Major Article The intraocular pressure and central corneal thickness in healthy premature infants Damla Erginturk Acar, MD,a Ugur Acar, MD,b Zuhal Ozen Tunay, MD,a Ozdemir Ozdemir, MD,a Anil Dolgun, PhD,c and Mesut Erdurmus, MDb PURPOSE
To describe the normal values of intraocular pressure (IOP) and central corneal thickness (CCT) in healthy premature infants.
METHODS
Infants of \32 weeks’ gestational age who underwent screened for retinopathy of prematurity were prospectively enrolled. The same ophthalmologist measured IOP by applanation tonometry and CCT using ultrasonic pachymetry. Infants were divided into four groups according to postconceptional ages (PCA). The mean values of the IOP and CCT were compared by nonparametric statistical tests, and the relationship of the PCA with IOP and CCT were analyzed with correlation tests. Only right eye measurements were analyzed.
RESULTS
A total of 470 infants (mean PCA, 35.94 4.00 weeks) were enrolled. The mean IOP with standard deviation was 16.86 2.93 mm Hg; the mean CCT, 590 58.26 mm. Both IOP and CCT values were found to be significantly higher in infants with lower versus higher PCA (P \ 0.001). There was a statistically significant negative linear relationship between the PCA and the values of IOP and CCT, separately.
CONCLUSIONS
IOP and CCT values may be higher in infants with lower PCA. Higher IOP values in these infants may be associated with higher CCT values. ( J AAPOS 2015;-:1-4)
T
he main screening methods for the diagnosis, management, and follow-up of ocular hypertension and/or glaucoma are measurement of intraocular pressure (IOP) and central corneal thickness (CCT), appearance of the optic nerve head, evaluation of retinal nerve fiber layer thickness, and computerized visual field test.1 Because the last two methods are not possible in premature infants in clinical practice, determining the normal ranges of IOP and CCT are important for glaucoma screening in premature infants. There are conflicting reports in the literature about the normal IOP and CCT ranges in premature infants. Several studies2-4 have demonstrated higher IOP and CCT values in premature infants; lower IOP measurements have also been reported.6,7 None of these studies included a sufficiently high number of patients to address the issue with any degree of certainty. The present study aimed to
Author affiliations: aDepartment of Ophthalmology, Zekai Tahir Burak Women’s Health Research and Education Hospital, Ankara, Turkey; bDepartment of Ophthalmology, Hacettepe University, Faculty of Medicine, Ankara, Turkey; cDepartment of Biostatistics, Hacettepe University, Faculty of Medicine Submitted June 23, 2014. Revision accepted October 31, 2014. Correspondence: Damla Erginturk Acar, MD, Department of Ophthalmology, Zekai Tahir Burak Women’s Health Research and Education Hospital, Ankara, Turkey (email: [email protected]). Copyright Ó 2015 by the American Association for Pediatric Ophthalmology and Strabismus. 1091-8531/$36.00 http://dx.doi.org/10.1016/j.jaapos.2014.10.027
Journal of AAPOS
report the IOP and CCT data of a large series of premature infants.
