Dr. Sanitha Sathyan, S12939, Dr. Elizabeth Joseph, Dr. Meena Chembil Kakkitampara
ABSTARCT:
AIM: To analyze the visual function in patients with cerebral visual impairment (CVI) using visual evoked potential (VEP) and to correlate it with severity of CVI and visual acuity.
METHODS: 23 patients with cerebral visual impairment of age less than 4 years and 23 healthy age and sex matched controls were recruited in the study, from January 2016 to January 2017. Institutional review board approval was obtained for this study and the research adhered to the tender of declaration of Helsinki. Visual acuity estimation, orthoptic assessment, cycloplegic refraction, anterior segment and posterior segment evaluation were done in all cases. Flash VEP was done in all patients using VEP Tommy EP-1000. Comparison of VEP parameters between cases and controls was done using unpaired t-test. Spearman rank correlation was used to correlate VEP parameters with visual acuity estimate and severity of CVI.
RESULTS: On comparing VEP parameters between cases and controls, a significant difference was found in amplitude of N2 wave (p<0.05) and latency of P2 wave (p<0.05). There was no significant difference in latency of N2 wave and amplitude of P2 wave between cases and controls. On correlating visual acuity estimate with VEP parameters, a significant positive correlation was found between visual acuity estimate and amplitude of P2 wave (p<0.05). No significant correlation was found between visual acuity and amplitude of N2 wave, latency of N2 wave or latency of P2 wave. A significant negative correlation was found between severity of PVL and amplitude of P2 wave (p<0.05). No significant correlation was found between severity of PVL and amplitude of N2 wave, latency of N2 or latency of P2 wave
CONCLUSION: VEP parameters showed a significant difference in amplitude of N2 wave and latency of P2 wave among CVI patients, when compared to age and sex matched controls. Visual acuity in children with CVI correlated with the amplitude of P2 wave and severity of disease and negatively correlated with the amplitude of P2 wave.
INTRODUCTION:
Cerebral visual impairment (CVI) is caused by cerebral damage, either to the optic radiations or to the visual cortex, resulting in reduction of bilateral central visual acuity.1 CVI can occur in isolation or along with anterior visual pathway dysfunction.2 In a study conducted in Northern Ireland by Flanagan et al, the prevalence of CVI was found to be 72 per 100,000 children.3 The Oxford Registry of early childhood visual Impairments report the overall prevalence of bilateral vision impairment of 0.5%, with 29.5% of cases due to CVI.4
Perinatal hypoxia/ ischemia is the leading cause of CVI. CVI can occur as a result of decreased cortical oxygenation and/ or damage to the brain tissue from cardio respiratory failure, increased intracranial pressure, head trauma, hydrocephaly etc. Congenital brain malformations secondary to genetic syndromes and/ or other birth defects, meningitis, encephalitis, cytomegalovirus, and herpes simplex virus infections, carbon monoxide poisoning, maternal intake of drugs like Cisplatin, anticonvulsants, cocaine etc can also cause CVI. Secondary complications like seizures, metabolic disorders, hypoglycemia and progressive genetic syndromes may cause or intensify CVI.5
Visual impairment in children with CVI can range from mild to severe forms.6 Some children may show some improvement in visual functions with age, whereas many others show no change.7,8 The most common neurological abnormalities reported with CVI are seizures, cerebral palsy, hemiparesis and hypotonia. Associated ophthalmological problems were strabismus, optic nerve atrophy, ocular motor apraxia, nystagmus and retinal diseases. 9,10,11
Visual Evoked potentials (VEPs) are visually evoked electrophysiological signals obtained from the electroencephalographic activity in the visual cortex, recorded from the overlying scalp. Visual cortex is activated mainly by the central visual field.12 VEP has been used to assess the vision of infants and young children since the 1970’s.13 VEP provides general information about geniculocalcrine function and occipital response to visual stimuli. Study by Tonya Watson et al on longitudinal evaluation of quantitative measurement of vision with VEP concluded that VEP parameters provide information about natural history of CVI and is beneficial in determining the prognosis of visual recovery in children with CVI.6 Imaging techniques such as computed tomography (CT), magnetic resonance imaging (MRl), and positron emission tomography (PET) are also helpful in identifying the site of damage in the brain.13
Existing literature suggests that VEP is useful in the objective assessment of visual acuity in preverbal children and that it is a useful tool to measure the visual function in children with CVI.13 Measurement of prognostic value of visual function in CVI using VEP has also been documented by Richard Huo et al9 and Aldrich et al.14
The variation in the VEP parameters between CVI patients and normal age matched infants has not been previously studied. Such information would be helpful in setting VEP based guidelines for characterization and prognostication of CVI patients. Therefore our study was designed to analyze the visual function in CVI and to compare it with an age and sex matched control group.
