Study reference

Study characteristics

Patient characteristics

Intervention (I)

Comparison / control (C)

Follow-up

Outcome measures and effect size

Comments

Huurneman, 2012

SR and meta-analysis of 22 quantitative studies and 8 additional studies.

Of the included quantitative studies, 4 were non-RCT’s, 3 were cohort studies, 4 were case control studies and 11 were cross-sectional studies; 2 cross-sectional studies focused on children with CVI.

Literature search up to May 2012

A: Jacobson, 1996

B: Pike, 1994

Setting and Country: eye hospital, The Netherlands

Source of funding:

This research was funded by ZonMW (grant number 60-00635-98-066,

ZonMW, program Insight).

Inclusion criteria SR: studies focused on: 1) foveal crowding in children with NV up to 18 years, individuals with VI, and children with CVI up to 18 years, or 2) PL studies designed to reduce crowding effects, i.e. reducing contour interaction area or improving crowded acuity (foveal and peripheral). two intervention studies in adult populations with amblyopia were also included.

Exclusion criteria SR: diagnoses other than those

specified above (e.g. dyslexia) were excluded

Important patient characteristics at baseline:

A: N=13

Age 5-14y

B: N=42

Age 2-9y

Describe intervention:

A: Stimulus: LH single/LH line at 3m

Interoptype spacing: 100%

Foveal/eccentric: foveal

B: Stimulus: Single Sheridan Gardener/7-letter Sheridan Gardener at 6m.

Interoptype spacing: 50%

Foveal/eccentric: foveal

Describe control:

A: -

B: -

End-point of follow-up:

A: -

B: -

For how many participants were no complete outcome data available?

(intervention/control)

A:-

B: -

Outcome measure-1 the contour interaction area

This was not studied in children with CVI

Outcome measure-2 crowding ratio

Two studies included children with CVI: Jacobson, 1996; Pike, 1994. Both studies found enhanced crowding effects in this population. One study (investigated patterns of visual impairment in children (n = 42) with different lesions seen on ultrasound before 35 weeks gestational age (severe leukomalacia, large intra ventricular haemorrhages (IVH), or cerebral infarction). Excessive crowding, here defined as a ratio ≥2, occurred in 13 out of 29 children and especially in those with impaired acuity (≤0.30 or ≤6/18) Furthermore, the authors found that visual impairments are more common in association with ischemic lesions (leukomalacia and infarcts) than in association with haemorrhagic lesions, but abnormal crowding ratios were not associated with any particular lesion location on MRI. In children with CVI, crowding ratios were elevated in both studies (2–3 lines lower score on line acuity chart compared to single acuity with 100% optotype spacing). Specific predictors of the amount of foveal crowding in children with CVI are: kind of lesion (ischemic lesion is associated with poorer visual outcome than hemorrhagic lesions), oculomotor deficits (inability to fixate), presence of nystagmus, and low acuity (≤0.30 or ≤6/18).

Facultative:

Three different groups were presented in this review:

1) children with NV, 2) visually impaired (VI) children and adults and 3) children with cerebral visual impairment (CVI) ; this summary focuses on children with CVI.

Study reference

Study characteristics

Patient characteristics ²

Intervention (I)

Comparison / control (C) ³

Follow-up

Outcome measures and effect size ⁴

Comments

Cavascan, 2013

Type of study: retrospective cross-sectional observational study

Setting: university hospital

Country: Brazil

Source of funding: Conselho Nacional de Desenvolvimento Cientifico e Tecnologico-CNPq research fellowship

Inclusion criteria: children with CVI and referred for VEP grating acuity measurement. Clinical diagnosis of CVI based on bilaterally reduced visual acuity, with evidence of post-chiasmatic brain lesion, poor visual behaviour, and normal ocular structure

Exclusion criteria: no ophthalmic examination and uncorrected refractive errors; binocular VEP grating acuity measurement and/or optic disk palor

N total at baseline: 115

Important prognostic factors²:

For example

Age (median) ± SD: 17 months, range 1.2 to 167 months

Sex: 57 % M

Etiology: prematurity (24%), seizures (16%), perinatal hypoxia (8%), brain malformations (7%), acquired hypoxia (6%), hydrocephalus (4%) and some other causes. In 19% there were combined etiologies

Describe intervention (treatment/procedure/test):

SWEEP VEP procedure

Monocular grating acuity testing was done using the Power Diva (digital infant vision assessment), sweep-VEP system (the Smith-Kettlewel Eye Research Institute). This system uses two computers: the ‘host’ computer selects the stimulus, establishes stimulus and trial parameters and analyses the evoked response.; the ‘video’ computer controls display monitor and shows the stimuli to the subject. The stimuli were phase-reversal sine-wave gratings presented on a 17.5 inch high-resolution monochromatic video monitor. Stimuli orientation was set vertical for participants without nystagmus and for those with either vertical or torsional nystagmus. Horizontal orientation was used for children with horizontal nystagmus. Mean luminance (142.35) as well as contrast 980%) was kept constant throughout the session. Patterns were temporarily alternated in counterphase with a temporal modulation of 6.6 Hz.

