Neurodevelopmental Outcomes in Cerebral Visual Impairment

NCT07212010 | Enrolling By Invitation

• 2 other identifiers: 2024-0772R01EY036154-01A1
• Study Type: observational
• Target: 600
• Locations: 1 country
• Sites: 1

Brief Summary

Cerebral visual impairment (CVI) is one of the leading causes of pediatric visual impairment and negatively impacts the development of motor, language, and cognitive skills. This study proposes to (1) establish a novel and easy to use CVI screening algorithm for infants and (2) develop CVI subtypes based on vision, motor, language, and cognition. The overarching goal is to identify CVI early and enhance our comprehension of CVI's impact on a child's development. The results will fundamentally change the approach to designing treatments for children with CVI.

Conditions

Cerebral Visual Impairment

Keywords

Cerebral visual impairment; screening; Neurodevelopment; vision; cortical visual impairment

Outcome Measures

Primary Outcomes (31)

• Preverbal Visual Assessment (PreViAs)

  The PreViAs (Preverbal Visual Assessment) is a questionnaire designed to assess visual cognitive behavior in infants under 24 months of age, through caregiver report. It consists of 30 questions that evaluate visual attention, communication, motor coordination, and processing skills. The questionnaire aims to identify visual difficulties that may not be detected through standard vision tests, allowing for early intervention and support for children at risk for visual impairments.

  Aim 1: 6, 9, and 12 months of age (corrected age if born preterm)

• Visual Acuity

  This study will offer several age and cognitively appropriate assessments to test visual acuity. Each child will participate in a visual acuity test. Optotype (recognition acuity) test of binocular visual acuity (Lea Number, Lea Symbol, or other Snellen equivalent) chart will be measured at a distance and near. Teller Acuity cards (grading resolution acuity) will be used with infants and young children who are nonverbal or pre-verbal and do not require a verbal response.

  Aim 1: If/when visual concern are indicated on the Preverbal Visual Assessment (PreViAs) screening tool and/or at 12 months age (corrected if preterm); Aim 2: At enrollment (baseline) and 12 months later

• Contrast sensitivity

  This study will offer several assessments to test visual function depending on age and cognitive ability. Contrast sensitivity threshold is a measure of visual function. Contrast sensitivity will be measured by the Heiding Heidi cards using 2 alternative forced choice, Lea symbols or numbers flip chart, Peli Robson near chart.

  Aim 1: If/when visual concern are indicated on the Preverbal Visual Assessment (PreViAs) screening tool and/or at 12 months age (corrected if preterm); Aim 2: At enrollment (baseline) and 12 months later.

• Visual Fields

  This study will offer several assessments to test the peripheral visual field depending on age and cognitive level. Assessing visual fields is a measure of visual function. Kinetic arc perimetry or confrontation visual field testing.

  Aim 1: If/when visual concern are indicated on the Preverbal Visual Assessment (PreViAs) screening tool and/or at 12 months age (corrected if preterm); Aim 2: At enrollment (baseline) and 12 months later

• Color Vision

  This study will offer several assessments to test color vision depending on age and cognitive level. The American Optical Hardy-Rand-Ritler (AO HRR) color plates using symbol detection or Panel 16 Quantitative Color Vision Test - Double Set (D-16) using chip alignment or matching paradigm.

  Aim 2: At enrollment (baseline) and 12 months later

• Eye Motility

  This study will offer several tests of eye motility depending on age and cognitive level. The following eye movements will be assessed by direct observation using developmentally appropriate targets: Fixation (absent, sporadic, unstable, stable); Smooth pursuit (absent, discontinuous, normal); Saccades (absent, hypometric, normal), and alignment to both distant and near targets. We will also measure eye gaze using a video-based eye tracking system.

  Aim 1: If/when visual concern are indicated on the Preverbal Visual Assessment (PreViAs) screening tool and/or at 12 months age (corrected if preterm); Aim 2: At enrollment (baseline) and 12 months later

• Objects in motion

  The ability to recognize objects that are in motion or the inability to recognize and/or attend to objects without motion. This will be assessed through clinical observation and parent report.