Subjects and Methods This study was approved by the Ethics Committee of Zekai Tahir Burak Women’s Health Education and Research Hospital. Written informed consent was obtained from all parents before the retinopathy of prematurity (ROP) screening examination in accordance with the Declaration of Helsinki. Infants of \32 weeks’ gestational age who were screened for ROP from May 2013 to March 2014 were prospectively enrolled. Infants with ocular abnormalities (eg, corneal, iris, lens and retinal pathologies, and glaucomatous optic nerve head changes), systemic abnormalities (eg, chromosomal disorders, visceral anomalies, and a history of topical or systemic corticosteroid use) were excluded because the study goal was to establish a normative database of IOP in healthy premature infants. Outborn premature infants were also excluded. After the topical administration of proparacaine 0.5% ophthalmic solution and the placement of an eyelid speculum, both the IOP and CCT measurements were performed in both eyes of all participants. All measurements were performed by the same ophthalmologist (DEA) at the same time of day (9:00– 12:00 am.) while infants were supine and in a peaceful state. Infants with an IOP of 5 mm Hg or 20 mm CCT difference between the two eyes were also excluded from the study. IOP measurements were performed with Tono-Pen XL (Reichert Inc, NY).8,9 The calibration of the tonometry was
1
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made strictly every morning according to the instructions in the user’s manual of the device. When the infants were calm and relaxed, the mean of 3 consecutive measurements (each of 10-valid measurements) with a standard deviation of \5% was calculated and recorded. The CCT measurements were performed using an ultrasonic pachymetry (Compact Touch 3-in-1 Ultrasound system; Cedex, France). The pachymeter probe was placed on the center of the cornea over an undilated pupil and the mean of 5 consecutive measurements within a standard deviation of 5 mm was calculated and recorded. All infants were examined only one time during the study period, not multiple times on different dates. After measurements were obtained, ROP screening was performed. For statistical analysis, data obtained from the right eyes of infants were used. Postconceptional age (PCA), in weeks, at the time of the examination of all infants were also recorded. Infants were divided into four subgroups according to PCA for further analysis: group 1, #32 weeks; group 2, 33-36 weeks; group 3: 37-40 weeks; and group 4, $41 weeks. Data analysis was performed using SPSS version 21.0 for Windows (IBM, Chicago, IL). IOP and CCT measurements were recorded as mean plus or minus standard deviation. Normality assumption was checked with Shapiro-Wilks test. Because values were not normally distributed, a nonparametric Kruskal-Wallis test was used. Conover-Dunn multiple comparison test was used to compensate the inflated type 1 error rate resulting from multiple comparisons. Correlation between the PCA and the values of IOP and CCT were analyzed with Spearman’s correlation analysis. A P value of \0.05 was considered statistically significant.
Results A total of 470 right eyes of 470 infants (268 females [57%], 202 males [43%]) who underwent ROP screening examination were included in the study. The mean gestational age at birth was 29.24 2.25 weeks; the mean PCA, 35.94 4.00 weeks. Patient demographics are summarized in Table 1. The mean IOP value was 16.86 2.93 mm Hg, and the mean CCT value was 590 58.26 mm. Group 1 included 89 (19%) infants, with mean IOP of 19.39 2.22 mm Hg and CCT of 653.99 42.02 mm; group 2, 206 (44%), with mean IOP of 17.60 2.28 mm Hg and CCT of 598.68 46.25 mm; group 3, 126 (27%), with mean IOP of 14.90 2.45 mm Hg and CCT of 554.27 42.09 mm; and group 4, 49 (10%), with mean IOP of 14.20 2.35 mm Hg and CCT of 535.61 43.55 mm (Table 2). The mean IOP and CCT differences between the groups were statistically significant (P \ 0.001), except the difference between groups 3 and 4. It was observed that IOP values of 83 infants (18%) were $20 mm Hg. Of these, 41 (46.07%) were in group 1; 36 (17%), in group 2; and 6 (5%), in group 3. There were none in group 4. A statistically significant negative linear relationship was present between the PCA and IOP (Sperman r 5 0.677;
Table 1. Demographic features of premature infants Demographic features
Values
Sex (%) Female Male GA, weeks, mean SD (range) PCA, weeks, mean SD (range)
268 (57.02) 202 (42.98) 29.24 2.25 (22-32) 35.94 4.00 (26-45)
GA, gestational age; PCA, postconceptional age; SD, standard deviation.
P \ 0.001; Figure 1). There was a statistically significant and stronger negative linear relationship between the PCA and CCT (Sperman r 5 0.698; P \ 0.001; Figure 2). There was also a statistically significant and the strongest positive linear association between the IOP and CCT (Sperman r 5 10.798; P \ 0.001; Figure 3).
