Ruth Manny - US grants

The complexities and capabilities of the adult visual system are quite remarkable. Perhaps equally impressive is the process by which these abilities are developed and refined during the first few years of life. The experiments described in this proposal are an extension of previous research on one critical aspect of this development, the development of cortical processing of vision. Specifically, the maturation of orientation tuning will be investigated in human infants using both electrophysiological and psychophysical techniques. Four different visually evoked potential (VEP) experiments and three psychophysical studies using preferential looking (PL) or optokinetic nystagmus (OKN) will be conducted. Masking, adaptation, cross orientational inhibition, and the orientation tuning of binocular interactions will be used to examine the development of orientation selectivity. By comparing the developmental time course of orientation selectivity with that of vernier acuity, it should be possible to determine if the development of vernier acuity (also believed to represent a cortical process) depends on, or is in some way linked to, the development of orientation tuning. The relationship between line detection thresholds and vernier acuity will also be explored in infants. These experiments have relevance not only to our understanding of development, but also may provide evidence regarding the mechanisms underlying vernier acuity. The orientation studies may also provide indirect evidence about the development of higher order cortical processes involved in the analysis of motion. Since normal development is easily altered during periods of rapid change, understanding normal visual development have important implications for understanding various anomalies of vision (e.g., amblyopia and strabismus).

DESCRIPTION: (Applicant's Abstract) This proposal is for the University of Houston, College of Optometry (UHCO) to serve as one of four clinical centers in the Correction of Myopia Evaluation Trial (COMET). COMET is a prospective, randomized clinical trial designed to assess whether progressive addition lenses (PAL's) slow the progression of juvenile-onset myopia, compared to conventional single vision lenses (SV). A total of four hundred children, 6-12 years of age with myopia (-1.25 to -4.50 D) in both eyes, who meet specific inclusion and exclusion criteria will be enrolled in the 4 participating centers. One hundred twelve children will be identified in Houston. These children will be recruited primarily from the University Eye Institute (UEI - the Clinic at UHCO). All eligible children will be examined at baseline and at six-month intervals for at least three years to measure changes in refractive error and to update prescriptions. A standardized, common protocol will be used at all four centers. The primary outcome measure is progression of myopia, as measured by cycloplegic autorefraction. A additional outcome measure is axial elongation as measured by A-scan ultrasonography. These outcome measures will be obtained by masked examiners. This application documents the ability of UHCO to recruit at least 112 children within one academic year, and to retain them for at least three years. Documentation is also provided that UHCO has the personnel, equipment, and facilities to conduct the study in accordance with the COMET Manual of Procedures (MOP). Complete details of the COMET rationale, design, and methods are contained in the MOP, which is submitted separately with the Study Chair and Coordinating Center applications. In addition to UHCO, the other clinical centers are located at Colleges of Optometry in Boston, Birmingham, and Philadelphia, with the Study Chair in Boston and the Coordinating Center at Stony Brook NY.

DESCRIPTION: (Applicant's Abstract) This proposal is for the University of Houston, College of Optometry (UHCO) to serve as one of four clinical centers in the Correction of Myopia Evaluation Trial (COMET). COMET is a prospective, randomized clinical trial designed to assess whether progressive addition lenses (PAL's) slow the progression of juvenile-onset myopia, compared to conventional single vision lenses (SV). A total of four hundred children, 6-12 years of age with myopia (-1.25 to -4.50 D) in both eyes, who meet specific inclusion and exclusion criteria will be enrolled in the 4 participating centers. One hundred twelve children will be identified in Houston. These children will be recruited primarily from the University Eye Institute (UEI - the Clinic at UHCO). All eligible children will be examined at baseline and at six-month intervals for at least three years to measure changes in refractive error and to update prescriptions. A standardized, common protocol will be used at all four centers. The primary outcome measure is progression of myopia, as measured by cycloplegic autorefraction. A additional outcome measure is axial elongation as measured by A-scan ultrasonography. These outcome measures will be obtained by masked examiners. This application documents the ability of UHCO to recruit at least 112 children within one academic year, and to retain them for at least three years. Documentation is also provided that UHCO has the personnel, equipment, and facilities to conduct the study in accordance with the COMET Manual of Procedures (MOP). Complete details of the COMET rationale, design, and methods are contained in the MOP, which is submitted separately with the Study Chair and Coordinating Center applications. In addition to UHCO, the other clinical centers are located at Colleges of Optometry in Boston, Birmingham, and Philadelphia, with the Study Chair in Boston and the Coordinating Center at Stony Brook NY.

