INTRODUCTION

Until the 20th century, little was known about ocular pressure in newborns, mainly because of the lack of suitable equipment for measuring ocular pressure. The physical properties of the neonatal cornea appear to be the main factors associated with difficulty in obtaining reliable measurements of intraocular pressure (IOP) using the majority of available tonometers. Corneal thickness is an independent risk factor for glaucoma development in adults with ocular hypertension⁽¹⁾. However, few studies have been conducted in Brazil on IOP values in full-term newborns, and these studies have not reported a correlation between IOP and central corneal thickness (CCT)⁽²⁾. Glaucoma is an important disease in children, accounting for 2.5%-10% of all cases of childhood blindness⁽³⁾. Knowledge of the reference values for IOP in newborns, in association with CCT, weight, sex, and post-conception age (PCA), is important for the early diagnosis of glaucoma, especially in children who have not yet developed the classic signs of primary congenital glaucoma (e.g., cloudy cornea, buphthalmia). The aim of the present study is to fill this knowledge gap.

METHODS

The study protocol was approved by the Ethics Committee of the Federal University of São Paulo. The parents/guardians of the newborns were informed about the tests, and provided their written consent.

IOP and CCT were measured in 52 full-term newborns with a mean gestational age (GA) of 39.43 ± 1.03 weeks and a mean birth weight of 3,273 ± 558 g. The mean age of the neonates at the time of taking the measurements was 1.15 ± 1.38 days after birth (Table 1). Newborns with abnormalities in biomicroscopy (deformities and abnormalities in the transparency of the cornea and defects of the iris, such as aniridia or coloboma), red reflex changes, or systemic syndromes were excluded.

The newborns were placed on a wheeled stretcher in the supine position. After the administration of topical anesthesia (one drop of 0.5% proparacaine), their eyelids were carefully parted by the operator’s fingers while avoiding placing the weight of the hand on the ocular globe, which can influence the accuracy of optical measurements. The measurement was only performed when the newborn was quiet and still. The mean IOP was calculated after three measurements with a Tono-Pen AVIA (Reichert, Depew, NY, USA). If the IOP results from the three measurements differed by >3 mmHg, the measurement was repeated. The mean CCT was calculated after eight measurements in each eye with an SP-100 portable pachymeter (Tomey, Nagoya, Japan). All measurements were centrally performed, and all tests were performed by the same operator during the same period of the day (between 13 h and 16 h).

Statistical analyses were initiated by the characterization of va­riables through measures of central tendency and variability. The Kolmogorov-Smirnov test was used to verify the normality of the data. Multiple linear regression was used to evaluate the relationship between variables. The premises of normality of the residuals (Kolmogorov-Smirnov), absence of serial autocorrelation (Durbin-Watson), absence of heteroscedasticity [(variance inflation factor (VIF)], and the absence of multicollinearity (robust standard error) were verified. The differences between the sexes of the tested variable. were determined by the Mann-Whitney test. The level of significance adopted was 5%, with a confidence interval of 95.0%. SPSS Statistics software (version 21; IBM Corp., Armonk, NY, USA) was used to perform all statistical analyses.

RESULTS

The overall mean IOP was 14 ± 2.91 mmHg (range 8-20 mmHg) (Table 1), and the mean IOP in male and female newborns was 13.77 ± 2.88 mmHg (range 8-19 mmHg) and 14.32 ± 3.05 mmHg (range 8-20 mmHg), respectively. The overall mean CCT was 605.87 ± 62.98 µm (range 483-794 µm), and the mean CCT in male and female newborns was 626.70 ± 67.46 µm (range 483-794 µm) and 577.45 ± 45.50 µm (range 521-686 µm), respectively. The mean CCT was significantly higher in male newborns (Tables 2 and 3).

Multiple linear regression analysis showed statistical signifi­cance for weight, female sex, and PCA. There was a positive re­­lationship between weight and CCT. Female neonates had significantly lower CCT than male neonates. Further, CCT decreased as the PCA increased (Table 4). Male weight was significantly asso­ciated with CCT; as the mean weight increased, the CCT also increased (Table 5). Conversely, no significance was found for any of the variables in the female neonates; that is, weight, IOP, and PCA were independent of CCT (Table 6).

The Mann-Whitney test showed significant differences between the sexes for two variables only, namely weight and CCT, and male sex obtained significantly higher means and median for both variables (Table 7).

