Study reference

Study characteristics

Patient characteristics ²

Intervention (I)

Comparison / control (C) ³

Follow-up

Outcome measures and effect size ⁴

Comments

Dutton, 1996

Type of study: retrospective clinical observational study

Setting: hospital

Country: Uk

Source of funding: The Wellcome Trust, the Scottish Office Home and Health Department, and the WRVS.

Inclusion criteria: 1. (a) Infants and young children deemed by referring clinicians to have poor vision. (b) Multiply handicapped children.

2. Apparently paradoxical visual behaviour for which an explanation and strategy of management is requested.

Exclusion criteria:

N total at baseline: 130

Important prognostic factors²:

Age distribution is displayed in figure 1 in this paper, range is from 0-16 years with a majority of patients begin 0-2 years of age

Sex:

Etiology: eye disorders such as ROP or albinism (26), optic nerve/chiasm disorders (e.g. ONH pituitary disorders) (10), eye movement disorders (e.g. oculomotor apraxia) (4), brain disorders (90)

Describe intervention (treatment/procedure/test):

Visual acuity using a Snellen visual acuity test. The majority underwent assessment of acuity by means of preferential looking (Cardiff acuity test and/or Keeler acuity cards) and visual.

A range of other methods of assessment of visual function was employed, including optokinetic nystagmus, fixation and following, near reaching thresholds and awareness of faces. The functional binocular acuity was determined on the basis of the results of successfully completed tests appropriate for each child. Values are expressed as Snellen equivalents, in order to provide an easily understood index of visual resolution for both parents and teachers.

Describe control (treatment/procedure/test):

Visual fields were assessed, particularly for evidence of homonymous hemianopia, in all children in whom behavioural or confrontation methods could be used. A wide range of other tests of visual function were available and employed when indicated.

Length of follow-up:

-

Loss-to-follow-up:

-

Incomplete outcome data:

-

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

90 of the 130 patients referred showed evidence of visual dysfunction due to cortical visual impairment.

Sixteen children showed no evidence of preferential looking behaviour and little, if any, evidence of vision as measured by visual evoked potentials.

Twenty children showed paradoxes in visual behaviour which parents and other carers found difficult to understand. Eight of these children had left homonymous visual field impairment (out of a total of 23 (34 %)), and 3 had right visual field impairment (out of a total of 16 (18%)). One child (case 60) exhibited consistent bilateral lower visual field impairment. The remaining 8 showed no gross visual field loss.

The disorders of cognitive visual function

could be divided into five categories and involved impairment of: recognition., orientation, depth perception, perception of movement and simultaneous perception.

Incidentie afwijkingen visual acuity en visual field bij CVI

Fazzi, 2007

Type of study: cross sectional study

Setting: centre of child neurophtalmology

Country: Italy

Source of funding: unknown

Inclusion criteria: children referred between January 2001 and June 2003; sample included at the end of a thorough evaluation, were deemed to be affected by CVI , diagnosed according to the criteria set out in the introduction

Exclusion criteria:

N total at baseline: 121

Important prognostic factors²:

Age (mean) ± SD: 54 months (3-180m), SD 39.7m

Half born at term, other half <=37 weeks gestation

Sex: 59% boys

73% of patients had cerebral palsy

Etiology: Hypoxic-ischemic encephalopathy 81 (67%), central nervous system malformations 15 (12%), metabolic and neurodegenerative diseases 11 (9%), hydrocephalus 4 (3%), CNS infections 3 (3%), cerebral neoplasia 2 (2%), cryptogenetic epilepsy 2 (2%), other CNS diseases 3(3%)

Describe intervention (treatment/procedure/test):

Neurophtalmologic evaluation:

Observation of spontaneous visual behaviour

Occulomotor assessment: fixation (absent, sporadic, unstable, stable, smooth pursuit (absent, discontinuous, normal), saccadic movements (abnormal, normal),visual axis alignment to detect strabismus (using the Hirschberg Test of corneal reflexes, the Cover Test, and the Paliaga test), and extrinsic and intrinsic ocular motility. In addition, they looked for abnormal ocular movements, such as nystagmus and paroxysmal ocular deviations.