Describe control (treatment/procedure/test):

Length of follow-up:

Loss-to-follow-up:

Intervention:

N (%)

Reasons (describe)

Control:

N (%)

Reasons (describe)

Incomplete outcome data:

Intervention:

N (%)

Reasons (describe)

Control:

N (%)

Reasons (describe)

Outcome measures and effect size (include 95%CI and p-value if available):

Grating acuity:

Tresholds ranged from 0.23 to 1.41 logMAR (mean 0.93 ± 0.26); median 0.95) for the better vision eye and 0.26 – 1.70 logMAR (mean 1.00 ± 0.27); median 1.02) for the worse vision eye.

Inter-ocular acuity difference:

IAD ranged from 0 to 0.49 log units (mean 0.06 ± 0.08; median 0.04). Normal IAD (<0.10 log units) was found in 96 (83%) of children. Children with strabismus and nystagmus had IAD significantly larger when compared to children with orthoposition.

VEP grating acuity deficit:

GAD ranged from 0.17 to 0.28 log units (mean 0.68 ± 0.27; median 0.71). Mild GAD was found in 23 (20%) children, moderate in 32 (28%) and severe in 60 (52%).

Purpose of this study was to determine grating acuity deficit magnitude measured by sweep-VEP and IAD in children with CVI

Clarke, 1997

Type of study: cohort study

Setting: hospital

Country: UK

Source of funding: unknown

Inclusion criteria: children referred by ophthalmologist because of lack of visual response

Exclusion criteria: ocular disorders demonstrated by clinical examination or electroretinography

N total at baseline: 44

Important prognostic factors²:

Age not specified

Sex: not specified

Describe intervention (treatment/procedure/test):

Flash visual evoked potential

Describe control (treatment/procedure/test):

Visual response was assessed by a preferential looking technique (Keeler cards), fixation behaviour, or response to a light source, and classified as shown in Measurements of Vision below. Visual responses were severely impaired or absent in all infants on presentation.

Length of follow-up: unclear

Loss-to-follow-up: unclear

Incomplete outcome data:

unclear

Outcome measures and effect size (include 95%CI and p-value if available):

Negative predictive value: 11/13 infants (84.6%)

Positive predictive value: 14/31 (45.1 %)

Sensitivity:

14/16 (87.5%) infants

Specificity:

11/28 (39.3%) infants

Accuracy:

25/44 (56.8%)

Frank, 1992

Type of study:

Setting: university hospital

Country: USA

Source of funding: grant HD101799 from the United States Public Health Service

Inclusion criteria: referred for VEP testing because of lack of spontaneous visual behaviour. Children had normal eye examinations, and patients with any evidence of ocular, retinal or prechiasmal visual abnormalities were excluded

Exclusion criteria:

N total at baseline: 60

Intervention:

Control:

Important prognostic factors²:

Age ± SD: 25.7 months ± 32.7, range 6 weeks to 10 years

Sex:

I: % M

C: % M

Etiology of cerebral blindness: perinatal asphyxia (N=5), postnatal anoxic episodes (N=4), metabolic degenerative neurologic disease (N=3), structural brain abnormalities (N=4), hydrocephalus (N=6), meningitis or encephalitis (N=7), severe dehydration (N=3) and head trauma (N=2)

Describe intervention (treatment/procedure/test):

VEP pattern stimulation: consisting of 100 reversals of checks subtending 40’ of visual angle. Since an alert and co-operative child is essential to obtain valid pattern VEP results, the testing session was kept as short as possible. Therefore an immediate decision was made as to whether a response occurred to 40’checks. If a response was present, even if deviant, two additional runs of 100 reversals were delivered. If no response was present to the first run of 40’stimuli, three runs of 120’checkebords were presented. Finally three runs of 50 flashes were presented to the child.

These spectral coefficients for each epoch were averaged together across trials for each participant, recording derivation (electrode position), harmonic, and stimulus condition. Statistical significance for each epoch was quantified using P values derived from the circular T (T2 circ) statistic,21 which tests whether a given response amplitude is significantly different from zero, taking into account both response amplitude and phase consistency across trials. Group sVEP amplitudes were also averaged coherently across observers

Describe control (treatment/procedure/test):

Cases were evaluated by age-matched controls.