DESCRIPTION (provided by applicant): This proposal is for the Houston Clinical Center to continue to annually examine the 116 currently enrolled COSMICC participants (only 2 subjects have withdrawn since recruited in 97-98) at the Houston center for an additional 5 yrs (total follow-up, 14 yrs) following the COSMICC2 protocol. The data collected from this center will be used to address specific aims described in more detail in the Chairman's grant and summarized briefly as :1)to use mathematical functions (the Gompers function and others) to model myopia progression in the 58% of COSMICC subjects with progressing myopia and to develop predictive models and test hypotheses based on previously identified risk factors (age, ethnicity, parental myopia); 2) to test 4 hypotheses related to environmental risk factors for myopia progression and stabilization and axial elongation in this well-characterized cohort of mopes; and 3) to test three hypotheses related to risk factors for the development of myopia-related changes in IOP, CCT and macular thickness in COSMICC subjects. The high prevalence of myopia (25% of the US adult population) and its prominence as a public health Problem (risk factor for conditions that can cause vision loss and blindness) emphasize the importance of gaining increased understanding of mechanisms underlying progression and eventual stabilization, so that in the future myopia might be limited to low levels. Better understanding of the factors predictive of myopia progression and stabilization also will help guide selection and timing of interventions as well as target those groups that may benefit the most from treatment.

Vision disorders such as significant refractive errors, amblyopia, and strabismus impact the developing visual system of 2 to 5% of preschool children. The long-term sequelae of these conditions that degrade visual acuity (VA) and/or binocular vision can be minimized by early detection and treatment. While early detection through a comprehensive eye examination of every infant is the ideal, the vast majority of infants and young children are without significant vision problems. Directing the limited health care resources towards those with problems or who are at risk for developing future vision problems through vision screening is a more reasoned and attainable approach. Currently, the primary responsibility for screening preschoolers for vision anomalies falls to pediatricians and family practitioners who rely on the direct measurement of one or more aspects of vision. Screening guidelines suggest inspection of eye health and red reflex at birth and 6 months to 1 year of age with VA and alignment added to the screening at age 3 to 3.5 years. Despite its common use, the efficacy of the red reflex test in screening has not been evaluated and concern over high false positive rates when used by non-ophthalmologist or in infants < 8 months suggest significant limitations. The lack of evidence to support routine vision screening in children less than 3 is reflected in the 2011 recommendations of the US Preventive Services Task Force (USPSTF) that excludes children less than 3 previously included in the 2004 recommendations. The long-term objective of this research is to provide sufficient evidence to restructure the current vision screening recommendations for children less than 3 years. The first step towards this goal and the aim of this application is to develop and validate a risk factors screening questionnaire that can be easily completed by a parent. The questionnaire will triage children into one of 3 categories that will direct the parent to: 1) schedule an eye examination as soon as possible, 2) schedule additional screening by trained personnel using existing/evolving technologies or 3) defer examination at age 3 to 5 years. A parent completed questionnaire will ease the time burden vision screening currently places on pediatricians and family practitioners and will reduce one of the often cited barriers to implementing vision screening by busy physicians. This targeted and tiered approach to vision screening will improve the efficiency and accuracy of our current, often cursory and fragmented, screening efforts. Early identification of those in need of additional assessment and/or care, through a low or no cost, widely accessible, valid and reliable questionnaire, will more effectively utilize the limited manpower and financial resources of the strained health care system.

The purpose of the Biostatistics Support Core Module is to support the statistical and computational needs of core investigators, their collaborators and students, and new investigators carrying out vision research at the University of Houston. Studies supported by the module will ranging from basic research to translational and clinical research. The biostatistics module will provide statistical support via a Core Biostatistician to the ongoing Core investigators, while facilitating future research and assisting in preparation of new grant proposals from seasoned investigators and new faculty who are establishing independent research careers. The scope of support by the BSM will include: study design (sample size and power calculations and writing statistical analysis plans), plans for data acquisition and/or management, performing statistical analysis (ranging from short consults to conducting analysis of the research data (including data management and exploratory analysis). The module also will provide advice on appropriate software packages and instruction on basic and advanced statistical concepts. A collaboration with the Texas Institute for Measurement, Evaluation, and Statistics (TIMES), a large statistical services center at UH will proved access to that institutes resources. The Core biostatistician holds a joint research faculty appointment in TIMES to strengthen the Core services by providing seamless access to additional resources of TIMES, and to strengthen TIMES by adding formally trained biostatistician to its ranks. Module strengths in epidemiology and clinical trials will be a resource for those doing clinical research. The Biostatistics core resources and expertise will stimulate collaboration and advance vision research at the University of Houston. The module will be directed by Charles Stewart Professor Ruth Manny OD, PhD with over 35 years of basic, transitional and clinical research experience, nearly 30 years of NEI funding and 10 years of module supervision. The Module will be co-directed by Heather Anderson, OD, PhD, with over 15 years of experience conducting basic, translational and clinical vision research.