Visual acuity: evaluated with the maximum possible dioptric correction and using different tests depending on the subject’s age and on the severity of the clinical picture. Children up to two years of age were evaluated using Teller acuity cards. In older children, able to collaborate several tests are used (Lea symbols, letter optotypes), which give recognition acuity expressed in tenths. In subjects whose vision is not assessable they looked for signs of visual perception, both direct and indirect.

Contrast sensitivity (not assessable, reduced, normal) evaluated using the Hiding Heidi Low contrast Face Test.

Describe control (treatment/procedure/test):

Optokinetic nystagmus (absent, asymmetric, present) evaluated using a semi rigid screen covered with black-and white square patterns, bent to form an arc, or using a computer-generated random-dot pattern in front of infant’s face.

Visual field (normal, reduced). Traditional methods cannot always be used to assess visual field. Kinetic perimetry is assessed and on the basis of behavioural reactions, the child’s ability to localize targets presented in the areas of the visual field is assessed.

Stereopsis (not assessable, absent, partial, present) is evaluated using the Lang Stereotest.

Visual-perceptual assessment is assessed using Developmental Test of Visual Perception in children >4 y and with IQ>55.

Ophtalmologic examination including assessment of refraction in cycoplegia and ophthalmology.

Length of follow-up:

Loss-to-follow-up:

-

Incomplete outcome data:

-

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

Refractive errors: 96/121=79%:

Hypermetria 28/96 (29%)

Astigmatism 21/96 (22%)

Myopia 11/96 (11%)

Fundus oculi:

53/121 (44%)

Visual acuity:

Binocular visual acuity was reduced in 105/121 (87%) and was normal in the other 16 (13%)

Contrast sensitivity:

Could be evaluated in 97/121 (80%) but not in the remaining 24/121.

Optokinetic nystagmus:

Was abnormal in 88/121 (73%) of patients, absent in 34 of 88 939%) of patients and asymmetric in 54/88 (61%).

Visual field:

Assessment was possible in 78/121 (65%) and not possible in the remaining 43/121 (36%).

Stereopsis:

Evaluated in 82/121 (68%) and could not be evaluated in remaining 39/121 (32%).

Oculomotor abilities:

Fixation was altered in 58 patients (48%), smooth pursuit in 95 (79%), and saccadic movements in 41 (34%).

Alignment of the visual axes:

Strabismus was present in 88 (73%) of patients.

Abnormal ocular movements : were found in 43 patients (36%).

Visual perceptual abilities:

Of the 27 (22%) patients in whom they could be assessed, visual-perceptual abilities were found to be impaired in 24. Fundus oculi abnormalities and refractive errors were frequently associated findings.

Definition of CVI: Cerebral visual impairment is defined as a deficit of visual function caused by damage to, or malfunctioning of, the retro geniculate visual pathways (optic radiations, occipital cortex, associative visual areas) in the absence of any major ocular disease.

Fazzi, 2012

Type of study: cross-sectional study

Setting: centre of child neurophtalmology

Country: Italy

Source of funding: unknown

Inclusion criteria: Between 1 January 2002 and 30 June 2005, a sample of 129 children (54 females, 75 males) with CP grouped according to the Hagberg international classification were consecutively enrolled

Exclusion criteria: severe visual deficits secondary to abnormalities of the anterior segment, inadequate correction of refractive errors, or sequelae of retinopathy of prematurity

N total at baseline: 129

Important prognostic factors²:

Age (mean) ± SD: 4y6m, SD 3y5m; (3m – 15y)

Sex: 58%

More than half of the children were born preterm.

Etiology: all had cerebral palsy and 51 diplegia, 61 tetralegia and 17 hemiplegia.

Independent walking was possible in 62 participants (48%)

Describe intervention (treatment/procedure/test):

assessment protocol including neurological examination, developmental and/or cognitive assessment, neuro-ophthalmological evaluation including ophthalmological assessment, evaluation of visual acuity, contrast sensitivity, optokinetic nystagmus, visual field and stereopsis, and neuroradiological investigations (see above Fazzi 2007)

Brain MRI

Describe control (treatment/procedure/test):

-

Length of follow-up:

-

Loss-to-follow-up:

-

Incomplete outcome data:

-

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

Visual dysfunction 44/51 in diplegia was characterized mainly by refractive errors 38/51 (75% of patients), strabismus 45/51 (90%), abnormal saccadic movements 44/51 (86%), and reduced visual acuity (82%).

