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Pupillary light reflexes in premature infants prior to 30 weeks postmenstrual age
Pupillary light reflexes in premature infants prior to 30 weeks postmenstrual age Maria Joana Osorio, MD,a Richard W. Hertle, MD,b Michael Painter, MD,c and Katherine Hinch, RNC, MSd
Data regarding the pupillary responses in very premature neonates is scarce; what data exist, moreover, is not recent. The purpose of this pilot study is to collect data on direct and consensual pupillary light responses before 30 weeks postmenstrual age. Six neonates were studied. Mean pupillary size at rest was 3.6 ± 0.4 mm. No direct or consensual responses to light were present in any of 12 eyes. Accurate information about pupillary reflexes in very premature neonates provides relevant information about the development of the visual and neurologic systems. Available information about the development of the Edinger-Westphal nucleus, sphincter pupillary muscle, optic nerve myelinization, and autonomic nervous system is briefly reviewed.
Methods This study was approved by the University of Pittsburgh Institutional Review Board and conformed to the requirements of the United States Health Insurance Portability and Accountability Act. Informed consent was obtained for all subjects. Newborn infants less than 30 weeks postmenstrual age with no serious systemic or neurologic abnormalities were enrolled. The primary outcome measure was the direct and consensual pupillary responses to light. Pupil diameter was measured with a strabismus caliper. Ambient light during testing was measured with a light meter and was maintained at less than 10 foot-candles. Pupils were illuminated using an indirect ophthalmoscope with consistent light intensity standardized by setting the rheostat at full intensity prior to each examination. Other variables analyzed included postmenstrual age, chronological age, Apgar scores, birth weight, medications, respiratory support, and phototherapy.
Results Six premature infants (5 boys) were enrolled in the study. Average gestational age was 185 15 days. Average postmenstrual age at the time of examination was 199 9 days, and mean chronological age was 10 11 days. Mean pupillary size at rest was 3.6 0.4 mm (with no difference between right and left eyes). There was Author affiliations: aDepartment of Pediatrics and Child Neurology; bDepartment of Ophthalmology and Bioengineering, and cDepartment of Neurology and Pediatrics, Children’s Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania; d Magee-Womens Hospital of UPMC, Pittsburgh, Pennsylvania Submitted June 18, 2009. Revision accepted September 2, 2009. Reprint requests: Maria Joana Osorio, MD, Resident in Pediatrics and Child Neurology, University of Pittsburgh, Children’s Hospital of Pittsburgh, 3705 Fifth Ave., Pittsburgh, PA 15213 (email: [email protected]). J AAPOS 2009;13:608-609. Copyright Ó 2009 by the American Association for Pediatric Ophthalmology and Strabismus. 1091-8531/2009/$36.00 1 0 doi:10.1016/j.jaapos.2009.09.005
608
no direct or consensual response to light in any of the 12 eyes (e-Supplement 1, available at jaapos.org, illustrates the ‘‘fixed’’ nonreactive pupils typical of the very premature neonate). Tunica vasculosa lentis was not observed in any of the subjects. Mean birth weight was 990 244 g. Mean Apgar scores were 7 at 1 minute and 8 at 5 minutes. Three patients received caffeine. Four patients had respiratory support. None was under phototherapy.
Discussion There is scarce existing literature regarding the absence of direct pupillary reflexes in very premature neonates.1-3 Isenberg and coworkers1-2 and Robinson and coworkers3 in 1989 and 1990 showed that consistent light response was present only after 30 weeks of gestational age. They found significant correlation with postmenstrual age, weight, Apgar scores, and corneal diameter. This is, to our knowledge, the first report describing the absence of a consensual pupillary light reflex in very premature neonates. We cannot exclude the influence of caffeine on the results, as it is a sympathomimetic agent that crosses the blood-brain barrier and could possibly influence the pupillary reflex due to increased sympathetic input. Accurate information about pupillary reflexes in very premature neonates assists the evaluation of the neurological system and provides relevant information concerning visual and nervous systems development. Assessing the presence of direct and consensual reflex will add information about the maturity of afferent and efferent fibers, as well as the maturity of intercalated fibers to the contralateral oculomotor nucleus. Isenberg and coworkers2 hypothesized that the development of pupillary light reflex was related to maturation of the Edinger-Westphal nucleus and/or its connections to the iris sphincter muscle. Postmortem studies showed that the Edinger-Westphal nucleus is the latest oculomotor nucleus to develop (dorsolateral and ventromedial appear first, median nucleus after, and finally accessory nucleus, classification by Kappers 1920). Accessory or Edinger-Westphal nucleus was first identified with adult characteristics by 20 weeks gestation.4 It is unclear when its connections are fully functional. The sphincter muscle of the pupil first appears at 16 weeks gestation but only becomes fully mature at 32 weeks.5 Other factors may be involved, including parasympathetic iris innervation (there is evidence supporting an important increase in parasympathetic function between 31 and 38 weeks postmenstrual age6) or visual pathways myelinization
Journal of AAPOS
Volume 13 Number 6 / December 2009 (myelinization of the optic nerve appears to start at 32 weeks and is completed only after birth).7 Further studies using electrophysiology will help to understand the maturation of the pupillary responses and its relation to the development of the previously described factors.