Length of follow-up:

Loss-to-follow-up:

Intervention:

N (%)

Reasons (describe)

Control:

N (%)

Reasons (describe)

Incomplete outcome data:

Intervention:

N (%)

Reasons (describe)

Control:

N (%)

Reasons (describe)

Outcome measures and effect size (include 95%CI and p-value if available):

Every patient with ‘cerebral blindness’had abnormal VEPs. Most of them, were abnormal under all stimulus conditions at all electrode sites. Abnormalities were always bilateral, although they could be assymetrical.

30% of patients had absent VEPs both to flash and pattern stimulation at all recording sites. 22% of patients had atypical or atypical and assymetric VEPs to all stimuli and recording sites.

24 of the remaining 29 cases displayed greater abnormality of pattern than flash VEPs and in two cases the flash and pattern VEP were equally abnormal. Three patients had only pattern or flash VEPs, which were abnormal in all cases.

Among those patients in whom some cortical response was present, atypical VEPs were the most common abnormality; the occipital responses of 34 patients received this designation (compared with 18 patients with absent responses).

Cortical responses to both flash and pattern stimulation, and we recorded VEPs from sites overlying occipital, parietal, and temporal scalp to sample the responses from both primary and secondary visual cortical areas.

Good, 2012

Type of study:

Setting: eye research institute

Country: USA

Source of funding: Grants EY015228 (WVG) and EY06579 (AMN) from the National Eye Institute, Bethesda, Maryland

Inclusion criteria: Children with CVI were diagnosed clinically on the basis of reduced visual acuity in both eyes, with the diagnosis corroborated by neuroimaging, history, and physical examination to exclude with certainty any coexisting eye disease. Pupillary reactions were normal.

Exclusion criteria:

N total at baseline: 34

Important prognostic factors²:

Age ± SD:

I: 1.94 ± 1.37 years, 5 months to five years

C: 2.19 ± 1.55

Sex:

I: 22/34 = 65 %M

C: % M

Etiology: hypoxicischemic encephalopathy in most, as well as infection, hydrocephalus, and metabolic disorders

Describe intervention (treatment/procedure/test):

sVEP measurements (Measurements of spatial frequency threshold (grating acuity) and

contrast sensitivity using the sVEP) were recorded from 34 patients with CVI ranging in age from 5 months to 5 years

To measure the response functions, sVEP recordings for each 10-second trial were divided into 10 sequential epochs that corresponded to the swept stimulus values. For each epoch, a recursive least square (RLS) adaptive filter20 was used to generate a series of complex-valued spectral coefficients representing the amplitude and phase of response components tuned to various multiples (harmonics) of stimulus frequency (e.g., 3.76 Hz in the current study).

Describe control (treatment/procedure/test):

16 age-matched healthy controls (mean +/- SD: 2.19 +/- 1.55). Controls were typically developing children recruited through letters mailed to parents. Names were obtained through the state registry. Infants with eye or systemic illness, or prematurity, were excluded from the control group.

Length of follow-up:

Loss-to-follow-up:

Intervention:

N (%)

Reasons (describe)

Control:

N (%)

Reasons (describe)

Incomplete outcome data:

Intervention:

N (%)

Reasons (describe)

Control:

N (%)

Reasons (describe)

Outcome measures and effect size (include 95%CI and p-value if available):

Grating acuity:

32 had measurable but reduced grating acuity with median threshold of 0.96 log unit (0.49 logarithm of the minimum angle of resolution (logMAR), 9.8 c/deg, range 5–14 c/deg).

Contrast threshold:

Among 34 children with CVI, 30 had measurable but reduced contrast thresholds with a median threshold of 1.10 log unit (10.8%, range 5.0%–30.0% Michelson)

These thresholds were reduced relative to the mean contrast threshold of 0.3 log unit (0.5% Michelson) of 9-week-old healthy infants,17 and relative to the median grating acuity of 1.36 log unit (0.13 logMAR, 22.3 c/deg) of age-matched control children, all of whom had measureable threshold (P <0.0001).

to compare visual evoked potential measures of contrast sensitivity and grating acuity in children with CVI with those of age-matched typically developing controls.

Khetpal, 2012

Type of study: cohort study

Setting: eye institute

Country: USA

Source of funding: unknown

Inclusion criteria: records of patients evaluated between 2002 to 2005 with a diagnosis of CVI were identified via a search of billing records.

Exclusion criteria: -

N total at baseline: 98

Important prognostic factors²:

Age (mean): 3.1 Y (0.2-19 y)

Sex: 57%

Etiology: perinatal hypoxia (35%), prematurity (29%), hydrocephalus (19%), structural nervous system abnormalities (11%) and seizures (10%).

