A Longitudinal Study to Establish the Normative Value and to Evaluate Perinatal Factors Affecting Intraocular Pressure in Preterm Infants Pak Cheung Ng,1 Barbara Sau Man Tam,2 Cheuk Hon Lee,1 Samuel Po Shing Wong,3 Hugh Simon Lam,1 Alvin Kwan Ho Kwok,2 and Tai Fai Fok1 PURPOSE. To establish a normative range of intraocular pressure vulnerable, high-risk infants after birth, and intraocular pres- (IOP) in preterm infants and to identify important perinatal sure (IOP) can be easily measured by a handheld instrument factors that could affect the IOP during the early weeks of during routine ophthalmic examination. An understanding of neonatal life. the natural maturation process of the visual system, establish- METHODS. The IOP of 104 preterm infants, with a median ment of a normative range of values, and identification of (interquartile range) gestational age of 29.8 (28.7–30.9) weeks important intrinsic or extrinsic factors that may affect various and birth weight of 1208 (1049–1370) g, were assessed in a ocular measurements, including IOP, are essential in assisting clinicians in assessing developmental abnormalities and con- university-affiliated tertiary neonatal center. These infants had 4 IOP measured by a handheld tonometer at 1, 4, 6, 8, and 10 genital diseases involving the eyes. To date, relatively few weeks of postnatal age. The mixed-effects models were used to studies have reported IOP in preterm infants. Of these studies, evaluate the longitudinal IOP measurements and to identify most obtained the IOP measurements in a cross-sectional man- ner.4–10 In only one small trial involving 20 preterm infants critical perinatal factors that would significantly affect the 11 ocular pressure. was IOP measured weekly during the first month of life. Although investigators performing earlier studies have been RESULTS. A percentile chart of IOP in preterm infants was meticulous in their examination techniques and in the mea- constructed, and the median (10th–90th percentile) IOP surement of ocular pressure, relatively little clinical informa- ranged from 16.9 (12.3–21.5) to 14.6 (10.1–19.2) mm Hg at tion concerning the characteristics and outcomes of patients 26.1 and 46.4 weeks of postconceptional age, respectively. were described.4–12 Important information included the mode The IOP was significantly and negatively associated with Ͻ ϭ of mechanical ventilation, presence or absence of intracranial postconceptional age (P 0.001), mean blood pressure (P complications, and interventions or drugs that may influence 0.01), Apgar score at 1 minute (P ϭ 0.04), and use of inhaled ϭ the IOP. However, the interrelationship and complexity of corticosteroids (P 0.03), but was positively correlated with different factors affecting the IOP renders normative data dif- the commencement of high-frequency oscillatory ventilation ϭ ficult to determine. Thus, the objectives of this study were (1) (P 0.01). to determine a normative range of IOP by longitudinally mea- CONCLUSIONS. A quantitative statistical model has been devel- suring the ocular pressure at standardized time intervals (1, 4, oped and a percentile chart of IOP constructed for preterm 6, 8, and 10 weeks) after birth and (2) to determine important infants that could be used for future reference. Pediatric oph- perinatal factors, both physiologic and environmental, that thalmologists and neonatal clinicians can compare the IOP of may affect the IOP during the early weeks of neonatal life. A preterm infants against this chart and make relevant quantita- percentile chart of IOP in preterm infants will provide neonatal tive adjustments for critical perinatal factors so that the IOP clinicians and pediatric ophthalmologists with the ability to may be properly evaluated, both in healthy and ill infants. compare ocular pressures between well and sick infants and to (Invest Ophthalmol Vis Sci. 2008;49:87–92) DOI:10.1167/ monitor infants who receive specific medications, such as iovs.07-0954 systemic corticosteroids, or undergo eye surgery and/or laser photocoagulation treatment. reterm, very-low-birth weight (VLBW; 1500 g) infants are Pfrequently exposed to high concentrations of oxygen and are at risk of development of retinopathy of prematurity METHODS (ROP).1–3 Regular screening for ROP is necessary for these Patients Preterm infants admitted consecutively into the neonatal intensive care unit (NICU), at the Prince of Wales Hospital, Hong Kong, who met the From the Departments of 1Pediatrics, 2Ophthalmology and Visual Science, and 3Statistics, Prince of Wales Hospital, The Chinese Univer- screening criteria for ROP were prospectively enrolled over a period of Ͻ sity of Hong Kong, Hong Kong. 32 months. The inclusion criteria were: (1) all infants 32 weeks of Supported by the Departmental Fund from the Department of gestational age or birth weight Ͻ1500 g, (2) moderately preterm Pediatrics, The