Literature Search PubMed and Scopus were searched using keywords consensual pupillary reflex or indirect pupillary reflex and neonate. Appendix. Supplementary Data Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.jaapos.2009.09.005.
Journal of AAPOS
Osorio et al
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References 1. Isenberg SJ, Dang Y, Jotterand V. The pupils of term and preterm infants. Am J Ophthalmol 1989;108:75-9. 2. Isenberg SJ, Molarte A, Vazquez M. The fixed and dilated pupils of preterm neonates. Am J Ophthalmol 1990;110:168-71. 3. Robinson J, Fielder AR. Pupillary diameter and reaction to light in preterm neonates. Arch Dis Child 1990;65:35-8. 4. Mann IC. The developing third nerve nucleus in human embryos. J Anat 1927;61(Pt. 4):424-38. 5. Barber AN. Embryology of the human eye. St Louis, MO: C.V. Mosby; 1955;134. 6. Clairambault J, Curzi-Dascalova L, Kauffmann F, Medigue C, Leffler C. Heart rate variablity in normal sleeping full-term and preterm neonates. Early Hum Dev 1992;28:169-83. 7. Magoon EH, Robb RM. Development of myelin in human optic nerve and tract. A light and electron microscopy study. Arch Ophthalmol 1981;99:655-9.
Data regarding the pupillary responses in very premature neonates is scarce; what data exist, moreover, is not recent. The purpose of this pilot study is to collect data on direct and consensual pupillary light responses before 30 weeks postmenstrual age. Six neonates were studied. Mean pupillary size at rest was 3.6 ± 0.4 mm. No direct or consensual responses to light were present in any of 12 eyes. Accurate information about pupillary reflexes in very premature neonates provides relevant information about the development of the visual and neurologic systems. Available information about the development of the Edinger-Westphal nucleus, sphincter pupillary muscle, optic nerve myelinization, and autonomic nervous system is briefly reviewed.
Methods This study was approved by the University of Pittsburgh Institutional Review Board and conformed to the requirements of the United States Health Insurance Portability and Accountability Act. Informed consent was obtained for all subjects. Newborn infants less than 30 weeks postmenstrual age with no serious systemic or neurologic abnormalities were enrolled. The primary outcome measure was the direct and consensual pupillary responses to light. Pupil diameter was measured with a strabismus caliper. Ambient light during testing was measured with a light meter and was maintained at less than 10 foot-candles. Pupils were illuminated using an indirect ophthalmoscope with consistent light intensity standardized by setting the rheostat at full intensity prior to each examination. Other variables analyzed included postmenstrual age, chronological age, Apgar scores, birth weight, medications, respiratory support, and phototherapy.