AIM:
- To analyze the VEP parameters in patients with CVI and to compare it with age matched controls.
- To correlate the VEP parameters with in patients with CVI with visual acuity and severity of the disease according to the features in neuroimaging.
MATERIALS AND METHODS:
In this case control study, 23 patients, between 1-6 years of age, with CVI, attending the Pediatric Ophthalmology clinic of a tertiary care eye facility were enrolled prospectively and VEP parameters were compared with 23 age matched controls. The correlation of VEP parameters with MRI findings and visual acuity was also determined.
Sample size determination: was done based on the study by Tonya Watson et al, 8 using the
formula n= Z 2 x p (1-p)/ M 2, where
n = sample size
Z = Z value (e.g. 1.96 for 95% confidence level)
P = population proportion (expressed as decimal)
M = Margin of Error at 5% (0.05)
The final sample was calculated as 23 cases and 23 controls.
Sampling technique: Simple random sampling, by using random number tables.
Inclusion criteria: Children with CVI with age ≤ 4 years during January, 2016 to January, 2017.
Exclusion criteria: Non cooperative children for VEP/ vision assessment, failure to obtain informed consent.
Ethical concern: The present study was approved in Institutional Ethical Committee of the study centre. The study followed the tenets of the declaration of Helsinki and informed consent was obtained from the parents of the patients enrolled in the study.
Operational definitions:
- Latency of N2 wave-It is the time from stimulus onset to the largest amplitude of a negative wave
- Latency of P2 wave-It is the time from stimulus onset to largest amplitude of P2 wave.
- Amplitude of N2 wave-It is measured from the negative N2 peak to the preceding P1 positive peak.
- Amplitude of P2 wave-Measurements of P2 amplitude made from the positive P2 peak to the preceding N2 negative peak.
Procedure: All the patients with a clinical diagnosis of CVI underwent detailed evaluation according to a standard protocol. Clinical history including mother’s obstetric history, birth history, and systemic history were noted and recorded in all cases.
Visual acuity was assessed depending on the response to flash light and grouped into 3 categories:
- Fixing and following
- Occasionally fixing
- Not fixing/ following
Based on neuroimaging of the brain, periventricular leucomalacia was graded according to the classification proposed by Bruno et al15 into the following grades:
Grade1- Areas of increased periventricular echogenicity without any cyst formation
Grade 2- The echogenicity has resolved into small periventricular cyst
Grade 3– Areas of increased periventricular echogenicity that develop into extensive periventricular cyst in the occipital and fronto parietal region
Grade 4- Area of increased periventricular echogenicity in the deep white matter developing into extensive subcortical cyst.
All the patients underwent the following tests including estimation of visual acuity using age-appropriate tests: fixation behavior, Cardiff chart, Teller acuity chart, Snellan chart), orthoptic evaluation (corneal reflex test, ocular motility, Modified Krimsky/ prism and cover test), cycloplegic retinoscopy, anterior segment examination including pupillary reations, and dilated fundus evaluation.