Describe intervention (treatment/procedure/test):

Pediatric ophthalmologic examination including: visual behaviour, pupillary reaction, the presence or absence of strabismus, nystagmus, optic atrophy, and cycoplegic retinoscopy

Describe control (treatment/procedure/test):-

Length of follow-up:

Follow-up available for 52 patients:

(range <1 year 10;

1-1.9 year 15;

2-4 years 21

>4 years 6)

161 patients with a diagnosis of CVI between 2002 and 2005 were identified, and 98 charts of patients were available for review

Outcome measures and effect size (include 95%CI and p-value if available):

Visual function tended to be poor in most children. Nearly 75% of children had level I or II of vision acuity (light perception only; occasional fixation with no following)

Visual acuity tended to improve slightly over time, although 40% had no improvement.

Ocular abnormalities:

Strabismus was common and was typically exotropic 41%

Mild optic atrophy 25%

Nystagmus 21%

Refractive error <- 2.0 or >+ 3.0

Esotropia 19%

Moderate/severe optic atrophy 17%

Amblyopia 12%

Photophobia 4%

Retinal diseases 4%

Kooiker, 2012

Type of study: longitudinal study

Setting: quiet room

Country: The Netherlands

Source of funding: unknown

Inclusion criteria: age 1-12y, (suspected) visual information processing impairments due to for example CVI, mild oculomotor abnormalities, albinism or other syndromes

Exclusion criteria: visual acuity <0.05, severe physical disability, severe epilepsy, oculomotor apraxia; prematurity (born before 36 weeks) and visual impairment of any kind

N total at baseline:

I: 149

C:127 typically developing children

Important prognostic factors²:

Mean age I: 7.3 (3.3)

C: 7.9 (2.8)

Sex I: 60%

C: 50%

Describe intervention (treatment/procedure/test):

Children attended special education for the visually impaired

Setup consisted of a 24-inch monitor with an integrated infrared eye-tracking system at 60 Hz, to measure visual orienting responses. First a standardized 5-point calibration procedure of both eyes was performed. Next, short movies were shown in 1-2 sessions of +/-7 min. All children from the risk group were shown cartoons, coherent form, motion expansion, motion detection, colour and contrast stimuli.

Measurements were: time it took to complete orienting responses to the above visual stimuli. Within the risk group, children were divided into a fast, medium or slow group based on the response times to a highly salient stimulus. The relationship between group specific response times and clinical risk factors was assessed.

Describe control (treatment/procedure/test):

Typically developing children recruited at daycare institutions in the surroundings

Length of follow-up:

-

Incomplete outcome data:

In 12 children there was insufficient measurement of gaze data and these children were excluded from analysis.

Outcome measures and effect size (include 95%CI and p-value if available):

The fast responding children in the risk group were significantly slower than children in the control group. Within the risk group, the prevalence of cerebral visual impairment, brain damage and intellectual disabilities was significantly higher in slow responding children compared to faster responding children. The presence of nystagmus, perceptual dysfunctions, mean visual acuity and mean age did not significantly differ between the subgroups. Orienting responses are related to risk factors for visual processing impairments known to be prevalent in visual rehabilitation practice.

Lim, 2005

Type of study:

Setting: university hospital

Country: USA

Source of funding: This study was supported in part by grants from the Blind Children Center, Los Angeles, Calif, and United Cerebral Palsy Foundation, Washington, DC

Inclusion criteria: a history of birth at term, antenatal or perinatal distress or both, moderate to severe neonatal encephalopathy with seizures, and magnetic resonance imaging evidence of brain injury in a pattern typical of hypoxic-ischemic encephalopathy, assessment of developmental quotient using the Bayley Scales of Infant Development, bot PL and VEP measurement at the same session on at least 1 date

Exclusion criteria: metabolic disorders, hypoglycemia, trauma, abnormal ocular structures (except mild optic atrophy), or malformations of the brain

N total at baseline: 19 children aged 6 months to 6 years

Important prognostic factors²:

median age at the first acuity test was 15 months (range, 6-36 months).

Describe intervention (treatment/procedure/test):

VEP measurement:

Sweep VEPs were recorded using the NUDiva system (Smith- Kettlewell, San Francisco, Calif).7,23,24 The spatial frequency of a high-contrast (80%) vertical square-wave grating (average luminance, 76 cd/m2) alternating at 5.5 Hz (11 reversals per second) was swept from low to high spatial frequency during a 10-second trial. To accommodate the large range of acuities, the test distances were 50 to 150 cm. This provides nominal test fields of approximately 42°

Describe control (treatment/procedure/test):

PL measurement:

A clinical variant of the Teller Acuity Card procedure was used to measure PL acuity. The acuity cards were presented horizontally or vertically, lateral to, or central to the gaze direction to ensure the child could view each grating position and the observer could judge the child’s detection of the grating. Such modifications minimize the effects of visual field defects and eye movement abnormalities. The stimuli were 12.5-cm squares of high-contrast (83%), black-and-white square-wave gratings (range, 0.23-26.0 cycles/cm, in approximately 0.5-octave steps) on rectangular cards. The gratings had the same space averaged luminance as the background of the gray cards. The luminance of the cards was at least 10 candela (cd)/m2. The tester, unaware of the right-left position of the stripes, presented the cards at a distance of 38 to 55 cm from the patient. Based on the patient’s looking behaviour, the tester judged the finest grating that the child detected. This was taken as the acuity, expressed in cycles per degree (cpd). The patient’s acuities were compared with normal binocular PL acuity for age.

