate the association between gestational age (GA), early and late postnatal growth variables and ophthalmologic outcome in ex-preterm children. methods: Children (GA < 32 weeks, n = 66), previously examined regarding insulin-like growth factor 1 (IGF-1) serum concentrations in relation to ROP, underwent ophthalmologic examination at median 5.6 years. Weight, height, and head circumference (HC) were measured and expressed as SDS. Growth variables were analysed in relation to ophthalmologic outcome. RESULTS: At follow-up 74% had some ophthalmologic abnormality and 17% had visual impairment. Poor visual acuity was correlated with low GA (r(s) = 0.29, p = 0.019), low weight at 32 weeks (r(s) = 0.30, p = 0.013), and low weight (r(s) = 0.37, p = 0.0025), height (r(s) = 0.41, p = 0.0007) and HC (r(s) = 0.55, p < 0.0001) at follow-up. Hyperopic children (25%) had low neonatal IGF-1 (p = 0.0096) and HC at follow-up (p = 0.022). Poor visual perception was correlated with low early weight (r(s) = 0.38, p = 0.0036) and HC at follow-up (r(s) = 0.39, p = 0.0024). Head circumference at follow-up was correlated with GA (r(s) = 0.40, p = 0.0012), neonatal IGF-1 (r(s) = 0.37, p = 0.0031), and early weight (r(s) = 0.27, p = 0.035). CONCLUSIONS: In very preterm children, early and later postnatal growth is closely related to visual acuity and perception at follow-up. In addition, IGF-1 concentrations and early growth are correlated with head circumference and refraction at follow-up.

New insights into the development of retinopathy of prematurity--importance of early weight gain.

UNLABELLED: Evidence is accumulating that one of the strongest predictors of retinopathy of prematurity (ROP), in addition to low gestational age, is poor weight gain during the first weeks of life. In infants born preterm, the retina is not fully vascularised. The more premature the child, the larger is the avascular area. In response to hypoxia, vascular endothelial growth factor (VEGF) is secreted. For appropriate VEGF-induced vessel growth, sufficient levels of insulin-like growth factor I (IGF-I) in serum are necessary. IGF-I is a peptide, related to nutrition supply, which is essential for both pre- and post-natal general growth as well as for growth of the retinal vasculature. In prematurely born infants, serum levels are closely related to gestational age and are lower in more prematurely born infants. At preterm birth the placental supply of nutrients is lost, growth factors are suddenly reduced and general as well as vascular growth slows down or ceases. In addition, the relative hyperoxia of the extra-uterine milieu, together with supplemental oxygen, causes a regression of already developed retinal vessels. Postnatal growth retardation is a major problem in very preterm infants. Both poor early weight gain and low serum levels of IGF-I during the first weeks/months of life have been found to be correlated with severity of ROP. CONCLUSION: This review will focus on the mechanisms leading to ROP by exploring factors responsible for poor early weight gain and abnormal vascularisation of the eye of the preterm infant.

Aicardi syndrome: follow-up investigation of Swedish children born in 1975-2002.

Aicardi syndrome has been defined by the triad of agenesis of the corpus callosum, early seizure onset and lacunar chorioretinopathy. In a nation-wide survey a total of 18 Swedish cases were found. Fourteen girls were re-examined by one of the authors at the ages of 1-27 years. One was seizure free following epilepsy surgery operation, 13 were drug resistant. Two were on ketogenic diet. Most of the girls had multifocal EEG discharges. All except one were severely disabled with severe mental retardation and total dependency on helpers for activities of daily life. Communication, nutrition, and motor function were severely affected areas. Visual function was difficult to evaluate because of mental retardation and lack of co-operation and varied from severely impaired to normal. In one case the appearance of the ocular fundus was documented to have changed with time. One girl was exceptional and seizure free with mild mental retardation. An update by March 2006 showed that 12/18 patients were still alive, at a median age of 13.5 years (range: 3-31 years). Six had died between the ages of 3-10 years. They had all suffered from intractable epilepsy and belonged to the most disabled group. Surprisingly two had died from malignant brain tumours.

Aicardi syndrome: presentation at onset in Swedish children born in 1975-2002.

