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Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study, The

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



The Orinda Longitudinal Study of Myopia (OLSM) was started in 1989 to investigate normal eye growth and the development of myopia in over 1,200 school-aged children to date. Beginning in 1997, three parallel study phases are being conducted. Phase 1 investigates additional factors that may predict the onset of juvenile myopia (accommodative function, peripheral refractive error, intraocular pressure, and school achievement). Phase 2 compares and contrasts the optical ocular components and refractive error profiles of other ethnic groups with the predominantly Caucasian Orinda database. Phase 3 conducts DNA-based studies on the prevalent OLSM myopes and their families to use these phenotypically well-characterized children and a panel of candidate genes to look for evidence of genetic factors. In parallel with the candidate gene association, family material is used in an allele sharing approach to identify loci using highly variable, PCR-based markers.

In Phase 1 we continue to examine Orinda Union School District children in grades 1 through 8 (ages 6 through 14 years) annually. The measurement of accommodative response, accommodative lag, phoria, response AC/A ratio, peripheral refractive error, and intraocular pressure will be added to the existing protocol, and photokeratoscopy and two measures of tonic accommodation will be eliminated to minimize respondent burden. Parents of children in the study will be contacted for their permission to release school achievement data (Iowa Test of Basic Skills).

Phase 2 adds a major component by adding three clinical centers to assess the influence of ethnicity on normal ocular and refractive error development. Children in these three are examined annually with initial enrollment in all grades from 1 through 8 using the revised OLSM protocol as described above.

Increased prevalence of myopia among children of myopic parents, twin studies, segregation analysis, and our own preliminary analyses from the OLSM support a genetic etiologic component for myopia. In phase 3, we use the phenotypic characterization of children in the Orinda Longitudinal Study of Myopia to identify prevalent cases of myopia and their families. These well-defined phenotypic myopes and non-myopic siblings and their parents are being explored, seeking to develop a panel of candidate genes for myopia and to conduct an allele sharing analysis in these families


The Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study is a multi-center, observational investigation of ocular development and refractive error development in schoolchildren. It adds three clinical centers to the Orinda Longitudinal Study of Myopia (OLSM), begun in 1989, specifically to describe normal ocular growth in children ages 6 to 14 years, and to develop the ability to predict juvenile onset myopia before it is clinically evident. In addition to the more than 1,300 predominantly Caucasian children enrolled in the OLSM, three additional clinical sites enroll African-American, Hispanic, and Asian children. The children are examined annually for at least four years. Examinations include visual acuity, refraction by a variety of methods (cycloplegic autorefraction being the primary outcome measure), cover test at distance and near, accommodative response assessment with the autorefractor, response AC/A ratio measurement, videophakometry, peripheral refraction, and A-scan ultrasonography.

Patients are examined at 4 clinical centers. The clinical centers have enrolled 3,493 patients as of April 28, 1999.

Patient Eligibility

Children were eligible if they were enrolled in the first through eighth grades in selected schools in Eutaw, Alabama; Houston, Texas; Orinda, California; or Irvine, California in the 1997-98 academic year and in the first grade only in Eutaw, Houston, and Irvine in the 1998-99 academic year.

Patient Recruitment Status

As of June 11, 2001, 4,034 subjects had been enrolled. Enrollment continues.

Current Status of Study



One early finding was that children who have parents who are myopic already have eyes that are shaped like those of a nearsighted person. Other results focus on the prediction of nearsightedness before it occurs. We have found that the refraction in the third grade is a good predictor of myopia onset between grades 4 and 8. We have also found that there are distinct ethnic differences in the prevalence of nearsightedness.


Mutti DO, Jones LA, Moeschberger ML, Zadnik K: AC/A ratio, age, and refractive error in children. Invest Ophthalmol Vis Sci 41: 2469-2478, 2000.

Zadnik K, Jones LA, Irvin BC, Kleinstein RN, Manny RE, Shin JA, Mutti DO for the CLEERE Study Group: Myopia and ambient night-time lighting. Nature 404: 143-144, 2000.

Mutti DO, Sholtz RI, Friedman NE, Zadnik K: Peripheral refraction and ocular shape in children. Invest Ophthalmol Vis Sci 41: 1022-1030, 2000.

Zadnik K, Mutti DO, Friedman NE, Qualley PA, Jones LA, Qiu P, Kim HS, Hsu JC, Moeschberger ML: Ocular predictors of the onset of juvenile myopia. Investigative Ophthalmology & Visual Science, August, 1999.

Shin JA, Manny RE, Kleinstein RN, Mutti DO, Zadnik K: Short-term repeatability of hand-held keratometry measurements. Optometry and Vision Science 76: 247-253, 1999.

Zadnik K, Mutti DO, Kim HS, Jones LA, Qiu P, Moeschberger ML: Tonic accommodation, age, and refractive error in children. Investigative Ophthalmology & Visual Science 40: 1050-1060, 1999.

Mutti DO, Zadnik K, Fusaro RE, Friedman NE, Sholtz RI, Adams AJ: Optical and structural development of the crystalline lens in childhood. Investigative Ophthalmology & Visual Science 39: 120-133, 1998.

Friedman NE, Mutti DO, Zadnik K: Corneal changes in schoolchildren. Optometry and Vision Science 73: 552-557, 1996.

Friedman NE, Zadnik K, Mutti DO, Fusaro RE: Quantifying corneal toricity from videokeratography with Fourier analysis. Journal of Refractive Surgery 12: 108-113, 1996.

Walline JJ, Zadnik K, Mutti DO: Validity of surveys reporting myopia, astigmatism, and presbyopia. Optometry and Vision Science 73: 376-381, 1996.

Zadnik K, Mutti DO, Fusaro RE, Adams AJ: Longitudinal evidence of crystalline lens thinning in children. Investigative Ophthalmology and Visual Science 36: 1581-1587, 1995.

Zadnik K, Friedman NE, Mutti DO: Repeatability of corneal topography. The “corneal field”. Journal of Refractive Surgery 11: 119-125, 1995.

Mutti DO, Zadnik K, Adams AJ: The equivalent refractive index of the crystalline lens in childhood. Vision Research 35: 1565-1573, 1995.

Zadnik K, Satariano WA, Mutti DO, Adams AJ, Sholtz RI: The effect of parental history of myopia on children's eye size. Journal of the American Medical Association 271: 1323-1327, 1994.

Zadnik K, Mutti DO, Friedman NE, Adams AJ: Initial cross-sectional results from the Orinda Longitudinal Study of Myopia. Optometry and Vision Science 70: 750-758, 1993.

Zadnik K, Mutti DO, Adams AJ: The repeatability of measurement of the ocular components. Investigative Ophthalmology and Visual Science 33: 2325-2333, 1992.

Mutti DO, Zadnik K, Adams AJ: A video technique for phakometry of the human crystalline lens. Investigative Ophthalmology and Visual Science 33: 1771-1782, 1992.

Kleinstein RN, Mutti DO, Manny RE, Shin JA, Zadnik K: Cycloplegia in African-American children. Optometry and Vision Science 76: 102-107.

NEI Representative

Donald F. Everett, MA
National Eye Institute
National Institutes of Health
Executive Plaza South, Suite 350
6120 Executive Boulevard MSC 7164
Rockville, MD 20892-7164
Telephone: (301) 496-5983
Fax: (301) 402-0528

Last Updated: 6/25/01

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