Controls were selected from age and sex matched children who underwent VEP recording for suspected visual impairment and turned out to have normal VEP parameters, during the study period.
Flash VEP was done in all patients using VEP TOMMY EP-1000 under standard condition, 12 prior to pupillary dilatation. The flash VEP was elicited by a brief flash that subtended a visual field of at least 200 presented in a dimly illuminated room. The strength of the flash stimulus used was 3 (2.7–3.3) photopic candelas seconds per meter squared (Cds/m2). This was achieved using a hand held stroboscopic light in front of the patient. The flash rate was 1 per second (1.0 Hz ± 10%).12 VEP parameters, including latency and amplitude of P2 and N2 waves were recorded in cases. Control group was selected from age and sex matched normal individuals who underwent VEP recording for evaluation of suspected defective vision and obtained normal VEP recordings.
Statistical Analysis: Data was entered to Microsoft Excel (Microsoft Corporation, Chicago) format and analyzed using SPSS Software for Windows version 20.0 (SPSS Inc, Chicago, Illinois, USA).Unpaired t test was used to compare the VEP parameters between cases and controls. Spearman rank correlation was used to correlate VEP parameters and visual acuity and is also used to find out correlation between severity of PVL and VEP parameters.
RESULTS:
46 eyes of 23 cases with CVI and 46 eyes of 23 controls were included for the final analysis. Mean age of the patients was 1.47±1.01 years. There were 13 (56.5%) females and 10 (43.5%) males among the cases and control groups. Out of the 23 (78%) patients with CVI, 18 (22%) had perinatal hypoxic ischemia and 5 had history of neonatal meningitis. Mean birth weight was 2.64±0.62 kg among the CVI patients. 13 (56.52%) patients were fixing and following, 4 (17.39%) were occasionally fixing and 6 (28.09%) were not fixing torch light. Table1 represent the demographic characteristics of the population.
Table 1: Demographic characteristics of the population.
| Parameter | Cases | Controls | p value |
| Mean age (years) | 1.47±1.01 | 1.48±0.09 | 0.93 |
| Males | 20 (43.48 %) | 20 (43.48 %) | 0.73 |
| females | 13 (56.52 %) | 13 (56.52 %) | 0.76 |
| Mean birth weight (kg) | 2.64±0.62 | 2.83±0.42 | 0.64 |
Seizure was the most common systemic association, found in 14 (60.86%) of CVI patients. Microcephaly (4.35%), septicemia (8.70%) and hydrocephalus (13.04%) were other systemic features seen in our population. 7 (30.43%) did not have any associated systemic abnormalities.
Out of 46 eyes, 15 eyes (32.61%) had myopic astigmatism and 3 eyes (6.52%) had simple myopia. 28 eyes (60.87%) did not show significant refractive error in cycloplegic retinoscopy. Exotropia was found in 13 patients (45.50%), esotropia in 6 (24.07%) and 7 (30.43%) had no ocular deviation. Out of 46 eyes, 12 eyes (26.00%) had nystagmus; optic disc pallor was present in 32 eyes (69.60%).
VEP parameters were compared between cases and controls. Table 2 represents the comparison of VEP parameters among cases and controls.
Table 2: Distribution of VEP parameters among cases and controls.
| VEP parameter | Cases
(Mean±SD) |
Controls
(Mean±SD) |
t-value | p-value | Significance |
| Mean amplitude of N2 wave | 7.07±5.52 | 4.52±1.07 | 2.22 | <0.05 | significant |
| Mean Latency of N2 wave | 75.19±18.01 | 78.23±16.48 | 0.85 | 0.4 | Not significant |
| Mean amplitude of P2 wave | 11.20±7.36 | 9.91±7.46 | 0.84 | 0.41 | Not significant |
| Mean latency of P2 wave | 128.55±20.98 | 114.19±18.03 | 3.52 | <0.05 | significant |
Figure: 1: Comparison of mean amplitude of N2 and P2 waves among cases and controls.
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