Chinese University of Hong Kong. infants (32–36 weeks gestational age) receiving supplemental oxygen Submitted for publication July 27, 2007; revised August 28, 2007; Ͼ7 days, and (3) parental consent to participate in the study. Infants accepted November 12, 2007. were excluded if they had undetermined gestational age; multiorgan Disclosure: P.C. Ng, None; B.S.M. Tam, None; C.H. Lee, None; dysfunction and were expected to die imminently; chromosomal ab- S.P.S. Wong, None; H.S. Lam, None; A.K.H. Kwok, None; T.F. Fok, normalities and dysmorphic syndromes; or congenital ocular abnor- None malities, such as corneal clouding or cataract. Patients who received The publication costs of this article were defrayed in part by page charge payment. This article must therefore be marked “advertise- postnatal systemic (i.e., oral or intravenous) corticosteroids treatment ment” in accordance with 18 U.S.C. §1734 solely to indicate this fact. were investigated separately, as previous trials in older children and Corresponding author: Pak Cheung Ng, Department of Pediatrics, adults have found that the use of systemic corticosteroids as well as Level 6, Clinical Sciences Building, Prince of Wales Hospital, Shatin, topical steroids applied locally to the eye are important factors associ- N.T., Hong Kong; [email protected]. ated with the development of ocular hypertension.13–16 Further, we Investigative Ophthalmology & Visual Science, January 2008, Vol. 49, No. 1 Copyright © Association for Research in Vision and Ophthalmology 87 Downloaded from iovs.arvojournals.org on 10/01/2021 88 Ng et al. IOVS, January 2008, Vol. 49, No. 1 monitored the latter group of infants differently, with IOP checked TABLE 1. Clinical Characteristics of the Study Population according to the dose regimen of the dexamethasone course received ؍ by the patient. Characteristics n 104 Gestational age (wk) 29.8 (28.7–30.9) Methods Birth weight (g) 1208 (1049–1370) Gestational and Postconceptional Ages. The gestational Length (cm) 37.6 (36.5–39.0) OFC (cm) 26.5 (25.8–27.7) age of an infant was obtained on the basis of maternal obstetric history Sex or early perinatal ultrasound, and was subsequently confirmed after Male (n) 52 (50%) birth by the New Ballard score.17 The postconceptional age was cal- Female (n) 52 (50%) culated by adding the postnatal age of the infant at the time of Apgar scores ophthalmic examination to the gestational age. 1 min 7 (6–9) Measurement of IOP. The IOP of preterm infants was longitu- 5 min 9 (8–10) dinally measured at standard time intervals at 1, 4, 6, 8, and 10 weeks Arterial cord blood pH 7.30 (7.23–7.34) after birth. The first eye examination at week 1 was voluntary and the Base excess (mmol/L) Ϫ4.0 (Ϫ7.2–Ϫ2.2) other four measurements coincided exactly with the timing of routine Mode of delivery ROP examinations provided by the NICU for at-risk infants. A single Cesarean section (n) 66 (63%) ophthalmologist (BSMT) performed the ocular examination in all stud- Vaginal (n) 38 (37%) ied infants. In each examination, 1 drop of 1% preservative-free ameth- Maternal diabetes (n) 14 (13.5%) ocaine hydrochloride (Chauvin Pharmaceuticals Ltd., Surrey, UK) was Prolonged rupture of membrane (n) 16 (15.4%) instilled before the eyelids were opened with a Cook’s infant specu- Histologic chorioamnionitis* (n) 19 (23%) lum. The infant was then held supine by an experienced neonatal Pre-eclampsia of pregnancy (n) 29 (28%) nurse. It usually took the patient 30 to 90 seconds become accustomed Antenatal dexamethasone (mg) 12 (6–24) Duration between the last dose of antenatal to the speculum and settle down. IOP was always measured before the dexamethasone and delivery (h) 6 (3–43) dilatation of pupils and indirect ophthalmic examination for ROP and CRIBS score 1 (1–2) never in irritable or crying infants. None of the patients received Oxygenation index (12 h of age) 3.7 (1.9–6.6) sedative drugs or muscle relaxants just before or during the eye RDS examination. IOP was measured with a handheld applanation tonom- ϽStage 2 60 (57%) eter (Tonopen II; Oculab, La Jolla, CA). Other methods of IOP mea- ՆStage 2 44 (43%) surement such as Goldmann applanation tonometry and noncontact Mechanical ventilation (week 1) (n) tonometry are impossible to perform at the bedside in preterm new- HFOV 11 (11%) borns, and Perkin’s tonometry is also not suitable because of the IPPV 5 (5%) CPAP 45 (43%) relatively large contact area on the cornea. Previous studies have No ventilatory support 43 (41%) reported good agreement in IOP measurement between the Tonopen Use of surfactant (n) 86 (83%) 18–20 and Goldmann applanation tonometers. In addition, applanation Duration of mechanical ventilation (days) 1.3 (0.4–6.3) tonometry was chosen over indentation tonometry because the latter Duration of O2 requirement (days) 17 (5–34) 21 method is substantially affected by scleral rigidity.