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Clinical Studies Supported by the NEI

A Prospective Study of Central Corneal Thickness in Children Less than 18 Years Old

Purpose | Background | Description | Patient Eligibility | Patient Recruitment Status | Current Status of Study | Results | Publications | Clinical Centers | NEI Representative | Resource Centers

Purpose:

The primary objective of the study is to determine the distribution of central corneal thickness (CCT) in a normal population of children aged 0 to <18 years and whether this distribution varies within race/ethnicity subpopulations and age groups. Secondary objectives include 1) the determination of the age at which adult CCT is reached, 2) the determination of other possible clinical correlates of CCT, including cycloplegic refractive error determined by retinoscopy and IOP, and 3) the comparison of IOP measurements with the GAT and Tonopen instruments in children aged 8 to <18 years and handheld GAT and Tonopen instruments in children 0 to 8 years while under anesthesia.

Primary Analysis

The primary analysis will consist of estimation of mean CCT and its 95% confidence interval within each of 10 age groups of interest separately for each of 3 race/ethnicity groups, i.e. Whites, African-Americans, and Hispanics.

Background:

The importance of central corneal thickness (CCT) in the diagnosis and treatment of ocular hypertension and open angle glaucoma has been recently reported. This led to several studies of adult corneal thickness, particularly among various ethnic groups. It has been determined to vary amongst racial subpopulations, with thinner CCT found in African-American groups.

It is unknown if the CCT data in adults can be extrapolated to a pediatric population. Knowledge of CCT in a large study of healthy children without glaucoma is important in order to establish normal CCT measurements among various age groups and races. In addition, a large cross-sectional study can determine when pediatric CCT reaches adult values. It is known that the axial growth of the eye occurs until the age of 10 years, although corneal diameter growth is complete by 3 years. It is unknown if CCT is affected by these developmental changes of the globe, or when CCT reaches adult thickness. These data can be utilized in planning for corneal refractive surgery. Refractive surgery is currently being performed on a limited basis in the pediatric age range. PRK and LASIK, the two most frequent procedures performed in this age group, result in a reduction of CCT. Knowledge of normal mean CCT in the pediatric population, among varying age ranges, can affect guidelines for the amount of laser which can be safely be administered.

There are few published studies of CCT in a pediatric age group. Hussein et al performed prospective central and paracentral corneal thickness measurements on 198 eyes of 108 children. CCT and paracentral corneal thickness were found to increase over time, and reached adult thickness between 5-9 years of age. Dai and Gunderson prospectively analyzed pediatric CCT among various ethnic groups, and found CCT was similar in Whites and Hispanics, and thinner in African-Americans. They found no difference among age groups within 0-18 years, when stratified into age groups of less than 2 years, 2-4 years, 5-9 years, and 10-18 years. No gender difference was noted. Muir et al conducted a retrospective chart review on 69 subjects, and found CCT to be higher in ocular hypertension than in control or glaucoma subjects. African-American children in the study had thinner corneas, although this was not found to be statistically significant. Cabrera et al studied preoperative CCT in subjects with congenital cataracts. They found thicker corneas in subjects who developed aphakic glaucoma after lensectomy. However, a recognized limitation was the lack of normative CCT data for the infantile age group.

Thinner CCT in African-American adults has led to erroneously normal intraocular pressure (IOP) measurements, and undertreated glaucoma. If a similar relationship with corneal thickness is found in children, vigilance for other signs of glaucoma would be required in subjects with thin corneas and borderline high IOP. In addition if race or ethnicity differences are found for CCT in children, this information will guide clinicians in their interpretation of the measured IOPs.

CCT has been measured using various modalities, including ultrasonic contact pachymeters and non-contact pachymeters. Ultrasound pachymetry is the current standard for CCT measurement and hence was chosen for use in the current study. Newer modalities include noncontact pachymeters such as scanning slit topography (i.e. Orbscan) and camera pachymeter (i.e. Pentacam). Recent studies have compared the reliability and reproducibility of the different pachymeter types. Airiani et al found agreement of CCT measurements in adult subjects regardless of pachymeter type. A DGH non-handheld contact ultrasound pachymeter unit was compared to a noncontact optical low-coherence reflectometry unit in the study. Amano et al reported ultrasound pachymetry in adults to have the smallest intraexaminer variability, compared to rotating camera pachymetry and scanning slit topography. Similar mean CCT and interexaminer reproducibility were noted regardless of pachymeter type used.

Intraocular Pressure Measurement in Pediatric Subjects

A prior comparison of the Tonopen XL to the Goldmann Applanation Tonometer (GAT) in adults with normal corneas found the IOP measurements to be similar. When the GAT-determined IOP measurement was greater than 20 mm Hg, the Tonopen values were lower and found to underestimate IOP. There were no significant differences between the two modalities of IOP measurement with respect to interobserver values or with sequence of IOP measurement (GAT before Tonopen versus Tonopen before GAT). In another study when compared to simultaneous manometry, applanation tonometry was found to overestimate pressure in young eyes, while the Tonopen was not sufficiently accurate.

The recently issued consensus statement from the World Glaucoma Congress stated that "the question of whether one tonometer is superior to the others in pediatric subjects is unresolved." Longitudinal care of children often involves obtaining IOP measurements with one or the other instrument. Evidence for (or against) comparability between measurements with the two instruments would serve to improve clinical care across settings.