The participants with hemiplegia showed strabismus 12/17 (71%) and refractive errors 15/17 (88%); oculomotor involvement was less frequent 7/17 (59%). This group had the largest percentage of patients with altered visual field 11/17 (64%).

Children with tetraplegia showed a severe neuro-ophthalmological profile, characterized by ocular abnormalities 16/17 (98%), oculomotor dysfunction 17/17 (100%), and reduced visual acuity 16/17 (98%).

Ruberto, 2006

Type of study: cross-sectional, comparative study

Setting: Regional Centre of Child Neurophthalmology

Country: Italy

Source of funding: unknown

Inclusion criteria: diagnosis of CVI was confirmed after examination of the available evidence by a multidisciplinary team that included a child neurologist, an ophthalmologist, a neuroradiologist, and a psychologist. We limited our study to cerebral damage caused by hypoxia-ischemia.

Exclusion criteria: cerebral malformations and metabolic or genetic diseases

N total at baseline: 24

Important prognostic factors²:

Age (mean) ± SD: 7.28 ± 2.7

Sex:

Etiology: spastic diplegia (10 cases), tetraparesis (8 cases) and hemiparesis

(5 cases)

Describe intervention (treatment/procedure/test):

Heidelberg Retinal Tomograph (HRT)-II .

The following parameters of the optic nerve head were examined: disc area, cup area, rim area, cup volume, rim volume, cup-to-disc area ratio, mean cup depth, maximum cup depth, cup shape measure, and mean retinal nerve fiber layer (RNFL) thickness. Assessed in children with CVI

Describe control (treatment/procedure/test):

Heidelberg Retinal Tomograph (HRT)-II assessed in 88 normal, alert subjects of similar age

Length of follow-up:

-

Loss-to-follow-up:

-

Incomplete outcome data:

-

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

It was possible to determine visual acuity only in 12 subjects.

The optic disc of patients with CVI appeared smaller than normal. Its excavation, however, was more pronounced. Several tomographic parameters were altered in CVI-affected subjects. Statistical analysis showed a highly significant probability in cup-to-disc area ratio (P <0.01, both eyes), rim area (P <0.01, both eyes), cup shape measure (P <0.01, right eye; P <0.01, left eye), and mean RNFL thickness (P <0.01, right eye; P <0.01, left eye). A novel observation was temporal atrophy of the optic nerve head in CVI.

Saidkasimova, 2006

Type of study: retrospective observational case series

Setting: children’s hospital

Country: UK

Source of funding: unknown

Inclusion criteria: patients with symptoms of cognitive visual impairment, reported by their parents and further refined by structured clinical history taking and MRI, identified in the general paediatric clinic over a period of 2 years. There was cognitive visual impairment (visuomotor dysfunction and impaired orientation, impaired perception of orientation, varying degrees of simultagnosia) despite near normal visual acuities. Symptoms of cognitive visual impairment were defined by a structured clinical history taking.

Exclusion criteria:

N total at baseline: 7

Important prognostic factors²:

For example

Age (mean) ± SD: 7.9 ± 2.9

Sex:

Etiology: 3/7 were born under 35 weeks of gestational age and 3/7 had seizures

Describe intervention (treatment/procedure/test):

(visual acuity, color vision, stereoacuity, visual fields, ocular motility, refraction, and fundoscopy)

Visual acuity were checked by different tests (Cardiff cards, Kay pictures, uncrowded and crowded logMAR chart) depending on the child’s age and intellectual ability. Visual acuities were measured separately in each eye except when the child objected to occlusion. Stereopsis was measured in children who cooperated.

Describe control (treatment/procedure/test):

-

Length of follow-up:

-

Loss-to-follow-up:

-

Incomplete outcome data:

-

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

Inferior visual field defect was observed in three of seven children. Four of seven had strabismus and two of seven had hyperopic refractive error >2.5D. Visual acuity was better than 20/30 in all children: 20/20 in better eye in 4/7 children (57%), 20/25 in one child and 20/30 in 2 children.

All seven children had previously had MRI scans, due to medical concerns. The MRI scan features of these children are shown in a figure. In each case, focal periventricular white matter abnormalities were present in similar locations ranging from mild to severe.

Van der zee, 2017

Type of study: cross-sectional exploratory study

Setting: university medical center

Country: the Netherlands

Source of funding: Royal Dutch Visio and the Intel-lectual Disability Medicine research group of the ErasmusUniversity Medical Center Rotterdam.