Discussion The present study investigated the normative values of IOP and CCT in 470 healthy premature infants. The mean IOP value was 16.86 2.93 mm Hg by applanation tonometry in infants whose mean PCA was 35.94 4.00 weeks. IOP and CCT were found to be positively correlated, whereas both IOP and CCT were negatively correlated with PCA. In 33 premature infants, Uva and colleauges2 found a mean IOP by Tono-Pen XL (Reichert Inc, NY) of 18.9 3.7 at age 34 3 weeks and 17 2.6 mm Hg at 40 1 weeks in 33 premature infants. Ng and colleagues4 found median IOP values (by Tono-Pen II) ranging from 16.9 to 14.6 mm Hg at 26.1 and 46.4 weeks’ PCA, respectively. Although our results confirmed these two studies, several studies document a wide range of IOP in premature infants.5-7 Lindenmeyer and colleagues5 found a mean IOP (by Tono-Pen XL) of 14.9 4.5 mm Hg in 50 infants with a mean gestational age of 29.7 1.6 weeks. Tucker and colleagues6 found a mean IOP (by Tono-Pen II) of 10.3 3.5 mm Hg in 70 infants with PCA of 25-37 weeks. They also determined that the upper 95% confidence limits were 18.0 for the right eye and 17.5 mm Hg for the left eye. Similar to Tucker and colleagues,6 Spierer and colleagues7 found a mean IOP (by noncontact tonometry) of 10.11 2.21 mm Hg in 53 infants with a mean gestational age of 37.0 2.2 weeks during afternoon hours. Contrary to these two studies, the present study found a mean IOP of 19.39 2.22 mm Hg in 89 healthy infants with the lowest PCA (group 1). Morever, IOP values were $20 mm Hg in nearly half of this group. However, the mean IOP was measured as 14.20 2.35 mm Hg in 49 healthy infants with the greatest PCA (group 4). Reported studies regarding the IOP variation in infants may be associated with several issues, including methods and instruments used to measure IOP, time of the day, use of eye speculum, experience of practitioners, and racial features. Our sample is the largest case series in the literature evaluating the IOP values in premature infants.
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Table 2. The values of mean IOP and CCT of premature infants according to the groups and their level of statistical significance between groups Groups
IOP, mm Hg, mean SD (range)
CCT, mm, mean SD (range)
Group 1 #32 week (n 5 89) Group 2 33-36 week (n 5 206) Group 3 37-40 week (n 5 126) Group 4 $ 41 week (n 5 49) Total (n 5 470)
19.39 2.22 (14-24) 17.60 2.28 (11-24) 14.90 2.45 (10-20) 14.20 2.35 (10-19) 16.86 2.93 (10-24)
653.99 42.02 (549-724) 598.68 46.25 (473-721) 554.27 42.09 (402-708) 535.61 43.55 (478-640) 590.67 58.26 (402-724)
CCT, central corneal thickness; IOP, intraocular pressure.
FIG 1. Graphical view of the association between PCA and IOP in premature infants. (Spearman’s r correlation analysis 5 0.677; P \ 0.001).
FIG 2. Graphical view of the association between PCA and CCT. (Spearman’s r 5 0.698; P \ 0.001).
Lindenmeyer and colleagues5 calculated that IOP values reduced by 0.29 mm Hg per week as PCA increased. Ng and colleagues4 demonstrated a strong negative relationship between IOP and PCA in infants, which finding is consistent with our results. This longitudinal study4 determined an average rate of 0.11 mm Hg IOP per week. Uva and colleagues2 speculated that the reduction of IOP with time may be related to simultaneous reduction in CCT. Ricci and colleagues10 showed a reduction of IOP from 13.25 2.86 mm Hg to 10.96 2.01 mm Hg in their longitudinal study throughout the 5 consecutive visits in 40 eyes of 20 preterm infants, with PCA ranging from 26 to 32 weeks. However, Tucker and colleagues6 and Spierer and colleagues7 did not find a significant association between IOP and PCA. Although the present study is not longitudinal, infants with greater PCA have lower IOP values compared to those with lower PCA. IOP measurement using an indentation tonometry is not recommended in premature infants, who have low scleral rigidity. External factors may also affect IOP measurements obtained from applanation tonometry.9 To measure lOP accurately in infants, certain requirements must be met,
including a comfortable and calming environment for the baby, local anesthetic application, and a reliable IOP measurement device. In our study, during all measurements we ensured that infants were quiet and relaxed, and anesthetic eyedrops were instilled. We have used Tono-Pen XL for IOP measurements because it is one of the most accessible and reliable tonometry in this age group.4,8,9 We found a mean CCT value of 590.67 58.26 mm using an ultrasonic pachymetry in infants with a mean PCA of 35.94 4.00 weeks. In 33 infants Uva and colleagues2 found mean CCT values of 599 36 mm at 34 3 weeks and 576 26 mm at 40 1 weeks. Autzen and Bjornstrom3 found a mean CCT was 660 mm in 13 infants of\33 weeks’ gestational age, and Kirwan and colleauges11 found a mean CCT of 691 mm in 35 infants at a mean PCA of 31 weeks. Although the measured CCT values in these two studies were greater than our results, the numbers of infants was much higher in the present study. We observed a strong negative correlation between PCA and CCT, as in Uva and colleagues’ study.2 Although Kirwan and colleagues11 showed that CCT decreased dramatically from approximately 31 weeks to term in 35 infants,
Journal of AAPOS
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Volume - Number - / - 2015 carefully performed by the same ophthalmologist with the latest generation of devices, the contact measurement method and requirement of a lid speculum might have led to erroneous outcomes. Use of topical anesthetic may also have affected CCT measurement. References
FIG 3. Graphical view of the association between CCT and IOP. (Spearman’s r 5 10.798; P \ 0.001).