Length of follow-up:

For the 9 patients who had both PL and VEP acuity tests in the same session at 4 or more ages, the median duration of follow-up was 29 months (range, 24-76 months).

The median period of observation was 2.7 years (range, 6 months to 6 years).

Outcome measures and effect size (include 95%CI and p-value if available):

PL acuity:

Nearly all visual acuities were below normal for age. Between the first and last measurement, acuity improved 1 octave on average (range, −2.1 to 5.0 octaves). One octave is often considered a clinically significant change. Three patients had a decrease in PL acuity. For individuals the average rate of change in PL acuity per year was +0.18 octave/y (range, −0.90 to +1.80 octaves/y). Final PL acuity was related to the neurological score (Spearman Þ=−0.70; P<.001); the more favourable the score, the better the acuity. The rate of change in PL acuity was independent of the neurological score.

VEP acuity:

Improvement in VEP acuity was also on average 1 octave (range -0,22 to 3.09 octaves). During the period of observation (median, 2 years; range, 6 months to 6 years), the average rate of change in VEP acuity was +0.41 octave/y (range, −0.34 to+1.30 octaves/y). For individuals, the rate of change in VEP acuity did not differ significantly from that for PL acuity (paired t test, t13=0.49; P=.63). The rate of VEP acuity change and the final VEP acuity were not related to the neurological score

Sakai, 2003

Type of study: case series

Setting: hospital

Country: Japan

Source of funding: supported in part by a grant-in-aid to the first author for scientific research by Ministry of Education, Science, Sports and Culture, Japan

Inclusion criteria: subjects with severe motor and intellectual disabilities and CVI

Exclusion criteria:

N total at baseline: 9

Important prognostic factors²:

Age 13.8 +/- 9.98

Sex: 78% male

Describe intervention (treatment/procedure/test):

1) detection of optokinetic nystagmus to drifting sinusoidal gratings by naked-eye observation and electronystagmography and

 (2) detection of ocular pursuit for a drifting Gabor patch by naked-eye observation. We succeeded in measuring the sensitivities of eight cases

Describe control (treatment/procedure/test):

Length of follow-up:

-

Outcome measures and effect size (include 95%CI and p-value if available):

Contrast sensitivity functions were obtained for 8 out of 9 subjects.

Most cases showed low contrast sensitivity in both higher (2 and 4 cycles/degree) and lower (0.125 and 0.25 cycles/degree) spatial frequencies and relatively high contrast sensitivity in the middle (0.5 and 1 cycle/degree) range of spatial frequencies

Diagnosis with CVI was made if five criteria were satisfied

Aim of this study was to find a proper visual

Salati, 2002

Type of study: retrospective chart review

Setting: paediatric ophthalmology department

Country: Italy

Source of funding: This study was supported in part by Italian National Institute of Health research funding (Ministero della Sanità; RC 00/C/3) and by a grant from Lombardy Region (2000)

Inclusion criteria: children referred between to the institute between 1995 and 2000 for neurological disorders; patients whose history showed a picture compatible with cerebral damage due to a pre-perinatal anoxic–ischemic event.

Exclusion criteria: Children with cerebral malformation and hereditary metabolic disorders; those with concomitant eye pathology, such as retinopathy of prematurity, microphthalmos, congenital cataract, or chorioretinal scars; brain damage occurring after the neonatal period.

N total at baseline: 51

Important prognostic factors²:

Age (mean) ± SD: 7y 1m, ± 4y (range 2-16)

Sex: 66% males

Etiology: all suffered from perinatal ischemia–hypoxia; tetraplegia (77%), hemiplegia (11%), diplegia (9%)

Describe intervention (treatment/procedure/test):

Ophtalmological assessment:

Visual assessment included visual acuity and an accurate examination of ocular motility, anterior segment, refraction in cycloplegia, and fundus oculi.

Ocular motility assessment:

We considered behaviour of gaze under four conditions: during scanning of the surrounding environment, fixation, execution of saccades, and pursuit. In addition, we studied three important oculomotor manifestations: strabismus, nystagmus, and paroxysmal ocular deviations

Visual scanning of the environment

This task tests the patient’s ability to look at the surrounding environment with precise sequences of saccadic movements. Visual scanning is evaluated in a room full of toys and new objects.

Stability of fixation

This evaluation assesses an individual’s ability to keep their gaze on a near target.