DISCUSSION

In the present study, we assessed the effect of CCT on IOP, weight, sex, and PCA in full-term newborns. The mean IOP was 14.42 ± 2.91 mmHg, which is lower than that observed in previous similar studies^(4-6).

As per the existing literature, IOP values obtained in the supine position tend to be higher than those measured in the sitting position as a result of changes in scleral venous pressure⁽⁷⁾. Although Goldmann applanation tonometry is the gold standard method for measuring IOP, it only provides estimated values^(8,9). Accuracy for this measurement depends on the use of correct technique, and in particular, the use of adequate amounts of fluorescein⁽¹⁰⁾. However, errors resulting from changes in the corneal thickness and rigidity cannot be avoided when using Goldmann applanation tonometry^(8,9). The Tono-Pen is the preferred instrument for pediatric patients because it is less affected by corneal thickness, according to a study by Yildirim et al.⁽¹⁰⁾.

In the present study, the mean CCT in full-term newborns was 605.87 ± 62.98 µm. This value is higher than that reported in several previous studies^(4,11-14) but similar to that reported by Rushood et al.⁽¹⁵⁾. Other studies have shown that CCT is significantly lower in children with congenital glaucoma or childhood glaucoma^(16,17).

In a study by Uva et al.⁽⁴⁾, premature and full-term newborns were compared; the results showed that IOP increased with an in­crease in CCT, and that CCT decreased with an increase in birth weight. The authors concluded that the main factor affecting IOP was CCT. In the present study, there was no correlation between CCT and IOP. Although a correlation between CCT and IOP has not been demonstrated in the literature, there is little information about this correlation in full-term newborns. Studies such as that conducted by Karahan et al.⁽⁶⁾ have similarly not shown an effect of CCT on IOP in premature newborns; however, these previous studies were limited by their small sample sizes.

In the present study, there was a significant negative correlation between PCA and CCT (Table 5). This finding corroborates the results found by Ehlers et al.⁽¹⁹⁾, who observed that corneal thickness in newborns is highest during the first 24 h and significantly decreases after 48h. Moreover, they reported a decrease in the mean CCT between the day-of-birth group and the 48h group of full-term newborns (from 632 µm to 569 µm, i.e., a 10% reduction after birth), possibly owing to improved regulation of corneal hydration and evaporation and corneal remodeling, with an increase in corneal diameter and a decrease in curvature^(12,14). This process of corneal thinning steadily continues until 3 years of age, when the corneal thickness becomes the same as that of an adult. Thereafter, there is a gradual, but non-significant, decrease in the corneal thickness⁽¹⁸⁾. Remon et al.⁽¹⁴⁾ also observed significant differences in corneal thickness between 1-day-olds and older children, and Ehlers et al.⁽¹⁹⁾ reported that corneal thickness decreases after birth. CCT is a sensitive parameter for early diagnosis of congenital glaucoma, and its measurement is important for monitoring suspected cases; CCT measurement is also important for the interpretation of IOP in acute cases, with or without corneal edema, and chronic cases of childhood glaucoma⁽¹⁵⁾.

In the present study, weight was correlated with CCT. There were significant differences between the sexes for the variables of weight and CCT; however, other authors⁽⁶⁾ have not reported any correlation between CCT and sex. We found that the mean CCT and mean weight were higher in male newborns than in female newborns. It is not surprising that weight correlates with CCT, since male newborns are tipically heavier on average than their female counterparts; however, the difference found between the sexes might be explained by differences in GA between these groups.

The few studies published on this topic confirm that there are several variables and many questions to be explored in order to determine the factors that are associated with a predisposition for glaucomatous disease in newborns.

The present study had several limitations, such as the small sample size as a consequence of excluding newborns with systemic conditions and abnormalities on biomicroscopy, which could have affected the results of the study by introducing selection bias; moreover, the measurements could be performed only when the newborns were quiet or in the absence of any movement that could trigger a Valsalva maneuver. Moreover, the chosen technique of parting the eyelids with the operator’s fingers requires great care to avoid placing the weight of the hand on the ocular globe. Therefore, eyes with intense palpebral edema had to be excluded. Finally, the lack of reliable equipment to quickly measure ocular pressure in newborns and obtain reliable mean values led to the need for repeated measurements, which is problematic because it is difficult to keep newborns quiet and still for long periods of time.

In conclusion, we found a relationship between weight and CCT, that is, as the mean weight increases, the CCT also increases. The mean CCT in Brazilian full-term newborns wass 605.87 µm and the mean IOP was 14.42 mmHg, and we found no relationship between these variables in the present study.