Spierer and colleagues7 found no correlation between PCA and CCT in 53 infants. Autzen and Bjornstrom3 found no difference between the corneal thickness in the 1st and 3rd postnatal week; however, they determined that the corneal thickness of premature babies at 3 months of age decreased significantly to the to the same level in full-term newborns.3,12 We found a dramatic decline in CCT up to 40th week, with no significant decline in CCT after that point. The possible cause of decrease in CCT during the first weeks of life may be due to corneal hydration and evaporation, and corneal remodeling.2,3,11,13 There are some limitations to our study. Although it was prospective and cross-sectional nature, the relationships between PCA, CCT, and IOP could be better identified in a longitudinal fashion. Although all procedures were
1. Song C, De Moraes CG, Forchheimer I, Prata TS, Ritch R, Liebmann JM. Risk calculation variability over time in ocular hypertensive subjects. J Glaucoma 2014;23:1-4. 2. Uva MG, Reibaldi M, Longo A, et al. Intraocular pressure and central corneal thickness in premature and full-term newborns. J AAPOS 2011;15:367-9. 3. Autzen T, Bjornstrom L. Central corneal thickness in premature babies. Acta Ophthalmol (Copenh) 1991;69:251-2. 4. Ng PC, Tam BS, Lee CH, et al. A longitudinal study to establish the normative value and to evaluate perinatal factors affecting intraocular pressure in preterm infants. Invest Ophthalmol Vis Sci 2008;49: 87-92. 5. Lindenmeyer RL, Farias L, Mendonc¸a T, Fortes Filho JB, Procianoy RS, Silveira RC. Intraocular pressure in very low birth weight preterm infants and its association with postconceptional age. Clinics (Sao Paulo) 2012;67:1241-5. 6. Tucker SM, Enzenauer RW, Levin AV, Morin JD. Hellmann J.Corneal diameter, axial length, and intraocular pressure in premature infants. Ophthalmology 1992;99:1296-300. 7. Spierer A, Huna R, Hirsh A, Chetrit A. Normal intraocular pressure in premature infants. Am J Ophthalmol 1994;117:801-3. 8. Bandyopadhyay M, Raychaudhuri A, Lahiri SK, Schwartz EC, Myatt M, Johnson GJ. Comparison of Goldmann applanation tonometry with the Tonopen for measuring intraocular pressure in a population-based glaucoma survey in rural West Bengal. Ophthalmic Epidemiol 2002;9:215-24. 9. Kanski JJ, Bowling B, Glaucoma J. Clinical Ophthalmology: A Systemic Approach. 7th ed. Philadelphia Elsevier/Saunders; 2011: 313-15. 10. Ricci B. Intraocular pressure in premature babies in the first month of life. J AAPOS 1999;3:125-7. 11. Kirwan C, O’Keefe M, Fitzsimon S. Central corneal thickness and corneal diameter in premature infants. Acta Ophthalmol Scand 2005;83:751-3. 12. Autzen T, Bjørnstrøm L. Central corneal thickness in full-term newborns. Acta Ophthalmol (Copenh) 1989;67:719-20. 13. Rem on L, Crist obal JA, Castillo J, Palomar T, Palomar A, Perez J. Central and peripheral corneal thickness in full-term newborns by ultrasonic pachymetry. Invest Ophthalmol Vis Sci 1992;33:3080-83.