  Aim 1: If/when visual concern are indicated on the Preverbal Visual Assessment (PreViAs) screening tool and/or at 12 months age (corrected if preterm); Aim 2: At enrollment (baseline) and 12 months later

• Accomodation

  Accommodative response will be measured through dynamic retinoscopy or the monocular estimation method.

  Aim 1: If/when visual concerns are indicated on the Preverbal Visual Assessment (PreViAs) screening tool and/or at 12 months of age (corrected if preterm); Aim 2: At enrollment (baseline) and 12 months later.

• Stereo Acuity

  Stereoacuity will be administered at near (40cm) in current spectacle correction using the Randot Butterfly and Randot Preschool stereoacuity tests. Stereoacuity is defined as the smallest disparity in which the subject can correctly name or match at least 3 out of 4 target objects in the Randot Preschool stereoacuity tests.

  Aim 2: At enrollment (baseline) and 12 months later

• Hemispatial neglect

  Hemispatial neglect is measured when indicated using line bisection, Teddy Bear, and/or bell test.

  Aim 2: At enrollment (baseline) and 12 months later

• Object recognition

  Formal and informal measures of object recognition are used. Formal measures include Lea Symbols (color puzzle, black and white puzzle, 2D representation). Informal measures include recognition of 2D and 3D materials, both near and at a distance.

  Aim 2: At enrollment (baseline) and 12 months later.

• Optic Ataxia

  The LEA Mailbox test will be used to evaluate optic ataxia. The movements of the wrist and fingers are observed as the subject attempts to pass a card through the slot of a large, round disc. The ability of the subject to move the card towards the slot and to orient in the direction of the slot will be recorded. Alternatively, for younger participants, toys such as a piggy bank will be used.

  Aim 2: At enrollment (baseline) and 12 months later

• Apraxia of the upper and lower limb

  Upper limb apraxia is measured through clinical observation of hand and arm movement toward an object of interest. This measurement will begin at 4 months of age. Lower limb apraxia will be measured through clinical observation of foot and leg movement toward an object of interest. This will be measured starting at 12 months of age.

  Aim 1: If/when visual concern are indicated on the Preverbal Visual Assessment (PreViAs) screening tool and/or at 12 months age (corrected if preterm); Aim 2: At enrollment (baseline) and 12 months later

• Spatial Perception

  The ability to identify and match rectangles of different orientations and sizes using the Lea Rectangle game, shape sorter, or puzzles.

  Aim 2: At enrollment (baseline) and 12 months later

• Simultanagnosia

  The ability to attend to more than one object simultaneously will be assessed through clinical observation, AO HRR color plates, and birthday party test.

  Aim 2: At enrollment (baseline) and 12 months later

• Facial Recognition

  The ability to recognize familiar and/or unfamiliar faces will be assessed through parent report, 9-gaze app and NEPSY.

  Aim 1: If/when visual concern are indicated on the Preverbal Visual Assessment (PreViAs) screening tool and/or at 12 months age (corrected if preterm); Aim 2: At enrollment (baseline) and 12 months later

• Facial Expressions

  The ability to interpret facial expresssions will be measured through parent report and Lea expressions test (two-alternative forced choice)

  Aim 1: If/when visual concern are indicated on the Preverbal Visual Assessment (PreViAs) screening tool and/or at 12 months age (corrected if preterm); Aim 2: At enrollment (baseline) and 12 months later

• Children's Visual Impairment Test (CVIT)

  This study will offer several assessments to test functional vision depending on age and ability level. The Children's Visual Impairment Test (CVIT) 3-6 is a measure of visual function. The CVIT is a standardized, non-verbal assessment designed to evaluate visual perceptual abilities in children aged 3 to 6 years who may have visual impairments or developmental delays. It is an assessment of how well a child can recognize and match visual patterns, independent of language or motor skills. It is completed on the computer. The domains assessed include form perception, spatial relationships, and object recognition.

