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Optic Nerve Morphology May Reveal Adverse Events During Prenatal and Perinatal Life—Digital Image Analysis

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Abstract

Objective: To evaluate optic nerve morphology in children with various conditions caused by adverse events during prenatal and/or perinatal life and to investigate whether optic nerve morphology can reveal brain lesions associated with these conditions, as well as provide insight into the etiology and timing of the prenatal and perinatal damage. Methods and patients: A digital image analysis technique was used to analyze fundus photographs. One hundred healthy Swedish individuals of various ages from childhood to adolescence constituted a reference group. The following patient groups were chosen to represent various clinical conditions affecting the newborn or fetus at different stages of development: children born preterm (N = 39), children with fetal alcohol syndrome (FAS [N = 16]), children with periventricular leukomalacia (PVL [N = 17]), and children with septo-optic dysplasia (SOD [N = 6]). Results: Preterm children without known brain lesions demonstrated normal optic disk morphology but abnormal retinal vascular pattern; children born preterm with an acquired brain lesion late in gestation (PVL) demonstrated normal disk size with enlarged cups in addition to the abnormal vascular pattern. Children with prenatal alcohol exposure (FAS) had a subnormal optic disk area with increased tortuosity of both arteries and veins, whereas children born at term with an early acquired brain lesion (SOD) had a markedly reduced optic disk area with isolated tortuosity of the retinal veins. Conclusions: Evaluation of optic nerve morphology, by digital image analysis, demonstrated that differences in ocular fundus morphology were correlated with differences in etiology and timing of the adverse event occurring in prenatal and perinatal life. In addition, digital image analysis may be a helpful tool for understanding variations in optic nerve and retinal vessel morphology and their relationship with central nervous pathology.

Section snippets

Digital image analysis

All fundus photographs were evaluated in a masked fashion by quantitative analysis of optic nerve morphology by means of a computer-assisted digital mapping system. A quality assessment of the measurement procedure for the digital image analyses is presented in Table 1. The reliability of the method demonstrates an overall (intraobserver, interobserver, and intergroup) variability in the measurements of optic disk area, expressed as standard deviation (SD), of 0.10 mm2.62

Fundus photographs were

Patients

This study was approved by the Medical Ethics Committee at the University of Göteborg and the Karolinska Institute in Stockholm. Informed consent was obtained from the parents of each child and, if they were old enough, from the children.

Preterm Birth

Thirty-nine preterm children (19 boys and 20 girls), with a mean age of 5 years (range, 3–9 years) and a median gestational age at birth of 29 weeks (range, 25–32 weeks) were selected for the study.31 Visual acuity (uncorrected) ranged from 0.15 to 1.0 (median, 0.65). Refraction ranged from −3 to +4 D.

Preterm birth carries a greatly increased risk of childhood morbidity, manifested, for example, by bronchopulmonary dysplasia, brain injury, and visual impairment.12, 20, 48 Preterm infants are at

Optic nerve morphology

The various groups demonstrated differences in optic nerve morphology Fig. 2, Fig. 3 compared to the reference group, as follows. The preterm children demonstrated normal optic disk morphology. The children with PVL had large cups (P = 0.002) in normal-sized disks and, consequently, small rim areas (P = 0.004). The children with FAS had smaller optic disk areas (P = 0.002), cup areas (P < 0.01), and rim areas (P = 0.004). The children with ONH and pituitary hormone insufficiency demonstrated

Discussion

Quantitative morphologic evaluation of the optic nerve and retinal vessels has for many years been a useful tool in the detection and follow-up of various disorders in adults. For example, it has contributed to our understanding of the underlying disease in various diagnoses in adults, e.g., diabetes, hypertension, and glaucoma. In children, however, optic nerve and retinal vessel morphology have traditionally been subjectively evaluated, and fundus morphology measurements have mainly been

Acknowledgements

The author is grateful for the constructive criticism of Prof. Kerstin Albertsson-Wikland, Prof. Kerstin Strömland, Assoc. Prof. Elisabeth Svensson, and Assoc. Prof. Lars Frisén, as well as for financial support from De Blindas Vänner, Kronprinsessan Margaretas Arbetsnämnd för synskadade, and from Knut och Alice Wallenbergs Stiftelse.

The author has no proprietory interest in any product or concept discussed in this article.

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