Journal of AAPOS
To describe the normal values of intraocular pressure (IOP) and central corneal thickness (CCT) in healthy premature infants.
METHODS
Infants of \32 weeks’ gestational age who underwent screened for retinopathy of prematurity were prospectively enrolled. The same ophthalmologist measured IOP by applanation tonometry and CCT using ultrasonic pachymetry. Infants were divided into four groups according to postconceptional ages (PCA). The mean values of the IOP and CCT were compared by nonparametric statistical tests, and the relationship of the PCA with IOP and CCT were analyzed with correlation tests. Only right eye measurements were analyzed.
RESULTS
A total of 470 infants (mean PCA, 35.94 4.00 weeks) were enrolled. The mean IOP with standard deviation was 16.86 2.93 mm Hg; the mean CCT, 590 58.26 mm. Both IOP and CCT values were found to be significantly higher in infants with lower versus higher PCA (P \ 0.001). There was a statistically significant negative linear relationship between the PCA and the values of IOP and CCT, separately.
CONCLUSIONS
IOP and CCT values may be higher in infants with lower PCA. Higher IOP values in these infants may be associated with higher CCT values. ( J AAPOS 2015;-:1-4)
T
he main screening methods for the diagnosis, management, and follow-up of ocular hypertension and/or glaucoma are measurement of intraocular pressure (IOP) and central corneal thickness (CCT), appearance of the optic nerve head, evaluation of retinal nerve fiber layer thickness, and computerized visual field test.1 Because the last two methods are not possible in premature infants in clinical practice, determining the normal ranges of IOP and CCT are important for glaucoma screening in premature infants. There are conflicting reports in the literature about the normal IOP and CCT ranges in premature infants. Several studies2-4 have demonstrated higher IOP and CCT values in premature infants; lower IOP measurements have also been reported.6,7 None of these studies included a sufficiently high number of patients to address the issue with any degree of certainty. The present study aimed to
Author affiliations: aDepartment of Ophthalmology, Zekai Tahir Burak Women’s Health Research and Education Hospital, Ankara, Turkey; bDepartment of Ophthalmology, Hacettepe University, Faculty of Medicine, Ankara, Turkey; cDepartment of Biostatistics, Hacettepe University, Faculty of Medicine Submitted June 23, 2014. Revision accepted October 31, 2014. Correspondence: Damla Erginturk Acar, MD, Department of Ophthalmology, Zekai Tahir Burak Women’s Health Research and Education Hospital, Ankara, Turkey (email: [email protected]). Copyright Ó 2015 by the American Association for Pediatric Ophthalmology and Strabismus. 1091-8531/$36.00 http://dx.doi.org/10.1016/j.jaapos.2014.10.027
Journal of AAPOS
report the IOP and CCT data of a large series of premature infants.
Subjects and Methods This study was approved by the Ethics Committee of Zekai Tahir Burak Women’s Health Education and Research Hospital. Written informed consent was obtained from all parents before the retinopathy of prematurity (ROP) screening examination in accordance with the Declaration of Helsinki. Infants of \32 weeks’ gestational age who were screened for ROP from May 2013 to March 2014 were prospectively enrolled. Infants with ocular abnormalities (eg, corneal, iris, lens and retinal pathologies, and glaucomatous optic nerve head changes), systemic abnormalities (eg, chromosomal disorders, visceral anomalies, and a history of topical or systemic corticosteroid use) were excluded because the study goal was to establish a normative database of IOP in healthy premature infants. Outborn premature infants were also excluded. After the topical administration of proparacaine 0.5% ophthalmic solution and the placement of an eyelid speculum, both the IOP and CCT measurements were performed in both eyes of all participants. All measurements were performed by the same ophthalmologist (DEA) at the same time of day (9:00– 12:00 am.) while infants were supine and in a peaceful state. Infants with an IOP of 5 mm Hg or 20 mm CCT difference between the two eyes were also excluded from the study. IOP measurements were performed with Tono-Pen XL (Reichert Inc, NY).8,9 The calibration of the tonometry was