  Aim 2: At enrollment (baseline) and 12 months later

• Beery-Buktenica Developmental test of Visual Motor Integration (Beery VMI)

  This study will offer several assessments to test functional vision depending on age and ability level. The Beery-Buktenica Developmental Test of Visual-Motor Integration (Beery VMI) is a measure of visual function. The Beery VMI is a standardized assessment tool designed to evaluate how well individuals can coordinate their visual perception and motor (finger and hand) control. There are three subtests. The main subtest is Visual Motor Integration and the optional subtests are Visual Perception and Motor Coordination. The Beery can be implemented with children 2-18 years. For this study, it will be implemented with children who have the ability to hold a pencil and complete pencil/paper tests.

  Aim 2: At enrollment (baseline) and 12 months later

• CVI Range

  This study will offer several assessments to test functional vision depending on age and ability level. The CVI Range is a measure of visual function developed by Dr. Christine Roman-Lantzy. The CVI Range is a functional assessment tool used to evaluate the visual abilities of individuals with Cortical/Cerebral Visual Impairment (CVI). The CVI Range helps determine how a person with CVI uses their vision in everyday settings. It is scored on a scale from 1-10 and can be used to assess children from 9 months to 18 years. In this study, it will be used to assess visual function in all participants.

  Aim 2: At enrollment (baseline) and 12 months later

• Austin Assessment

  The Austin Assessment will be used to measure eye movements and the ability to recognize and match cards with increasing complexity. The test measures search patterns, time to complete, accuracy, and time to initiate the task.

  Aim 2: At enrollment (baseline) and 12 months later

• A Developmental NEuroPSYchological Assessment (NEPSY) - Affect Recognition subtest

  This study will offer several assessments to test functional vision depending on age and ability level. The NEPSY Affect Recognition subtest measures an aspect of visual function. It designed to assess a child's ability to recognize and interpret facial expressions of emotion. It's part of the Social Perception domain in the NEPSY-II battery. It can be administered to children between 4 to 16 years. It assesses matching faces showing the same emotion, identifying emotions from facial expressions and understanding subtle differences in affect.

  Aim 2: At enrollment (baseline) and 12 months later

• Bayley Scale of Infant Development (BSID-IV)

  The BSID-IV assesses the three neurodevelopmental domains of interest including cognition, language (receptive and expressive) and motor (fine and gross). The BSID will be used to test children 28 months and younger (corrected age if born preterm).

  Aim 2: Enrollment (Baseline) and 12 Months later

• The Peabody Developmental Motor Scales (PDMS)

  The Peabody Developmental Motor Scales (PDMS-2) is a standardized assessment tool used to evaluate gross and fine motor skills in children from birth through 5 years of age.

  Aim 2: Enrollment (Baseline) and 12 Months later

• Gross Motor Function Measure-66 (GMFM-66)

  The Gross Motor Function Measure-66 (GMFM-66) is a standardized observational assessment used to evaluate gross motor function in children with cerebral palsy and other motor impairments. It measures changes in gross motor abilities over time or in response to intervention. It can be used for children aged 5 months to 16 years,

  Aim 2: Enrollment (Baseline) and 12 Months later

• The Movement Assessment Battery for Children (MABC)

  The Movement Assessment Battery for Children (MABC) is a standardized tool used to assess motor coordination and movement difficulties in children and adolescents aged 3 to 16 years. It is used to identify motor impairments and supports diagnosis of conditions like Developmental Coordination Disorder (DCD).

  Aim 2: At enrollment (baseline) and 12 months later

• The Preschool Language Scales- 5th Edition (PLS-5)

  This study will offer several assessments to test speech and language, depending on age and ability level. The Preschool Language Scales, Fifth Edition (PLS-5) is a standardized assessment tool used to evaluate language development in children from birth through 7 years, 11 months. It assesses both receptive (understanding) and expressive (speaking) language skills.

  Aim 2: Enrollment (Baseline) and 12 Months later

• Rosetti Infant Toddler Language Scale

  This study will offer several assessments to test speech and language, depending on age and ability level. The Rossetti Infant-Toddler Language Scale is a criterion-referenced assessment tool used to evaluate communication and language development in children from birth to 3 years of age. It identifies delays in preverbal and verbal communication skills.