In a nation-wide survey of Aicardi syndrome, defined as the onset of epilepsy in the first six months of life, agenesis of the corpus callosum (partial or total) and lacunar chorioretinopathy, 18 patients, all girls, born between 1975 and 2002 were identified in Sweden. Fifteen were definite cases and three were regarded as probable, since they only fulfilled two of three inclusion criteria in addition to other cerebral malformations and/or chorioretinal changes. Calculations based on this survey and population-based studies on epilepsy in retarded children yielded a prevalence rate in the range of 2 - 15 : 100 000 girls. All but one had an ordinary birth weight, length and head circumference for gestational age. One was born preterm, one post term. The age at diagnosis varied from three days to 12 years and decreased during the period reflecting the increased awareness of the syndrome. Eleven came to medical attention because of seizures. Six had myoclonic, four generalized tonic-clonic and eight tonic, clonic or complex partial seizures. One had hypsarrhythmia, five multifocal epileptiform activity, three bilateral independent bursts, two burst-suppression pattern, six other types of spikes and one slowing of background activity. Asymmetrical EEG abnormalities indicating independent hemispheric dysfunction were detected in 13/18 (72 %). Complete absence of the corpus callosum was found in 13/18 (72 %), although not identical with the previous group, a partial defect in 3/18 (17 %), and a thinning in 2/18 (11 %). Of 15 children with definite Aicardi syndrome, 13 had binocular and two monocular lacunae. In one of the latter two, subtle monocular lacunae were found on fundus photographs, but had been missed on repeated clinical examinations. Of three children with probable Aicardi syndrome typical lacunae were reported in one and other kinds of depigmentation in the other two. Most of the children had anomalous optic discs. Neuroimaging in infancy or early childhood combined with ophthalmological examination and ocular fundus photography will facilitate an early diagnosis of Aicardi syndrome. Seizure type and EEG abnormalities may be non-specific at onset.

Subnormal visual perception in school-aged ex-preterm patients in a paediatric eye clinic.

PURPOSE: The aim of this study was to assess visual perception at school age of children born preterm with known lesions to the posterior visual pathways or with ophthalmologic signs that might indicate such lesions. METHODS: The study group consisted of 91 patients born before the 37th gestational week. Visual perception was assessed using the TVPS-R (Test of Visual Perceptual Skills - Revised) and a structured interview. In addition, ophthalmologic and orthoptic examinations were performed. RESULTS: On the test of visual perception, 67% of the patients had results below the third percentile of the American reference group. This is to be compared with 10% of Swedish full-term controls. Scores below the third percentile were observed in 87% of the patients with known brain lesions, 48% of those with strabismus without known brain lesion, and 86% of those with reduced visual acuity in the absence of strabismus and known brain lesion. CONCLUSIONS: Reduced visual perception is common among children born preterm who have strabismus and/or reduced visual acuity, as well as in those with known brain lesions. This study emphasises the need to find tools to identify and assess those patients who have visual perceptual problems that may restrict their ability to meet the demands of daily life.

Optic disc morphology may reveal timing of insult in children with periventricular leucomalacia and/or periventricular haemorrhage.

AIMS: To evaluate the relation between optic disc morphology and timing of periventricular white matter damage, defined as either periventricular leucomalacia (PVL) or periventricular haemorrhage (PVH), as estimated by neuroradiology. METHODS: 35 children with periventricular white matter damage who had had neuroradiology performed and ocular fundus photographs taken had their photographs analysed by digital image analysis and compared with a control group of 100 healthy full term children. Timing of brain lesion was estimated by analysis of the brain lesion pattern on neuroradiological examinations (magnetic resonance imaging or computed tomography). RESULTS: Four of 35 children had a small optic disc area; these four children had a brain lesion estimated to have occurred before 28 weeks of gestation. Nine of 11 children with a large cup area had a PVL/PVH estimated to have occurred after 28 weeks of gestation. The children with PVL/PVH had a significantly larger cup area (median 0.75 mm(2)) than the control group (median 0.33 mm(2)) (p = 0.001) and a significantly smaller neuroretinal rim area (median 1.58 mm(2)) than the controls (median 2.07 mm(2)) (p = 0.001). CONCLUSION: In a child with PVL/PVH and abnormal optic disc morphology, the possibilities of timing of the lesion should be considered.

Large variability in performance IQ associated with postnatal morbidity, and reduced verbal IQ among school-aged children born preterm.