Describe intervention:

Quality of saccadic movements

This assessment studies the ability of patients to make a normal saccade when an eccentric target is presented. Saccades can also be tested asking the child to look either at the one end of a rod or at the other.

Quality of smooth pursuit movements

This task determines the ability to perform smooth pursuit. Targets were the same as in the previous task.

Presence of paroxysmal ocular deviations

Paroxysmal ocular deviations were described as conjugate drift movements of the eyes that resemble oculogyric spasms of epileptic origin (Yokochi 1991).

Variable-angle squint

Considerable variability in the angle of squint was observed. We observed participants with variable-degree esotropia ranging from 15° to 35°.

Length of follow-up:

-

Loss-to-follow-up:

-

Incomplete outcome data:

-

Outcome measures and effect size (include 95%CI and p-value if available):

Typical features of ocular motility in CVI were: paroxysmal ocular deviations (present in 78%); the presence of variable angle strabismus (86%); and defective coordination of saccades (93%). Exploration of the environment and fixation were also impaired (88% and 84%, respectively). Disorders of initiation and performing saccades, absence of smooth pursuit, vergence abnormalities, nystagmus beats, instability of fixation, and difficulty in the systematic exploration of the environment were observed.

Skoczenski, 2004

Type of study:

Setting: eye research institute

Country: USA

Source of funding: NIH: EY12692 and EY00384, a Rachel C. Atkinson Fellowship (AMS), the Smith-Kettlewell Eye Research Foundation and the Pacific Vision Foundation

Inclusion criteria: patients referred by paediatric ophtalmologists or by the Blind Baby Foundation of Northern California; eye examination ruled out problems in anterior visual pathway. CVI was diagnosed when vision was clearly subnormal from a clinical standpoint;

Exclusion criteria:

N total at baseline: 35

Important prognostic factors²:

Age (mean): 3y 6m (SD 3y 5m) (range 4m-16y)

Sex: 57% male

Etiology: hypoxic ischemic encephalopathy 21/35; encephalitis 3/35; and other causes (9/35), unknown origin 2/35.

Describe intervention (treatment/procedure/test):

Measurements in the included patients

Grating acuity

Sinewave gratings were presented that appeared and disappeared at a fixed temporal frequency of 5 Hz, while spatial frequency changed in linear steps from low to high during 10-second trial presentations.

Vernier acuity

Square wave gratings were used, with Vernier offsets appearing and disappearing within each grating bar at a fixed temporal frequency of 5 Hz. Vernier offset size changed from large to small in logarithmic steps over each 10-second trial presentation. Both stimulus types had a Michelson contrast of 80%, and a mean luminance of 100 cd/m².

One goal of the sweep VEP is to observe changes in the amplitude of evoked responses as the visual stimulus changes from above to below sensory threshold.

Describe control (treatment/procedure/test):

Data from participants with normal vision are taken from Skoczenski and Norcia et al., 2002, and were collected with identical test parameters on the same apparatus.

Length of follow-up:

Outcome measures and effect size (include 95%CI and p-value if available):

Both measures were obtained in 27/35 patients. In 8 patients grating acuity was measurable, but grating acuity not.

Grating acuity:

Vernier acuity:

Across all age groups tested, both Vernier and grating acuity were lower in patients with CVI compared with children with normal visual experience.

Ratios were calculated for each child; dividing the acuity of a child with CVI by the acuity from aged-matched children with normal vision. An acuity ratio of 1 would indicate normal vision.

In a graph it shows that grating acuity ratios were closer to normal (ie 1), illustrating that Vernier acuity ratios, and that Vernier acuity was more severely degraded than grating acuity in most children with CVI.

Mean Vernier acuity ratio in these children was 0.196, while the mean grating acuity ratio was 0.395.

Watson, 2007

Type of study: retrospective study

Setting:

Country: USA

Source of funding: NEI grant EYE07043

Inclusion criteria: children with CVI

Exclusion criteria:

N total at baseline: 39

Important prognostic factors²:

Age at first VEP: 1 to 16 years, mean 5.0 SD 3.2 y

Sex:

I: % M

C: % M

Etiology CVI: HIE=14, PVL=7, hydrocephalus=4, hypoxic event in childhood=4, infection=3, trauma=2,static encephalopathy=1, abnormal white matter=1, haemorrhage at birth=1, unknown=2

Describe intervention (treatment/procedure/test):

Sweep VEP:

The children were presented with 80% Michelson contrast sinusoidal luminance gratings on a video monitor with an average luminance of 80 cd/m². Over a period of 10 s, the spatial frequency of the reverse grating was incremented in 19 steps , spanning a 10 to 1 range of spatial frequencies expressed in cycles/degree. Visual acuity was initially swept linearly. But, because of the severely reduced acuity values in the study population, spatial frequency often had to be swept logarithmically.