  Aim 2: At enrollment (baseline) and 12 months later

• Goldman Fristoe Test of Articulation (GFTA)

  This study will offer several assessments to test speech and language, depending on age and ability level. For children who present with an articulation deficit, the Goldman Fristoe Test of Articulation will be administered. The GFTA is a standardized assessment used to evaluate articulation skills in individuals aged 2 to 21 years.

  Aim 2: At enrollment (baseline) and 12 months later

• The Weschler Preschool & Primary Scale of Intelligence - Fourth Edition (WPPSI-IV)

  This study will offer several assessments to test cognition, depending on age and ability level. The Wechsler Preschool and Primary Scale of Intelligence - Fourth Edition (WPPSI-IV) is a standardized cognitive assessment designed for children aged 2 years 6 months to 7 years 7 months. It measures intellectual functioning and helps identify cognitive strengths and weaknesses.

  Aim 2: At enrollment (baseline) and 12 months later

• The Leiter International Performance Scale 3 (Leiter 3)

  This study will offer several assessments to test cognition, depending on age and ability level. The Leiter International Performance Scale - Third Edition (Leiter-3) is a nonverbal intelligence and cognitive abilities test designed for children aged 3 to 18 years. It assesses nonverbal IQ, attention, memory, and processing speed.

  Aim 2: At enrollment (baseline) and 12 months later

Study Arms (2)

Screening

This group will be screened for CVI in the first year of life. Children with positive screens for CVI will undergo a comprehensive CVI evaluation.

Neurodevelopment

Children in this group will participate in a multi-disciplinary CVI clinic as well as neurodevelopmental testing and a neuro-ophthalmic eye exam at baseline and 12 months later.

Eligibility Criteria

• Age: 6 Months - 72 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Aim 1: (at risk group) Children with medical and neuroimaging conditions that put children at high risk for cerebral visual impairment (control group) age matched peers without high-risk medical and neuroimaging conditions. Aim 2: Children with a diagnosis of cerebral visual impairment confirmed by a CVI multidisciplinary team visit.

You may qualify if:

• Aim 1 (CVI Risk Group): Infants 8 months of age and who meet any of the following:
• The presence of any of the following comorbid diagnoses (CVI risk criteria): brain injury, hypoxia/ischemia, congenital structural abnormalities of the brain, genetic syndromes, epilepsy, infantile spasms/seizures, central nervous system infection, intrauterine drug/alcohol exposure, brain volume loss, or periventricular leukomalacia.
• Presence of any of the following abnormal neuro-imaging findings (CVI risk criteria): Vascular insults, underlying genetic/structural/migrational abnormality, brain atrophy, prematurity sequelae, hydrocephalus, presumed metabolic findings, presumed infection findings.
• Aim 1: (control group): Infants less than 8 months of age negative for CVI risk criteria (see above).

You may not qualify if:

• Children 12-\< 60 months of age
• Confirmed diagnosis of CVI
• Children must meet at least 1 of these 2 criteria to confirm the diagnosis of CVI during a CVI clinic visit: I: (1) the presence of visual function impairment (e.g., visual acuity) not attributed to anterior visual pathway abnormalities (except mild optic atrophy) or 2) evidence of visual perception/functional vision deficit.
• Children with autism spectrum disorder
• Children with ocular conditions including inherited retinal diseases, congenital cataracts, anterior segment dysgenesis, optic nerve hypoplasia, and retinopathy of prematurity with profound visual impairment due to anatomical abnormalities

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead
• National Eye Institute (NEI): collaborator

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

MeSH Terms

Conditions

Blindness, Cortical

Condition Hierarchy (Ancestors)

Blindness; Vision Disorders; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Eye Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Karen L Harpster, PhD, OTR/L

  Cincinnati Childrens Hospital Medical Center

  PRINCIPAL INVESTIGATOR

• Veeral Shah, MD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2025
• First Posted: October 8, 2025
• Study Start: July 31, 2025
• Primary Completion (Estimated): August 1, 2030
• Study Completion (Estimated): August 1, 2031
• Last Updated: October 9, 2025

Record last verified: 2025-10

Locations

US (1)