AIM: To assess cognitive ability in a population-based group of prematurely born school-aged children and to relate these findings to postnatal morbidity. METHOD: The study group consisted of a cohort of 51 children born preterm, 43 (26 boys, 17 girls) of whom were available for psychological evaluation At evaluation, their median age was 10 y (range 8-11 y). They were all born between 1988 and 1991, with gestational age less than 29 wk (median 27, range 24-28). Their median birthweight was 1060g (range 450-1450). The Wechsler Intelligence Scale for Children (WISC-III) was used, and the test results were compared with those of a standardized, age-matched, normative group of children. RESULTS: Thirteen children (30%) performed below average [intelligence quotient (IQ) < 80] for Full Scale IQ (FSIQ). Thirty-six children had a Verbal IQ (VIQ) below the mean value of 100 [84%, 95% confidence interval 73-95%], p < 0.0001. The Performance IQ (PIQ) was within the expected range of a normal population, although a large variability was observed. Discrepancies between VIQ and PIQ of more than 15 IQ units were found in 42% of the children. High postnatal morbidity (days with assisted ventilation, number of blood transfusions) and low birthweight standard deviation scores (SDS) were associated with lower PIQ than VIQ, while low postnatal morbidity and high birthweight were associated with higher PIQ than VIQ. CONCLUSION: This cohort of preterm children had reduced overall verbal capacity independent of morbidity, and a large variability in performance capacity that was associated with postnatal morbidity. The findings suggest that there are different mechanisms influencing the outcome of verbal and performance capacity in preterm children.

Low IGF-I suppresses VEGF-survival signaling in retinal endothelial cells: direct correlation with clinical retinopathy of prematurity.

Retinopathy of prematurity is a blinding disease, initiated by lack of retinal vascular growth after premature birth. We show that lack of insulin-like growth factor I (IGF-I) in knockout mice prevents normal retinal vascular growth, despite the presence of vascular endothelial growth factor, important to vessel development. In vitro, low levels of IGF-I prevent vascular endothelial growth factor-induced activation of protein kinase B (Akt), a kinase critical for endothelial cell survival. Our results from studies in premature infants suggest that if the IGF-I level is sufficient after birth, normal vessel development occurs and retinopathy of prematurity does not develop. When IGF-I is persistently low, vessels cease to grow, maturing avascular retina becomes hypoxic and vascular endothelial growth factor accumulates in the vitreous. As IGF-I increases to a critical level, retinal neovascularization is triggered. These data indicate that serum IGF-I levels in premature infants can predict which infants will develop retinopathy of prematurity and further suggests that early restoration of IGF-I in premature infants to normal levels could prevent this disease.

Ocular fundus abnormalities in children born before 29 weeks of gestation: a population-based study.

PURPOSE: Preterm birth has been found to be associated with increased morbidity of the central nervous and vascular tissues. To investigate the influence of preterm birth on the optic disc and retinal vessels, we examined the ocular fundus in school-aged children born very preterm. METHODS: A prospective, population-based study was performed in 50 very preterm children (median age 7 years, range 5-9 years) with a median gestational age at birth of 27 weeks (range 24-28 weeks) and a median birth weight of 1055 g (range 450-1520 g). The ocular fundus was examined by ophthalmoscopy in 50 children, and the optic nerve and retinal vessel morphology was evaluated by digital image analysis of ocular fundus photographs in 45 of these children. RESULTS: The median optic disc area was significantly smaller (p = 0.0002) in the preterm children compared with a reference group. There was no difference in cup area and, consequently, the rim area was significantly smaller (p = 0.0002) in the preterm children. Children with early signs of brain lesions commonly had a rim area below the median of the reference group. Preterm children also commonly had an abnormal retinal vascular pattern that was independent of a previous history of retinopathy of prematurity. CONCLUSION: Very preterm birth was associated with subnormal optic disc and rim areas and an abnormal vascular pattern. The findings clearly demonstrate the effect of preterm birth on the development of these structures. The long term clinical prognosis of these findings has yet to be determined.

Visual function in school-aged children born before 29 weeks of gestation: a population-based study.

The aim of this study was to assess visual function, including visual perception, in a geographically-based population of school-aged children, with a median age of 7.2 years (range 5.1 to 9.3 years), born before 29 weeks of gestation to mothers living in Goteborg, Sweden. Fifty-one preterm children participated in the study, six of whom had known brain lesions. Visual acuity, visual fields, stereoacuity, and visual perception were tested. The Test of Visual Perceptual Skills Revised (TVPS-R, Gardner 1996) was used to measure visual perception, and the results were compared with those of 50 term (control) subjects. Six percent of the preterm children were visually impaired, with a visual acuity of less than 0.3 (6/18), while 42% of all the preterm children and 34% of those without known brain lesions had a total score below the 5th centile of the reference material for the test, compared with 14% of the control subjects. In conclusion, visual-perceptual problems seem to be common among very preterm children and should be screened for and assessed before the children start school.

Ocular fundus morphology in preterm children. Influence of gestational age, birth size, perinatal morbidity, and postnatal growth.