The viewing distance was initially 50 cm and increased to 100 or 200 cm iff significant VEP responses remained at the end of this sweep range.

Acuity was determined by linear extrapolation of the final portion of the VEP amplitude to zero amplitude.

Describe control (treatment/procedure/test):

Contrast threshold:

The sweep VEP was used to measure contrast threshold for a single, low-spatial frequency grating. The children were presented with 0.6 cycles/degree vertical grating that was swept logarithmically from 1 to 80% Michelson contrast. Over a period of 10s, the contrast of reversing grating was incremented in 19 steps. Again, multiple sweeps were recorded and the best one was selected. The contrast threshold was derived by linear extrapolation of the final portion of the VEP amplitude to zero amplitude.

Length of follow-up: time between measures ranged from 0.6 to 13.7 years, first and last measure of each subject were included, some were seen multiple times

Outcome measures and effect size (include 95%CI and p-value if available):

Visual Acuity:

Mean initial acuity was 0.88 log MAR (20/152) grating visual acuity. The initial and final visual acuities for the group as a whole were analysed using ANOVA and showed a significant improvement (F=3.97; df 38, p=0.004). T

Contrast threshold (available for 34 children):

Mean initial Michelson contrast thresholds for the whole group was 7.03%, which represents substantial visual impairment. The initial and final contrast thresholds for the group as a whole were analysed using ANOVA and showed a significant effect (F=3.99; df=33, p=0.011).

Goal was to assess role of various factors on vision function in children with CVI:

This study does not fit PICO

Watson, 2009

Type of study:

Setting: university hospital

Country: USA

Source of funding: unknown

Inclusion criteria:

Exclusion criteria: ocular pathology or whose

reduction in visual acuity could be attributed to a condition other than CVI

N total at baseline: 37 (29)

Important prognostic factors²:

Age ± SD:

3.2 to 22.7 years (median 13.6); mean 12.1; SD 5.4)

I:

C:

Sex:

I: % M

C: % M

Etiology: hypoxic injury (52%), infection (14%), hydrocephalus (10%), trauma (3%), unknown (21%)

Describe intervention (treatment/procedure/test):

Sweep VEP:

Recorded using NUDIVA system, electrodes were placed 3 cm above the inion and 3 cm to the left and to the right, with a reference electrode at the vertex and a ground electrode further forward on the scalp.

Grating stimulus:

The patients were presented with 80% Michelson contrast sinusoidal gratings on a video monitor. During each 10-second trial, the spatial frequency of the reversing grating pattern was incremented logarithmically in 19 steps, from low to high spatial frequency37. The gratings were modulated at a rate of 15 contrast reversals per second (or 7.5 Hz). The viewing distance was initially 100 cm in order to present a range of spatial frequencies from 1 to 10 cycles/degree. If significant VEP responses remained at the end of this sweep range, the viewing distance was increased to 200 cm (for a 2 to 20 cy/deg sweep range).

Describe control (treatment/procedure/test):

Vernier Stimulus:

The patients were presented with 80% Michelson contrast vertical square wave gratings on a video monitor. Portions of each vertical bar were temporally modulated to make offsets appear and disappear at a fixed temporal frequency of 5 Hz. The vernier offset size changed in 19 logarithmic steps from small to large offsets over each 10-second trial presentation.

Forced Choice Preferential Looking (PL) Test—The Berkeley Grating Cards38, a clinical variation of the Teller Acuity Card procedure39–41 was used to measure PL visual acuity. The acuity cards were presented either horizontally or vertically to minimize the effects of visual field defects and either lateral to or central to the gaze direction to minimize the effects of oculomotor abnormalities. The examiner presented the acuity cards in sequential order from lower to higher spatial frequencies. Each card was presented as many times as necessary to decide whether the patient could resolve the grating on the card.

Length of follow-up:

Loss-to-follow-up:

Intervention:

N (%)

Reasons (describe)

Control:

N (%)

Reasons (describe)

Incomplete outcome data:

All three measures of acuity were obtained in 29 of the 37 patients tested.

Reason Behavioral (PL) acuity could not be assessed in eight of the patients, and these patients were excluded from the comparison.

Outcome measures and effect size (include 95%CI and p-value if available):

VEP grating acuity:

average VEP grating acuity was 12.7 c/deg (SD: 4.9; median: 11.2), a deficit of 0.4 log units. The range of VEP grating acuity was from near normal (22.8 c/deg) to a deficit of nearly 0.8 log units (5.2 c/deg).

VEP Vernier acuity:

2.7 min arc (SD: 2.4; median: 1.9), a deficit of 0.6 log units. The VEP vernier acuity range was from normal (0.5 min arc) to a deficit of nearly 1.4 log units (11.3 min arc).