1
2
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Acar et al
made strictly every morning according to the instructions in the user’s manual of the device. When the infants were calm and relaxed, the mean of 3 consecutive measurements (each of 10-valid measurements) with a standard deviation of \5% was calculated and recorded. The CCT measurements were performed using an ultrasonic pachymetry (Compact Touch 3-in-1 Ultrasound system; Cedex, France). The pachymeter probe was placed on the center of the cornea over an undilated pupil and the mean of 5 consecutive measurements within a standard deviation of 5 mm was calculated and recorded. All infants were examined only one time during the study period, not multiple times on different dates. After measurements were obtained, ROP screening was performed. For statistical analysis, data obtained from the right eyes of infants were used. Postconceptional age (PCA), in weeks, at the time of the examination of all infants were also recorded. Infants were divided into four subgroups according to PCA for further analysis: group 1, #32 weeks; group 2, 33-36 weeks; group 3: 37-40 weeks; and group 4, $41 weeks. Data analysis was performed using SPSS version 21.0 for Windows (IBM, Chicago, IL). IOP and CCT measurements were recorded as mean plus or minus standard deviation. Normality assumption was checked with Shapiro-Wilks test. Because values were not normally distributed, a nonparametric Kruskal-Wallis test was used. Conover-Dunn multiple comparison test was used to compensate the inflated type 1 error rate resulting from multiple comparisons. Correlation between the PCA and the values of IOP and CCT were analyzed with Spearman’s correlation analysis. A P value of \0.05 was considered statistically significant.
Results A total of 470 right eyes of 470 infants (268 females [57%], 202 males [43%]) who underwent ROP screening examination were included in the study. The mean gestational age at birth was 29.24 2.25 weeks; the mean PCA, 35.94 4.00 weeks. Patient demographics are summarized in Table 1. The mean IOP value was 16.86 2.93 mm Hg, and the mean CCT value was 590 58.26 mm. Group 1 included 89 (19%) infants, with mean IOP of 19.39 2.22 mm Hg and CCT of 653.99 42.02 mm; group 2, 206 (44%), with mean IOP of 17.60 2.28 mm Hg and CCT of 598.68 46.25 mm; group 3, 126 (27%), with mean IOP of 14.90 2.45 mm Hg and CCT of 554.27 42.09 mm; and group 4, 49 (10%), with mean IOP of 14.20 2.35 mm Hg and CCT of 535.61 43.55 mm (Table 2). The mean IOP and CCT differences between the groups were statistically significant (P \ 0.001), except the difference between groups 3 and 4. It was observed that IOP values of 83 infants (18%) were $20 mm Hg. Of these, 41 (46.07%) were in group 1; 36 (17%), in group 2; and 6 (5%), in group 3. There were none in group 4. A statistically significant negative linear relationship was present between the PCA and IOP (Sperman r 5 0.677;
Table 1. Demographic features of premature infants Demographic features
Values
Sex (%) Female Male GA, weeks, mean SD (range) PCA, weeks, mean SD (range)
268 (57.02) 202 (42.98) 29.24 2.25 (22-32) 35.94 4.00 (26-45)
GA, gestational age; PCA, postconceptional age; SD, standard deviation.
P \ 0.001; Figure 1). There was a statistically significant and stronger negative linear relationship between the PCA and CCT (Sperman r 5 0.698; P \ 0.001; Figure 2). There was also a statistically significant and the strongest positive linear association between the IOP and CCT (Sperman r 5 10.798; P \ 0.001; Figure 3).