PURPOSE: To determine the influence of gestational age, birth size, perinatal morbidity, and postnatal growth on fundus morphology in preterm children using digital image analysis of fundus photographs. METHODS: Thirty-nine preterm children (mean postmenstrual gestational age, 29.1 weeks; range, 24.6 to 32) were included in the study. Thirty-nine healthy children, born at term, were used as control subjects. Fundus photographs were obtained at a mean age of 4.8 years (preterm) and 6.1 years (control subjects). RESULTS: There was no difference in optic disc, excavation, or peripapillary crescent area between the two groups. In the group of preterm children, a large optic disc size was associated with a low birth weight (rs = -0.29, P = 0.07), duration of assisted ventilation (rs = 0.43, P = 0.006), and number of blood transfusions (rs = 0.33, P = 0.04). The girls born prematurely showed a negative relation between the length of gestation and the area of the optic disc (r2 = 0.28, P = 0.009). No such relation was found in boys. The preterm children had increased tortuosity of retinal vessels (P < 0.001 and P < 0.002 for arteries and veins, respectively) and reduced number of vascular branching points (P < 0.001) compared with those of the control subjects. There were no associations between these vascular abnormalities and the perinatal and postnatal variables studied. CONCLUSIONS: No difference in optic disc morphology between preterm children and control subjects was found. However, preterm birth seems to affect the retinal vascular pattern close to the optic disc, independently of retinopathy of prematurity. Among the girls born preterm, optic disc size was negatively correlated to gestational age.

Do we have optimal screening limits in Sweden for vision testing at the age of 4 years?

The purpose of this study was to evaluate the Swedish screening criteria for referral of children to ophthalmic care after visual acuity testing at the age of 4 years. The screening limit has generally been 0.8. To what extent do children with 0.65 in each eye (0.65/0.65) or 0.65 in one and 0.8 in the other (0.65/0.8) at the age of 4 years have visual defects needing early treatment? Sixty-three children who had failed screening underwent orthoptic and ophthalmologic evaluation. Twenty-four patients (38%) saw 0.65/0.65 or 0.65/0.8 and were studied further. None of them had manifest strabismus. Refractive errors were minor except in 2 patients who had significant hyperopia. Twenty-two of these 24 patients returned for reevaluation at the age of five years and that time 18 of them saw 0.8 or more without treatment. Our findings suggest that children with visual acuity of no less than 0.65 and no more than one line's difference between the eyes at 4 years of age seldom have visual defects needing treatment.

Glare measurements before and after cataract surgery.

The efficacy of cataract surgery in improving visual performance was evaluated in 10 patients by measuring changes in intraocular light scatter, contrast sensitivity and glare induced visual loss. Two different methods were used to estimate these functions before and after cataract extraction with implantation of a monofocal posterior intraocular lens. By one method intraocular light scattering was assessed. By the other, letter contrast sensitivity and glare induced visual loss were determined. Preoperatively most patients had various glare problems, glare induced visual loss and increased intraocular light scatter. Following surgery the letter contrast sensitivity increased by a factor of 3 or more (mean 4.3). The glare problems diminished or disappeared after surgery, although several patients still had increased intraocular light scattering and glare induced visual loss compared to normals. Postoperatively the contrast sensitivity both with and without glare had increased to a level where the glare induced visual loss did not create any visual problems.

Comparison of two glare measurement methods through light scattering modeling.

Two methods used for evaluation of glare in patients with opacities of the ocular media are compared. One is a low contrast letter test and the other is a direct light scattering meter. Theoretical expressions for the measures obtained from the two different glare tests are derived in terms of the point spread function. Measurements on healthy test persons wearing diffusive glasses with known light scattering properties were in good agreement with the theory. Data from 26 cataractous eyes are presented and discussed in light of the theory.

A new glare test based on low contrast letters--evaluation in cataract patients.

A new simple glare test was designed and evaluated regarding clinical usefulness and reproducibility. The ability to recognize letters of equal size and varying contrast was determined with the absence and presence of glare sources above and below the letters. Ten patients with cataract, visual acuity of at least 0.3 and glare problems, and three age matched controls were tested, as well as one patient with glare complaints and exophoria, one with lens subluxation and one with cataract and no glare problem. The test was found to be cheap and simple to produce and useful for clinical testing. Normal eyes had no detectable reduction of letter contrast sensibility with glare. All cataractous eyes had a letter contrast sensitivity without glare that was well below that of the controls and under glare conditions they all had a drop in visual function that was unrelated to their visual acuity. The reproducibility was of a magnitude similar to that of other low contrast letter tests. Our conclusion is that this test will be a valuable tool in the evaluation of cataract patients providing information not only about glare-induced visual loss but also about contrast sensitivity, separating eyes with increased intraocular light scattering from normal eyes.