Results Six premature infants (5 boys) were enrolled in the study. Average gestational age was 185 15 days. Average postmenstrual age at the time of examination was 199 9 days, and mean chronological age was 10 11 days. Mean pupillary size at rest was 3.6 0.4 mm (with no difference between right and left eyes). There was Author affiliations: aDepartment of Pediatrics and Child Neurology; bDepartment of Ophthalmology and Bioengineering, and cDepartment of Neurology and Pediatrics, Children’s Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania; d Magee-Womens Hospital of UPMC, Pittsburgh, Pennsylvania Submitted June 18, 2009. Revision accepted September 2, 2009. Reprint requests: Maria Joana Osorio, MD, Resident in Pediatrics and Child Neurology, University of Pittsburgh, Children’s Hospital of Pittsburgh, 3705 Fifth Ave., Pittsburgh, PA 15213 (email: [email protected]). J AAPOS 2009;13:608-609. Copyright Ó 2009 by the American Association for Pediatric Ophthalmology and Strabismus. 1091-8531/2009/$36.00 1 0 doi:10.1016/j.jaapos.2009.09.005
608
no direct or consensual response to light in any of the 12 eyes (e-Supplement 1, available at jaapos.org, illustrates the ‘‘fixed’’ nonreactive pupils typical of the very premature neonate). Tunica vasculosa lentis was not observed in any of the subjects. Mean birth weight was 990 244 g. Mean Apgar scores were 7 at 1 minute and 8 at 5 minutes. Three patients received caffeine. Four patients had respiratory support. None was under phototherapy.
Discussion There is scarce existing literature regarding the absence of direct pupillary reflexes in very premature neonates.1-3 Isenberg and coworkers1-2 and Robinson and coworkers3 in 1989 and 1990 showed that consistent light response was present only after 30 weeks of gestational age. They found significant correlation with postmenstrual age, weight, Apgar scores, and corneal diameter. This is, to our knowledge, the first report describing the absence of a consensual pupillary light reflex in very premature neonates. We cannot exclude the influence of caffeine on the results, as it is a sympathomimetic agent that crosses the blood-brain barrier and could possibly influence the pupillary reflex due to increased sympathetic input. Accurate information about pupillary reflexes in very premature neonates assists the evaluation of the neurological system and provides relevant information concerning visual and nervous systems development. Assessing the presence of direct and consensual reflex will add information about the maturity of afferent and efferent fibers, as well as the maturity of intercalated fibers to the contralateral oculomotor nucleus. Isenberg and coworkers2 hypothesized that the development of pupillary light reflex was related to maturation of the Edinger-Westphal nucleus and/or its connections to the iris sphincter muscle. Postmortem studies showed that the Edinger-Westphal nucleus is the latest oculomotor nucleus to develop (dorsolateral and ventromedial appear first, median nucleus after, and finally accessory nucleus, classification by Kappers 1920). Accessory or Edinger-Westphal nucleus was first identified with adult characteristics by 20 weeks gestation.4 It is unclear when its connections are fully functional. The sphincter muscle of the pupil first appears at 16 weeks gestation but only becomes fully mature at 32 weeks.5 Other factors may be involved, including parasympathetic iris innervation (there is evidence supporting an important increase in parasympathetic function between 31 and 38 weeks postmenstrual age6) or visual pathways myelinization
Journal of AAPOS
Volume 13 Number 6 / December 2009 (myelinization of the optic nerve appears to start at 32 weeks and is completed only after birth).7 Further studies using electrophysiology will help to understand the maturation of the pupillary responses and its relation to the development of the previously described factors.
Literature Search PubMed and Scopus were searched using keywords consensual pupillary reflex or indirect pupillary reflex and neonate. Appendix. Supplementary Data Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.jaapos.2009.09.005.
Journal of AAPOS
Osorio et al
609
References 1. Isenberg SJ, Dang Y, Jotterand V. The pupils of term and preterm infants. Am J Ophthalmol 1989;108:75-9. 2. Isenberg SJ, Molarte A, Vazquez M. The fixed and dilated pupils of preterm neonates. Am J Ophthalmol 1990;110:168-71. 3. Robinson J, Fielder AR. Pupillary diameter and reaction to light in preterm neonates. Arch Dis Child 1990;65:35-8. 4. Mann IC. The developing third nerve nucleus in human embryos. J Anat 1927;61(Pt. 4):424-38. 5. Barber AN. Embryology of the human eye. St Louis, MO: C.V. Mosby; 1955;134. 6. Clairambault J, Curzi-Dascalova L, Kauffmann F, Medigue C, Leffler C. Heart rate variablity in normal sleeping full-term and preterm neonates. Early Hum Dev 1992;28:169-83. 7. Magoon EH, Robb RM. Development of myelin in human optic nerve and tract. A light and electron microscopy study. Arch Ophthalmol 1981;99:655-9.