Discussion The present study investigated the normative values of IOP and CCT in 470 healthy premature infants. The mean IOP value was 16.86 2.93 mm Hg by applanation tonometry in infants whose mean PCA was 35.94 4.00 weeks. IOP and CCT were found to be positively correlated, whereas both IOP and CCT were negatively correlated with PCA. In 33 premature infants, Uva and colleauges2 found a mean IOP by Tono-Pen XL (Reichert Inc, NY) of 18.9 3.7 at age 34 3 weeks and 17 2.6 mm Hg at 40 1 weeks in 33 premature infants. Ng and colleagues4 found median IOP values (by Tono-Pen II) ranging from 16.9 to 14.6 mm Hg at 26.1 and 46.4 weeks’ PCA, respectively. Although our results confirmed these two studies, several studies document a wide range of IOP in premature infants.5-7 Lindenmeyer and colleagues5 found a mean IOP (by Tono-Pen XL) of 14.9 4.5 mm Hg in 50 infants with a mean gestational age of 29.7 1.6 weeks. Tucker and colleagues6 found a mean IOP (by Tono-Pen II) of 10.3 3.5 mm Hg in 70 infants with PCA of 25-37 weeks. They also determined that the upper 95% confidence limits were 18.0 for the right eye and 17.5 mm Hg for the left eye. Similar to Tucker and colleagues,6 Spierer and colleagues7 found a mean IOP (by noncontact tonometry) of 10.11 2.21 mm Hg in 53 infants with a mean gestational age of 37.0 2.2 weeks during afternoon hours. Contrary to these two studies, the present study found a mean IOP of 19.39 2.22 mm Hg in 89 healthy infants with the lowest PCA (group 1). Morever, IOP values were $20 mm Hg in nearly half of this group. However, the mean IOP was measured as 14.20 2.35 mm Hg in 49 healthy infants with the greatest PCA (group 4). Reported studies regarding the IOP variation in infants may be associated with several issues, including methods and instruments used to measure IOP, time of the day, use of eye speculum, experience of practitioners, and racial features. Our sample is the largest case series in the literature evaluating the IOP values in premature infants.
Journal of AAPOS
Volume - Number - / - 2015
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3
Table 2. The values of mean IOP and CCT of premature infants according to the groups and their level of statistical significance between groups Groups
IOP, mm Hg, mean SD (range)
CCT, mm, mean SD (range)
Group 1 #32 week (n 5 89) Group 2 33-36 week (n 5 206) Group 3 37-40 week (n 5 126) Group 4 $ 41 week (n 5 49) Total (n 5 470)
19.39 2.22 (14-24) 17.60 2.28 (11-24) 14.90 2.45 (10-20) 14.20 2.35 (10-19) 16.86 2.93 (10-24)
653.99 42.02 (549-724) 598.68 46.25 (473-721) 554.27 42.09 (402-708) 535.61 43.55 (478-640) 590.67 58.26 (402-724)
CCT, central corneal thickness; IOP, intraocular pressure.
FIG 1. Graphical view of the association between PCA and IOP in premature infants. (Spearman’s r correlation analysis 5 0.677; P \ 0.001).
FIG 2. Graphical view of the association between PCA and CCT. (Spearman’s r 5 0.698; P \ 0.001).
Lindenmeyer and colleagues5 calculated that IOP values reduced by 0.29 mm Hg per week as PCA increased. Ng and colleagues4 demonstrated a strong negative relationship between IOP and PCA in infants, which finding is consistent with our results. This longitudinal study4 determined an average rate of 0.11 mm Hg IOP per week. Uva and colleagues2 speculated that the reduction of IOP with time may be related to simultaneous reduction in CCT. Ricci and colleagues10 showed a reduction of IOP from 13.25 2.86 mm Hg to 10.96 2.01 mm Hg in their longitudinal study throughout the 5 consecutive visits in 40 eyes of 20 preterm infants, with PCA ranging from 26 to 32 weeks. However, Tucker and colleagues6 and Spierer and colleagues7 did not find a significant association between IOP and PCA. Although the present study is not longitudinal, infants with greater PCA have lower IOP values compared to those with lower PCA. IOP measurement using an indentation tonometry is not recommended in premature infants, who have low scleral rigidity. External factors may also affect IOP measurements obtained from applanation tonometry.9 To measure lOP accurately in infants, certain requirements must be met,
including a comfortable and calming environment for the baby, local anesthetic application, and a reliable IOP measurement device. In our study, during all measurements we ensured that infants were quiet and relaxed, and anesthetic eyedrops were instilled. We have used Tono-Pen XL for IOP measurements because it is one of the most accessible and reliable tonometry in this age group.4,8,9 We found a mean CCT value of 590.67 58.26 mm using an ultrasonic pachymetry in infants with a mean PCA of 35.94 4.00 weeks. In 33 infants Uva and colleagues2 found mean CCT values of 599 36 mm at 34 3 weeks and 576 26 mm at 40 1 weeks. Autzen and Bjornstrom3 found a mean CCT was 660 mm in 13 infants of\33 weeks’ gestational age, and Kirwan and colleauges11 found a mean CCT of 691 mm in 35 infants at a mean PCA of 31 weeks. Although the measured CCT values in these two studies were greater than our results, the numbers of infants was much higher in the present study. We observed a strong negative correlation between PCA and CCT, as in Uva and colleagues’ study.2 Although Kirwan and colleagues11 showed that CCT decreased dramatically from approximately 31 weeks to term in 35 infants,
Journal of AAPOS
4
Acar et al
Volume - Number - / - 2015 carefully performed by the same ophthalmologist with the latest generation of devices, the contact measurement method and requirement of a lid speculum might have led to erroneous outcomes. Use of topical anesthetic may also have affected CCT measurement. References
FIG 3. Graphical view of the association between CCT and IOP. (Spearman’s r 5 10.798; P \ 0.001).