A survey of PEDIG sites found that approximately one-third of sites primarily used Tonopen for all IOP measurement in the ambulatory setting, while one-third of sites used Tonopen in younger children and slit-lamp mounted GAT in older children, and 10% primarily used only GAT. For an exam under anesthesia, more than half of sites used the Tonopen, while 10% used Tonopen or hand-held GAT (eg., Perkins Applanation Tonometer) depending on the child’s age or used GAT exclusively. The handheld GAT is based on the same principles as the slit-lamp mounted applanator and uses the same Goldmann prism. Given the preponderant use of two types of instruments, the Tonopen and GAT, at PEDIG sites and lack of comparative data on IOP measurement with these instruments in children, the current study will obtain Tonopen IOP and slit-lamp mounted GAT IOP measurements in cooperative children 8 years of age or older. In addition we propose in those sites with a Tonopen and hand-held GAT to obtain both measurements in children less than 8 years under anesthesia. The instrument comparison data collection will be limited to a subset of sites that have a slit-lamp mounted and/or handheld GAT and have at least 2 testers able to perform IOP measurements.

We will not be able to pool the IOP measurements obtained in awake subjects with those under general anesthesia. Inhalation anesthetic agents have been shown to lower IOP. Commonly used agents such as halothane and sevoflurane have been reported to lower IOP during induction of anesthesia. Endotracheal intubation is known to increase IOP, while a laryngeal mask airway does not have a similar effect. It has been clinical practice to measure IOP in the operating room under general anesthesia within the first 2 minutes after induction of mask inhalation anesthesia, for fear of the gradual reduction observed in the measured pressure. A recent report measuring IOP every minute from induction found that this reduction did not occur until 6 minutes after induction. This time course would appear to be sufficiently slow to not affect our inter-instrument comparisons. By protocol we will try to make our measurements within three minutes of induction whenever medically possible, prior to the anesthesia-induced decline.

Description:

A subject is considered for the study after undergoing a routine eye examination by an investigator (as part of standard care) that identifies normal corneas and no history of current or past glaucoma diagnosis or treatment.

Treatment

The sequence of examination procedures for subjects at sites not participating in comparison of Tonopen with GAT measurement of IOP is as follows: (1) CCT measurement, (2) Tonopen IOP measurement and (3) cycloplegic refraction with dilated fundus examination, if not performed within the prior 6 months.

The sequence of examination procedures for subjects at sites participating in the comparison of Tonopen with GAT measurement of IOP is as follows (two testers available): (1) CCT measurement, (2) randomization to EITHER IOP Tonopen measurement first, followed by IOP GAT measurement, OR IOP GAT measurement first, followed by IOP Tonopen measurement, and (3) cycloplegic refraction with dilated fundus examination, if not performed within the prior 6 months. For children examined under general anesthesia, IOP must be measured within 3 minutes of induction of anesthesia.

CCT will be performed on both eyes of each subject. IOP measurements for this study will be performed on the right eye only. The IOP measurements will be performed by two separate testers.

Visit Schedule

Study procedures will be performed during a single routine office or operating room visit being conducted for subject care purposes.

Patient Eligibility:

The following criteria must be met for the subject to be enrolled in the study:

  • Age 0 to <18 years
  • Ability in either a clinic or an operating room setting to have CCT measured by ultrasound pachymetry
  • Documentation of cycloplegic refraction of both eyes at the time of enrollment, or within 6 months prior to enrollment
The following can be included:
  • Subjects with strabismus, nasolacrimal duct obstruction, or other eye disorders that do not affect corneal thickness
None of the following are present:
  • Anterior segment dysgenesis
  • Congenital cataract
  • Contact lens use (no current use, regardless of frequency)
  • Periocular or oral steroid use
  • Uveitis
  • Corneal abnormality
  • Microphthalmia
  • Marfan syndrome
  • Current or past glaucoma diagnosis or treatment
  • History of intraocular surgery or refractive surgery
  • Optic nerve edema, abnormal optic nerve elevation (pseudopapilledema), or optic nerve drusen
  • History of prematurity <37 weeks gestational age

No subjects will be withdrawn from the study, even if glaucoma is diagnosed upon completion of the examination procedures. Those data will be collected, but not used in the analysis of the primary study outcome.

Patient Recruitment Status:

Not yet recruiting. Comments: Recruitment began in June 2008.

Current Status of Study:

Comments:

Results:

None

Publications

None

Clinical Centers



For participating centers visit:
Pediatric Eye Disease Investigator Group website
URL: http://public.pedig.jaeb.org/myInvestigators.php

NEI Representative



Donald F. Everett, M.A.
National Eye Institute
National Institutes of Health
Suite 1300
5635 Fishers Lane, MSC 9300
Bethesda , MD 20892-9300
USA
Fax: (301) 402-0528

Resource Centers


Co-Chairman
Michael X. Repka, M.D.
Wilmer Eye Institute
233 N. Wolfe Street
Baltimore , MD 21287-9028
USA

Co-Chairman
Jonathan M. Holmes, M.D.
Mayo Clinic
Department of Ophthalmology W7
200 First Street Southwest
Rochester , MN 55905
USA

Data Coordinating Center
Roy W. Beck, M.D., Ph.D.
Nicole M. Boyle
Christina M. Cagnia-Morales
Danielle Chandler, M.S.P.H.
Laura Clark
Katrina Dawson
Heidi A. Gillespie
Joseph Kaplon
Raymond T. Kraker, M.S.P.H.
Stephanie V. Lee
B. Michele Melia, Sc.M.
Pamela S. Moke, M.S.P.H.
Nicole Reese
Diana Rojas

Jaeb Center for Health Research
15310 Amberly Drive
Suite 350
Tampa, FL 33647
USA
Telephone: 813-975-8690
Email: pedig@jaeb.org
URL: PEDIG Public Website

Protocol Chair
Yasmin S. Bradfield, M.D.
University of Wisconsin
Department of Ophthalmology and Visual Sciences
2870 University Ave, #206
Madison, WI 53705

Last Updated: 10/9/2008

 

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