Behavioural acuity:

9.3 c/deg (SD: 8.3; median: 5.5), a deficit of 0.7 log units. The range of behavioral acuity was from normal (30 c/deg) to a deficit of nearly 1.6 log units (0.83 c/deg)

log reduction in VEP Vernier acuity was significantly related (r=0.70; p<0.001). However, the slope was 1.31 indicating that on average, Vernier acuity showed a 0.2 log unit deficit compared to VEP grating acuity.

log reduction in VEP grating acuity and the log reduction in

behavioral grating acuity were significantly related (r=0.64; p<0.001). The slope was 1.55,

indicating that on average behavioral acuity was more reduced (approximately a 0.3 log unit

greater deficit) than the VEP grating acuity.

log reduction in VEP vernier acuity and the log reduction in

behavioral grating acuity were significantly related (r=0.66; p<0.001). The slope relating log

VEP vernier loss to log behavioral acuity loss was 0.85; thus, the regression line aligned

closer to the 1:1 line than for the previous two comparisons.

purpose of this study is to determine the relationship between VEP vernier acuity,

VEP grating acuity and behavioral grating acuity in patients with CVI

Watson, 2010

Type of study: retrospective study

Setting: university hospital

Country: USA

Source of funding: T32 EY07043, K12 EY017269, and NIDRR H133E060001

Inclusion criteria: young patients with CVI, Sweep VEP testing was performed at the first visit as part of a comprehensive eye examination. A behavioral measure of visual acuity (either preferential looking cards or single symbols, depending on the patient’s cognitive and motor ability) was also measured. The patients were then followed over time and retested at a later date.

Exclusion criteria:

Ocular pathology, or whose reduction in vision could be attributed to a condition other than CVI

N total at baseline: 33

Important prognostic factors²:

Age ± SD: median age: 4.8y (range 1.3 to 19.2)

Etiology: birth asphyxia (8), acute episode of hypoxia (4), infection (4), PVL (3), trauma (2), static encephalopathy (2), hydrocephalus (1), multiple complications (3), unknown (6)

Describe intervention (treatment/procedure/test):

VEP technique:

The patients were presented with high contrast (80% Michelson) sinusoidal luminance vertical gratings on a high-resolution video display monitor with an average luminance of 80 cd/m2. Over a period of 10 seconds, the spatial frequency of the reversing grating was incremented logarithmically in 19 steps, spanning a 10 to 1 range of spatial frequencies expressed in cycles/degree. Testing was performed under binocular viewing with proper refractive error correction.

The gratings were modulated at a rate of 12 contrast reversals per second. The second harmonic component of the response at 12Hz is extracted by a Discrete Fourier Transform (DFT) and compared to an adjacent frequency band at 14 Hz, which did not contain any visual evoked activity. The adjacent frequency measurements were used to estimate the noise background during the trial and reject portions of the record with muscle spikes or movement artifacts. Sweep VEP acuity was estimated by the method described by Norcia and Tyler. Determination of visual acuity was based on the linear decline of the VEP amplitude and the increase in the implicit time near the acuity threshold.

Describe control (treatment/procedure/test):

Behavioural acuity technique:

Berkeley Grating Acuity Cards26, a clinical variation of the Teller Acuity Card procedure was used to measure forced choice preferential looking (PL) acuity. The patient was presented with a rectangular card that had two targets positioned on a gray homogenous background. One target matched the gray background and the other target contained a grating pattern. If the patient responded by turning his/her eyes or head in the direction of the grating pattern, then the patient’s response was interpreted as an ability of the patient to see the target. Threshold visual acuity was determined by observing the finest grating to which the patient reliably oriented their gaze for a minimum of three out-of four presentations (75% correct).

Lea single symbols cards were used for the patients who were capable of performing a recognition acuity task. The patient was presented with a pair of 10cm square cards. One card had the Lea house (or arrow) symbol and the other card had the Lea apple (or heart) symbol positioned in the center of the card.

Length of follow-up: on average 6.9 years (SD 3.5 y)

Outcome measures and effect size (include 95%CI and p-value if available):

mean initial VEP acuity was 20/94 (0.67 logMAR), and the mean initial behavioural acuity was 20/475 (1.38 logMAR). The average difference between the two measures of acuity was 0.55 log unit, with the behavioural measure reporting a poorer visual acuity in all patients. Therefore, at the initial test, the behavioural measure of acuity was significantly worse than the VEP measure of acuity (t=9.68; df=30; p<0.0001).

mean final behavioural acuity was 20/150 (0.88 logMAR). The average difference between the initial VEP acuity and the final behavioural acuity was 0.01 log unit. The initial VEP measure was not statistically different from the final behavioural measure (t=0.11; df=32; p=0.45).

purpose of this study was to determine if an early VEP measure of acuity is related to a young patient’s future behavioural acuity