Spierer and colleagues7 found no correlation between PCA and CCT in 53 infants. Autzen and Bjornstrom3 found no difference between the corneal thickness in the 1st and 3rd postnatal week; however, they determined that the corneal thickness of premature babies at 3 months of age decreased significantly to the to the same level in full-term newborns.3,12 We found a dramatic decline in CCT up to 40th week, with no significant decline in CCT after that point. The possible cause of decrease in CCT during the first weeks of life may be due to corneal hydration and evaporation, and corneal remodeling.2,3,11,13 There are some limitations to our study. Although it was prospective and cross-sectional nature, the relationships between PCA, CCT, and IOP could be better identified in a longitudinal fashion. Although all procedures were
1. Song C, De Moraes CG, Forchheimer I, Prata TS, Ritch R, Liebmann JM. Risk calculation variability over time in ocular hypertensive subjects. J Glaucoma 2014;23:1-4. 2. Uva MG, Reibaldi M, Longo A, et al. Intraocular pressure and central corneal thickness in premature and full-term newborns. J AAPOS 2011;15:367-9. 3. Autzen T, Bjornstrom L. Central corneal thickness in premature babies. Acta Ophthalmol (Copenh) 1991;69:251-2. 4. Ng PC, Tam BS, Lee CH, et al. A longitudinal study to establish the normative value and to evaluate perinatal factors affecting intraocular pressure in preterm infants. Invest Ophthalmol Vis Sci 2008;49: 87-92. 5. Lindenmeyer RL, Farias L, Mendonc¸a T, Fortes Filho JB, Procianoy RS, Silveira RC. Intraocular pressure in very low birth weight preterm infants and its association with postconceptional age. Clinics (Sao Paulo) 2012;67:1241-5. 6. Tucker SM, Enzenauer RW, Levin AV, Morin JD. Hellmann J.Corneal diameter, axial length, and intraocular pressure in premature infants. Ophthalmology 1992;99:1296-300. 7. Spierer A, Huna R, Hirsh A, Chetrit A. Normal intraocular pressure in premature infants. Am J Ophthalmol 1994;117:801-3. 8. Bandyopadhyay M, Raychaudhuri A, Lahiri SK, Schwartz EC, Myatt M, Johnson GJ. Comparison of Goldmann applanation tonometry with the Tonopen for measuring intraocular pressure in a population-based glaucoma survey in rural West Bengal. Ophthalmic Epidemiol 2002;9:215-24. 9. Kanski JJ, Bowling B, Glaucoma J. Clinical Ophthalmology: A Systemic Approach. 7th ed. Philadelphia Elsevier/Saunders; 2011: 313-15. 10. Ricci B. Intraocular pressure in premature babies in the first month of life. J AAPOS 1999;3:125-7. 11. Kirwan C, O’Keefe M, Fitzsimon S. Central corneal thickness and corneal diameter in premature infants. Acta Ophthalmol Scand 2005;83:751-3. 12. Autzen T, Bjørnstrøm L. Central corneal thickness in full-term newborns. Acta Ophthalmol (Copenh) 1989;67:719-20. 13. Rem on L, Crist obal JA, Castillo J, Palomar T, Palomar A, Perez J. Central and peripheral corneal thickness in full-term newborns by ultrasonic pachymetry. Invest Ophthalmol Vis Sci 1992;33:3080-83.
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