Inclusion criteria:

A heterogeneic group was recruited in the Rotterdam area through primary schools, two rehabilitation centres, and the Rotterdam Eye Hospital

Exclusion criteria:

N total at baseline: 107

Group 1:

Group 2:

Group 3:

Important prognostic factors²:

Age (median) ± SD: range 3-12y

Sex: 58% boys

Etiology ocular abnormalities (group 2): multiple ocular abnormalities (8) other than refractive errors or strabis-mus. Glasses and/or contact lenses (15), including seven because of pseudophakia or aphakia.

Strabismus (9), other ocular abnormalities (8). Contrast sensitivity was reduced (3) (>5% contrast needed),whereas in one child the right visual field seemed to be somewhat impaired (confrontation test).

Etiology brain damage (group 3):

aetiology of brain damage in group 3 was: hypoxicischaemic encephalopathy (11: 4 intraventricular haemorr-hage, 6 periventricular leucomalacia, 1 both), asphyxia (4),brain malformation (2), leukoencephalopathy with opticneuropathy (1), Beckwith Wiedemann syndrome (1), menin-gitis (2) and unknown (3 cerebral palsy, 2 visual problemsnot explained by ocular abnormalities).

Describe intervention (treatment/procedure/test):

Children with ocular abnormalities without indications of neurological abnormalities (group 2)

Children with indications of brain damage with or without ocular abnormalities

visual acuity: Cambridge Crowding Cardsto assess uncrowded and crowded opto-type acuity, and the Teller Acuity Cards-II to assess grating acuity.

Crowding, which is defined as the acuity presenting a single optotype, divided by the acuity presenting several optotypes (linear optotype acuity).

And the following ratios were assessed: between grating acuity (Teller Acuity Cards-II) and optotype acuity (Cambridge Crowding Cards)

Describe control (treatment/procedure/test):

Typically developing school children (group 1)

visual acuity, crowding ratio and the ratios between grating acuity (Teller Acuity Cards-II) and optotype acuity (Cambridge Crowding Cards)

Length of follow-up:

-

Loss-to-follow-up:

-

Incomplete outcome data:

-

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

visual acuity:

results are presented in table 3: Median grating acuity only differed significantly between group 1 and 2 (t_w(16) = 2.43,p = 0.03), whereas the differences in median uncrowded and crowded acuities between groups were all significant(p ≤ 0.02).

Uncrowded acuity/crowded acuity:

A crowding ratio of 1.5 (crowded acuity is a half octave or one step lower than uncrowded acuity) or lower was found in 76% of group 1, 86% of group 2, and 33% of group 3.

Grating acuity/uncrowded acuity Group 2 had significantly higher ratio of grating acuity to uncrowded acuity, compared to group 1 (t_w(72) = 4.90,p <0.01) and group 3 (t_w(35) = 2.24, p = 0.03), whereas ratios for group 1 and 3 did not differ significantly.

Grating acuity/crowding acuity The ratios between grating acuity and crowded acuity of group 2 and 3 did not differ significantly, but were significantly higher than in group 1 (tw(72) = 3.90, p <0.01and tw(24.8) = 2.23, p = 0.04).

Youth health care physicians best continue to use subnormal crowded acuity, i.e. routinely used acuity tests, to discriminate between children with and without any visual abnormalities (area under the curve (AUC) = 0.80,95%-CI: 0.71---0.89, p <0.01).

For ophthalmologists, the primary choice for the detection of children at risk of cerebral visual impairments would be the crowding ratio (AUC = 0.68, 95%-CI = 0.54---0.83,p = 0.01). Subnormal vision and the ratio between grating acuity and crowded acuity resulted in comparable sensitivities, but lower specificities.

Within low vision services, too, the crowding ratio with a cut-off value of 2 is currently the best option for screening for a risk of cerebral visual impairment (AUC = 0.76, 95%-CI = 0.60---0.91, p <0.01).

In order to refer properly, youth health care physicians want to identify all children with visual problems irrespective of their cause (target: groups 2 and 3, controls: group 1), whereas ophthalmologists and specialists at low vision services want to differentiate between children at risk of cerebral visual impairment(target: group 3) and children with ocular abnormalities only (controls ophthalmologist: group 1 and 2, controls low vision centre: group 2).